Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UNIPROT:P10415 (Bcl-2)
 33,771 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The survival benefit of adjuvant chemotherapy in node-positive patients with breast cancer compared with surgery alone has been established. The survival benefit differs considerably between hormone receptor-positive and -negative patients, and it is believed that the effectiveness of adjuvant chemotherapy can be increased by hormonal therapy with tamoxifen. In the present review, we discuss the rationale behind the effectiveness of combination treatment with anticancer drugs and tamoxifen in terms of the paradoxical role of Bcl-2 in apoptosis in breast cancer. The survival benefit between receptor-positive and -negative patients was assessed using previous reports of randomized controlled studies for postoperative adjuvant chemotherapy in node-positive breast cancer. Tamoxifen induces the anti-apoptotic gene, Bcl-2, by its effect on estradiol (E2), via an E2-response element in the promotor region of Bcl-2. The efficicacy of chemoendocrine therapy was assessed in terms of the influence of tamoxifen on the effect of anticancer drugs. Adjuvant chemotherapy, including anthracycline and non-anthracycline based regimens, has an overall survival benefit in node-positive breast cancer, with a 23.5% reduction in the annual odds of recurrence and a 15% reduction in mortality (P<0.00001). A comparison of the reduction of the relative risk indicates that the survival benefit in receptor-negative patients is superior to that in receptor-positive patients by approximately 3-fold. Further, in contrast to receptor-negative patients, there is no additional benefit from paclitaxel over doxorubicin and cyclophosphamide (AC) in receptor-positive patients. The possible reasons that the chemotherapy benefit in receptor-positive patients is small and marginal are the following: i) concurrent treatment or pretreatment with tamoxifen can increase plasma E2 levels in premenopausal patients, thereby inducing Bcl-2 in residual cancer cells, which might decrease drug-sensitivity in combination with chemotherapy; ii) induction of Bcl-2 might be involved predominantly in the resistance to taxanes, the cytotoxic action of which targets Bcl-2. Co-treatment or pretreatment with tamoxifen for adjuvant therapy might decrease the efficacy of anticancer drugs, an effect that is mediated by induction of Bcl-2, especially in premenopausal patients with node-positive breast cancer. Treatment with anticancer drugs should be followed by treatment with tamoxifen to produce a survival benefit from combination therapy in receptor-positive patients.
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PMID:A pitfall in the survival benefit of adjuvant chemotherapy for node- and hormone receptor-positive patients with breast cancer: the paradoxical role of Bcl-2 oncoprotein (review). 1160 12

Preoperative chemoradiotherapy (CRT) is an effective tool for local control that functions by inducing cancer cell apoptosis and inhibiting cell growth. The aim of this study was to evaluate the expression of caspase-cleaved keratin 18 cytoskeletal protein, M30, which is known as an apoptotic marker in residual rectal cancer following preoperative CRT. A total of 72 patients with rectal cancer who had undergone preoperative CRT were enrolled in this study. Immunostaining with M30 cytodeath antibody was performed and the correlation between M30 staining and clinicopathological variables was analyzed. Furthermore, we examined the correlation of M30 staining with the expression of Bax, Bcl-2, Ki67 and PCNA using transcriptional and immunohistochemical analyses. The results showed that 34 (47%) patients were positive for M30 staining. Lack of M30 expression was significantly correlated with advanced T stage, postoperative stage and tumor recurrence (P<0.05). Patients with M30 staining had better recurrence-free survival (RFS) than those without it (P=0.0301). In the immunohistochemical analysis, residual cancer cells with M30 staining lacked Ki67 expression. No significant correlation was observed between M30 positivity and the gene expression of apoptotic and proliferative markers. In conclusion, findings of the present study suggested that the evaluation of M30 expression may be useful in the prediction of tumor recurrence in rectal cancer patients who have been treated with preoperative CRT.
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PMID:Lack of M30 expression correlates with factors reflecting tumor progression in rectal cancer with preoperative chemoradiotherapy. 2464 15