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Malignant Behavior (malignant + behavior)
Selected AbstractsBRCA1 modulates malignant cell behavior, the expression of survivin and chemosensitivity in human breast cancer cells,INTERNATIONAL JOURNAL OF CANCER, Issue 12 2009Moltira Promkan Abstract BRCA1 is a multifunctional tumor-suppressive protein. Many functional aspects of BRCA1 are not fully understood. We used a shRNA approach to probe the function of BRCA1 in human breast cancer cells. Knocking down BRCA1 expression by shRNA in the wild-type BRCA1 human breast cancer MCF-7 and MDA-MB-231 cells resulted in an increase in cell proliferation, anchorage-independent growth, cell migration, invasion and a loss of p21/Waf1 and p27Kip1 expression. In BRCA1 knocked-down cells, the expression of survivin was significantly up regulated with a concurrent decrease in cellular sensitivity to paclitaxel. We also found that cells harboring endogenous mutant or defective BRCA1 (MDA-MB-436 and HCC1937) were highly proliferative and expressed a relatively low level of p21/Waf1 and p27Kip1 by comparison to wild-type BRCA1 cells. Cells harboring mutated BRCA1 also expressed a high level of survivin and were relatively resistant to paclitaxel by comparison to wild-type cells. Increase resistance to paclitaxel was due to an increase in the expression of survivin in both the BRCA1 knocked-down and mutant BRCA1 cells because knocking down survivin expression by siRNA restored sensitivity to paclitaxel. We conclude that BRCA1 down-modulates the malignant behavior of breast cancer cells, promotes the expression of p21/Waf1, p27Kip1 and inhibits the expression of survivin. Moreover, loss of BRCA1 expression or function leads to an increase in survivin expression and a reduction in chemosensitivity to paclitaxel. © 2009 UICC [source] Molecular imaging of regional brain tumor biologyJOURNAL OF CELLULAR BIOCHEMISTRY, Issue S39 2002A.M. Spence Abstract Energy metabolism measurements in gliomas in vivo are now performed widely with positron emission tomography (PET). This capability has developed from a large number of basic and clinical science investigations that have cross fertilized one another. This article presents several areas that exemplify questions that have been explored over the last two decades. While the application of PET with [18F]-2-fluoro-2-deoxyglucose (FDG-PET) has proven useful for grading and prognosis assessments, this approach is less clinically suitable for assessing response to therapy, even though results to date raise very intriguing biological questions. Integration of metabolic imaging results into glioma therapy protocols is a recent and only preliminarily tapped method that may prove useful in additional trials that target DNA or membrane biosynthesis, or resistance mechanisms such as hypoxia. There are exciting future directions for molecular imaging that will undoubtedly be fruitful to explore, especially apoptosis, angiogenesis and expression of mutations of genes, e.g., epidermal growth factor receptor, that promote or suppress cellular malignant behavior. J. Cell. Biochem. Suppl. 39: 25,35, 2002. © 2002 Wiley-Liss, Inc. [source] Low expression of XIAP-associated factor 1 in human colorectal cancersJOURNAL OF DIGESTIVE DISEASES, Issue 1 2005Tian Le MA OBJECTIVE: Eight cellular homologs of the inhibitors-of-apoptosis proteins (IAP) have been identified in humans and of them, the X-linked IAP (XIAP) is the most potent. XIAP-associated factor 1 (XAF1) is a newly discovered XIAP-binding protein that negatively regulates the caspase-inhibiting activity of XIAP. It is either not expressed or present at extremely low levels in many cancer cell lines. The aims of the present study were: (i) to investigate the expression of XAF1 in human colorectal cancers (CRC) both in vitro and in vivo, and (ii) to evaluate the possibility of XAF1 as a new tumor marker. METHODS: The expression of XAF1 in four human colon cancer cell lines (Colo205, Colo320, SW1116, LoVo) and in samples from 70 patients with CRC was analyzed by reverse transcriptase-polymerase chain reaction. XAF1 concentrations were also detected in the peripheral circulation of the 70 patients, as well as three traditional circulating cancer-associated antigens. RESULTS: A low concentration of XAF1 mRNA was detectable in the three colon cancer cell lines other than Colo205, which showed the strongest expression of XAF1. The expression of XAF1 in tissue was relatively lower in primary CRC compared with a relatively higher level in benign colorectal tumors (P < 0.01). Although the XAF1 expression in circulation of those with CRC was also lower than in those with benign tumors, there was no statistical significance (P > 0.05). CONCLUSIONS: The present results suggest that the low expression of XAF1 in tumor tissue coincides with a similar level in the peripheral circulation, which contributes at least part to the malignant behavior of CRC. Integrating the XAF1 relative expression value with the other three traditional tumor biomarkers created a four-parameter assay that significantly improved the rate of diagnosis of CRC. [source] Increased staining for phosphorylated AKT and nuclear factor-,B p65 and their relationship with prognosis in epithelial ovarian cancerPATHOLOGY INTERNATIONAL, Issue 12 2008Rui-Xia Guo AKT plays an important role in malignant behavior of tumors. The purpose of the present study was to determine the expression of phosphorylated AKT (P-AKT) and nuclear factor-,B (NF-,B) p65 and their association with clinicopathological parameters and prognosis in epithelial ovarian tumor. On immunohistochemistry 115 samples of ovarian tissue that included 68 specimens of epithelial ovarian cancer, 12 of borderline tumor, 24 of epithelial benign tumor and 11 of normal ovary, were evaluated. Sixty-three patients with ovarian cancer were followed up from 7 to 68 months. The positive expression rate of P-AKT and NF-,B p65 were higher in epithelial ovarian cancer than in normal ovarian tissue (P < 0.01). Elevated P-AKT or NF-,B p65 expression was significantly correlated with late clinical stage (P < 0.05 and P < 0.01) and poor histological differentiation (both P < 0.01). P-AKT expression was significantly correlated with NF-,B p65 immunostaining (, = 0.272, P < 0.05). Elevated expression of P-AKT was negatively correlated with the survival of ovarian cancer patients, but it was not an independent prognostic factor after multivariate analysis. Overexpression of P-AKT and NF-,B p65 were involved in the carcinogenesis and metastasis of ovarian cancer. P-AKT might contribute to the malignant transformation through NF-,Bp65 upregulation. [source] Does retroperitoneal lymph node dissection have a curative role for patients with sex cord,stromal testicular tumors?CANCER, Issue 4 2003Ashraf A. Mosharafa M.D. Abstract BACKGROUND Sex cord,stromal tumors account for < 5% of all adult testicular tumors, and 10% are malignant. Due to the limited reported experience, there is no agreement on the best management, especially in patients who have tumors with malignant pathologic features or who present with metastatic disease. The authors attempt to evaluate the role of retroperitoneal lymph node dissection (RPLND) in the management of patients with these malignant sex cord,stromal tumors. METHODS Reviewing the Indiana University testis cancer registry revealed 17 patients who underwent RPLND for sex cord,stromal tumors. Pathology was reviewed for features suggestive of malignancy. The data examined included clinical and pathologic stage, surgical procedure, additional therapy received, and outcome. RESULTS Pathology included Leydig tumors in six patients, Sertoli tumors in four patients, sex cord,stromal tumors in five patients, a granulosa cell tumor in one patient, and a poorly differentiated non,germ cell tumor in one patient. Nine patients had histologic features suggestive of malignancy. Clinical stage at surgery was Stage I in nine patients and Stage IIA,IIIA in eight patients. Patients underwent modified or bilateral RPLND. Nine patients had pathologic Stage I tumors, and the remaining eight patients and had pathologic Stage IIB,IIIA tumors. Follow-up ranged from 8 months to 11 years. Of the eight patients with Stage II,III disease, six patients eventually died of metastatic disease despite additional radiotherapy and/or chemotherapy. CONCLUSIONS Sex cord,stromal tumors have a potentially aggressive malignant behavior that is difficult to predict based on clinical and pathologic features. Although the therapeutic role of RPLND in patients with small-volume metastatic retroperitoneal tumors is unclear, RPLND remains an option to be performed immediately after orchiectomy, especially in patients who have tumors with malignant features and/or small-volume metastatic disease. Cancer 2003;98:753,7. © 2003 American Cancer Society. [source] It takes two to tango: Combinations of conventional cytotoxics with compounds targeting the vascular endothelial growth factor,vascular endothelial growth factor receptor pathway in patients with solid malignanciesCANCER SCIENCE, Issue 1 2010Ingrid A. Boere Through advances in molecular biology, insight into the mechanisms driving malignancies has improved immensely and as a result, various factors playing an essential role in the biology of numerous tumor types have been revealed. By using compounds that specifically block the function of a single factor being crucial for tumor pathogenesis, it was hoped to exert antitumor activity while avoiding toxicities characteristic for conventional chemotherapy. One of the processes of crucial importance in the development of cancer, and consequently an attractive target, is angiogenesis. In recent years, several key factors for angiogenesis have been identified, including ligands, receptors, and transduction signaling factors. Of these, the vascular endothelial growth factor (VEGF) pathway has been found to be activated in numerous tumor types and considered one of the main drivers of angiogenesis. Roughly, VEGF-mediated angiogenesis can be inhibited by two approaches: either by monoclonal antibodies directed towards VEGF or its corresponding receptors, or by kinase inhibitors targeting the signal transduction of the VEGF receptors. As monotherapy, several kinase inhibitors exert antitumor activity in tumor types such as renal cell carcinoma. However, in most tumor types, the antitumor activity of compounds targeting the VEGF pathway is limited. In recent years, evidence is mounting that the paradigm of one single factor that drives malignant behavior applies rarely and is an oversimplification for most tumors in which there are multiple driving pathways. Consequently, multitargeting rather than single-targeting approaches are required. One of the means is by combining targeted agents with conventional cytotoxics. As the VEGF pathway also affects the sensitivity of tumor cells to chemotherapeutics, combinations of compounds targeting this pathway and conventional cytotoxics have been explored. This review addresses such combinations. (Cancer Sci 2009; 00: 000,000) [source] Carbohydrate-mediated cell adhesion in cancer metastasis and angiogenesisCANCER SCIENCE, Issue 5 2004Reiji Kannagi Malignant transformation is associated with abnormal glycosylation, resulting in the synthesis and expression of altered carbohydrate determinants including sialyl Lewisa and sialyl Lewisx. The sialyl Lewisa and sialyl Lewisx determinants appear in the sera of patients with cancer, and are extensively utilized for serum diagnosis of cancers in Japan. Sialyl Lewisa and sialyl Lewisx are involved in selectin-mediated adhesion of cancer cells to vascular endothelium, and these determinants are thought to be closely associated with hematogenous metastasis of cancers. Recent progress in this area includes the following: 1. Substantial increases in solid clinical statistics that further confirm the contribution of these determinants in the progression of a wide variety of cancers; 2. Elucidation of the ligand specificity of the three family members of selectins and evaluation of the roles of these molecules in cancer cell adhesion; and 3. Advances in the study of the mechanism that leads to the enhanced expression of the sialyl Lewisa/x determinants in malignant cells. These recent results have confirmed that these determinants are not merely markers for cancers, but are functionally implicated in the malignant behavior of cancer cells. The results also suggested that the increase of these determinants in malignant cells is an inevitable consequence of the malignant transformation of cells. Considerable new knowledge has also been accumulated regarding the therapeutic implications for suppression of hematogenous metastasis targeting this cell adhesion system. [source] | ||||||||||