The identification of genes related to the sensitivity against anti-cancer drug, and application for clinical treatment

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1. The research for the prediction of anti-cancer drug sensitivity by gene profilesTo investigate the molecules that regulate the acquisition of cisplatin-resistance, we performed cDNA microarrays using two pairs of parental and its cisplatin-resistant bladder cancer cell lines. We found a markedly reduced expression of Inositol 1,4,5-trisphosphate receptor type 1(IP3R1), S100P, Annexin 8,COX-2 etc. We found an interesting association between nuclear localization of S 100P and cisplatin resistance. Furthermore, the overexpression of S 100P increased the sensitivity against cisplatin.(1) The analyses of genetic polymorphism and prostate cancer susceptibility(1) The analyses of genetic polymorphism and prostate cancer susceptibilityWe selected candidate genes such as HER-2,HPC/ELAC2,LH-beta,PSA,CYP1B1. We found that HPC/ELAC2 and HER-2 polymorphism are significantly associated with prostate cancer susceptibility in Japanese cohot.(2) The association analysis on genetic polymorphism and t … More he adverse events by chemotherapy.Glutathione-S-transferase P1 (GSTP1) detoxifies a wide variety of endogenous or exogenous carcinogens and anticancer agents such as cisplatin (CDDP) and doxorubicin (ADM). We examined the association between GSTP1 polymorphism and both urothelial cancer susceptibility and the adverse events by M-VAC (methotrexate, vinblastine, doxorubicin and cisplatin) chemotherapy in Japanese urothelial cancer patients. The GSTP1IIe105Val polymorphism was associated with myelosuppressive adverse event by M-VAC chemotherapy.(3) The prediction of cytokine therapy outcome for metastatic renal cell carcinoma (RCC).To predict the interferon alpha treatment outcome in each patient, the association analysis on genetic polymorphisms and its treatment outcome of metastatic renal cell carcinoma patients was performed. As a result, the polymorphisms of STAT3 gene were closely associated with the treatment effect. These STAT3 polymorphisms were possibly important predictive marker in this treatment.3. Nonmyeloablative allogeneic cell therapy for RCCThe novel mouse model system was established for nonmyeloablative allogeneic cell therapy. The anti-tumor effect was successfully induced with less graft-versus-host disease using our model. Less