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

Apoptosis, via caspase cascade, is involved in tumorigenesis and progression, and thus, altered apoptosis-related protein expressions have clinical and prognostic significance. Moreover, the apoptosis pathway is highlighted due to the recent introduction of apoptosis-targeted therapy for several genes such as the X-linked inhibitor of apoptosis protein (XIAP). XIAP is the most potent direct inhibitor of caspase, and XIAP-associated factor 1 (XAF1) and secondary mitochondrial activator of caspase/direct IAP-binding protein with low PI (Smac/DIABLO) are negative regulators of XIAP. In this study, we evaluated the expression of these proteins and investigated their clinical and prognostic significance in gastric carcinomas. Immunohistochemical analysis by using the tissue array method was performed for XIAP, survivin, Bcl-2, XAF1, Smac/DIABLO, and cleaved caspase-3 proteins in 1,162 surgically resected gastric carcinoma cases. XIAP expression was related to the advanced stage. The expression of XIAP showed negative relationship with XAF1 and Smac/DIABLO expressions. In addition, XIAP expression was associated with a poor prognosis and was also proved to be an independent prognostic factor. Cleaved caspase-3 expression was related to the early stage. In addition, cleaved caspase-3 expression was associated with a favorable prognosis and was also proved to be an independent prognostic factor. The expression of XIAP showed an inverse relationship with cleaved caspase-3. In addition, the expression of XAF1 and Smac/DIABLO had a positive relationship with cleaved caspase-3. These findings are consistent with their known functions, and they may help to identify individuals best suited for apoptosis-targeted therapy as a baseline data in gastric carcinoma.
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PMID:Expression of apoptosis-related proteins and its clinical implication in surgically resected gastric carcinoma. 2194 31

Despite recent advances in the treatment of human colon cancer, the chemotherapy efficacy against colon cancer is still unsatisfactory. In the present study, effects of concomitant inhibition of the epidermal growth factor receptor (EGFR) and DNA methyltransferase were examined in human colon cancer cells. We demonstrated that decitabine (a DNA methyltransferase inhibitor) synergized with gefitinib (an EGFR inhibitor) to reduce cell viability and colony formation in SW1116 and LOVO cells. However, the combination of the two compounds displayed minimal toxicity to NCM460 cells, a normal human colon mucosal epithelial cell line. The combination was also more effective at inhibiting the AKT/mTOR/S6 kinase pathway. In addition, the combination of decitabine with gefitinib markedly inhibited colon cancer cell migration. Furthermore, gefitinib synergistically enhanced decitabine-induced cytotoxicity was primarily due to apoptosis as shown by Annexin V labeling that was attenuated by z-VAD-fmk, a pan caspase inhibitor. Concomitantly, cell apoptosis resulting from the co-treatment of gefitinib and decitabine was accompanied by induction of BAX, cleaved caspase 3 and cleaved PARP, along with reduction of Bcl-2 compared to treatment with either drug alone. Interestingly, combined treatment with these two drugs increased the expression of XIAP-associated factor 1 (XAF1) which play an important role in cell apoptosis. Moreover, small interfering RNA (siRNA) depletion of XAF1 significantly attenuated colon cancer cells apoptosis induced by the combination of the two drugs. Our findings suggested that gefitinib in combination with decitabine exerted enhanced cell apoptosis in colon cancer cells were involved in mitochondrial-mediated pathway and induction of XAF1 expression. In conclusion, based on the observations from our study, we suggested that the combined administration of these two drugs might be considered as a novel therapeutic regimen for treating colon cancer.
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PMID:Combination of gefitinib and DNA methylation inhibitor decitabine exerts synergistic anti-cancer activity in colon cancer cells. 2487 86