Biomedical subjects

Luc Xerri

Publications and source records attributed to Luc Xerri.

23 records · Page 2Linked to original sources

PubMed2003

Constitutive nuclear localization and initial cytoplasmic apoptotic activation of endogenous caspase-3 evidenced by confocal microscopy.

The localization of caspases and their substrates in different cellular compartments may be one way to regulate apoptosis. Caspase-3-dependent proteolysis of inhibitor caspase-activated deoxyribonuclease (ICAD) activates caspase-activated deoxyribonuclease (CAD), which induces apoptotic internucleosomal DNA degradation. The nuclear localization of ICAD, pro- and active-caspase-3 molecules remains a controversial issue. Using a combination of immunodetection of endogenous molecules and confocal microscopy, we analysed the kinetics of the procaspase-3 and CAD activation induced by FAS triggering in Jurkat cells. Through a semi-quantitative image analysis, we showed a constitutive nuclear localization of pro-caspase 3 and ICAD in non-apoptotic cells. FAS stimulation induced 7A6 apoptotic antigen expression, which could be related to three different sequential patterns of nuclear chromatin organization. Active-caspase-3 first appeared in the cytoplasm and was next observed in the nucleus. Simultaneously, the amount of ICAD located in the nucleus decreased, whereas the amount of ICAD located in the cytoplasm remained unchanged. Thus, our experiments using in situ immunodetection of endogenous molecules show that the ICAD cleavage by the active-caspase-3 probably takes place in the nucleus. These results provide new perspectives about the subcellular compartmentation and traffic of caspases during the apoptotic process.

Apoptosis↗

PubMed2003

Characterization of Hodgkin's lymphoma-like undifferentiated carcinoma of the nasopharyngeal type as a particular UCNT subtype mimicking Hodgkin's lymphoma.

Undifferentiated carcinoma of the nasopharyngeal type (UCNT) that histologically mimics Hodgkin's lymphoma (HL) ("Hodgkin's lymphoma-like UCNT"--HL-like UCNT) is known as a diagnostic pitfall. Using immunohistochemistry, Western blot and cDNA array technology, we wanted to document its phenotypical and molecular characteristics. We report herein 5 cases of UCNT that morphologically mimic HL and 3 classical UCNT cases. We compared the expression profiles of a thousand selected genes in HL-like UCNT and in classical UCNT cases. No difference in the profile of EBV infection was noted between the HL-like UCNT and control cases. Significant differences were detected in the expression of genes involved in the matrix modelling, angiogenesis, apoptosis and regulation of the Th-2 interleukins. The eosinophil chemoattractant eotaxin was expressed in the stroma of HL-like UCNT, but not in the control cases. The eotaxin receptor CCR3 was expressed in both stromal and carcinoma cell populations of HL-like UCNT, this pattern being similar to the one observed in HL. These results show that UCNT morphologically resembling HL share also some specific phenotypical and molecular features with HL, and might deserve to be isolated as a particular UCNT subtype.

Apoptosis↗

PubMed2003

[Inflammatory breast carcinoma: towards molecular characterization?].

Inflammatory Breast Carcinoma (IBC) is a rare but aggressive form of breast carcinoma. Characteristic clinical and pathological features are well documented. Pathological response to chemotherapy is currently the only identified prognostic factor. This high-grade tumor exhibits phenotypical features of an aggressive tumor: absence of hormonal receptors in 56 to 83% of cases, high proliferating index, p53 expressed in 30 to 69%, Immunohistochemistry (IHC) detection of HER2 over expression in 38 to 60%. Current work on IBC points out specific molecular mechanisms: adhesion molecules such as E-Cadherin, apomucin MUC1 and angiogenesis processes contribute to the IBC phenotype. So does a gene named WISP3. This gene has been recently cloned and sequenced. It has been shown to be lost in IBC and could control tumor growth, invasion, and angiogenesis. This paper summarizes current knowledge on IBC and describes a new basis for a molecular definition of IBC.

Breast Neoplasms↗

PubMed2002

Gene expression profiling defines molecular subtypes of classical Hodgkin's disease.

Although the prognosis of Hodgkin's disease is relatively good, around 20% of patients do not benefit from current therapies and succumb to their disease. A large-scale molecular characterization of disease might help improve HD management. Using cDNA arrays, we studied the mRNA expression levels of approximately 1000 selected genes in 34 benign and malignant lymphoid samples including 21 classical Hodgkin's disease (HD) tissue samples. Hierarchical clustering identified three main molecular groups of HD tumours relevant with respect to histology and clinical outcome (response to therapy and survival). Samples from all bad outcome HD (BOHD) patients clustered in one group whereas the two other groups contained most good outcome HD (GOHD) cases. The nodular sclerosis GOHD samples overexpressed genes involved in apoptotic induction and cell signalling, including cytokines, while the BOHD samples were characterized by the upregulation of genes involved in fibroblast activation, angiogenesis, extracellular matrix remodelling, cell proliferation, and the downregulation of tumour suppressor genes. Our results establish a molecular taxonomy of HD correlating with response to therapy and clinical outcome, thereby suggesting the possibility of improving the current prognostic classification.

Apoptosis↗

PubMedDate not supplied

[Prognostic value of gene expression profiling using cDNA arrays in lymphomas].

Lymphomas are the most frequent haematological malignancies in France. Their histoclinical heterogeneity reflects their complex and combinatorial nature which remains poorly elucidated at the molecular level. Today, DNA arrays allow to tackle this diversity by measuring the mRNA expression level of thousands of genes simultaneously in one sample. Recent publications show the potential of DNA arrays to improve the prognostic classification of diffuse large B cell lymphomas and of Hodgkin's lymphoma, by identifying new tumour classes unrecognised by classical factors.

Gene Expression Profiling↗