Oncology reports
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E-cadherin is a transmembrane glycoprotein involved in intercellular adhesion. Abnormal (i.e., lost or decreased) expression of E-cadherin has been linked to invasiveness of many malignant tumors, including bladder carcinomas. To our knowledge, studies analyzing the prognostic impact of E-cadherin immunoreactivity especially in minimally invasive transitional cell bladder carcinomas (stage pT1) have not been published in the Anglo-American literature. ⋯ In a multivariate analysis, this parameter was identified, besides tumor grade (p=0.002), as an independent predictor of recurrence-free survival (p=0.016). Concerning tumor progression, age was identified as the single independent prognostic parameter (p=0.041), but E-cadherin immunoreactivity displayed a tendentious independent predictive value in this respect (p=0.071). We conclude from our data that immunohistochemical E-cadherin staining may provide additional prognostic information in patients with pT1 bladder carcinomas.
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Comparative Study
Genetic susceptibility of catechol-O-methyltransferase polymorphism in Japanese patients with breast cancer.
Polymorphic catechol-O-methyltransferase (COMT) catalyzes the O-methylation of catechol estrogens. It has been reported that COMT polymorphism is a representative genetic trait related to the susceptibility of an individual to breast cancer. However, there is no consensus concerning the association between breast cancer in Japanese patients and COMT polymorphism. ⋯ Furthermore, the distribution of genotypes in post-menopausal patients with breast cancer showed a significant difference with that of healthy subjects of the same menopausal status (p=0.01). No significant difference was found between the distribution of genotypes and clinicopathological features of the cancer. These results suggest that COMT polymorphism may thus be implicated as a genetic trait affecting the susceptibility of an individual to breast cancer in a Japanese population and be an important genetic risk factor in the development of breast cancer in post-menopausal women.
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Estrogen receptor (ER) and human epidermal growth factor 2 (HER2) are well-investigated molecules and the focus of many breast cancer therapies. There is a group of breast cancers lacking ER and HER2, but it is not fully understood. Treatment for these patients is limited to cytotoxic chemotherapy. ⋯ Overall, the ER(-)/HER2(-) breast cancer showed the highest Ki-67 LI, the most frequent expression of EGFR, p53 and vimentin, as well as the lowest expression of cyclinD1. It is unlikely that gene amplification contributes to EGFR expression. ER(-)/HER2(-) breast cancers have potential in the development of novel therapeutics, including targeted medicines.
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Clusterin has been shown to be implicated in the acquisition of resistant phenotype to various kinds of apoptotic stimuli, including radiation. In bladder cancer, our previous study demonstrated that overexpression of clusterin is closely associated with disease progression and recurrence. The objective of this study was to investigate whether radiation sensitivity was enhanced by suppressing clusterin gene expression with antisense (AS) oligodeoxynucleotide (ODN) in the human bladder cancer KoTCC-1 model. ⋯ In vivo systemic administration of AS clusterin ODN enhanced radiation sensitivity, significantly reducing subcutaneous KoTCC-1 tumor volume in nude mice, compared with that of mismatch control ODN. Moreover, additional administration of cisplatin to this combined regimen further achieved potential antitumor effects on subcutaneous KoTCC-1 tumor growth in nude mice. Collectively, these findings suggest that clusterin acts as a cell survival protein mediating radioresistance through the inhibition of apoptosis, and that inactivation of clusterin using AS technology might offer a novel strategy to improve the outcome of radiation therapy for patients with bladder cancer.
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We comprehensively reviewed the published scientific literature on non-steroidal anti-inflammatory drugs (NSAIDs) and cancer and evaluated results based upon epidemiologic criteria of judgment: consistency of results, strength of association, dose response, molecular specificity, and biological plausibility. Sufficient data from 91 epidemiologic studies were available to examine the dose response of relative risk and level of NSAID intake for ten human malignancies. Dose response curves were fitted by exponential regression. ⋯ Overexpression of cyclooxygenase-2 (COX-2) and increased prostaglandin biosynthesis correlates with carcinogenesis and metastasis at most anatomic sites. Preclinical investigations provide consistent evidence that both selective and non-selective NSAIDs effectively inhibit chemically-induced carcinogenesis of epithelial tumors. This review provides compelling and converging evidence that regular intake of NSAIDs that non-selectively block COX-2 protects against the development of many types of cancer.