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Abstract : Current Concepts and New Insights from Mouse Models of Mammary Tumors on Epithelial Mesenchymal Transition and its Synergy with Mutant p53
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Abstract: Epithelial Mesenchymal Transition (EMT) is the transdifferentiation of epithelial cells into a mesenchymal phenotype. This process occurs during embryogenesis but also in wound healing and in tumors. The neoplastic EMT is characterized by variably complete shedding of epithelial architectural features and acquisition of mesenchymal traits. In immunohistochemistry a variable coexpression of cytokeratins, vimentin or alpha-smooth muscle actin with loss of E-cadherin and other interepithelial adhesion molecules is characteristic. Such transition is associated with mutations both at the genetic (somatic) and epigenetic levels and is believed to confer a more advantageous phenotype for local and distant spread of cancer cells. Mammary carcinoma can exhibit EMT features in humans and mice and it tends to occur more frequently in women with tumors bearing a worse prognosis such as the claudin low subtype within the triple negative cancer. Missense mutation of TP53 is one of the most common mutations in cancer and it is frequently found in EMT tumor types, often with a more aggressive behavior. The current literature and survey of our mouse EMT cases in the Genomic Pathology Center image archives demonstrate a synergy between p53 and EMT that is independent of the initiating oncogene. However, p53 mutation is not sufficient or causal for EMT. Moreover, despite the local malignant behavior, processes such as spontaneous metastases and Mesenchymal Epithelial Transition (MET) appear not to be as frequent and obvious as previously hypothesized. Keywords: p53, EMT, metastasis, MET, breast cancer, mouse model, triple negative, claudin low.Download Full Article |
Abstract : TCTP Silencing in Ovarian Cancer Cells Results in Actin Cytoskeleton Remodeling and Motility Increase
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Abstract: Translationally Controlled Tumor-associated Protein (TCTP) plays a role in a plethora of normal and cancer cell functions including cell cycle progression, cell growth and metastasis. Our previous studies showed that TCTP interacts with cellular cytoskeleton and is localized, in cell-type specific manner, on actin filaments in various types of ovarian cancer cells. Here we used small interfering RNA (siRNA) for silencing TCTP expression in human ovarian surface epithelial noncancerous cell line HIO180, ovarian carcinoma cell lines SKOV3 and OVCAR3 and analyzed effect of TCTP silencing on actin cytoskeleton and cell motility. We show that a down regulation of TCTP caused dramatic restructuring and redistribution of actin filaments in HIO180, SKOV3 and OVCAR3 cells and resulted in cell motility increase. This previously unidentified dependence of actin cytoskeleton remodeling and cell motility on TCTP level might be responsible for high metastatic potential and aggressiveness of ovarian cancer cells and will help to pinpoint novel targets for anticancer therapies.. Keywords: TCTP, siRNA, ovarian cancer cells, actin cytoskeleton, cell motility.Download Full Article |
Abstract : Standardized Extract of the Persian Gulf Sponge, Axinella Sinoxea Selectively Induces Apoptosis through Mitochondria in Human Chronic Lymphocytic Leukemia Cells
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Abstract: Sponges are important components of the Persian Gulf animal communities. The marine sponges of the genus Axinella sinoxea is are a genus of sponges in the family Axinellidae. Species of Axinella sinoxea occur in the India, Pacific Oceans and also Persian Gulf. Chronic lymphocytic leukemia (CLL) is a disease characterized by the relentless accumulation of CD5+ B lymphocytes. CLL is the most common leukemia in adults, about 25–30% of all leukemias. In this study B lymphocytes mitochondria (both cancerous and non-cancerous) were isolated using differential centrifugation from peripheral blood samples and succinate dehydrogenase activity, mitochondrial reactive oxygen species (ROS) production, collapse of mitochondrial membrane potential (MMP), mitochondrial swelling and finally release of cytochrome C were examined following the addition of methanolic extract of Axinella sinoxea. Our results showed that only in mitochondria isolated from cancerous BUT NOT normal lymphocytes a significant (P < 0.05) increase in mitochondrial ROS formation, MMP collapse, mitochondrial swelling and cytochrome c release. These results showed that Axinella sinoxea extract has a selective toxicity on chronic lymphocytic leukemia lymphocytes and their mitochondria and hence may be considered as a promising anti CLL candidate for further studies needed as a supplement for cancer patients in the future. Keywords: Sponge, Axinella sinoxea, Mitochondria, Chronic Lymphocytic Leukemia.Download Full Article |
Abstract : pH Monitoring of Tumor Microenvironment and Low Volume of Urine in Experimental Rats
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Abstract: The pH monitoring of the tumor microenvironment in vivo seems to be in fact complicated and technically quite challenging nowadays. Also the strategy of measuring urine pH of a little amount is not fully solved. Thus, the aim of our study was to monitor pH of urine samples (< 0.1 ml) and of tumor microenvironment of anesthetized rats in a minimal invasive way. The small urine volumes of rats or mice make pH measurements difficult, as standard pH electrodes usually need a minimal volume of several milliliters to function. The manual micromanipulator together with a needle-type housed pH microsensor offers a simple and effective way to do so. Our results show that pH of urine and tumor microenvironment was lower in tumor bearing rats compared to healthy subjects. The unique technology of pH microsensors could be a promising way to monitor the pH in many experimental designs and clinical praxis. Keywords: pH, tumor microenvironment, urine, monitoring, in vivo, rats.Download Full Article |
Abstract : Editorial: Epithelial – to - Mesenchymal Transition in Cancer
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Editorial Keywords: TCTP, siRNA, ovarian cancer cells, actin cytoskeleton, cell motility.Download Full Article |