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Volume 3, Problème 8 (2011)

Article de révision

An Eye on Breast and Prostate Cancers

Shalini Gandi, Phaneendra M, Anamika K and Jyothi J

Cancer is a class of diseases characterized by out-of-control cell growth. There are over 100 different types of cancer, and each is classified by the type of cell that is initially affected. In all these types of cancers breast and prostate cancers are the most prevalent and dangerous. In this review article a field of vision is given on these two hazardous cancers.

article de recherche

Evaluation of Prognostic Significance of Immunological Cells (Tissue Eosinophil and Mast Cell) Infiltration in Oral Squamous Cell Carcinoma

Priyanka Debta, Fakir Mohan Debta, Minal Chaudhary and Vijay

Background: In oral carcinoma much effort has been made to predict the prognosis of patients but a sound understanding of underlying cell biology is likely to need progress. Recently, attention has been directed towards tumour associated tissue eosinophils and mast cells and their role in the biologic behavior of tumours. Aim: The retrospective study was used to evaluate the influence of tumour associated tissue eosinophils and mast cells on prognosis of oral squamous cell carcinoma (OSCC). Material and methods: The follow-up, of histopathologically diagnosed thirty cases of OSCC, was carried out for minimum period of 3 years. Special stains are wonderful they allow us to see which we can not see clear with routine H&E stain.Tissue sections were stained with special stains, Carbol Chromotrope for tissue eosinophil and Toluidine blue for tissue mast cell staining. Result: The results of the present study shows that increase infiltration of tissue eosinophils and mast cells in OSCC, associated with favourable prognosis. Conclusion: We concludes that infiltration of tissue eosinophils and mast cells are indicators of favourable prognosis in OSCC. Thus quantitative assessment of eosinophils and mast cells are the most important aspects of the microscopic evaluation of OSCC.

article de recherche

Cancer Stem Cells - Therapeutic Boon!

Shrihari TG

Cancer stem cells (CSC) are recently proposed to be the cancer initiating cells responsible for tumorigenesis and contribute to cancer resistance. Like normal stem cells, cancer stem cells should be rare, quiescent and capable of self renewing & maintaining tumor growth and heterogeneity. Although the concept of cancer stem cells originates from that of normal stem cells, cancer stem cells are not necessarily aberrant counterparts of normal stem cells. In fact, they may arise from stem cells or committed progenitors of corresponding tissues & even cells from other tissues. At the molecular level, the alteration of stem cell self-renewal pathways has been recognized as an essential step for cancer stem cells transformation. Better understanding of cancer stem cell will no doubt lead to new era of both basic & clinical research, reclassification of human tumors & development of novel therapeutic strategies specifically targeting cancer stem cells.

Rapport de cas

Intracranial Hypertension Syndrome Revealing Cerebral Thrombophlebitis in a Patient treated for Breast Cancer by Tamoxifen after Chemotherapy

Karima Oualla, Samia Arifi, Sihame Tizniti and Omar El Mesbahi

Cancer is a major risk factor for thromboembolic disease. This risk is increased by the therapies applied including hormone therapy. We report a case of a 54 years old patient, postmenopausal, treated for breast cancer who presented an intracranial hypertension syndrome 15 months after starting Tamoxifen. A brain scan with injection of contrast was performed and revealed a left lateral sinus thrombophlebitis extended to the ipsilateral jugular vein. Curative anticoagulation was started the same day of diagnosis with low molecular weight heparin. Symptoms were improved 5 days after starting anticoagulation.

article de recherche

Combining the Ras Inhibitor Salirasib and Proteasome Inhibitors: A Potential Treatment for Multiple Myeloma

Shira Yaari-Stark, Yael Nevo-Caspi, Jasmine Jacob-Hirsch, Gideon Rechavi, Arnon Nagler and Yoel Kloog

Multiple myeloma (MM) is an incurable disease that develops resistance to chemotherapy. New treatments with thalidomide or bortezomib are partially successful. Drug resistance, differentiation block, and increased survival in MM result from genomic alterations, including high overexpression of cyclin D and fibroblast growth factor receptor 3 (FGFR3) and mutations in NRas. Oncogenic Ras isoforms can be inhibited by the Ras inhibitor farnesylthiosalicylic acid (FTS, salirasib), which also inhibits fibroblast growth factor (FGF)-stimulated Ras activation. Here we compared the effects of FTS on the proliferation of NCIH929 (harboring oncogenic NRas) and of two other MM cell lines, MM.1S and U266, which do not harbor oncogenic NRas. NCIH929 responded significantly better than the other cell lines to FTS treatment. FTS also inhibited FGF-stimulated GTP loading of wild-type NRas, and hence ERK activation, in MM-NCIH929. Gene-expression analysis of FTS-treated NCIH929 cells demonstrated downregulation of FGFR3, and the FGFR3 protein in these cells declined after FTS treatment. Combined treatment with FTS and the proteasome inhibitor MG132 or bortezomib yielded synergistic inhibition of NCIH929 MM cell growth. These data strongly suggest that FGFR3 acts together with NRas to activate the MAPK pathway, and that inhibition of Ras by FTS affects both early Ras-dependent signaling and long-term Ras-dependent control of gene expression and protein translation. We suggest that salirasib be considered, both alone and in combination with proteasome inhibitors, as a potential treatment for MM.

article de recherche

Tumor Specific Oligomeric Forms of Nucleophosmin

Natalia M Vladimirova, Maria A Pisareva, Oksana O Zharskaya, Natalia L Deineko, Tatiana I Bulycheva and Olga M Volpina

Background: According to recent data malignization of cells is accompanied not only by overexpression of protein B23/nucleophosmin, but also by formation of its new structural forms including unusual oligomers. The aim of this study was to evaluate the structural features of nucleophosmin in tumor cells. Materials and methods: Structural state of nucleophosmin was analyzed in different human tumor cells (HeLa, NGP, Hep G2, Osa-CL, Jurkat, Ramos, K-562) and human lymphocytes stimulated to proliferate by phytohemagglutinin. Commercially available monoclonal antibodies and new obtained by us antipeptide antibodies were used for analysis of monomer-oligomer state of nucleophosmin by immunochemical method and for determination of intracellular localization of monomers and oligomers by immunocytochemical method. Results: We revealed unusual SDS-resistant oligomeric forms of nucleophosmin in tumor cells of different type. Using protein chemistry strategy we showed the presence of truncated B23 isoforms in HeLa cells and their ability to form SDS-resistant oligomers. For the first time we created antipeptide antibodies which allowed differentiate monomeric and oligomeric nucleophosmin forms in tumor cells. Using these antibodies we showed different intracellular localization of monomers and oligomers in tumor cells. Conclusions: We propose that formation of SDS-resistant oligomeric forms of nucleophosmin is a common feature of human tumor cells and their detection with described antipeptide antibodies may be used for tumor diagnostics.

article de recherche

Rapid Quantification of Telomerase Activity Employing an Improved Real-time Telomeric Repeat Amplification Protocol in Clinical Tissue Samples Eliminates Interference by PCR Inhibitors

Telomerase, a ribonucleoprotein with reverse transcriptase activity, enables human cells to maintain chromosomal stability and to proliferate without limits. Various studies demonstrated telomerase activation in human cancer, including hepatocellular carcinoma. Therefore, quantification of telomerase activity has been proposed as diagnostic and prognostic tool. In this study, we optimized a 1-step real-time quantitative telomeric repeat amplification protocol for the robust and rapid quantification of telomerase activity in clinical tissue samples. To ensure undisturbed PCR kinetics even in samples with high telomerase activity, we initially determined optimal sample dilution for our assay. Next, we assessed highly diluted samples and did not observe relevant interference by tissue inhibitors of PCR, which constitute a major problem analyzing clinical tissue samples with end-point assays. To test our real-time assay, we evaluated human liver samples and detected increased telomerase activity in malignant liver lesions, whereas benign liver tissue displayed only minimal telomerase activity. In conclusion, our optimized assay is suitable to quantify telomerase activity in clinical tissue samples without interference by PCR inhibitors. The assay may be employed to detect telomerase activity during carcinogenesis and to monitor telomerase activity during cancer progression and treatment.

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