Wednesday, 23 August 2017

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2017

Papers

L. Verset, J. Tommelein, C. Decaestecker, E. De Vlieghere, M. Bracke, I. Salmon, O. De Wever, P. Demetter,
ADAM-17/FHL2 Colocalisation Suggests Interaction and Role of These Proteins in Colorectal Cancer
Tumor biology, Vol. 39, 3, 2017
Bibtex
Bibtex : info:hdl:2013/242103
Note : Language of publication: en



Y. Van Eycke, J. Allard, I. Salmon, O. Debeir, C. Decaestecker,
Image processing in digital pathology: an opportunity to solve inter-batch variability of immunohistochemical staining
Scientific Reports, Vol. 7, 2017
Bibtex
Bibtex : info:hdl:2013/246463
Note : SCOPUS: ar.j
Abstract : Immunohistochemistry (IHC) is a widely used technique in pathology to evidence protein expression in tissue samples. However, this staining technique is known for presenting inter-batch variations. Whole slide imaging in digital pathology offers a possibility to overcome this problem by means of image normalisation techniques. In the present paper we propose a methodology to objectively evaluate the need of image normalisation and to identify the best way to perform it. This methodology uses tissue microarray (TMA) materials and statistical analyses to evidence the possible variations occurring at colour and intensity levels as well as to evaluate the efficiency of image normalisation methods in correcting them. We applied our methodology to test different methods of image normalisation based on blind colour deconvolution that we adapted for IHC staining. These tests were carried out for different IHC experiments on different tissue types and targeting different proteins with different subcellular localisations. Our methodology enabled us to establish and to validate inter-batch normalization transforms which correct the non-relevant IHC staining variations. The normalised image series were then processed to extract coherent quantitative features characterising the IHC staining patterns.



L. Buisseret, C. Desmedt, S. Garaud, M. Fornili, X. Wang, G. Van den Eyden, A. de Wind, S. Duquenne, A. Boisson, C. Naveaux, F. Rothe, S. Rorive, C. Decaestecker, D. Larsimont, M. Piccart-Gebhart, E. Biganzoli, C. Sotiriou, K. Willard-Gallo,
Reliability of tumor-infiltrating lymphocyte and tertiary lymphoid structure assessment in human breast cancer.
Modern pathology, 2017
Bibtex
Bibtex : info:hdl:2013/253706
Note : Language of publication: en
Abstract : The presence of tumor-infiltrating lymphocytes (TIL), reflecting host immune activity, is frequently correlated with better clinical outcomes, particularly in HER2-positive and triple-negative breast cancer. Recent findings suggest that organization of immune infiltrates in tertiary lymphoid structures also has a beneficial effect on survival. This study investigated inter- and intra-observer variation in TIL assessment using conventional hematoxylin-eosin versus immunohistochemical staining to identify immune cells. Global, intratumoral, and stromal TIL, as well as tertiary lymphoid structures were scored independently by experienced pathologists on full-face tumor sections (n=124). The fidelity of scoring infiltrates in core biopsies compared to surgical specimens, and pathological assessment compared to quantitative digital analysis was also evaluated. The inter-observer concordance correlation coefficient was 0.80 for global, 0.72 for intratumoral, and 0.71 for stromal TIL, while the intra-observer concordance correlation coefficient was 0.90 for global, 0.77 for intratumoral, and 0.89 for stromal TIL using immunohistochemical stains. Correlations were lower with hematoxylin-eosin stains, particularly for intratumoral TIL, while global scores had the highest concordance correlation coefficients. Our study concluded that tertiary lymphoid structures are accurately and consistently scored using immunohistochemical but not hematoxylin-eosin stains. A strong association was observed between TIL in core biopsies and surgical samples (R(2)=0.74) but this did not extend to tertiary lymphoid structures (R(2)=0.26). TIL scored by pathologists and digital analysis were correlated but our analysis reveals a constant bias between these methods. These data challenge current criteria for TIL and tertiary lymphoid structure assessment in breast cancer and recommend that how pathologists evaluate immune infiltrates be reexamined for future studies.Modern Pathology advance online publication, 16 June 2017; doi:10.1038/modpathol.2017.43.




2016

Papers

G. Descamps, Y. Karaca, J. Lechien, N. Kindt, C. Decaestecker, M. Remmelink, D. Larsimont, G. Andry, S. Hassid, A. Rodriguez, M. Khalifé, F. Journé, S. Saussez,
Classical risk factors, but not HPV status, predict survival after chemoradiotherapy in advanced head and neck cancer patients
Journal of cancer research and clinical oncology, Vol. 142, 10, pp. 2185-2196, 2016
Bibtex
Bibtex : info:hdl:2013/237944
Note : SCOPUS: ar.j
Abstract : Purpose: Despite the advent of concomitant chemoradiotherapy (CCRT), the prognosis of advanced head and neck squamous cell carcinoma (HNSCC) patients remains particularly poor. Classically, HNSCC, especially oropharyngeal carcinomas, associated with human papillomavirus (HPV) exhibits better treatment outcomes than HNSCCs in non-infected patients, eliciting a call for the de-escalation of current therapies. To improve the management of HNSCC patients, we aimed to determine the impact of active HPV infection on patient response, recurrence and survival after CCRT in a population of heavy tobacco and alcohol consumers. Methods: Paraffin-embedded samples from 218 advanced HNSCC patients, mostly smokers and/or drinkers treated by CCRT, were tested for the presence of HPV DNA by surrogate type-specific E6/E7 qPCR and p16 immunohistochemistry. Associations between the response to CCRT and patient outcomes according to HPV status and clinical data were evaluated by Kaplan–Meier analysis and both univariate and multivariate Cox regression. Results: Type-specific E6/E7 PCR demonstrated HPV positivity in 20 \% of HNSCC. Regarding HPV status, we did not find any significant relation with response to therapy in terms of progression-free survival or overall survival. However, we observed a significantly worse prognosis for consumers of alcohol and tobacco compared to nondrinkers (p = 0.003) and non-smokers (p = 0.03). Survival analyses also revealed that the outcome is compromised in stage IV patients (p = 0.007) and, in particular, for oral cavity, hypopharynx and oropharynx carcinoma patients (p = 0.001). Conclusion: The risk of death from HNSCC significantly increases when patients are exposed to tobacco and alcohol during their therapy, regardless of HPV status.



Conferences

L. Verset, J. Tommelein, C. Decaestecker, I. Salmon, O. De Wever, P. Demetter,
ADAM-17/FHL2 Colocalisation Suggests Interaction and Role of These Proteins in Colorectal Cancer
Conference: Joint Meeting of the British Division of the International Academy of Pathology and the Pathological Society of Great Britain & Ireland(9th: 28 June – 1 July 2016: Nottingham), 2016
Bibtex
Bibtex : info:hdl:2013/242090
Note : Language of publication: en



D. Bonatto, S. Rogge, A. Schenkel, R. Ercek, G. Lafruit,
Explorations for Real-Time Point Cloud Rendering of Natural Scenes in Virtual Reality
International Conference on 3D Imaging, 2016
Bibtex
Bibtex : info:hdl:2013/239092
Note : Language of publication: fr



Y. Van Eycke, J. Allard, M. Derock, I. Salmon, O. Debeir, C. Decaestecker,
Image normalization for quantitative immunohistochemistry in digital pathology
2016 IEEE 13th International Symposium on Biomedical Imaging (ISBI), pp. 795 - 798, Prague, Czech Republic, 2016
Bibtex
Bibtex : info:hdl:2013/233019
Note : SCOPUS: cp.p
Abstract : We propose to adapt to immunohistochemistry (IHC) some methods proposed to normalize images from histological slices stained with hematoxylin-eosin (H&E). Our final aim is to provide a coherent quantitative characterization of IHC biomarkers across different IHC batches with possible staining variations. In contrast to H&E, IHC staining strongly varies with the tissue analyzed and the protein targeted, making image normalization challenging. To solve this problem, we added in each IHC batch a slice from a reference tissue microarray (TMA) and then digitalized it to establish an inter-batch normalization transform. A comparison of two methods adapted to the specificity of IHC-stained slides evidences some normalization requirements to make valid IHC biomarker quantification across different staining batches.



X. Fan, R. Ercek, N. Gaspard, X. De Tiege, L. Benjamin, A. Nonclercq, others,
Study of dynamics underlying epileptic seizure crisis based on a neural mass model
Conference: (2016: Prague), 2016
Bibtex
Bibtex : info:hdl:2013/238283
Note : Language of publication: fr



L. Lebrun, D. Milowich, M. Le Mercier, J. Allard, Y. Van Eycke, T. Roumeguere, C. Decaestecker, I. Salmon, S. Rorive,
UCA1 Overexpression is a New Independent Prognostic Marker in Bladder Cancer Associated with Increased Patient Survival
Conference: Joint Meeting of the British Division of the International Academy of Pathology and the Pathological Society of Great Britain & Ireland(9th: 28 June – 1 July 2016: Nottingham), 2016
Bibtex
Bibtex : info:hdl:2013/242095
Note : Language of publication: en



A. Trepant, N. D'Haene, J. Allard, Y. Van Eycke, C. Decaestecker, I. Salmon, P. Demetter,
Vascular Insulin-Like Growth Factor Receptor Type 2 (IGF2R) Expression is Upregulated in Malignant Tumours
Conference: Joint Meeting of the British Division of the International Academy of Pathology and the Pathological Society of Great Britain & Ireland(9th: 28 June – 1 July 2016: Nottingham), 2016
Bibtex
Bibtex : info:hdl:2013/242086
Note : Language of publication: en




2015

Papers

P. Masuzzo, L. Martens, . 2014 Cell Migration Workshop Participants, C. Ampe, K. Anderson, J. Barry, O. De Wever, O. Debeir, C. Decaestecker, H. Dolznig, P. Friedl, C. Gaggioli, B. Geiger, I. Goldberg, E. Horn, R. Horwitz, Z. Kam, S. Le Dévédec, D. Vignjevic, J. Moore, J. Olivo-Marin, E. Sahai, S. Sansone, V. Sanz-Moreno, S. Str{\"o}mblad, J. Swedlow, J. Textor, M. Van Troys, R. Zantl,
An open data ecosystem for cell migration research.
Trends in cell biology, Vol. 25, 2, pp. 55-58, 2015
Bibtex
Bibtex : info:hdl:2013/197899
Note : SCOPUS: no.j
Abstract : Cell migration research has recently become both a high content and a high throughput field thanks to technological, computational, and methodological advances. Simultaneously, however, urgent bioinformatics needs regarding data management, standardization, and dissemination have emerged. To address these concerns, we propose to establish an open data ecosystem for cell migration research.



D. Milowich, M. Le Mercier, N. De Nève, F. Sandras, T. Roumeguere, C. Decaestecker, I. Salmon, S. Rorive,
Diagnostic value of the UCA1 test for bladder cancer detection: a clinical study.
SpringerPlus, Vol. 4, pp. 349, 2015
Bibtex
Bibtex : info:hdl:2013/208027
Note : SCOPUS: ar.j
Abstract : To evaluate the efficiency of the UCA1 test as a diagnostic tool for the detection of bladder cancer.



A. Trepant, C. Bouchart, S. Rorive, S. Sauvage, C. Decaestecker, P. Demetter, I. Salmon,
Identification of OLIG2 as the most specific glioblastoma stem cell marker starting from comparative analysis of data from similar DNA chip microarray platforms.
Tumor biology, Vol. 36, 3, pp. 1943-1953, 2015
Bibtex
Bibtex : info:hdl:2013/197897
Note : SCOPUS: ar.j
Abstract : Despite advances in surgical and adjuvant treatments, overall survival of glioblastoma (GBM) patients remains poor. The cancer stem cell concept suggests that a rare stem cell population, called glioma stem cells (GSCs), has high ability to self-renewal leading to recurrence in GBM. The identification of specific markers of GSCs would provide a powerful tool to detect and to characterise them in order to develop targeted therapies. We carried out a comparative analysis based on the identification of inter-study concordances to identify the genes that exhibit at best differential levels of expression between GSC-enriched cell cultures and differentiated tumour cell cultures from independent studies using DNA chip microarray technologies. We finally studied the protein expression of the marker we considered the most specific by immunohistochemistry and semi-quantitative analysis on a retrospective series of 18 GBMs. Of the selected studies, 32 genes were retained. Among them, eight genes were identified to be overexpressed in GSC-enriched cultures compared to differentiated tumour cell cultures. Finally, among the eight genes, oligodendrocyte lineage transcription factor 2 (OLIG2) was characterised by the most different expression level in the "GSC model" compared to the "differentiated tumour cells model". Our approach suggests that OLIG2 is the most specific GSC marker; additional investigations with careful considerations about methodology and strategies of validation are, however, mandatory.



C. Maris, N. D'Haene, A. Trepant, M. Le Mercier, S. Sauvage, J. Allard, S. Rorive, P. Demetter, C. Decaestecker, I. Salmon,
IGF-IR: a new prognostic biomarker for human glioblastoma.
British Journal of Cancer, Vol. 113, 5, pp. 729-737, 2015
Bibtex
Bibtex : info:hdl:2013/219347
Note : SCOPUS: ar.j
Abstract : Glioblastomas (GBMs) are the most common malignant primary brain tumours in adults and are refractory to conventional therapy, including surgical resection, radiotherapy and chemotherapy. The insulin-like growth factor (IGF) system is a complex network that includes ligands (IGFI and IGFII), receptors (IGF-IR and IGF-IIR) and high-affinity binding proteins (IGFBP-1 to IGFBP-6). Many studies have reported a role for the IGF system in the regulation of tumour cell biology. However, the role of this system remains unclear in GBMs.



L. Verset, J. Tommelein, X. Moles Lopez, C. Decaestecker, T. Boterberg, E. De Vlieghere, I. Salmon, M. Mareel, M. Bracke, O. De Wever, P. Demetter,
Impact of neoadjuvant therapy on cancer-associated fibroblasts in rectal cancer.
Radiotherapy and oncology, Vol. 116, 3, pp. 449-54, 2015
Bibtex
Bibtex : info:hdl:2013/200672
Note : SCOPUS: cp.j
Abstract : Cancer-associated fibroblasts (CAFs) are increasingly recognised as promoters of tumour progression. It is poorly investigated whether cancer management protocols, such as neoadjuvant radio(chemo)therapy, have an impact on CAFs and, by consequence, on tumour progression. This prompted us to study the impact of neoadjuvant radio(chemo)therapy on the α-SMA/epithelial area ratio in rectal cancer, and the impact of this ratio on recurrence-free survival.



L. De Smedt, J. Lemahieu, S. Palmans, O. Govaere, T. Tousseyn, E. van Cutsem, H. Prenen, S. Tejpar, M. Spaepen, G. Matthijs, C. Decaestecker, X. Moles Lopez, P. Demetter, I. Salmon, X. Sagaert,
Microsatellite instable vs stable colon carcinomas: analysis of tumour heterogeneity, inflammation and angiogenesis.
British Journal of Cancer, Vol. 113, 3, pp. 500-9, 2015
Bibtex
Bibtex : info:hdl:2013/205313
Note : SCOPUS: ar.j
Abstract : Microsatellite instability (MSI) accounts for 15\% of all colorectal tumours. Several specific clinicopathologicals (e.g., preference for the proximal colon over the distal colon, improved prognosis and altered response to chemotherapeutics) are described for this subset of tumours. This study aimed to analyse morphological, inflammatory and angiogenic features of MSI vs microsatellite stable (MSS) tumours.



T. Gevaert, X. Moles Lopez, X. Sagaert, L. Libbrecht, T. Roskams, S. Rorive, C. Decaestecker, I. Salmon, D. De Ridder,
Morphometric and quantitative immunohistochemical analysis of disease-related changes in the upper (suburothelial) lamina propria of the human bladder dome.
PloS one, Vol. 10, 5, pp. e0127020, 2015
Bibtex
Bibtex : info:hdl:2013/200671
Note : SCOPUS: ar.j
Abstract : The upper (suburothelial) lamina propria (ULP) is a distinct region in the human bladder with dense populations of interstitial cells (IC), fine vascular networks and variable development of muscularis mucosae (MM). It is more and more obvious that the ULP plays an important role in bladder physiology and bladder disease, and in the present study we have quantified changes in the cellular key players of the ULP in bladders from patients with carcinoma in situ (CIS), multiple sclerosis (MS) and bladder pain syndrome (BPS). Tissue samples for the different patient groups were obtained from radical cystectomy-specimens. Standardized immunohistochemistry with a panel of specific cell markers was used to characterise the ULP cellular structures, followed by digitalised morphometry and quantitative staining analysis. Alterations in the ULP area were most pronounced in MS bladders, but also present in BPS and CIS bladders. We observed an increased thickness and increased variability in thickness of the ULP IC area in MS and BPS bladders; a significantly increased development of MM in MS bladders; a changed organization of vascular plexuses in the lamina propria in most pathologic bladders and a changed phenotype of ULP IC: a significantly decreased expression of progesterone receptor in MS bladders and a trend towards decreased expression of alpha-smooth muscle actin in BPS bladders. We show here for the first time the presence of disease-specific changes in organisation and/or phenotype of the different key players of the ULP area in human bladder. The present findings further support the hypothesis that the ULP area is involved and altered in different bladder diseases.



X. Moles Lopez, P. Barbot, Y. Van Eycke, L. Verset, A. Trepant, L. Larbanoix, I. Salmon, C. Decaestecker,
Registration of whole immunohistochemical slide images: an efficient way to characterize biomarker colocalization.
Journal of the American Medical Informatics Association, Vol. 22, 1, pp. 86-99, 2015
Bibtex
Bibtex : info:hdl:2013/177042
Note : JOURNAL ARTICLE
Abstract : Extracting accurate information from complex biological processes involved in diseases, such as cancers, requires the simultaneous targeting of multiple proteins and locating their respective expression in tissue samples. This information can be collected by imaging and registering adjacent sections from the same tissue sample and stained by immunohistochemistry (IHC). Registration accuracy should be on the scale of a few cells to enable protein colocalization to be assessed.



M. Gilson, G. Deliens, R. Leproult, A. Bodart, A. Nonclercq, R. Ercek, P. Peigneux,
REM‐Enriched Naps Are Associated with Memory Consolidation for Sad Stories and Enhance Mood‐ Related Reactivity
Brain sciences, 2015
Bibtex
Bibtex : info:hdl:2013/223113
Note : Language of publication: fr



Conferences

X. Fan, R. Ercek, N. Gaspard, A. Nonclercq,
Analysis of a neural mass model that simulates epileptiform/background eeg activities
14th Belgian Day on Biomedical Engineering - joint meeting with IEEE EMBS Benelux Chapter, 2015
Bibtex
Bibtex : info:hdl:2013/225786
Note : Language of publication: fr



Y. Van Eycke, O. Debeir, L. Verset, P. Demetter, I. Salmon, C. Decaestecker,
Automated Tissue Microarray Image Processing in Digital Pathology.
Proceedings of the Fifth joint WIC/IEEE SP Symposium on Information Theory and Signal Processing in the Benelux, Brussels, Belgium, 2015
Bibtex
Bibtex : info:hdl:2013/199489
Note : Language of publication: en



Y. Van Eycke, O. Debeir, L. Verset, P. Demetter, I. Salmon, C. Decaestecker,
High-Throughput Analysis of Tissue-Based Biomarkers in Digital Pathology
EMBC'15 Proceedings (IEEE Engineering in Medicine and Biology Society), pp. 7732 - 7735, Milan, 2015
Bibtex
Bibtex : info:hdl:2013/205314
Note : Language of publication: en



L. Verset, J. Tommelein, X. Moles Lopez, C. Decaestecker, T. Boterberg, E. De Vlieghere, I. Salmon, M. Mareel, M. Bracke, O. De Wever, P. Demetter,
Impact of neoadjuvant therapy on cancer-associated fibroblast in rectal cancer
Conference: Joint Meeting of the British Division of the International Academy of Pathology and the Pathological Society of Great Britain & Ireland(8th: 23 – 25 June 2015: Dublin), 2015
Bibtex
Bibtex : info:hdl:2013/223057
Note : Language of publication: en



L. De Smedt, J. Lemahieu, S. Palmans, O. Govaere, T. Tousseyn, E. van Cutsem, H. Prenen, S. Tejpar, C. Decaestecker, X. Moles Lopez, P. Demetter, I. Salmon, X. Sagaert,
Microsatellite instability versus microsatellite stability in colon carcinoma: documentation of tumour heterogeneity and inflammation
Conference: Belgian Week of Gastroenterology(XXVIIth : February 2015: Brussels), 2015
Bibtex
Bibtex : info:hdl:2013/223062
Note : Language of publication: en



A. Trepant, C. Maris, N. D'Haene, S. Sauvage, S. Rorive, C. Decaestecker, I. Salmon, P. Demetter,
Role of IGFIIR/Man-6-P in Glioblastoma angiogenesis
Conference: Joint Meeting of the British Division of the International Academy of Pathology and the Pathological Society of Great Britain & Ireland(8 th: 23 – 25 June 2015: Dublin), 2015
Bibtex
Bibtex : info:hdl:2013/223051
Note : Language of publication: en




2014

Papers

A. Duray, T. De Maesschalck, C. Decaestecker, M. Remmelink, G. Chantrain, J. Neiveyans, M. Horoi, X. Leroy, H. Gabius, S. Saussez,
Galectin fingerprinting in naso-sinusal diseases.
Oncology Reports, Vol. 32, 1, pp. 23-32, 2014
Bibtex
Bibtex : info:hdl:2013/174705
Note : Journal Article
Abstract : Galectins, a family of endogenous lectins, are multifunctional effectors that act at various sites and can be used in immunohistochemical localization studies of diseased states. Since they form a potentially cooperative and antagonistic network, we tested the hypothesis that histopathological fingerprinting of galectins could refine the molecular understanding of naso-sinusal pathologies. Using non-cross-reactive antibodies against galectin-1, -3, -4, -7, -8 and -9, we characterized the galectin profiles in chronic rhinosinusitis, nasal polyposis, inverted papillomas and squamous cell carcinomas. The expression, signal location and quantitative parameters describing the percentage of positive cells and labeling intensity were assessed for various cases. We discovered that inverted papillomas showed a distinct galectin immunohistochemical profile. Indeed, epithelial overexpression of galectin-3 (p=0.0002), galectin-4 (p<10-6), galectin-7 (p<10-6) and galectin-9 (p<10-6) was observed in inverted papillomas compared to non-malignant diseases. Regarding carcinomas, we observed increased expression of galectin-9 (p<10-6) in epithelial cells compared to non-tumor pathologies. Our results suggest that galectin-3, -4, -7 and -9 could be involved in the biology of inverted papillomas. In addition, we observed that the expression of galectin in naso-sinusal diseases seems to be affected by tumor progression and not inflammatory or allergic phenomena.



N. D'Haene, C. Maris, S. Rorive, C. Decaestecker, M. Le Mercier, I. Salmon,
Galectins and neovascularization in central nervous system tumors.
Glycobiology, Vol. 24, 10, pp. 892-898, 2014
Bibtex
Bibtex : info:hdl:2013/175597
Note : Journal Article
Abstract : Despite advances in diagnosis and treatment, the overall outcomes for patients with brain tumors remain unpredictable. New prognostic markers are still needed to identify high-risk patients for whom the standard treatment has poor outcomes and would thus be well suited for more aggressive therapies. Neovascularization has long been implicated as a salient feature of glioma progression. In fact, high-grade gliomas are among the most vascular of all solid tumors, and vascular proliferation is a pathological hallmark of glioblastomas. Galectins are known to play important roles in cancer biology, including cancer cell migration, tumor immune escape or tumor angiogenesis. Moreover, galectins were reported to be involved in glioma progression. Given the key role of angiogenesis in brain tumors, the expression of galectins in tumor-associated endothelial cells (EC) and the implication of galectins in angiogenesis, the present review will focus on the expression of galectins in ECs of normal brain and brain tumors.



V. Arcolia, P. Paci, L. Dhont, G. Chantrain, N. Sirtaine, C. Decaestecker, M. Remmelink, A. Belayew, S. Saussez,
Helicase-like transcription factor: a new marker of well-differentiated thyroid cancers.
BMC cancer, Vol. 14, 1, pp. 492, 2014
Bibtex
Bibtex : info:hdl:2013/174707
Note : Journal Article
Abstract : The preoperative characterization of thyroid nodules is a challenge for the clinicians. Fine-needle aspiration (FNA) is the commonly used pre-operative technique for diagnosis of malignant thyroid tumor. However, many benign lesions, with indeterminate diagnosis following FNA, are referred to surgery. There is an urgent need to identify biomarkers that could be used with the FNA to distinguish benign thyroid nodules from malignant tumors. The purpose of the study is to examine the level of expression of the helicase-like transcription factor (HLTF) in relation to neoplastic progression of thyroid carcinomas.



J. Allard, X. Moles Lopez, K. Li, O. Blanchard, P. Barbot, S. Rorive, C. Decaestecker, R. Pochet, D. Bohl, A. Lepore, I. Salmon, C. Nicaise,
Immunohistochemical toolkit for tracking and quantifying xenotransplanted human stem cells.
Regenerative medicine, Vol. 9, 4, pp. 437-452, 2014
Bibtex
Bibtex : info:hdl:2013/174921
Note : Journal Article
Abstract : Biomarker-based tracking of human stem cells xenotransplanted into animal models is crucial for studying their fate in the field of cell therapy or tumor xenografting.



V. Richard, N. Kindt, C. Decaestecker, H. Gabius, G. Laurent, J. No{\"e}l, S. Saussez,
Involvement of macrophage migration inhibitory factor and its receptor (CD74) in human breast cancer.
Oncology Reports, Vol. 32, 2, pp. 523-529, 2014
Bibtex
Bibtex : info:hdl:2013/174706
Note : Journal Article
Abstract : Macrophage migration inhibitory factor (MIF) and its receptor CD74 appear to be involved in tumorigenesis. We evaluated, by immunohistochemical staining, the tissue expression and distribution of MIF and CD74 in serial sections of human invasive breast cancer tumor specimens. The serum MIF level was also determined in breast cancer patients. We showed a significant increase in serum MIF average levels in breast cancer patients compared to healthy individuals. MIF tissue expression, quantified by a modified Allred score, was strongly increased in carcinoma compared to tumor-free specimens, in the cancer cells and in the peritumoral stroma, with fibroblasts the most intensely stained. We did not find any significant correlation with histoprognostic factors, except for a significant inverse correlation between tumor size and MIF stromal positivity. CD74 staining was heterogeneous and significantly decreased in cancer cells but increased in the surrounding stroma, namely in lymphocytes, macrophages and vessel endothelium. There was no significant variation according to classical histoprognostic factors, except that CD74 stromal expression was significantly correlated with triple-negative receptor (TRN) status and the absence of estrogen receptors. In conclusion, our data support the concept of a functional role of MIF in human breast cancer. In addition to auto- and paracrine effects on cancer cells, MIF could contribute to shape the tumor microenvironment leading to immunomodulation and angiogenesis. Interfering with MIF effects in breast tumors in a therapeutic perspective remains an attractive but complex challenge. Level of co-expression of MIF and CD74 could be a surrogate marker for efficacy of anti-angiogenic drugs, particularly in TRN breast cancer tumor.



N. Komen, J. Slieker, P. Willemsen, G. Mannaerts, P. Pattyn, T. Karsten, H. de Wilt, E. van der Harst, W. Van Leeuwen, C. Decaestecker, H. Jeekel, J. Lange,
Polymerase chain reaction for Enterococcus faecalis in drain fluid: the first screening test for symptomatic colorectal anastomotic leakage. The Appeal-study: analysis of parameters predictive for evident anastomotic leakage.
International journal of colorectal disease, Vol. 29, 1, pp. 15-21, 2014
Bibtex
Bibtex : info:hdl:2013/157762
Note : Journal Article
Abstract : With current diagnostic methods, the majority of patients with symptomatic colorectal anastomotic leakage(CAL) is identified approximately 1 week after operation.The aim of this study is to determine whether real-time polymerase chain reaction (RT-PCR) for detection of Escherichia coli and Enterococcus faecalis on drain fluid can serve as a screening test for CAL in the early postoperative phase.



Conferences

A. Trepant, C. Bouchart, S. Rorive, S. Sauvage, C. Decaestecker, P. Demetter, I. Salmon,
Identification of OLIG2 as most specific glioblastoma stem cell marker starting from comparative analysis of data from similar DNA chip microarray platforms
Conference: 19th World Congress on Advances in Oncology and 17th International Symposium on Molecular Medecine(October 9-11, 2014: Athens), 2014
Bibtex
Bibtex : info:hdl:2013/193429
Note : Language of publication: en



Y. Van Eycke, X. Moles Lopez, J. Allard, M. Derock, S. Rorive, I. Salmon, C. Decaestecker,
Multiresolution registration of whole slide images to evidence and quantify virtual colocalization of tissue-based biomarkers
Conference: Digital Pathology Congress(4-5 December 2014: London), 2014
Bibtex
Bibtex : info:hdl:2013/193430
Note : Language of publication: en
Abstract : Extracting relevant information from actors involved in complex biological processes (such as cancers or treatment responses) requires to target different antigens simultaneously. Multichromogenic (brightfield) immunohistochemistry (IHC) suffers from limitations that notably prevent the analysis of proteins expressed in the same cellular compartment. We thus developed an alternative based on the analysis of adjacent, or serial, tissue sections on which different proteins were targeted by means of standard IHC. For this analysis, we developed a multiresolution method for registering serial slide images. This method uses the pyramidal and multimodal registration framework of the elastix software to optimize two parametric registrations. The first, low-resolution registration, is applied on the 1X equivalent magnification images (4,000 by 3,000 pixels). The result of this first step was then used to initialize high-resolution registrations independently performed on 20X equivalent fields of view. Our method shows accuracy levels compatible with biomarker colocalization characterization. Indeed, registration error on serial slides was evaluated to be at most between 20 µm and 80 µm, depending respectively of the presence or absence of histological structures in the tissue (e.g. in colonic tumor as compared to brain gliomas). In the latter situation, a sequential IHC technique applied on the same slide can be usefully employed. This “Sequential Immunoperoxidase Labeling and Erasing” (SIMPLE) method is based on cycles of staining/digitization/erasing, where after IHC staining and slide digitization, staining is erased through an antibody elution technique. We improved the original SIMPLE method and successfully utilized it to identify antigens expressed in the same cellular compartment of high-grade glioma samples. We tested our registration on the virtual slides so obtained and achieved very good results, i.e. about 5 µm of registration error. We then implemented a method to extract biomarker colocalization measurements taking the level of registration error into account and validated our complete procedure by comparison to colocalization information obtained by means of double staining (with different cell locations).



X. Moles Lopez, C. Maris, T. Chattaway, M. Remmelink, B. Weynand, S. Rorive, C. Decaestecker, I. Salmon,
SecundOS: A Belgian digital pathology initiative to implement an inter-university network for second opinions and collaboration between expert pathologists.
Conference: Digital Pathology Congress(4-5 December 2014: London), 2014
Bibtex
Bibtex : info:hdl:2013/193431
Note : Available at http://www.globalengage.co.uk/pathology/posters14.pdf (Abstract No 11)



Books chapters

Moles Lopez, Xavier, Debeir, Olivier, Salmon, Isabelle, Decaestecker, Christine,
Whole slide imaging and analysis for biomarker evaluation in digital pathology
A. Méndez-Vilas (Ed.), Microscopy: advances in scientific research and education, Vol. 2, pp. 776-787, 2014
Bibtex
Bibtex : info:hdl:2013/175598
Note : Language of publication: na




2013

Papers

L. Twyffels, C. Wauquier, R. Soin, C. Decaestecker, C. Gueydan, V. Kruys,
A Masked PY-NLS in Drosophila TIS11 and Its Mammalian Homolog Tristetraprolin.
PloS one, Vol. 8, 8, pp. e71686, 2013
Bibtex
Bibtex : info:hdl:2013/150049
Note : Journal Article
Abstract : Many RNA-binding proteins (RBPs) dynamically shuttle between the nucleus and the cytoplasm, often exerting different functions in each compartment. Therefore, the nucleo-cytoplasmic distribution of RBPs has a strong impact on their activity. Here we describe the localization and the shuttling properties of the tandem zinc finger RBP dTIS11, which is the Drosophila homolog of mammalian TIS11 proteins. Drosophila and mammalian TIS11 proteins act as destabilizing factors in ARE-mediated decay. At equilibrium, dTIS11 is concentrated mainly in the cytoplasm. We show that dTIS11 is a nucleo-cytoplasmic shuttling protein whose nuclear export is mediated by the exportin CRM1 through the recognition of a nuclear export signal (NES) located in a different region comparatively to its mammalian homologs. We also identify a cryptic Transportin-dependent PY nuclear localization signal (PY-NLS) in the tandem zinc finger region of dTIS11 and show that it is conserved across the TIS11 protein family. This NLS partially overlaps the second zinc finger ZnF2. Importantly, mutations disrupting the capacity of the ZnF2 to coordinate a Zinc ion unmask dTIS11 and TTP NLS and promote nuclear import. All together, our results indicate that the nuclear export of TIS11 proteins is mediated by CRM1 through diverging NESs, while their nuclear import mechanism may rely on a highly conserved PY-NLS whose activity is negatively regulated by ZnF2 folding.



X. Moles Lopez, E. D'Andrea, P. Barbot, A. Bridoux, S. Rorive, I. Salmon, O. Debeir, C. Decaestecker,
An Automated Blur Detection Method for Histological Whole Slide Imaging
PloS one, Vol. 8, 12, 2013
Bibtex
Bibtex : info:hdl:2013/152899
Note : Language of publication: en
Abstract : Whole slide scanners are novel devices that enable high-resolution imaging of an entire histological slide. Furthermore, the imaging is achieved in only a few minutes, which enables image rendering of large-scale studies involving multiple immunohistochemistry biomarkers. Although whole slide imaging has improved considerably, locally poor focusing causes blurred regions of the image. These artifacts may strongly affect the quality of subsequent analyses, making a slide review process mandatory. This tedious and time-consuming task requires the scanner operator to carefully assess the virtual slide and to manually select new focus points. We propose a statistical learning method that provides early image quality feedback and automatically identifies regions of the image that require additional focus points.



L. Verset, J. Tommelein, X. Moles Lopez, C. Decaestecker, M. Mareel, M. Bracke, I. Salmon, O. De Wever, P. Demetter,
Epithelial expression of FHL2 is negatively associated with metastasis-free and overall survival in colorectal cancer
British Journal of Cancer, Vol. 109, 1, pp. 114-120, 2013
Bibtex
Bibtex : info:hdl:2013/149047
Note : SCOPUS: ar.j
Abstract : Background:Four-and-a-half LIM domains protein 2 (FHL2) is a component of the focal adhesion structures and has been suggested to have a role in cancer progression. It has been shown to be overexpressed in the colorectal cancer (CRC).Methods:Here, we examined a possible prognostic value of FHL2 in CRC. Immunohistochemistry for FHL2 was performed on 296 CRCs without distant metastases at the time of surgery. Staining in the epithelial compartment was quantitatively evaluated using image analysis, and results were related to clinical variables. Antibody specificity was tested using small-interfering RNA transfection in hTERT-immortalised myofibroblasts.Results:Varying degrees of cytoplasmic FHL2 expression by neoplastic epithelial cells were detectable in all cases. Higher FHL2 expression in the epithelial compartment was an independent adverse prognostic factor. Multivariate Cox analysis shows that expression in the tumour invasion front (P<0.001) as well as in the centre of the tumour (P<0.001) was associated with metachronous metastases independently of the clinicopathological variables; expression in the tumour invasion front was also associated with overall survival independently of the clinicopathological variables (P<0.01).Conclusion:Higher FHL2 expression is involved in CRC progression and correlates with the development of metachronous metastases and overall survival, suggesting that FHL2 is an independent adverse prognostic indicator for CRC. © 2013 Cancer Research UK. All rights reserved.



A. Duray, G. Descamps, C. Decaestecker, N. Sirtaine, A. Gilles, M. Khalifé, G. Chantrain, C. Depuydt, P. Delvenne, S. Saussez,
Human papillomavirus predicts the outcome following concomitant chemoradiotherapy in patients with head and neck squamous cell carcinomas.
Oncology Reports, Vol. 30, 1, pp. 371-376, 2013
Bibtex
Bibtex : info:hdl:2013/150048
Note : Journal Article
Abstract : We investigated the prevalence of human papillomavirus (HPV) in a clinical series of 72 patients with head and neck squamous cell carcinoma (HNSCC) using a retrospective and prospective study design. The majority of patients were smokers and/or drinkers and were treated with concomitant chemoradiotherapy (CCR). Furthermore, we assessed the impact of HPV positivity on the response to CCR. Paraffin-embedded samples from HNSCC patients (n=72) were evaluated for the presence of HPV DNA using both GP5+/GP6+ consensus PCR and type-specific E6/E7 PCR to detect HPV types 6, 11, 16, 18, 31, 33, 35, 39, 45, 51, 52, 53, 56, 58, 59, 66, 67 and 68. The type-specific E6/E7 PCR demonstrated that 20 out of 69 HNSCC patients (29\%) presented with high-risk (HR) HPV types and that 5 of the 69 HNSCC patients (7\%) presented with low-risk (LR) HPV types. Using the GP5+/GP6+ PCR, we observed that the rate of response was statistically lower in the HPV+ group (P=0.02). Concerning patient outcomes in terms of recurrence and survival, we observed that the prognosis was poorer for HPV+ patients. We showed for the first time that patients with HPV+ HNSCC present with a worse prognosis after CCR. This observation highlights the need for prospective studies with large numbers of patients and a detailed history of tobacco and alcohol consumption before validating HPV as a marker of prognosis following CCR.



N. Kindt, J. Preillon, H. Kaltner, H. Gabius, D. Chevalier, A. Rodriguez, B. Johnson, V. Megalizzi, C. Decaestecker, G. Laurent, S. Saussez,
Macrophage migration inhibitory factor in head and neck squamous cell carcinoma: clinical and experimental studies.
Journal of cancer research and clinical oncology, Vol. 139, 5, pp. 727-737, 2013
Bibtex
Bibtex : info:hdl:2013/158182
Note : Journal Article
Abstract : The present in vivo/in vitro study was undertaken in order to evaluate the importance of macrophage migration inhibitory factor (MIF) in the progression of head and neck squamous cell carcinoma (HNSCC).



A. Nonclercq, C. Urbain, D. Verheulpen, C. Decaestecker, P. Van Bogaert, P. Peigneux,
Sleep spindle detection through amplitude-frequency normal modelling
Journal of neuroscience methods, Vol. 214, 2, pp. 192-203, 2013
Bibtex
Bibtex : info:hdl:2013/139889
Note : Language of publication: na



N. D'Haene, S. Sauvage, C. Maris, I. Adanja, M. Le Mercier, C. Decaestecker, L. Baum, I. Salmon,
VEGFR1 and VEGFR2 Involvement in Extracellular Galectin-1- and Galectin-3-Induced Angiogenesis
PloS one, Vol. 8, 6, 2013
Bibtex
Bibtex : info:hdl:2013/148927
Note : SCOPUS: ar.j
Abstract : Aim:Accumulating evidence suggests that extracellular galectin-1 and galectin-3 promote angiogenesis. Increased expression of galectin-1 and/or galectin-3 has been reported to be associated with tumour progression. Thus, it is critical to identify their influence on angiogenesis.Methods:We examined the individual and combined effects of galectin-1 and galectin-3 on endothelial cell (EC) growth and tube formation using two EC lines, EA.hy926 and HUVEC. The activation of vascular endothelial growth factor receptors (VEGFR1 and VEGFR2) was determined by ELISA and Western blots. We evaluated the VEGFR1 and VEGFR2 levels in endosomes by proximity ligation assay.Results:We observed different responses to exogenous galectins depending on the EC line. An enhanced effect on EA.hy926 cell growth and tube formation was observed when both galectins were added together. Focusing on this enhanced effect, we observed that together galectins induced the phosphorylation of both VEGFR1 and VEGFR2, whereas galectin-1 and -3 alone induced VEGFR2 phosphorylation only. In the same way, the addition of a blocking VEGFR1 antibody completely abolished the increase in tube formation induced by the combined addition of both galectins. In contrast, the addition of a blocking VEGFR2 antibody only partially inhibited this effect. Finally, the addition of both galectins induced a decrease in the VEGFR1 and VEGFR2 endocytic pools, with a significantly enhanced effect on the VEGFR1 endocytic pool. These results suggest that the combined action of galectin-1 and galectin-3 has an enhanced effect on angiogenesis via VEGFR1 activation, which could be related to a decrease in receptor endocytosis. © 2013 D'Haene et al.



Conferences

X. Moles Lopez, P. Barbot, N. D'Haene, C. Maris, S. Rorive, I. Salmon, C. Decaestecker,
How Digital Image Analysis Applied to Immunohistochemistry Helps To Assess Biomarker Coexpression.
Conference: 102nd USCAP Annual Meeting, 2013
Bibtex
Bibtex : info:hdl:2013/193241
Note : Language of publication: na



L. Verset, J. Tommelein, X. Moles Lopez, C. Decaestecker, M. Mareel, M. Bracke, I. Salmon, O. De Wever, P. Demetter,
Investigation of a possible link between epithelial four-and-a-half LIM domains protein 2 expression and prognosis in colorectal cancer
Conference: 2013 Gastrointestinal Cancers Symposium, 2013
Bibtex
Bibtex : info:hdl:2013/193428
Note : Language of publication: en



N. D'Haene, F. Hulet, J. Allard, C. Maris, C. Decaestecker, I. Salmon,
VEGFR1: Target for Anti-Angiogenic Therapy? An Immunohistochemical Study Highlighting Heterogeneity of Tumor-Associated Endothelial Cells
Conference: the 102nd USCAP Annual Meeting(Baltimore), 2013
Bibtex
Bibtex : info:hdl:2013/193242
Note : Language of publication: na




2012

Papers

M. Le Mercier, D. Hastir, X. Moles Lopez, N. De Nève, C. Maris, A. Trepant, S. Rorive, C. Decaestecker, I. Salmon,
A simplified approach for the molecular classification of glioblastomas.
PloS one, Vol. 7, 9, 2012
Bibtex
Bibtex : info:hdl:2013/132976
Note : Journal Article
Abstract : Glioblastoma (GBM) is the most common malignant primary brain tumors in adults and exhibit striking aggressiveness. Although GBM constitute a single histological entity, they exhibit considerable variability in biological behavior, resulting in significant differences in terms of prognosis and response to treatment. In an attempt to better understand the biology of GBM, many groups have performed high-scale profiling studies based on gene or protein expression. These studies have revealed the existence of several GBM subtypes. Although there remains to be a clear consensus, two to four major subtypes have been identified. Interestingly, these different subtypes are associated with both differential prognoses and responses to therapy. In the present study, we investigated an alternative immunohistochemistry (IHC)-based approach to achieve a molecular classification for GBM. For this purpose, a cohort of 100 surgical GBM samples was retrospectively evaluated by immunohistochemical analysis of EGFR, PDGFRA and p53. The quantitative analysis of these immunostainings allowed us to identify the following two GBM subtypes: the "Classical-like" (CL) subtype, characterized by EGFR-positive and p53- and PDGFRA-negative staining and the "Proneural-like" (PNL) subtype, characterized by p53- and/or PDGFRA-positive staining. This classification represents an independent prognostic factor in terms of overall survival compared to age, extent of resection and adjuvant treatment, with a significantly longer survival associated with the PNL subtype. Moreover, these two GBM subtypes exhibited different responses to chemotherapy. The addition of temozolomide to conventional radiotherapy significantly improved the survival of patients belonging to the CL subtype, but it did not affect the survival of patients belonging to the PNL subtype. We have thus shown that it is possible to differentiate between different clinically relevant subtypes of GBM by using IHC-based profiling, a method that is advantageous in its ease of daily implementation and in large-scale clinical application.



D. Tondeleir, A. Lambrechts, M. Mueller, V. Jonckheere, T. Doll, D. Vandamme, K. Bakkali, D. Waterschoot, M. Lemaistre, O. Debeir, C. Decaestecker, B. Hinz, A. Staes, E. Timmerman, N. Colaert, K. Gevaert, J. Vanderkerckove, C. Ampe,
Cells lacking β-actin are genetically reprogrammed and maintain conditional migratory capacity
Molecular & cellular proteomics, Vol. 11, 8, pp. 255-71, 2012
Bibtex
Bibtex : info:hdl:2013/113768
Note : SCOPUS: ar.j
Abstract : Vertebrate nonmuscle cells express two actin isoforms: cytoplasmic β- and γ-actin. Because of the presence and localized translation of β-actin at the leading edge, this isoform is generally accepted to specifically generate protrusive forces for cell migration. Recent evidence also implicates β-actin in gene regulation. Cell migration without β-actin has remained unstudied until recently and it is unclear whether other actin isoforms can compensate for this cytoplasmic function and/or for its nuclear role. Primary mouse embryonic fibroblasts lacking β-actin display compensatory expression of other actin isoforms. Consistent with this preservation of polymerization capacity, β-actin knockout cells have unchanged lamellipodial protrusion rates despite a severe migration defect. To solve this paradox we applied quantitative proteomics revealing a broad genetic reprogramming of β-actin knockout cells. This also explains why reintroducing β-actin in knockout cells does not restore the affected cell migration. Pathway analysis suggested increased Rho-ROCK signaling, consistent with observed phenotypic changes. We therefore developed and tested a model explaining the phenotypes in β-actin knockout cells based on increased Rho-ROCK signaling and increased TGFβ production resulting in increased adhesion and contractility in the knockout cells. Inhibiting ROCK or myosin restores migration of β-actin knockout cells indicating that other actins compensate for β-actin in this process. Consequently, isoactins act redundantly in providing propulsive forces for cell migration, but β-actin has a unique nuclear function, regulating expression on transcriptional and post-translational levels, thereby preventing myogenic differentiation. © 2012 by The American Society for Biochemistry and Molecular Biology, Inc.



L. Ferdinande, C. Decaestecker, L. Verset, A. Mathieu, X. Moles Lopez, A. Negulescu, T. Van Maerken, I. Salmon, C. Cuvelier, P. Demetter,
Clinicopathological significance of indoleamine 2,3-dioxygenase 1 expression in colorectal cancer.
British Journal of Cancer, Vol. 106, 1, pp. 141-147, 2012
Bibtex
Bibtex : info:hdl:2013/106373
Note : JOURNAL ARTICLE
Abstract : Background:Indoleamine 2,3-dioxygenase 1 (IDO1) is a tryptophan-catabolising enzyme that induces immune tolerance by modulating T-cell responses. Carcinomas may create an immunosuppressive state via IDO1 expression. Here we examined a possible contribution of IDO1 on this phenomenon and investigated whether IDO1 has prognostic value in colorectal cancer (CRC).Methods:IDO1 expression was investigated by quantitative PCR and western blotting in three colon cancer cell lines, in basal state and after interferon (IFN)-γ stimulation. Semi-quantitative immunohistochemistry was used to evaluate IDO1 expression in 265 pT1-4N0-2Mx-staged CRCs. Results were related to clinical variables and correlated with amounts of CD3(+) and CD8(+) T lymphocytes, which were quantitatively evaluated using image analysis.Results:In vitro expression of IDO1 depended on IFN-γ stimulation. Higher IDO1 expression at the tumour invasion front was an independent adverse prognostic factor in pT1-4N1Mx-staged CRC. It was associated with overall survival (P=0.001) and with metachronous metastases (P=0.018). IDO1 expression was not associated with the presence of CD3(+) or CD8(+) T lymphocytes.Conclusion:Higher IDO1 expression at the tumour invasion front is involved in CRC progression and correlates with impaired clinical outcome, suggesting that IDO1 is an independent prognostic indicator for CRC.British Journal of Cancer advance online publication, 22 November 2011; doi:10.1038/bjc.2011.513 www.bjcancer.com.



X. Moles Lopez, O. Debeir, C. Maris, S. Rorive, I. Roland, M. Saerens, I. Salmon, C. Decaestecker,
Clustering methods applied in the detection of Ki67 hot-spots in whole tumor slide images: An efficient way to characterize heterogeneous tissue-based biomarkers.
Cytometry. Part A, Vol. 81, 9, pp. 765-775, 2012
Bibtex
Bibtex : info:hdl:2013/127791
Note : Journal Article
Abstract : Whole-slide scanners allow the digitization of an entire histological slide at very high resolution. This new acquisition technique opens a wide range of possibilities for addressing challenging image analysis problems, including the identification of tissue-based biomarkers. In this study, we use whole-slide scanner technology for imaging the proliferating activity patterns in tumor slides based on Ki67 immunohistochemistry. Faced with large images, pathologists require tools that can help them identify tumor regions that exhibit high proliferating activity, called "hot-spots" (HSs). Pathologists need tools that can quantitatively characterize these HS patterns. To respond to this clinical need, the present study investigates various clustering methods with the aim of identifying Ki67 HSs in whole tumor slide images. This task requires a method capable of identifying an unknown number of clusters, which may be highly variable in terms of shape, size, and density. We developed a hybrid clustering method, referred to as Seedlink. Compared to manual HS selections by three pathologists, we show that Seedlink provides an efficient way of detecting Ki67 HSs and improves the agreement among pathologists when identifying HSs. © 2012 International Society for Advancement of Cytometry.



N. Kindt, J. Lechien, C. Decaestecker, A. Rodriguez, G. Chantrain, M. Remmelink, G. Laurent, H. Gabius, S. Saussez,
Expression of macrophage migration-inhibitory factor is correlated with progression in oral cavity carcinomas.
Anticancer research, Vol. 32, 10, pp. 4499-4505, 2012
Bibtex
Bibtex : info:hdl:2013/132977
Note : Journal Article
Abstract : We have previously reported that macrophage migration-inhibitory factor (MIF) is associated with an unfavorable prognosis in hypopharyngeal carcinoma. Here, we quantified MIF expression in oral cavity carcinomas and looked for possible correlations with clinical outcome.



A. Duray, G. Descamps, C. Decaestecker, M. Remmelink, N. Sirtaine, J. Lechien, P. Ernoux-Neufcoeur, N. Bletard, J. Somja, C. Depuydt, P. Delvenne, S. Saussez,
Human papillomavirus DNA strongly correlates with a poorer prognosis in oral cavity carcinoma.
The Laryngoscope, Vol. 122, 7, pp. 1558-1565, 2012
Bibtex
Bibtex : info:hdl:2013/127793
Note : Journal Article
Abstract : The prevalence of human papillomavirus (HPV) in a clinical series of 162 patients with oral squamous cell carcinoma (OSCC) was studied. Furthermore, we analyzed the correlation between the immunohistochemical expression of p16, p53, epidermal growth factor receptor (EGFR), and HPV status to predict survival in OSCC patients.



V. Megalizzi, M. Le Mercier, C. Decaestecker,
Sigma receptors and their ligands in cancer biology: overview and new perspectives for cancer therapy.
Medicinal research reviews, Vol. 32, 2, pp. 410-427, 2012
Bibtex
Bibtex : info:hdl:2013/68368
Note : JOURNAL ARTICLE
Abstract : A large number of drugs are known to bind with high affinity to sigma receptors (sigma-Rs) and have been used in the clinic to treat mental disorders for many years. However, recent publications highlighting sigma-R overexpression in many cancer tissues suggest potential applications for sigma-R ligands in cancer diagnosis and therapy. The present review focuses on the involvement of sigma-Rs in cancer biology and the potential therapeutic contributions of their pharmacologic ligands in oncology. After summarizing the current and general knowledge regarding sigma-Rs, we detail data reported in the particular context of oncology. We then investigate the potential and specific signal transduction pathways and mechanisms involved in the actions of sigma-R ligands in cancer biology. These processes include modulations of (1) the plasma membrane and lipid raft components, (2) intracellular calcium levels, (3) cytoskeletal protein functions, and (4) endoplasmic reticulum stress. Finally, we conclude by speculating on the roles of sigma-R overexpression and sigma-R ligands in cancer biology and offer perspectives on cancer therapy. (c) 2010 Wiley Periodicals, Inc. Med Res Rev.




2011

Papers

I. Adanja, V. Megalizzi, O. Debeir, C. Decaestecker,
A New Method to Address Unmet Needs for Extracting Individual Cell Migration Features from a Large Number of Cells Embedded in 3D Volumes
PloS one, Vol. 6, 7, 2011
Bibtex
Bibtex : info:hdl:2013/94206
Note : SCOPUS: ar.j
Abstract : Background: In vitro cell observation has been widely used by biologists and pharmacologists for screening molecule-induced effects on cancer cells. Computer-assisted time-lapse microscopy enables automated live cell imaging in vitro, enabling cell behavior characterization through image analysis, in particular regarding cell migration. In this context, 3D cell assays in transparent matrix gels have been developed to provide more realistic in vitro 3D environments for monitoring cell migration (fundamentally different from cell motility behavior observed in 2D), which is related to the spread of cancer and metastases. Methodology/Principal Findings: In this paper we propose an improved automated tracking method that is designed to robustly and individually follow a large number of unlabeled cells observed under phase-contrast microscopy in 3D gels. The method automatically detects and tracks individual cells across a sequence of acquired volumes, using a template matching filtering method that in turn allows for robust detection and mean-shift tracking. The robustness of the method results from detecting and managing the cases where two cell (mean-shift) trackers converge to the same point. The resulting trajectories quantify cell migration through statistical analysis of 3D trajectory descriptors. We manually validated the method and observed efficient cell detection and a low tracking error rate (6\%). We also applied the method in a real biological experiment where the pro-migratory effects of hyaluronic acid (HA) were analyzed on brain cancer cells. Using collagen gels with increased HA proportions, we were able to evidence a dose-response effect on cell migration abilities. Conclusions/Significance: The developed method enables biomedical researchers to automatically and robustly quantify the pro- or anti-migratory effects of different experimental conditions on unlabeled cell cultures in a 3D environment. © 2011 Adanja et al.



P. Ernoux-Neufcoeur, M. Arafa, C. Decaestecker, A. Duray, M. Remmelink, X. Leroy, M. Herfs, J. Somja, C. Depuydt, P. Delvenne, S. Saussez,
Combined analysis of HPV DNA, p16, p21 and p53 to predict prognosis in patients with stage IV hypopharyngeal carcinoma.
Journal of cancer research and clinical oncology, Vol. 137, 1, pp. 173-181, 2011
Bibtex
Bibtex : info:hdl:2013/106372
Note : Journal Article
Abstract : We examined p16, p21 and p53 expression in combination with the presence of human papillomavirus (HPV) DNA as molecular markers to predict survival in patients with stage IV hypopharyngeal squamous cell carcinoma (HSCC).



A. Duray, G. Descamps, M. Arafa, C. Decaestecker, M. Remmelink, N. Sirtaine, P. Ernoux-Neufcoeur, E. Mutijima, J. Somja, C. Depuydt, P. Delvenne, S. Saussez,
High incidence of high-risk HPV in benign and malignant lesions of the larynx.
International journal of oncology, Vol. 39, 1, pp. 51-59, 2011
Bibtex
Bibtex : info:hdl:2013/97507
Note : Journal Article
Abstract : The aim of this study was to determine the prevalence of human papillomavirus (HPV) in patients with laryngeal benign lesions (LBLs) and laryngeal squamous cell carcinomas (LSCCs) using a sensitive E6/E7 type-specific PCR. Paraffin-embedded samples from LBL (n=39) and LSCC patients (n=67) were evaluated for the presence of HPV DNA by GP5+/GP6+ consensus PCR and E6/E7 type-specific PCR for HPV types 6, 11, 16, 18, 31, 33, 35, 39, 45, 51, 52, 53, 56, 58, 59, 66 and 68. In LSCCs, immunohistochemical staining of p16, p53 and EGFR was also assessed. The E6/E7 type-specific PCR showed that 44 out of 59 LSCC patients (i.e., 75\%) had high-risk (hr) HPV types and that 27 out of 35 LBL patients (i.e., 77\%) had hrHPV types. HPV-16 viral load was significantly higher in LSCC than in LBL patients (p<10-6). The presence of hrHPV DNA did not correlate with the proportion of disease-free patients. Comparable levels of p16, p53 and EGFR expression were observed in the hrHPV+ tumor group (100\% p16+, 56\% p53+ and 97\% EGFR+) and in the HPV- or low-risk (lr) HPV+ tumor group (92\% p16+, 66\% p53+ and 100\% EGFR+). A very high prevalence of oncogenic HPV-16 was found in a series of benign and malignant laryngeal lesions. LSCC appears to be characterized by an active hrHPV infection. In LSCCs, the hrHPV+ subgroup had a similar prognosis (in terms of risk of recurrence) as the HPV- subgroup.



M. Remmelink, L. de Leval, C. Decaestecker, A. Duray, E. Crompot, N. Sirtaine, S. André, H. Kaltner, X. Leroy, H. Gabius, S. Saussez,
Quantitative immunohistochemical fingerprinting of adhesion/growth-regulatory galectins in salivary gland tumours: divergent profiles with diagnostic potential.
Histopathology, Vol. 58, 4, pp. 543-556, 2011
Bibtex
Bibtex : info:hdl:2013/97506
Note : Journal Article
Abstract : This study tests the hypothesis that histopathological fingerprinting of galectins, which are emerging multifunctional effectors in cell sociology, could refine the differential diagnosis of salivary tumours.



Conferences

N. D'Haene, S. Sauvage, C. Maris, A. Trepant, M. Le Mercier, C. Decaestecker, I. Salmon,
Involvement of Vascular Endothelial Growth Factor Receptors in Endothelial Cell Response to Galectin-1 and Galectin-3
Conference: 6th Joint Meeting of the British Division of the International Academy of Pathology and the Pathological Society of Great Britain & Ireland(May 2011), 2011
Bibtex
Bibtex : info:hdl:2013/193240
Note : Language of publication: na



A. Schenkel, R. Ercek, B. Penelle, A. Hubrecht, T. Saroléa, N. Warzée,
Tridimensional laser scanning to retrieve engineering site drawings. The experience of the Brussels Park Bunker rehabilitation project.
2011 International Conference on 3D Imaging (IC3D 2011), Liège, Belgium, 2011
Bibtex
Bibtex : info:hdl:2013/148261
Note : Language of publication: na




2010

Papers

A. Pozdzik, A. Berton, H. Schmeiser, W. Missoum, C. Decaestecker, I. Salmon, J. Vanherweghem, J. Nortier,
Aristolochic acid nephropathy revisited: a place for innate and adaptive immunity?
Histopathology, Vol. 56, 4, pp. 449-463, 2010
Bibtex
Bibtex : info:hdl:2013/68372
Note : Journal Article
Abstract : AIMS: The histological features of aristolochic acid nephropathy (AAN) consist of paucicellular interstitial fibrosis, severe tubular atrophy, and almost intact glomeruli with media lesions of interlobular arteries. As an early phase of interstitial inflammation preceded peritubular fibrosis in the rat model of AAN, the aim was to investigate the presence of inflammatory cells in human AAN. METHODS AND RESULTS: Reports of confirmed cases and case series of AAN were reviewed in terms of interstitial inflammation and found to have very conflicting results. This prompted us to search for and characterize inflammatory cells within the native kidneys provided from four end-stage AAN patients. Prior aristolochic acid exposure was attested by the intrarenal presence of the typical aristolactam I-derived DNA adduct. Besides the tubulointerstitial lesions usually seen in the cortex, a massive infiltration of macrophages, T and B lymphocytes was detected by immunohistochemistry in the medullary rays and in the outer medullae with some extension to the upper cortical labyrinth. CONCLUSIONS: In parallel with histological findings reported in the rat model, inflammatory cells are present preferentially in the interstitium of the medullary rays and of the outer medulllae in renal interstitium from human AAN cases, even in the terminal stages. Further studies must be undertaken to determine the respective roles of innate and adaptive immunity in the progression of AAN.



I. Adanja, O. Debeir, V. Megalizzi, R. Kiss, N. Warzée, C. Decaestecker,
Automated tracking of unmarked cells migrating in three-dimensional matrices applied to anti-cancer drug screening.
Experimental cell research, Vol. 316, 2, pp. 181-193, 2010
Bibtex
Bibtex : info:hdl:2013/52535
Note : Journal Article
Abstract : In oncology, combating the spread of tumor cells is a clinical need which currently remains unsatisfied. Identifying anti-migratory compounds usually requires in vitro screening of a large number of molecules. Efficient and realistic (i.e., preferably 3D) in vitro tests are thus required in order to quantify the anti-migratory effects of anti-cancer drugs. To remain compatible with high-throughput screening, we focus on assays where unlabeled cells are migrating in 3D transparent gels and are observed under time-lapse 3D phase-contrast microscopy. In this context, we present a method for automatically tracking cells that combines a template matching preprocessing step with a mean-shift process. The preprocessing step consists in performing a correlation of a cell template with each observed volume in order to provide a phase-contrast artifact-free volume where the cells appear as correlation peaks surrounded by smooth gradients. This transformation enables the cells to be efficiently tracked by a mean-shift process. Robustness and efficiency of this approach are qualitatively and quantitatively shown in various experiments. Finally, we successfully applied our method to the quantitative characterization of the anti-migratory impact of cytochalasin-D on cancer cells. In conclusion, our method can efficiently be used for drug screening aiming to evidence drug-induced effects on cell migration in 3D transparent environments, such as matrix gels.



S. Saussez, L. de Leval, C. Decaestecker, N. Sirtaine, S. Cludts, A. Duray, D. Chevalier, S. André, H. Gabius, M. Remmelink, X. Leroy,
Galectin fingerprinting in Warthin's tumors: lectin-based approach to trace its origin?
Histology and histopathology, Vol. 25, 5, pp. 541-550, 2010
Bibtex
Bibtex : info:hdl:2013/68369
Note : Journal Article
Abstract : Warthin's tumor of the parotid gland is assumed to originate from the proliferation of epithelial inclusions within parotid lymph nodes. In that case, these cells are supposed to retain characteristics similar to common salivary gland ductal cells. Using immunohistochemical fingerprinting with four members of the family of adhesion/growth-regulatory galectins and comparison to intra- and interlobular ducts, marked similarities were noted for presence of galectins-3, -7 and -8. Notably, profiles of lectin binding, determined by applying human lectins as probes, were also similar when testing biotinylated galectins-3 and -8. Besides defining the galectin histochemical parameters in Warthin's tumors this study adds support to the hypothesis of heterotopia.



A. Pozdzik, A. Berton, H. Schmeiser, W. Missoum, C. Decaestecker, I. Salmon, J. Vanherweghem, J. Nortier,
Histopathology of human aristolochic acid nephropathy updated: a place for innate and adaptive immunity?
Histopathology, Vol. 56, pp. 449-463, 2010
Bibtex
Bibtex : info:hdl:2013/159377
Note : Language of publication: en



E. Balde, V. Megalizzi, M. Traoré, P. Cos, L. Maes, C. Decaestecker, L. Pieters, A. Balde,
In vitro antiprotozoal, antimicrobial and antitumor activity of Pavetta crassipes K. Schum leaf extracts.
Journal of ethnopharmacology, Vol. 130, 3, pp. 529-535, 2010
Bibtex
Bibtex : info:hdl:2013/68373
Note : Journal Article
Abstract : AIM OF THE STUDY: To study the potential benefit of the traditional medicinal plant Pavetta crassipes K. Schum (Rubiaceae), which is widely distributed throughout West Africa, the methanol and dichloromethane extracts were isolated from the plant leaves to determine if they exhibited antiprotozoal, antibacterial, antifungal or antitumor activity in vitro. MATERIALS AND METHODS: The methanol and dichloromethane extracts and their specific fractions were obtained using bioassay-guided fractionation and investigated for antiproliferative activity in vitro in microorganisms (Staphylococcus aureus, Escherichia coli and Candida albicans), protozoans (Trypanosoma cruzi, Trypanosoma brucei, Leishmania infantum and Plasmodium falciparum), and cancer (U373, PC3, MXT and A549) and normal cell lines (NHDF and MRC-5). RESULTS: Most of the alkaloid fractions investigated exhibited antiproliferative activity in all the cancer cell lines, microorganisms and protozoans studied. CONCLUSIONS: The benefit of Pavetta crassipes as a traditional medicinal remedy was confirmed using antiprotozoal and cytotoxicity assays in vitro. These analyses revealed that the components present in the alkaloid extract of Pavetta crassipes are responsible for its antiprotozoal and cytotoxic efficacy.



N. Wauthoz, P. Deleuze, J. Hecq, I. Roland, S. Saussez, I. Adanja, O. Debeir, C. Decaestecker, V. Mathieu, R. Kiss, K. Amighi,
In vivo assessment of temozolomide local delivery for lung cancer inhalation therapy.
European journal of pharmaceutical sciences, Vol. 39, pp. 402-411, 2010
Bibtex
Bibtex : info:hdl:2013/51846
Note : JOURNAL ARTICLE
Abstract : The aim of this study was to compare the efficacy of local drug delivery by inhalation to intravenous delivery in a B16F10 melanoma metastatic lung model. Temozolomide was formulated as a suspension, which was elaborated and evaluated in terms of particle size, shape and agglomeration. An endotracheal administration device was used to aerosolise the suspension. This mode of delivery was evaluated at different temozolomide concentrations and was optimized for the uniformity of delivered dose, the droplet size distribution and the distribution of droplets in vivo. Of the particles in the stabilised suspension, 79\% were compatible with the human respirable size range, and this formulation retained 100\% in vitro anticancer activity as compared to temozolomide alone in three distinct cancer cell lines. The pulmonary delivery device provided good reproducibility in terms of both the dose delivered and the droplet size distribution. Most of the lung tissues that were exposed to aerosol droplets contained the particles, as revealed by fluorescent microscopy techniques. The global in vivo antitumour activity of the inhaled temozolomide provided a median survival period similar to that for intravenous temozolomide delivery, and three out of 27 mice (11\%) survived with almost complete eradication of the lung tumours. The present study thus shows that inhalation of a simple liquid formulation is well tolerated and active against a very biologically aggressive mouse melanoma pulmonary pseudo-metastatic model. This inhalation delivery could be used to deliver other types of anticancer drugs.



S. Cludts, C. Decaestecker, B. Johnson, J. Lechien, X. Leroy, N. Kindt, H. Kaltner, S. André, H. Gabius, S. Saussez,
Increased expression of macrophage migration inhibitory factor during progression to hypopharyngeal squamous cell carcinoma.
Anticancer research, Vol. 30, 9, pp. 3313-3319, 2010
Bibtex
Bibtex : info:hdl:2013/68384
Note : Journal Article
Abstract : BACKGROUND/AIM: To examine the presence of macrophage migration inhibitory factor (MIF) quantitatively in relation to neoplastic progression of hypopharyngeal squamous cell carcinoma (HSCC). MATERIALS AND METHODS: The presence of MIF was analysed by quantitative immunohistochemistry in sections of 81 HSCCs, and compared to 15 specimens of tumour-free epithelia (TF\_E), 29 low-grade dysplasias (Low\_D) and 25 high-grade dysplasias (High\_D). In parallel, MIF expression was studied using Western blotting on a series of 19 fresh biopsies. RESULTS: A significant increase in MIF staining intensity (mean optical density) was observed in carcinoma samples compared to TF\_E (p<10(-6)), Low\_D (p=0.0006) or High\_D (p=0.0006). Immunohistochemical MIF positivity was significantly higher in HSCCs than in TF\_E (p=0.00001) or Low\_D (p=0.001). The percentage of MIF-immunopositive cells (labelling index) significantly decreased in parallel with an apparent loss of histological differentiation (p=0.003). CONCLUSION: This study identified the presence of MIF as a parameter that positively correlates with neoplastic progression of HSCC and cell differentiation status.



V. Mancilla, C. Decaestecker, C. Ligny, L. Matagne, P. Simon, I. Courtmans,
La surdité moyenne: {\'E}tiologie, évaluation linguistique et scolaire
Cahiers de l'audition, Vol. 23, 3, pp. 5-9, 2010
Bibtex
Bibtex : info:hdl:2013/200158
Note : SCOPUS: ar.j



B. Le Calve, M. Rynkowski, M. Le Mercier, C. Bruyère, C. Lonez, T. Gras, B. Haibe-Kains, G. Bontempi, C. Decaestecker, J. Ruysschaert, R. Kiss, F. Lefranc,
Long-term in vitro treatment of human glioblastoma cells with temozolomide increases resistance in vivo through up-regulation of GLUT transporter and aldo-keto reductase enzyme AKR1C expression.
Neoplasia (New York, N.Y.), Vol. 12, 9, pp. 727-739, 2010
Bibtex
Bibtex : info:hdl:2013/68382
Note : Journal Article
Abstract : Glioblastoma (GBM) is the most frequent malignant glioma. Treatment of GBM patients is multimodal with maximum surgical resection, followed by concurrent radiation and chemotherapy with the alkylating drug temozolomide (TMZ). The present study aims to identify genes implicated in the acquired resistance of two human GBM cells of astrocytic origin, T98G and U373, to TMZ. Resistance to TMZ was induced by culturing these cells in vitro for months with incremental TMZ concentrations up to 1 mM. Only partial resistance to TMZ has been achieved and was demonstrated in vivo in immunocompromised mice bearing orthotopic U373 and T98G xenografts. Our data show that long-term treatment of human astroglioma cells with TMZ induces increased expression of facilitative glucose transporter/solute carrier GLUT/SLC2A family members, mainly GLUT-3, and of the AKR1C family of proteins. The latter proteins are phase 1 drug-metabolizing enzymes involved in the maintenance of steroid homeostasis, prostaglandin metabolism, and metabolic activation of polycyclic aromatic hydrocarbons. GLUT-3 has been previously suggested to exert roles in GBM neovascularization processes, and TMZ was found to exert antiangiogenic effects in experimental gliomas. AKR1C1 was previously shown to be associated with oncogenic potential, with proproliferative effects similar to AKR1C3 in the latter case. Both AKR1C1 and AKR1C2 proteins are involved in cancer pro-proliferative cell chemoresistance. Selective targeting of GLUT-3 in GBM and/or AKR1C proteins (by means of jasmonates, for example) could thus delay the acquisition of resistance to TMZ of astroglioma cells in the context of prolonged treatment with this drug.



D. Lamoral-Theys, M. Le Mercier, B. Le Calve, M. Rynkowski, C. Bruyère, C. Decaestecker, B. Haibe-Kains, G. Bontempi, J. Dubois, F. Lefranc, R. Kiss,
Long-term temozolomide treatment induces marked amino metabolism modifications and an increase in TMZ sensitivity in Hs683 oligodendroglioma cells.
Neoplasia (New York, N.Y.), Vol. 12, 1, pp. 69-79, 2010
Bibtex
Bibtex : info:hdl:2013/51182
Note : Journal Article
Abstract : Gliomas account for more than 50\% of all primary brain tumors. The worst prognosis is associated with gliomas of astrocytic origin, whereas gliomas with an oligodendroglial origin offer higher sensitivity to chemotherapy, especially when oligodendroglioma cells display 1p19q deletions. Temozolomide (TMZ) provides therapeutic benefits and is commonly used with radiotherapy in highly malignant astrocytic tumors, including glioblastomas. The actual benefits of TMZ during long-term treatment in oligodendroglioma patients have not yet been clearly defined. In this study, we have investigated the effects of such a long-term TMZ treatment in the unique Hs683 oligodendroglioma model. We have observed increased TMZ sensitivity of Hs683 orthotopic tumors that were previously treated in vitro with months of progressive exposure to increasing TMZ concentrations before being xenografted into the brains of immunocompromised mice. Whole-genome and proteomic analyses have revealed that this increased TMZ sensitivity of Hs683 oligodendroglioma cells previously treated for long periods with TMZ can be explained, at least partly, by a TMZ-induced p38-dependant dormancy state, which in turn resulted in changes in amino acid metabolism balance, in growth delay, and in a decrease in Hs683 oligodendroglioma cell-invasive properties. Thus, long-term TMZ treatment seems beneficial in this Hs683 oligodendroglioma model, which revealed itself unable to develop resistance against TMZ.



D. Lamoral-Theys, C. Decaestecker, V. Mathieu, J. Dubois, A. Kornienko, R. Kiss, A. Evidente, L. Pottier,
Lycorine and its derivatives for anticancer drug design.
Mini-reviews in medical chemistry, Vol. 10, 1, pp. 41-50, 2010
Bibtex
Bibtex : info:hdl:2013/70175
Note : Journal Article
Abstract : Amaryllidaceae alkaloids are extensively studied for their biological activities in several pharmaceutical areas, including, for example, Alzheimer's disease for which galanthamine has already reached the market. Among this chemical family, lycorine displays very promising anti-tumor properties. This review first focuses on the chemical diversity of natural and synthetic analogues of lycorine and their metabolites, and then on mechanisms of action and biological targets through which lycorine and its derivatives display their anti-tumor activity. Our analysis of the structure-activity relationships of this family of compounds highlights the existence of various potential leads for the development of novel anticancer agents.



S. Rorive, X. Moles Lopez, C. Maris, A. Trepant, S. Sauvage, N. Sadeghi-Meibodi, I. Roland, C. Decaestecker, I. Salmon,
TIMP-4 and CD63: new prognostic biomarkers in human astrocytomas.
Modern pathology, Vol. 23, 10, pp. 1418-1428, 2010
Bibtex
Bibtex : info:hdl:2013/68379
Note : Journal Article
Abstract : Based on the molecular profiling of astrocytomas, we previously identified a series of genes involved in astrocytoma invasion. Of these, tissue inhibitor of metalloproteinase-4 (TIMP-4) was found to be overexpressed in pilocytic astrocytomas relative to diffuse astrocytomas of any histological grade. Although some data suggest that TIMP-4 may be an anti-tumoral actor in astrocytomas, recent findings challenge this concept. The present study aims to investigate the diagnostic and prognostic values of TIMP-4 and its putative partner CD63 in human astrocytomas. Tissue microarray and image analysis were first carried out to quantitatively analyze the immunohistochemical expression of these proteins in 471 gliomas including 354 astrocytomas. Pathological semi-quantitative scores of both markers' expression were then established and correlated to astrocytoma diagnosis and patient prognosis. TIMP-4 and CD63 expressions were both overexpressed in astrocytomas compared with oligodendrogliomas (P<0.001) and in pilocytic astrocytomas compared with grade II diffuse astrocytomas (P<0.001). In glioblastomas, high TIMP-4/CD63 co-expression scores were identified as independent prognostic factors associated with progression and shorter survival. In conclusion, this work provides the first evidence of a TIMP-4/CD63 association in astrocytoma tumor cells. It identifies TIMP-4 and CD63 as markers of the astrocytic phenotype in patients with gliomas. In addition, this work highlights the contribution of high TIMP-4/CD63 co-expression to the adverse outcomes of patients with glioblastomas.



S. Rorive, N. D'Haene, C. Fossion, I. Delpierre, N. Abarguia, E. Avni, C. Decaestecker, I. Salmon,
Ultrasound-guided fine-needle aspiration of thyroid nodules: stratification of malignancy risk using follicular proliferation grading, clinical and ultrasonographic features.
European journal of endocrinology, Vol. 162, 6, pp. 1107-1115, 2010
Bibtex
Bibtex : info:hdl:2013/59300
Note : Journal Article
Abstract : OBJECTIVE: To evaluate the diagnostic value of fine-needle aspiration (FNA) cytology and the additive contribution brought by clinical and ultrasound (US) features. METHOD: Cytological and histological diagnoses were compared in a series of 924 patients who underwent US-guided FNA before surgery. We additionally developed a grading system for follicular proliferation (FP) FNA diagnosis, and investigated its impact on the malignancy risk as well as the additive contribution of clinical and US features by means of decision tree analysis. RESULTS: Excluding FP cases (n=395), our data demonstrated that strictly benign or malignant FNA diagnoses exhibit great concordance with benign or malignant histological diagnoses (97.8\% accuracy). Our grading system that was applied to the 395 FP cases revealed that grades 1, 2 and 3 were associated with a 7.7, 17.7 and 45.7\% incidence of malignancy respectively. Decision tree analysis resulted in a classification model which involved FP grade, patient's age, serum thyroglobulin level, nodule size and nodule uniqueness. This model identified a subgroup of patients with grade 1 FP nodules who were older than 50 years, and who had a higher risk of malignancy (17.9\%). In addition, high serum thyroglobulin levels were associated with a very high malignancy risk (75.0\%) for patients with grade 3 FP nodules. Finally, among grade 2 FP patients, unique and large nodules were associated with a high malignancy risk of 36.1\%. CONCLUSIONS: The integration of FP grade, clinical and US features allows the stratification of patients with FP cytology according to their risk of malignancy.



Conferences

X. Moles Lopez, O. Debeir, C. Maris, I. Roland, I. Salmon, C. Decaestecker,
Ki-67 hot-spots detection on glioblastoma tissue sections
Proc. of the 2010 IEEE International Symposium on Biomedical Imaging: From Nano to Macro (ISBI 2010), pp. pp 149-152, Rotterdam, 2010
Bibtex
Bibtex : info:hdl:2013/70188
Note : Language of publication: en




2009

Papers

S. Saussez, C. Decaestecker, S. Cludts, P. Ernoux-Neufcoeur, D. Chevalier, Smetana Jr. Karel, S. André, X. Leroy, H. Gabius,
Adhesion/growth-regulatory tissue lectin galectin-1 in relation to angiogenesis/lymphocyte infiltration and prognostic relevance of stromal up-regulation in laryngeal carcinomas
Anticancer research, Vol. 29, 1, pp. 59-65, 2009
Bibtex
Bibtex : info:hdl:2013/111872
Note : SCOPUS: ar.j



A. Mathieu, B. Weynand, E. Verbeken, S. Da Silva, C. Decaestecker, I. Salmon, P. Demetter,
Comparison of four antibodies for immunohistochemical evaluation of epidermal growth factor receptor expression in non-small cell lung cancer.
Lung cancer, Vol. 1301, pp. 152-162, 2009
Bibtex
Bibtex : info:hdl:2013/53634
Note : JOURNAL ARTICLE
Abstract : Agents acting on signalling molecules of growth pathways have emerged as therapeutics for non-small cell lung cancer (NSCLC). Among them are inhibitors of the epidermal growth factor receptor (EGFR). To meet Belgian reimbursement criteria for erlotinib, patients must have an EGFR-positive tumour, defined as at least 10\% of cells showing membranous staining on immunohistochemistry. This study compares results obtained with the Dako pharmDx kit versus other anti-EGFR antibodies in 634 NSCLC. More than 80\% of patients qualify for erlotinib therapy using the Dako pharmDx kit or antibodies from Zymed or Novocastra; when NeoMarkers antibodies are used, less than 70\% will do. Although immunohistochemical stainings for EGFR can be performed on biopsies, surgical and cytological samples from primary and metastatic NSCLC, highest positivity rates were obtained in biopsies from primary tumours. In conclusion, immunohistochemistry for patient selection for erlotinib therapy needs standardization in order to avoid results influenced by technical issues.



M. Le Mercier, S. Fortin, V. Mathieu, I. Roland, S. Spiegl-Kreinecker, B. Haibe-Kains, G. Bontempi, C. Decaestecker, W. Berger, F. Lefranc, R. Kiss,
Galectin 1 proangiogenic and promigratory effects in the Hs683 oligodendroglioma model are partly mediated through the control of BEX2 expression.
Neoplasia (New York, N.Y.), Vol. 11, 5, pp. 485-496, 2009
Bibtex
Bibtex : info:hdl:2013/51190
Note : Journal Article
Abstract : We have previously reported that galectin 1 (Gal-1) plays important biological roles in astroglial as well as in oligodendroglial cancer cells. As an oligodendroglioma model, we make use of the Hs683 cell line that has been previously extensively characterized at cell biology, molecular biology, and genetic levels. Galectin 1 has been shown to be involved in Hs683 oligodendroglioma chemoresistance, neoangiogenesis, and migration. Down-regulating Gal-1 expression in Hs683 cells through targeted small interfering RNA provokes a marked decrease in the expression of the brain-expressed X-linked gene: BEX2. Accordingly, the potential role of BEX2 in Hs683 oligodendroglioma cell biology has been investigated. The data presented here reveal that decreasing BEX2 expression in Hs683 cells increases the survival of Hs683 orthotopic xenograft-bearing mice. Furthermore, this decrease in BEX2 expression impairs vasculogenic mimicry channel formation in vitro and angiogenesis in vivo, and modulates glioma cell adhesion and invasive features through the modification of several genes previously reported to play a role in cancer cell migration, including MAP2, plexin C1, SWAP70, and integrin beta(6). We thus conclude that BEX2 is implicated in oligodendroglioma biology.



S. Cludts, C. Decaestecker, V. Mahillon, D. Chevalier, H. Kaltner, S. André, M. Remmelink, X. Leroy, H. Gabius, S. Saussez,
Galectin-8 up-regulation during hypopharyngeal and laryngeal tumor progression and comparison with galectin-1, -3 and -7.
Anticancer research, Vol. 29, 12, pp. 4933-4940, 2009
Bibtex
Bibtex : info:hdl:2013/75903
Note : Comparative Study
Abstract : To define specific staining patterns for the adhesion/growth-regulatory lectin tandem-repeat-type galectin-8 in hypopharyngeal and laryngeal tumor progression and relate these parameters to galectins 1, 3 and 7 in the quest to explore the galectin network.



L. Yen, F. Fouss, C. Decaestecker, P. Francq, M. Saerens,
Graph nodes clustering with the sigmoid commute-time kernel: a comparative study
Data & knowledge engineering, Vol. 68, 3, pp. 338-361, 2009
Bibtex
Bibtex : info:hdl:2013/68825
Note : Language of publication: en



R. Marechal, P. Demetter, N. Nagy, A. Berton, C. Decaestecker, M. Polus, J. Closset, J. Devière, I. Salmon, J. Van Laethem,
High expression of CXCR4 may predict poor survival in resected pancreatic adenocarcinoma.
British Journal of Cancer, Vol. 100, 9, pp. 1444-1451, 2009
Bibtex
Bibtex : info:hdl:2013/51024
Note : Journal Article
Abstract : Chemokines and their receptors are involved in tumourigenicity and clinicopathological significance of chemokines receptor expression in pancreatic adenocarcinoma (PA) is not fully understood. This study was conducted to determine patients' outcome according to the expressions of CXCR4, CXCR7 and HIF-1alpha after resection of PA. Immunohistochemistry for CXCR4, CXCR7 and HIF-1alpha expressions as well as cell proliferative index (Ki-67) was conducted in 71 resected (R0) PA and their 48 related lymph nodes (LN) using tissue microarray. CXCR4 and CXCR7 expressions were positively correlated to HIF-1alpha suggesting a potential role of HIF-1alpha in CXCR4 and CXCR7 transcription activation. Patients with CXCR4(high) tumour expression had shorter OS than those with low expression (median survival: 9.7 vs 43.2 months, P=0.0006), a higher risk of LN metastases and liver recurrence. In multivariate analysis, high CXCR4 expression, LN metastases and poorly differentiated tumour are independent negative prognosis factors. In a combining analysis, patients with CXCR4(low)/CXCR7(low) tumour had a significantly shorter DFS and OS than patients with a CXCR7(high)/CXCR4(high) tumour. CXCR4 in resected PA may represent a valuable prognostic factor as well as an attractive target for therapeutic purpose.



S. Saussez, S. Cludts, A. Capouillez, G. Mortuaire, K. Smetana, H. Kaltner, S. André, X. Leroy, H. Gabius, C. Decaestecker,
Identification of matrix metalloproteinase-9 as an independent prognostic marker in laryngeal and hypopharyngeal cancer with opposite correlations to adhesion/growth-regulatory galectins-1 and -7.
International journal of oncology, Vol. 34, 2, pp. 433-439, 2009
Bibtex
Bibtex : info:hdl:2013/75906
Note : Journal Article
Abstract : The enzymatic activity of matrix metalloproteinase-9 (MMP-9) suggests that its presence in hypopharyngeal and laryngeal squamous cell carcinomas (HSCCs, LSCCs) could have prognostic value. We tested this hypothesis by quantitative morphometric analysis of immunohistochemical staining in histological sections of 73 stage IV HSCCs and 45 LSCCs (30 cases of stage I/II, 15 cases of stage IV). As compared to tumour-free epithelium an increase for the labelling index in LSCCs reached statistical significance (p=0.04). Specimens of Reinke's edema were strongly higher in this parameter compared to tumour-free tissue area (p=0.000001), underscoring an association between the level of MMP-9 expression and inflammation. Focusing on patients' recurrence status we identified thresholds for the labelling index of 10\% for HSCCs and 18\% for LSCCs, both indicating rapid recurrence and dismal prognosis unless surpassed. When relating data for MMP-9 to those for three adhesion/growth-regulatory galectins, a positive correlation with galectin-7 expression was detected in LSCCs. This finding suggests a possible potential role of this endogenous lectin as inducer of MMP-9 gene expression in situ. Of note, galectin-1 expression was negatively correlated with MMP-9 and that of galectin-3, a substrate of MMP-9, not related. In conclusion our study delineated a prognostic role of MMP-9 immunodetection in high-stage HSCCs and in LSCCs when separating patients by a distinct threshold for the labelling index. Moreover, it indicated associations between MMP-9 and multifunctional galectins-1 and -7 in situ.



C. Decaestecker, X. Moles Lopez, N. D'Haene, I. Roland, S. Guendouz, C. Duponchelle, A. Berton, O. Debeir, I. Salmon,
Requirements for the valid quantification of immunostains on tissue microarray materials using image analysis.
Proteomics, Vol. 9, 19, pp. 4478-4494, 2009
Bibtex
Bibtex : info:hdl:2013/52938
Note : Journal Article
Abstract : Antibody-based proteomics applied to tissue microarray (TMA) technology provides a very efficient means of visualizing and locating antigen expression in large collections of normal and pathological tissue samples. To characterize antigen expression on TMAs, the use of image analysis methods avoids the effects of human subjectivity evidenced in manual microscopical analysis. Thus, these methods have the potential to significantly enhance both precision and reproducibility. Although some commercial systems include tools for the quantitative evaluation of immunohistochemistry-stained images, there exists no clear agreement on best practices to allow for correct and reproducible quantification results. Our study focuses on practical aspects regarding (i) image acquisition (ii) segmentation of staining and counterstaining areas and (iii) extraction of quantitative features. We illustrate our findings using a commercial system to quantify different immunohistochemistry markers targeting proteins with different expression patterns (cytoplasmic, nuclear or membranous) in colon cancer or brain tumor TMAs. Our investigations led us to identify several steps that we consider essential for standardizing computer-assisted immunostaining quantification experiments. In addition, we propose a data normalization process based on reference materials to be able to compare measurements between studies involving different TMAs. In conclusion, we recommend certain critical prerequisites that commercial or in-house systems should satisfy in order to permit valid immunostaining quantification.



V. Megalizzi, C. Decaestecker, O. Debeir, S. Spiegl-Kreinecker, W. Berger, F. Lefranc, R. Kast, R. Kiss,
Screening of anti-glioma effects induced by sigma-1 receptor ligands: potential new use for old anti-psychiatric medicines.
European journal of cancer, Vol. 45, 16, pp. 2893-2905, 2009
Bibtex
Bibtex : info:hdl:2013/51188
Note : Journal Article
Abstract : The prognosis of glioblastoma (GBM) remains poor. Diffuse invasion of distant brain tissue by migrating cells from the primary tumour mass has already occurred at time of diagnosis. Anti-cancer effects of a selective sigma-1 agonist, 4-(N-benzylpiperidin-4-yl)-4-iodobenzamide (4-IBP), in glioblastoma were shown previously, leading to the present work where the effects on glioblastoma cells of 17 agonists or antagonists of sigma-1 receptors were studied, including currently marketed drugs fluvoxamine, dextromethorphan, donepezil, memantine and haloperidol. We first showed that established GBM cell lines, primary cultures and surgical specimens express sigma-1 receptors. In vitro analyses then focused on anti-proliferation and anti-migratory effects on human glioblastoma cell lines using quantitative videomicroscopy analyses. These cell monitoring assays revealed specific impacts on the mitotic cell process. Using an aggressive glioma model orthotopically grafted into the brains of immunocompromised mice, we showed that combining donepezil and temozolomide gave additive benefit in terms of long survivors as compared to temozolomide or donepezil alone. Clinical study is planned if further rodent dose-ranging studies of donepezil with temozolomide continue to show evidence of benefit in this model.



A. Capouillez, G. Debauve, C. Decaestecker, O. Filleul, D. Chevalier, G. Mortuaire, F. Coppée, X. Leroy, A. Belayew, S. Saussez,
The helicase-like transcription factor is a strong predictor of recurrence in hypopharyngeal but not in laryngeal squamous cell carcinomas.
Histopathology, Vol. 55, 1, pp. 77-90, 2009
Bibtex
Bibtex : info:hdl:2013/75904
Note : Comparative Study
Abstract : To examine the immunohistochemical expression of helicase-like transcription factor (HLTF) in relation to the prognosis of hypopharyngeal (HSCCs) and laryngeal (LSCCs) squamous cell carcinomas, and to characterize the HLTF protein variants expressed in biopsy specimens of head and neck squamous cell carcinoma (HNSCC) as well as the HeLa cell line.



S. Leyman, M. Sidani, L. Ritsma, D. Waterschoot, R. Eddy, D. Dewitte, O. Debeir, C. Decaestecker, J. Vandekerckhove, J. van Rheenen, C. Ampe, J. Condeelis, M. Van Troys,
Unbalancing the phosphatidylinositol-4,5-bisphosphate-cofilin interaction impairs cell steering.
Molecular biology of the cell, Vol. 20, 21, pp. 4509-4523, 2009
Bibtex
Bibtex : info:hdl:2013/52937
Note : Journal Article
Abstract : Cofilin is a key player in actin dynamics during cell migration. Its activity is regulated by (de)phosphorylation, pH, and binding to phosphatidylinositol-4,5-bisphosphate [PI(4,5)P(2)]. Here, we here use a human cofilin-1 (D122K) mutant with increased binding affinity for PI(4,5)P(2) and slower release from the plasma membrane to study the role of the PI(4,5)P(2)-cofilin interaction in migrating cells. In fibroblasts in a background of endogenous cofilin, D122K cofilin expression negatively affects cell turning frequency. In carcinoma cells with down-regulated endogenous cofilin, D122K cofilin neither rescues the drastic morphological defects nor restores the effects in cell turning capacity, unlike what has been reported for wild-type cofilin. In cofilin knockdown cells, D122K cofilin expression promotes outgrowth of an existing lamellipod in response to epidermal growth factor (EGF) but does not result in initiation of new lamellipodia. This indicates that, next to phospho- and pH regulation, the normal release kinetics of cofilin from PI(4,5)P(2) is crucial as a local activation switch for lamellipodia initiation and as a signal for migrating cells to change direction in response to external stimuli. Our results demonstrate that the PI(4,5)P(2) regulatory mechanism, that is governed by EGF-dependent phospholipase C activation, is a determinant for the spatial and temporal control of cofilin activation required for lamellipodia initiation.



Conferences

S. Safin, A. Defays, A. Billon, C. Decaestecker, N. Warzée,
Influence d’images évocatrices et distractrices sur une t{\^a}che de jugement en acoustique des salles
IHM 2009, ACM International Conference Proceeding Series, pp. 241-248, 2009
Bibtex
Bibtex : info:hdl:2013/71594
Note : Language of publication: en



N. Warzée, M. Groenen, J. Rosoux, O. Debeir, R. Ercek, C. Reichling,
Numérisation 3D de la grotte d'El Castillo (Puente Viesgo)
Actes du colloque Virtual Retrospect 2007, pp. 221-229, 2009
Bibtex
Bibtex : info:hdl:2013/71566
Note : Consultable à l'adresse suivante : http://archeovision.cnrs.fr/spip.php?article91



R. Ercek, D. Viviers, N. Warzée,
Reconstruction and Digitalization of an archaeological site, Itanos, Crete
International Meeting on Archaeology and Graphic Informatics, ARQUEOLOGICA 2.0, pp. 6, Sevilla (Spain), 2009
Bibtex
Bibtex : info:hdl:2013/127110
Note : Language of publication: en




2008

Papers

N. Sadeghi-Meibodi, N. D'Haene, C. Decaestecker, M. Levivier, T. Metens, C. Maris, D. Wikler, D. Balériaux, I. Salmon, S. Goldman,
Apparent diffusion coefficient and cerebral blood volume in brain gliomas: relation to tumor cell density and tumor microvessel density based on stereotactic biopsies.
American journal of neuroradiology, Vol. 29, 3, pp. 476-482, 2008
Bibtex
Bibtex : info:hdl:2013/51761
Note : Journal Article
Abstract : BACKGROUND AND PURPOSE: MR imaging-based apparent diffusion coefficient (ADC) and regional cerebral blood volume (rCBV) measurements have been related respectively to both cell and microvessel density in brain tumors. However, because of the high degree of heterogeneity in gliomas, a direct correlation between these MR imaging-based measurements and histopathologic features is required. The purpose of this study was to correlate regionally ADC and rCBV values with both cell and microvessel density in gliomas, by using coregistered MR imaging and stereotactic biopsies. MATERIALS AND METHODS: Eighteen patients (9 men, 9 women; age range, 19-78 years) with gliomas underwent diffusion-weighted and dynamic susceptibility contrast-enhanced MR imaging before biopsy. Eighty-one biopsy samples were obtained and categorized as peritumoral, infiltrated tissue, or bulk tumor, with quantification of cell and microvessel density. ADC and rCBV values were measured at biopsy sites and were normalized to contralateral white matter on corresponding maps coregistered with a 3D MR imaging dataset. ADC and rCBV ratios were compared with quantitative histologic features by using the Spearman correlation test. RESULTS: The highest correlations were found within bulk tumor samples between rCBV and cell density (r=0.57, P < .001) and rCBV and microvessel density (r=0.46, P < .01). An inverse correlation was found between ADC and microvessel density within bulk tumor (r=-0.36, P < .05), whereas no significant correlation was found between ADC and cell density. CONCLUSION: rCBV regionally correlates with both cell and microvessel density within gliomas, whereas no regional correlation was found between ADC and cell density.



A. Pozdzik, I. Salmon, F. Debelle, C. Decaestecker, C. Van den Branden, D. Verbeelen, M. Deschodt Lanckman, J. Vanherweghem, J. Nortier,
Aristolochic acid induces proximal tubule apoptosis and epithelial to mesenchymal transformation.
Kidney international, Vol. 73, 5, pp. 595-607, 2008
Bibtex
Bibtex : info:hdl:2013/53619
Note : Journal Article
Abstract : Aristolochic acid contamination in herbal remedies leads to interstitial fibrosis, tubular atrophy, and renal failure in humans. To study the cellular mechanisms contributing to the pathophysiology of this renal disease, we studied Wistar rats treated with aristolochic acid and measured tubular and interstitial cell proliferation, epithelial/mesenchymal cell marker expression, tubular membrane integrity, myofibroblast accumulation, oxidative stress, mitochondrial damage, tubular apoptosis, and fibrosis. Oxidative stress, a loss of cadherin concomitant with vimentin expression, basement membrane denudation with active caspase-3 expression, and mitochondrial injury within tubular cells were evident within 5 days of administration of the toxin. During the chronic phase, interstitial mesenchymal cells accumulated in areas of collagen deposits. Impaired regeneration and apoptosis of proximal tubular cells resulted in tubule atrophy with a near absence of dedifferentiated cell transmembrane migration. We suggest that resident fibroblast activation plays a critical role in the process of renal fibrosis during aristolochic acid toxicity.



N. D'Haene, X. Catteau, C. Maris, B. Martin, I. Salmon, C. Decaestecker,
Endothelial hyperplasia and endothelial galectin-3 expression are prognostic factors in primary central nervous system lymphomas.
British journal of haematology, Vol. 140, 4, pp. 402-410, 2008
Bibtex
Bibtex : info:hdl:2013/53617
Note : Journal Article
Abstract : Recently, considerable attention has been focused on the identification of clinically relevant prognostic markers for primary central nervous system lymphomas (PCNSL). The present study investigated whether three morphological features, i.e. necrosis, reactive perivascular T-cell infiltrate and endothelial hyperplasia, and galectin-1 and galectin-3 immunohistochemical expression have prognostic roles in a series of 58 PCNSL samples from 44 immunocompetent and 14 immunocompromised patients. The presence of endothelial hyperplasia (identified in 21\% of the assessable cases) was identified as a bad prognostic factor for immunocompetent PCNSL patients, whereas the other morphological features were not associated with any prognostic value. Lymphomatous cells of eight PCNSL cases expressed galectin-3 without any prognostic value, and lymphomatous cells did not express galectin-1. In contrast, endothelial expression of galectin-3 was identified (by means of uni- and multi-variate analyses) as a bad prognostic factor for immunocompetent PCNSL patients. In addition, a combination of endothelial hyperplasia and/or endothelial galectin-3 expression was shown to be an independent prognostic factor for immunocompetent PCNSL patients treated with methotrexate-based chemotherapy. In summary, this study suggests that endothelial-related markers can identify risk groups of PCNSL patients and indicates that galectin-3 could be involved in PCNSL angiogenesis.



M. Le Mercier, F. Lefranc, T. Mijatovic, O. Debeir, B. Haibe-Kains, G. Bontempi, C. Decaestecker, R. Kiss, V. Mathieu,
Evidence of galectin-1 involvement in glioma chemoresistance.
Toxicology and applied pharmacology, Vol. 229, 2, pp. 172-183, 2008
Bibtex
Bibtex : info:hdl:2013/51198
Note : Journal Article
Abstract : Glioblastomas (GBMs) are resistant to apoptosis but less so to autophagy; a fact that may at least partly explain the therapeutic benefits of the pro-autophagic drug temozolomide in the treatment of GBM patients. Galectin-1 (Gal1) whose expression is stimulated by hypoxia is a potent modulator of GBM cell migration and a pro-angiogenic molecule. Hypoxia is also known to confer cancer cells with resistance to chemotherapy and radiotherapy and to modulate the unfolded protein response (UPR) during endoplasmic reticulum (ER) stress. The present study investigates whether decreasing Gal1 expression (by means of a siRNA approach) in human Hs683 GBM cells increases their sensitivity to pro-autophagic or pro-apoptotic drugs. The data reveal that temozolomide, the standard treatment for glioma patients, increases Gal1 expression in Hs683 cells both in vitro and in vivo. However, reducing Gal1 expression in these cells by siRNA increases the anti-tumor effects of various chemotherapeutic agents, in particular temozolomide both in vitro and in vivo. This decrease in Gal1 expression in Hs683 cells does not induce apoptotic or autophagic features, but is found to modulate p53 transcriptional activity and decrease p53-targeted gene expression including DDIT3/GADD153/CHOP, DUSP5 ATF3 and GADD45A. The decrease in Gal1 expression also impairs the expression levels of seven other genes implicated in chemoresistance: ORP150, HERP, GRP78/Bip, TRA1, BNIP3L, GADD45B and CYR61, some of which are located in the ER and whose expression is also known to be modified by hypoxia. This novel facet of Gal1 involvement in glioblastoma biology may be amenable to therapeutic manipulation.



P. Dumont, A. Berton, N. Nagy, F. Sandras, S. Tinton, P. Demetter, F. Mascart, A. Allaoui, C. Decaestecker, I. Salmon,
Expression of galectin-3 in the tumor immune response in colon cancer.
Laboratory investigation, Vol. 88, 8, pp. 896-906, 2008
Bibtex
Bibtex : info:hdl:2013/50112
Note : Journal Article
Abstract : The role of tumor-associated macrophages (TAMs) is controversial. Although most studies on different cancer types associate them with a poorer prognosis, interestingly in colon cancer, most articles indicate that TAMs prevent tumor development; patients with high TAMs have better prognosis and survival rate. M1-polarized macrophages produce high level of tumor necrosis factor-alpha, interleukin-1 beta or reactive oxygen species, which can effectively kill susceptible tumor cells. In contrast, M2-polarized macrophages can secrete different factors that promote tumor cell growth and survival or favor angiogenesis and tissue invasion. Considering the beneficial role of TAMs in colon cancer, we speculated that they may not display the M2 polarization commonly observed in tumor microenvironment, but rather develop M1 properties. Therefore, we used an in vitro model to analyze the effects of supernatants from M1-polarized macrophages on DLD-1 colon cancer cells. Our data indicate that the conditioned medium from LPS-activated macrophages (CM-LAM) contains a high level of granulocyte-macrophage colony-stimulating factor, interleukins-1 beta, -6, -8 and tumor necrosis factor-alpha, and that it exerts a marked growth inhibitory activity on DLD-1 cells. Prolonged exposure to CM-LAM results in cell death by apoptosis. Such exposure to CM-LAM leads to the modulation of gal-3 expression: we observed a marked downregulation of gal-3 mRNA and protein expression following CM-LAM treatment. We also describe that the knockdown of gal-3 sensitizes DLD-1 cells to CM-LAM. These data suggest an involvement of gal-3 in the response of colon cancer cells to proinflammatory stimuli, such as the conditioned medium from activated macrophages.



A. Mathieu, N. Nagy, C. Decaestecker, L. Ferdinande, K. Vandenbroucke, P. Rottiers, C. Cuvelier, I. Salmon, P. Demetter,
Expression of galectins-1, -3 and -4 varies with strain and type of experimental colitis in mice.
International journal of experimental pathology, Vol. 89, 6, pp. 438-446, 2008
Bibtex
Bibtex : info:hdl:2013/54123
Note : Comparative Study
Abstract : Galectins are increasingly the focus of biomedical research. Although they are involved at different stages in inflammation, data on galectins in colitis remain scarce. The aim of this study was to determine and compare the expression of galectins in acute and chronic experimental colitis in mice. Immunohistochemistry for galectins-1, -3 and -4 was performed on colon tissue from C57BL/6 and BALB/c mice with acute dextran sodium sulphate colitis and from 129 Sv/Ev IL-10 knock-out (IL-10(-/-)) mice. From these three mouse strains, we first detected major differences in galectin expression related to the genetic background in the control animals. With regard to inflammation, chronic colitis in IL-10(-/-) mice was associated with increased galectin-4 expression; in contrast with the two other models, no galectin-1 and -3 alterations were observed in IL-10(-/-) mice. Acute colitis in C57BL/6 and BALB/c mice showed increased galectin-3 expression in the lamina propria and the crypt epithelium, together with a decreased nuclear expression. These results suggest an involvement of galectins in the development and perpetuation of colonic inflammation and illustrate that the choice of the mouse strain for studying galectins might influence the outcome of the experiments.



S. Saussez, C. Decaestecker, V. Mahillon, S. Cludts, A. Capouillez, D. Chevalier, H. Vet, S. André, G. Toubeau, X. Leroy, H. Gabius,
Galectin-3 upregulation during tumor progression in head and neck cancer.
The Laryngoscope, Vol. 118, 9, pp. 1583-1590, 2008
Bibtex
Bibtex : info:hdl:2013/75908
Note : Comparative Study
Abstract : To examine the level of expression of galectin-3 in relation to neoplastic progression of hypopharyngeal squamous cell carcinomas (HSCCs) and laryngeal squamous cell carcinomas (LSCCs).



A. Capouillez, C. Decaestecker, O. Filleul, D. Chevalier, F. Coppee, X. Leroy, A. Belayew, S. Saussez,
Helicase-like transcription factor exhibits increased expression and altered intracellular distribution during tumor progression in hypopharyngeal and laryngeal squamous cell carcinomas.
Virchows Archiv, Vol. 453, 5, pp. 491-499, 2008
Bibtex
Bibtex : info:hdl:2013/75907
Note : Journal Article
Abstract : The helicase-like transcription factor (HLTF) belongs to the SWI/SNF family of proteins that use the energy from adenosine triphosphate hydrolysis to remodel chromatin during a variety of cellular processes. HLTF is also involved in DNA repair. Using computer-assisted microscopy, the immunohistochemical expression of HLTF was determined using a series of 100 hypopharyngeal and 56 laryngeal squamous cell carcinomas (SCCs) compared to tumor-free epithelia (60 cases) and dysplasias (92 cases). In hypopharyngeal SCC tumor progression, increased HLTF expression was associated with the percentage of immunopositive epithelial tissue areas (p = 0.02) and the staining intensity of the positive area (p = 0.0005). In the cases of laryngeal lesions, the immunolabeling intensity of HLTF significantly decreased with malignancy (p = 0.01). We also observed a significant shift of HLTF expression from the cytoplasm toward the nuclear compartment (p = 0.0007). Our data reveal an association between the presence of HLTF and neoplastic progression of hypopharyngeal and laryngeal SCCs.



S. Saussez, C. Decaestecker, F. Lorfevre, D. Chevalier, G. Mortuaire, H. Kaltner, S. André, G. Toubeau, H. Gabius, X. Leroy,
Increased expression and altered intracellular distribution of adhesion/growth-regulatory lectins galectins-1 and -7 during tumour progression in hypopharyngeal and laryngeal squamous cell carcinomas.
Histopathology, Vol. 52, 4, pp. 483-493, 2008
Bibtex
Bibtex : info:hdl:2013/75909
Note : Comparative Study
Abstract : To examine the level of expression of the pleiotropic regulators galectins-1 and -7 in relation to neoplastic progression of hypopharyngeal (HSCCs) and laryngeal (LSCCs) squamous cell carcinomas.



M. Le Mercier, V. Mathieu, B. Haibe-Kains, G. Bontempi, T. Mijatovic, C. Decaestecker, R. Kiss, F. Lefranc,
Knocking down galectin 1 in human hs683 glioblastoma cells impairs both angiogenesis and endoplasmic reticulum stress responses.
Journal of neuropathology and experimental neurology, Vol. 67, 5, pp. 456-469, 2008
Bibtex
Bibtex : info:hdl:2013/51203
Note : Journal Article
Abstract : Galectin (Gal) 1 is a hypoxia-regulated proangiogenic factor that also directly participates in glioblastoma cell migration. To determine how Gal-1 exerts its proangiogenic effects, we investigated Gal-1 signaling in the human Hs683 glioblastoma cell line. Galectin 1 signals through the endoplasmic reticulum transmembrane kinase/ribonuclease inositol-requiring 1alpha, which regulates the expression of oxygen-regulated protein 150. Oxygen-regulated protein 150 controls vascular endothelial growth factor maturation. Galectin 1 also modulates the expression of 7 other hypoxia-related genes (i.e. CTGF, ATF3, PPP1R15A, HSPA5, TRA1, and CYR61) that are implicated in angiogenesis. Decreasing Gal-1 expression in Hs683 orthotopic xenografts in mouse brains by siRNA administration impaired endoplasmic reticulum stress and enhanced the therapeutic benefits of the proautophagic drug temozolomide. These results suggest that decreasing Gal-1 expression (e.g. through brain delivery of nonviral infusions of anti-Gal-1 siRNA in patients) can represent an additional therapeutic strategy for glioblastoma.



A. Lemy, K. Wissing, S. Rorive, A. Zlotta, T. Roumeguere, M. Muniz Martinez, C. Decaestecker, I. Salmon, D. Abramowicz, J. Vanherweghem, J. Nortier,
Late onset of bladder urothelial carcinoma after kidney transplantation for end-stage aristolochic acid nephropathy: a case series with 15-year follow-up.
American journal of kidney diseases, Vol. 51, 3, pp. 471-477, 2008
Bibtex
Bibtex : info:hdl:2013/53618
Note : Journal Article
Abstract : BACKGROUND: Aristolochic acids are nephrotoxins and predispose to upper-tract urothelial carcinoma. The risk of bladder urothelial carcinoma after kidney transplantation and its relationship to upper-tract urothelial carcinoma is not well defined. STUDY DESIGN: Case series. SETTING & PARTICIPANTS: Single-center cohort of 38 women given kidney transplants for end-stage aristolochic acid nephropathy. OUTCOMES & MEASUREMENTS: The prevalence of upper urinary tract urothelial carcinoma was determined by collecting pathological results of specimens obtained by means of bilateral ureteronephrectomy. We also established the cumulative incidence of bladder urothelial carcinoma in biopsies performed during prospective screening cystoscopies during a 15-year follow-up. RESULTS: Upper-tract urothelial carcinoma was found in 17 patients with aristolochic acid nephropathy (44.7\%). During follow-up, bladder urothelial carcinoma was diagnosed in 15 patients 68 to 169 months after cessation of aristolochic acid exposure (39.5\%): 8 urothelial carcinoma in situ, 4 noninvasive low-grade papillary urothelial carcinoma, and 3 infiltrating urothelial carcinoma. 12 of 17 patients (71\%) with a history of upper-tract urothelial carcinoma developed bladder urothelial carcinoma during follow-up, whereas this occurred in only 3 of 21 patients (14\%) without upper-tract urothelial carcinoma (P < 0.01). Despite local and/or systemic chemotherapy, 3 patients died and 2 radical cystectomies were performed. LIMITATIONS: Small sample size of this case series. CONCLUSIONS: Upper-tract and bladder urothelial carcinoma are dramatic complications in kidney transplant recipients with aristolochic acid nephropathy, confirming the carcinogenic properties of aristolochic acids. We identified upper-tract urothelial carcinoma as a potent risk factor for the subsequent development of bladder urothelial carcinoma after kidney transplantation for aristolochic acid nephropathy. Because this complication may occur years after aristolochic acid discontinuation, we suggest regular cystoscopies in addition to the bilateral ureteronephrectomy in kidney transplant recipients with aristolochic acid nephropathy.



S. Rorive, A. Berton, N. D'Haene, C. Takacs, O. Debeir, C. Decaestecker, I. Salmon,
Matrix metalloproteinase-9 interplays with the IGFBP2-IGFII complex to promote cell growth and motility in astrocytomas.
GLIA, Vol. 56, 15, pp. 1679-1690, 2008
Bibtex
Bibtex : info:hdl:2013/52950
Note : Journal Article
Abstract : Insulin-like growth factor II (IGFII) acts as a potent mitogen for several tumor types and has been reported to positively influence astrocytoma cell growth and motility. In the central nervous system, IGFII bioavailability is mainly modulated by insulin-like growth factor binding protein 2 (IGFBP2), which sequestrates IGFII and therefore prevents its interaction with the type-1 IGF receptor (IGF-IR). Proteolysis of IGFBP2 is the predominant mechanism recognized to reduce the binding affinity of IGFBP2 for IGFII, thus favoring dissociation of IGFII from the IGFBP2-IGFII complex. It is known that certain proteases involved in astrocytoma malignancy, such as matrix metalloproteinase-7 (MMP-7), plasmin, and cathepsin D, are able to proteolyze IGFBP2 in vitro. The present study aims to investigate whether other proteases expressed by astrocytomas, specifically MMP-2, MMP-9, and membrane-type 1 matrix metalloprotease (MT1-MMP), are able to proteolyze the IGFBP2-IGFII complex. Our results show the following: (i) MMP-9 proteolyzes the IGFBP2-IGFII complex in vitro, while MMP-2 and MT1-MMP do not; (ii) this MMP-9-induced IGFBP2-IGFII complex proteolysis releases free IGFII, which contributes to enhance the motility and the growth of LN229 astrocytoma cells. Furthermore, this study also highlights that the formation of the IGFBP2-IGFII complex inhibits IGFBP2's cell motility promoting effect by reducing the pool of free IGFBP2. In conclusion, MMP-9-induced IGFBP2 proteolysis may be regarded as an important post-translational event involved in astrocytoma aggressiveness. These new findings support drug targeting of MMP-9 as an interesting approach in the treatment of astrocytoma.



T. Mijatovic, N. De Nève, P. Gailly, V. Mathieu, B. Haibe-Kains, G. Bontempi, J. Lapeira, C. Decaestecker, V. Facchini, R. Kiss,
Nucleolus and c-Myc: potential targets of cardenolide-mediated antitumor activity.
Molecular cancer therapeutics, Vol. 7, 5, pp. 1285-1296, 2008
Bibtex
Bibtex : info:hdl:2013/52071
Note : Journal Article
Abstract : The use of cardenolides like ouabain, digitoxin, or oleandrin has been reported previously many times as a means of potentially combating human refractory prostate cancer by inducing apoptosis through an increase in intracellular calcium concentrations. The aims of the current study were to investigate if part of the antitumor effects mediated by cardenolides concerned disorganization of nucleolar structure and whether this was further associated with a marked decrease in c-Myc expression. Accordingly, the antitumor activity of a novel hemisynthetic cardenolide [1R,3aS,3bR,5aS,6aR,7aS,9R,12aR,13aR,15aR]-3a,11a-dihydroxy-13a-(hydroxymethyl)-9,15a-dimethyl-1-(5-oxo-2,5-dihydrofuran-3-yl)icosahydro-1H,4'H-spiro[cyclopenta [7,8]phenanthro[2,3-b]pyrano[3,2-e][1,4]dioxine-11,2'-[1,3]thiazolidin]-4'-one (UNBS1450)] was compared with that of classic cardenolides and reference anticancer agents in prostate cancer cell lines in vitro and in vivo following s.c. and orthotopic prostate cancer cell grafting into mice. The present study indicates that UNBS1450 markedly decreases the in vitro viability/proliferation of human prostate cancer cell lines but not of normal cells. The induced effects are not linked to an increase in intracellular calcium concentrations and subsequent induction of apoptosis. Rather, they appear to relate to the compound's capacity to disorganize nucleolar structure and function (through an impairment of cyclin-dependent kinase and c-Myc expression and related signaling pathways; paralleled by the disorganization of cancer cell-specific perinucleolar bodies as revealed by disruption of Sam68). This nonapoptotic cancer cell death mediated by severe nucleolar targeting and down-regulation of c-Myc expression is a completely new cardenolide-induced mechanism of antitumor action.



A. Pozdzik, I. Salmon, C. Husson, C. Decaestecker, E. Rogier, M. Bourgeade, M. Deschodt Lanckman, J. Vanherweghem, J. Nortier,
Patterns of interstitial inflammation during the evolution of renal injury in experimental aristolochic acid nephropathy.
Nephrology, dialysis, transplantation, Vol. 23, 8, pp. 2480-2491, 2008
Bibtex
Bibtex : info:hdl:2013/53622
Note : Journal Article
Abstract : BACKGROUND: Interstitial inflammation is a prominent feature associated with the severity of renal injury and progressive kidney failure. We utilized an animal model of aristolochic acid (AA)-induced nephropathy (AAN) to assess patterns of infiltration and inflammation during the evolution of tubulointerstitial damage and to relate them to the development of fibrosis. METHODS: Male Wistar rats receiving sc daily AA or vehicle were sacrificed between Days 1 and 35. Infiltrating mononuclear cells were characterized by immunohistochemistry. The kidney infiltrating T lymphocytes were phenotyped by flow cytometry. Urinary levels of Th-1/ Th-2 cytokines, of monocyte chemoattractant protein-1 and of active transforming growth factor-beta (TGF-beta) were measured. Tissue expression of phosphorylated smad 2/3 protein was used to examine the TGF-beta signalling pathway. RESULTS: In AA rats, monocytes/macrophages and T lymphocytes predominantly infiltrated areas of necrotic proximal tubular cells. The coexpressions of ED1 and/or Ki-67/MHCII by infiltrating cells reflected monocyte/macrophage proliferation and their activation, respectively. The accumulation of cytotoxic T lymphocytes was attested by severe signs of CD8+ cell tubulitis. The CD8/E-cadherin costaining confirmed intrarenal homing of CD8+CD103+ cells. Urinary levels of proinflammatory cytokines and of active TGF-beta significantly increased at Days 10 and 35. An early and persistent nuclear overexpression of phosphorylated smad 2/3 protein was detected in tubular and interstitial compartments. CONCLUSION: An early and massive interstitial inflammation characterized by activated monocytes/macrophages and cytotoxic CD8+CD103+ T lymphocytes is demonstrated for the first time during the progression of experimental AAN. The involvement in an interstitial fibrosis onset of active TGF-beta is highly suggested, at least via the psmad 2/3 intracellular signalling pathway.



C. Maris, S. Rorive, F. Sandras, N. D'Haene, N. Sadeghi-Meibodi, I. Bièche, M. Vidaud, C. Decaestecker, I. Salmon,
Tenascin-C expression relates to clinicopathological features in pilocytic and diffuse astrocytomas.
Neuropathology and applied neurobiology, Vol. 34, 3, pp. 316-329, 2008
Bibtex
Bibtex : info:hdl:2013/53624
Note : Journal Article
Abstract : AIMS: Tenascin-C (TN-C) is an extracellular matrix brain glycoprotein for which conflicting in vitro and in vivo results are reported in the literature dealing with its involvement in astrocytoma aggressiveness, in particular astrocytoma invasion. In view of these conflicting results and the lack of data available on low-grade astrocytomas, the present study focuses on pilocytic World Health Organization (WHO) grade I, and diffuse WHO grade II astrocytomas, that is, two histological entities associated with very different invasive abilities. METHODS: Using real-time reverse transcription polymerase chain reaction and immunohistochemistry, we analysed the TN-C expression in normal brain tissue as well as in a series of 54 pilocytic and 53 grade II astrocytomas. CONCLUSIONS: Our data on normal brain showed that while TN-C is largely expressed in supratentorial white matter, it was largely absent in infratentorial white matter. Paralleling these observations, we showed that TN-C expression in low-grade astrocytomas similarly varies according to tumour site. Cox regression analysis evidenced that TN-C provided an independent prognostic value which is enhanced in the case of grade II astrocytomas for which positive TN-C expression is associated with a higher risk of recurrence. We also analysed TN-C expression specifically in vascular areas of low-grade astrocytomas without demonstrating any prognostic value for this additional feature. RESULTS: Similarly to normal brain, low-grade astrocytomas exhibit variations in TN-C expression with site, and this expression is associated with an independent prognostic value in terms of recurrence.



S. Saussez, F. Lorfevre, T. Lequeux, G. Laurent, G. Chantrain, F. Vertongen, G. Toubeau, C. Decaestecker, R. Kiss,
The determination of the levels of circulating galectin-1 and -3 in HNSCC patients could be used to monitor tumor progression and/or responses to therapy.
Oral oncology, Vol. 44, 1, pp. 86-93, 2008
Bibtex
Bibtex : info:hdl:2013/52093
Note : Journal Article
Abstract : To evaluate galectin-1, -3 and -7 serum levels as diagnostic and/or prognostic markers for head and neck squamous cell carcinomas (HNSCCs). ELISA was employed to test sera from 102 patients with HNSCCs and from 38 healthy control volunteers for galectin-1, -3 and -7 serum levels. Serum galectin levels were assayed by ELISA and the levels of galectin expression in HNSCCs were determined by means of immunohistochemistry. HNSCCs display significant immunohistochemical amounts of galectin-7, but this galectin cannot be detected in the blood of HNSCC patients. Galectin-3 levels differ significantly (p=0.03) in healthy volunteers and HNSCC patients. Using a threshold value of 4.3 ng/ml, galectin-3 serum level enabled a significant level of discrimination (p=0.03) to be established between the cancer patients and the healthy volunteers, with 90\% level of specificity and 36\% level of sensitivity. The discrimination was even better when using a threshold value of 13.5 ng/ml for galectin-1 (p=0.001), with 100\% level of specificity and 22\% level of sensitivity. A subgroup of stage IV HNSCC patients displayed significantly reduced levels of circulating galectin-1 (p=0.003) and galectin-3 (p=0.001) after treatment as opposed to before. Galectin-3 concentrations in sera from the patients with a metastatic disease were significantly (p=0.01) higher than in sera from the patients with localized tumors. The determination of circulating levels of galectin-1 and -3 could be used to monitor the progression of their disease or their response to therapy.



P. Demetter, N. Nagy, B. Martin, A. Mathieu, P. Dumont, C. Decaestecker, I. Salmon,
The galectin family and digestive disease.
Journal of pathology, Vol. 215, 1, pp. 1-12, 2008
Bibtex
Bibtex : info:hdl:2013/53621
Note : Journal Article
Abstract : The soluble-type lectins or galectins constitute a family of proteins defined by shared consensus amino acid sequence and affinity for beta-galactose-containing oligosaccharides. These molecules are widely distributed in the animal kingdom; to date, 15 mammalian galectins have been described but more are likely to be discovered. These proteins are involved in many biological processes including cell-cell and cell-matrix adhesion, growth regulation, signaling, and cytokine secretion. Over the last decade, a vast amount of reports has shown the importance of several galectins in the development and progression of malignancies in the digestive tract, mainly colorectal cancers. More recent data indicate that some of these molecules are also involved in inflammatory bowel diseases. This review focuses on the current knowledge of galectin expression and putative functions in the oesophagus, stomach, small intestine, and colon. It also highlights that the rapid accumulation of research data promises future scenarios in which individual members of the galectin family and/or their ligands will be used as diagnostic and therapeutic modalities for neoplastic as well as inflammatory disorders. However, the concretization of these potential modalities requires substantial improvements in terms of standardization of galectin expression evaluation together with prospective validation of the present data.



T. Mijatovic, T. Mahieu, C. Bruyère, N. De Nève, J. Dewelle, G. Simon, M. Dehoux, E. van der Aar, B. Haibe-Kains, G. Bontempi, C. Decaestecker, E. Van Quaquebeke, F. Darro, R. Kiss,
UNBS5162, a novel naphthalimide that decreases CXCL chemokine expression in experimental prostate cancers.
Neoplasia (New York, N.Y.), Vol. 10, 6, pp. 573-586, 2008
Bibtex
Bibtex : info:hdl:2013/52069
Note : Journal Article
Abstract : Several naphthalimides have been evaluated clinically as potential anticancer agents. UNBS3157, a naphthalimide that belongs to the same class as amonafide, was designed to avoid the specific activating metabolism that induces amonafide's hematotoxicity. The current study shows that UNBS3157 rapidly and irreversibly hydrolyzes to UNBS5162 without generating amonafide. In vivo UNBS5162 after repeat administration significantly increased survival in orthotopic human prostate cancer models. Results obtained by the National Cancer Institute (NCI) using UNBS3157 and UNBS5162 against the NCI 60 cell line panel did not show a correlation with any other compound present in the NCI database, including amonafide, thereby suggesting a unique mechanism of action for these two novel naphthalimides. Affymetrix genome-wide microarray analysis and enzyme-linked immunosorbent assay revealed that in vitro exposure of PC-3 cells to UNBS5162 (1 microM for 5 successive days) dramatically decreased the expression of the proangiogenic CXCL chemokines. Histopathology additionally revealed antiangiogenic properties in vivo for UNBS5162 in the orthotopic PC-3 model. In conclusion, the present study reveals UNBS5162 to be a pan-antagonist of CXCL chemokine expression, with the compound displaying antitumor effects in experimental models of human refractory prostate cancer when administered alone and found to enhance the activity of taxol when coadministered with the taxoid.



O. Debeir, V. Megalizzi, N. Warzée, R. Kiss, C. Decaestecker,
Videomicroscopic extraction of specific information on cell proliferation and migration in vitro.
Experimental cell research, Vol. 314, 16, pp. 2985-2998, 2008
Bibtex
Bibtex : info:hdl:2013/52065
Note : Journal Article
Abstract : In vitro cell imaging is a useful exploratory tool for cell behavior monitoring with a wide range of applications in cell biology and pharmacology. Combined with appropriate image analysis techniques, this approach has been shown to provide useful information on the detection and dynamic analysis of cell events. In this context, numerous efforts have been focused on cell migration analysis. In contrast, the cell division process has been the subject of fewer investigations. The present work focuses on this latter aspect and shows that, in complement to cell migration data, interesting information related to cell division can be extracted from phase-contrast time-lapse image series, in particular cell division duration, which is not provided by standard cell assays using endpoint analyses. We illustrate our approach by analyzing the effects induced by two sigma-1 receptor ligands (haloperidol and 4-IBP) on the behavior of two glioma cell lines using two in vitro cell models, i.e., the low-density individual cell model and the high-density scratch wound model. This illustration also shows that the data provided by our approach are suggestive as to the mechanism of action of compounds, and are thus capable of informing the appropriate selection of further time-consuming and more expensive biological evaluations required to elucidate a mechanism.



Conferences

O. Debeir, I. Adanja, N. Warzée, P. Van Ham, C. Decaestecker,
Phase contrast image segmentation by weak watershed transform assembly
Proceedings of 5th IEEE International Symposium on Biomedical Imaging : From Nano to Macro (ISBI), pp. 724-727, ISBI)(Paris, France, 2008
Bibtex
Bibtex : info:hdl:2013/53020
Note : Language of publication: en



Books chapters

O. Debeir, I. Adanja, R. Kiss, C. Decaestecker,
Models of cancer cell migration and cellular imaging and analysis
Anja Lambrechts, Christophe Ampe (Eds). The Motile Actin System in Health and Disease, pp. 123-156, 2008
Bibtex
Bibtex : info:hdl:2013/99600
Note : Language of publication: en




2007

Papers

V. Megalizzi, V. Mathieu, T. Mijatovic, P. Gailly, O. Debeir, N. De Nève, M. Van Damme, G. Bontempi, B. Haibe-Kains, C. Decaestecker, Y. Kondo, R. Kiss, F. Lefranc,
4-IBP, a sigma1 receptor agonist, decreases the migration of human cancer cells, including glioblastoma cells, in vitro and sensitizes them in vitro and in vivo to cytotoxic insults of proapoptotic and proautophagic drugs.
Neoplasia (New York, N.Y.), Vol. 9, 5, pp. 358-369, 2007
Bibtex
Bibtex : info:hdl:2013/51212
Note : Journal Article
Abstract : Although the molecular function of sigma receptors has not been fully defined and the natural ligand(s) is still not known, there is increasing evidence that these receptors and their ligands might play a significant role in cancer biology. 4-(N-benzylpiperidin-4-yl)-4-iodobenzamide (4-IBP), a selective sigma1 agonist, has been used to investigate whether this compound is able to modify: 1) in vitro the migration and proliferation of human cancer cells; 2) in vitro the sensitivity of human glioblastoma cells to cytotoxic drugs; and 3) in vivo in orthotopic glioblastoma and non-small cell lung carcinoma (NSCLC) models the survival of mice co-administered cytotoxic agents. 4-IBP has revealed weak antiproliferative effects on human U373-MG glioblastoma and C32 melanoma cells but induced marked concentration-dependent decreases in the growth of human A549 NSCLC and PC3 prostate cancer cells. The compound was also significantly antimigratory in all four cancer cell lines. This may result, at least in U373-MG cells, from modifications to the actin cytoskeleton. 4-IBP modified the sensitivity of U373-MG cells in vitro to proapoptotic lomustin and proautophagic temozolomide, and markedly decreased the expression of two proteins involved in drug resistance: glucosylceramide synthase and Rho guanine nucleotide dissociation inhibitor. In vivo, 4-IBP increased the antitumor effects of temozolomide and irinotecan in immunodeficient mice that were orthotopically grafted with invasive cancer cells.



C. Decaestecker, O. Debeir, P. Van Ham, R. Kiss,
Can anti-migratory drugs be screened in vitro? A review of 2D and 3D assays for the quantitative analysis of cell migration.
Medicinal research reviews, Vol. 27, 2, pp. 149-176, 2007
Bibtex
Bibtex : info:hdl:2013/51824
Note : Journal Article
Abstract : The aim of the present review is to detail and analyze the pros and cons of in vitro tests available to quantify the anti-migratory effects of anti-cancer drugs for their eventual use in combating the dispersal of tumor cells, a clinical need which currently remains unsatisfied. We therefore briefly sum up why anti-migratory drugs constitute a promising approach in oncology while at the same time emphasizing that migrating cancer cells are resistant to apoptosis. To analyze the pros and cons of the various in vitro tests under review we also briefly sum up the molecular and cellular stages of cancer cell migration, an approach that enables us to argue both that no single in vitro test is sufficient to characterize the anti-migratory potential of a drug and that standardization is needed for the efficient quantitative analysis of cell locomotion in a 3D environment. Before concluding our review we devote the final two parts (i) to the description of new prototypes which, in the near future, could enter the screening process with a view to identifying novel anti-migratory compounds, and (ii) to the anti-migratory compounds currently developed against cancer, with particular emphasis on how these compounds were selected before entering the clinical trial phase.



S. Saussez, C. Decaestecker, F. Lorfevre, D. Cucu, G. Mortuaire, D. Chevalier, A. Wacreniez, H. Kaltner, S. André, G. Toubeau, I. Camby, H. Gabius, R. Kiss,
High level of galectin-1 expression is a negative prognostic predictor of recurrence in laryngeal squamous cell carcinomas.
International journal of oncology, Vol. 30, 5, pp. 1109-1117, 2007
Bibtex
Bibtex : info:hdl:2013/52089
Note : Journal Article
Abstract : Monitoring of gene-expression profiles is assumed to refine tumor characterization of laryngeal squamous cell carcinomas (LSCCs) with a therapeutic perspective. This is especially expected for adhesion/growth-regulatory effectors such as galectins, a class of endogenous lectins. Using computer-assisted microscopy, we investigated the prognostic value contributed by the quantitative determination of the immunohistochemical levels of expression of galectin-1, -3 and -7 in a series of 62 LSCCs including 42 low- and 20 high-stage LSCCs. As galectin-1 may have a key role leading to a tumor escape from immune surveillance, we also investigated whether or not the level of galectin-1 expression correlated with lymphocyte infiltration in LSCCs. The immunohistochemical determination of expression of galectin-1 is of prognostic value in human squamous laryngeal cancers. LSCCs that display high levels of galectin-1 have worse prognoses than laryngeal cancers with low levels of galectin-1 expression. Elevation of galectin-1 levels in laryngeal cancers can contribute to the process of tumor immune escape by killing the activated T-cells and other protumoral activities such as promoting motility or activity of oncogenic H-Ras proteins. The quantitative determination of galectin-1 in LSCCs is an independent prognostic marker when opposed to TNM staging. It has the potential to identify patients unlikely to benefit from T-cell-mediated immunotherapy, although the definitive effector function from its pro- and antitumoral activity profile has not been delineated.



T. Mijatovic, P. Gailly, V. Mathieu, N. De Nève, P. Yeaton, R. Kiss, C. Decaestecker,
Neurotensin is a versatile modulator of in vitro human pancreatic ductal adenocarcinoma cell (PDAC) migration.
Cellular oncology, Vol. 29, 4, pp. 315-326, 2007
Bibtex
Bibtex : info:hdl:2013/52082
Note : Journal Article
Abstract : BACKGROUND: While the neurotensin (NT) roles in pancreatic cancer growth are well documented, its effects on pancreatic cancer cell migration have not been described. METHODS: The NT-induced effects on the migration process of human pancreatic ductal adenocarcinoma cells (PDACs) were characterized by means of various assays including computer-assisted video-microscopy, fluorescence microscopy, ELISA-based, small GTPase pull-down and phosphorylation assays. RESULTS: The NT-induced modifications on in vitro PDACs migration largely depended on the extra-cellular matrix environment and cell propensity to migrate collectively or individually. While NT significantly reduced the level of migration of collectively migrating PDACs on vitronectin, it significantly increased the level of individually migrating PDACs. These effects were mainly mediated through the sortilin/NTR3 receptor. Neurotensin both induced altered expression of alphaV and beta5 integrin subunits in PDACs cultured on vitronectin resulting in modified adhesion abilities, and caused modifications to the organization of the actin cytoskeleton through the NT-mediated activation of small Rho GTPases. While the NT effects on individually migrating PDACs were mediated at least through the EGFR/ERK signaling pathways, those on collectively migrating PDACs appeared highly dependent on the PI 3-kinase pathway. CONCLUSION: This study strongly suggests the involvement of neurotensin in the modulation of human PDAC migration.



N. Sadeghi-Meibodi, I. Salmon, C. Decaestecker, M. Levivier, T. Metens, D. Wikler, V. Denolin, S. Rorive, N. Massager, D. Balériaux, S. Goldman,
Stereotactic comparison among cerebral blood volume, methionine uptake, and histopathology in brain glioma.
American journal of neuroradiology, Vol. 28, 3, pp. 455-461, 2007
Bibtex
Bibtex : info:hdl:2013/51732
Note : Comparative Study
Abstract : BACKGROUND AND PURPOSE: Vascularity, metabolism, and histologic grade are related in gliomas but the exact determinants of these relationships are not fully defined. We used image coregistration and stereotactic biopsies to regionally compare cerebral blood volume (CBV) and (11)C-methionine (MET) uptake measurements in brain gliomas and to assess their relationship by histopathologic examination. MATERIALS AND METHODS: Fourteen patients with brain gliomas underwent MR imaging, including dynamic susceptibility contrast-enhanced MR and positron-emission tomography (PET) using MET acquired in identical stereotactic conditions before biopsy. MR-based CBV maps were calculated and both CBV maps and PET images were coregistered to anatomic images. Sixty-five biopsy samples were obtained on trajectories targeted toward high MET uptake area. The following histopathologic features were semiquantified in each sample: mitotic activity, endothelial proliferation, cellular pleomorphism, and tumor necrosis. CBV and MET uptake values were measured in the biopsy area and normalized to contralateral white matter. CBV ratios were compared with MET uptake ratios, and both measurements were compared with histologic features of each sample. RESULTS: CBV ratios ranged from 0.08 to 10.24 (median = 1.73), and MET uptake ratios ranged from 0.30 to 4.91 (median = 1.67). There was a positive correlation between CBV ratios and MET uptake ratios (r = 0.65, P < .001). Both CBV and MET uptake ratios were found to be significantly related to endothelial proliferation and mitotic activity (P < .01). CONCLUSION: Within glial tumors, there is a local relationship between CBV and MET uptake measurements. Both provide indices of focal malignant activity.



Conferences

M. Le Mercier, I. Camby, V. Mathieu, P. Dumont, N. De Nève, I. Roland, B. Haibe-Kains, G. Bontempi, T. Mijatovic, Y. Kondo, C. Decaestecker, R. Kiss, F. Lefranc,
Decreasing Galectin-1 Expression in Human Hs683 Glioblastoma Cells Impairs their Response to Endoplasmic Reticulum Stress
Conference: Belgium Society for Cell and Developmental Biology Autumn Meeting 2006(14 October 2006: Ghent), 2007
Bibtex
Bibtex : info:hdl:2013/158305
Note : Language of publication: en
Abstract : Glioblastomas (GBMs) are resistant to apoptosis, but not to autophagy, a fact that can, at least partly, explain the therapeutic benefits of the pro-autophagic drug temozolomide in the treatment of GBM patients. Galectin-1 is a potent modulator of GBM cell migration and a close partner of Ras, whose importance as a signaling molecule in the case of GBMs has already been highlighted. The data in the present study show that the depletion by anti-galectin-1 siRNA of galectin-1 expression in human Hs683 GBM cells does not induce apoptotic or autophagic features. In contrast, this galectin-1 depletion decreases the levels of expression of several genes involved in the response to the endoplasmic reticulum (ER) stress (ERS), and including DUSP5, HERP, DNAJB9/MDG1/Erdj4 and ORP150/HYOU1, the latter of which modulates angiogenesis via the processing of VEGF. The depletion of galectin-1 expression in Hs683 tumor cells leads to sustained decreases in VEGF expression, with severe in vivo impairments of angiogenesis in Hs683 orthotopic xenografts. The in vivo delivery of a non-viral infusion of anti-galectin-1 siRNA into the ventricular system of the brains of adult mice orthotopically grafted with Hs683 GBM cells increases the anti-tumor effects of temozolomide. This novel facet of galectin-1 involvement in glioblastoma biology may be amenable to therapeutic manipulation.



M. Le Mercier, F. Lefranc, T. Mijatovic, O. Debeir, B. Haibe-Kains, G. Bontempi, C. Decaestecker, R. Kiss, V. Mathieu,
Galectin-1 regulates p53 and is implicated in glioma cell resistance to cytotoxic drugs
Conference: Belgium Society for Cell and Developmental Biology Autumn Meeting(Louvain-la-Neuve), 2007
Bibtex
Bibtex : info:hdl:2013/158306
Note : Language of publication: en
Abstract : Purpose: Glioblastomas (GBMs) are resistant to apoptosis but less so to autophagy, a fact that may at least partly explain the therapeutic benefits of the pro-autophagic drug temozolomide in the treatment of GBM patients. Galectin-1 (Gal1) is a potent modulator of GBM cell migration and a pro-angiogenic molecule whose expression is stimulated by hypoxia. The present study investigates whether decreasing galectin-1 expression in human Hs683 GBM cells increases their sensitivity to pro-autophagic or pro-apoptotic drugs.Experimental design: A siRNA approach was used to decrease Gal1 expression in Hs683 GBM cells. The effects of temozolomide and of pro-apoptotic drugs in this model in vitro and in vivo were studied. Additionally genome-wide microarray analysis was employed to identify chemoresistance-related genes.Results: Temozolomide treatment increased Gal1 expression in Hs683 cells both in vitro and in vivo. Reducing Gal1 expression in these cells increased the anti-tumor effects of chemotherapeutical agents, in particular temozolomide both in vitro and in vivo. Decreasing Gal1 expression in Hs683 cells did not induce apoptotic or autophagic features, but decreased p53 transcriptional activity along with p53-targeted gene expression including DDIT3/GADD153/CHOP, DUSP5, ATF3 and GADD45A. The reduction in Gal1 expression also paralleled decreases in the expression levels of seven other genes implicated in chemoresistance: ORP150, HERP, Grp78/Bip, TRA1, BNIP3L, GADD45B and CYR61.Conclusions: This novel facet of Gal1 involvement in the chemoresistance of GBM cells may be amenable to therapeutic manipulation.



L. Yen, F. Fouss, C. Decaestecker, P. Francq, M. Saerens,
Graph Nodes Clustering based on the Commute-Time Kernel
Proceedings of the 11th Pacific-Asia Conference on Knowledge Discovery and Data Mining (PAKDD 2007): Lecture Notes in Computer Science, pp. pp. 1037-1045, 2007
Bibtex
Bibtex : info:hdl:2013/70191
Note : Language of publication: en



O. Debeir, R. Van Ginckel, I. Adanja, F. Darro, R. Kiss, C. Decaestecker,
High throughput characterization of anticancer compounds by means of cellular imaging and automatic image analysis.
Conference: (April 14-18: Los Angeles - USA), 2007
Bibtex
Bibtex : info:hdl:2013/71810
Note : Présentation orale (abstract 4965)




2006

Papers

R. Ghanooni, C. Decaestecker, P. Simon, H. Gabius, S. Hassid, G. Choufani,
Characterization of patterns of expression of protein kinase C-alpha, -delta, -eta, -gamma and -zeta and their correlations to p53, galectin-3, the retinoic acid receptor-beta and the macrophage migration inhibitory factor (MIF) in human cholesteatomas.
Hearing research, Vol. 214, 1-2, pp. 7-16, 2006
Bibtex
Bibtex : info:hdl:2013/75910
Note : Journal Article
Abstract : Cholesteatoma is a benign disease characterized by the presence of an unrestrained growth and the accumulation of keratin in the middle ear cavity. Due to roles in cell proliferation, apoptosis and differentiation members of the protein kinase C (PKC) family could be involved in disease progression. This study focuses on the expression of protein kinase C-alpha, -delta, -eta, -gamma and -zeta in the epithelial tissues of 56 human cholesteatomas and their correlations with those of previously characterized distributions of p53, galectin-3, retinoic acid receptor-beta (RARbeta) and macrophage migration inhibitory factor (MIF). We have previously reported this marker set to be correlated with keratinocyte differentiation in human cholesteatomas. Our present data clearly show that the percentage of PKC-alpha (but not PKC-delta, -gamma, -eta and -zeta)-immunopositive cells in epithelial tissue fro recurrent cholesteatomas was significantly higher than in non-recurrent cases. Correlations between the PKC isoenzymes and the biological markers were non-uniform. PKC-alpha (but not PKC-delta, -gamma, -eta and -zeta) expression in epithelial cholesteatoma cells correlated significantly and positively with the percentages of p53-immunopositive cells. The patterns of PKC-alpha and -delta expression, but not of PKC-gamma, -eta and -zeta, correlated significantly and positively with galectin-3 expression. In addition, the correlation levels between the expression of PKC-alpha and -delta and that of galectin-3 varied depending on the infection and recurrence status. Presence of RARbeta correlated significantly (and positively) with the expression of PKC-gamma and -zeta and also in relation to the infection and recurrence status. MIF correlated presence significantly (and positively) with that of the five PKCs under study, depending on whether the cholesteatomas were non-infected or infected as well as non-recurrent or recurrent. In conclusion, the present study suggests that modifications occurring at the level of keratinocyte differentiation in human cholesteatomas involve distinct effectors, to which the activation of PKC-alpha, -delta, -eta, -gamma and -zeta can be added.



C. Hayot, O. Debeir, P. Van Ham, M. Van Damme, R. Kiss, C. Decaestecker,
Characterization of the activities of actin-affecting drugs on tumor cell migration.
Toxicology and applied pharmacology, Vol. 211, 1, pp. 30-40, 2006
Bibtex
Bibtex : info:hdl:2013/52107
Note : Comparative Study
Abstract : Metastases kill 90\% of cancer patients. It is thus a major challenge in cancer therapy to inhibit the spreading of tumor cells from primary tumor sites to those particular organs where metastases are likely to occur. Whereas the actin cytoskeleton is a key component involved in cell migration, agents targeting actin dynamics have been relatively poorly investigated. Consequently, valuable in vitro pharmacological tools are needed to selectively identify this type of agent. In response to the absence of any standardized process, the present work aims to develop a multi-assay strategy for screening actin-affecting drugs with anti-migratory potentials. To validate our approach, we used two cancer cell lines (MCF7 and A549) and three actin-affecting drugs (cytochalasin D, latrunculin A, and jasplakinolide). We quantified the effects of these drugs on the kinetics of actin polymerization in tubes (by means of spectrofluorimetry) and on the dynamics of actin cytoskeletons within whole cells (by means of fluorescence microscopy). Using quantitative videomicroscopy, we investigated the actual effects of the drugs on cell motility. Finally, the combined drug effects on cell motility and cell growth were evaluated by means of a scratch-wound assay. While our results showed concordant drug-induced effects on actin polymerization occurring in vitro in test tubes and within whole cells, the whole cell assay appeared more sensitive than the tube assay. The inhibition of actin polymerization induced by cytochalasin D was paralleled by a decrease in cell motility for both cell types. In the case of jasplakinolide, which induces actin polymerization, while it significantly enhanced the locomotion of the A549 cells, it significantly inhibited that of the MCF-7 ones. All these effects were confirmed by means of the scratch-wound assay except of the jasplakinolide-induced effects on MCF-7 cell motility. These later seemed compensated by an additional effect occurring during wound recolonization (possibly acting on the cell growth features). In conclusion, the use of multi-assays with different levels of sophistication and biological relevance is recommended in the screening of new actin-affecting drugs with potentially anti-migratory effects.



F. Dubois, C. Yourassowsky, O. Monnom, J. Legros, O. Debeir, P. Van Ham, R. Kiss, C. Decaestecker,
Digital holographic microscopy for the three-dimensional dynamic analysis of in vitro cancer cell migration.
Journal of biomedical optics, Vol. 11, 5, pp. 054032, 2006
Bibtex
Bibtex : info:hdl:2013/52096
Note : Evaluation Studies
Abstract : Cancer cell motility and invasion are critical targets for anticancer therapeutics. Whereas in vitro models could be designed for rapid screening with a view to investigate these targets, careful consideration must be given to the construction of appropriate model systems. Most investigations focus on two-dimensional (2-D) assays despite the fact that increasing evidence suggests that migration across rigid and planar substrates fails to recapitulate in vivo behavior. In contrast, few systems enable three-dimensional (3-D) cell migration to be quantitatively analyzed. We previously developed a digital holographic microscope (DHM) working in transmission with a partially spatial coherence source. This configuration avoids the noise artifacts of laser illumination and makes possible the direct recording of information on the 3-D structure of samples consisting of multiple objects embedded in scattering media, such as cell cultures in matrix gels. The software driving our DHM system is equipped with a time-lapse ability that enables the 3-D trajectories of living cells to be reconstituted and quantitatively analyzed.



S. Rorive, C. Maris, O. Debeir, F. Sandras, M. Vidaud, I. Bièche, I. Salmon, C. Decaestecker,
Exploring the distinctive biological characteristics of pilocytic and low-grade diffuse astrocytomas using microarray gene expression profiles.
Journal of neuropathology and experimental neurology, Vol. 65, 8, pp. 794-807, 2006
Bibtex
Bibtex : info:hdl:2013/52951
Note : Journal Article
Abstract : Although World Health Organization (WHO) grade I pilocytic astrocytomas and grade II diffuse astrocytomas have been classified for decades as different clinicopathologic entities, few, if any, data are available on the biologic features explaining these differences. Although more than 50 microarray-related studies have been carried out to characterize the molecular profiles of astrocytic tumors, we have identified only 11 that provide sound data on low-grade astrocytomas. We have incorporated these data into a comparative analysis for the purpose of identifying the most relevant molecular markers characterizing grade I pilocytic and grade II diffuse astrocytomas. Our analysis has identified various interesting genes that are differentially expressed in either grade I or grade II astrocytomas when compared with normal tissue and/or high-grade (WHO grade III and IV) astrocytomas. A large majority of these genes encode adhesion, extracellular matrix, and invasion-related proteins. Interestingly, a group of 6 genes (TIMP4, C1NH, CHAD, THBS4, IGFBP2, and TLE2) constitute an expression profile characteristic of grade I astrocytomas as compared with all other categories of tissue (normal brain, grade II, and high-grade astrocytomas). The end products (proteins) of these genes act as antimigratory compounds, a fact that could explain why pilocytic astrocytomas behave as compact (well-circumscribed) tumors as opposed to all the other astrocytic tumor types that diffusely invade the brain parenchyma. Having validated these molecular markers by means of real-time reverse transcriptase-polymerase chain reaction, an integrated model was proposed illustrating how and why pilocytic astrocytomas constitute a distinct biologic and pathologic entity when compared with diffuse astrocytomas.



S. Saussez, D. Cucu, C. Decaestecker, D. Chevalier, H. Kaltner, S. André, A. Wacreniez, G. Toubeau, I. Camby, H. Gabius, R. Kiss,
Galectin 7 (p53-induced gene 1): a new prognostic predictor of recurrence and survival in stage IV hypopharyngeal cancer.
Annals of surgical oncology, Vol. 13, 7, pp. 999-1009, 2006
Bibtex
Bibtex : info:hdl:2013/52101
Note : Journal Article
Abstract : BACKGROUND: Eighty percent of hypopharyngeal squamous cell carcinoma patients have advanced stages (III and IV) of the disease, and biological markers are required to predict high-risk head and neck squamous cell carcinoma patients in need of highly aggressive treatments after surgery to improve the survival rate. We analyzed the potential prognostic value of galectin 7 in a series of 81 stage IV hypopharyngeal SCCs because galectin 7 is an emerging marker involved in the epidermal development of pluristratified epithelia and in epidermal cell migration. METHODS: The immunohistochemical expression of galectin 7 was determined on a series of 81 stage IV hypopharyngeal SCCs and was compared with that of galectins 1 and 3. RESULTS: High levels of galectin 7 expression were associated with rapid recurrence rates and dismal prognoses in these 81 stage IV hypopharyngeal SCCs, a feature not observed with galectin 3 and one observed weakly, if at all, with galectin 1. CONCLUSIONS: These data suggest that the immunohistochemical determination of galectin 7 expression in the case of high-risk hypopharyngeal cancers is a meaningful tool to identify patients who should benefit from aggressive postsurgical adjuvant therapy after surgery, including not only radiotherapy, but also chemotherapy.



A. Daelemans, T. Leloup, C. Decaestecker, A. De Mey,
New digital method for quantitative assessment of nasal morphology.
Scandinavian journal of plastic and reconstructive surgery and hand surgery, Vol. 40, 6, pp. 335-344, 2006
Bibtex
Bibtex : info:hdl:2013/75911
Note : Journal Article
Abstract : Our aim was to develop and validate a new method to assess objectively and quantitatively the morphology of the nostrils after nasal or nasolabial surgery. We used digital analysis using specific mathematical algorithms to assess several geometric measurements, particularly of facial asymmetry, expressed in adimensional units. Forty-five patients with no facial anomalies (control group) were used initially to evaluate the method and to obtain variables for statistical reference. Thirty-five patients operated on for unilateral cleft lip and palate (cleft group) were then analysed and compared with the control group. Individual scores were obtained for each patient, computed, and correlated with those established by a lay panel. Statistical analysis showed good sensitivity and reliability (R>0.8).



R. Ercek, P. De Doncker, F. Grenez,
Statistical study of NLOS-Multipath in Urban Canyons
European journal of navigation, Vol. 4, 3, pp. 41-48, 2006
Bibtex
Bibtex : info:hdl:2013/78477
Note : Language of publication: en



S. Servotte, I. Camby, O. Debeir, C. Deroanne, C. Lambert, C. Lapière, R. Kiss, B. Nusgens, C. Decaestecker,
The in vitro influences of neurotensin on the motility characteristics of human U373 glioblastoma cells.
Neuropathology and applied neurobiology, Vol. 32, 6, pp. 575-584, 2006
Bibtex
Bibtex : info:hdl:2013/52097
Note : In Vitro
Abstract : Astrocytic tumours are associated with dismal prognoses due to their pronounced ability to diffusely invade the brain parenchyma. Various neuropeptides, including gastrin, are able to modulate tumour astrocyte migration. While neurotensin has been shown to influence the proliferation of glioma cells and the migratory ability of a large set of other cell types, its role in glioma cell migration has never been investigated. Neurotensin-induced modifications to the motility features of human U373 glioblastoma cells therefore constitute the topic of the present study. We evidenced that three subtypes of neurotensin receptors (NTR1, NTR2 and NTR3) are expressed in U373 glioblastoma cells, at least as far as their mRNAs are concerned. Treating U373 tumour cells with 10 nM neurotensin markedly modified the morphological patterns of these cells and also profoundly altered the organization of their actin cytoskeletons. Pull-down assays revealed that neurotensin induced the activation in U373 cells of both Rac1 and Cdc42 but not RhoA. Scratch wound assays evidenced that neurotensin (0.1 and 10 nM) very significantly inhibited wound colonization by U373 cells cultured in the absence of serum. In addition, quantitative phase-contrast videomicroscopy analyses showed that neurotensin decreases the motility levels of U373 glioblastoma cells when these cells are cultured on plastic. In sharp contrast, neurotensin stimulates the motility of U373 cells when they are cultured on laminin, which is a pro-adhesive extracellular matrix component ubiquitously secreted by glioma cells. Our data thus strongly suggest that, in addition to gastrin, neurotensin is a neuropeptide capable of modulating tumour astrocyte migration into the brain parenchyma.



Conferences

O. Debeir, I. Adanja, R. Kiss, C. Decaestecker,
Automatic in vitro cell division characterization by automatic image sequence analysis
Conference: Annual Symposium of the IEEE/EMBS Benelux Chapter(I: 7-8 December 2006: Brussels), 2006
Bibtex
Bibtex : info:hdl:2013/158307
Note : Language of publication: en
Abstract : In vitro cell observation has been widely used by biologists for years and covers a wide range of applications: cancer and cell proliferation, cell migration or chemotactism, embryology, drug testing. Nowadays the use of computer assisted-microscopy (or time-laps microscopy) allows the handling of considerably large amount of image data, which is acquired during experiments possibly lasting from several hours to several days. If cell cultures are observed for long periods of time (2-4 days), it becomes possible to detect less frequent cell events, such as cell division or cell death. We describe in this work a semi-automatic approach of studying the cell division event itself - starting from the cell exhibiting a round shaped form to the final daughter cells separation.



O. Debeir, R. Kiss, C. Decaestecker,
Cell division characterization by automatic cell tracking and cell lineage reconstruction
Conference: Belgium Society for Cell and Developmental Biology Autumn Meeting 2006(2006: Ghent), 2006
Bibtex
Bibtex : info:hdl:2013/158308
Note : Language of publication: en
Abstract : In vitro cell observation is widely used by biologists since years. Nowadays the use of computer assisted-microscopy (or time-laps microscopy) allows the management of huge amounts of image data generated during experiments of various durations. Periods of time from several hours to 1 day are generally sufficient to analyze cell trajectories in cell migration and chemotaxis studies. If cell cultures are observed during longer periods of time (3-4 days), it is possible to detect less frequent cell events, such as cell division or cell death. A wide range of applications can be covered by theses time-laps microscopy approaches, including embryology studies and anti-cancer drug testing.We showed in previous works that unmarked cells observed in vitro under classical phase-contrast microscopy during several days can be efficiently and automatically tracked, and their individual trajectories reconstituted and characterized by various measurements. We are now extending this technique for cell division detection using backward cell tracking (from the last to the 1st frame of the image sequence) and cell trajectory recombinations. In the present study, we describe a semi-automatic extension which is able to reconstruct tree structures characterizing cell lineages. The use of backward cell tracking enables easy cell division detection (by identifying cell trajectory merging), except in some cases when the tracking procedure fails. We thus added a “light” interactive step in order to select the actual cell division events among all the automatically detected ones; the operator has only to accept or to reject each proposed event.In order to characterize the action of specific drugs on cell motility and also on cell behavior during and just after cell division, specific features characterizing cell division events are extracted (in addition to those concerning cell movements). We illustrated our methodology on different examples including drug actions on cytokinesis, i.e. the cell separation event occurring at the end of cell division.



R. Ercek, P. De Doncker, F. Grenez,
NLOS-Multipath effects on pseudo-Range estimation in urban canyons for GNSS applications
Eur. Conf. on Antennas and Propagation (Eucap 2006), Nice, France, 2006
Bibtex
Bibtex : info:hdl:2013/70278
Note : Language of publication: en



R. Ercek, P. De Doncker, F. Grenez,
Statistical determination of the PR error due to NLOS-Multipath in urban canyons
Proc. of the ION GNSS 2006, Fort Worth, USA, 2006
Bibtex
Bibtex : info:hdl:2013/70280
Note : Language of publication: en




2005

Papers

F. Darro, C. Decaestecker, J. Gaussin, S. Mortier, R. Van Ginckel, R. Kiss,
Are syngeneic mouse tumor models still valuable experimental models in the field of anti-cancer drug discovery?
International journal of oncology, Vol. 27, 3, pp. 607-616, 2005
Bibtex
Bibtex : info:hdl:2013/71058
Note : Comparative Study
Abstract : To establish the pharmacological profile of a molecule with anti-cancer potential, it seems essential to add an in vivo approach to the first pharmacological experiments carried out in vitro. The present study aims to characterize the degree of sensitivity of seven syngeneic models (two leukemias and five solid tumors) to eleven molecules which have proven to be clinically reliable. We also used some of these models to investigate whether the molecular effects on the extent of growth in a subcutaneously grafted experimental model correlate with the effects of the same drug on the survival of the animals so grafted. Our data show that all the molecules demonstrated significant anti-tumor activities in two mouse leukemia models (with some discrepancies between the two). Two lymphoma models displayed weaker chemosensitivity profiles than the two leukemia models from which they were developed. Two other models, namely the MXT-HS mammary carcinoma and the B16 melanoma, appeared to be rather chemoresistant. However, a direct relationship was evident between the drug-induced decrease in the tumor growth rate and the increase observed in the survival periods of the MXT tumor-bearing mice. This relationship was also observed in the L1210\_LYM lymphoma, though to a lesser extent, and was completely absent from the B16 melanoma model. Finally, our data indicated that we had developed a pair of metastasizing, as opposed to non-metastasizing, lymphoma and mammary carcinoma models. In conclusion, the present study shows that syngeneic mouse tumor models can be used as valuable in vivo experimental models for the screening of potential anti-cancer agents.



F. Lefranc, C. Decaestecker, J. Brotchi, C. Heizmann, O. De Witte, R. Kiss, T. Mijatovic,
Co-expression/co-location of S100 proteins (S100B, S100A1 and S100A2) and protein kinase C (PKC-beta, -eta and -zeta) in a rat model of cerebral basilar artery vasospasm.
Neuropathology and applied neurobiology, Vol. 31, 6, pp. 649-660, 2005
Bibtex
Bibtex : info:hdl:2013/51220
Note : Journal Article
Abstract : OBJECT: The cellular events leading to cerebral vasospasm after subarachnoid haemorrhages (SAH) involve a number of members of the protein kinase C (PKC) family. However, whereas calcium is thought to play a number of major roles in the pathophysiology of SAH, a number of PKCs function independently of calcium. We recently emphasized the potential role of the calcium-binding S100 proteins in a 'double haemorrhage' rat model of SAH-induced vasospasm. A number of S100 proteins are known to interfere directly with PKC, or indirectly with PKC substrates. We therefore investigated whether specific S100 proteins and PKCs are co-expressed/co-located in a rat model of SAH-induced vasospasm. METHODS AND RESULTS: SAH-induced vasospasm in rats (by means of a double cisternal injection of autologous blood from a rat femoral artery) distinctly modified the expression levels of calcium-dependent PKC-alpha and PKC-beta and calcium-independent PKC-eta and PKC-zeta in endothelial and smooth-muscle cells. The RNA levels of these four PKC isotypes were determined by quantitative RT-PCR. The present study reveals that, in endothelial cells, the S100B expression/location correlate well with those of PKC-eta, and those of S100A1 with PKC-beta. In smooth-muscle cells S100A2 expression/location correlate with those of PKC-eta, and those of S100B with PKC-zeta. CONCLUSION: The present data argue in favour of a joint action of the S100 protein network and the PKC signalling pathway during cerebral vasospasm.



I. Camby, C. Decaestecker, F. Lefranc, H. Kaltner, H. Gabius, R. Kiss,
Galectin-1 knocking down in human U87 glioblastoma cells alters their gene expression pattern.
Biochemical and biophysical research communications, Vol. 335, 1, pp. 27-35, 2005
Bibtex
Bibtex : info:hdl:2013/51219
Note : Journal Article
Abstract : We have previously reported that (i) progression of malignancy in patients bearing astrocytic tumors correlates with increased tumor levels of galectin-1; (ii) in vitro addition of purified galectin-1 to U87 human glioblastoma cells enhances tumor cell motility; and (iii) conversely, knocking down galectin-1 expression in this cell line by stable transfection with antisense galectin-1 mRNA impairs motility and delays mortality after their intracranial grafting to nude mice. We here used cDNA microarray analysis to compare the effect on gene expression of stable transfection with antisense galectin-1 vector to mock-transfected and wild-type cells. Among the 631 spots probing genes potentially involved in cancer that were valid for analysis on all the arrays the expression of 86 genes was increased at least 2-fold. Confirmation of increased protein levels was provided by immunocytochemistry for p21waf/cip1, cullin-2, p53, ADAM-15, and MAP-2. Major differences in the expression patterns of ADAM-15 and the actin stress fiber organization were also observed. U87 cells stably deficient for galectin-1 expression were significantly less motile than control. We conclude that the stable inhibition of galectin-1 expression alters the expression of a number of genes that either directly or indirectly influence adhesion, motility and invasion of human glioblastoma cells.



I. Saal, N. Nagy, M. Lensch, M. Lohr, J. Manning, C. Decaestecker, S. André, R. Kiss, I. Salmon, H. Gabius,
Human galectin-2: expression profiling by RT-PCR/immunohistochemistry and its introduction as a histochemical tool for ligand localization.
Histology and histopathology, Vol. 20, 4, pp. 1191-1208, 2005
Bibtex
Bibtex : info:hdl:2013/52106
Note : Journal Article
Abstract : Sugar-encoded information of glyco-conjugates is translated into cellular responses by endogenous lectins. Galectins stand out against other lectin families due to their wide range of functions including cell adhesion, tissue invasion or growth regulation exerted at extracellular, membrane, cytoplasmic and nuclear sites. This remarkable versatility warrants close scrutiny of their emerging network, in this study with focus on homodimeric human galectin-2. We first detected presence of specific mRNA in various tissue types by processing post mortem and surgical specimens by RT-PCR protocols. Overlap of gene expression was noted with proto-type galectins-1 and -7 and also family members from the other two subgroups. To monitor expression on the level of protein a polyclonal anti-galectin-2 antibody was raised. Immunopositivity was semi-quantitatively assessed in sections of 209 human samples establishing an array both of normal tissues and samples with inflammation or benign/malignant growth. In general, positivity was predominantly epithelial without restriction of staining to certain tissue types, as fittingly indicated by our RT-PCR analysis. Staining was not limited to the cytoplasm but also included nuclear sites. To examine the suitability of the labeled lectin as a histochemical probe we biotinylated galectin-2 under activity-preserving conditions and introduced it to tissue profiling. Specific cytoplasmic staining proved the validity of the concept. Our results encourage systematic histopathologic studies by immuno- and lectin histochemistry, especially by adding galectin-2 as study object to galectin fingerprinting which has already yielded prognostic information on galectins-1, -3, -4 and -8 and hereby contributed to define functional overlap/divergence in this lectin family.



M. Remmelink, T. Mijatovic, A. Gustin, A. Mathieu, K. Rombaut, R. Kiss, I. Salmon, C. Decaestecker,
Identification by means of cDNA microarray analyses of gene expression modifications in squamous non-small cell lung cancers as compared to normal bronchial epithelial tissue.
International journal of oncology, Vol. 26, 1, pp. 247-258, 2005
Bibtex
Bibtex : info:hdl:2013/53540
Note : Comparative Study
Abstract : The present work analyzed the gene pattern profiles in 6 squamous non-small cell lung cancers (NSCLCs) versus 4 normal lung epithelial tissues by means of cDNA microarrays. In addition to cDNA microarray analyses, quantitative RT-PCR and immunohisto-chemical analyses were used to validate some of the results obtained. Our data enabled 7 genes to be selected by looking at the genes which were detected as being expressed in all the tumors and not expressed in all the normal samples, or inversely. Additionally, 19 genes were detected as being overexpressed in the tumors when compared to the normal tissue specimens. Of these 26 genes, 16 are not yet suspected of influencing NSCLC biology. These genes are involved in cell proliferation (G2 cyclin), signal transduction (SMARCC2, TM4SF3), apoptosis (CFLAR/FLIP), cell cytoskeleton (cytokeratins-14 and 16, alpha-tubulin isoform 1 and S100A10), cell adhesion (JUP), invasion (cathepsins H and O) and other biological processes (OAZ1, IGHG3, SCYA5/RANTES, beta-sarcoglycan and transcobalamin I). In conclusion, we identified a number of genes as being differentially expressed in squamous NSCLCs as compared to normal lung epithelial tissue. Some of these genes (such as those involved in invasion) could be used as new prognostic markers and others, like CFLAR/FLIP, could even constitute new therapeutic targets.



E. Van Quaquebeke, G. Simon, A. André, J. Dewelle, M. El Yazidi, F. Bruyneel, J. Tuti, O. Nacoulma, P. Guissou, C. Decaestecker, J. Braekman, R. Kiss, F. Darro,
Identification of a novel cardenolide (2''-oxovoruscharin) from Calotropis procera and the hemisynthesis of novel derivatives displaying potent in vitro antitumor activities and high in vivo tolerance: structure-activity relationship analyses.
Journal of medicinal chemistry, Vol. 48, 3, pp. 849-856, 2005
Bibtex
Bibtex : info:hdl:2013/52110
Note : Journal Article
Abstract : Analysis of the methanolic extract of Calotropis procera root barks enabled the identification of a novel cardenolide (2''-oxovoruscharin) to be made. Of the 27 compounds that we hemisynthesized, one (23) exhibited a very interesting profile with respect to its hemisynthetic chemical yield, its in vitro antitumor activity, its in vitro inhibitory influence on the Na+/K+-ATPase activity, and its in vivo tolerance. Compound 23 displayed in vitro antitumor activity on a panel of 57 human cancer cell lines similar to taxol, and higher than SN-38 (the active metabolite of irinotecan), two of the most potent drugs used in hospitals to combat cancer.



R. Ercek, P. De Doncker, F. Grenez,
Modeling of NLOS-multipath in urban canyons for GNSS applications
Revue HF, Vol. 1, pp. 79, 2005
Bibtex
Bibtex : info:hdl:2013/74123
Note : Forum URSI, Bruxelles



F. Lefranc, T. Mijatovic, C. Decaestecker, H. Kaltner, S. André, J. Brotchi, I. Salmon, H. Gabius, R. Kiss,
Monitoring the expression profiles of integrins and adhesion/growth-regulatory galectins in adamantinomatous craniopharyngiomas: their ability to regulate tumor adhesiveness to surrounding tissue and their contribution to prognosis.
Neurosurgery, Vol. 56, 4, pp. 763-776, 2005
Bibtex
Bibtex : info:hdl:2013/51223
Note : Journal Article
Abstract : OBJECTIVE: The purpose of this study was to identify biological markers that may be involved in the adhesiveness of craniopharyngiomas to optical chiasms and/or pituitary stalks. METHODS: We determined the complete pattern of integrin expression in three craniopharyngiomas by means of a complementary deoxyribonucleic acid microarray. We quantitatively determined the levels of immunohistochemical expression of the different integrins in a series of 37 cases and the pattern of immunohistochemical expression of 10 extracellular matrix components (acting as integrin ligands) in 7 optical chiasms and 11 pituitary stalks. We also quantitatively (computer-assisted microscopy) determined the levels of immunohistochemical expression of galectin-1, -3, -4, -7, and -8 in 50 adamantinomatous craniopharyngiomas. RESULTS: The present study shows that at both the ribonucleic acid and protein levels, adamantinomatous craniopharyngiomas express the alpha2, alpha6, alpha(v), beta1, beta5, and beta8 integrin subunits, whereas optical chiasms and pituitary stalks express vitronectin, thrombospondin, and various forms of collagens. CONCLUSION: Our data suggest that at least part of the adhesiveness of craniopharyngiomas to the surrounding tissue, such as optical chiasms and pituitary stalks, could be explained by the interactions between alpha(2beta1) integrin expressed by craniopharyngiomas and collagens on the one hand, and vitronectin expressed by the surrounding tissue on the other hand. In addition, a Cox regression analysis has revealed that the levels of galectin-4 contribute significant information toward the delay in recurrence independently of surgical status.



A. Mathieu, I. Saal, A. Vuckovic, V. Ransy, P. Vereerstraeten, H. Kaltner, H. Gabius, R. Kiss, C. Decaestecker, I. Salmon, M. Remmelink,
Nuclear galectin-3 expression is an independent predictive factor of recurrence for adenocarcinoma and squamous cell carcinoma of the lung.
Modern pathology, Vol. 18, 9, pp. 1264-1271, 2005
Bibtex
Bibtex : info:hdl:2013/52109
Note : Journal Article
Abstract : The tumor stage is the most powerful prognostic tool for predicting the survival rates of lung carcinoma patients. However, prognosis of individual patients is difficult in part because of the marked clinical heterogeneity among such patients. Galectins are involved in cell growth, apoptosis and cell migration features, and their diagnostic and prognostic values have already been demonstrated in various types of cancers. In the present paper we analyze the potential prognostic value of immunohistochemical galectin-3 expression in lung adenocarcinomas and squamous cell carcinomas. In all, 165 squamous cell carcinomas and 121 adenocarcinomas were immunostained for galectin-3. In each case the immunohistochemical analyses consisted of an evaluation of the percentage of tumor cells stained and the intensity of staining. An IP score (ie Intensity x Percentage) was thus determined for each lung carcinoma. A large majority of cases displayed galectin-3 expression. While the cytoplasmic staining in the squamous cell carcinomas was focal and moderately intense, the staining in the adenocarcinomas was diffuse and intense. The IP scores were significantly (P=0.0001) higher in the adenocarcinomas than in the squamous cell carcinomas. The difference in nuclear expression profiles between the two cancer types was statistically significant (P=0.0005). Cox multivariate analysis carried out on the patients' genders, the TNM classification and the galectin-3-related variables showed that of the galectin-3-related variables, only the nuclear location of galectin-3 was identified as a prognostic indicator of recurrence independent of the clinicopathological features characterizing the patients (P=0.02). The prognostic contribution of this latter variable was enhanced when the patients with relapse-free follow-ups longer than 8 months were considered (P=0.005). Galectin-3 immunohistochemical expression differs between squamous cell carcinomas and adenocarcinomas, but the nuclear expression of galectin-3 behaves as a significant prognostic predictor for all the cases as a group.



N. D'Haene, C. Maris, F. Sandras, M. Dehou, M. Remmelink, C. Decaestecker, I. Salmon,
The differential expression of Galectin-1 and Galectin-3 in normal lymphoid tissue and non-Hodgkin's and Hodgkin's lymphomas.
International journal of immunopathology and pharmacology, Vol. 18, 3, pp. 431-443, 2005
Bibtex
Bibtex : info:hdl:2013/53542
Note : Comparative Study
Abstract : The WHO classification of lymphomas was established on the basis of clinical, morphological, immunohistochemical and genetic criteria. However, each entity displays its own spectrum of clinical aggressiveness. Treatment success varies widely and is not predictable. Since galectins are involved in oncogenesis and the physiology of immune cells, we investigated whether galectin-1 and galectin-3 immunohistochemical expression could differ in 25 normal lymphoid tissues, 42 non-Hodgkins and 14 Hodgkins lymphomas. Immunohistochemical galectin expression was submitted to semi-quantitative and quantitative (computer-assisted microscopy) evaluations. This study is completed by an analysis (by means of quantitative RT-PCR) of galectin-3 mRNA expression in 3 normal lymph nodes, 3 follicular lymphomas (FLs) and 3 diffuse large B-cell lymphomas (DLBCLs). The data show that in normal lymphoid tissue, lymphocytes do not express galectin-1 and rarely express galectin-3. In contrast, galectin-3 was expressed in 8 of the 16 DLBCL cases and in 1 of the 8 FL cases. Furthermore, galectin-3 mRNA was expressed 3 times more in the DLBCLs than in the FLs. While the blood vessel walls of the lymphomas expressed galectin-1, the vessel walls of normal lymphoid tissues did not. This expression of galectin-1 in blood vessel walls was correlated with vascular density. The present study thus shows that DLBCL can be distinguished from normal lymphoid tissue and other lymphomas on the basis of galectin-3 expression.



O. Debeir, P. Van Ham, R. Kiss, C. Decaestecker,
Tracking of migrating cells under phase-contrast video microscopy with combined mean-shift processes.
IEEE transactions on medical imaging, Vol. 24, 6, pp. 697-711, 2005
Bibtex
Bibtex : info:hdl:2013/52108
Note : Evaluation Studies
Abstract : In this paper, we propose a combination of mean-shift-based tracking processes to establish migrating cell trajectories through in vitro phase-contrast video microscopy. After a recapitulation on how the mean-shift algorithm permits efficient object tracking we describe the proposed extension and apply it to the in vitro cell tracking problem. In this application, the cells are unmarked (i.e., no fluorescent probe is used) and are observed under classical phase-contrast microscopy. By introducing an adaptive combination of several kernels, we address several problems such as variations in size and shape of the tracked objects (e.g., those occurring in the case of cell membrane extensions), the presence of incomplete (or noncontrasted) object boundaries, partially overlapping objects and object splitting (in the case of cell divisions or mitoses). Comparing the tracking results automatically obtained to those generated manually by a human expert, we tested the stability of the different algorithm parameters and their effects on the tracking results. We also show how the method is resistant to a decrease in image resolution and accidental defocusing (which may occur during long experiments, e.g., dozens of hours). Finally, we applied our methodology on cancer cell tracking and showed that cytochalasin-D significantly inhibits cell motility.



Conferences

O. Debeir, D. Milojevic, T. Leloup, P. Van Ham, R. Kiss, C. Decaestecker,
Mitotic Tree Construction by Computer In Vitro Cell Tracking : a Tool for Proliferation and Motility Features Extraction
Proc. of the EUROCON 2005, pp. 951-954, Belgrade, Serbia, 2005
Bibtex
Bibtex : info:hdl:2013/53176
Note : Language of publication: en



S. Servotte, I. Camby, O. Debeir, C. Deroanne, C. Lapière, R. Kiss, B. Nusgens, C. Decaestecker,
Neurotensin activates rac1 and cdc42, but not rhoa, in human U373 glioblastoma cells, and modifies their migratory patterns
Conference: Cell migration in cancer and immunity: Joint BSCDB-BIS meeting(27-28 May 2005: Brussels), 2005
Bibtex
Bibtex : info:hdl:2013/158309
Note : Language of publication: en
Abstract : Astrocytic tumors are associated with dismal prognoses due to their pronounced ability to diffusely invade the brain parenchyma (Lefranc et al., J Clin Oncol 2005). Various neuropeptides display a large number of functions in the central and peripheral nervous system. Gastrin has already been shown to affect both cell proliferation and migration (Camby et al., J Natl Cancer Inst 1996; DeHauwer et al., J Neurobiol 1998; Lefranc et al., Lab Invest 2002) in human experimental gliomas. While we already suggested a role for neurotensin in glioma cell proliferation (Camby et al., Neuropeptide 1996), its action on glioma cell migration has never been investigated. Therefore, the present study aims at analyzing the neurotensin-induced alterations of the migratory patterns of human U373 glioblastoma cells. Most of the neuropeptides displaying physiological roles in the brain act through their binding to specific G-protein-coupled-receptors (GPCRs) on the surface of their target cells. Once a neuropeptide binds to its GPCR(s), it can induce profound changes in the organization of the actin cytoskeleton which is a major actor in the cell migration process (Rozengurt and Walsch, Annu Rev Physiol 2001). Three subtypes of neurotensin receptors have been cloned. While NT-R1 and NT-R2 belong to the GPCR family, NT-R3 is a new type of neuropeptide receptor which is a 95 kDa protein (identical to gp95/sortilin) with a single transmembrane domain. RT-PCR analyses evidenced that U373 tumor cells express mRNAs for NT-R1, -R2 and -R3. Treating U373 cells with 10 nM neurotensin markedly modified their morphological patterns as well as the organization of their actin cytoskeleton. The family of the Rho-GTPase proteins plays a pivotal role in regulating the actin cytoskeleton organization. While RhoA regulates the assembly of contractile actin-myosin filaments, Rac1 and Cdc42 regulate actin polymerization to form peripheral lamellipodial and filopodial protrusions respectively. Pull-down assays revealed that neurotensin induced a dose-dependent activation in U373 cells of both Rac1 and Cdc42, and, to a lesser extent, RhoA. By using a scratch wound assay, we observed that 0.1 and 10 nM neurotensin very significantly decreased the ability of U373 glioblastoma cells to migrate and colonize the wound (in the absence of fetal calf serum). Computer-assisted phase-contrast microscope analyses showed that neurotensin decreases the motility levels of U373 glioblastoma cells cultured on uncoated flasks (plastic). In sharp contrast, neurotensin stimulates the motility of U373 cells cultured on laminin (a pro-adhesive extracellular matrix component ubiquitously secreted by glioma cells, known for stimulating their migration in vitro and upregulated in high-grade astrocytic tumors). In conclusion, our data strongly suggest that neurotensin, in addition to gastrin, is a neuropeptide able to modulate tumor astrocyte migration into the brain parenchyma.



R. Ercek, P. De Doncker, F. Grenez,
Statistical study of NLOS-Multipath in urban canyons
Proc. Eur. Navigation Conf., Munich, Germany, 2005
Bibtex
Bibtex : info:hdl:2013/70377
Note : Language of publication: en



R. Ercek, P. De Doncker, F. Grenez,
Study of pseudo-range error due to non-line-of-sight-multipath in urban canyons
Proc. ION GNSS, Long Beach, USA, 2005
Bibtex
Bibtex : info:hdl:2013/70285
Note : Language of publication: en




2004

Papers

O. Debeir, I. Camby, R. Kiss, P. Van Ham, C. Decaestecker,
A model-based approach for automated in vitro cell tracking and chemotaxis analyses
Cytometry. Part A, Vol. 60, 1, pp. 29-40, 2004
Bibtex
Bibtex : info:hdl:2013/52124
Note : Journal Article
Abstract : BACKGROUND: Chemotaxis may be studied in two main ways: 1) counting cells passing through an insert (e.g., using Boyden chambers), and 2) directly observing cell cultures (e.g., using Dunn chambers), both in response to stationary concentration gradients. This article promotes the use of Dunn chambers and in vitro cell-tracking, achieved by video microscopy coupled with automatic image analysis software, in order to extract quantitative and qualitative measurements characterizing the response of cells to a diffusible chemical agent. METHODS: Previously, we set up a videomicroscopy system coupled with image analysis software that was able to compute cell trajectories from in vitro cell cultures. In the present study, we are introducing a new software increasing the application field of this system to chemotaxis studies. This software is based on an adapted version of the active contour methodology, enabling each cell to be efficiently tracked for hours and resulting in detailed descriptions of individual cell trajectories. The major advantages of this method come from an improved robustness with respect to variability in cell morphologies between different cell lines and dynamical changes in cell shape during cell migration. Moreover, the software includes a very small number of parameters which do not require overly sensitive tuning. Finally, the running time of the software is very short, allowing improved possibilities in acquisition frequency and, consequently, improved descriptions of complex cell trajectories, i.e. trajectories including cell division and cell crossing. RESULTS: We validated this software on several artificial and real cell culture experiments in Dunn chambers also including comparisons with manual (human-controlled) analyses. CONCLUSIONS: We developed new software and data analysis tools for automated cell tracking which enable cell chemotaxis to be efficiently analyzed.



F. Lefranc, T. Mijatovic, V. Mathieu, S. Rorive, C. Decaestecker, O. Debeir, J. Brotchi, P. Van Ham, I. Salmon, R. Kiss,
Characterization of gastrin-induced proangiogenic effects in vivo in orthotopic U373 experimental human glioblastomas and in vitro in human umbilical vein endothelial cells.
Clinical cancer research, Vol. 10, 24, pp. 8250-8265, 2004
Bibtex
Bibtex : info:hdl:2013/51225
Note : In Vitro
Abstract : PURPOSE: This study aims to investigate the role of gastrin-17 (G17) on angiogenesis features in gliomas both in vitro and in vivo. EXPERIMENTAL DESIGN: The influences of G17 and G17 receptor antagonists were characterized in vitro in terms of angiogenesis on human umbilical vein endothelial cell (HUVEC) tubulogenesis processes on Matrigel and in vivo with respect to U373 orthotopic glioma xenografts. The influence of phosphatidylinositol 3'-kinase, protein kinase C, and nuclear factor-kappaB inhibitors was characterized in vitro on G17-mediated HUVEC tubulogenesis. G17-mediated release of interleukin (IL)-8 from HUVECs and G17-induced modifications in nuclear factor-kappaB DNA binding activity were characterized by means of specific enzyme-linked immunosorbent assays. The influence of G17 on E- and P-selectin expression was determined by means of computer-assisted microscopy, whereas the influence of E- and P-selectin on HUVEC migration was approached by means of antisense oligonucleotides. The chemotactic influence of G17 and IL-8 on HUVEC migration was characterized by means of computer-assisted videomicroscopy with Dunn chambers. RESULTS: Messenger RNAs for cholecystokinin (CCK)A, CCKB, and CCKC receptors were present in HUVECs and microvessels dissected from a human glioblastoma. Whereas G17 significantly increased the levels of angiogenesis in vivo in the U373 experimental glioma model and in vitro in the HUVECs, the CCKB receptor antagonist L365,260 significantly counteracted the G17-mediated proangiogenic effects. G17 chemoattracted HUVECs, whereas IL-8 failed to do so. IL-8 receptor alpha (CXCR1) and IL-8 receptor beta (CXCR2) mRNAs were not detected in these endothelial cells. Gastrin significantly (but only transiently) decreased the level of expression of E-selectin, but not P-selectin, whereas IL-8 increased the expression of E-selectin. Specific antisense oligonucleotides against E- and P-selectin significantly decreased HUVEC tubulogenesis processes in vitro on Matrigel. CONCLUSIONS: The present study shows that gastrin has marked proangiogenic effects in vivo on experimental gliomas and in vitro on HUVECs. This effect depends in part on the level of E-selectin activation, but not on IL-8 expression/release by HUVECs.



S. Hancq, I. Salmon, J. Brotchi, H. Gabius, C. Heizmann, R. Kiss, C. Decaestecker,
Detection of S100B, S100A6 and galectin-3 ligands in meningiomas as markers of aggressiveness
International journal of oncology, Vol. 25, 5, pp. 1233-1240, 2004
Bibtex
Bibtex : info:hdl:2013/53536
Note : Journal Article
Abstract : The biological factors responsible for the increased aggressiveness in atypical meningiomas are not well known. The aim of this study is to evaluate the discriminatory value of a number of biological markers (S100 proteins and galectin-3 and its ligand profile) with respect to benign and atypical meningiomas. Using 63 meningiomas (39 benign and 24 atypical), we performed a semi-quantitative histochemical analysis of both the expression of galectin-3 and its ligand profile and the Ca2+-binding proteins S100A5, S100A6 and S100B. Three features were considered for each marker, namely the labeling index (LI), the staining intensity (SI) and the global score (LI + SI). A low S100A6 labeling index was observed in 51\% of the benign and 25\% of the atypical meningiomas (P=0.035). Furthermore, high S100B scores were observed in 46\% of the benign and in only 8\% of the atypical meningiomas (P=0.001). Seventy-one percent of the atypical meningiomas exhibited a low level of staining intensity for the galectin-3-binding sites as compared to only 36\% of the benign meningiomas (P=0.007). The combination of these three markers (by means of a decision tree) enabled an improved discriminatory criterion to be established between the benign and the atypical meningiomas. Our results thus suggest that the galectin-3-binding sites and S100B (and S100A6 to a lesser extent) could play a role in the aggressiveness characterizing atypical meningiomas.



H. Legendre, C. Decaestecker, M. Goris Gbenou, N. Nagy, A. Hendlisz, S. André, J. Pector, R. Kiss, H. Gabius,
Prognostic stratification of Dukes B colon cancer by a neoglycoprotein
International journal of oncology, Vol. 25, 2, pp. 269-276, 2004
Bibtex
Bibtex : info:hdl:2013/71060
Note : Journal Article
Abstract : Disease progression of tumors is accompanied by structural changes of the glycan chains of cellular glycoconjugates. Within the concept of the sugar code the presence of complementary receptors such as lectins translates changes in ligand presentation into biological effects, for example in growth regulation and adhesion. By introducing neoglycoproteins to histopathological colon cancer analysis the questions are addressed as to whether specific binding sites for main N- and O-glycan components are present and whether they harbor potential for prognostic predictions. Synthetic conjugation of fucose, lactose, and mannose derivatives to a carrier protein yielded neoglycoproteins for glycohistochemical analysis. The tumor panel included routinely fixed tissue sections from 67 cancer cases (15 Dukes A, 20 Dukes B, 15 Dukes C, and 17 metastatic tumors) and 6 hepatic metastases as well as 20 normal biopsy specimens as control. Quantitative image analysis determined the labeling index and the mean optical density in each case, separating tumor and peritumoral connective tissue. Specific carbohydrate-dependent binding with inter-individual heterogeneity was observed. The distinct staining profiles were not associated with disease stage or metastasis formation. Strong expression of lactose-binding sites in the peritumoral connective tissue especially in terms of the labeling index was significantly correlated with reduced survival in Dukes B patients (p=0.02). A similar tendency was observed in the Dukes C group. In conclusion, the application of the synthetic markers aimed at lectin detection defines lactose binding as new prognostic marker. It has potential relevance for improving the benefit from adjuvant therapy in Dukes B colorectal cancer patients. Technically, chemical ligand immobilization to an inert carrier can find useful application beyond glycosciences in the quest to extend the panel of tumor markers.



S. Hancq, I. Salmon, J. Brotchi, O. De Witte, H. Gabius, C. Heizmann, R. Kiss, C. Decaestecker,
S100A5: a marker of recurrence in WHO grade I meningiomas
Neuropathology and applied neurobiology, Vol. 30, 2, pp. 178-187, 2004
Bibtex
Bibtex : info:hdl:2013/52131
Note : Comparative Study
Abstract : Some WHO grade I intracranial meningiomas resected from the same sites and with the same quality of resection (Simpson's grading scale) recur, while others do not. The reasons for this variability in occurrence of recurrence have not yet been determined. We therefore investigated the prognostic recurrence value of seven biological markers on a series of completely resected WHO grade I meningiomas. For this purpose, we analysed a series of 33 WHO grade I meningiomas totally resected between 1980 and 1990 (a follow-up of 10 years), including 14 cases of recurrence. The fixed tumour material from each meningioma was submitted to histochemical analyses targeting galectin-3 and its binding sites, the S100A5, S100A6 and S100B proteins, and cathepsin-B and -D. The levels of expression were assessed semi-quantitatively (in terms of the staining intensity and the labelling index) and submitted to uni- and multivariate analyses. Of all the markers investigated, only S100A5 expression can be associated with any significant prognostic value in the matter of recurrence. More particularly, the meningiomas with high levels of S100A5 staining intensity either did not recur, or recurred later than those with a low immunopositive S100A5 intensity (P = 0.004). Cox regression analyses demonstrated that this latter marker was associated with significant prognostic values independent of the patients' ages. Furthermore, the combination of the patients' ages and S100A5 staining intensity permitted the identification of a group with a particularly high risk of recurrence, that is, the patients younger than 55 and with meningiomas exhibiting low S100A5 intensities (P = 0.001). In conclusion, the S100A5 protein could play a role in the recurrence of totally resected WHO grade I meningiomas.



A. Gaigneaux, C. Decaestecker, I. Camby, T. Mijatovic, R. Kiss, J. Ruysschaert, E. Goormaghtigh,
The infrared spectrum of human glioma cells is related to their in vitro and in vivo behavior
Experimental cell research, Vol. 297, 1, pp. 294-301, 2004
Bibtex
Bibtex : info:hdl:2013/52127
Note : Journal Article
Abstract : The present research investigates whether infrared spectra can be related to the biological characteristics of glioma cell lines. We used nine human glioma cell lines for which a series of in vitro and in vivo biological features had already been established [Glia 36 (2001) 375] and were able to show that their characteristic infrared spectra reflect their in vitro migration (i.e., motility and invasiveness) properties and their in vivo aggressiveness. More particularly, the infrared data evidenced correlations at the level of the lipid/protein ratio. These relationships were found to be tissue-dependent when controlled on seven pancreatic carcinoma cell lines. We also showed that oligodendroglial and astrocytic tumor cells, whose identification remains difficult, can easily be identified by their infrared spectra in the lipid acyl chain region as well as in the nucleic acid region. We concluded that infrared spectroscopy could usefully complement information provided by more conventional diagnostic and prognostic (e.g., morphological and molecular) approaches.



Conferences

R. Ercek, P. De Doncker, F. Grenez,
Modeling of NLOS-Multipath in Urban Canyons for GNSS Applications
Proc. of URSI FORUM 2004, pp. 88, Brussels (Belgium), 2004
Bibtex
Bibtex : info:hdl:2013/127213
Note : Language of publication: en




2003

Papers

I. Camby, C. Decaestecker, L. Gordower, R. Dedecker, Y. Kacem, A. Lemmers, H. Siebert, N. Bovin, P. Wesseling, A. Danguy, I. Salmon, H. Gabius, R. Kiss,
A prospective comparative study of push and wireless-capsule enteroscopy in patients with obscure digestive bleeding
Acta gastro-enterologica Belgica (Ed. multilingue), Vol. 66, 3, pp. 199-205, 2003
Bibtex
Bibtex : info:hdl:2013/83103
Note : SCOPUS: ar.j



A. Hittelet, I. Camby, N. Nagy, H. Legendre, Y. Bronckart, C. Decaestecker, H. Kaltner, N. Nifant'ev, N. Bovin, J. Pector, I. Salmon, H. Gabius, R. Kiss, P. Yeaton,
Binding sites for Lewis antigens are expressed by human colon cancer cells and negatively affect their migration.
Laboratory investigation, Vol. 83, 6, pp. 777-787, 2003
Bibtex
Bibtex : info:hdl:2013/52156
Note : Journal Article
Abstract : In colon cancer, endothelial cell selectins can promote tumor cell attachment via interactions with sialylated Lewis antigens present at the surface of tumor cells, thereby facilitating tumor cell arrest and transmigration into the extravascular space. However, it is not known whether Lewis antigens interact with colon tumor cells and modify their migration. Our aim was to detect the presence of binding sites on human tumor cells for Lewis(a/x) antigens and their sialylated derivatives in vitro and in vivo and to analyze their influence on migration of colon cancer cells. The immunocytochemical and histochemical levels of expression of the four Lewis antigens were quantitatively determined in four human colon cancer cell lines and in in vivo nude mice xenografts. The levels of expression of specific binding sites for these sugar epitopes were determined by synthetic neoglycoconjugates. The influence of binding of these carbohydrate ligands on cancer cell migration was quantitatively evaluated by computer-assisted phase-contrast videomicroscopy performed on Matrigel culture supports either left uncoated or coated with neoglycoconjugate presenting synthetic Lewis(a), sialyl Lewis(a), Lewis(x), or sialyl Lewis(x) antigens. The influence of the calcium concentration in the culture medium on the Lewis antigen-mediated effects was checked. Human colon cancer cells expressed significant amounts of specific binding sites detected by the synthetic probes in addition to the oligosaccharide epitopes. The expression levels differed considerably between the four cell lines and between in vitro and in vivo specimens. Cell migration analysis revealed that the four Lewis antigens markedly decreased the levels of migration of the HCT-15 and LoVo cancer cells. This effect depends on the calcium concentration in the culture medium. Binding sites for Lewis epitopes are present on colon cancer cells. The functional relevance of these sites is indicated by the negative influence on cell migration of a matrix containing the oligosaccharides as ligand parts.



P. Pelc, N. Vanmuylder, F. Lefranc, C. Heizmann, S. Hassid, I. Salmon, R. Kiss, S. Louryan, C. Decaestecker,
Differential expression of S100 calcium-binding proteins in epidermoid cysts, branchial cysts, craniopharyngiomas and cholesteatomas.
Histopathology, Vol. 42, 4, pp. 387-394, 2003
Bibtex
Bibtex : info:hdl:2013/51227
Note : Journal Article
Abstract : AIMS: To investigate whether epidermoid cysts, branchial cysts, craniopharyngiomas and cholesteatomas express S100 proteins differentially by immunohistochemical assaying the presence of S100A1, S100A2, S100A3, S100A4, S100A5, S100A6 and S100B. METHODS AND RESULTS: Immunopositivity/negativity was recorded for each S100 protein in a series of 52 cases consisting of 12 epidermoid cysts, 12 branchial cysts, 15 adamantinomatous craniopharyngiomas and 13 acquired cholesteatomas. Except in the case of the craniopharyngiomas, immunoreactivity was assessed independently in the basal membrane and the basal, the internal and the keratin layers. Our data show that in contrast to S100B, which was rarely expressed, S100A1, S100A2, S100A4 and S100A5 were often present in these four types of epithelial lesions. S100A3 and S100A6 and, to a lesser extent, S100A5 were the most differentially expressed proteins across the different histopathological groups analysed. These three proteins are expressed more often in craniopharyngiomas and cholesteatomas, the two more aggressive types of lesions. CONCLUSIONS: This is the first study to report data on the expression of seven S100 proteins in different histopathological groups of epithelial head and neck lesions, whose precise embryological origins are still a matter of debate. S100 proteins could possibly be used as markers to target this embryonic origin, since our results show that S100A3 and S100A6 (and, to a lesser extent, S100A5) are expressed differentially across these different groups of epithelial lesions.



N. Sadeghi-Meibodi, I. Camby, S. Goldman, H. Gabius, D. Balériaux, I. Salmon, C. Decaestecker, R. Kiss, T. Metens,
Effect of hydrophilic components of the extracellular matrix on quantifiable diffusion-weighted imaging of human gliomas: preliminary results of correlating apparent diffusion coefficient values and hyaluronan expression level.
American journal of roentgenology, Vol. 181, 1, pp. 235-241, 2003
Bibtex
Bibtex : info:hdl:2013/51644
Note : Journal Article
Abstract : OBJECTIVE: The purpose of this study was to evaluate the relationship between apparent diffusion coefficient (ADC) measured by MR imaging and the level of immunohistochemical expression of hyaluronan or hyaluronic acid as one of the main hydrophilic components of the extracellular matrix in brain glial tumors. MATERIALS AND METHODS: Nineteen patients with primary glial brain tumors were included in the study. Mean ADC values were calculated in all tumors and were normalized with the ADC values of the contralateral normal-appearing brain ratios. All tumors underwent surgical resection, and the histologic diagnosis was based on the analysis of the surgical specimen. Mean values of the labeling index of hyaluronan (LI-HA) were calculated to determine quantifiably the histochemical expression of hyaluronan in the tumor. The mean ADC values and the mean ADC ratios (ADC(ratio)) of the tumors were then correlated to the mean values of the LI-HA. RESULTS: The mean ADC (93 x 10(-5) mm(2)/sec) and the mean ADC(ratio) (1.25) of the high-grade glial tumors were significantly lower than the mean ADC (123 x 10(-5) mm/sec) and the mean ADC(ratio) (1.64) of the low-grade glial tumors (p < 0.01). The mean LI-HA (72.8\%) was also significantly lower in the high-grade gliomas than the mean LI-HA (93.4\%) in the low-grade gliomas (p < 0.001). A positive correlation was found between mean ADC values and the mean LI-HA (tau = 0.35, p < 0.05) and also between the mean ADC(ratio) and the mean LI-HA (tau = 0.33, p < 0.05). CONCLUSION: Hyaluronan as one of the main hydrophilic components of the extracellular matrix in gliomas likely contributes to differences in the ADC values between high- and low-grade glial tumors.



C. Delbrouck, H. Gabius, H. Kaltner, C. Decaestecker, R. Kiss, S. Hassid,
Expression patterns of galectin-1 and galectin-3 in nasal polyps and middle and inferior turbinates in relation to growth regulation and immunosuppression.
Archives of otolaryngology--head & neck surgery, Vol. 129, 6, pp. 665-669, 2003
Bibtex
Bibtex : info:hdl:2013/52153
Note : Journal Article
Abstract : BACKGROUND: The term nasal polyposis describes benign growth processes in the nasal and sinus mucosa, which are mainly located in the middle meatus and never in the inferior meatus. As a step to define the biochemical determinants relevant for growth regulation, we focused on endogenous lectins known for anti-apoptotic (galectin-3) and immunomodulatory (galectin-1) activities. DESIGN: Using computer-assisted microscopy, we performed an immunohistochemical investigation defining the quantitative parameters of expression of galectin-1 and galectin-3 in 10 nasal polyps, 10 middle turbinates, and 10 inferior turbinates, all of which were obtained from surgical resection. RESULTS: Our data show that galectin-3 expression is markedly (P<.001) higher in nasal polyps than in turbinates. No relation to the allergic status was discovered. Galectin-1 expression is higher in nasal polyps than in middle turbinates (P<.001) in nonallergic patients compared with allergic ones (in glandular epithelium, P =.009; in connective tissue, P =.006). The lowest galectin-1 expression was observed in the middle turbinate. CONCLUSIONS: These data are in line with a positive influence of galectin-3 on growth and an immunoregulatory role of galectin-1, mimicking an increased expression dependent on glucocorticoid.



H. Legendre, C. Decaestecker, N. Nagy, A. Hendlisz, M. Sch{\"u}ring, I. Salmon, H. Gabius, J. Pector, R. Kiss,
Prognostic values of galectin-3 and the macrophage migration inhibitory factor (MIF) in human colorectal cancers.
Modern pathology, Vol. 16, 5, pp. 491-504, 2003
Bibtex
Bibtex : info:hdl:2013/52162
Note : Journal Article
Abstract : This study aims to investigate whether the immunohistochemical levels of expression of galectin-3 and the macrophage migration inhibitory factor (MIF) are associated with prognostic values in human colorectal tumors. This was performed on 99 specimens including 69 colorectal tumors (17 Dukes A, 19 Dukes B, 15 Dukes C and 18 metastatic tumors that we labeled as D), 10 hepatic metastases from colorectal cancers and 20 normal specimens (biopsies). The immunohistochemical levels of expression of MIF and galectin-3 were quantified on routine histological slides by means of computer-assisted microscopy. Separate analyses were performed on epithelial and connective tissue. The levels of expression of both MIF and galectin-3 were very significantly higher in epithelial tumor tissue when compared with normal epithelial specimens. A positive and significant correlation between MIF and galectin-3 expression was evidenced in connective tumor tissue, and in particular in the cases associated with short survival periods (less than 5 years). In the case of the Dukes A or B tumors, we established two new prognostic groups (labeled I and II) on the basis of the levels of galectin-3 expression measured in the tumor epithelium. In the case of the Dukes C or D tumors, we established two other prognostic groups (labeled III and IV) on the basis of the levels of MIF expression measured in the connective tissue. Kaplan-Meyer analyses confirmed the additional prognostic values (as compared with conventional clinical staging) given by this new classification (groups I to IV). They show that the Dukes A or B tumors characterized by low levels of galectin-3 expression in the tumor epithelium are associated with significantly better prognoses than those characterized by high levels. In addition, the Dukes C or D tumors characterized by high levels of MIF expression in the connective tumor tissue are associated with significantly better prognoses than those characterized by low levels. In conclusions, MIF and galectin-3 expression levels in colorectal tumors are related to their levels of biological aggressiveness. These markers could be used to identify patients at risk, for whom more aggressive adjuvant therapy seems to be indicated.



N. Nagy, H. Legendre, O. Engels, S. André, H. Kaltner, K. Wasano, Y. Zick, J. Pector, C. Decaestecker, H. Gabius, I. Salmon, R. Kiss,
Refined prognostic evaluation in colon carcinoma using immunohistochemical galectin fingerprinting.
Cancer, Vol. 97, 8, pp. 1849-1858, 2003
Bibtex
Bibtex : info:hdl:2013/52166
Note : Comparative Study
Abstract : BACKGROUND: Knowledge of the expression of the galectins in human colon carcinomas is mainly restricted to galectin-3 and, to a lesser extent, galectin-1. The current study analyzed the prognostic values contributed by galectin-1, galectin-3, galectin-4, and galectin-8 in cases of colon carcinoma. METHODS: The authors selected 55 colon carcinomas (including 10 Dukes A, 16 Dukes B, 15 Dukes C, and 14 metastatic tumors that the authors labeled "Stage D"). The immunohistochemical levels of expression of the four galectins were determined quantitatively by means of computer-assisted microscopy. RESULTS: The data from the current study indicate that the four galectins under study are associated with significant and separate prognostic values that depend on the Dukes stage of the colon tumor. In particular, the authors observed a significant prognostic value associated with galectins-1, -3, and -4 in Dukes A and B colon tumors. In addition, significant prognostic value also was associated with galectin-8 in Dukes C and D colon tumors. The prognostic values associated with the levels of expression of galectin-1 and galectin-4 in Dukes A and B tumors appear to be independent of the Dukes stage. The same feature was observed when galectin-4 and galectin-8 were analyzed in the complete series. CONCLUSIONS: The data from the current study strongly suggest that galectins-1, -3, and -4 may be involved in the early stages of human colon carcinoma development and that galectin-8 is involved in the later stages.




2002

Papers

B. Joseph, F. Darro, A. Béhard, B. Lesur, F. Collignon, C. Decaestecker, A. Frydman, G. Guillaumet, R. Kiss,
3-Aryl-2-quinolone derivatives: synthesis and characterization of in vitro and in vivo antitumor effects with emphasis on a new therapeutical target connected with cell migration
Journal of medicinal chemistry, Vol. 45, 12, pp. 2543-2555, 2002
Bibtex
Bibtex : info:hdl:2013/52231
Note : Journal Article
Abstract : Among 25 3-aryl-2-quinolone derivatives synthesized, the antitumor activity of some of them was characterized both in vitro and in vivo. In this series, no compound appeared to be cytotoxic in vitro, as was known by the colorimetric MTT assay carried out on 12 distinct human cancer cell lines obtained from the American Type Culture Collection. Indeed, the concentration values decreasing the growth of the 12 cell lines by at least 50\% (IC(50) index) were always higher than 10(-5) M. We then made use of a computer-assisted phase-contrast videomicroscopy system to quantitatively determine in vitro the level of migration of living MCF-7 human breast cancer cells. For example, at 10(-7) M, compounds 7, 13, 16, and 28 markedly decreased the migration level of these MCF-7 human breast cancer cells. The in vivo determination of the maximum tolerated dose showed that all compounds tested were definitively nontoxic. When the nontoxic, antimigratory compound 16 was combined with either doxorubicin or etoposide, two cytotoxic compounds routinely used in the clinic, this led to additive in vivo benefits from this treatment (as compared to individual administrations of the drugs) when the MXT mouse mammary adenocarcinoma was used. Thus, nontoxic antimigratory compounds, including the 2-quinolone derivatives synthesized here, can actually improve the efficiency of antitumor treatment when combined with conventional cytotoxic agents.



M. Saerens, P. Latinne, C. Decaestecker,
Adjusting the outputs of a classifier to new a priori probabilities: a simple procedure
Neural computation, Vol. 14, 1, pp. 21-41, 2002
Bibtex
Bibtex : info:hdl:2013/68391
Note : Journal Article
Abstract : It sometimes happens (for instance in case control studies) that a classifier is trained on a data set that does not reflect the true a priori probabilities of the target classes on real-world data. This may have a negative effect on the classification accuracy obtained on the real-world data set, especially when the classifier's decisions are based on the a posteriori probabilities of class membership. Indeed, in this case, the trained classifier provides estimates of the a posteriori probabilities that are not valid for this real-world data set (they rely on the a priori probabilities of the training set). Applying the classifier as is (without correcting its outputs with respect to these new conditions) on this new data set may thus be suboptimal. In this note, we present a simple iterative procedure for adjusting the outputs of the trained classifier with respect to these new a priori probabilities without having to refit the model, even when these probabilities are not known in advance. As a by-product, estimates of the new a priori probabilities are also obtained. This iterative algorithm is a straightforward instance of the expectation-maximization (EM) algorithm and is shown to maximize the likelihood of the new data. Thereafter, we discuss a statistical test that can be applied to decide if the a priori class probabilities have changed from the training set to the real-world data. The procedure is illustrated on different classification problems involving a multilayer neural network, and comparisons with a standard procedure for a priori probability estimation are provided. Our original method, based on the EM algorithm, is shown to be superior to the standard one for a priori probability estimation. Experimental results also indicate that the classifier with adjusted outputs always performs better than the original one in terms of classification accuracy, when the a priori probability conditions differ from the training set to the real-world data. The gain in classification accuracy can be significant.



M. Saerens, P. Latinne, C. Decaestecker,
Any reasonable cost function can be used for a posteriori probability approximation.
IEEE transactions on neural networks, Vol. 13, 5, pp. 1204-1210, 2002
Bibtex
Bibtex : info:hdl:2013/68401
Note : Journal Article
Abstract : In this paper, we provide a straightforward proof of an important, but nevertheless little known, result obtained by Lindley in the framework of subjective probability theory. This result, once interpreted in the machine learning/pattern recognition context, puts new light on the probabilistic interpretation of the output of a trained classifier. A learning machine, or more generally a model, is usually trained by minimizing a criterion-the expectation of the cost function-measuring the discrepancy between the model output and the desired output. In this letter, we first show that, for the binary classification case, training the model with any "reasonable cost function" can lead to Bayesian a posteriori probability estimation. Indeed, after having trained the model by minimizing the criterion, there always exists a computable transformation that maps the output of the model to the Bayesian a posteriori probability of the class membership given the input. Then, necessary conditions allowing the computation of the transformation mapping the outputs of the model to the a posteriori probabilities are derived for the multioutput case. Finally, these theoretical results are illustrated through some simulation examples involving various cost functions.



K. Pelc, S. Vincent, M. Ruchoux, R. Kiss, R. Pochet, E. Sariban, C. Decaestecker, C. Heizmann,
Calbindin-D28k: a marker of recurrence for medulloblastomas
Cancer, Vol. 95, 2, pp. 410-419, 2002
Bibtex
Bibtex : info:hdl:2013/51629
Note : Journal Article
Abstract : BACKGROUND: The expression of the Ca(2+)-binding protein calbindin-D(28k) was analyzed in medulloblastomas in relation to clinical features and other biologic markers related to cell proliferation, differentiation, p53, and cerebellar developmental regulated gene expression. METHODS: Immunohistochemistry was carried out on histologic slides from a first retrospective series of 29 nonmetastatic and 10 metastatic medulloblastoma formalin-fixed, paraffin-embedded tissues, using specific antibodies against calbindin-D(28k), calretinin, alpha-parvalbumin and beta-parvalbumin, and S100 proteins. Informed consent was obtained from the subjects and/or guardians. Other biologic markers for differentiation, cell proliferation, the expression of the p53 tumor suppressor gene protein, and cerebellar developmental regulated genes were similarly investigated. A second series of 16 medulloblastomas from young patients (younger than 15 years) was added in order to validate the results obtained in the first series. RESULTS: Of all the markers investigated, only calbindin-D(28k) was significantly associated with prognosis. Survival and remission (i.e. recurrence free) time analysis performed on all the cases (n = 55) confirmed a high risk of death (P = 0.004) and recurrence (P = 0.003) associated with calbindin-positivity. As calbindin-positivity was predominantly observed in tumors from young patients, the authors confirmed its prognostic value in the subgroup of patients younger than 15 years (n = 37). Cox regression analysis showed a significant and independent prognostic value for calbindin expression and, to a lesser extent, the type of surgery (total or subtotal). Three risk groups were thus identified, distinguishing among the cases characterized by a total resection and calbindin-negativity (good prognosis), by a subtotal resection and calbindin-negativity (intermediary), and by calbindin-positivity (bad prognosis). CONCLUSIONS: The current study suggests that calbindin-positive medulloblastomas represent a subclass of aggressive tumors more frequently seen in younger patients.



S. Rorive, B. Eddafali, S. Fernandez, C. Decaestecker, S. André, H. Kaltner, I. Kuwabara, F. Liu, H. Gabius, R. Kiss, I. Salmon,
Changes in galectin-7 and cytokeratin-19 expression during the progression of malignancy in thyroid tumors: diagnostic and biological implications.
Modern pathology, Vol. 15, 12, pp. 1294-1301, 2002
Bibtex
Bibtex : info:hdl:2013/52189
Note : Journal Article
Abstract : Galectin-7 is associated with p53-dependent onset of apoptosis and proliferation control/differentiation in keratinocyte development. It is also up-regulated in chemically induced rat mammary carcinogenesis. Because the levels of expression of galectin-7 have never been investigated in thyroid tumors (in contrast to those of galectin-1 and -3 associated with malignancy), we initiated analysis of the expression of galectin-7 in benign and malignant thyroid lesions together with that of cytokeratin-19 (CK19), a marker already demonstrated to be useful in diagnosing this kind of lesion. The immunohistochemical expression levels were quantitatively determined by means of computer-assisted microscopy on a series of 84 thyroid lesions including 10 multinodular goiters, 32 adenomas, and 42 carcinomas. Our data clearly indicate a marked down-regulation of galectin-7 expression in a large proportion of adenomas (including the normomacrofollicular, microfollicular, and trabecular variants) if compared with carcinomas. In accordance with results of previous studies, a marked up-regulation of CK19 expression was observed in the thyroid carcinomas, and this contrasted in particular with the low CK19 expression observed in the microfollicular adenomas. Of importance for diagnostic implications, the combination of these two markers enabled our series of microfollicular adenomas (characterized by low galectin-7 and CK19 expression) to be efficiently distinguished from the encapsulated follicular variant of papillary thyroid carcinomas (high galectin-7 and CK19 expression).



F. Lefranc, J. Golzarian, C. Chevalier, O. De Witte, R. Pochet, C. Heizmann, C. Decaestecker, J. Brotchi, I. Salmon, R. Kiss,
characterization of the level of expression of S100B, S100A1, S100A2, S100A4 and S100A6 calcium-binding proteins in a rat model of cerebral basilar artery vasospasm
Journal of neurosurgery, Vol. 97, pp. 408-415, 2002
Bibtex
Bibtex : info:hdl:2013/52537
Note : Language of publication: en



P. Latinne, O. Debeir, C. Decaestecker,
Combining Different Methods and Numbers of Weak Decision Trees
Pattern Analysis and Applications, Vol. 5, 2, pp. 201-209, 2002
Bibtex
Bibtex : info:hdl:2013/52956
Note : Language of publication: en



F. Lefranc, J. Golzarian, C. Chevalier, O. De Witte, R. Pochet, C. Heizman, C. Decaestecker, J. Brotchi, I. Salmon, R. Kiss,
Expression of members of the calcium-binding S-100 protein family in a rat model of cerebral basilar artery vasospasm
Journal of neurosurgery, Vol. 97, 2, pp. 408-415, 2002
Bibtex
Bibtex : info:hdl:2013/51239
Note : Journal Article
Abstract : OBJECT: The aim of this study was to investigate the role of S-100 proteins in the onset of vasospasm induced by subarachnoid hemorrhage (SAH), which leads to severe neurological morbidity and death. It has recently been argued that modifications in the levels of expression of some intracellular signaling elements controlling the organization of the actin cytoskeleton (including the rho A small guanosine triphosphatase and its related kinases) play significant roles in the induction of smooth-muscle cell contraction, a calcium-dependent process that is pathognomonic of SAH-induced vasospasm at the molecular level. Several members of the calcium-binding S-100 protein family are known to exercise significant control over the organization of the actin cytoskeleton. METHODS: The levels of expression of S-100 proteins in SAH-induced vasospasm have never been investigated. The authors therefore used a double-hemorrhage rat model of SAH-induced vasospasm to determine whether the levels of expression of S-100B, S-100A1, S-100A2, S-100A4, and S-100A6 proteins on immunohistochemical studies were significantly modified in this pathological condition. Quantitative determination of immunohistochemically confirmed expression of S-100 proteins (accomplished with the aid of computer-assisted microscopy) revealed that SAH-induced vasospasm is accompanied by a very significant increase in S-100B, S-100A2, and, to a lesser extent, in S-100A4 and S-100A6 expression, whereas this condition is not accompanied by significant modifications to S-100A1 expression. CONCLUSIONS: Such significant modifications in the levels of expression of different members of the S-100 protein family in SAH-induced vasospasm could relate to the various roles played by this specific class of calcium-binding proteins at the level of actin cytoskeleton organization. These modifications in S-100 protein expression seem relatively specific to SAH-induced vasospasm, because heparin-induced epilepsy-like symptoms were accompanied by dramatically distinct profiles of S-100 protein expression.



N. Belot, R. Pochet, C. Heizmann, R. Kiss, C. Decaestecker,
Extracellular S100A4 stimulates the migration rate of astrocytic tumor cells by modifying the organization of their actin cytoskeleton.
Biochimica et biophysica acta, Vol. 1600, 1-2, pp. 74-83, 2002
Bibtex
Bibtex : info:hdl:2013/52191
Note : Journal Article
Abstract : In previous studies, we have shown that numbers of S100 calcium-binding proteins (including S100A4) are expressed differentially in astrocytic tumors according to their levels of malignancy. S100A4 is involved in tumor progression, cell migration and metastasis. This protein is able to play extracellular roles such as neuritogenic and angiogenic activities. The present study aims to investigate the possible role played by extracellular S100A4 in the in vitro migration of astrocytic tumor cells. The speed and rate of migration of living cells were measured using computer-assisted videomicroscopy. In parallel, we also analyzed the effects of extracellular S100A4 on the organization of the actin cytoskeleton and the expression of a number of its molecular regulators. These included small Rho-GTPases (RhoA, Rac1 and Cdc42) and some of their direct effectors (mDia and N-WASP), and also actin-binding proteins such as profilin and alpha-actinin. Our data demonstrate the influence of S100A4 on astrocytic tumor cells with respect to these different aspects. Indeed, we show that extracellular S100A4 treatments decrease both the amount of polymerized F-actin and the levels of expression of RhoA, mDia and profilin. While a decrease in the Cdc42 and N-WASP expression was also observed, the Rac1 expression remained unchanged. All these activities, which result in the stimulation of cell motility, contribute to the understanding of the extracellular role of S100A4.



C. Delbrouck, I. Doyen, N. Belot, C. Decaestecker, R. Ghanooni, A. De Lavareille, H. Kaltner, G. Choufani, A. Danguy, G. Vandenhoven, H. Gabius, S. Hassid, R. Kiss,
Galectin-1 is overexpressed in nasal polyps under budesonide and inhibits eosinophil migration
Laboratory investigation, Vol. 82, 2, pp. 147-158, 2002
Bibtex
Bibtex : info:hdl:2013/70171
Note : Journal Article
Abstract : Because of the importance of galectins for various cellular activities, the influence of the glucocorticoid budesonide on the level of expression of galectins-1 and -3 was investigated in human nasal polyposis. Ten nasal polyps obtained from surgical resection were maintained for 24 hours in the presence of various concentrations of budesonide. As quantitatively demonstrated by means of computer-assisted microscopy, 250 ng/ml (the highest dose tested) induced a pronounced increase of galectin-1 expression. This feature was observed in nasal polyps from allergic patients but not in those from nonallergic patients. Since eosinophils represent the main inflammatory cell population in nasal polyps, we investigated the effect of galectin-1 on their migration levels by means of quantitative phase-contrast computer-assisted videomicroscopy. Our results show that galectin-1 (coated on plastic supports) markedly reduced the migration levels of eosinophils in comparison to P-selectin. On the cellular level, marked modifications in the polymerization/depolymerization dynamics of the actin cytoskeleton (as revealed by means of computer-assisted fluorescence microscopy) and, to a much lesser extent, an increase in the adhesiveness of eosinophils to tested substrata were detectable. The present study therefore reveals a new galectin-1-mediated mechanism of action for glucocorticoid-mediated anti-inflammatory effects.



C. Hayot, S. Farinelle, R. De Decker, C. Decaestecker, F. Darro, R. Kiss, M. Van Damme,
In vitro pharmacological characterizations of the anti-angiogenic and anti-tumor cell migration properties mediated by microtubule-affecting drugs, with special emphasis on the organization of the actin cytoskeleton
International journal of oncology, Vol. 21, 2, pp. 417-425, 2002
Bibtex
Bibtex : info:hdl:2013/71059
Note : Comparative Study
Abstract : The aim of the present work is to investigate whether microtubule-affecting drugs including vincristine, vinblastine, vindesine and vinorelbine are able to produce an anti-angiogenic effect at non-cytotoxic doses in the same way of taxol. The cytotoxic effects were determined by means of the colorimetric MTT assay, and the anti-angiogenic effects on HUVEC cells growing on Matrigel and forming capillary networks. Sixteen additional drugs (camptothecin, SN38, topothecan, adriamycin, daunomycin, etoposide, bleomycin, melphalan, mitomycin C, TNP-470, cisplatin, carboplatin, 5-fluorouracil, methotrexate, suramin and batimastat) were used as control in order to test the specificity of the microtubule-affecting drug effects. We also investigated by means of videomicroscopy whether microtubule-affecting drugs could produce anti-migratory effects at non-cytotoxic doses on tumor cells. Finally, we used computer-assisted fluorescence microscopy to characterize the influence of microtubule-affecting drugs on the polymerization/depolymerization dynamics of the actin cytoskeleton in tumor cells. Our results show that taxol, vincristine and vindesine behave similarly in their ability to reduce the capillary network formation by HUVEC cells cultured on Matrigel. These anti-angiogenic effects appear at non-cytotoxic concentrations. In contrast, vinblastine and vinorelbine produce apparent anti-angiogenic effects by direct cytotoxicity. Microtubule-affecting agents are also able to significantly reduce the level of migration of tumor cells at non-cytotoxic concentrations, some of these effects may occur via modifications to the actin cytoskeleton organization. Several types of microtubule-affecting agents could be used as anti-angiogenic agents by administering them at non-cytotoxic concentrations, and some microtubule-affecting agents abandoned in pharmacological assays could turn out to be potent anti-migratory drugs acting on tumor cells, though without being too cytotoxic.



E. Nemec, S. Van De Putte, C. Van Pachterbeke, R. Vokaer, V. Budel, C. Deprez, R. Kiss, C. Decaestecker,
Ploidy and chromatin pattern analysis as an aid for cervical smear diagnosis
Histology and histopathology, Vol. 17, 2, pp. 403-409, 2002
Bibtex
Bibtex : info:hdl:2013/52208
Note : Journal Article
Abstract : In the present study we used computer-assisted microscopy to analyze the morphology of Feulgen-stained cell nuclei in cell populations obtained at the same time as routinely performed cervical smears and in the same way. We investigated in a series of 110 cases whether the quantitative morphonuclear description of cytological cervical samples is able to aid pathologists to distinguish between benign and more suspect premalignant lesions. For this task nuclear DNA content, nuclear morphometry (size and anisonucleosis level) and chromatin pattern-related parameters were compiled for each specimen enrolled in the database. A set of 32 normal and 17 high-grade squamous intraepithelial lesion (HSIL) specimens (with diagnostic confirmations) were selected as references and used to establish a discriminant model on the basis of cytometry-generated variables. This model was then used to score the remaining 61 cases in our series (including cases exhibiting benign cellular changes, squamous cells of undetermined significance, low-grade SIL and cancers). The results show that a model discriminating efficiently between normal and HSIL groups can be obtained by combining 5 quantitative features (1 DNA ploidy-related, 2 morphometrical and 2 chromatin texture features). A 97\% specificity and an 88\% sensitivity characterized the boundary so established. When applied to new cases, the model was in fact able to correct diagnoses for cases which had been down- or up-graded on the basis of the Bethesda system, and provided scores in accordance with histological control.



N. Nagy, D. Hoyaux, I. Gielen, B. Sch{\"a}fer, R. Pochet, C. Heizmann, R. Kiss, I. Salmon, C. Decaestecker,
The Ca2+-binding S100A2 protein is differentially expressed in epithelial tissue of glandular or squamous origin
Histology and histopathology, Vol. 17, 1, pp. 123-130, 2002
Bibtex
Bibtex : info:hdl:2013/52229
Note : Journal Article
Abstract : It has been previously shown that S100A2 is downregulated in tumor cells. The level of immunohistochemical S100A2 expression was therefore characterized in 424 normal and tumoral (benign and malignant) tissues of various origins, but mostly epithelial (with either glandular, squamous, respiratory or urothelial differentiation). We also investigated whether S100A2 could be co-localized with cytokeratin K14, an intermediate filament protein expressed in basal proliferative keratinocytes. Our data show that S100A2 has a low level of expression in non-epithelial tissue. In epithelial tissue S100A2 expression decreases remarkably in the tumors when compared to the normal specimens, and was correlated with the level of keratin K14. This decrease in S100A2 staining from normal to cancer cases is more pronounced in glandular than in squamous epithelial tissue. In addition, the patterns of S100A2 staining also differ between glandular and squamous tissue. These data suggest distinct functional roles for S100A2 in epithelial tissue of squamous or glandular origins.



S. Hassid, A. Hashemi Afrapoli, C. Decaestecker, G. Choufani,
UPPP for snoring: long-term results and patient satisfaction
Acta oto-rhino-laryngologica Belgica, Vol. 56, 2, pp. 157-162, 2002
Bibtex
Bibtex : info:hdl:2013/148878
Note : SCOPUS: cp.j
Abstract : UPPP for snoring: long-term results and patient satisfaction. We retrospectively survey 57 patients who underwent uvulopalatopharyngoplasty (UPPP) because of habitual snoring over a five-year period. A total of 100 patients were sent questionnaires concerning persistent snoring, excessive daytime sleepiness (EDS), body mass index (BMI) and postoperative complications. After 5 years the success rate was 53\%. The mean snoring score was 16.7 preoperatively and decreased to 10.6 postoperatively. There was a relationship between the body mass index (BMI) preoperatively and the efficiency of the surgery. The mean EDS score was 11.1 before and 9.4 after surgery. UPPP in patients complaining of snoring is quite successful but the results decline significantly with time and patients should be warned of the possibility of snoring remaining or returning.




2001

Papers

G. Choufani, R. Ghanooni, C. Decaestecker, C. Delbrouck, P. Simon, M. Sch{\"u}ring, Y. Zick, S. Hassid, H. Gabius, R. Kiss,
Detection of macrophage migration inhibitory factor (MIF) in human cholesteatomas and functional implications of correlations to recurrence status and to expression of matrix metalloproteinases-3/9, retinoic acid receptor-beta, and anti-apoptotic galectin-3.
The Laryngoscope, Vol. 111, 9, pp. 1656-1662, 2001
Bibtex
Bibtex : info:hdl:2013/52446
Note : Journal Article
Abstract : OBJECTIVES: To investigate whether the expression of the macrophage migration inhibitory factor (MIF) 1) is detectable, 2) changes in relation to recurrence and infection status, and 3) relates to the levels of expression of growth regulators/differentiation markers, including galectin-1, -3, and -8, retinoid acid receptors (RAR)]-alpha, -beta, and -gamma, binding sites for sarcolectin, and invasion markers (cathepsins -B and -D, and matrix metalloproteinases [MMP]-2, -3, and -9) in human cholesteatomas. STUDY DESIGN: An analysis of 56 cholesteatomas resected by the same surgeon using canal wall up and canal wall down surgical procedures. METHODS: The immunohistochemical levels of expression of MIF and the proteases were quantitatively determined (using computer-assisted microscopy) on routine histologic slides by specific antibodies, and statistically correlated to parameters of the other markers determined previously in conjunction with data on apoptosis/proliferation. RESULTS: MIF expression was detected. It was significantly higher in the epithelium (P =.002) and vessels (P =.04) of the connective tissues (but not in the connective tissue itself) of recurrent as opposed to non-recurrent cholesteatomas. The MIF expression is significantly correlated (P =.006) to the RAR beta expression in non-infected cholesteatomas, and to MMP-3 (P <.01) and anti-apoptotic galectin-3 (P =.01) in infected cholesteatomas. The level of MIF expression was also correlated significantly to MMP-9 (P = 0.003), RAR beta (P <.001), and galectin-8 (P =.003) expression in the cholesteatomas regardless of their infection status. CONCLUSIONS: MIF expression in human cholesteatomas is related to the levels of biologic aggressiveness reflected in their recurrence status and MMP expression, and to the differentiation status reflected in their galactin and RAR beta expressions. Together with galectin-3, it could cooperate to form an anti-apoptotic feedback loop.



Y. Bronckart, C. Decaestecker, N. Nagy, L. Harper, B. Sch{\"a}fer, I. Salmon, R. Pochet, R. Kiss, C. Heizmann,
Development and progression of malignancy in human colon tissues are correlated with expression of specific Ca(2+)-binding S100 proteins.
Histology and histopathology, Vol. 16, 3, pp. 707-712, 2001
Bibtex
Bibtex : info:hdl:2013/52440
Note : Journal Article
Abstract : The expression levels of seven different S100 proteins (S100A1, S100A2, S100A3, S100A4, S100A5, S100A6, and S100B) were characterized by immunohistochemistry in the epithelial versus connective tissues of a series of 35 colon specimens, including 6 normal samples, 5 adenomas with low-grade dysplasia, 5 adenomas with high-grade dysplasia, and 19 cancers. The results showed that S100A2, S100A3, and S100B proteins could not (or only marginally) be detected in colon tissues. On the other hand, the expression of S100A6 increased in epithelial tissues directly proportional to the increase of malignancy. The percentage of epithelial (or connective tissue) cells expressing S100A4 significantly decreased as the malignancy grade increased. The expression level of S100A1 proteins was somewhat higher in the connective tissues of normal cases and adenomas with low-grade dysplasia than in adenomas with high-grade dysplasia and cancers. This pattern of expression was not observed in epithelial tissues. While the node-positive cancers did not express S100A1, about half of the node-negative specimens did. The expression levels of S100A5 were similar in different epithelial tissues. However, in the connective tissues the expression levels decreased inversely proportional to the increase in pathological grading of the specimens. Therefore, the present study implicates several S100 proteins as useful tools for histochemical typing of colon cancer malignancy development.



I. Camby, C. Decaestecker, L. Gordower, R. Dedecker, Y. Kacem, A. Lemmers, H. Siebert, N. Bovin, P. Wesseling, A. Danguy, I. Salmon, H. Gabius, R. Kiss,
Distinct differences in binding capacity to saccharide epitopes in supratentorial pilocytic astrocytomas, astrocytomas, anaplastic astrocytomas, and glioblastornas
Journal of neuropathology and experimental neurology, Vol. 60, 1, pp. 75-84, 2001
Bibtex
Bibtex : info:hdl:2013/83104
Note : SCOPUS: ar.j
Abstract : We monitored the expression of glycan-binding sites on a panel of 10 biotinylated neoglycoconjugates by means of quantitative computer-assisted microscopy to further study the molecular mechanisms in the extensive infiltration of the surrounding brain parenchyma by most astrocytic tumors. Three distinct histological compartments were analyzed for each of the 108 astrocytic tumors (15 pilocytic astrocytomas (WHO grade I), 25 astrocytomas (WHO grade II), 30 anaplastic astrocytomas (WHO grade III), and 38 glioblastomas (WHO grade IV) included in our series. These compartments were tumors (nonperivascular tumor astrocytes), perivascular tumor astrocytes, and blood vessel walls. Clear differences were observed between the pilocytic and the diffuse astrocytic tumors. Furthermore, malignant progression in the latter category was paralleled by a decrease in cells' ability to bind distinct sugar epitopes, especially the D-GalNAc(alpha1-3)-D-GalNAc-beta1-R determinant of the Forssman pentasaccharide in tumors, the alpha-L-fucose in perivascular tumor areas, and the beta-D-glucose in tumor vessel walls. Markedly, the level of binding site expression for alpha-D-mannose decreased in the tumors, the perivascular tumor areas, and the vessel walls. These glycohistochemical results imply the functional relevance of protein-carbohydrate interactions in this tumor system.



S. Rorive, N. Belot, C. Decaestecker, F. Lefranc, L. Gordower, S. Micik, C. Maurage, H. Kaltner, M. Ruchoux, A. Danguy, H. Gabius, I. Salmon, R. Kiss, I. Camby,
Galectin-1 is highly expressed in human gliomas with relevance for modulation of invasion of tumor astrocytes into the brain parenchyma.
GLIA, Vol. 33, 3, pp. 241-255, 2001
Bibtex
Bibtex : info:hdl:2013/51246
Note : Journal Article
Abstract : Protein (lectin)-carbohydrate interaction is supposed to be relevant for tumor cell behavior. The aims of the present work are to investigate whether galectin-1 modulates migration/invasion features in human gliomas in vitro, whether it can be detected in human gliomas immunohistochemically, and whether its expression is attributable to certain glioma subgroups with respect to invasion and prognosis. For this purpose, we quantitatively determined (by computer-assisted microscopy) the immunohistochemical expression of galectin-1 in 220 gliomas, including 151 astrocytic, 38 oligodendroglial, and 31 ependymal tumors obtained from surgical resection. We also xenografted three human glioblastoma cell lines (the H4, U87, and U373 models) into the brains of nude mice in order to characterize the in vivo galectin-1 expression pattern in relation to tumor invasion of the normal brain parenchyma. In addition, we characterized the role in vitro of galectin-1 in U373 tumor astrocyte migration and kinetics. Our data reveal expression of galectin-1 in all human glioma types with no striking differences between astrocytic, oligodendroglial, and ependymal tumors. The level of galectin-1 expression correlated with the grade in the group of astrocytic tumors only. Furthermore, immunopositivity of high-grade astrocytic tumors from patients with short-term survival periods was stronger than that of tumors from patients with long-term survivals. In human glioblastoma xenografts, galectin-1 was preferentially expressed in the more invasive parts of these xenografts. In vitro experiments revealed that galectin-1 stimulates migration of U373 astrocytes.



J. Kucharczak, J. Pannequin, I. Camby, C. Decaestecker, R. Kiss, J. Martinez,
Gastrin induces over-expression of genes involved in human U373 glioblastoma cell migration
Oncogene, Vol. 20, 48, pp. 7021-7028, 2001
Bibtex
Bibtex : info:hdl:2013/52235
Note : Journal Article
Abstract : Astrocytic tumors are the most common and the most malignant primary tumors of the central nervous system. We had previously observed that gastrin could significantly modulate both cell proliferation and migration of astrocytoma cells. We have investigated in the present study which genes could be targeted by gastrin in tumor astrocyte migration. Using a subtractive hybridization PCR technique we have cloned genes differentially over-expressed in human astrocytoma U373 cells treated or not with gastrin. We found about 70 genes over-expressed by gastrin. Among the genes overexpressed by gastrin, we paid particular attention to tenascin-C, S100A6 and MLCK genes because their direct involvement in cell migration features. Their gastrin-induced overexpression was quantitatively determined by competitive RT-PCR technique. We also showed by means of a reporter gene system that S100A6 and tenascin-C respective promoters were upregulated after gastrin treatment. These data show that gastrin-mediated effects in glioblastoma cells occur through activation of a number of genes involved in cell migration and suggest that gastrin could be a target in new therapeutic strategies against malignant gliomas.



A. Danguy, S. Rorive, C. Decaestecker, Y. Bronckart, H. Kaltner, Y. Hadari, R. Goren, Y. Zich, M. Petein, I. Salmon, H. Gabius, R. Kiss,
Immunohistochemical profile of galectin-8 expression in benign and malignant tumors of epithelial, mesenchymatous and adipous origins, and of the nervous system.
Histology and histopathology, Vol. 16, 3, pp. 861-868, 2001
Bibtex
Bibtex : info:hdl:2013/52449
Note : Journal Article
Abstract : This study aims to investigate whether the immunohistochemical expression of galectin-8 could be used as a diagnostic marker in tumor tissues of various histogenetic origins including specimens from epithelial (n=145), mesenchymatous (n=16), adipous (n=10) and central and peripheral nervous system (n=25) tissue, and 4 mesotheliomas. Immunohistochemical reactions were carried out with a polyclonal anti-galectin-8 antibody and histological slides from tissues derived from the files of the Laboratory of Anatomopathology of University Erasmus Hospital, Brussels. Formalin-fixed paraffin-embedded tissues of 45 normal cases as well as 41 benign and 114 malignant tumors were studied. Marked decreases in immunohistochemical galectin-8 expression were observed in colon (p=0.001), pancreas (p=0.007), liver (p=0.0008), skin (p=0.002) and larynx (p=0.02) tissue when comparing malignant tissue to normal tissue and/or benign tumors. The reverse relationship was observed for breast tissue (p=0.007). No statistically significant differences (p>0.05) were detected when comparing normal tissue and/or benign to malignant tumors in lung, bladder, kidney, prostate and stomach tissue. Significant galectin-8 expression was also measured in non-epithelial tissue including tumors of the central and peripheral nervous system as well as in skeletal muscle and mesotheliomas. Immunohistochemical monitoring of galectin-8 thus reveals an organ-type-dependent regulation of expression upon malignant transformation of various tissue types of epithelial origin. This observation will prompt further studies to delineate any relationship with prognosis.



P. Latinne, O. Debeir, C. Decaestecker,
Limiting the number of trees in random forests
Lecture notes in computer science, Vol. 2096, pp. 178-187, 2001
Bibtex
Bibtex : info:hdl:2013/229196
Note : SCOPUS: cp.k
Abstract : The aim of this paper is to propose a simple procedure that a priori determines a minimum number of classifiers to combine in order to obtain a prediction accuracy level similar to the one obtained with the combination of larger ensembles. The procedure is based on the McNe- mar non-parametric test of significance. Knowing a priori the minimum size of the classifier ensemble giving the best prediction accuracy, constitutes a gain for time and memory costs especially for huge data bases and real-time applications. Here we applied this procedure to four multiple classifier systems with C4.5 decision tree (Breiman's Bagging, Ho's Random subspaces, their combination we labeled ‘Bagfs', and Breiman's Random forests) and five large benchmark data bases. It is worth noticing that the proposed procedure may easily be extended to other base learning algorithms than a decision tree as well. The experimental results showed that it is possible to limit significantly the number of trees. We also showed that the minimum number of trees required for obtaining the best prediction accuracy may vary from one classifier combination method to another.



N. Belot, S. Rorive, I. Doyen, F. Lefranc, E. Bruyneel, R. Dedecker, S. Micik, J. Brotchi, C. Decaestecker, I. Salmon, R. Kiss, I. Camby,
Molecular characterization of cell substratum attachments in human glial tumors relates to prognostic features
GLIA, Vol. 36, 3, pp. 375-390, 2001
Bibtex
Bibtex : info:hdl:2013/51243
Note : Journal Article
Abstract : Glioma cell attachments to substratum play crucial roles in the invasion by glioma cells of normal brain tissue. These attachments are mediated through interactions between extracellular matrix (ECM) components, integrins, focal adhesion-linked molecules, and the actin cytoskeleton. In the present study, we investigate the molecular elements involved in cell substratum attachments in human glial tumors and their potential relationships to prognostic features. We used 10 human glioma cell lines, for which we characterized glial differentiation by means of quantitative RT-PCR for nestin, vimentin, and GFAP mRNA. We quantitatively determined the amounts of laminin, fibronectin, vitronectin, and thrombospondin secreted by these glioma cell lines in vitro, as well as the amount of each of the eight beta integrin subunits and the adhesion complex-related molecules, including talin, vinculin, profilin, zyxin, alpha-actinin, paxillin, and VASP. After quantification of the levels of migration and invasion of these 10 cell lines in vitro and, through grafts into the brains of nude mice, of their biological aggressiveness in vivo, it appeared that the levels of the beta 5 integrin subunit and alpha-actinin were directly related to biological aggressiveness. These experimental data were clinically confirmed because increasing immunohistochemical amounts of the beta 5 integrin subunit and alpha-actinin were directly related to dismal prognoses in the case of astrocytic tumors. In addition, we show that the beta 4 integrin subunit are expressed significantly more in oligodendrogliomas than in astrocytic tumors. A potential role for the beta 8 integrin subunit in glioma cell substratum attachments is also emphasized.



C. Pilette, V. Godding, R. Kiss, M. Delos, E. Verbeken, C. Decaestecker, K. De Paepe, J. Vaerman, M. Decramer, Y. Sibille,
Reduced epithelial expression of secretory component in small airways correlates with airflow obstruction in chronic obstructive pulmonary disease.
American journal of respiratory and critical care medicine, Vol. 163, 1, pp. 185-194, 2001
Bibtex
Bibtex : info:hdl:2013/52444
Note : Journal Article
Abstract : The epithelial polymeric immunoglobulin receptor/transmembrane secretory component (pIgR/SC) transports into secretions polymeric immunoglobulin A (pIgA), which is considered the first line of defense of the respiratory tract. The present study, done with quantitative immunohistochemistry, evaluated epithelial expression of secretory component (SC) and Clara cell protein (CC16) and neutrophil infiltration into the airways of eight patients with severe chronic obstructive pulmonary disease (COPD) who were undergoing lung transplantation, as compared with these processes in six nonsmoking patients with pulmonary hypertension who were used as controls and in lung specimens from five smokers without chronic bronchitis. Staining for SC was significantly decreased in the COPD patients as compared with the controls, both in large (mean optical density [MOD]: 23.4 [range: 21.1 to 27.8] versus 42.2 [range: 28.2 to 49.3], p = 0.003) and in small airways (MOD: 30.8 [range: 20.3 to 39.4] versus 41.5 [range: 39.2 to 46.2], p = 0.003). SC expression in small airways correlated strongly with functional parameters such as FEV1 (Kendall's tau (K) = 0.76, p = 0.008), FVC (K = 0.64, p = 0.03), and midexpiratory flow at 50\% of VC (MEF50) (K = 0.74, p = 0.01). The reduced expression of SC in large airways correlated with neutrophil infiltration in submucosal glands (K = -0.47, p = 0.03). Expression of CC16 in the bronchial epithelium of COPD patients was also significantly decreased as compared with that of controls, especially in small airways (MOD: 28.3 [range: 26.8 to 32.4] versus 45.8 [range: 40.7 to 56.0], p = 0.002), but no correlation was observed with lung function tests. In conclusion, this study shows that reduced expression of SC in airway epithelium is associated with airflow obstruction and neutrophil infiltration in severe COPD.



N. Nagy, C. Brenner, N. Markadieu, C. Chaboteaux, I. Camby, B. Sch{\"a}fer, R. Pochet, C. Heizmann, I. Salmon, R. Kiss, C. Decaestecker,
S100A2, a putative tumor suppressor gene, regulates in vitro squamous cell carcinoma migration.
Laboratory investigation, Vol. 81, 4, pp. 599-612, 2001
Bibtex
Bibtex : info:hdl:2013/52442
Note : Journal Article
Abstract : It has been previously shown that S100A2 is down-regulated in tumor cells and can be considered a tumor suppressor. We have recently shown that this down-regulation can be observed particularly in epithelial tissue, where S100A2 expression decreases remarkably in tumors as compared with normal specimens. In the present paper we investigate whether S100A2 could play a tumor-suppressor role in certain epithelial tissues by acting at the cell migration level. To this end, we made use of five in vitro human head and neck squamous cell carcinoma lines in which we characterized S100A2 expression at both RNA and protein level. To characterize the influence of S100A2 on cell kinetic and cell motility features, we used two complementary approaches involving specific antisense oligonucleotides and the addition of S100A2 to the culture media. The different expression analyses gave a coherent demonstration of the fact that the FADU and the RPMI-2650 cell lines exhibit high and low levels of S100A2 expression, respectively. Antisense oligonucleotides (in FADU) and extracellular treatments (in RPMI) showed that, for these two models, S100A2 had a clear inhibitory influence on cell motility while modifying the cell kinetic parameters only slightly. These effects seem to be related, at least in part, to a modification in the polymerization/depolymerization dynamics of the actin microfilamentary cytoskeleton. Furthermore, we found evidence of the presence of the receptor for advanced glycation end-products (RAGE) in RPMI cells, which may act as a receptor for extracellular S100A2. The present study therefore presents experimentally based evidence showing that S100A2 could play a tumor-suppressor role in certain epithelial tissues by restraining cell migration features, at least in the case of head and neck squamous cell carcinomas.



E. Delfourne, F. Darro, N. Bontemps-Subielos, C. Decaestecker, J. Bastide, A. Frydman, R. Kiss,
Synthesis and characterization of the antitumor activities of analogues of meridine, a marine pyridoacridine alkaloid.
Journal of medicinal chemistry, Vol. 44, 20, pp. 3275-3282, 2001
Bibtex
Bibtex : info:hdl:2013/52447
Note : Journal Article
Abstract : Marine compounds with pyridoacridine skeletons are known to exhibit interesting antitumor activities. Among these compounds, meridine has already been reported as having significant antitumor activities in vitro. We synthesized 24 analogues of meridine substituted on ring A with the aim of obtaining compounds that display significantly higher in vitro antitumor activities than meridine. The 24 compounds and meridine used as a control compound were tested at 6 different concentrations on 12 different human cancer cell lines including various histopathological types (glioblastomas and breast, colon, lung, prostate, and bladder cancers). The IC(50) value (i.e., the drug concentration inhibiting the mean growth value of the 12 cell lines by 50\%) of these 25 compounds ranged over 5 log concentrations, i.e., between 10 and 0.0001 microM, with four of the compounds exhibiting a significantly higher in vitro antitumor activity than meridine. These compounds will now be subjected to further pharmacological investigation including in vivo testing on both conventional murine tumors and human tumors grafted onto nude mice.



J. Berthe, M. Remmelink, J. Werry, I. Salmon, R. Kiss, C. Decaestecker,
The contribution of image cytometry to the characterization of clinical subgroups of lipomas.
International journal of oncology, Vol. 18, 6, pp. 1315-1321, 2001
Bibtex
Bibtex : info:hdl:2013/53516
Note : Journal Article
Abstract : The aim of the present study was to investigate whether biological features determined through image cytometry are able to characterize clinical subpopulations of lipomas. Forty lipomas excised from 36 patients were studied. On the one hand, the tumors were clinically characterized by means of patient-related and pre- and post-operative features. On the other, the tumors were analyzed by means of the computer-assisted microscopy analysis of Feulgen-stained nuclei. This analysis generated 3 groups of biological quantitative variables describing morphonuclear aspects (i.e. the chromatin pattern of the cell nuclei), the nuclear DNA content (DNA ploidy level), and architectural features (such as the cell density and the topographical cell nuclei organization). Possible relations between the clinical and the biological features of the lipomas were investigated by means of univariate and multivariate statistical analyses. The results show the existence of such relations, in particular between the morphonuclear and architectural features of lipomas, on the one hand, and their consistency, volume and weight, on the other. Furthermore, multivariate analysis made it possible to distinguish two subpopulations of lipomas exhibiting different biological characteristics in terms of morphonuclear patterns.



R. Sheikholeslam-zadeh, C. Decaestecker, C. Delbrouck, A. Danguy, I. Salmon, Y. Zick, H. Kaltner, S. Hassid, H. Gabius, R. Kiss, G. Choufani,
The levels of expression of galectin-3, but not of galectin-1 and galectin-8, correlate with apoptosis in human cholesteatomas.
The Laryngoscope, Vol. 111, 6, pp. 1042-1047, 2001
Bibtex
Bibtex : info:hdl:2013/52438
Note : Journal Article
Abstract : OBJECTIVES: To investigate whether galectins 1, 3, and 8 are expressed in human cholesteatomas and whether any such expression does correlate with the level of apoptosis, which is, as we have previously shown, predictive of recurrence.7 STUDY DESIGN: The analysis of 52 cholesteatomas resected by the same surgeon by means of canal wall up and canal wall down procedures. METHODS: The immunohistochemical levels of expression of galectins 1, 3, and 8 were quantitatively determined (using computer-assisted microscopy) on conventional histological slides by means of specific anti-galectin-1, anti-galectin-3, and anti-galectin-8 antibodies. The level of apoptosis in each cholesteatoma under study had already been determined 7 by means of the in situ labeling of nuclear DNA fragmentation (Tolt-mediated dUTP nick end labeling [TUNEL] staining). RESULTS: Galectin-1 was expressed markedly in both the epithelial and the connective tissue areas of all the cholesteatomas under study. The levels of expression of galectin-3 and galectin-8 were considerably lower than that of galectin-1. The level of expression of galectin-3 correlated both highly and positively with the level of apoptosis. CONCLUSIONS: An upregulation of galectin-3 (known to have an antiapoptotic and antianoikis effect in certain model systems) expression, which is associated with pronounced apoptotic activity, could have a physiologically protective effect against the characteristically substantial apoptotic features occurring in recurrent cholesteatomas.



P. Simon, C. Decaestecker, G. Choufani, C. Delbrouck, A. Danguy, I. Salmon, Y. Zick, H. Kaltner, S. Hassid, H. Gabius, R. Kiss, F. Darro,
The levels of retinoid RARβ receptors correlate with galectin-1, -3 and -8 expression in human cholesteatomas
Hearing research, Vol. 156, 1-2, pp. 1-9, 2001
Bibtex
Bibtex : info:hdl:2013/52439
Note : Journal Article
Abstract : Cholesteatoma is a benign disease characterized by the presence of an unrestrained growth and the accumulation of keratin debris in the middle ear cavity. This often recurs, even when surgical resection is thought to be complete. In a previous study we showed that cholesteatomas with the highest apoptotic indices recurred more rapidly and also exhibited a high level of p53 immunopositive cells. In view of their relevance to the characterization of the cell differentiation status, the present study focuses on the expression of retinoid acid receptors (RARs) and galectins in human cholesteatomas. Retinoids control the differentiation processes in keratinocytes while galectins play strikingly modulatory roles at apoptosis and cell adhesion levels in a wide variety of tissue (embryonic, normal and neoplastic). To clarify the expression of these two protein families in human cholesteatomas we examined and quantified the levels of immunohistochemical expression of RARalpha, beta and gamma, and also galectin-1, -3 and -8 in a series of 70 human cholesteatomas. Our data show clearly that predominantly RARbeta and galectin-1 were expressed. The RARgamma concentration was significantly lower than that of the RARalpha; this was also observed for the galectin-8 concentration in comparison with the galectin-3 one. Furthermore, the level of RARbeta expression correlated highly (P=0.00001) with the level of galectin-8 expression, which also correlated significantly with the level of RARalpha and RARgamma expression. In addition, this parameter also correlated with the level of galectin-1 and galectin-3 expression. These data suggest that cholesteatomas may originate in an undifferentiated population of keratinocytes, and that a relation may exist between retinoid activity and galectins.



Conferences

P. Latinne, M. Saerens, C. Decaestecker,
Adjusting the outputs of a classifier to new a priori probabilities may significantly improve classification accuracy: Evidence from a multi-class problem in remote sensing
Proceedings of the Eighteenth International Conference on Machine Learning (ICML 2001), pp. pp 298-305, 2001
Bibtex
Bibtex : info:hdl:2013/70186
Note : Language of publication: en



A. Lyazghi, C. Decaestecker, I. Camby, R. Kiss, P. Van Ham,
Characterization of acting filaments in cancer cells by the Hough transform
Proceedings of the 2001 IASTED International Conference on Signal Processing, Pattern Recognition and Applications, pp. pp. 138-142, Rhodes, Greece, 2001
Bibtex
Bibtex : info:hdl:2013/70187
Note : Language of publication: en



P. Latinne, O. Debeir, C. Decaestecker,
Limiting the Number of Trees in Random Forests
Multiple Classifier Systems: Proceedings of the Second International Workshop, pp. 178-187, 2001
Bibtex
Bibtex : info:hdl:2013/53183
Note : Language of publication: en




2000

Papers

S. Steinfeld, S. Rommes, C. Francois, C. Decaestecker, A. Maho, T. Appelboom, C. Heizmann, R. Kiss, R. Pochet,
Big prolactin 60 kDa is overexpressed in salivary glandular epithelial cells from patients with Sj{\"o}gren's syndrome.
Laboratory investigation, Vol. 80, 2, pp. 239-247, 2000
Bibtex
Bibtex : info:hdl:2013/52528
Note : Journal Article
Abstract : Characterization of endogenous synthesis of prolactin (PRL) proteins and their cellular localization in labial salivary glands of patients with Sjogren's syndrome (SS) were achieved. PRL, PRL-receptors (PRL-R), and S100A6 protein were detected by immunohistochemistry. In situ prolactin synthesis was investigated in controls and SS patients by ex vivo incubation of minor salivary glands biopsies and immunoprecipitation assay. Increased PRL-immunoreactivity was found in cytoplasmic acinar epithelial cells in SS patients compared with normal subjects. PRL-R was distributed only in ductal epithelial cells in which S100A6 protein (a PRL-R-associated protein) was also present. PRL, PRL-R, or S100A6-immunoreactivity was not detected in infiltrating mononuclear cells. Immunoprecipitation demonstrated that PRL synthesis occurred in minor salivary glands with increased synthesis of two distinct PRL-like proteins (one major band at 60 kDa and a minor at 16 kDa) in SS glands compared with normal glands. Expression of PRL gene was demonstrated in SS salivary glands using RT-PCR. A positive correlation was found between the presence of PRL-like proteins in acinar epithelial cells of SS patients and clinical extraglandular manifestations. The presence of anti-Ro and anti-La antibodies also positively correlated with a higher percentage of PRL in acinar epithelial cells. In conclusion, PRL-like proteins are synthetized and overexpressed in glandular epithelial cells of labial salivary glands from SS patients and correlate with the aggressiveness of the disease.



N. Nagy, C. Decaestecker, X. Dong, H. Kaltner, M. Sch{\"u}ring, P. Rocmans, A. Danguy, H. Gabius, R. Kiss, I. Salmon,
Characterization of ligands for galectins, natural galactoside-binding immunoglobulin G subfractions and sarcolectin and also of the expression of calcyclin in thyroid lesions.
Histology and histopathology, Vol. 15, 2, pp. 503-513, 2000
Bibtex
Bibtex : info:hdl:2013/52525
Note : Journal Article
Abstract : The purpose of this study was to characterize ligands for galectins, natural galactoside-binding immunoglobulin G subfractions and sarcolectin and also the expression of calcyclin in various benign and malignant thyroid lesions. The extent of the binding of eight glycochemical probes was quantitatively assessed using computer-assisted microscopy on 76 thyroid lesions including 10 not-otherwise-specified multinodular goiters (S\_MNG), 11 multinodular goiters with adenomatous hyperplasia (AH\_MNG), 8 normomacrovesicular (NM\_ADE) and 12 microvesicular (MIC\_ADE) adenomas, and 9 papillary (P\_CAR), 10 follicular variants of papillary (FvarP\_CAR), 7 follicular (F\_CAR) and 9 anaplastic (A\_CAR) carcinomas. The 8 histochemical probes included 5 animal lectins (including galectins and sarcolectin), 1 polyclonal antibody (raised against calcyclin) and 2 immunoglobulin G subfractions from human serum with selectivity to alpha- and beta-galactosyl residues. The results show that multinodular goiters with adenomatous hyperplasia exhibited histochemical characteristics intermediate to those of normal multinodular goiters and microvesicular adenomas. Normomacrovesicular adenomas behaved very distinctly from microvesicular ones. Microvesicular adenomas were more closely related to differentiated thyroid carcinomas than any other type of benign thyroid lesions of epithelial origin. Papillary and follicular carcinomas seemed to represent the two extremes of the same biological entity with the follicular variant of the papillary carcinoma serving as a biological link between these two extremes. Anaplastic carcinomas behaved in a significantly different manner when compared to the differentiated forms of thyroid carcinomas. The results suggest that the patterns of expression of the glycoconjugates investigated in the present study may constitute useful tools for characterizing lesions in the human thyroid.



F. Darro, G. Schwarz, M. Petein, S. Schwarz, C. Chaboteaux, J. Nogaret, C. Decaestecker, I. Salmon, R. Kiss,
Characterization of steroid hormone sensitivity in human breast cancers maintained ex vivo under organotypical culture conditions.
Journal of cancer research and clinical oncology, Vol. 126, 5, pp. 257-262, 2000
Bibtex
Bibtex : info:hdl:2013/52533
Note : Journal Article
Abstract : PURPOSE: The methodology we propose combines the immunohistochemical determination of the oestrogen and progesterone receptors (ER and PgR) with the characterization of the oestradiol- and progesterone-induced influence on cell proliferation in breast cancers in order to characterize their steroid hormone sensitivity at both the "static" and "dynamic" level. METHODS: ER and PgR have been immunohistochemically quantified by means of computer-assisted microscopy. Cell proliferation has been determined by means of tritiated thymidine autoradiography in tumour samples maintained in vitro as organotypic cultures. A series of 14 patients was investigated. RESULTS: Of the 14 breast cancers under study, one with an unequivocally "very ER-rich"/"very PgR-rich" immunohistochemical phenotype totally failed to exhibit any modification in its cell proliferation level after both oestradiol and progesterone stimulation. Two cases definitively associated with an "ER-poor"/"PgR-poor" immunohistochemical phenotype nevertheless responded noticeably to the dynamic stimulation of their cell proliferation by oestradiol and progesterone. While our series of cases covers 14 patients only, it suffices to demonstrate the limits of ER and PgR determination in characterizing steroid hormone sensitivity in breast cancer. DISCUSSION: The present work therefore presents an in vitro approach to test growth regulation of human breast cancer by steroid hormones. The clinical value of the present approach should be further determined by showing that steroid hormone-induced modifications in cell proliferation level are actually associated with clinical response.



S. Farinelle, H. Malonne, C. Chaboteaux, C. Decaestecker, R. Dedecker, T. Gras, F. Darro, J. Fontaine, G. Atassi, R. Kiss,
Characterization of TNP-470-induced modifications to cell functions in HUVEC and cancer cells.
Journal of pharmacological and toxicological methods, Vol. 43, 1, pp. 15-24, 2000
Bibtex
Bibtex : info:hdl:2013/52520
Note : Comparative Study
Abstract : The aim of the present work is to characterize (both in vitro and in vivo) the influence of TNP-470 on different cell functions involved in angiogenesis and, more particularly, on endothelial cell growth, cell migration and vessel formation. In addition, a possible direct anti-tumor activity was investigated. To this end, we made use in vitro of human umbilical cord endothelial vein (HUVEC) cells and two human cancer cell lines. The TNP-470 effects on the growth of cancer cell lines were compared to those of Taxol (an inhibitor of microtubule depolymerization), a cytotoxic reference which also displays strong antiogenic activity at low (non-toxic) doses. The in vitro effects were characterized on the mouse mammary MXT adenocarcinoma, on which we also characterized the influence of three clinically active anti-tumor compounds (as cytotoxic references). The purpose of this part of the study was to determine the actual TNP-470-related anti-tumor activity and to evaluate the possible toxic side-effects at the doses at which this compound induces tumor growth inhibition. These investigations were completed by analyzing the TNP-470 effects on HUVEC cell motility and in vitro and in vivo vessel formation. The results show that in vitro, TNP-470 inhibited the growth not only of HUVEC, but also of neoplastic cells. Furthermore, TNP-470 clearly inhibited in vitro endothelial cell motility (p<10(-5)). However, it had only a minor effect (p=0.02) on the formation of HUVEC cell networks on Matrigel(R). In vivo, TNP-470 was able to inhibit tumor growth (on the MXT model) at a dose (50 mg/kg) associated with toxic side-effects. Histological examination showed a significant inhibition of vessel formation (p<0.001) at high (toxic) and intermediary (non-toxic) doses (50 and 20 mg/kg). However, we also observed that TNP-470 stimulated lymphocyte proliferation. Thus, care must be taken with the TNP-470 compound in combination with other anti-tumoral agents in order to avoid certain unfortunate clinical complications.



P. Latinne, O. Debeir, C. Decaestecker,
Different ways of weakening decision trees and their impact on classification accuracy of DT combination
Lecture notes in computer science, Vol. 1857 LNCS, pp. 200-209, 2000
Bibtex
Bibtex : info:hdl:2013/192154
Note : SCOPUS: cp.k
Abstract : Recent classifier combination frameworks have proposed several ways of weakening a learning set and have shown that these weakening methods improve prediction accuracy. In the present paper we focus on learning set sampling (Breiman's bagging) and random feature subset selections (Bay's Multiple Feature Subsets). We present a combination scheme labeled 'Bagfs', in which new learning sets are generated on the basis of both bootstrap replicates and selected feature subsets. The performances of the three methods (Bagging, MFS and Bagfs) are assessed by means of a decision-tree inducer (C4.5) and a majority voting rule. In addition, we also study whether the way in which weak classifiers are created has a significant influence on the performance of their combination. To answer this question, we undertook the strict application of the Cochran Q test. This test enabled us to compare the three weakening methods together on a given database, and to conclude whether or not these methods differ significantly. We also used the McNemar test to compare algorithms pair by pair. The first results, obtained on 14 conventional databases, show that on average, Bagfs exhibits the best agreement between prediction and supervision. The Cochran Q test indicated that the weak classifiers so created significantly influenced combination performance in the case of at least 4 of the 14 databases analyzed. © Springer-Verlag Berlin Heidelberg 2000.



I. Camby, F. Lefranc, G. Titeca, S. Neuci, M. Fastrez, L. Dedecken, B. Sch{\"a}fer, J. Brotchi, C. Heizmann, R. Pochet, I. Salmon, R. Kiss, C. Decaestecker,
Differential expression of S100 calcium-binding proteins characterizes distinct clinical entities in both WHO grade II and III astrocytic tumours.
Neuropathology and applied neurobiology, Vol. 26, 1, pp. 76-90, 2000
Bibtex
Bibtex : info:hdl:2013/51250
Note : Journal Article
Abstract : The computer-assisted microscopic analysis of Feulgen-stained nuclei enabled us to identify two subgroups of astrocytomas (WHO grade II) and two subgroups of anaplastic astrocytomas (WHO grade III) with significantly distinct clinical outcomes (Decaestecker et al. Brain Pathol 1998; 8: 29-38). The astrocytomas labelled in the present study as typical (TYP-ASTs) behaved clinically like real astrocytomas while atypical astrocytomas (ATYP-ASTs) behaved similarly to anaplastic astrocytomas. The anaplastic astrocytomas that we labelled as typical (TYP-ANAs) behaved clinically like anaplastic astrocytomas while atypical ones (ATYP-ANAs) behaved like glioblastomas. In the present study, we investigate whether some biological characteristics could be evidenced across these four groups of TYP- and ATYP-ASTs and TYP- and ATYP-ANAs. The data show that the levels of expression (immunohistochemically assayed and quantitatively determined by means of computer-assisted microscopy) of vimentin, the glial fibrillary acidic protein and the platelet-derived growth factor-alpha did not differ significantly across these four groups of astrocytic tumours. The level of cell proliferation (determined by means of both the anti-proliferating cell nuclear antigen and the anti-MIB-1 antibodies; P < 0.001 to P < 0.0001) differed very significantly between the astrocytomas and anaplastic astrocytomas, but not between the typical and atypical variants identified in each group. In sharp contrast, the levels of expression of the S100A3 and S100A5 proteins differed markedly in the solid tumour tissue in relation to the astrocytic tumour types and grades. In addition, while the levels of expression of S100A6 did not change in the astrocytic tumour tissue in relation to histopathological grade, the levels of expression of this S100 protein (but not those of S100A3 and S100A5) differed markedly in the blood vessel walls according to whether these vessels originated from low- or high-grade astrocytic tumours.



A. Hittelet, P. Yeaton, C. Decaestecker, M. Remmelink, N. Nagy, M. Cremer, I. Salmon, R. Kiss, N. Bourgeois,
Discrimination between dysplastic and malignant epithelium of the ampulla of vater based on quantitative image cytometric data.
Analytical and quantitative cytology and histology, Vol. 22, 2, pp. 98-106, 2000
Bibtex
Bibtex : info:hdl:2013/52526
Note : Journal Article
Abstract : OBJECTIVE: To assess the ability to associate histopathologic grading with objective criteria obtained by nuclear image cytometry in epithelium of the ampulla of Vater. STUDY DESIGN: Forty-one resected ampullary specimens were studied, including 8 dysplastic ampullomas together with 22 well-differentiated and 11 poorly differentiated ampullary adenocarcinomas. The nuclei were Feulgen stained and analyzed using a computer-assisted microscope, which generated 38 quantitative variables describing chromatin texture and nuclear DNA content (DNA ploidy level). These variables were explored by discriminant analysis to determine the most stable and informative variables. Univariate analysis was performed on the four most informative ones. The whole set of variables was also subjected to principal component analysis in order to characterize intragroup and intergroup heterogeneity. RESULTS: The univariate analysis defined two morphonuclear variables (related to nuclear chromatin distribution) discriminating between dysplasia and well-differentiated cancers. Aneuploidy occurrence was associated with discrimination between well-differentiated and poorly differentiated cancers. CONCLUSION: While alterations in chromatin distribution may be an early event in the malignant degeneration of this epithelium, alterations in nuclear DNA content should correspond to a later phenomenon. Quantification of these features can be exploited to assist in diagnosis.



S. Hassid, G. Choufani, C. Decaestecker, C. Delbrouck, S. Dawance, P. Pelc, N. Nagy, H. Kaltner, I. Salmon, A. Danguy, H. Gabius, R. Kiss,
Glycohistochemical characteristics of nasal polyps from patients with and without cystic fibrosis.
Archives of otolaryngology--head & neck surgery, Vol. 126, 6, pp. 769-776, 2000
Bibtex
Bibtex : info:hdl:2013/52530
Note : Journal Article
Abstract : OBJECTIVE: To investigate whether cystic fibrosis (CF)-related nasal polyps exhibit significantly distinct glycohistochemical characteristics when compared with single vs massive nasal polyps obtained from patients without CF. DESIGN: Glycohistochemical characteristics were identified by means of 8 histochemical probes, including 5 plant lectins (peanut, gorse seed, wheat germ, Maackia amurensis, and Sambucus nigra agglutinins), 2 animal lectins (14- and 16-kd galectins), and 1 neoglycoprotein (exposing the Thomsen-Friedenreich antigen). The binding of the 8 glycohistochemical markers was determined by means of computer-assisted microscopy. For each probe, 3 quantitative parameters were computed: the labeling index, which describes the percentage of tissue area specifically stained by a given marker; the mean optical density, which reflects the staining intensity; and the concentrational heterogeneity, which characterizes the level of heterogeneity of the staining intensity. SUBJECTS: A series of 61 nasal mucosa specimens was analyzed, including 6 normal cases, 23 single and 18 massive polyposis cases without CF, and 14 nasal polyps associated with CF. RESULTS: Normal and polyposal nasal mucosa differed in terms of the amounts and linkage types of sialic acids (revealed by the wheat germ, M amurensis, and S nigra agglutinins) rather than the characteristics of galactoside expression (monitored with the peanut agglutinin and 2 animal galectins). In contrast, nasal polyps markedly differed between patients with and without CF with respect to galactoside expression (revealed by the peanut agglutinin and the 14-kd galectin) and the display of binding site(s) for the neoglycoprotein. CONCLUSION: Normal and polyposal nasal mucosa differ essentially in sialic acid presentation, while nasal polyps from patients with CF have a higher level of various lectin-reactive galactoside residues than nasal polyps from those without CF.



P. Philippart, L. Harper, C. Chaboteaux, C. Decaestecker, Y. Bronckart, L. Gordover, L. Lesueur-Ginot, H. Malonne, O. Lavergne, D. Bigg, P. Mendes Da Costa, R. Kiss,
Homocamptothecin, an E-ring-modified camptothecin, exerts more potent antiproliferative activity than other topoisomerase I inhibitors in human colon cancers obtained from surgery and maintained in vitro under histotypical culture conditions.
Clinical cancer research, Vol. 6, 4, pp. 1557-1562, 2000
Bibtex
Bibtex : info:hdl:2013/52532
Note : Comparative Study
Abstract : Topoisomerase I (Topo I) is overexpressed in cancer colon tissues compared with normal colon tissues. Several anti-Topo I inhibitors are already successfully used in the clinic. We illustrate here the antiproliferative activity of a new class of Topo I inhibitors, i.e., E-ring-modified camptothecins with enhanced lactone stability (L. Lesueur-Ginot et al., Cancer Res., 59: 2939-2943, 1999). Forty-three human colon cancers were obtained from surgical resection and maintained under organotypical culture conditions for 48 h. Cell proliferation was assessed in these ex vivo tumor tissue cultures by tritiated thymidine autoradiography. As a validation of the methodology, we first analyzed in our model the antiproliferative activity of two clinically active topoisomerase II (Topo II) inhibitors, Adriamycin and etoposide, which are not active for colon cancers; and three Topo I inhibitors, camptothecin (CPT) and two clinically active compounds (especially for colon cancers), i.e., topotecan and the active metabolite of irinothecan, SN-38. We then compared the antiproliferative activity of CPT, topotecan, and SN-38 against those of two investigational E-ring-modified camptothecins, i.e., BN80245 and BN80915. Three concentrations (1, 10, and 100 nM) were studied for each compound. The results indicate that the three Topo I inhibitors used as references, i.e., CPT, irinothecan, and SN-38, were much more active than the two Topo II inhibitors, i.e., Adriamycin and etoposide, with SN-38 being the most efficient. The two investigational compounds BN80245 and BN80915 exerted higher antiproliferative activity than the three anti-Topo I reference compounds, with the highest activity observed for BN80915.



M. Remmelink, M. Lopes, N. Nagy, S. Rorive, K. Rombaut, C. Decaestecker, R. Kiss, I. Salmon,
How could static telepathology improve diagnosis in neuropathology?
Analytical cellular pathology : the journal of the European Society for Analytical Cellular Pathology, Vol. 21, 3-4, pp. 177-182, 2000
Bibtex
Bibtex : info:hdl:2013/52456
Note : Journal Article
Abstract : The present paper reports our experience with, and our opinion of static telepathology as applied to neuropathology by means of the PHAROS acquisition system and conventional telephone data transmission (modem). The classical procedure of expert consultation based on surface mailing of histological slides is routinely performed, especially in highly specialized fields of pathology. Telepathology is an easy means of sharing scientific expertise at international level and could thus improve diagnosis particularly in neuropathology, where certain tumor types are very rare and complex to diagnose. Dynamic telepathology allows the referring pathologist to capture by himself images supporting their diagnosis. Using static telepathology the pathologist could be limited in diagnosis by problems in fields selection. We devoted a whole year to collecting all the technical parameters characterizing the use of digitized neuropathological data files in order to investigate the feasibility of telepathology and the extent to which its use could improve diagnoses. Our results on a series of 38 histological brain examinations illustrate how we successfully established an international connection between two departments of pathology in Belgium and the USA. The referring pathologists gave diagnoses in 35 cases and deferred only 3. Despite a time-consuming procedure for the telepathology session of a few cases, this tool provides easy access to expert diagnosis and real-time discussion, both of which are of considerable interest and offer significant improvements in neuropathology.



R. Van Velthoven, M. Petein, W. Oosterlinck, T. De Wilde, J. Mattelaer, M. Hardeman, R. Kiss, C. Decaestecker,
Identification by quantitative chromatin pattern analysis of patients at risk for recurrence of superficial transitional bladder carcinoma.
The Journal of urology, Vol. 164, 6, pp. 2134-2137, 2000
Bibtex
Bibtex : info:hdl:2013/52459
Note : Journal Article
Abstract : PURPOSE: Based on the actual clinical outcomes of 132 fully documented patients with superficial transitional cell carcinoma of the bladder, we characterize the risk of recurrence and/or progression by computer assisted image microscopy applied to Feulgen stained nuclei. MATERIALS AND METHODS: Each tumor was characterized by the conventional grading and staging systems as well as by cytometry generated variables describing nuclear DNA content, nuclear morphometry and chromatin patterns. These data were submitted to discriminant analysis to establish a model distinguishing between 2 groups of patients. Group 1 included cases with remission for more than 60 months and group 2 cases presented with recurrence with or without progression within 12 months of transurethral bladder resection. This latter model was then validated by Kaplan-Meyer analysis of the full data set. RESULTS: As evidenced by Kaplan-Meier analysis, the discriminant factor generated by discriminant analysis of cytometry generated variables provided a cutoff value for distinguishing between low and high risks of recurrence (p <0.00001). In contrast, conventional grading and staging systems were not able to make such efficient distinction. CONCLUSIONS: These 2 groups can be used as references with which new cases can be compared to prognosticate disease behavior independently of histopathological grading and/or clinical staging.



C. Francois, C. Moreno, J. Teitelbaum, G. Bigras, I. Salmon, A. Danguy, G. Brugal, R. Van Velthoven, R. Kiss, C. Decaestecker,
Improving accuracy in the grading of renal cell carcinoma by combining the quantitative description of chromatin pattern with the quantitative determination of cell kinetic parameters.
Cytometry, Vol. 42, 1, pp. 18-26, 2000
Bibtex
Bibtex : info:hdl:2013/52527
Note : Journal Article
Abstract : The determination of grade and stage in renal cell carcinomas (RCCs) often fails to predict the actual clinical outcome for individual patients. The aim of the present work was to investigate whether it is possible to significantly improve the prognostic accuracy of the grading system by using the combination of two independent computer-assisted microscopy techniques. The first technique relates to the quantitative description of morphonuclear and nuclear DNA content features by means of the image analysis of Feulgen-stained cell nuclei, and the second quantitatively characterizes tumor growth by means of different cell kinetic parameters. These parameters consist of a duplication of a time-related parameter determined by means of the technique of using silver-stained proteins in interphase nucleolar organizer regions (AgNOR), a proliferation index determined by means of MIB-1 immunohistochemistry, and an apoptotic index determined by means of the terminal dUTP nick end labeling technique. The prognostic value of these quantitative features was investigated in a series of 60 RCCs. The quantitative analysis of Feulgen-stained nuclei made it possible to identify subgroups of patients with significantly different prognoses in both grade II and grade III RCCs. We labeled the RCCs associated with the most favorable prognoses as grade II- and III- and those with the least favorable ones as grade II+ and III+. The two most important kinetic variables to identify patients with different clinical outcomes were the MIB-1 index and the mean AgNOR area in the MIB-1-positive cells. Three significantly different survival curves were obtained for the 53 grade II and III RCC patients. Our results show that conventional RCC grading can be significantly improved by the quantitative analysis of Feulgen-stained nuclei, by cell kinetic parameter determination, and, more importantly, by combining the proliferation index with the mean AgNOR area parameter.



H. Malonne, S. Farinelle, C. Decaestecker, L. Gordower, J. Fontaine, F. Chaminade, J. Saucier, G. Atassi, R. Kiss,
In vitro and in vivo pharmacological characterizations of the antitumor properties of two new olivacine derivatives, S16020-2 and S30972-1.
Clinical cancer research, Vol. 6, 9, pp. 3774-3782, 2000
Bibtex
Bibtex : info:hdl:2013/52531
Note : Comparative Study
Abstract : S16020-2, a new olivacine derivative and a topoisomerase II inhibitor, has recently entered clinical trials. New analogues and derivatives have been synthesized from the S16020-2 compound. Preliminary data indicate that S30972-1, one of these S16020-2 derivatives, may exhibit a comparatively higher level of antitumor potency associated with an improved therapeutic index than does S16020-2. The antitumor activities of S16020-2 and S30972-1 were therefore characterized both in vitro and in vivo, with Adriamycin and etoposide chosen as reference compounds. The in vitro data show that S30972-1 is a topoisomerase II inhibitor, mediating its activity through an ATP-dependent mechanism such as S16020-2. The two olivacine derivatives exhibited similar activities in vitro at the levels of the global growth of six human cancer cell lines, of the induction of apoptosis, and of the G2 cell cycle phase arrest. The in vivo antitumor activity characterization included the use of two murine leukemia types (P388-LEU and L1210-LEU), two murine lymphoma-like models (P388-LYM and L1210-LYM), two mammary adenocarcinomas (MXT-HI and MXT-HS), and one melanoma (B16). The data show that S30972-1 is actually more efficient in vivo than S16020-2, a feature that may relate to the fact that S30972-1 is less toxic than S16020-2. The S30972-1 compound exhibited in vivo a level of antitumor activity that was also actually higher than that exhibited by Adriamycin and similar to that exhibited by etoposide.



S. Steinfeld, A. Penaloza, C. Decaestecker, S. Rommes, S. André, M. Sch{\"u}ring, A. Danguy, T. Appelboom, R. Kiss, H. Gabius,
Labeled neoglycoproteins and human lectins as diagnostic and potential functional markers in salivary glands of patients with Sj{\"o}gren's syndrome.
Journal of rheumatology, Vol. 27, 8, pp. 1910-1916, 2000
Bibtex
Bibtex : info:hdl:2013/52523
Note : Journal Article
Abstract : OBJECTIVE: The profile of glycans and their recognition by endogenous receptors (lectins) are increasingly attributed to disease process. Monitoring this can provide information on the pathogenesis of Sj{\"o}gren's syndrome (SS). Commonly, plant lectins are employed for phenomenological glycan mapping. To go beyond this approach restricted to binding of exogenous probes, new markers measure ligand properties of glycans to human (not plant) lectins and the presence of sugar receptors completing a protein-carbohydrate recognition system. Carrier-immobilized sugar epitopes (neoglycoproteins) and purified human lectins establish this innovative panel. METHODS: The host defence molecules mannan binding lectin, serum amyloid P component, and the macrophage migration inhibitory factor-binding sarcolectin, selected for their involvement in cell destructive mechanisms, were purified and labeled. The plant lectins SNA and MAA were employed to monitor regulation of potential ligand sites for I-type lectins and galectins. Asialofetuin was tested as a "pan-galectin selective" probe. The specific binding characteristics were determined by quantitative morphometry and statistical analysis. RESULTS: Diagnostic information emerged from this analysis. The percentage of stained tissue area was significantly different between SS and control specimens after processing with GlcNAc and Man-bearing neoglycoproteins and the 2 tested serum lectins. For separation of cases of primary and secondary SS, the staining intensity with the asialoglycoprotein, sarcolectin, and the exogenous alpha2,6-sialylated glycan-binding lectin SNA was statistically significant. CONCLUSION: Saccharide-presenting probes to measure the cellular capacity to bind glycan epitopes and human lectins as sensors for endogenous binding sites have proven to be useful as diagnostic tools. We suggest the differences we observed reflect aberrations from the normal cellular homeostasis with relevance for the pathogenesis of SS and its manifestation as a primary or secondary syndrome.



D. Hoyaux, C. Decaestecker, C. Heizmann, T. Vogl, B. Sch{\"a}fer, I. Salmon, R. Kiss, R. Pochet,
S100 proteins in Corpora amylacea from normal human brain.
Brain research, Vol. 867, 1-2, pp. 280-288, 2000
Bibtex
Bibtex : info:hdl:2013/52521
Note : Journal Article
Abstract : Corpora amylacea (C.A.) also named polyglucosan bodies (P.B.) are one of the hallmarks of normal brain aging. Although their functions are not yet clear, C.A. increase in number in patients suffering from neurodegenerative diseases. C.A. contain 88\% of hexoses and 4\% of proteins. Most of the proteins in C.A. are aging or stress proteins such as heat shock proteins, ubiquitinated proteins and advanced glycation end products which are also proinflammatory products. Stimulated by the potential role played by some S100 proteins in the inflammatory process which may be triggered in C.A., we investigated, by immunohistochemistry, the presence of different S100 proteins (S100A1, S100A2, S100A3, S100A4, S100A5, S100A6, S100A8, S100A9, S100A12 and S100B) in C.A. from normal human brain. Among the ten S100 proteins analyzed, nine (S100A) were detected in C.A. Three S100 proteins (S100A8, S100A9, S100A12) which are highly expressed in activated macrophages and used as inflammatory markers were detected in C.A. S100A8 was, in addition, found in thick neuronal processes from the pons. One (S100B) could not be found in C.A. although it was highly expressed in astrocytes. In C.A., the staining intensity was estimated by computer-assisted microscopy and gave the following order: S100A1 congruent withS100A8 congruent with S100A9>S100A5> or =S100A4>S100A12>S100A6> S100A2=S100A3. The potential inflammatory role played by S100 proteins in C.A. is discussed.



Conferences

P. Latinne, O. Debeir, C. Decaestecker,
Different Ways of Weakening Decision Trees and Their Impact on Classification Accuracy of DT Combination
Multiple Classifier Systems: Proceedings of the First International Workshop, pp. 200-209, 2000
Bibtex
Bibtex : info:hdl:2013/53188
Note : Language of publication: en



P. Latinne, O. Debeir, C. Decaestecker,
Mixing Bagging and Multiple Feature Subsets to Improve Classification Accuracy of Decision Tree Combination
BENELEARN 2000, Tenth Belgian-Dutch Conference on Machine Learning, Tilburg University, Netherland, 2000
Bibtex
Bibtex : info:hdl:2013/53190
Note : Language of publication: en




1999

Papers

N. Nagy, C. Decaestecker, R. Kiss, F. Rypens, D. Van Gansbeke, J. Mockel, P. Rocmans, I. Salmon,
A pilot study for identifying at risk thyroid lesions by means of a decision tree run on clinicocytological variables.
International Journal of Molecular Medicine, Vol. 4, 3, pp. 299-308, 1999
Bibtex
Bibtex : info:hdl:2013/58405
Note : Journal Article
Abstract : Fine-needle aspiration biopsy (FNAB) is safe, inexpensive, minimally invasive, and highly accurate in the diagnosis of nodular diseases of the thyroid. However, FNAB does not provide a reliable benign versus malignant diagnosis for 100\% of the cases analysed. It is possible to increase the accuracy of the cytological diagnosis by means of information contributed by different clinical variables. In the present study we evaluate the diagnostic value of 10 variables in addition to FNAB on a series of 218 specimens for which we obtained histological diagnoses including 37 cancers (17\%). The diagnostic information contributed by these variables was analyzed by means of the Decision Tree technique, an artificial intelligence-related method which forms part of the Supervised Learning algorithms. The results show that Decision Trees enable some subpopulations of patients with uncertain FNAB results to be characterized.



O. Debeir, C. Decaestecker, J. Pasteels, I. Salmon, R. Kiss, P. Van Ham,
Computer-assisted analysis of epiluminescence microscopy images of pigmented skin lesions.
Cytometry, Vol. 37, 4, pp. 255-266, 1999
Bibtex
Bibtex : info:hdl:2013/52957
Note : Journal Article
Abstract : BACKGROUND: Epiluminescence microscopy (ELM) is a noninvasive clinical tool recently developed for the diagnosis of pigmented skin lesions (PSLs), with the aim of improving melanoma screening strategies. However, the complexity of the ELM grading protocol means that considerable expertise is required for differential diagnosis. In this paper we propose a computer-based tool able to screen ELM images of PSLs in order to aid clinicians in the detection of lesion patterns useful for differential diagnosis. METHODS: The method proposed is based on the supervised classification of pixels of digitized ELM images, and leads to the construction of classes of pixels used for image segmentation. This process has two major phases, i.e., a learning phase, where several hundred pixels are used in order to train and validate a classification model, and an application step, which consists of a massive classification of billions of pixels (i.e., the full image) by means of the rules obtained in the first phase. RESULTS: Our results show that the proposed method is suitable for lesion-from-background extraction, for complete image segmentation into several typical diagnostic patterns, and for artifact rejection. Hence, our prototype has the potential to assist in distinguishing lesion patterns which are associated with diagnostic information such as diffuse pigmentation, dark globules (black dots and brown globules), and the gray-blue veil. CONCLUSIONS: The system proposed in this paper can be considered as a tool to assist in PSL diagnosis.



S. Steinfeld, A. Penaloza, P. Riba{\"i}, C. Decaestecker, A. Danguy, H. Gabius, I. Salmon, T. Appelboom, R. Kiss,
D-mannose and N-acetylglucosamine moieties and their respective binding sites in salivary glands of Sj{\"o}gren's syndrome.
Journal of rheumatology, Vol. 26, 4, pp. 833-841, 1999
Bibtex
Bibtex : info:hdl:2013/56407
Note : Comparative Study
Abstract : OBJECTIVE: Sj{\"o}gren's syndrome (SS) is an autoimmune exocrinopathy. The mannose binding lectin (MBL), a pluripotent molecule of the innate immune system, is involved in the pathogenesis of autoimmune diseases. We investigated whether specific ligands for MBL and MBL related structures could be reliable markers in cases of SS. METHODS: The labial salivary glands of 19 patients fulfilling the diagnostic criteria for primary (n=11) and secondary SS (n=8) were studied. Seven healthy women served as controls. Computer assisted microscopy was employed to determine quantitatively the percentage of positive structures (acini, ducts, and interlobular connective tissue), the staining intensity, and the level of staining heterogeneity for 4 glycohistochemical probes including wheat germ agglutinin and concanavalin (Con A) as lectins, and mannose and N-acetylglucosamine as parts of neoglycoproteins. The data were evaluated by discriminant analysis. RESULTS: The data strongly suggest that MBL related structures, if not MBL itself, could play distinct roles in the pathogenesis of primary versus secondary SS. Further, quantitative determination of the level of expression of D-mannose and N-acetylglucosamine and their respective binding sites in labial salivary gland acini offers a powerful diagnostic tool for distinguishing primary from secondary SS. CONCLUSION: In SS labial salivary glands, determination of the level of acceptor sites for wheat germ agglutinin, Con A, D-mannose, and N-acetylglucosamine provides information on the roles played by glycoforms in SS. The methodology and data described in this paper should provide pathologists with objective diagnostic markers for SS. Our results should enhance the biological understanding of this pathology.



G. Choufani, V. Mahillon, C. Decaestecker, T. Lequeux, A. Danguy, I. Salmon, H. Gabius, S. Hassid, R. Kiss,
Determination of the levels of expression of sarcolectin and calcyclin and of the percentages of apoptotic but not proliferating cells to enable distinction between recurrent and nonrecurrent cholesteatomas.
The Laryngoscope, Vol. 109, 11, pp. 1825-1831, 1999
Bibtex
Bibtex : info:hdl:2013/56404
Note : Journal Article
Abstract : OBJECTIVES: To investigate in a series of cholesteatomas 1. whether subgroups of cholesteatomas with specific proliferative/apoptotic features exhibit distinct differentiation markers and 2. whether these different subgroups identified at the biological level relate to specific groups of clinically identified cholesteatomas. STUDY DESIGN: Analysis of 55 cholesteatomas resected by the same surgeon, by means of canal wall up and canal wall down surgical procedures. METHODS: Two differentiation markers were used: biotinylated sarcolectin (to identify sarcolectin-binding sites) and a monoclonal antibody directed against calcyclin (which is the S100A6 protein). The growth pattern in cholesteatomas was characterized at three distinct levels: 1. the cell proliferation level determined by means of the MIB-1 antibody, which enables the Ki-67 cell-cycle-related antigen to be identified on archival material; 2. the apoptosis level determined by means of the in situ labeling of nuclear DNA fragmentation (TUNEL staining); and 3. the p53 tumor suppressor gene-related product determined by means of p53 immunohistochemistry. RESULTS: The cholesteatomas that exhibited the highest proportion of apoptotic cells were those which exhibited the highest level of sarcolectin-binding sites (i.e., sialic acids). In contrast, the cholesteatomas exhibiting the lowest level of both proliferation and apoptosis showed the highest level of calcyclin. Recurrent cholesteatomas can be identified from nonrecurrent ones on the basis of three features, namely, the level of apoptotic cells, the way in which the apoptotic cells are distributed (i.e., homogeneously vs. heterogeneously), and the percentage of calcyclin-positive cells. CONCLUSIONS: The present data emphasize the existence of distinct subgroups of cholesteatomas identifiable at both cell kinetic and differentiation levels. Some of the biological variables used here to identify distinct biological subgroups of cholesteatomas in turn enabled some biological variables to be identified, so making it possible to classify the cholesteatomas in terms of recurrence versus nonrecurrence.



G. Schwarz, M. Remmelink, C. Decaestecker, I. Gielen, V. Budel, M. Burchert, F. Darro, A. Danguy, H. Gabius, I. Salmon, R. Kiss,
Galectin fingerprinting in tumor diagnosis. Differential expression of galectin-3 and galectin-3 binding sites, but not galectin-1, in benign vs malignant uterine smooth muscle tumors.
American journal of clinical pathology, Vol. 111, 5, pp. 623-631, 1999
Bibtex
Bibtex : info:hdl:2013/56408
Note : Journal Article
Abstract : Cell-matrix interactions are governed by a distinct set of proteins, with 2 nonintegrin laminin-binding proteins, galectin-1 and galectin-3, providing 1 aspect. The expression patterns of laminin and the 2 galectins and galectin binding sites were quantitatively determined by means of computer-assisted microscopy with the aim of differentiating between 16 leiomyomas and 10 leiomyosarcomas of the uterus. Three quantitative variables were computed for each of the 5 histochemical markers: labeling index, which describes the percentage of tissue area specifically stained by a given marker; mean optical density which reflects the concentration of the marker; and concentrational heterogeneity, which characterizes the degree of heterogeneity of the marker distribution in the tumor tissue areas. The results reveal evident differences in the galectin-3-related parameters in the 2 tumors groups. Whereas the concentration of galectin-3 binding sites was significantly (P = .01) weaker in the leiomyosarcomas than in the leiomyomas, the percentages of tumor tissue expressing galectin-3 (P = .02) and its binding sites (P = .002) were significantly higher in the leiomyosarcomas than in the leiomyomas. Although significantly (P = .02) higher, the concentration of laminin was more heterogeneously distributed (P = .01) in the leiomyosarcomas than in the leiomyomas. In contrast, the levels of expression of galectin-1 and its accessible binding sites remained similar for both the leiomyomas and the leiomyosarcomas. Finally we document how the levels of expression of galectin-3 and its binding sites can be of assistance in reliably differentiating leiomyomas from leiomyosarcomas.



C. Francois, R. Van Velthoven, O. De Lathouwer, C. Moreno, A. Peltier, H. Kaltner, I. Salmon, H. Gabius, A. Danguy, C. Decaestecker, R. Kiss,
Galectin-1 and galectin-3 binding pattern expression in renal cell carcinomas.
American journal of clinical pathology, Vol. 112, 2, pp. 194-203, 1999
Bibtex
Bibtex : info:hdl:2013/56405
Note : Journal Article
Abstract : We studied 2 families of molecules whose role remains uncharacterized or obscure in the progress of renal cell carcinoma (RCC): galectins, a major class of glycoproteins, and the Thomsen-Friedenreich (T) antigen. We characterized the level of expression of galectin-1 and galectin-3 and their respective binding sites in a series of 74 RCCs. We also characterized the level of expression of laminin, a natural ligand for galectins. Finally, we characterized the level of T antigen expression and the T antigen binding sites. All levels of expression were quantitatively determined by using computer-assisted microscopy on immunohistochemically or glycohistochemically stained slides. A small concentration of galectin-1 binding sites or a large concentration heterogeneity of galectin-3 can be associated with unfavorable prognoses for patients with grade II or III RCCs. In contrast, T antigen and T antigen binding sites revealed no change across the 2 RCC groups that exhibited different clinical outcomes. We established discriminant scores that permitted a clear distinction between the 2 RCC groups analyzed. Modifications to the expression of galectin-1 and galectin-3, but not of T antigen, parallel an increase in RCC aggressiveness. Galectins represent a family of molecules with a meaningful role in RCC progression.



L. Gordower, C. Decaestecker, Y. Kacem, A. Lemmers, J. Gusman, M. Burchert, A. Danguy, H. Gabius, I. Salmon, R. Kiss, I. Camby,
Galectin-3 and galectin-3-binding site expression in human adult astrocytic tumours and related angiogenesis
Neuropathology and applied neurobiology, Vol. 25, 4, pp. 319-330, 1999
Bibtex
Bibtex : info:hdl:2013/122529
Note : Language of publication: en



Y. Bronckart, N. Nagy, C. Decaestecker, Y. Bouckaert, M. Remmelink, I. Gielen, A. Hittelet, F. Darro, J. Pector, P. Yeaton, A. Danguy, R. Kiss, I. Salmon,
Grading dysplasia in colorectal adenomas by means of the quantitative binding pattern determination of Arachis hypogaea, Dolichos biflorus, Amaranthus caudatus, Maackia amurensis, and Sambucus nigra agglutinins.
Human pathology, Vol. 30, 10, pp. 1178-1191, 1999
Bibtex
Bibtex : info:hdl:2013/56397
Note : Journal Article
Abstract : The current study deals with the setting up of a new tool that enables the benign versus the malignant nature of colorectal adenomas to be determined accurately. The 2 objectives are to determine (1) whether adenomas should, or should not, be included in a 2- or a 3-tier grading system, and (2) whether severe dysplasias and carcinomas in situ share common or different biological characteristics. The levels of expression of different types of glycoconjugates were characterized in a series of 166 colorectal specimens, including 14 normal, 90 dysplastic, and 62 cancerous cases. The glycoconjugate expressions were demonstrated for 5 lectins, namely, Arachis hypogaea (PNA), Dolichos biflorus (DBA), Amaranthus caudatus (ACA), Maackia amurensis (MAA) and Sambucus nigra (SNA). The glycoconjugates demonstrated by these 5 lectins belong to the family of the Thomsen-Friedenreich antigens. The binding patterns of the 5 lectins were quantitatively determined by means of computer-assisted microscopy. The quantitative data were submitted to discriminant analyses. Our results show that the specific glycochemical staining patterns could be identified unambiguously and without misclassification between benign (normal and low dysplasia) and malignant (ie, either as moderate/severe dysplasia, carcinoma in situ, or cancer) cases. The data also strongly suggested that (1) dysplasias seem to be distinguishable in 2 instead of 3 groups, that is, low versus moderate/severe (high); and (2) moderate/severe dysplasias are biologically distinct from carcinomas in situ. The methodology developed can be applied directly in routine diagnosis to identify moderate/severe dysplasia specimens already exhibiting features common to carcinomas, and which therefore should be treated consistently in view of the fact that our data strongly suggest that most moderate/severe dysplasias are still benign, whereas carcinomas in situ are real carcinomatous lesions.



C. Francois, C. Decaestecker, O. De Lathouwer, C. Moreno, A. Peltier, T. Roumeguere, A. Danguy, J. Pasteels, E. Wespes, I. Salmon, R. Van Velthoven, R. Kiss,
Improving the prognostic value of histopathological grading and clinical staging in renal cell carcinomas by means of computer-assisted microscopy.
Journal of pathology, Vol. 187, 3, pp. 313-320, 1999
Bibtex
Bibtex : info:hdl:2013/56410
Note : Journal Article
Abstract : The present work aims to refine prognosis in cases of renal cell carcinoma (RCC) by integrating a variety of parameters with the prognostic information provided by histopathological grading and clinical staging, carried out on a series of 97 RCCs. To this end, Feulgen-stained RCC cell nuclei were characterized by means of 38 variables describing nuclear DNA ploidy levels and morphology. All of these data were subjected to a principal components analysis. On the basis of this multivariate analysis, Fuhrman grade II was subdivided into grades II- and II+, and Fuhrman grade III into grade III- and III+. The same kind of subcategorization was performed in the case of the T2 and T3 clinical stages. The results show that the classification into grade II- and III- RCCs correspond to a more favourable prognosis than grade II+ and III+, to which shorter survival periods were attributable. Similar results were obtained for the subcategorization of the T2 and T3 clinical stages. Very simple biological characterizations of these grade- or stage-related RCC groups were obtained by means of a decision tree approach applied to the cytometry-generated variables. The resulting classification rules were validated on a new series of 18 patients and enabled very accurate predictions of survival.



M. Remmelink, F. Darro, C. Decaestecker, R. De Decker, N. Bovin, M. Gebhart, H. Kaltner, H. Gabius, R. Kiss, I. Salmon, A. Danguy,
In vitro influence of lectins and neoglycoconjugates on the growth of three human sarcoma cell lines.
Journal of cancer research and clinical oncology, Vol. 125, 5, pp. 275-285, 1999
Bibtex
Bibtex : info:hdl:2013/56400
Note : Journal Article
Abstract : PURPOSE: The aim of our study is to investigate the in vitro effects of plant lectins, galectins and neoglycoconjugates on the proliferation of three human sarcoma cell lines. METHODS: Proliferation was assessed by means of the tetrazolium derivative reduction (MTT) assay. In addition, glycohistochemistry was used to make visible the plant-lectin-specific binding sites; the intensity of the lectin binding pattern was quantified by means of image analysis. RESULTS: Depending on the cell lines, the staining intensity and the percentage of labelled cells were different. With respect to growth modulation, the cell lines also responded differently to the probes used. Besides a predominant inhibitory effect elicited by the probes at 50 microg/ml, dose-dependent effects, including growth stimulation, were detectable in several instances. These effects relate to the animal galectins tested and several neoglycoconjugates, e.g. the lactose- and blood-group-A-trisaccharide-bearing probes. CONCLUSIONS: Endogenous lectins and lectin-reactive cellular glycoconjugates can apparently affect the regulation of the growth of human sarcoma cells. We suggest that these results are relevant for further histopathological monitoring in correlation with prognosis and in vitro assays to reveal possible clinical applications.



C. De Hauwer, F. Darro, I. Camby, R. Kiss, P. Van Ham, C. Decaestecker,
In vitro motility evaluation of aggregated cancer cells by means of automatic image processing.
Cytometry, Vol. 36, 1, pp. 1-10, 1999
Bibtex
Bibtex : info:hdl:2013/56402
Note : Journal Article
Abstract : BACKGROUND: Set up of an automatic image processing based method that enables the motility of in vitro aggregated cells to be evaluated for a number of hours. METHODS: Our biological model included the PC-3 human prostate cancer cell line growing as a monolayer on the bottom of Falcon plastic dishes containing conventional culture media. Our equipment consisted of an incubator, an inverted phase contrast microscope, a Charge Coupled Device (CCD) video camera, and a computer equipped with an image processing software developed in our laboratory. This computer-assisted microscope analysis of aggregated cells enables global cluster motility to be evaluated. This analysis also enables the trajectory of each cell to be isolated and parametrized within a given cluster or, indeed, the trajectories of individual cells outside a cluster. RESULTS: The results show that motility inside a PC-3 cluster is not restricted to slight motion due to cluster expansion, but rather consists of a marked cell movement within the cluster. CONCLUSIONS: The proposed equipment enables in vitro aggregated cell motility to be studied. This method can, therefore, be used in pharmacological studies in order to select anti-motility related compounds. The compounds selected by the equipment described could then be tested in vivo as potential anti-metastatic.



A. Penaloza, C. Decaestecker, P. Riba{\"i}, N. Nagy, I. Salmon, T. Appelboom, A. Danguy, R. Kiss, S. Steinfeld,
Sialic acid residues in the labial salivary glands from Sj{\"o}gren's syndrome patients.
Clinical and Experimental Rheumatology, Vol. 17, 6, pp. 713-717, 1999
Bibtex
Bibtex : info:hdl:2013/56396
Note : Journal Article
Abstract : OBJECTIVE: To investigate the composition and expression of sialic acid in the labial salivary glands (LSG) in Sj{\"o}gren's syndrome (SS). METHODS: LSG of 19 patients with primary SS (n = 11) or secondary SS (n = 8) were studied. Specimens from 7 healthy women served as controls. Computer-assisted microscopy was employed to quantitatively determine the percentage of positive structures, the staining intensity and the heterogeneity for the 4 biotinylated plant lectins Tritricum vulgaris L. (WGA), Maackia amurensis (MAA), Sambucus nigra (SNA) and Canavalia ensiformis L. (Con A). RESULTS: In the acini there was a significant decrease in the staining heterogeneity of WGA in SS compared to controls; the same was observed with respect to MAA staining in the connective tissue and extralobular ducts. In the intralobular ducts, primary SS differed from normal and secondary SS mainly in terms of a decrease in the percentage of positively labeled MAA tissue. In addition, Con A stained acinar cells were significantly more numerous in secondary SS compared with primary SS. CONCLUSION: Differences in the degree of glycoconjugate sialylation were found in SS labial salivary glands, and may play a role in the disease process.



I. Camby, N. Nagy, M. Lopes, B. Sch{\"a}fer, C. Maurage, M. Ruchoux, P. Murmann, R. Pochet, C. Heizmann, J. Brotchi, I. Salmon, R. Kiss, C. Decaestecker,
Supratentorial pilocytic astrocytomas, astrocytomas, anaplastic astrocytomas and glioblastomas are characterized by a differential expression of S100 proteins.
Brain pathology, Vol. 9, 1, pp. 1-19, 1999
Bibtex
Bibtex : info:hdl:2013/56403
Note : Journal Article
Abstract : The levels of expression of the S100A1, S100A2, S100A3, S100A4, S100A5, S100A6 and S100B proteins were immunohistochemically assayed and quantitatively determined in a series of 95 astrocytic tumors including 26 World Health Organization (WHO) grade I (pilocytic astrocytomas), 23 WHO grade II (astrocytomas), 25 WHO grade III (anaplastic astrocytomas) and 21 WHO grade IV (glioblastomas) cases. The level of the immunohistochemical expression of the S100 proteins was quantitatively determined in the solid tumor tissue (tumor mass). In addition twenty blood vessel walls and their corresponding perivascular tumor astrocytes were also immunohistochemically assayed for 10 cases chosen at random from each of the four histopathological groups. The data showed modifications in the level of S100A3 protein expression; these modifications clearly identified the pilocytic astrocytomas from WHO grade II-IV astrocytic tumors as a distinct biological group. Modifications in the level of S100A6 protein expression enabled a clear distinction to be made between low (WHO grade I and II) and high (WHO grade III and IV) grade astrocytic tumors. Very significant modifications occurred in the level of S100A1 protein expression (and, to a lesser extent, in their of the S100A4 and S100B proteins) in relation to the increasing levels of malignancy. While the S100A5 protein was significantly expressed in all the astrocytic tumors (but without any significant modifications in the levels of malignancy), the S100A2 protein was never expressed in these tumors. These data thus indicate that several S100 proteins play major biological roles in human astrocytic tumors.



N. Nagy, I. Camby, C. Decaestecker, C. Chaboteaux, T. Gras, F. Darro, P. Rocmans, R. Kiss, I. Salmon,
The influence of L-triiodothyronine, L-thyroxine, estradiol-17β, the luteinizing-hormone-releasing hormone, the epidermal growth factor and gastrin on cell proliferation in organ cultures of 35 benign and 13 malignant human thyroid tumors
Journal of cancer research and clinical oncology, Vol. 125, 6, pp. 361-368, 1999
Bibtex
Bibtex : info:hdl:2013/56401
Note : Journal Article
Abstract : PURPOSE: To characterize the influence of six factors on human thyroid tissues at the cell-proliferation level. These six factors were the epidermal growth factor (EGF), the luteinizing-hormone-releasing hormone (LHRH), triiodothyronine, thyroxine, estradiol and gastrin. METHODS: Forty-eight human thyroid specimens were obtained from surgical resection and maintained alive for 48 h ex vivo (in vitro) under organotypic culture conditions. These specimens comprised 35 benign cases (17 multinodular goiters and 18 adenomas) and 13 cancers. Cell proliferation in the control and treated conditions (at a 5 nM dose) was assessed by means of the thymidine labeling index, which enables the percentage of cells in the S phase of the cell cycle to be determined in accordance with autoradiographic procedures. RESULTS: The results show that, of the six factors tested here, EGF significantly (P < 0.05 to P < 0.001) increased cell proliferation in the greatest number of cancers as compared to what happened with the remaining five. Each of these six factors significantly increased or decreased proliferative cell activity in some 10\%-30\% of the cases under study. CONCLUSIONS: Triiodothyronine, thyroxine, LHRH and gastrin may increase or decrease cell proliferation in human thyroid tissues, whether benign or malignant, to the same extent as other hormones and/or growth factors such as thyrotropin, EGF, insulin-like growth factor 1, transforming growth factor beta1 and estradiol the effects of which on thyroid cell proliferation are already well documented in the literature.




1998

Papers

A. Danguy, C. Decaestecker, F. Genten, I. Salmon, R. Kiss,
Applications of lectins and neoglycoconjugates in histology and pathology.
Acta anatomica, Vol. 161, 1-4, pp. 206-218, 1998
Bibtex
Bibtex : info:hdl:2013/58382
Note : Comparative Study
Abstract : The biological importance of oligosaccharide sequences in many different settings is undeniable. Glycan histochemistry has brought together the histological and biochemical approaches and provided insight into the mutual importance of both approaches. The aim of the authors is to take a look at a number of ways in which modern glycohistochemistry contributes to acquiring knowledge about the key role played by carbohydrates in the physiology of vertebrate tissues and human disease. The versatility of lectin and neoglycoconjugate histochemical procedures is emphasized.



C. Decaestecker, I. Camby, L. Gordower, O. De Witte, P. Cras, J. Martin, J. Pasteels, P. Van Ham, J. Brotchi, R. Kiss, I. Salmon,
Characterization of astroglial versus oligodendroglial phenotypes in glioblastomas by means of quantitative morphonuclear variables generated by computer-assisted microscopy.
Journal of neuropathology and experimental neurology, Vol. 57, 8, pp. 791-802, 1998
Bibtex
Bibtex : info:hdl:2013/56338
Note : Comparative Study
Abstract : The current WHO classification places glioblastomas in the astrocytoma category. However, whether or not glioblastomas also show oligodendroglial differentiation remains a matter of controversy. This study investigates, at the morphonuclear level, the hypothesis that some glioblastomas (GBMs) may also represent the ultimate level of malignancy in the oligodendroglial lineage. Using a series of 164 GBMs, we sought to ascertain whether any of these GBMs exhibited phenotypical characteristics that were more closely related to oligodendroglial lineages than astrocytic lineages. Phenotypical features were quantitatively determined by means of the computer-assisted microscope analysis of Feulgen-stained nuclei, a process that made it possible to quantitatively describe the patterns of the cell nuclei (and, more specifically, of their chromatin) through 16 variables, and the distribution of the nuclear DNA content (DNA ploidy) through 8 variables. The phenotypical characteristics typical of astrocytic and oligodendroglial tumors were analyzed by means of Discriminant Analysis, a statistical multivariate analysis, performed on a series of 65 astrocytic and oligodendroglial tumors. This series consisted of 14 WHO grade II and 19 grade III astrocytomas and 24 WHO grade II and 8 grade III oligodendrogliomas. This multivariate analysis enabled an accurate model to be produced that distinguished between astrocytomas and oligodendrogliomas on the basis of 5 cytometry-generated variables. This model was used to characterize the phenotype of each of the 164 glioblastomas. The results show that of these 164 glioblastomas, 6 (about 3.5\%) displayed phenotypes that were very similar to oligodendrogliomas, and 141 displayed phenotypes that were very similar to astrocytomas. The phenotypes of the 17 remaining GBMs were too ambiguous to be categorized as having a pure astrocytic or oligodendroglial lineage.



E. Wespes, G. Raviv, J. Vanegas Merino, C. Decaestecker, M. Petein, A. Danguy, C. Schulman, R. Kiss,
Corporeal veno-occlusive dysfunction: a distal arterial pathology?
The Journal of urology, Vol. 160, 6 Pt 1, pp. 2054-2057, 1998
Bibtex
Bibtex : info:hdl:2013/71124
Note : Journal Article
Abstract : Alteration of intracavernous smooth muscle cells has been demonstrated in patients with pure venous leakage. This modification seems correlated with reduction of intracavernous oxygen tension. However, Doppler imaging of the cavernous arteries in these patients is normal. To understand the ischemic factor we studied the endothelium of the terminal arteries with computerized image analysis and immunohistochemical staining with 2 types of lectin in patients with venous leakage and those with normal erections. Lectins are glycoproteins that can be used as histological markers to monitor functional and pathological changes.



L. Gordower, C. Decaestecker, M. Lopes, I. Camby, N. Nagy, C. Francois, P. Cras, J. Martin, J. Brotchi, R. Kiss, I. Salmon,
Determination of growth fraction and cell density to evaluate the potential growth of human oligodendroglial and astrocytic tumours.
Journal of cancer research and clinical oncology, Vol. 124, 8, pp. 427-434, 1998
Bibtex
Bibtex : info:hdl:2013/56409
Note : Journal Article
Abstract : The object of this work was PURPOSE: to develop a methodology that enables net tumour growth, a balance between actual tumour growth and tumour cell loss, to be approximately evaluated. METHODS: The methodology proposed relies on detecting the growth fraction immunohistochemically by means of MIB-1 antibody labelling combined with cell density determination, carried out on 5-microm-thick Feulgen-stained histological sections with computer-assisted microscopy. The series investigated included 25 oligodendrogliomas (OLG-II), 9 anaplastic oligodendrogliomas (OLG-III). 13 astrocytomas (AST), 14 anaplastic astrocytomas (ANA) and 8 mixed oligoastrocytomas (OLG-AST). RESULTS: The results show that the biological characteristics of some cases were in total accordance with their histopathological diagnoses. This was the case for the "weakly proliferating weakly dense" OLG-II and AST-II tumours, and for the "highly proliferating highly dense" OLG-III and AST-III ones. In contrast, the biological characteristics of some cases seemed to contradict the histopathological case labels. This was the case for the "highly proliferating highly dense" OLG-II and AST-II tumours, the biological aggressiveness of which would be undervalued on the basis of the morphology-based grading system alone, and also for the "weakly proliferating weakly dense" OLG-III and AST-III tumours, the aggressiveness of which would be overvalued. CONCLUSIONS: Combining the determinations of the MIB-1 and the cell density variables appears to be satisfactory in terms of the cell kinetic characterization of glial tumours as a complement to the prognostic information given by a morphology-based grading system alone.



R. Kiss, C. Decaestecker, I. Camby, F. Darro, I. Salmon, A. Danguy, J. Pasteels, P. Yeaton,
Direct relationship between hormone sensitivity level and growth pattern. Evidence in 18 gastrointestinal neoplastic cell lines.
Analytical and quantitative cytology and histology, Vol. 20, 2, pp. 133-143, 1998
Bibtex
Bibtex : info:hdl:2013/58371
Note : Journal Article
Abstract : OBJECTIVE: We investigated whether a relationship exists in terms of growth pattern and hormone sensitivity in 18 gastrointestinal neoplastic cell lines. Hormones studied included gastrin, epidermal growth factor, estradiol and luteinizing hormone-releasing hormone. STUDY DESIGN: The growth patterns were assessed by means of computer-assisted microscope analysis of Feulgen-stained nuclei combined with the mathematical Delaunay triangulation and Voronoi paving techniques. This methodology enabled four variables characterizing the cell colony patterns to be computed. The information contributed by these variables was analyzed by means of discriminant analysis and the decision tree technique. RESULTS: Each phenotype (sensitivity level) exhibited distinct growth pattern (or cell colony) characteristics in the case of each hormone and/or growth factor under study. Furthermore, the sensitivity of the gastrointestinal cell lines to a given hormone (or growth factor) appeared to be peculiar to the hormone (or growth factor). CONCLUSION: A direct relationship seems to exist between growth pattern and hormone sensitivity levels in gastrointestinal cancers, particularly colorectal.



P. Yeaton, R. Sears, T. Ledent, I. Salmon, R. Kiss, C. Decaestecker,
Discrimination between chronic pancreatitis and pancreatic adenocarcinoma using artificial intelligence-related algorithms based on image cytometry-generated variables.
Cytometry, Vol. 32, 4, pp. 309-316, 1998
Bibtex
Bibtex : info:hdl:2013/56411
Note : Comparative Study
Abstract : The incidence of pancreatic adenocarcinomas (PA) is increased in the setting of chronic pancreatitis. Distinguishing chronic pancreatitis from pancreatic adenocarcinomas is often difficult, and is based on routine brush cytological specimens provided during endoscopic retrograde cholangiopancreatography (ERCP). Reactive epithelial changes in chronic pancreatitis may appear similar to those of a well-differentiated cancer. Brush cytology specimens were obtained during ERCP from 49 patients with diseases for which the differential diagnosis included chronic pancreatitis and/or pancreatic adenocarcinoma Image cytometry was performed involving the assessment of between 200-400 Feulgen-stained nuclei per case; for each case, 40 quantitative cytometric variables were generated. Data analysis was performed using artificial intelligence methods of data classification that produced decision trees and production rule systems. Different classification models were produced for a subset of 34 patients. The best models were identified by the use of a sampling technique (leave-one-out), and were tested on the remaining 15 patients. These models were based on 5 of the 40 variables associated with a significant discriminatory function. Pancreatic adenocarcinoma was diagnosed in the training data set of 34 patients during a leave-one-out process with an estimated sensitivity of 91\% and specificity of 87\%. Both sensitivity and specificity were 80\% in the independent test set of 15 patients. We conclude that inflammatory and malignant pancreatic epithelia exhibit distinct morphological features that can be distinguished by decision tree-based classifiers employing image-cytometric numerical data.



C. De Hauwer, I. Camby, F. Darro, I. Migeotte, C. Decaestecker, C. Verbeek, A. Danguy, J. Brotchi, I. Salmon, P. Van Ham, R. Kiss,
Gastrin inhibits motility, decreases cell death levels and increases proliferation in human glioblastoma cell lines.
Journal of neurobiology, Vol. 37, 3, pp. 373-382, 1998
Bibtex
Bibtex : info:hdl:2013/58839
Note : Journal Article
Abstract : Whether they are of low or high histopathological grade, human astrocytic tumors are characterized by a marked propensity to diffuse into large areas of normal brain parenchyma. This invasion relates mainly to cell motility, which enables individual cell migration to take place. The present study characterizes in vitro the gastrin-mediated effects on both the growth (cell proliferation vs. cell death) and motility dynamics of the human U87 and U373 glioblastoma cell lines. A computer-assisted phase-contrast microscope was used to track the number of mitoses versus cell deaths every 4 min over a 72-h period and so to quantitatively describe the trajectories of living U373 and U87 cells growing on plastic supports in culture media both with and without the addition of 0.1, 5, or 100 nM gastrin. While 5 or 100 nM gastrin only weakly (p < .05 to p < .01) increased cell proliferation in the U87 cell line and not in U373 one, it very significantly (p < .001) inhibited the amount of cell death at 5 and 100 nM in both the U87 and U373 lines. In addition, 5 nM gastrin markedly inhibited cell mobility in U87 (p < .00001) and U373 (p < .0001) glioblastoma models. All these data strongly suggest that gastrin plays a major role in the biological behavior of the in vitro U87 and U373 human glioblastoma cell lines in matters concerning their levels of cell motility and growth dynamics.



F. Darro, P. Cahen, A. Vianna, C. Decaestecker, J. Nogaret, B. Leblond, C. Chaboteaux, C. Ramos, M. Petein, V. Budel, A. Schoofs, B. Pourrias, R. Kiss,
Growth inhibition of human in vitro and mouse in vitro and in vivo mammary tumor models by retinoids in comparison with tamoxifen and the RU-486 anti-progestagen.
Breast cancer research and treatment, Vol. 51, 1, pp. 39-55, 1998
Bibtex
Bibtex : info:hdl:2013/56415
Note : Comparative Study
Abstract : Retinoids constitute a very promising class of agents for the chemoprevention or treatment of breast cancer. These retinoids exert their biological activity through two distinct classes of retinoic acid (RA) receptors (R), the RAR isotypes (alpha, beta, and gamma) and the three RXR isotypes (alpha, beta, and gamma) and their numerous isoforms which bind as RXR/RAR heterodimers to the polymorphic cis-acting response elements of RA target genes. With respect to these numerous receptor sub-types, the retinoid-induced effects at the biological level include marked modifications with respect to both cell proliferation and cell death (apoptosis), and also in the induction of differentiation processes. The present study aims to characterize the effect which four retinoids (TTNPB, 9-cis-RA, LGD 1069, 4-HPR) with distinct RAR/RXR binding properties induced on various in vitro and in vivo mouse and human breast cancer models. The experiments with the retinoids were carried out in comparison with the anti-estrogen tamoxifen and the anti-progestagen RU-486 compounds. The results show that the 6 compounds under study were markedly more efficient in terms of growth inhibition in the human T-47D cell line when maintained under anchorage-independent culture conditions than when maintained under anchorage-dependent ones. While RU-486 exhibited a weak statistically significant (p < 0.05) influence on the growth of the T-47D stem cells, tamoxifen had a marked inhibitory influence on the growth of these cells. Of the four retinoids, 4-HPR was the least effective since the lowest doses tested (1 and 0.1 nM) exhibited no statistically (p > 0.05) significant influence on the growth of the stem cells. The most efficient retinoid was TTNPB. It was only at the highest dose (10 microM) that tamoxifen and RU-486 showed a weak inhibitory influence on the growth of the T-47D non-stem cells while all 4 retinoids exerted a significant inhibitory influence on the growth of these non-stem cells, with 4-HPR being the most efficient (P < 0.001) at the highest dose, but ineffective (P > 0.05) at the lowest. Tamoxifen and TTNPB were tested in vivo on hormone-sensitive (HS) and hormone-insensitive (HI) strains of the MXT murine mammary carcinoma. While TTNPB appeared to be equally efficient in terms of growth inhibition in both MXT-HS and MXT-HI models, tamoxifen had only a marginal inhibitory influence on the growth of the MXT-HI strain but did inhibit growth in the case of the MXT-HS one. TTNPB was markedly more efficient than tamoxifen in terms of both inhibiting the cell proliferation level (measured by means of computer-assisted microscopy applied to Feulgen-stained nuclei, a method which enables the percentage of cells in the S phase of the cell cycle to be determined) and triggering cell death (measured by means of the determination of the transglutaminase activity) in both the MXT-HI and MXT-HS models. The very significant TTNPB-induced inhibition of the macroscopic MXT-HS growth rate relates to the triggering of cell death (apoptosis) rather than to an inhibition of cell proliferation. All these results clearly indicate that retinoids are very efficient agents against breast cancer, at least as efficient as tamoxifen.



R. Sears, C. Duckworth, C. Decaestecker, N. Bourgeois, T. Ledent, J. Devière, I. Salmon, R. Kiss, P. Yeaton,
Image cytometry as a discriminatory tool for cytologic specimens obtained by endoscopic retrograde cholangiopancreatography.
Cancer, Vol. 84, 2, pp. 119-126, 1998
Bibtex
Bibtex : info:hdl:2013/56413
Note : Journal Article
Abstract : BACKGROUND: Routine brush cytology is relatively insensitive for the diagnosis of biliary and pancreatic malignancy. Sensitivity can be improved by measuring DNA and proliferation. The goal of this study was to assess the discriminatory capacity of image cytometry using pancreaticobiliary brush cytology specimens obtained during endoscopic retrograde cholangiopancreatography (ERCP). Analysis included morphometry, DNA quantification, and characterization of nuclear chromatin distribution and condensation. METHODS: Brush cytology specimens were obtained during ERCP from 22 chronic pancreatitis specimens, 11 pancreatic adenocarcinoma specimens, 13 primary sclerosing cholangitis specimens, and 11 cholangiocarcinoma specimens and contrasted with 25 normal epithelia specimens. A SAMBA 2005 image processor was used to analyze Feulgen stained chromatin density and distribution. Discriminant analysis of 37 morphonuclear variables was performed to characterize differences between: 1) chronic pancreatitis and pancreatic adenocarcinoma, and 2) primary sclerosing cholangitis and cholangiocarcinoma. RESULTS: Chronic pancreatitis was distinguished from pancreatic adenocarcinoma (P < or = 0.001); sensitivity and specificity were both estimated to be 82\%. Primary sclerosing cholangitis was distinguished from cholangiocarcinoma (P < or = 0.01); sensitivity and specificity were estimated to be 82\% and 85\%, respectively. CONCLUSIONS: Multiparameter image cytometry has potential as an adjuvant diagnostic technique in patients with pancreaticobiliary malignancy.



C. Decaestecker, I. Camby, N. Nagy, J. Brotchi, R. Kiss, I. Salmon,
Improving morphology-based malignancy grading schemes in astrocytic tumors by means of computer-assisted techniques.
Brain pathology, Vol. 8, 1, pp. 29-38, 1998
Bibtex
Bibtex : info:hdl:2013/56414
Note : Journal Article
Abstract : We propose an original methodology which improves the accuracy of the prognostic values associated with conventional morphologically-based classifications in supratentorial astrocytic tumors in the adult. This methodology may well help neuropathologists, who must determine the aggressiveness of astrocytic tumors on the basis of morphological criteria. The proposed methodology comprises two distinct steps, i.e. i) the production of descriptive quantitative variables (related to DNA ploidy level and morphonuclear aspects) by means of computer-assisted microscopy and ii) data analysis based on an artificial intelligence-related method, i.e. the decision tree approach. Three prognostic problems were considered on a series of 250 astrocytic tumors including 39 astrocytomas (AST), 47 anaplastic astrocytomas (ANA) and 164 glioblastomas (GBM) identified in accordance with the WHO classification. These three problems concern i) variations in the aggressiveness level of the high-grade tumors (ANA and GBM), ii) the detection of the aggressive as opposed to the less aggressive low-grade astrocytomas (AST), and iii) the detection of the aggressive as opposed to the less aggressive anaplastic astrocytomas (ANA). Our results show that the proposed computer-aided methodology improves conventional prognosis based on conventional morphologically-based classifications. In particular, this methodology enables some reference points to be established on the biological continuum according to the sequence AST-->ANA-->GBM.



C. Francois, C. Decaestecker, I. Salmon, M. Petein, M. Remmelink, T. Janssen, E. Wespes, A. Peltier, C. Schulman, R. Van Velthoven, R. Kiss,
Prognostic value of stem cell line identification for renal cell carcinomas.
Analytical and quantitative cytology and histology, Vol. 20, 3, pp. 207-214, 1998
Bibtex
Bibtex : info:hdl:2013/58376
Note : Journal Article
Abstract : OBJECTIVE: To investigate the prognostic value of nuclear DNA content (DNA ploidy level) in a series of 95 renal cell carcinomas (RCCs). STUDY DESIGN: Eight variables were used to characterize DNA ploidy levels. They included DNA index and seven others characterizing the presence of specific stem cell lines in each of the 95 RCCs under study. All these variables were determined by means of computer-assisted microscopy applied to Feulgen-stained nuclei. The actual information contributed by each of the eight variables was determined by means of univariate statistical analyses. RESULTS: The results showed that in the DNA ploidy-related eight variables, the presence of at least 4\% aneuploid nuclei with > 5C DNA content was associated with the most significant prognostic value in RCCs with intermediate (T2, T3) invasion levels. CONCLUSION: The present study clearly showed that stem cell line characterization, and particularly the presence of highly aneuploid cells (with > 5C DNA content), is associated in RCCs with significant prognostic value. This kind of marker may help the identification of patients who will develop metastases after surgery and for whom adjuvant therapy might thus be indicated.



S. Saussez, H. Marchant, N. Nagy, C. Decaestecker, S. Hassid, A. Jortay, M. Sch{\"u}ring, H. Gabius, A. Danguy, I. Salmon, R. Kiss,
Quantitative glycohistochemistry defines new prognostic markers for cancers of the oral cavity.
Cancer, Vol. 82, 2, pp. 252-260, 1998
Bibtex
Bibtex : info:hdl:2013/58370
Note : Journal Article
Abstract : BACKGROUND: Histopathologic grading and clinical staging cannot provide a precise prognosis of oral cavity cancer patients. The use of glycohistochemical markers may improve the level of prognostic accuracy of such conventional classification systems. METHODS: Computer-assisted microscopy was employed in a series of 40 oral cavity cancers to determine quantitatively the percentage of positive cells, the staining intensity, and the level of staining heterogeneity for 3 glycohistochemical markers, including peanut agglutinin (PNA), Thomsen-Friedenreich antigen (T antigen) as part of a neoglycoprotein, and sarcolectin. Data were evaluated by discriminant analysis. RESULTS: Although the level of differentiation (P < 0.01 to P < 0.001) and the T variable of the TNM staging system (P < 0.05 to P < 0.01) related mainly to the level of expression of the acceptor sites for PNA and the T antigen, the patient survival period (P < 0.05) was largely a fraction of the level of expression of the acceptor sites for the carrier-immobilized T antigen and for sarcolectin. CONCLUSIONS: In oral cavity cancer, determining the level of acceptor sites for PNA, T antigen, and sarcolectin provides useful information on histopathologic differentiation, clinical staging, and survival. Because these processes of determination were carried out quantitatively, a discriminant model was set up, which enabled the level of oral cavity cancer aggressiveness to be characterized precisely. The current methodology described in this article should therefore afford pathologists original and quantitative (and thus objective) prognostic markers for oral cavity cancers.



S. Farinelle, C. De Hauwer, F. Darro, C. Decaestecker, J. Fontaine, J. Pasteels, P. Van Ham, G. Atassi, R. Kiss,
Setting up of an original computer-assisted methodology to characterize in vitro drug-induced anti-angiogenic effects.
International Journal of Molecular Medicine, Vol. 2, 5, pp. 545-553, 1998
Bibtex
Bibtex : info:hdl:2013/71123
Note : Journal Article
Abstract : The development of angiogenesis within a tumor brings on a sequence of extremely complex molecular events. We have developed a methodology which enables a wide set of biological parameters to be quantitatively determined in the field of anti-angiogenesis pharmacology. This methodology which includes a video cell tracking device, is unique because it offers the possibility of evaluating the specific influence of a given compound with potential anti-angiogenic properties on cell cycle kinetics, cell death, global cell line growth, and cell motility. We chose TNP-470, a synthetic analogue of fumagilin, to test our methodology on HUVEC cell lines taken from various human umbilical cord veins. The experiments carried out with TNP-470 did not confirm all the data reported in the literature. Our results show that i) TNP-470 could be considered as a cytotoxic agent; ii) this compound had an apparently marginal cytostatic effect; and iii) it did not increase the apoptosis level. Our methodology also revealed that the HUVEC cell lines are very heterogeneous in terms of different biological parameters. This highlights the problem of the reproductibility of the result.



C. Francois, M. Remmelink, M. Petein, R. Van Velthoven, A. Danguy, E. Wespes, I. Salmon, R. Kiss, C. Decaestecker,
The chromatin pattern of cell nuclei is of prognostic value for renal cell carcinomas.
Analytical cellular pathology : the journal of the European Society for Analytical Cellular Pathology, Vol. 16, 3, pp. 161-175, 1998
Bibtex
Bibtex : info:hdl:2013/58379
Note : Journal Article
Abstract : Using a series of 105 renal cell carcinomas (RCCs) we investigated whether features quantitatively describing the appearance of Feulgen-stained nuclei and, more particularly, of their chromatin (on the basis of computer-assisted microscopy) can contribute any significant prognostic information. Thirty morphonuclear and 8 nuclear DNA content-related variables were thus generated. The actual prognostic values of this set of cytometric variables was compared (by means of discriminant statistical analysis) to conventional diagnostic and/or prognostic markers including histopathological grades, tumour invasion levels and the presence or absence of metastases. We obtained complete clinical follow-ups for 49 of the 105 RCC patients under study, making it possible to define a subset of patients with a bad prognosis (i.e., who died in the 12 months following nephrectomy) and a subset of patients with a good prognosis (i.e., who survived at least 24 months following nephrectomy). An original method of data analysis related to artificial intelligence (decision tree induction) enabled a strong prognostic model to be set up. In the case of 10 new patients, this model identified all the dead patients as having a bad survival status, with a total of 8 correct predictions. Another prognostic model similarly generated enabled the correct predictions to be confirmed.



M. Remmelink, C. Decaestecker, F. Darro, D. Goldschmidt, M. Gebhart, J. Pasteels, R. Kiss, I. Salmon,
The in vitro influence of eight hormones and growth factors on the proliferation of eight sarcoma cell lines.
Journal of cancer research and clinical oncology, Vol. 124, 3-4, pp. 155-164, 1998
Bibtex
Bibtex : info:hdl:2013/56412
Note : Journal Article
Abstract : Little is known about the regulation of sarcoma proliferation by hormones and/or growth factors. We therefore characterised the in vitro proliferative influence on eight sarcoma cell lines of the platelet-derived growth factor, the insulin-like growth factor 1, triiodothyronine, the epidermal growth factor, the luteinising-hormone-releasing hormone, progesterone, gastrin and 17 beta-oestradiol. The influence of the different factors on the proliferation of sarcoma cell lines was measured by the colorimetric 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide test. Two culture media were studied: (1) a nutritionally poor medium containing 2\% of fetal calf serum and (2) a nutritionally rich one containing 5\% or 10\% FCS both with and without the addition of non-essential amino acids. The results were analysed either by conventional statistical analyses or by a classification method based on a decision-tree approach developed in Machine Learning. This latter method was also compared to other classifiers (such as logistic regression and k nearest neighbours) with respect to its accuracy of classification. Monovariate statistical analysis showed that each of the eight cell lines exhibited sensitivity to at least one factor, and each factor significantly modified the proliferation of five or six of the eight cell lines under study. Of these eight lines one of fibrosarcoma origin was the most "factor-sensitive". Decision-tree-related data analysis enabled the specific pattern of factor sensitivity to be characterised for the three histological types of cell line under study. The effects of hormone and growth factors are significantly influenced by the type of culture medium used. The method used appeared to be an accurate classifier for the kind of data analysed. Sarcoma proliferation can be modulated, at least in vitro, by various hormones and growth factors, and the proliferation of each histopathological type exhibited a distinct sensitivity to different hormone and/or growth-factors.



P. Yeaton, H. Frierson, A. Hittelet, C. Duckworth, C. Deprez, N. Bourgeois, I. Salmon, R. Jones, R. Kiss, C. Decaestecker,
Use of image cytometry to classify biliary and ampullary adenocarcinomas.
Analytical and quantitative cytology and histology, Vol. 20, 6, pp. 509-516, 1998
Bibtex
Bibtex : info:hdl:2013/58388
Note : Journal Article
Abstract : OBJECTIVE: To create an objective classification system to perform TNM classification of ampullary adenocarcinoma and cholangiocarcinoma using image cytometric data derived from Feulgen-stained tumor nuclei. STUDY DESIGN: Surgically resected cases of ampullary adenocarcinoma and cholangiocarcinoma with established TNM classifications were selected on the basis of available formalin-fixed, paraffin-embedded tissue. Fifteen numerical variables related to morphometric, densitometric and textural features of each tumor nucleus were recorded. We employed a methodology based on multivariate statistical tools to characterize the association of morphonuclear variables with TNM classification. The first step consisted of identifying and selecting representative nuclei of each T class. From this "purified" data set an objective classification system was created. The classification system was assessed using internal and external validation. RESULTS: Employing ANOVA, all 15 variables were significantly associated with T classification, 11 of 15 with N and 4 with M. Multivariate analysis was employed to distinguish between T1, T2 and T3 lesions. Our methodology correctly classified 76\% of T1 nuclei, 47\% of T2 nuclei and 84\% of T3 nuclei. Heterogeneity within an individual tumor was defined in 61\% of cases included in the training set. Complete concordance between pathologic classification and the classification system was observed in 71\% of an independent validation.




1997

Papers

S. Hassid, C. Decaestecker, C. Hermans, I. Salmon, J. Pasteels, A. Danguy, R. Kiss,
Algorithm analysis of lectin glycohistochemistry and Feulgen cytometry for a new classification of nasal polyposis
The Annals of otology, rhinology & laryngology, Vol. 106, 12, pp. 1043-1051, 1997
Bibtex
Bibtex : info:hdl:2013/229150
Note : Language of publication: en
Abstract : The aim of this study is to present a new classification of nasal polyps. This classification is based both on morphologic criteria relating to morphonuclear features from isolated Feulgen-stained nuclei and on glycohistochemical characteristics from histologic slides submitted to three lectins (peanut, wheat germ, and gorse seed agglutinins) and one neoglycoconjugate glycohistochemical stain. While the morphonuclear features (including 30 variables) relate essentially to chromatin pattern, the glycohistochemical stains (including 16 variables) are linked to the presence of specific carbohydrate moieties in cell membranes and cytoplasm. Forty-nine nasal polyps, including single polyps, diffuse polyposis, cystic fibrosis-related polyposis, and aspirin idiosyncracy-related polyposis associated with asthma, were thus characterized. All the variables were obtained quantitatively by means of computer-assisted microscopy. Two complementary methods of data classification were used to determine the actual diagnostic value contributed by each quantitative variable, namely, discriminant analysis, which forms part of multifactorial statistical analysis, and the decision tree technique, which is an artificial intelligence-related algorithm. The data so obtained show that our morphologic classification of nasal polyps fits in with the classification of nasal polyps defined on the basis of clinical criteria.



N. Renard, D. Goldschmidt, C. Decaestecker, P. Loréa, J. Berthe, S. Verraes, G. Ghanem, I. Salmon, R. Kiss,
Characterization of the nuclear deoxyribonucleic acid content and nuclear morphometry in 71 primary cutaneous melanomas.
Dermatology, Vol. 194, 4, pp. 318-324, 1997
Bibtex
Bibtex : info:hdl:2013/55923
Note : Journal Article
Abstract : BACKGROUND: While the determination of nuclear deoxyribonucleic acid (DNA) content (DNA ploidy level) and nuclear morphometry characterization has proved to be of prognostic value in melanocytic lesions, there are several ways of performing these determinations. OBJECTIVE: To identify which of 9 DNA ploidy- and 2 nuclear morphometry-related variables are of prognostic and/or diagnostic value in 71 primary melanomas. METHODS: Histological typing, Breslow depth determination, the evaluation of Clark's level of invasion and the 11 quantitative variables (calculated in Feulgen-stained nuclei using computer-assisted microscope analysis) determined for each melanoma were submitted to discriminant analysis. RESULTS: The discriminant analysis of image cytometric variables enabled specific cell subpopulations to be identified in histological and the Breslow-related groups, but not in the Clark-related ones. CONCLUSION: The characterization of melanoma heterogeneity by means of the identification of specific DNA ploidy level-related cell subpopulations in specific Breslow-related groups enables the problem of intra- and interobserver variability in Breslow depth determination to be reduced and therefore can help dermatologists in their daily routine.



C. Francois, C. Decaestecker, M. Petein, P. Van Ham, A. Peltier, J. Pasteels, A. Danguy, I. Salmon, R. Van Velthoven, R. Kiss,
Classification strategies for the grading of renal cell carcinomas, based on nuclear morphometry and densitometry.
Journal of pathology, Vol. 183, 2, pp. 141-150, 1997
Bibtex
Bibtex : info:hdl:2013/57948
Note : Journal Article
Abstract : The various grading systems proposed for renal cell carcinomas all suffer from problems related to inter-observer variability. Some of these grading systems are based, either partially or wholly, on morphonuclear criteria, such as nuclear size and shape, anisonucleosis, and chromatin pattern. These criteria can be quantitatively (and thus objectively) evaluated by means of the computer-assisted microscopic analysis of Feulgen-stained nuclei. In the present work, 39 quantitative variables, including two morphometric, 28 chromatin pattern-related, and nine DNA ploidy level-related, were computed for 65 renal cell carcinomas. The actual diagnostic information contributed by each variable was determined by means of multifactorial statistical analysis (discriminant analysis) and two artificial intelligence-related methods of data classification (the decision tree and production rule methods). The results show that quantitative information, as provided by the computer-assisted microscopy of Feulgen-stained nuclei and analysed by means of artificial intelligence-related methods of data classification, contributes significant diagnostic information for the grading of renal cell carcinoma, thus reducing the problem of inter-observer reproducibility.



M. Lopes, I. Salmon, N. Nagy, C. Decaestecker, J. Pasteels, E. Laws, R. Kiss,
Computer-Assisted Microscope Analysis of Feulgen-Stained Nuclei in Gonadotroph Adenomas and Null-Cell Adenomas of the Pituitary Gland.
Endocrine pathology, Vol. 8, 2, pp. 109-120, 1997
Bibtex
Bibtex : info:hdl:2013/57968
Note : JOURNAL ARTICLE
Abstract : The current classification of clinically nonfunctioning pituitary adenomas is based on immunocytochemical and ultrastructural studies. However, a number of cases have less distinctive features that cannot be easily conformed with the prevailing morphologic classifications. The diagnostic information contributed by the determination of the nuclear DNA content (DNA ploidy level) and quantitative chromatic pattern description as opposed to the morphofunctional diagnosis in clinically nonfunctioning adenomas was consequently investigated in a series of 71 pituitary adenomas, including 31 null-cell adenomas, 35 gonadotropin adenomas, and 5 nonfunctioning adenomas that were not examined by electron microscopy. DNA ploidy level (8 variables) and quantitative chromatin pattern description (30 variables) were carried out by means of the computer-assisted microscope analysis of 80-1600 Feulgen-stained nuclei analyzed/case. The diagnostic information contributed by the 38 quantitative variables was determined by multifactorial statistical analysis (i.e., Discriminant Analysis). This computer-assisted classification significantly differentiated nulLcell adenomas from gonadotropin adenomas (p = 0.0025). In addition, it was able to differentiate three major subtypes of nonfunctioning adenomas on the basis of their immunohistochemical profiles. These were the immunonegative adenomas, the follicle-stimulating hormone (FSH)-positive adenomas, and the a-subunit (a) and/or luteiwizing hormone (LH)-positive adenomas (p < 0.0001 to p < 0.001). We thus suggest that the cytometric image analysis of Feulgen-stained nuclei can contribute on the discrimination of subtypes of clinically nonfunctioning pituitary adenomas.



D. Goldschmidt, L. Gordower, J. Berthe, M. Remmelink, C. Decaestecker, M. Petein, I. Salmon, R. Kiss, A. Danguy,
Contribution of quantitative lectin histochemistry to characterizing well-differentiated, dedifferentiated and poorly differentiated liposarcomas.
Analytical and quantitative cytology and histology, Vol. 19, 3, pp. 215-226, 1997
Bibtex
Bibtex : info:hdl:2013/58355
Note : Journal Article
Abstract : OBJECTIVE: To find new diagnostic markers in the group of lipomatous tumors. STUDY DESIGN: The histochemical lectin staining pattern was characterized in a series of 45 lipomatous lesions, including 10 typical lipomas, 6 atypical lipomas, 8 well-differentiated, 6 myxoid, 5 dedifferentiated and 10 pleomorphic liposarcomas. Three lectins were used-peanut (Arachis hypogaea) agglutinin, which binds to terminal Gal(beta 1,3)GalNAc residues; wheat germ (Triticum vulgare) agglutinin (s-WGA, the succinylated form of WGA), which binds to ((1-4)-D-GlcNAc)n and Neu5NAc residues; and jack bean (Concanavalia ensiformis) agglutinin which binds to alpha-D-Man and alpha-D-Glc residues. Histochemical staining was quantitatively measured by means of a cell image processor. RESULTS: In the case of certain carbohydrate residues, typical lipomas closely resemble atypical lipomas, which in turn closely resemble well-differentiated liposarcomas; typical lipomas differ significantly from well-differentiated liposarcomas. This indicates that atypical lipomas, or at least some of them, could represent a biologic link between typical lipomas and well-differentiated liposarcomas. While well-differentiated and pleomorphic liposarcomas differed significantly from each other, the poorly differentiated component of dedifferentiated liposarcomas included histochemical lectin properties, which were common to both well-differentiated and pleomorphic liposarcomas. CONCLUSION: Some atypical lipomas exhibit glycohistochemical characteristics that are common to those of well-differentiated liposarcoma. The poorly differentiated component of dedifferentiated liposarcomas remains more differentiated in terms of glycohistochemical markers than do poorly differentiated pleomorphic liposarcomas.



P. Loréa, C. Decaestecker, D. Goldschmidt, N. Renard, J. André, D. Lipski, B. Van Den Heule, I. Salmon, F. Darro, R. Kiss,
Correlation between gender and cytomorphonuclear characteristics in human melanomas and in vitro evidence of sex steroid-induced modifications in the morphonuclear characteristics of three human melanoma cell lines.
Melanoma research, Vol. 7, 5, pp. 382-392, 1997
Bibtex
Bibtex : info:hdl:2013/58360
Note : Journal Article
Abstract : The influence of gonadal steroids on human melanoma still remains a controversial issue. The aim of our study was to investigate whether sex steroids may influence the biological characteristics of human melanoma. Such biological characteristics were monitored at the morphological level by means of computer-assisted microscope analysis of Feulgen-stained nuclei, which provides 28 quantitative variables describing the nucleus morphometry (size, anisonucleosis level) and chromatin pattern. This methodology was used to characterize the morphonuclear features in a series of 69 human melanomas (from formalin-fixed paraffin embedded tissues) including 28 male, 17 premenopausal and 24 postmenopausal female patients, and to investigate the effect of two sex steroids (5-alpha-dihydrotestosterone [DHT] and 17-beta-oestradiol [E2]) on three human melanoma in vitro models--the HT-144, SK-MEL-28 and C32 cell lines. The results show that the morphonuclear characteristics of melanoma originating from male and female patients are very distinct (P < 0.01). This difference is still more marked (P < 0.0005) when only premenopausal female patients are compared with male patients. The in vitro data show that both DHT and E2 are able to modify markedly (P < 0.001 to P < 0.0001) the nucleus morphometry and chromatin pattern of the three cell lines. Although the mechanism and the physiological outcome are still unknown, the present work shows that there is in vivo and in vitro evidence that the biological behaviour of human melanoma is influenced by sex steroids.



C. Decaestecker, I. Camby, M. Remmelink, N. Nagy, M. Petein, J. Pasteels, P. Van Ham, I. Salmon, R. Kiss,
Decision tree induction: a useful tool for assisted diagnosis and prognosis in tumor pathology.
Laboratory investigation, Vol. 76, 6, pp. 799-808, 1997
Bibtex
Bibtex : info:hdl:2013/57953
Note : Comparative Study
Abstract : The aim of the present work is to show that decision tree induction algorithms are a useful tool for extracting reliable information from data series, with the objective of assisting pathologists in identifying specific diagnostic and prognostic markers in various types of tumor pathologies. In terms of accuracy, we show that the decision tree technique exceeds other more sophisticated techniques, such as multilayer neural networks. Furthermore, because of the case with which decision tree results can be interpreted (logical classification rules), new methodologies can be readily developed to further assist in analyzing complex data that mix heterogeneous features. In this paper, we illustrate such capabilities in the context of different complex diagnostic and/or prognostic problems in tumor pathology relating to bladder, astrocytomas, and adipose tissues.



S. Hassid, M. Degaute, S. Dawance, K. Rombaut, N. Nagy, G. Choufani, C. Decaestecker, A. Danguy, I. Salmon, R. Kiss,
Determination of proliferative activity in nasal polyps.
Journal of Clinical Pathology, Vol. 50, 11, pp. 923-928, 1997
Bibtex
Bibtex : info:hdl:2013/57945
Note : Journal Article
Abstract : AIMS: To determine the level of proliferative activity in 39 nasal polyps with clear cut distinct clinical behaviour patterns. METHODS: The 39 nasal polyps included 11 polyps labelled as "single" and taken from the lateral nasal wall and the middle turbinate; 12 polyps labelled as "massive" and relating to diffuse polyposis involving the entire nasal cavity; six polyps labelled as "ASA" and relating to nasal polyps from patients with acetylsalicylic acid intolerance and asthma; and 10 polyps from cystic fibrosis related polyposis. Cell proliferation was determined by two independent methods: first, the computer assisted microscope analysis of isolated Feulgen stained nuclei for the measurement of the percentage of cells in the S phase of the cell cycle; and second, the immunohistochemical evaluation of a proliferation associated protein by means of the MIB 1 monoclonal antibody. RESULTS: The cystic fibrosis related polyposis exhibited the highest proliferative activity of all the clinically identified nasal polyp groups. Acute inflammatory nasal polyps exhibited a higher cell proliferation than chronic ones. The results also show that while the immunohistochemical determination of cell proliferation by means of the MIB 1 monoclonal antibody is a valuable tool in determining cell proliferation in nasal polyps, the cytometrical image analysis of Feulgen stained nuclei is not useful for this purpose. CONCLUSION: Cell proliferation activity identifies cystic fibrosis as being distinct from the other nasal polyp groups.



C. De Hauwer, I. Camby, F. Darro, C. Decaestecker, T. Gras, I. Salmon, R. Kiss, P. Van Ham,
Dynamic characterization of glioblastoma cell motility.
Biochemical and biophysical research communications, Vol. 232, 2, pp. 267-272, 1997
Bibtex
Bibtex : info:hdl:2013/58348
Note : Journal Article
Abstract : The cell motility dynamic of two glioblastoma cell lines (U373 and U87) was studied by means of an automatic video-cell-tracking-system enabling each cell in a colony to be tracked for several hours. Twenty-five experiments were performed on both models growing on three different supports (glass, plastic and Matrigel). Cell motility was significantly different in each cell line and also for different growth support in a given cell line. We observed that U87 cells are significantly (p < 0.00001) less motile than U373 cells. The most favorable growth supports for cell motility studies were Matrigel and glass. A significant (p < 0.001) correlation between cell colony density and cell motility was highlighted, with isolated cells exhibiting a motility level distinct from the one observed for colonies. The present methodology, which enabled cell motility to be quantified in human glioblastoma cells, represents an original tool for identifying new classes of compounds able to reduce glioblastoma cell motility and cell migration potential into the brain.



C. Decaestecker,
Finding prototypes for nearest neighbour classification by means of gradient descent and deterministic annealing
Pattern recognition, Vol. 30, 2, pp. 281-288, 1997
Bibtex
Bibtex : info:hdl:2013/194973
Note : Language of publication: en



C. Decaestecker, I. Salmon, O. De Witte, I. Camby, P. Van Ham, J. Pasteels, J. Brotchi, R. Kiss,
Nearest-neighbor classification for identification of aggressive versus nonaggressive low-grade astrocytic tumors by means of image cytometry-generated variables.
Journal of neurosurgery, Vol. 86, 3, pp. 532-537, 1997
Bibtex
Bibtex : info:hdl:2013/56341
Note : Journal Article
Abstract : The authors investigated whether cytometry-related variables generated by means of computer-assisted microscopic analysis of Feulgen-stained nuclei can contribute significant information toward the characterization of low-grade astrocytic tumor aggressiveness. This investigation was conducted using the nearest-neighbor rule (a traditional classification method used in pattern recognition) to analyze a series of 250 supratentorial astrocytic tumors from adult patients. This series included 39 low-grade astrocytomas and 211 high-grade astrocytic tumors (including 47 anaplastic astrocytomas and 164 glioblastomas multiforme [GBMs]). The results show that the 3-nearest-neighbors rule enabled a subgroup of "atypical" astrocytomas to be distinguished from the "typical" tumors. The atypical astrocytoma species exhibited a DNA content (DNA ploidy level) and morphonuclear characteristics that were statistically more similar to the characteristics of GBMs than to those exhibited by the typical astrocytomas. An analysis of survival data revealed that patients with atypical astrocytomas survived for a significantly shorter period (p < 0.001) than patients with typical lesions of this kind. In fact, patients with atypical astrocytomas had a survival period similar to that of patients with anaplastic astrocytomas, whereas patients with typical astrocytomas had a survival period significantly longer (p < 0.0001) than those associated with anaplastic astrocytomas and GBMs.



V. Budel, P. Gasperin, S. Hatschbach, T. Cavalcanti, M. Petein, C. Decaestecker, F. Darro, I. Salmon, R. Kiss,
Ploidy level determination and quantitative chromatin pattern description in pregnancy-associated breast cancers.
Breast cancer research and treatment, Vol. 45, 2, pp. 109-120, 1997
Bibtex
Bibtex : info:hdl:2013/158282
Note : Journal Article
Abstract : The present study deals with the characterization of hormone-sensitivity in pregnancy-associated breast cancers (PBCs). This characterization was carried out in 22 PBCs as opposed to 88 non-pregnancy-associated breast cancers (NPBCs). For this study, we used the digital cell image analysis of Feulgen-stained nuclei to assess the type of hormone-sensitivity. In a previous study it was demonstrated that the chromatin pattern in breast cancers is related to the amounts of estrogen receptors they contain. Our results demonstrated that the quantitative description of the chromatin pattern by means of 15 parameters (relating to morphometric, densitometric, and textural features) made it possible to identify typical cell nuclei populations in the PBC and NPBC groups. The use of specific statistical analyses (principal-components and discriminant) made it possible to quantify the proportion of each cell nucleus type in the PBCs. Furthermore, of the 22 PBCs under study, 13 contained a large majority of cell nuclei whose chromatin pattern was characteristic of hormone-sensitive cells, while 5 cases contained a large majority of typically hormone-insensitive ones. The remaining 4 cases contained a relatively similar proportion of typically hormone-sensitive and insensitive cell nuclei. The quantitative chromatin pattern description thus made it possible to characterize the hormone-sensitivity level in PBCs, whereas DNA ploidy level determination did not enable any such characterization to be carried out. The chromatin pattern assay described here, which enables hormone-sensitive pregnancy-associated breast cancers to be identified from hormone-insensitive ones independently from biochemical assays, should help the physician regarding therapy adaptation.



C. Decaestecker, M. Lopes, L. Gordower, I. Camby, P. Cras, J. Martin, R. Kiss, S. VandenBerg, I. Salmon,
Quantitative chromatin pattern description in Feulgen-stained nuclei as a diagnostic tool to characterize the oligodendroglial and astroglial components in mixed oligo-astrocytomas.
Journal of neuropathology and experimental neurology, Vol. 56, 4, pp. 391-402, 1997
Bibtex
Bibtex : info:hdl:2013/58351
Note : Journal Article
Abstract : The oligoastrocytoma, as a mixed glioma, represents a nosologic dilemma with respect to precisely defining the oligodendroglial and astroglial phenotypes that constitute the neoplastic cell lineages of these tumors. In this study, cell image analysis with Feulgen-stained nuclei was used to distinguish between oligodendroglial and astrocytic phenotypes in oligodendrogliomas and astrocytomas and then applied to mixed oligoastrocytomas. Quantitative features with respect to chromatin pattern (30 variables) and DNA ploidy (8 variables) were evaluated on Feulgen-stained nuclei in a series of 71 gliomas using computer-assisted microscopy. These included 32 oligodendrogliomas (OLG group: 24 grade II and 8 grade III tumors according to the WHO classification), 32 astrocytomas (AST group: 13 grade II and 19 grade III tumors), and 7 oligoastrocytomas (OLGAST group). Initially, image analysis with multivariate statistical analyses (Discriminant Analysis) could identify each glial tumor group. Highly significant statistical differences were obtained distinguishing the morphonuclear features of oligodendrogliomas from those of astrocytomas, regardless of their histological grade. When compared with the 7 mixed oligoastrocytomas under study, 5 exhibited DNA ploidy and chromatin pattern characteristics similar to grade II oligodendrogliomas, I to grade III oligodendrogliomas, and I to grade II astrocytomas. Using multifactorial statistical analyses (Discriminant Analysis combined with Principal Component Analysis). It was possible to quantify the proportion of "typical" glial cell phenotypes that compose grade II and III oligodendrogliomas and grade II and III astrocytomas in each mixed glioma. Cytometric image analysis may be an important adjunct to routine histopathology for the reproducible identification of neoplasms containing a mixture of oligodendroglial and astrocytic phenotypes.



R. Kiss, O. De Witte, C. Decaestecker, I. Camby, L. Gordower, K. Delbecque, J. Pasteels, J. Brotchi, I. Salmon,
The combined determination of proliferative activity and cell density in the prognosis of adult patients with supratentorial high-grade astrocytic tumors.
American journal of clinical pathology, Vol. 107, 3, pp. 321-331, 1997
Bibtex
Bibtex : info:hdl:2013/56342
Note : Journal Article
Abstract : Tumor growth represents the ratio between cell gain (number of mitoses per unit of time, i.e., proliferative activity) and cell loss (number of cell deaths during the same unit of time). While in adults, proliferative activity parallels the level of malignancy in astrocytic tumors and therefore represents a useful diagnostic marker, cell loss has never been concomitantly assessed in tumors of this type. We hypothesize that cell density assessable on histologic slides represents the ratio between cell gain and cell loss. This hypothesis concerns only the diffuse type of astrocytic tumors. Proliferative activity (assessed by MIB1 antigen immunostain) and cell density were thus quantitatively assessed by means of a cell image processor in a series of 54 supratentorial astrocytic tumors of adult patients, which included 15 astrocytomas (ASTs), 18 anaplastic astrocytomas (ANAs), and 21 glioblastomas (GBMs). The results show that proliferative activity and cell density were highly correlated (P = .003) and that both correlated with histopathologic grade. The patients with a high-grade astrocytic tumor (i.e., ANA or GBM) that exhibited a low level of proliferative activity but high cell density survived for significantly shorter periods than did patients with a tumor that exhibited low proliferative activity and low cell density (P = .002). The patients with a high-grade astrocytic tumor that exhibited high proliferative activity and high cell density survived for significantly less time than did the patients with a tumor that exhibited high proliferative activity but low cell density (P < .05). A marked difference in survival periods was observed between the patients with a high-grade astrocytic tumor that exhibited a low level of proliferative activity and low cell density and the patients with a tumor that exhibited a high level of proliferative activity and high cell density (P < .001). The concomitant determination of proliferative activity and cell density seems likely to enable determination of the few adult patients who have high-grade astrocytic tumors and who will survive for a considerable period (several years).




1996

Papers

M. Petein, C. Decaestecker, V. Segers, T. Janssen, M. Fourmarier, P. Van Leer, R. Van Velthoven, C. Schulman, J. Pasteels, R. Kiss,
Does any correlation exist between the Gleason classification system and the computer-assisted microscope analysis of Feulgen-stained nuclei features in human prostate adenocarcinoma?
Analytical cellular pathology : the journal of the European Society for Analytical Cellular Pathology, Vol. 12, 3, pp. 159-171, 1996
Bibtex
Bibtex : info:hdl:2013/57970
Note : Journal Article
Abstract : Grading prostatic adenocarcinomas remains an important problem. Various systems exist (including those proposed by Gleason) but none of these systems seems able to reliably predict either the lethal potential of a tumor in an individual patient or the responsiveness of an individual tumor to various forms of therapy. The most frequently used grading system, as proposed by Gleason, is essentially based on the description of tumor growth pattern. The aim of the present work is therefore to investigate whether the quantitative description of morphonuclear features (including cell anaplasia) and the DNA ploidy level can contribute significant information to the Gleason grading, thus partly at least reducing its subjective nature. This quantitative description was carried out by means of the Feulgen-stained nuclei image cytometry computation of 24 variables in 101 prostatic adenocarcinomas. The results show that both DNA ploidy- and morphonuclear-related variables were weak discriminators for the various grades of the Gleason classification system, and particularly between the high (Gleason 4 and 5) and the other Gleason-grades, i.e. the low (Gleason 1 and 2) and intermediate (Gleason 3) ones. The morphonuclear evidence of anaplasia is thus not redundant data on tumor growth pattern and may be expected to provide additional diagnostic information.



J. Berthe, D. Goldschmidt, I. Salmon, C. Decaestecker, M. Remmelink, M. Petein, J. Pasteels, H. Roels, H. Frierson, R. Kiss,
Image cytometry analysis of Feulgen-stained nuclei in 72 lipomatous lesions including atypical lipomas and well-differentiated liposarcomas.
American journal of clinical pathology, Vol. 106, 3, pp. 289-297, 1996
Bibtex
Bibtex : info:hdl:2013/57974
Note : Journal Article
Abstract : Well-differentiated lipomatous tumors constitute a histopathologic category whose nomenclature has been controversial, particularly with respect to the distinction between atypical lipomas of the extremities and well-differentiated liposarcomas of the retroperitoneum. To determine whether there were differences in image analytic parameters between these neoplasms, 72 lesions including 21 typical lipomas, 7 atypical lipomas, 16 retroperitoneal and 5 nonretroperitoneal well-differentiated, 9 dedifferentiated, and 14 pleomorphic liposarcomas were submitted to the computer-assisted microscopic analysis of Feulgen-stained nuclei. This methodology enabled four groups of variables to be calculated. These included: (1) quantitative chromatin pattern description (14 variables); (2) the measurement of proliferative activity (1 variable); (3) nuclear DNA content (DNA ploidy level, 5 variables); and (4) the measurement of cell density and topographical cell nuclei organization (2 variables). The results strongly suggest that atypical lipomas, whether superficial or deep, and well-differentiated liposarcomas, whether retroperitoneal or not, belong to the same category in terms of the variables analyzed.



S. Hassid, G. Choufani, O. El-Kattabi, S. Dawance, C. Decaestecker, M. Brugmans, A. Danguy, J. Pasteels, I. Salmon, R. Kiss,
Image cytometry characterization of ploidy level, proliferative activity and chromatin pattern in 50 nasal polyps
International journal of oncology, Vol. 9, 1, pp. 137-143, 1996
Bibtex
Bibtex : info:hdl:2013/170155
Note : SCOPUS: ar.j
Abstract : A computer-assisted microscope analysis of Feulgen-stained nuclei was carried out on a series of 50 nasal polyps in order to try to identify specific biological subgroups. The present series of 50 nasal polyps includes single polyps both associated (n=9) and unassociated (n=9) with allergy and diffuse polyposis both associated (n=7) and unassociated (n=9) with allergy, cystic fibrosis (n=9) and ASA (aspirin-sinusitis-asthma) related polyposis (n=7). The computer-assisted microscope analysis provides 36 quantitative variables which include 1 variable describing proliferative activity, 9 describing the nuclear desoxyribonucleic acid distribution (DNA ploidy level) and 26 describing nucleus morphology, i.e. its size and chromatin pattern. The results show that the methodology proposed here enabled four major groups of nasal polyps to be identified, i.e. diffuse polyposis associated with allergy, cystic fibrosis-related polyposis, single polyps both associated and unassociated either with allergy and a fourth group including diffuse polyposis not associated with allergy and ASA-related polyposis. These four groups of nasal polyps differed markedly in their morphonuclear characteristics, but not in the proliferative activity- and DNA ploidy- related variables.



C. Decaestecker, M. Remmelink, I. Salmon, I. Camby, D. Goldschmidt, M. Petein, P. Van Ham, J. Pasteels, R. Kiss,
Methodological aspects of using decision trees to characterise leiomyomatous tumors.
Cytometry, Vol. 24, 1, pp. 83-92, 1996
Bibtex
Bibtex : info:hdl:2013/57978
Note : Journal Article
Abstract : The aim of the present work is to present the potential uses of a classification technique labeled the "decision tree" for tumor characterisation when faced with a large number of features. The decision tree technique enables multifeature logical classification rules to be produced by determining discriminatory values for each feature selected. In this report, we propose a methodology that used decision trees to compare and evaluate the information contributed by different types of features for tumor characterisation. This methodology is able to produce a set of hypotheses related to a diagnosis and or prognosis problem. For example, hypotheses can be producted (on the basis of a set of descriptive features) to explain why tumor cases belong to a given histopathological group. To illustrate our purpose, this methodology was applied to the difficult problem of leiomyomatous tumour diagnosis. The aim was to illustrate what kind of diagnostic information can be extracted from a sample data set including 23 smooth muscle tumors (14 benign leiomyomas and 9 malignant leiomyosarcomas) described by a large set of computer-assisted, microscope-generated features. Three groups of features were used relating to: (1) ploidy level determination (10 features), (2) quantitative chromatin pattern description (15 features), and (3) immunohistochemically related antigen specificities (6 features). All these features were quantified by digital cell image analysis. The results suggest that an objective distinction between leiomyomas and leiomyosarcomas can be established by means of simple logical rules depending on only a few features among which the immunohistochemically revealed antigen expression of desmin plays a preponderant part. One of the combinations of features proposed by the methodology is interesting for pathologists, because it includes two features describing the appearance of a nucleus in terms of chromatin distribution homogeneity and density, two features widely used by pathologists in tumor-grading systems.



M. Remmelink, I. Salmon, D. Goldschmidt, C. Decaestecker, E. Nemec, J. Berthe, M. Petein, J. Pasteels, R. Kiss,
Quantitative measurements of desmin and vimentin immunostains and cell density in leiomyomas and leiomyosarcomas.
Analytical cellular pathology : the journal of the European Society for Analytical Cellular Pathology, Vol. 12, 1, pp. 25-44, 1996
Bibtex
Bibtex : info:hdl:2013/57971
Note : Journal Article
Abstract : The distinction between benign and malignant smooth muscle tumours relying on histological features such as the mitotic index and pleomorphism remains a generally acknowledged difficulty in modern pathology. A cell image processor was therefore used to quantitatively assess the desmin and vimentin immunostain in 39 smooth muscle tumours which included 26 benign (leiomyomas) and 13 malignant (leiomyosarcomas) cases. The 13 leiomyosarcomas were primary (non-recurrent and non-metastatic). Ploidy level and cell density were also assessed on each of these 39 tumours by means of the computer-assisted microscopic analysis of 5-microns thick Feulgen-stained histological sections. The results show that while neither the ploidy level determination nor the quantitative assessment of the vimentin immunostain made it possible to distinguish between leiomyomas and leiomyosarcomas, cell density determination and the quantitative assessment of the desmin immunostain enabled such a distinction to be made. Indeed, the leiomyomas exhibited a much higher level of desmin positivity than the leiomyosarcomas, as did diploid tumours as compared to the aneuploid (benign or malignant) ones. Furthermore, the leiomyoma group exhibited a significantly lower mean cell density value than the leiomyosarcoma group. The present study further confirms the lack of relationship between ploidy level and cytological malignancy in smooth muscle tumours.



D. Goldschmidt, C. Decaestecker, J. Berthe, M. Remmelink, M. Petein, A. Swift, J. Pasteels, I. Salmon, R. Kiss,
The characterization of biological features in dedifferentiated liposarcomas by means of principal components and discriminant analyses of 25 computer-generated variables from Feulgen-stained nuclei and histological slides
International journal of oncology, Vol. 9, 5, pp. 963-970, 1996
Bibtex
Bibtex : info:hdl:2013/83137
Note : SCOPUS: ar.j



C. Decaestecker, M. Petein, R. Van Velthoven, T. Janssen, G. Raviv, J. Pasteels, C. Schulman, P. Van Ham, R. Kiss,
The computer-assisted microscope analysis of Feulgen-stained nuclei linked to a supervised learning algorithm as an aid to prognosis assessment in invasive transitional bladder cell carcinomas.
Analytical cellular pathology : the journal of the European Society for Analytical Cellular Pathology, Vol. 10, 3, pp. 263-280, 1996
Bibtex
Bibtex : info:hdl:2013/57982
Note : Journal Article
Abstract : The aim of the present work is to ascertain whether additional information to grading and staging can be obtained for the prognosis of invasive bladder tumours (T2, T3, T4) by means of two computer-assisted methodologies. The first methodology relates to the digital image analysis of Feulgen-stained nuclei and the second to a supervised learning algorithm named Decision Tree. The digital image analysis of Feulgen-stained nuclei generated 11 variables for nuclear DNA content and 15 for quantitatively describing chromatin pattern. These 26 variables were submitted to a Decision Tree technique which produces multi-attribute logical classification rules by selecting informative variables and determining discriminatory values for each of them. A series of 41 patients for which the majority of the T2 bladder tumours (68\%) were associated with a 'good' prognosis (remission) while the majority of the T3-T4 ones (77\%) were associated with a 'bad' one (clinical progression or death) were submitted to the proposed approach. The results show that the decision tree was able to characterise the tumours associated with a 'bad' prognosis in the T2 sub-group (32\%) and the tumours associated with a 'good' prognosis in the T3-T4 one (23\%), by using only few image-generated variables (added to the clinical stage).



D. Goldschmidt, C. Decaestecker, J. Berthe, L. Gordower, M. Remmelink, A. Danguy, J. Pasteels, I. Salmon, R. Kiss,
The contribution of image cytometry and artificial intelligence-related methods of numerical data analysis for adipose tumor histopathologic classification.
Laboratory investigation, Vol. 75, 3, pp. 295-306, 1996
Bibtex
Bibtex : info:hdl:2013/57973
Note : Journal Article
Abstract : Thirty-five lipomatous tumors were quantitatively described using 47 variables generated by means of computer-assisted microscope analysis. Of these 47 quantitative variables, 27 were computed on Feulgen-stained specimens (25 on cytologic and 2 on histologic samples) and, of the remaining 20, 8 related to vimentin and S-100 protein immunostaining patterns and the other 12 to the glycohistochemical staining patterns of peanut agglutinin, succinylated wheat germ agglutinin, and concavalin A agglutinin. The 35 lipomatous tumors included 6 atypical lipomas and 8 well differentiated, 5 dedifferentiated, 6 myxoid, and 10 pleomorphic liposarcomas. The actual diagnostic value contributed by each of the 47 variables with respect to the 5 lipomatous tumor groups was determined by means of the decision tree technique, an artificial intelligence-related algorithm that forms part of the supervised learning algorithms. Of the 47 quantitative variables, the decision tree technique retained 8: i.e., 2 tissue architecture-, 2 DNA ploidy level-, 2 morphonuclear-, 1 lectin histochemical-, and 1 vimentin immunostain-related variables. The decision tree technique made use of these 8 variables to set up logical rules that make it possible to identify atypical lipomas from well differentiated liposarcomas, on the one hand, and dedifferentiated liposarcomas from those that are well differentiated and pleomorphic, on the other. Thus, the combination of an artificial intelligence algorithm analyzing quantitative variables generated by means of the computer-assisted microscope analysis of cytologic and histologic samples from lipomatous tumors can be considered an expert system contributing significant diagnostic information to conventional diagnosis.



C. Decaestecker, R. Van Velthoven, M. Petein, T. Janssen, I. Salmon, J. Pasteels, P. Van Ham, C. Schulman, R. Kiss,
The use of the decision tree technique and image cytometry to characterize aggressiveness in World Health Organization (WHO) grade II superficial transitional cell carcinomas of the bladder.
Journal of pathology, Vol. 178, 3, pp. 274-283, 1996
Bibtex
Bibtex : info:hdl:2013/58344
Note : Journal Article
Abstract : The aggressiveness of human bladder tumours can be assessed by means of various classification systems, including the one proposed by the World Health Organization (WHO). According to the WHO classification, three levels of malignancy are identified as grades I (low), II (intermediate), and III (high). This classification system operates satisfactorily for two of the three grades in forecasting clinical progression, most grade I tumours being associated with good prognoses and most grade III with bad. In contrast, the grade II group is very heterogeneous in terms of their clinical behaviour. The present study used two computer-assisted methods to investigate whether it is possible to sub-classify grade II tumours: computer-assisted microscope analysis (image cytometry) of Feulgen-stained nuclei and the Decision Tree Technique. This latter technique belongs to the Supervised Learning Algorithm and enables an objective assessment to be made of the diagnostic value associated with a given parameter. The combined use of these two methods in a series of 292 superficial transitional cell carcinomas shows that it is possible to identify one subgroup of grade II tumours which behave clinically like grade I tumours and a second subgroup which behaves clinically like grade III tumours. Of the nine ploidy-related parameters computed by means of image cytometry [the DNA index (DI), DNA histogram type (DHT), and the percentages of diploid, hyperdiploid, triploid, hypertriploid, tetraploid, hypertetraploid, and polyploid cell nuclei], it was the percentage of hyperdiploid and hypertetraploid cell nuclei which enabled identification, rather than conventional parameters such as the DI or the DHT.



M. Remmelink, I. Salmon, D. Goldschmidt, C. Decaestecker, M. Petein, J. Pasteels, R. Kiss,
The value of nuclear DNA and texture analysis by digital image processing in the diagnosis of lipomatous and leiomyomatous tumours.
Analytical cellular pathology : the journal of the European Society for Analytical Cellular Pathology, Vol. 10, 1, pp. 45-58, 1996
Bibtex
Bibtex : info:hdl:2013/57986
Note : Journal Article
Abstract : The present study investigates whether the quantitative chromatin pattern description carried out by means of the digital cell image analysis of Feulgen-stained nuclei can contribute valuable diagnostic information on sarcomas. A series of 77 soft tissue tumours was consequently studied. This series included 9 benign lipomas versus 26 malignant liposarcomas and 26 benign leiomyomas versus 16 malignant leiomyosarcomas. Of the 26 liposarcomas, 14 were primary and 12 recurrent tumours. Of the 16 leiomyosarcomas, 13 were primary and three recurrent tumours. The results show that the combined use of principal-components analysis and the discriminant analyses of digital data obtained by means of the computer-assisted microscope analysis of Feulgen-stained nuclei made it possible to obtain a clear-cut distinction between the three histopathological groups relating to the lipoma/liposarcoma group of soft tumours. In contrast, while a clear-cut distinction could be made between the recurrent leiomyosarcomas and the primary leiomyosarcomas, such a distinction was not possible between the benign leiomyomas and the malignant primary leiomyosarcomas. This feature, along with previous ones obtained through DNA ploidy level determination, suggests to us that leiomyomas, or at least some of them, are in the process of malignant transformation. In other words, leiomyomas might be the pre-malignant counterpart of leiomyosarcomas, a feature that the present results do not suggest for lipomas versus liposarcomas.




1995

Papers

C. Decaestecker, I. Salmon, I. Camby, O. De Witte, J. Pasteels, J. Brotchi, P. Van Ham, R. Kiss,
Identification of high versus lower risk clinical subgroups in a group of adult patients with supratentorial anaplastic astrocytomas.
Journal of neuropathology and experimental neurology, Vol. 54, 3, pp. 371-384, 1995
Bibtex
Bibtex : info:hdl:2013/56345
Note : Journal Article
Abstract : The present work investigates whether computer-assisted techniques can contribute any significant information to the characterization of astrocytic tumor aggressiveness. Two complementary computer-assisted methods were used. The first method made use of the digital image analysis of Feulgen-stained nuclei, making it possible to compute 15 morphonuclear and 8 nuclear DNA content-related (ploidy level) parameters. The second method enabled the most discriminatory parameters to be determined. This second method is the Decision Tree technique, which forms part of the Supervised Learning Algorithms. These two techniques were applied to a series of 250 supratentorial astrocytic tumors of the adult. This series included 39 low-grade (astrocytomas, AST) and 211 high-grade (47 anaplastic astrocytomas, ANA, and 164 glioblastomas, GBM) astrocytic tumors. The results show that some AST, ANA and GBM did not fit within simple logical rules. These "complex" cases were labeled NC-AST, NC-ANA and NC-GBM because they were "non-classical" (NC) with respect to their cytological features. An analysis of survival data revealed that the patients with NC-GBM had the same survival period as patients with GBM. In sharp contrast, patients with ANA survived significantly longer than patients with NC-ANA. In fact, the patients with ANA had the same survival period as patients who died from AST, while the patients with NC-ANA had a survival period similar to those with GBM. All these data show that the computer-assisted techniques used in this study can actually provide the pathologist with significant information on the characterization of astrocytic tumor aggressiveness.



I. Salmon, S. Rorive, I. Camby, C. Decaestecker, B. Pirotte, K. Rombaut, J. Haot, J. Pasteels, J. Brotchi, R. Kiss,
Stereotactic biopsies from astrocytic tumors. Diagnostic information contributed by the quantitative chromatin pattern description.
Analytical and quantitative cytology and histology, Vol. 17, 5, pp. 332-343, 1995
Bibtex
Bibtex : info:hdl:2013/58005
Note : Journal Article
Abstract : OBJECTIVE: To reduce the problem of heterogeneity in astrocytic tumors by means of computer-assisted microscope analysis of Feulgen-stained nuclei. STUDY DESIGN: Thirty-eight glial tumors for which we obtained 227 stereotactic biopsies were subjected to digital cell image analysis of Feulgen-stained nuclei. This series of 38 glial tumors included 36 supratentorial astrocytic tumors (13 astrocytomas, 7 anaplastic astrocytomas and 16 glioblastoma multiformes) and 2 grade 3 astrocytic tumors of the cerebellum. RESULTS: The results suggest a new methodology, enabling the biologic characteristics of the brain parenchymal area surrounding a given glial tumor to be characterized. This methodology relies on the performance of three successive steps. The first is quantitative characterization of nuclear morphology and its chromatin pattern by means of 15 morphonuclear variables. This characterization is carried out by means of the computer-assisted microscope analysis of Feulgen-stained nuclei. The second step consists of setting up morphonuclear data banks, with each process giving the precise portrait of a given cell nuclear population. This process is carried out by means of multivariate analysis, taking into account the 15 variables mentioned above. Multivariate analysis includes principal components analysis followed by the canonical transformation of the data. The third step consists of testing unknown cases against these morphonuclear data banks. This is carried out by means of linear discriminant analysis, which enables the various cell nuclear types in the stereotactic biopsy to be quantified. CONCLUSION: The present methodology makes it possible to investigate whether infiltrating tumor cells are present in or absent from the parenchymal brain area surrounding a glial tumor. It can therefore contribute additional information to that contributed by computed tomography and/or magnetic resonance imaging with respect to the precise delineation of the volume of a brain tumor. This delineation must be as precise as possible to allow total surgical resection of the tumor and prevention of its recurrence.



C. Decaestecker, M. Remmelink, I. Camby, I. Salmon, D. Goldschmidt, P. Van Ham, J. Pasteels, R. Kiss,
The combination of a decision tree technique with the computer-assisted microscope analysis of Feulgen-stained nuclei to assess aggressiveness in lipomatous and smooth muscle tumors.
Anticancer research, Vol. 15, 4, pp. 1311-1317, 1995
Bibtex
Bibtex : info:hdl:2013/58343
Note : Journal Article
Abstract : The present study describes a computer-assisted methodology whose purpose is to reduce the degree of subjectivity in the diagnosis of soft tissue tumors. This methodology associates three complementary techniques, namely digital cell image analysis, the discretisation of numerical data and a Decision Tree technique (DT). The first technique relies on the use of the digital cell image analysis of Feulgen-stained nuclei, a technique which makes possible a quantitative and thus objective description of nuclei with the help of 24 numerical parameters (15 morphonuclear and 9 DNA content- (ploidy level and proliferation activity) related). The second technique transforms each numerical parameter into an ordinal one with a small number of values (2 to 4) so that only the relevant physical significance of the parameters is retained. The Decision Tree technique generates classification rules on the basis of the discretised parameters quoted above. This methodology was applied to 53 human soft tissue tumors which included 26 lipomatous tumors (13 malignant liposarcomas and 13 benign lipomas) and 27 smooth muscle tumors (11 malignant leiomyosarcomas and 16 benign leiomyomas). The results show that a distinction between benign (lipoma) and malignant (liposarcoma) lipomatous tumors can easily be made by means of simple logical rules depending on only four discretised cytological parameters (two ploidy- and two morphonuclear-related). In contrast, no stable or predictive characterisation can be obtained with respect to the difference between leiomyosarcomas and the leiomyomas. Hence, while lipomas and liposarcomas appeared to be two completely distinct biological entities, leiomyomas and leiomyosarcomas seem to involve a continuous biological process.



C. Decaestecker, I. Camby, I. Salmon, J. Brotchi, J. Pasteels, R. Kiss, P. Van Ham,
The combined use of the decision tree technique and the computer-assisted microscope analysis of Feulgen-stained nuclei as an aid for astrocytic tumour aggressiveness characterization
International journal of oncology, Vol. 7, 1, pp. 183-189, 1995
Bibtex
Bibtex : info:hdl:2013/58440
Note : Language of publication: en



Conferences

H. Bersini, G. Bontempi, C. Decaestecker,
Comparing RBF and fuzzy inference systems on theoretical and practical basis
ICANN '95: conférence internationale sur les Réseaux de neurones artificiels, pp. 169-174, Maison de la Chimie, Paris, France, 1995
Bibtex
Bibtex : info:hdl:2013/228119
Note : Language of publication: en



C. Decaestecker, M. Saerens,
Comparisons of different RBF networks for pattern classification
Industrial applications of neural networks, pp. 591-596, Paris, 1995
Bibtex
Bibtex : info:hdl:2013/70184
Note : Language of publication: en



T. Van de Merckt, C. Decaestecker,
Multiple-Knowledge Representation in Concept Learning
Machine Learning: ECML-95, pp. 200 - 217, April 25-27, 1995: Heraclion, Crete, Greece, 1995
Bibtex
Bibtex : info:hdl:2013/70190
Note : Language of publication: en



H. Bersini, G. Bontempi, C. Decaestecker,
Towards Neuro-Fuzzy Defuzzification in Benelearn '95
Proceedings of the 5th Belgian-Dutch Conference on Machine Learning, pp. 91-98, September 1995: Bruxelles, Belgium, 1995
Bibtex
Bibtex : info:hdl:2013/75862
Note : Language of publication: en




1994

Conferences

T. Van de Merckt, C. Decaestecker,
A Unifying Framework for Analyzing Bias in Similarity Based Learning
Proceedings of the MlNet Workshop on Declarative Bias, Catania, Italy, 1994
Bibtex
Bibtex : info:hdl:2013/141261
Note : Language of publication: en



C. Decaestecker, T. Van de Merckt,
Cognitive and Semantic interpretation of a NN classifier using prototypes
World Congress on Neural Networks, pp. 453-458, Town and Country Hotel, San Diego, California, USA, 1994
Bibtex
Bibtex : info:hdl:2013/70182
Note : Language of publication: en



C. Decaestecker, T. Van de Merckt,
How to "secure" the decisions of a NN classifier
The 1994 IEEE International Conference on Neural Networks, pp. 263-268, Walt Disney World Dolphin Hotel, Orlando Florida, 1994
Bibtex
Bibtex : info:hdl:2013/70183
Note : Language of publication: en




1993

Papers

C. Decaestecker,
Apprentissage et outils statistiques en classification conceptuelle incrémentale
Revue d'intelligence artificielle, Vol. 7, 1, pp. 33-71, 1993
Bibtex
Bibtex : info:hdl:2013/75912
Note : Language of publication: fr



Conferences

C. Decaestecker,
NNP: a neural net classifier using prototypes
1993 IEEE International Conference on Neural Networks, pp. 822-824, San Francisco, California, 1993
Bibtex
Bibtex : info:hdl:2013/70181
Note : Language of publication: en
Abstract : We present a three-layer neural net classifier for multiclass object recognition problems requiring piecewise nonlinear discriminant surfaces. The hidden layer is composed of prototypes of each class. The weights from the input to the hidden layer are the vector descriptions of prototypes (in the input feature space). The output layer neurons represent the classes, the hidden-to-output weights being binary and fixed. They map each prototype neuron to one of the class output neurons. Only the input-to-hidden weights are adapted by an algorithm using deterministic annealing and gradient descent techniques. This algorithm permits the distribution of prototypes in classes while minimising the classification error rate.



C. Decaestecker,
Using prototypes to solve problems in neural net classifiers
Third International Conference on Artificial Neural Networks, 1993., pp. 195-199, Brighton, 1993
Bibtex
Bibtex : info:hdl:2013/127796
Note : Language of publication: na




1991

Conferences

C. Decaestecker,
Description Contrasting in Incremental Concept Formation
Machine Learning–EWSL-91, pp. 220-233, 1991
Bibtex
Bibtex : info:hdl:2013/68841
Note : Language of publication: en



C. Decaestecker,
Incremental Classification, a Multidisciplinary Viewpoint
Symbolic-numeric data analysis and learning: proceedings of the conference, pp. 283-285, Versailles, 1991
Bibtex
Bibtex : info:hdl:2013/70180
Note : Language of publication: en



C. Decaestecker,
Statistical Strategies in Incremental Conceptual Classification
Applied stochastic models and data analysis : proceedings of the Fifth International Symposium on ASMDA, pp. 150-161, Granada, Spain, 1991
Bibtex
Bibtex : info:hdl:2013/70179
Note : Language of publication: en




1990

Papers

J. Poortmans, H. Brauman, M. Staroukine, A. Verniory, C. Decaestecker, R. Leclercq,
Hormone and protein excretion responses to maximal exercise in humans
Science & sports, Vol. 5, 2, pp. 103-110, 1990
Bibtex
Bibtex : info:hdl:2013/111870
Note : SCOPUS: ar.j
Abstract : The increases in plasma renin activity (PRA) and in the plasma concentration in angiotensin II (AII), aldosterone (ALDO), vasopressin (ADH) after exercise were compared to the urine protein excretion of well-hydrated healthy subjects submitted to a 2-min supramaximal bicycle exercise. Venous blood and urine samples were obtained at rest and after exercise. PRA, AII and ALDO were increased to about 4, 2 and 2-fold respectively of the resting basal values. ALDO continued to rise following exercise while PRA and AII returned to resting values (P < 0.05). Urine total protein, albumin and β2-microglobulin (β2-m) increased 7, 38 and 162-fold during the first 20 min postexercise period respectively. The enhanced total protein, albumin and (β2-m) excretion were related to a decrease in plasma volume at 20 min postexercise. A positive relationship (r = 0.515; P < 0.05) after exercise was observed between albumin excretion and PRA. No correlation was noted between the PRA-AII-ALDO system and the β2-m excretion following exercise. It was concluded that: 1) postexercise proteinuria was negatively correlated with the reduction in plasma volume; 2) the PRA-AII-ALDO system does not develop concomitantly with this transient kidney impairment.



Conferences

C. Decaestecker,
Formation de concepts en intelligence artificielle: Comparaison avec l'analyse relationnelle
Proceedings of the XXIIe Journées de Statistiques, pp. 175-177, May, 1990: Tours, 1990
Bibtex
Bibtex : info:hdl:2013/228913
Note : Language of publication: fr
Abstract : Des des travaux précédents ([Decaes89 a,b][Decaes90]), l'auteure a étudié des mécanismes incrémentaux de "Formation de Concepts", et a développé ADECLU, un système incrémental de "Conceptual Clustering". Dans cet article, l'auteure présente les différentes version de ADECLU et les compare, du point de vue conceptuel et des performances, aux méthodes développées en Analyse Relationnelle (Agrégation et Bloc Sériation) [Marc81, 87][Mich87]




1989

Conferences

C. Decaestecker,
Formation incrémentale de concepts par un critère d'adéquation
Actes des 4èmes Journées Fran{\cc}aise d'Apprentissage, pp. 63-78, May 22-24, 1989: Saint-Malo, 1989
Bibtex
Bibtex : info:hdl:2013/228899
Note : Language of publication: fr



C. Decaestecker,
Incremental concept formation via a suitability criterion
Data analysis, learning symbolic and numeric knowledge: proceedings of the Conference on Data Analysis, Learning Symbolic and Numeric Knowledge, pp. 435-442, Antibes, 1989