CARCINOSARCOME DU SEIN. A PROPOS D’UN CAS

Breast Carcinosarcome is a rare and aggressive cancer. We report a case of Carcinosarcoma of the right breast in a 51 year old patient, single person, diabetic, treated by surgery first, six cycles of adjuvant chemotherapy then radiotherapy on the right wall. The patient is in complete remission after a 12 months of follow up. The goal of our work is to bring back the anatomopathologic, therapeutic and finally prognostic characteristics of this rare entity.Le Carcinosarcome du sein est un cancer rare et agressif. Nous rapportons un cas de Carcinosarcome du sein droit chez une patiente de 51 ans, célibataire, diabétique type II, traitée par chirurgie première, six cycles de chimiothérapie en adjuvant puis radiothérapie sur la paroi droite. La patiente est en rémission complète après un recul de 12 mois. Le but de notre travail est de rapporter les caractéristiques anatomopathologiques, thérapeutiques et enfin pronostiques de cette entité rare

TUMEUR D’ASKIN. A PROPOS DE HUIT OBSERVATIONS

La tumeur d’Askin est une tumeur neuroectodermique primitive de la région thoracopulmonaire. Elle est rare représentant 6.5% des sarcomes, survenant chez l’enfant et le sujet jeune. Son pronostic est très défavorable ; la survie à 2 ans étant de 38% [1]. Le traitement est basé sur la chimiothérapie néo-adjuvante, suivie d'une chirurgie radicale si possible et/ou d'une irradiation, puis d'une chimiothérapie adjuvante selon la réponse de la tumeur à la chimiothérapie initiale [2,3] .Nous rapportons 8 cas de tumeurs d’Askin traités dans notre service. C’est une étude rétrospective de 8 cas de tumeurs d’Askin colligés au centre d’oncologie Ibn Rochd de Casablanca, durant la période 1998 -2003. Nous rapportons les résultats de notre expérience ainsi qu’une revue de la littérature

Analysis of Intracellular State Based on Controlled 3D Nanostructures Mediated Surface Enhanced Raman Scattering

Near-infrared surface-enhanced Raman spectroscopy (SERS) is a powerful technique for analyzing the chemical composition within a single living cell at unprecedented resolution. However, current SERS methods employing uncontrollable colloidal metal particles or non-uniformly distributed metal particles on a substrate as SERS-active sites show relatively low reliability and reproducibility. Here, we report a highly-ordered SERS-active surface that is provided by a gold nano-dots array based on thermal evaporation of gold onto an ITO surface through a nanoporous alumina mask. This new combined technique showed a broader distribution of hot spots and a higher signal-to-noise ratio than current SERS techniques due to the highly reproducible and uniform geometrical structures over a large area. This SERS-active surface was applied as cell culture system to study living cells in situ within their culture environment without any external preparation processes. We applied this newly developed method to cell-based research to differentiate cell lines, cells at different cell cycle stages, and live/dead cells. The enhanced Raman signals achieved from each cell, which represent the changes in biochemical compositions, enabled differentiation of each state and the conditions of the cells. This SERS technique employing a tightly controlled nanostructure array can potentially be applied to single cell analysis, early cancer diagnosis and cell physiology research

A New Mixed-Backbone Oligonucleotide against Glucosylceramide Synthase Sensitizes Multidrug-Resistant Tumors to Apoptosis

Enhanced ceramide glycosylation catalyzed by glucosylceramide synthase (GCS) limits therapeutic efficiencies of antineoplastic agents including doxorubicin in drug-resistant cancer cells. Aimed to determine the role of GCS in tumor response to chemotherapy, a new mixed-backbone oligonucleotide (MBO-asGCS) with higher stability and efficiency has been generated to silence human GCS gene. MBO-asGCS was taken up efficiently in both drug-sensitive and drug-resistant cells, but it selectively suppressed GCS overexpression, and sensitized drug-resistant cells. MBO-asGCS increased doxorubicin sensitivity by 83-fold in human NCI/ADR-RES, and 43-fold in murine EMT6/AR1 breast cancer cells, respectively. In tumor-bearing mice, MBO-asGCS treatment dramatically inhibited the growth of multidrug-resistant NCI/ADR-RE tumors, decreasing tumor volume to 37%, as compared with scrambled control. Furthermore, MBO-asGCS sensitized multidrug-resistant tumors to chemotherapy, increasing doxorubicin efficiency greater than 2-fold. The sensitization effects of MBO-asGCS relied on the decreases of gene expression and enzyme activity of GCS, and on the increases of C18-ceramide and of caspase-executed apoptosis. MBO-asGCS was accumulation in tumor xenografts was greater in other tissues, excepting liver and kidneys; but MBO-asGCS did not exert significant toxic effects on liver and kidneys. This study, for the first time in vivo, has demonstrated that GCS is a promising therapeutic target for cancer drug resistance, and MBO-asGCS has the potential to be developed as an antineoplastic agent

Thrombospondin-1 C-terminal-derived peptide protects thyroid cells from ceramide-induced apoptosis through the adenylyl cyclase pathway.

Thrombospondin-1, a multi-modular matrix protein is able to interact with a variety of matrix proteins and cell-surface receptors. Thus it is multifunctional. In this work, we examined the role of thrombospondin-1 in ceramide-induced thyroid apoptosis. We focused on the VVM containing sequence localized in the C-terminal domain of the molecule. Primary cultured thyroid cells synthesize thrombospondin-1 depending on their morphological organization. As it leads thyrocytes to organize into monolayers before inducing apoptosis ceramide can modulate this organization. Here, we established that C(2)-ceramide treatment decreased thrombospondin-1 expression by interfering with the adenylyl cyclase pathway, thus leading to apoptosis. Furthermore, we demonstrated that the thrombospondin-1-derived peptide 4N1 (RFYVVMWK) abolished ceramide-induced thyroid cell death by preventing intracellular cAMP levels from dropping. Finally, we reported that 4N1-mediated inhibition of ceramide-induced apoptosis was consistently associated with a down-regulation of the caspase-3 processing. Integrin-associated protein receptor (IAP or CD47) was identified as a molecular relay mediating the observed 4N1 effects. Taken together, our results shed light for the first time on anti-apoptotic activities of the thrombospondin-1-derived peptide 4N1 and provide new information on how thrombospondin-1 may control apoptosis of non-tumoral cells