198 results on '"Robert Kiss"'
Search Results
2. PREDICTORS OF PLATELET REACTIVITY ON PRASUGREL AND THEIR IMPACT ON CLINICAL OUTCOMES: INSIGHTS FROM THE TROPICAL ACS RANDOMIZED TRIAL
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Robert Kiss, Lisa Gross, Dirk Sibbing, Martin Hadamitzky, Konstantinos D. Rizas, Béla Merkely, Daniel Aradi, Dietmar Trenk, Steffen Massberg, Ralph Hein-Rothweiler, and András Komócsi
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Platelet reactivity ,medicine.medical_specialty ,Prasugrel ,Randomized controlled trial ,law ,business.industry ,Internal medicine ,medicine ,Cardiology and Cardiovascular Medicine ,business ,medicine.drug ,law.invention - Published
- 2020
3. Viral contamination in biologic manufacture and implications for emerging therapies
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Mark Plavsic, Lionel Gerentes, Dan Gold, Jurgen Mullberg, Richard Snyder, James C. Leung, James F. Bouressa, Jacqueline Wolfrum, Richard Schicho, Anthony J. Sinskey, Robert Kiss, Michael Ruffing, Audrey Brussel, Houman Dehghani, Laurent Mallet, Paul W. Barone, Marie Murphy, Mark Moody, David J. Roush, Serge Monpoeho, Ming Chong, Nathan J. Roth, Yuling Li, Daniel Stark, Flora J. Keumurian, Chun Zhang, Dayue Chen, Christian Menzel, René Labatut, Thomas R. Kreil, James Gilbert, Michael E. Wiebe, Islam T. M. Hussein, Stacy L. Springs, and Massachusetts Institute of Technology. Center for Biomedical Innovation
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medicine.medical_specialty ,Drug Industry ,Biomedical Engineering ,Cell Culture Techniques ,Bioengineering ,Applied Microbiology and Biotechnology ,03 medical and health sciences ,0302 clinical medicine ,medicine ,Humans ,Intensive care medicine ,Drug industry ,030304 developmental biology ,0303 health sciences ,Biological Products ,business.industry ,Information Dissemination ,Data Collection ,Massachusetts ,Plasma products ,Viruses ,Molecular Medicine ,Viral contamination ,business ,Drug Contamination ,030217 neurology & neurosurgery ,Biotechnology - Abstract
Recombinant protein therapeutics, vaccines, and plasma products have a long record of safety. However, the use of cell culture to produce recombinant proteins is still susceptible to contamination with viruses. These contaminations cost millions of dollars to recover from, can lead to patients not receiving therapies, and are very rare, which makes learning from past events difficult. A consortium of biotech companies, together with the Massachusetts Institute of Technology, has convened to collect data on these events. This industry-wide study provides insights into the most common viral contaminants, the source of those contaminants, the cell lines affected, corrective actions, as well as the impact of such events. These results have implications for the safe and effective production of not just current products, but also emerging cell and gene therapies which have shown much therapeutic promise.
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- 2018
4. TCT-804 Comparative Validation of the ALPHA Score, a Novel Risk Model Including Vascular Access Site for Predicting 30-Day Mortality in Patients Treated With Primary PCI
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Attila Cziráki, Dávid Becker, Gergely Nagy, Tamás Forster, János Tomcsányi, Péter Andréka, Lajos Nagy, Béla Herczeg, Zoltán Ruzsa, Gábor Veress, Ebrahim Noori, Béla Merkely, András Katona, Istvan Hizoh, Andrea Buttl, Dominika Domokos, András Jánosi, István Édes, Péter Andrássy, Gyongyver Banhegyi, Csaba András Dézsi, Zsolt Koszegi, Robert Kiss, Laszlo Major, and Géza Lupkovics
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medicine.medical_specialty ,business.industry ,Vascular access ,Alpha (ethology) ,Risk model ,30 day mortality ,Life support ,Emergency medicine ,Heart rate ,Conventional PCI ,Medicine ,In patient ,Cardiology and Cardiovascular Medicine ,business - Abstract
Transradial primary PCI has been shown to cut mortality risk and is gaining popularity worldwide. To reflect this change in practice, a new risk model including access site has been developed for predicting 30-day mortality. Though the ALPHA (Age, Life support, Pressure, Heart rate, Access site; <
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- 2018
5. THE IMPACT OF BLEEDING AND COMORBIDITIES ON THE RISK OF MORTALITY IN PATIENTS WITH ATRIAL FIBRILLATION
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Csaba András Dézsi, Robert Kiss, Béla Merkely, Daniel Aradi, György Rokszin, and Ibolya Fábián
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medicine.medical_specialty ,business.industry ,Internal medicine ,Risk of mortality ,Cardiology ,Medicine ,Atrial fibrillation ,In patient ,Cardiology and Cardiovascular Medicine ,business ,medicine.disease - Published
- 2019
6. Altered galectin-1 serum levels in patients diagnosed with high-grade glioma
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Florence Lefranc, Véronique Mathieu, Matthias Van Woensel, Stefaan Van Gool, Steffen Fieuws, Steven De Vleeschouwer, Tina Verschuere, and Robert Kiss
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Adult ,Male ,Oncology ,Surgical resection ,Cancer Research ,Treatment response ,medicine.medical_specialty ,animal structures ,Neurology ,Adolescent ,Galectin 1 ,Enzyme-Linked Immunosorbent Assay ,Biology ,Young Adult ,Internal medicine ,Biomarkers, Tumor ,otorhinolaryngologic diseases ,medicine ,Humans ,In patient ,Prospective Studies ,Aged ,High-Grade Glioma ,Brain Neoplasms ,Brain ,Glioma ,Human brain ,Middle Aged ,Prognosis ,stomatognathic diseases ,medicine.anatomical_structure ,Case-Control Studies ,Immunology ,Galectin-1 ,Biomarker (medicine) ,Female ,Neurology (clinical) ,Neoplasm Grading ,Neoplasm Recurrence, Local ,Follow-Up Studies - Abstract
High-grade gliomas (HGG) are the most common and most aggressive intrinsic human brain tumors in adults. Galectin-1, a glycan-binding protein that is overexpressed in HGG, has been shown to contribute significantly to the aggressive nature of HGG. It is unknown whether increased galectin-1 expression levels are exclusively found at the tumor site or whether galectin-1 can also be detected in the serum of HGG patients. Galectin-1 serum levels were analyzed in a prospective dataset of 43 healthy controls and 125 patients with newly diagnosed or recurrent HGG. Samples were taken at the moment of surgical resection and/or 2-3 weeks after surgery. Galectin-1 serum levels were determined using an ELISA for galectin-1. Galectin-1 serum levels depended significantly on age and sex in the control group. Age- and sex-adjusted galectin-1 serum levels were significantly higher in all patient subgroups compared to healthy controls with a high discriminative ability that increased with age. We did not observe a significant decrease in the galectin-1 serum levels upon surgical resection of the tumor. Collectively, the data presented here may represent a first step to establish galectin-1 as a biomarker in HGG disease monitoring. Further longitudinal evaluation is required and ongoing to investigate the value of galectin-1 serum levels in HGG patients as an additional diagnostic marker, but more importantly as a predictor of treatment response and prognosis. Furthermore, galectin-1 serum levels could also provide an important tool for the identification of HGG patients that could benefit from galectin-1 directed therapies that are currently under development.
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- 2013
7. AGE AND OUTCOMES FOLLOWING GUIDED DE-ESCALATION OF ANTIPLATELET TREATMENT IN ACUTE CORONARY SYNDROME PATIENTS UNDERGOING PERCUTANEOUS CORONARY INTERVENTION: RESULTS OF A RANDOMIZED MULTICENTRE TRIAL
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Martin Hadamitzky, Tobias Geisler, Julinda Mehilli, Radosław Parma, András Komócsi, Dirk Sibbing, Kurt Huber, Lisa Gross, Lukasz Koltowski, Robert Kiss, Tommaso Gori, Franz-Josef Neumann, Joerg Hausleiter, Stephan B. Felix, Steffen Massberg, Dietmar Trenk, Monika Baylacher, Robert H. G. Schwinger, Claudius Jacobshagen, Béla Merkely, Zenon Huczek, and Daniel Aradi
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Acute coronary syndrome ,medicine.medical_specialty ,Prasugrel ,business.industry ,medicine.medical_treatment ,Percutaneous coronary intervention ,medicine.disease ,Clopidogrel ,Internal medicine ,Conventional PCI ,medicine ,cardiovascular diseases ,Cardiology and Cardiovascular Medicine ,business ,De-escalation ,circulatory and respiratory physiology ,Alternative strategy ,medicine.drug - Abstract
Guided de-escalation of antiplatelet treatment with a switch from prasugrel to clopidogrel was identified recently as an effective alternative strategy in ACS patients undergoing PCI in the TROPICAL-ACS trial. Safety and efficacy of such a strategy may differ in relation to patient's age. This pre
- Published
- 2018
8. Long-term Temozolomide Treatment Induces Marked Amino Metabolism Modifications and an Increase in TMZ Sensitivity in Hs683 Oligodendroglioma Cells
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Christine Decaestecker, Céline Bruyère, Benjamin Haibe-Kains, Michal Rynkowski, Gianluca Bontempi, Robert Kiss, Marie Le Mercier, Jacques Dubois, Benjamin Le Calvé, Florence Lefranc, and Delphine Lamoral-Theys
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Proteomics ,Cancer Research ,Pathology ,medicine.medical_specialty ,Time Factors ,medicine.medical_treatment ,Dacarbazine ,Blotting, Western ,Oligodendroglioma ,Mice, Nude ,Apoptosis ,Biology ,lcsh:RC254-282 ,Mice ,Cancer stem cell ,Cell Line, Tumor ,Temozolomide ,medicine ,Animals ,Humans ,Neoplasm Invasiveness ,Amino Acids ,Antineoplastic Agents, Alkylating ,neoplasms ,Cell Proliferation ,Chemotherapy ,Brain Neoplasms ,Reverse Transcriptase Polymerase Chain Reaction ,O-6-methylguanine-DNA methyltransferase ,Genomics ,Sciences bio-médicales et agricoles ,lcsh:Neoplasms. Tumors. Oncology. Including cancer and carcinogens ,medicine.disease ,Xenograft Model Antitumor Assays ,nervous system diseases ,Gene Expression Regulation, Neoplastic ,Radiation therapy ,Neoplastic Stem Cells ,Cancer research ,Female ,HT29 Cells ,Research Article ,medicine.drug - 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., Journal Article, Research Support, Non-U.S. Gov't, info:eu-repo/semantics/published
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- 2010
9. Galectins and Gliomas
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Véronique Mathieu, Florence Lefranc, Robert Kiss, Shannon Fortin, and Marie Le Mercier
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Pathology ,medicine.medical_specialty ,Angiogenesis ,Cell growth ,General Neuroscience ,Integrin ,Biology ,medicine.disease ,Pathology and Forensic Medicine ,Apoptosis ,Glioma ,Parenchyma ,medicine ,Cancer research ,biology.protein ,Cytotoxic T cell ,Neurology (clinical) ,neoplasms ,Galectin - Abstract
Malignant gliomas, especially glioblastomas, are associated with a dismal prognosis. Despite advances in diagnosis and treatment, glioblastoma patients still have a median survival expectancy of only 14 months. This poor prognosis can be at least partly explained by the fact that glioma cells diffusely infiltrate the brain parenchyma and exhibit decreased levels of apoptosis, and thus resistance to cytotoxic drugs. Galectins are a family of mammalian beta-galactoside-binding proteins characterized by a shared characteristic amino acid sequence. They are expressed differentially in normal vs. neoplastic tissues and are known to play important roles in several biological processes such as cell proliferation, death and migration. This review focuses on the role played by galectins, especially galectin-1 and galectin-3, in glioma biology. The involvement of these galectins in different steps of glioma malignant progression such as migration, angiogenesis or chemoresistance makes them potentially good targets for the development of new drugs to combat these malignant tumors.
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- 2010
10. Selective osteopontin knockdown exerts anti-tumoral activity in a human glioblastoma model
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Robert Kiss, Florence Lefranc, Marie Le Mercier, Akeila Bellahcene, Andreas Bikfalvi, Martin Hagedorn, Sophie Javerzat, Vincent Castronovo, and Virginie Lamour
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Cancer Research ,Gene knockdown ,Pathology ,medicine.medical_specialty ,Small interfering RNA ,biology ,Cell growth ,Angiogenesis ,Cell migration ,Transfection ,medicine.disease ,nervous system diseases ,stomatognathic system ,Oncology ,Glioma ,biology.protein ,medicine ,Cancer research ,Osteopontin ,neoplasms - Abstract
Osteopontin (OPN), a member of the SIBLING (Small Integrin-Binding LIgand N-linked Glycoprotein) family, is overexpressed in human glioblastoma. Higher levels of OPN expression correlate with increased tumor grade and enhanced migratory capacity of tumor cells. Based on these observations, we explored the possibility that knocking down OPN expression in glioblastoma cells could exert an anti-tumoral activity using an avian in vivo glioblastoma model that mimics closely human gliobastoma. Human U87-MG glioma cells transfected with specific anti-OPN small interfering RNAs (siRNAs) were grafted onto the chicken chorio-allantoic membrane (CAM). OPN-deficient U87-MG cells gave rise to tumors that were significantly smaller than tumors formed from untransfected cells (paired t-test, p < 0.05). Accordingly, the amount of proliferating cells in OPN-deficient tumors showed a six-fold reduction when compared to control tumors. However, OPN inhibition did not affect significantly tumor-associated angiogenesis. In vitro, OPN-silenced U87-MG and U373-MG cells showed decreased motility and migration. This is the first demonstration that OPN inhibition blocks glioma tumor growth, making this invasion-related protein an attractive target for glioma therapy.
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- 2009
11. 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
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Francois Lorfevre, Thomas Lequeux, Guy Laurent, Sven Saussez, Gilbert Chantrain, Robert Kiss, Christine Decaestecker, Gérard Toubeau, and Françoise Vertongen
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Adult ,Male ,Cancer Research ,Pathology ,medicine.medical_specialty ,animal structures ,Galectin 1 ,Galectin 3 ,Galectins ,Cell ,Enzyme-Linked Immunosorbent Assay ,Sensitivity and Specificity ,Gastroenterology ,Internal medicine ,Biomarkers, Tumor ,otorhinolaryngologic diseases ,Carcinoma ,Humans ,Medicine ,Head and neck ,Aged ,Galectin ,Aged, 80 and over ,business.industry ,Cancer ,Middle Aged ,medicine.disease ,stomatognathic diseases ,medicine.anatomical_structure ,Oncology ,Head and Neck Neoplasms ,Tumor progression ,Galectin-1 ,Carcinoma, Squamous Cell ,Feasibility Studies ,Immunohistochemistry ,Female ,Oral Surgery ,business - 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.
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- 2008
12. Increased galectin-3 expression and intra-epithelial neutrophils in small airways in severe COPD
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Jean-Pierre Vaerman, Marc Decramer, Monique Delos, Robert Kiss, Hans-Joachim Gabius, Charles Pilette, Herbert Kaltner, Benoît Colinet, Yves Sibille, and Sabine André
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Adult ,Male ,Pulmonary and Respiratory Medicine ,Pathology ,medicine.medical_specialty ,Vital capacity ,Chronic bronchitis ,Galectin 3 ,Blotting, Western ,Bronchi ,Enzyme-Linked Immunosorbent Assay ,Statistics, Nonparametric ,Immunoenzyme Techniques ,Pulmonary Disease, Chronic Obstructive ,Humans ,Medicine ,Asthma ,COPD ,Lung ,business.industry ,Smoking ,Respiratory disease ,Middle Aged ,respiratory system ,Airway obstruction ,medicine.disease ,respiratory tract diseases ,medicine.anatomical_structure ,Neutrophil Infiltration ,Immunology ,Respiratory epithelium ,Female ,business - Abstract
Galectins-1 and -3 regulate epithelial proliferation/apoptosis and neutrophil activation, and are implicated in lung cancer and asthma. The role of galectins in chronic obstructive pulmonary disease (COPD), characterised by epithelial changes and neutrophil infiltration, remains unknown. In the present study, galectin-1 and -3 expression was assessed by immunohistology in the bronchial epithelium of lung specimens from eight severe COPD patients and compared with nine nonsmokers and six smokers without COPD. Findings were related to epithelial proliferation (Ki-67), tissue inflammation and lung function. Epithelial galectin-3 immunostaining was increased only in the small airways of COPD patients when compared with nonsmokers and smokers. In contrast, galectin-1 was only significantly increased in the small airways of the group of smokers. Ki-67+ epithelial cells and neutrophils were increased in the small airways of COPD patients when compared with smokers. Furthermore, intra-epithelial neutrophils correlated in the small airways with Ki-67+ epithelial cells and with the forced expiratory volume in one second/forced vital capacity ratio. However, no correlation was observed with galectin expression. The present study supports the hypothesis that distal airways represent an important site for detecting changes in chronic obstructive pulmonary disease. In patients with severe disease, an increased galectin-3 expression and neutrophil accumulation in the small airway epithelium was demonstrated, correlating with epithelial proliferation and airway obstruction.
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- 2007
13. Galectin 7 (p53-Induced Gene 1): A New Prognostic Predictor of Recurrence and Survival in Stage IV Hypopharyngeal Cancer
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Sven Saussez, Hans-Joachim Gabius, Diana-Raluca Cucu, Christine Decaestecker, Herbert Kaltner, Gérard Toubeau, Isabelle Camby, Robert Kiss, Dominique Chevalier, Agnes Wacreniez, and Sabine André
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Adult ,Male ,Oncology ,medicine.medical_specialty ,Galectin 3 ,Galectins ,medicine.medical_treatment ,Adenocarcinoma ,Immunoenzyme Techniques ,Surgical oncology ,Internal medicine ,Biomarkers, Tumor ,otorhinolaryngologic diseases ,medicine ,Adjuvant therapy ,Humans ,Survival rate ,Aged ,Neoplasm Staging ,Galectin ,Hypopharyngeal Neoplasms ,business.industry ,Hypopharyngeal cancer ,Middle Aged ,Prognosis ,medicine.disease ,Head and neck squamous-cell carcinoma ,Survival Rate ,Radiation therapy ,stomatognathic diseases ,Galectin-3 ,Carcinoma, Squamous Cell ,Female ,Surgery ,Neoplasm Recurrence, Local ,business - Abstract
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. 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. 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. 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.
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- 2006
14. Improving Morphology-Based Malignancy Grading Schemes in Astrocytic Tumors by Means of Computer-Assisted Techniques
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Nathalie Nagy, Robert Kiss, Christine Decaestecker, Isabelle Salmon, Isabelle Camby, and Jacques Brotchi
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Adult ,Pathology ,medicine.medical_specialty ,Astrocytoma ,Pathology and Forensic Medicine ,Artificial Intelligence ,Image Processing, Computer-Assisted ,medicine ,Humans ,Descriptive quantitative ,Dna ploidy ,Ploidies ,Brain Neoplasms ,General Neuroscience ,Decision Trees ,Reproducibility of Results ,DNA ,Prognosis ,medicine.disease ,Malignancy grading ,Neurology (clinical) ,Glioblastoma ,Who classification ,Psychology ,Research Article ,Anaplastic astrocytoma - 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.
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- 2006
15. 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
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Christine Decaestecker, Robert Kiss, Claus W. Heizmann, Jacques Brotchi, O. Dewitte, Tatjana Mijatovic, and Florence Lefranc
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Pathology ,medicine.medical_specialty ,Protein Kinase C-alpha ,Histology ,Blotting, Western ,Cerebral arteries ,Protein Kinase C beta ,S100 Calcium Binding Protein beta Subunit ,Biology ,S100 protein ,Pathology and Forensic Medicine ,Cerebral vasospasm ,Physiology (medical) ,Gene expression ,Vertebrobasilar Insufficiency ,medicine ,Animals ,Vasospasm, Intracranial ,Nerve Growth Factors ,RNA, Messenger ,cardiovascular diseases ,Protein Kinase C ,Protein kinase C ,Chemotactic Factors ,Reverse Transcriptase Polymerase Chain Reaction ,Calcium-Binding Proteins ,S100 Proteins ,Vasospasm ,Subarachnoid Hemorrhage ,medicine.disease ,Rats ,nervous system diseases ,Cell biology ,Disease Models, Animal ,Neurology ,Basilar Artery ,Neurology (clinical) - 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.
- Published
- 2005
16. Nuclear galectin-3 expression is an independent predictive factor of recurrence for adenocarcinoma and squamous cell carcinoma of the lung
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Myriam Remmelink, Christine Decaestecker, Anne Mathieu, Valérie Ransy, Robert Kiss, Hans-Joachim Gabius, Pierre Vereerstraten, Herbert Kaltner, Isabelle Salmon, Aline Vuckovic, and Isabelle Saal
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Adult ,Male ,Pathology ,medicine.medical_specialty ,Lung Neoplasms ,Galectin 3 ,Cell ,Adenocarcinoma ,Biology ,Pathology and Forensic Medicine ,Biomarkers, Tumor ,medicine ,Carcinoma ,Humans ,Aged ,Neoplasm Staging ,Retrospective Studies ,Aged, 80 and over ,Cell Nucleus ,Squamous-cell carcinoma of the lung ,Lung ,Cancer ,Middle Aged ,Prognosis ,medicine.disease ,Immunohistochemistry ,stomatognathic diseases ,medicine.anatomical_structure ,Galectin-3 ,Carcinoma, Squamous Cell ,Female ,Neoplasm Recurrence, Local - 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.
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- 2005
17. 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
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Isabelle Salmon, Jacques Brotchi, Sabine André, Tatjana Mijatovic, Hans-Joachim Gabius, Christine Decaestecker, Robert Kiss, Herbert Kaltner, and Florence Lefranc
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Integrins ,Pituitary gland ,Pathology ,medicine.medical_specialty ,Microarray ,Galectins ,Integrin ,Biology ,Extracellular matrix ,Craniopharyngioma ,Cell Adhesion ,medicine ,Humans ,Pituitary Neoplasms ,RNA, Messenger ,Galectin ,Thrombospondin ,Gene Expression Profiling ,Prognosis ,Cell biology ,medicine.anatomical_structure ,Optic Chiasm ,Pituitary Gland ,biology.protein ,Immunohistochemistry ,Surgery ,Vitronectin ,Neurology (clinical) ,Carotid Artery, Internal - 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.
- Published
- 2005
18. Toward functional glycomics by localization of tissue lectins: immunohistochemical galectin fingerprinting during diethylstilbestrol-induced kidney tumorigenesis in male Syrian hamster
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Sabine André, Denis Nonclercq, Ruddy Wattiez, Hans-Joachim Gabius, Guy Laurent, Gérard Toubeau, Robert Kiss, Sven Saussez, and Herbert Kaltner
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Male ,Pathology ,medicine.medical_specialty ,Histology ,Galectin 1 ,Galectin 3 ,Galectins ,Galectin 4 ,Diethylstilbestrol ,Hamster ,Context (language use) ,Cross Reactions ,Biology ,Kidney ,medicine.disease_cause ,Cell Line, Tumor ,Cricetinae ,otorhinolaryngologic diseases ,medicine ,Animals ,Neoplastic transformation ,Molecular Biology ,Glycoproteins ,Galectin ,Mesocricetus ,Cell Biology ,Immunohistochemistry ,Kidney Neoplasms ,Disease Models, Animal ,Medical Laboratory Technology ,Cell Transformation, Neoplastic ,medicine.anatomical_structure ,Carcinogens ,Carcinogenesis ,medicine.drug - Abstract
The current study focused on galectins (-1, -3, -4, -7, and -8) and deliberately performed immunohistochemical fingerprinting to explore their complexity in a context of experimental renal carcinogenesis. The diethylstilbestrol (DES)-induced renal tumors in male Syrian hamster kidney (SHKT) represent a unique animal model for the study of estrogen-dependent renal malignancies. Kidney sections of DES-treated hamsters (3 days to 11 months of DES exposure) were analyzed by immunohistochemistry using a panel of non-crossreactive antibodies raised against galectins-1, -3, -4, -7, and -8. Levels of expression were quantitatively determined by using computer-assisted microscopy on immunostained tissue sections. Except for galectin-4, all above mentioned galectins were expressed in kidney tumors. Small clusters of galectin-1-positive, most likely preneoplastic cells at the corticomedullary junction were already evident 1 week after DES administration. Galectin-1 and -3 expression was apparently associated with the first steps of the neoplastic transformation, because small tumorous buds were found to be positive after 1 month of treatment. In contrast, galectins-7 and -8 were detected in large tumors and medium-sized tumors, respectively, thereby indicating an involvement in later stages of DES-induced SHKT. Galectins-1, -3, -7, and -8 were also detected by immunofluorescence staining in the HKT-1097 cell line established from SHKT, thus illustrating the stability of galectin expression in tumor cells. Our data document the presence and differential regulation of galectins in the course of renal tumorigenesis in the model of DES-induced SHKT.
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- 2004
19. Characterization of Gastrin-Induced Proangiogenic Effects In vivo in Orthotopic U373 Experimental Human Glioblastomas and In vitro in Human Umbilical Vein Endothelial Cells
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Florence Lefranc, Sandrine Rorive, Véronique Mathieu, Olivier Debeir, Jacques Brotchi, Christine Decaestecker, Robert Kiss, Isabelle Salmon, Philippe Van Ham, and Tatjana Mijatovic
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Cancer Research ,medicine.medical_specialty ,Matrigel ,medicine.drug_class ,Angiogenesis ,Biology ,Receptor antagonist ,Umbilical vein ,Cell biology ,Endothelial stem cell ,Endocrinology ,Oncology ,In vivo ,Internal medicine ,cardiovascular system ,medicine ,Human umbilical vein endothelial cell ,Receptor - 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-κB 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-κB 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 α (CXCR1) and IL-8 receptor β (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.
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- 2004
20. S100A5: a marker of recurrence in WHO grade I meningiomas
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Robert Kiss, Jacques Brotchi, Isabelle Salmon, O. De Witte, Claus W. Heizmann, S Hancq, Christine Decaestecker, and Hans-Joachim Gabius
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medicine.medical_specialty ,Pathology ,Histology ,Multivariate analysis ,Proportional hazards model ,Biology ,Who grade ,medicine.disease ,Gastroenterology ,Pathology and Forensic Medicine ,Tumor recurrence ,Resection ,Meningioma ,Neurology ,Physiology (medical) ,Internal medicine ,otorhinolaryngologic diseases ,medicine ,Neurology (clinical) ,Grading scale - 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.
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- 2003
21. Glycohistochemical characterization of vascular muscle cell destruction in CADASIL subjects by lectins, neoglycoconjugates and galectin-specific antibodies
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Marie-Magdeleine Ruchoux, J. De Reuck, Robert Kiss, Nicolai V. Bovin, Hans-Joachim Gabius, Claude-Alain Maurage, J-J Hauw, P Brulin-Fardoux, Isabelle Camby, C Godfrain, and Herbert Kaltner
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Pathology ,medicine.medical_specialty ,Kidney ,Histology ,Lung ,biology ,Lectin ,medicine.disease ,Pathology and Forensic Medicine ,carbohydrates (lipids) ,Leukoencephalopathy ,medicine.anatomical_structure ,Neurology ,Physiology (medical) ,biology.protein ,medicine ,Immunohistochemistry ,Neurology (clinical) ,Antibody ,CADASIL ,Galectin - Abstract
CADASIL (Cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy) is a type of small-artery stroke and vascular dementia-inducing pathology of the brain. In order to explain the molecular mechanisms behind the alterations to the blood vessels in CADASIL subjects, we scrutinized the expression of glycan and glycan-binding sites in the wall of vessels taken from five such subjects (vs. five control subjects matched for age and sex). Specimens were taken from the brain, heart, kidney, liver and lung. Although the main vessel lesions were observed in the tissues depending on the blood-brain barrier, alterations to systemic vessels were also observed despite the absence of any symptoms. The histochemical expression of a panel of 10 biotinylated neoglycoconjugates [Gal-beta(1-4)-D-Glc, Galbeta(1-3)GalNAc, alpha-D-GalNAc, beta-D-GalNAc, GalNAcalpha(1-3)-D-GalNAcalpha, GalNAcalpha(1-3)-D-GalNAcbeta, beta-D-Glc, alpha-D-Man, l-Fucose and D-Glcalpha(1-4)-D-Glc], eight plant lectins (PNA, MAA, SNA, DBA, WGA, ConA, GNA and UEA-1) and two antigalectin antibodies was monitored by means of semiquantitative and quantitative computer-assisted microscopy. The data show the altered histochemical binding of plant lectins, such as UEA-1 and ConA, in the vessel walls of CADASIL subjects. The present work, based upon staining by a panel of neoglycoconjugates, provides a biochemical characterization of the alteration of vessel walls in the brain compared to other organs including the heart, kidney, lung and liver in CADASIL as opposed to control subjects. These glycohistochemical results suggest a functional relevance of protein-carbohydrate interactions in this disease.
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- 2003
22. Prognostic Values of Galectin-3 and the Macrophage Migration Inhibitory Factor (MIF) in Human Colorectal Cancers
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Isabelle Salmon, Alain Hendlisz, Christine Decaestecker, Robert Kiss, Jean Claude Pector, Nathalie Nagy, Hans-Joachim Gabius, Max-Peter Schüring, and Hugues Legendre
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Adult ,Male ,Pathology ,medicine.medical_specialty ,Galectin 3 ,Blotting, Western ,Connective tissue ,Adenocarcinoma ,Pathology and Forensic Medicine ,Immunoenzyme Techniques ,Image Processing, Computer-Assisted ,otorhinolaryngologic diseases ,medicine ,Adjuvant therapy ,Humans ,Macrophage Migration-Inhibitory Factors ,Survival rate ,Aged ,Retrospective Studies ,Aged, 80 and over ,business.industry ,Liver Neoplasms ,Middle Aged ,Prognosis ,Epithelium ,Survival Rate ,medicine.anatomical_structure ,Connective Tissue ,Galectin-3 ,Connective tissue metabolism ,Immunohistochemistry ,Female ,Macrophage migration inhibitory factor ,Colorectal Neoplasms ,business - 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.
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- 2003
23. Refined prognostic evaluation in colon carcinoma using immunohistochemical galectin fingerprinting
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Herbert Kaltner, Kojiro Wasano, Yehiel Zick, Olivier Engels, Hugues Legendre, Isabelle Salmon, Christine Decaestecker, Sabine André, Nathalie Nagy, Hans-Joachim Gabius, Robert Kiss, and Jean Claude Pector
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Adult ,Male ,Cancer Research ,Pathology ,medicine.medical_specialty ,animal structures ,Colorectal cancer ,Galectins ,Peptide Mapping ,Immunoenzyme Techniques ,Colon carcinoma ,Biomarkers, Tumor ,Image Processing, Computer-Assisted ,otorhinolaryngologic diseases ,Carcinoma ,medicine ,Humans ,Stage (cooking) ,Survival rate ,Dukes' Classification ,Aged ,Neoplasm Staging ,Galectin ,Aged, 80 and over ,business.industry ,Middle Aged ,Prognosis ,medicine.disease ,humanities ,Survival Rate ,stomatognathic diseases ,Oncology ,Disease Progression ,Cancer research ,Immunohistochemistry ,Female ,Colorectal Neoplasms ,business - 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.
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- 2003
24. Characterization of Gastrin-induced Cytostatic Effect on Cell Proliferation in Experimental Malignant Gliomas
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Niloufar Sadeghi, Florence Lefranc, Robert Kiss, Thierry Metens, Isabelle Salmon, and Jacques Brotchi
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medicine.medical_specialty ,Gliosarcoma ,Biology ,Polymerase Chain Reaction ,digestive system ,Cholecystokinin receptor ,Cell cycle phase ,In vivo ,Cyclins ,Internal medicine ,Gastrins ,Image Processing, Computer-Assisted ,Tumor Cells, Cultured ,medicine ,Animals ,Humans ,Protein Isoforms ,Receptor ,Gastrin ,Brain Neoplasms ,Cell growth ,Cell Cycle ,digestive, oral, and skin physiology ,Glioma ,Cell cycle ,medicine.disease ,Rats ,Receptor, Cholecystokinin A ,Gene Expression Regulation, Neoplastic ,Endocrinology ,Microscopy, Fluorescence ,Receptors, Cholecystokinin ,Surgery ,Neurology (clinical) ,Protein Kinases ,Cell Division ,hormones, hormone substitutes, and hormone antagonists - Abstract
OBJECTIVE Growth patterns of astrocytic tumors can be modulated in vitro by gastrin. In this study, the influence of gastrin on the in vitro cell cycle kinetics and the in vivo growth features of three experimental malignant gliomas was investigated. METHODS Gastrin-induced influence on overall growth was assayed in vitro by means of the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium colorimetric assay for human U373 and rat C6 gliomas and for rat 9L gliosarcoma. Although cell cycle analyses were performed by means of computer-assisted microscope analyses of Feulgen-stained nuclei, the gastrin-induced effects of the levels of expression of cyclins D3 and E, CDK2, CDK4, CDK5, CDK7, p15, p16, E2F1, and E2F2 were assayed by means of quantitative Western blot test. The presence of ribonucleic acids for the CCK(B) and CCK(C) gastrin receptors in the U373, C6, and 9L models was assayed by means of quantitative reverse transcriptase-polymerase chain reaction, and the presence or absence of ribonucleic acids for CCK(A) receptor was checked by means of conventional polymerase chain reaction. The influence of gastrin was also characterized in vivo in terms of the survival periods of conventional rats orthotopically grafted with the C6 and 9L models and nude rats with the U373 model. RESULTS Gastrin significantly decreased the overall growth rate in the rat C6 and the human U373 high-grade astrocytic tumor models with either CCK(B) or CCK(C) gastrin receptor but not in the 9L rat gliosarcoma, which had no CCK(B) gastrin receptor (but had CCK(A) receptor) and only weak amounts of CCK(C) receptor. This effect seems to occur via a cytostatic effect; that is, an accumulation of tumor astrocytes occurs in the G(1) cell cycle phase. The cytostatic effect could relate to a gastrin-induced decrease in the amounts of the cyclin D3-CDK4 complex in both C6 and U373 glioma cells. In vivo, gastrin significantly increased the survival periods of C6 and U373 glioma-bearing rats, but not of 9L gliosarcoma-bearing rats. CONCLUSION Gastrin is able to significantly modify the growth levels of a number of experimental gliomas.
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- 2003
25. Differential expression of S100 calcium-binding proteins in epidermoid cysts, branchial cysts, craniopharyngiomas and cholesteatomas
- Author
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Stéphane Louryan, Nathalie Vanmuylder, Isabelle Salmon, Robert Kiss, Claus W. Heizmann, Christine Decaestecker, Florence Lefranc, Sergio Hassid, and Patricia Pelc
- Subjects
chemistry.chemical_classification ,Pathology ,medicine.medical_specialty ,Histology ,Branchial arch ,Branchial Cyst ,General Medicine ,Anatomy ,Epidermoid cyst ,Biology ,medicine.disease ,S100 protein ,Pathology and Forensic Medicine ,Basal (phylogenetics) ,chemistry ,Keratin ,medicine ,Immunohistochemistry ,Cyst - 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.
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- 2003
26. Postnatal maturation of the dog stria vascularis? an immunohistochemical study
- Author
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Luc Poncelet, Isabelle Salmon, Robert Kiss, Claus W. Heizmann, and Angélique Coppens
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Male ,Pathology ,medicine.medical_specialty ,Cell type ,Time Factors ,Nerve Tissue Proteins ,Cochlear duct ,Vimentin ,macromolecular substances ,Nestin ,Immunolabeling ,Dogs ,Intermediate Filament Proteins ,Fibrocyte ,otorhinolaryngologic diseases ,medicine ,Animals ,biology ,Calcium-Binding Proteins ,Stria Vascularis ,Immunohistochemistry ,Agricultural and Biological Sciences (miscellaneous) ,Cochlea ,Isoenzymes ,medicine.anatomical_structure ,Animals, Newborn ,nervous system ,Spiral ligament ,biology.protein ,Keratins ,Female ,sense organs ,Sodium-Potassium-Exchanging ATPase ,Anatomy - Abstract
The lateral wall of the dog cochlear duct was investigated by classical staining and immunohistochemistry for NaK/ATPase beta2 isoform, cytokeratins (Cks), vimentin, nestin, and S100A6 during the postnatal cochlear maturation, i.e., from birth to postnatal day 110. The dog stria vascularis was immature at birth. Fine melanin granules were evident in the stria from the second week of life, and melanin concentration increased drastically beyond the first month. The marginal cells were NaK/ATPase- and Ck-positive; intermediate cells were either nestin- and S100A6-positive or vimentin-positive; the basal cells were vimentin-positive; the capillary endothelium showed vimentin and nestin labeling; the cell layer underlying the stria was nestin-positive. The fibrocytes of the spiral ligament and spiral prominence expressed nestin and vimentin. The epithelial cells overlaying the spiral prominence and the external sulcus were Ck-positive, and transiently nestin- and vimentin-positive. Double immunolabeling, for S100A6 and either nestin, vimentin, or NaK/ATPase, and for nestin and vimentin suggested the presence of two distinct intermediate cell types. The results enabled us to differentiate the cell types forming the lateral wall of the dog cochlear duct, and to follow their postnatal maturation. This study may form a basis for future investigations about spontaneous cochleosaccular degeneration in dogs. This species is an important companion animal, and a possible model for the study of comparable diseases in humans.
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- 2002
27. Glucocorticoid-Induced Differential Expression of the Sialylated and Nonsialylated Lewisa Epitopes and Respective Binding Sites in Human Nasal Polyps Maintained under ex vivo Tissue Culture Conditions
- Author
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Nicolai V. Bovin, André Danguy, Robert Kiss, Herbert Kaltner, Sergio Hassid, Carine Delbrouck, Hans-Joachim Gabius, Nikolay E. Nifant'ev, and Guy Vandenhoven
- Subjects
Budesonide ,Pathology ,medicine.medical_specialty ,CA-19-9 Antigen ,Intercellular Adhesion Molecule-1 ,Anti-Inflammatory Agents ,Drug Evaluation, Preclinical ,Vascular Cell Adhesion Molecule-1 ,030204 cardiovascular system & hematology ,Biology ,Epitope ,Epitopes ,03 medical and health sciences ,Lewis Blood Group Antigens ,Nasal Polyps ,0302 clinical medicine ,Culture Techniques ,Gangliosides ,Hypersensitivity ,medicine ,Humans ,Nasal polyps ,030223 otorhinolaryngology ,Cell adhesion molecule ,General Medicine ,medicine.disease ,Immunohistochemistry ,Molecular biology ,Epithelium ,Eosinophils ,P-Selectin ,medicine.anatomical_structure ,Gene Expression Regulation ,Otorhinolaryngology ,Cell culture ,Binding Sites, Antibody ,E-Selectin ,Ex vivo ,medicine.drug - Abstract
We characterized the anti-inflammatory effects of budesonide on the expression of adhesion molecules involving Lewisa (Lea) epitope, its sialylated derivative (sLea), and their respective binding sites in human nasal polyposis. By computer-assisted microscopy, we quantitatively characterized the level of histochemical expression of L- and P-selectins, sialylated and nonsialylated Lea epitopes, and their respective binding sites in both surface epithelium and glandular epithelium of human nasal polyps obtained from surgical resection, maintained under ex vivo tissue culture conditions for 24 hours, and treated or not with budesonide. Intercellular adhesion molecule 1 (ICAM-1) and vascular cell adhesion molecule 1 (VCAM-1) were chosen as methodological controls, because data already published in the literature clearly indicated budesonide-mediated effects on ICAM-1 and VCAM-1 levels of expression. The present data show that budesonide significantly modified the levels of expression of ICAM-1 and VCAM-1, and to a lesser extent that of P-selectin, in the surface and glandular epithelia. Budesonide markedly decreased the levels of expression of the binding sites for both Lea and sLea, while those of Lea and sLea remained globally unchanged. In conclusion, the present study documents that glucocorticoid-induced effects can encompass receptors for Lea epitopes different from E- and P-selectins on epithelial cells of human nasal polyps.
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- 2002
28. Gastrin Significantly Modifies the Migratory Abilities of Experimental Glioma Cells
- Author
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Robert Kiss, Nathalie Belot, Isabelle Camby, Marcus Mareel, Florence Lefranc, Carole Chaboteaux, Isabelle Salmon, Erik Bruyneel, and Jacques Brotchi
- Subjects
medicine.medical_specialty ,Gliosarcoma ,RHOA ,Motility ,Biology ,Pathology and Forensic Medicine ,Cell Movement ,Internal medicine ,Glioma ,Gastrins ,Tumor Cells, Cultured ,medicine ,Animals ,Humans ,RNA, Messenger ,Rats, Wistar ,Molecular Biology ,Cytoskeleton ,Gastrin ,Astrocytic Tumor ,Cell Biology ,medicine.disease ,Actin cytoskeleton ,Receptor, Cholecystokinin B ,Rats ,Receptor, Cholecystokinin A ,Endocrinology ,medicine.anatomical_structure ,Cancer research ,biology.protein ,Receptors, Cholecystokinin ,rhoA GTP-Binding Protein ,Neoplasm Transplantation ,hormones, hormone substitutes, and hormone antagonists ,Astrocyte - Abstract
Malignant astrocytic tumors are characterized by the pronounced and diffuse migration of tumor astrocytes into the brain parenchyma. The present study shows that gastrin is a brain neuropeptide that is able to significantly modulate astrocytic tumor migration at both invasion and motility levels. In the matter of invasion, gastrin severely reduces the in vitro invasive abilities of C6 rat glioma, 9L rat gliosarcoma, and U373 human glioma cells in a collagen matrix. In vitro, gastrin also markedly modifies the motility features in both C6 and U373 cells, at least partly through a decrease in the expression of the RhoA small GTPase, and so brings about some dramatic modifications to the organization in the actin cytoskeleton. The in vitro preincubation of C6 tumor cells with gastrin significantly increases the life spans of rats stereotactically implanted with these cells as compared with the survival periods of rats implanted with gastrin-untreated C6 cells. As suggested by our in vitro experiments, these effects, observed in vivo cannot relate to only the gastrin-induced decrease in tumor astrocyte migratory abilities. Indeed, gastrin also induces immunomodulatory effects, because we observed a marked gastrin-induced recruitment of lymphocytes into C6 gliomas and 9L gliosarcomas. These data all suggest that gastrin can act as an endogenous modulator of glioma progression.
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- 2002
29. Expression of members of the calcium-binding S-100 protein family in a rat model of cerebral basilar artery vasospasm
- Author
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Claus Heizman, Olivier Dewitte, Catherine Chevalier, Christine Decaestecker, Jafar Golzarian, Isabelle Salmon, Robert Kiss, Florence Lefranc, Jacques Brotchi, and Roland Pochet
- Subjects
Pathology ,medicine.medical_specialty ,Subarachnoid hemorrhage ,Protein family ,Actin cytoskeleton organization ,Gene expression ,medicine ,Animals ,Vasospasm, Intracranial ,cardiovascular diseases ,Kinase ,business.industry ,Binding protein ,Calcium-Binding Proteins ,S100 Proteins ,Vasospasm ,Subarachnoid Hemorrhage ,medicine.disease ,Actin cytoskeleton ,Rats ,nervous system diseases ,Cell biology ,Disease Models, Animal ,Basilar Artery ,Cerebrovascular Circulation ,Nervous System Diseases ,business ,Signal Transduction - 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.
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- 2002
30. Calbindin-D28k
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Marie-Magdeleine Ruchoux, Claus W. Heizmann, Karine Pelc, Robert Kiss, Eric Sariban, Christine Decaestecker, Sylvie Vincent, and Roland Pochet
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Adult ,Male ,Oncology ,Calbindins ,Cancer Research ,Pathology ,medicine.medical_specialty ,Adolescent ,Calbindin ,Central nervous system disease ,S100 Calcium Binding Protein G ,Proliferating Cell Nuclear Antigen ,Internal medicine ,mental disorders ,Biomarkers, Tumor ,Humans ,Medicine ,Cerebellar Neoplasms ,Child ,Survival rate ,Medulloblastoma ,Biologic marker ,business.industry ,Proportional hazards model ,Nuclear Proteins ,Antigens, Nuclear ,Middle Aged ,Prognosis ,medicine.disease ,Immunohistochemistry ,nervous system diseases ,Survival Rate ,nervous system ,Child, Preschool ,Female ,Tumor Suppressor Protein p53 ,Calretinin ,business - 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.
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- 2002
31. Galectin-8 expression decreases in cancer compared with normal and dysplastic human colon tissue and acts significantly on human colon cancer cell migration as a suppressor
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Hugues Legendre, Hans-Joachim Gabius, Yaron R. Hadari, Paul Yeaton, Nathalie Nagy, Harald Lahm, Yehiel Zick, Isabelle Salmon, André Danguy, Robert Kiss, Jean Claude Pector, Yves Bronckart, Isabelle Camby, P. Van Ham, and Herbert Kaltner
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Pathology ,medicine.medical_specialty ,Colon ,Colorectal cancer ,Galectins ,Transplantation, Heterologous ,Cell ,Mice, Nude ,Lactose ,Biology ,Mice ,Cell Movement ,In vivo ,Lectins ,Biomarkers, Tumor ,Tumor Cells, Cultured ,otorhinolaryngologic diseases ,medicine ,Animals ,Humans ,Neoplasm Invasiveness ,Neoplasm Staging ,Cancer ,Galectin ,Binding Sites ,Gastroenterology ,Galactose ,Cell migration ,medicine.disease ,Culture Media ,Neoplasm Proteins ,Galectin-8 ,Glucose ,medicine.anatomical_structure ,Cell culture ,Colonic Neoplasms ,Cancer research ,Neoplasm Transplantation - Abstract
Background and aims: Galectins are β-galactoside binding proteins. This ability may have a bearing on cell adhesion and migration/proliferation in human colon cancer cells. In addition to galectins-1 and -3 studied to date, other members of this family not investigated in detail may contribute to modulation of tumour cell features. This evident gap has prompted us to extend galectin analysis beyond the two prototypes. The present study deals with the quantitative determination of immunohistochemical expression of galectin-8 in normal, benign, and malignant human colon tissue samples and in four human colon cancer models (HCT-15, LoVo, CoLo201, and DLD-1) maintained both in vitro as permanent cell lines and in vivo as nude mice xenografts. The role of galectin-8 (and its neutralising antibody) in cell migration was investigated in HCT-15, LoVo, CoLo201, and DLD-1 cell lines. Methods: Immunohistochemical expression of galectin-8 and its overall ability to bind to sugar ligands (revealed glycohistochemically by means of biotinylated histochemically inert carrier bovine serum albumin with α- and β-d-galactose, α-d-glucose, and lactose derivatives as ligands) were quantitatively determined using computer assisted microscopy. The presence of galectin-8 mRNA in the four human colon cancer cell lines was examined by reverse transcriptase-polymerase chain reaction. In vitro, cellular localisation of exogenously added galectin-8 in the culture media of these colon cancer cells was visualised by fluorescence microscopy. In vitro galectin-8 mediated effects (and the influence of its neutralising antibody) on migration levels of living HCT-15, LoVo, CoLo201, and DLD-1 cells were quantitatively determined by computer assisted phase contrast microscopy. Results: A marked decrease in immunohistochemical expression of galectin-8 occurred with malignancy development in human colon tissue. Malignant colon tissue exhibited a significantly lower galectin-8 level than normal or benign tissue colon cancers; those with extensive invasion capacities (T3–4/N+/M+) harboured significantly less galectin-8 than colon cancers with localised invasion capacities (T1–2/N0/M0). The four experimental models (HCT-15, LoVo, CoLo201, and DLD-1) had more intense galectin-8 dependent staining in vitro than in vivo. Grafting the four experimental human colon cancer models onto nude mice enabled us to show that the immunohistochemical expression of galectin-8 was inversely related to tumour growth rate. In vitro, galectin-8 reduced the migration rate of only those human experimental models (HCT-15 and CoLo201) that exhibited the lowest growth rate in vivo. Conclusions: Expression of galectin-8 correlated with malignancy development, with suppressor activity, as shown by analysis of clinical samples and xenografts. In vitro, only the two models with low growth rates were sensitive to the inhibitory potential of this galectin. Future investigations in this field should involve fingerprinting of these newly detected galectins, transcending the common focus on galectins-1 and -3.
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- 2002
32. Evaluation of the efficiency of chemotherapy in in vivo orthotopic models of human glioma cells with and without 1p19q deletions and in C6 rat orthotopic allografts serving for the evaluation of surgery combined with chemotherapy
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Fabrice Branle, Isabelle Camby, Anneke Geurts-Moespot, Florence Lefranc, Robert Kiss, Judith W. M. Jeuken, Sandra H. E. Sprenger, Fred C.G.J. Sweep, and Isabelle Salmon
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Male ,Cancer Research ,Pathology ,medicine.medical_treatment ,Pathophysiology of Brain and Behaviour ,Nitrosourea Compounds ,Nestin ,Rats, Sprague-Dawley ,Mice ,Nude mouse ,Intermediate Filament Proteins ,Antineoplastic Combined Chemotherapy Protocols ,Tumor Cells, Cultured ,Medicine ,Glutathione Transferase ,Chemical Endocrinology ,biology ,Nucleic Acid Hybridization ,Astrocytoma ,DNA, Neoplasm ,Glioma ,Middle Aged ,Combined Modality Therapy ,Immunohistochemistry ,Dacarbazine ,Treatment Outcome ,Matrix Metalloproteinase 9 ,Oncology ,Chromosomes, Human, Pair 1 ,Matrix Metalloproteinase 2 ,Chromosome Deletion ,medicine.drug ,medicine.medical_specialty ,Mice, Nude ,Nerve Tissue Proteins ,Pathofysiologie van Hersenen en Gedrag ,Organophosphorus Compounds ,Temozolomide ,Animals ,Humans ,Vimentin ,Tumor pathology ,Chemotherapy ,Carmustine ,business.industry ,Neoplasms, Experimental ,Tumor pathologie ,biology.organism_classification ,medicine.disease ,DNA Fingerprinting ,Survival Analysis ,Xenograft Model Antitumor Assays ,Rats ,Surgery ,Oligodendroglioma ,Tumor Suppressor Protein p53 ,business ,Neoplasm Transplantation ,Anaplastic astrocytoma - Abstract
Item does not contain fulltext BACKGROUND: Malignant gliomas of the central nervous system remain associated with dismal prognoses because of their diffuse invasion of the brain parenchyma. Very few experimental models that mimic clinical reality are available today to test potentially new therapies. The authors set up experimental in vivo glioma models of anaplastic astrocytomas of human and rat origins and anaplastic oligodendroglioma of human origin. Standard hospital chemotherapies were employed to test the validity of these models. METHODS: Three glioma cells lines obtained from the American Type Culture Collection (i.e., human Hs683 and U373 cells and rat C6 cells) were implanted into nude mouse brains (Hs683 and U373 cells) and rat brains (C6 cells). The astrocytic nature, as opposed to the oligodendrocytic nature, of the Hs683 and U373 models was investigated by using quantitative (computer-assisted microscopy) immunohistochemical characterizations of nestin, vimentin, glutathione-S-transferase alpha (GSTalpha), GSTmu, GSTpi, and p53 expression. Comparative genomic hybridization (CGH) was employed to investigate 1p19q losses. Chronic administrations of carmustine (BCNU), fotemustin, or temozolomide were assayed in the xenografted U373 and Hs683 models. Both BCNU-related chemotherapy and surgery were assayed in the C6 model. RESULTS: The quantitative phenotypic analyses pointed to the oligodendroglial nature of the Hs683 cell line and the astrocytic nature of the U373 cell line. The Hs683 cells exhibited 1p19q losses, whereas the U373 cells did not. BCNU, fotemustin, and temozolomide dramatically increased the time of survival of the Hs683 oligodendroglioma-bearing mice, whereas temozolomide only induced a weak but nevertheless statistically significant increase in the U373 glioma-bearing mice. In the C6 rat glioma model, surgery and BCNU chemotherapy were more efficient than either treatment alone. CONCLUSIONS: The in vivo models of gliomas of the central nervous system developed in the current work best mimicked clinical reality. They can be used either to identify new therapies against human gliomas or to optimize existing therapies.
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- 2002
33. Incorporation of Ophiobolin A into Novel Chemoembolization Particles for Cancer Cell Treatment
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Robert Kiss, Rachel R. Morrison, Antonio Evidente, Helen H. Townley, Chris Gardiner, Rachel, Morrison, Chris, Gardiner, Evidente, Antonio, Robert, Ki, and Helen, Townley
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Pathology ,medicine.medical_specialty ,Programmed cell death ,Sesterterpenes ,Cell Survival ,Surface Properties ,Pharmaceutical Science ,Apoptosis ,Microscopy, Electron, Transmission ,Cell Line, Tumor ,medicine ,Humans ,Rhabdomyosarcoma, Embryonal ,Pharmacology (medical) ,Chemoembolization, Therapeutic ,Particle Size ,Rhabdomyosarcoma ,Survival rate ,Pharmacology ,Drug Carriers ,business.industry ,Soft tissue sarcoma ,Organic Chemistry ,Cancer ,Flow Cytometry ,Silicon Dioxide ,medicine.disease ,Antineoplastic Agents, Phytogenic ,Microvesicles ,Drug Liberation ,Cell culture ,Cancer cell ,Cancer research ,Nanoparticles ,Polystyrenes ,Molecular Medicine ,business ,Biotechnology - Abstract
Purpose To design and synthesize chemoembolization particles for the delivery of Ophiobolin A (OphA), a promising fungal-derived chemotherapeutic, directly at the tumour location. To investigate cell death mechanism of OphA on a Rhabdomyosarcoma cancer (RD) cell line. Rhabdomyosarcoma is the most common soft tissue sarcoma in children; with a 5-year survival rate of between 30 and 65%. Methods Multimodal chemoembolization particles were prepared by sintering mesoporous silica nanoparticles, prepared by the sol-gel method, onto the surface of polystyrene microspheres, prepared by suspension copolymerisation. The chemoembolization particles were subsequently loaded with OphA. The effects of OphA in vitro were characterised by flow cytometry and nanoparticle tracking analysis (NanoSight). Results High loading of OphA onto the chemoembolization particles was achieved. The subsequent release of OphA onto RD cells in culture showed a 70% reduction in cell viability. OphA caused RD cells to round up and their membrane to bleb and caused cell death via apoptosis. OphA caused both an increase in the number of microvesicles produced and an increase in DNA content within these microvesicles. Conclusions The prepared chemoembolization particles showed good efficacy against RD cells in culture.
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- 2014
34. An original inner ear neuroepithelial degeneration in a deaf Rottweiler puppy
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Claus W. Heizmann, Paul Deltenre, Luc Poncelet, Angélique Coppens, and Robert Kiss
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Pathology ,medicine.medical_specialty ,Hearing loss ,Deafness ,Biology ,Dogs ,otorhinolaryngologic diseases ,medicine ,Animals ,Inner ear ,Dog Diseases ,Organ of Corti ,Spiral ganglion ,Cochlea ,Anatomy ,Immunohistochemistry ,Sensory Systems ,Neuroepithelial cell ,medicine.anatomical_structure ,nervous system ,Ear, Inner ,Nerve Degeneration ,sense organs ,medicine.symptom ,Calretinin ,Spiral Ganglion ,Rottweiler - Abstract
Histopathological investigation was conducted on both inner ears from a 4.5-month-old Rottweiler puppy with electrophysiologically confirmed bilateral deafness. The lesions were restricted to the organ of Corti and spiral ganglion that both displayed severe degenerative changes. The outer hair cells were less affected than the inner hair cells. The number of spiral ganglion neurons was reduced, and remaining neurons were altered. The basal and middle cochlear turns were more affected than the apical one. The vestibules were normal. Immunostaining with calbindin, calretinin, S100A1 and S100A6 polyclonal antisera was helpful in identifying different cell-types in the degenerated cochlea. The early and severe spiral ganglion cell degeneration is an uncommon finding no matter the species. Such lesions bear significance within the frame of cochlear implants technology for deaf infants.
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- 2001
35. 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-??, and Anti-apoptotic Galectin-3
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Yehiel Zick, Max-Peter Schüring, Georges Choufani, Rose Ghanooni, Patricia Simon, Hans-Joachim Gabius, Karine Delbrouck, Christine Decaestecker, Sergio Hassid, and Robert Kiss
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Adult ,Male ,Pathology ,medicine.medical_specialty ,Adolescent ,Receptors, Retinoic Acid ,Galectin 3 ,Retinoic acid ,Retinoic acid receptor beta ,Biology ,Matrix metalloproteinase ,chemistry.chemical_compound ,Recurrence ,otorhinolaryngologic diseases ,medicine ,Humans ,Child ,Receptor ,Macrophage Migration-Inhibitory Factors ,Aged ,Galectin ,Inflammation ,Cholesteatoma, Middle Ear ,Bacterial Infections ,Middle Aged ,Antigens, Differentiation ,Immunohistochemistry ,Gene Expression Regulation ,Matrix Metalloproteinase 9 ,Otorhinolaryngology ,chemistry ,Galectin-3 ,Cancer research ,Matrix Metalloproteinase 2 ,Female ,Matrix Metalloproteinase 3 ,Macrophage migration inhibitory factor - 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)]-α, -β, and -γ, 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 RARβ expression in non-infected cholesteatomas, and to MMP-3 (P
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- 2001
36. S100A2, a Putative Tumor Suppressor Gene, Regulates In Vitro Squamous Cell Carcinoma Migration
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Carmen Brenner, Claus W. Heizmann, Beat W. Schäfer, Carole Chaboteaux, Christine Decaestecker, Nathalie Nagy, Isabelle Salmon, Robert Kiss, Isabelle Camby, Nicolas Markadieu, and Roland Pochet
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Pathology ,medicine.medical_specialty ,Tumor suppressor gene ,Polymers ,Receptor for Advanced Glycation End Products ,Cell ,Down-Regulation ,Biology ,Pathology and Forensic Medicine ,Cell Movement ,Tumor Cells, Cultured ,medicine ,Extracellular ,Humans ,Genes, Tumor Suppressor ,RNA, Messenger ,Receptors, Immunologic ,Receptor ,Molecular Biology ,Actin ,Chemotactic Factors ,S100 Proteins ,Cell migration ,Cell Biology ,Oligonucleotides, Antisense ,Actins ,Cell biology ,Kinetics ,medicine.anatomical_structure ,Epidermoid carcinoma ,Head and Neck Neoplasms ,Cell culture ,Carcinoma, Squamous Cell - 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.
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- 2001
37. Distinct differences in binding capacity to saccharide epitopes in supratentorial pilocytic astrocytomas, astrocytomas, anaplastic astrocytomas, and glioblastomas
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Laurence Gordower, Robert Dedecker, Hans-Christian Siebert, Nicolai V. Bovin, Robert Kiss, Isabelle Salmon, Isabelle Camby, Christine Decaestecker, Yasmine Kacem, Arnaud Lemmers, Hans-Joachim Gabius, Pieter Wesseling, and André Danguy
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Adult ,Male ,Pathology ,medicine.medical_specialty ,Carbohydrates ,Perivascular epithelioid cell tumour ,Oligosaccharides ,Pathofysiologie van Hersenen en Gedrag ,Biology ,Astrocytoma ,Pathophysiology of Brain and Behaviour ,Epitope ,Pathology and Forensic Medicine ,Central nervous system disease ,Cellular and Molecular Neuroscience ,Epitopes ,Parenchyma ,medicine ,Humans ,Tissue Distribution ,Tumor pathology ,Receptor ,Cerebellar Neoplasms ,Aged ,Fucose ,Glycoproteins ,Aged, 80 and over ,Forssman Antigen ,Binding Sites ,General Medicine ,Middle Aged ,Tumor pathologie ,medicine.disease ,Glucose ,Neurology ,Immunohistochemistry ,Blood Vessels ,Carbohydrate Metabolism ,Female ,Neurology (clinical) ,Glioblastoma ,Infiltration (medical) ,Glycoconjugates ,Anaplastic astrocytoma - Abstract
Item does not contain fulltext 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.
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- 2001
38. Infliximab in patients with primary Sj�gren's syndrome: A pilot study
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Serge Steinfeld, Paul Demols, Robert Kiss, Thierry Appelboom, and Isabelle Salmon
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medicine.medical_specialty ,Chemotherapy ,medicine.diagnostic_test ,business.industry ,medicine.medical_treatment ,Immunology ,Dry mouth ,Infliximab ,Surgery ,Clinical trial ,Regimen ,Rheumatology ,Internal medicine ,Immunopathology ,Erythrocyte sedimentation rate ,medicine ,Immunology and Allergy ,Pharmacology (medical) ,medicine.symptom ,business ,Adverse effect ,medicine.drug - Abstract
Objective Tumor necrosis factor α (TNFα) is a proinflammatory cytokine involved in the pathogenesis of Sjogren's syndrome (SS), and blockade of TNFα may reduce the activity of the disease. The purpose of this study was to evaluate the safety and potential efficacy of infliximab, a chimeric human–mouse anti-TNFα monoclonal antibody, in patients with active primary SS. Methods This was a single-center, open-label pilot study. Sixteen patients with active primary SS received 3 infusions of infliximab (3 mg/kg) at 0, 2, and 6 weeks. Standard clinical assessment, complete ophthalmologic testing, and functional evaluation of salivary flow were performed at baseline and at weeks 2, 6, 10, and 14. Results All patients completed the study. There was statistically significant improvement in all clinical and functional parameters, including global assessments (patient's global assessment, patient's assessment of pain and fatigue, physician's global assessment), erythrocyte sedimentation rate, salivary flow rate, the Schirmer I test, tender joint count, fatigue score, and dry eyes and dry mouth. This clinical benefit was observed at week 2 and was maintained throughout the study and the 2-month followup period. The treatment was well tolerated in all patients, and no significant adverse events were seen. No lupus-like syndrome was observed, and no anti–double-stranded DNA antibodies were observed that were attributable to infliximab therapy. Conclusion In patients with active primary SS, a loading-dose regimen of 3 infusions of infliximab provided a fast and significant clinical benefit without major adverse reactions. It was possible to maintain statistically significant improvement for up to 8 weeks after the third infusion.
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- 2001
39. [Corrigendum] Temozolomide-induced modification of the CXC chemokine network in experimental gliomas
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Robert Kiss, Tatjana Mijatovic, Walter Berger, Richard E. Kast, Céline Bruyère, Sabine Spiegl-Kreinecker, Jean Marie Ruysschaert, Florence Lefranc, and Caroline Lonez
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Oncology ,Cancer Research ,medicine.medical_specialty ,Temozolomide ,CxC chemokine ,Internal medicine ,medicine ,Cancer research ,Biology ,medicine.drug - Abstract
After the publication of the article, the authors noted an error. The changes are as follows: In the initial and published version of Fig. 5, the data relied on triplicates in both the control (SCR) and treated (siCXCL2)conditions. In fact, the experiments were carried out in tetraplicates. However, the cells in one of the control (SCR) replicates died for unknown reasons. Thus, the data are here presented as the means ± SEM calculated from triplicates in the SCR control condition and from tetraplicates in the siCXCL2 condition. Therefore, shown below is the corrected version of Fig. 5.
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- 2013
40. Prolactin Up-Regulates Cathepsin B and D Expression in Minor Salivary Glands of Patients with Sjögren's Syndrome
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Roland Pochet, Thierry Appelboom, Robert Kiss, Serge Steinfeld, Carole Chaboteaux, Philippe Daelemans, and Arielle Maho
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Male ,medicine.medical_specialty ,Ductal cells ,Cathepsin D ,Peripheral blood mononuclear cell ,Salivary Glands ,Cathepsin B ,Pathology and Forensic Medicine ,Organ Culture Techniques ,Internal medicine ,Gene expression ,medicine ,Humans ,RNA, Messenger ,Molecular Biology ,DNA Primers ,Base Sequence ,biology ,Cell Biology ,Middle Aged ,Immunohistochemistry ,Prolactin ,Up-Regulation ,Sjogren's Syndrome ,Endocrinology ,Case-Control Studies ,biology.protein ,Female ,Antibody - Abstract
Various proteases are expressed in the minor salivary glands (MSG) of patients with Sjogren's syndrome (SS), and as we have already shown, prolactin is neosynthesized in the acinar cells of patients with SS. The present study aims to characterize the influence of PRL on the expression of cathepsin B and D in the MSG of patients with SS. Cathepsin B and D expression was investigated immunohistochemically in MSG of 30 patients with SS and 15 healthy volunteers. The presence of cathepsin B and D mRNAs was checked in three SS patients and three control subjects by means of reverse transcription-polymerase chain reaction (RT-PCR). The specificity of the anti-cathepsin B and D antibodies used for the immunohistochemistry was checked by means of western blotting analysis. The influence of prolactin on the immunohistochemical expression of cathepsin B and D was quantitatively assayed by computer-assisted microscopy at three different doses (5, 50, and 500 ng/ml) on eight MSGs (four control subjects and four patients with SS) maintained ex vivo under organotypic cultures. This influence was also investigated at the mRNA level. Whereas cathepsin B immunopositivity was absent from glandular epithelial cells of healthy subjects and only slightly present in SS patients, cathepsin D immunoreactivity was considerably greater (p < 0.0001) in both the acini and the ducts of patients with SS as compared with control subjects. Cathepsin B, but not D, was also expressed in about 20% of infiltrating mononuclear cells of SS patients. Treatment of both healthy and SS minor salivary glands with PRL significantly (p < 0.05 top < 0.0001) enhanced cathepsin B and D expression in acinar and ductal cells at both protein and mRNA levels. PRL produced locally in MSGs of SS patients, but not those of healthy subjects, could play a role in the pathogenesis of Sjogren's syndrome, if only through the activation of proteolytic activity on the part of cathepsins B and D.
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- 2000
41. S100 proteins in Corpora Amylacea from normal human brain11Published on the World Wide Web on 5 May 2000
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Daphné Hoyaux, Isabelle Salmon, Christine Decaestecker, Claus W. Heizmann, Beat W. Schäfer, Thomas Vogl, Robert Kiss, and Roland Pochet
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Senescence ,medicine.medical_specialty ,General Neuroscience ,Inflammation ,Human brain ,Biology ,Inclusion bodies ,Cell biology ,Proinflammatory cytokine ,medicine.anatomical_structure ,Endocrinology ,Glycation ,Internal medicine ,Heat shock protein ,medicine ,Neurology (clinical) ,medicine.symptom ,Corpora amylacea ,Molecular Biology ,Developmental Biology - 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.
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- 2000
42. 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
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Roland Van Velthoven, Isabelle Salmon, Christine Decaestecker, Christine Francois, Christophe Moreno, André Danguy, Robert Kiss, Joel Teitelbaum, Gilbert Bigras, and Gérard Brugal
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Male ,Silver Staining ,Pathology ,medicine.medical_specialty ,Proliferation index ,Biophysics ,Apoptosis ,Biology ,Kidney ,Bioinformatics ,Pathology and Forensic Medicine ,Endocrinology ,Renal cell carcinoma ,In Situ Nick-End Labeling ,Nucleolus Organizer Region ,Rosaniline Dyes ,medicine ,Humans ,Coloring Agents ,Carcinoma, Renal Cell ,Survival analysis ,Cell Nucleus ,Electronic Data Processing ,Cell Cycle ,Nuclear Proteins ,Antigens, Nuclear ,Cell Biology ,Hematology ,Middle Aged ,Prognosis ,medicine.disease ,Immunohistochemistry ,Survival Analysis ,Kidney Neoplasms ,Ki-67 Antigen ,Image Cytometry ,Female ,Interphase ,Nucleolus organizer region ,Quantitative analysis (chemistry) - 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.
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- 2000
43. Differential expression of S100 calcium-binding proteins characterizes distinct clinical entities in both WHO grade II and III astrocytic tumours
- Author
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Florence Lefranc, Christine Decaestecker, Géraldine Titeca, M Fastrez, Isabelle Salmon, Claus W. Heizmann, Jacques Brotchi, Robert Kiss, Beat W. Schäfer, S Neuci, L Dedecken, Isabelle Camby, and Roland Pochet
- Subjects
Pathology ,medicine.medical_specialty ,Histology ,Glial fibrillary acidic protein ,biology ,Astrocytoma ,Vimentin ,medicine.disease ,S100 protein ,nervous system diseases ,Pathology and Forensic Medicine ,Neurology ,Physiology (medical) ,Glioma ,biology.protein ,medicine ,Immunohistochemistry ,Neurology (clinical) ,medicine.symptom ,neoplasms ,Anaplasia ,Anaplastic astrocytoma - 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.
- Published
- 2000
44. Critical roles for IL-4, IL-5, and eosinophils in chronic skin allograft rejection
- Author
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Jean Christophe Noël, Michel Goldman, Murielle Surquin, François-Xavier Demoor, Marina Pretolani, Robert Kiss, Alain Le Moine, Daniel Abramowicz, Véronique Flamand, and Marie-Anne Nahori
- Subjects
Graft Rejection ,Pathology ,medicine.medical_specialty ,T-Lymphocytes ,Mice, Nude ,Article ,Pathogenesis ,Mice ,medicine ,Animals ,Transplantation, Homologous ,Interleukin 5 ,Interleukin 4 ,Mice, Knockout ,Mice, Inbred BALB C ,business.industry ,Antibodies, Monoclonal ,Skin Transplantation ,General Medicine ,Eosinophil ,medicine.disease ,Mixed lymphocyte reaction ,Interleukin-10 ,Eosinophils ,Mice, Inbred C57BL ,Transplantation ,Interleukin 10 ,medicine.anatomical_structure ,Gene Expression Regulation ,Chronic Disease ,Immunology ,Cytokines ,Female ,Interleukin-4 ,Interleukin-5 ,Lymphocyte Culture Test, Mixed ,business ,Infiltration (medical) - Abstract
C57BL/6 mice injected with the 145-2C11 anti-CD3 mAb and grafted with MHC class II disparate bm12 skin develop a chronic rejection characterized by interstitial dermal fibrosis, a marked eosinophil infiltrate, and an obliterative intimal vasculopathy. Because these changes occur in the absence of alloreactive antibodies, we examined the contribution of cytokines in their pathogenesis. Chronically rejected grafts showed a marked accumulation of both IL-4 and IL-5 mRNA. Mixed lymphocyte reaction experiments established that mice undergoing chronic rejection were primed for IL-4, IL-5, and IL-10 secretion. In vivo administration of anti-IL-4 mAb completely prevented allograft vasculopathy as well as graft eosinophil infiltration and dermal fibrosis. Injection of anti-IL-5 mAb or the use of IL-5-deficient mice as recipients also resulted in the lack of eosinophil infiltration or dermal fibrosis, but these mice did develop allograft vasculopathy. Administration of anti-IL-10 mAb did not influence any histologic parameter of chronic rejection. Thus, in this model, IL-4- and IL-5-mediated tissue allograft eosinophil infiltration is associated with interstitial fibrosis. IL-4, but not eosinophils, is also required for the development of obliterative graft arteriolopathy.
- Published
- 1999
45. [Untitled]
- Author
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Ingrid Langer, Ghanem Atassi, Hugues Malonne, and Robert Kiss
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Cancer Research ,medicine.medical_specialty ,Hematology ,Cell adhesion molecule ,Angiogenesis ,General Medicine ,Matrix metalloproteinase ,Biology ,Hypoxia (medical) ,Neovascularization ,Oncology ,Internal medicine ,Immunology ,medicine ,Cancer research ,Signal transduction ,medicine.symptom ,Receptor - Abstract
Angiogenesis is the development of new blood vessels from the existing vascular bed. In normal conditions this tightly regulated process occurs only during embryonic development, the female reproductive cycle and wound repair. In contrast, in pathological conditions such as malignant growth, atherosclerosis and diabetic retinopathy, angiogenesis becomes persistent due to an imbalance in the interplay between the positive and negative regulatory signals controlling the process. Thus, the control of tumor neovascularization may lead to new therapeutic approaches. Indeed, several anti-angiogenic drugs are currently undergoing preclinical characterization and/or clinical investigation. Recent achievement has clarified the mechanisms of action leading to pathological angiogenesis and has highlighted the role of hypoxia, growth factors, growth factor-receptors, enzymes and cell adhesion molecules involved in the process. This knowledge has permitted the design of receptor antagonists, adhesion molecule blockers and new targeted vascular approaches including gene therapy.
- Published
- 1999
46. CORPOREAL VENO-OCCLUSIVE DYSFUNCTION
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André Danguy, Claude Schulman, Christine Decaestecker, Eric Wespes, Michel Petein, Juan Pablo Vanegas, Robert Kiss, and Gil Raviv
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Adult ,Pathology ,medicine.medical_specialty ,Endothelium ,business.industry ,Wheat Germ Agglutinins ,Urology ,Ischemia ,Middle Aged ,medicine.disease ,Doppler imaging ,Oxygen tension ,Pathogenesis ,Impotence, Vasculogenic ,medicine.anatomical_structure ,Lectins ,medicine ,Immunohistochemistry ,Penile cancer ,Humans ,Endothelium, Vascular ,Plant Lectins ,Vein ,business - 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.Four patients 44 to 59 years old with normal erections who were operated on for penile cancer and 11 patients 27 to 62 years old with pure venous leakage (flow to maintain erection greater than 15 ml. per minute and cavernous flow velocity greater than 35 cm. per second) were included in the study. Immunohistochemical staining with 2 lectins, wheat germ agglutinin and Ulex europeaus agglutinin I, was performed and analyzed with computerized image analysis. The labeling index which relates to the percentage of staining indicates the distribution of the endothelial cells, and mean optical density which relates to the staining intensity indicates the function of these cells.Mean labeling index values for the 2 lectins were similar in both groups (p0.05). Mean optical density values for the 2 lectins were significantly greater for the patients with normal erections (p0.01). Therefore, the distribution of the endothelial cells was the same while their function was different in patients with corporeal veno-occlusive dysfunction.Staining with wheat germ agglutinin and Ulex europeaus agglutinin I lectin types allowed us to detect alteration in the glyco-histochemistry of the endothelial cells of the small arteries, and venous leakage could be the first step in vasculogenic impotence.
- Published
- 1998
47. Determination of growth fraction and cell density to evaluate the potential growth of human oligodendroglial and astrocytic tumours
- Author
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Christine Decaestecker, Isabelle Camby, Patrick Cras, Jacques Brotchi, Jean-Jacques Martin, Maria Beatriz Lopes, Robert Kiss, Nathalie Nagy, Christine Francois, Laurence Gordower, and Isabelle Salmon
- Subjects
Adult ,Male ,Cancer Research ,medicine.medical_specialty ,Pathology ,Oligodendroglioma ,Cell Count ,Astrocytoma ,Biology ,Predictive Value of Tests ,Internal medicine ,Glioma ,Cell density ,medicine ,Humans ,Aged ,Aged, 80 and over ,Hematology ,Brain Neoplasms ,Cell growth ,General Medicine ,Middle Aged ,medicine.disease ,Immunohistochemistry ,Oncology ,Tumor progression ,Female ,Anaplastic astrocytoma - 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-μm-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.
- Published
- 1998
48. Image cytometry as a discriminatory tool for cytologic specimens obtained by endoscopic retrograde cholangiopancreatography
- Author
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Christine Decaestecker, Paul Yeaton, Robert Kiss, Jacques Deviere, Charles W. Duckworth, Richard J. Sears, Isabelle Salmon, Nadine Bourgeois, and Thomas Ledent
- Subjects
Cancer Research ,medicine.medical_specialty ,Pathology ,Pancreatic disease ,Cholangitis, Sclerosing ,Adenocarcinoma ,Sensitivity and Specificity ,Gastroenterology ,Primary sclerosing cholangitis ,Cholangiocarcinoma ,Diagnosis, Differential ,Internal medicine ,medicine ,Humans ,Image Cytometry ,Cholangiopancreatography, Endoscopic Retrograde ,Endoscopic retrograde cholangiopancreatography ,medicine.diagnostic_test ,business.industry ,Biopsy, Needle ,DNA, Neoplasm ,medicine.disease ,Pancreatic Neoplasms ,Bile Ducts, Intrahepatic ,Biliary Tract Neoplasms ,medicine.anatomical_structure ,Pancreatitis ,Oncology ,Cytopathology ,Pancreas ,business - 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 ≤ 0.001); sensitivity and specificity were both estimated to be 82%. Primary sclerosing cholangitis was distinguished from cholangiocarcinoma (P ≤ 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. Cancer (Cancer Cytopathol) 1998;84:119-26. © 1998 American Cancer Society.
- Published
- 1998
49. Algorithm Analysis of Lectin Glycohistochemistry and Feulgen Cytometry for a New Classification of Nasal Polyposis
- Author
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Christine Decaestecker, Robert Kiss, Sergio Hassid, André Danguy, Isabelle Salmon, Jean Lambert Pasteels, and Christine Hermans
- Subjects
Pathology ,medicine.medical_specialty ,Data classification ,Biology ,Stain ,03 medical and health sciences ,Nasal Polyps ,0302 clinical medicine ,Lectins ,Biopsy ,Image Processing, Computer-Assisted ,Rosaniline Dyes ,otorhinolaryngologic diseases ,medicine ,Humans ,Nasal polyps ,Feulgen stain ,Coloring Agents ,030223 otorhinolaryngology ,Retrospective Studies ,Microscopy ,medicine.diagnostic_test ,Histocytochemistry ,Decision Trees ,Discriminant Analysis ,Reproducibility of Results ,General Medicine ,Flow Cytometry ,medicine.disease ,Linear discriminant analysis ,Otorhinolaryngology ,030220 oncology & carcinogenesis ,Immunology ,Image Cytometry ,Cytometry ,Algorithm ,Algorithms - 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.
- Published
- 1997
50. BIOCHEMICAL ALTERATIONS OF THE TUNICA ALBUGINEA IN IMPOTENCE
- Author
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Claude Schulman, Michel Petein, Eric Wespes, André Danguy, Juan Pablo Vanegas, Gil Raviv, and Robert Kiss
- Subjects
Adult ,Male ,Glycan ,Pathology ,medicine.medical_specialty ,biology ,Urology ,Cell ,Lectin ,Anatomy ,Middle Aged ,Arachis hypogaea ,Staining ,Impotence, Vasculogenic ,Tunica albuginea (ovaries) ,medicine.anatomical_structure ,Concanavalin A ,Lectins ,biology.protein ,medicine ,Humans ,Immunohistochemistry ,Collagen ,Penis - Abstract
The objectives of this study were to quantify the immunohistochemical stainings of collagen types I, III and IV, and investigate the value of glycohistochemical staining with 3 lectin types specific to a particular glycan structure, Arachis hypogaea, Triticum vulgare and concanavalin A, as a method of defining possible changes in the collagen structure of the tunica albuginea in potent and impotent patients.The study involved 4 normal men, 4 with pure venous leakage and 4 with pure arterial disease. Collagen types I, III and IV, and lectins Arachis hypogaea, Triticum vulgare and concanavalin A were studied using a cell image processor. The labeling index relates to the percentage of staining and mean optical density relates to the staining intensity.Mean labeling index values for the 3 types of collagen and lectins were similar (p0.05). Mean optical density value relating to collagen type I was significantly higher in the arteriogenic group than in the other groups (p0.05), while mean optical density value of collagen type IV was significantly higher in the venogenic group than in the 2 other groups (p0.05). Mean optical density values relating to the 3 lectin types were similar in the 3 clinical groups (p0.05).An alteration in the distribution and structure of the various collagen types and lectins in the tunica albuginea of impotent patients has been shown that may interfere with normal function and lead to impotence.
- Published
- 1997
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