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

1.基因表达谱预测抗癌药物敏感性的研究为了研究调控顺铂耐药获得的分子，我们使用两对亲本膀胱癌细胞系及其顺铂耐药细胞系进行了cDNA微阵列。我们发现1型肌醇1，4，5-三磷酸受体（IP 3R 1）、S 100 P、Annexin 8、考克斯-2等的表达明显降低。我们发现S 100 P的核定位与顺铂耐药之间存在有趣的联系。S100 P的过表达增加了顺铂的敏感性。(1)基因多态性与前列腺癌易感性分析（1）基因多态性与前列腺癌易感性分析筛选出HER-2、HPC/ELAC 2、LH-β、PSA、CYP 1B 1等候选基因。我们发现HPC/ELAC 2和HER-2多态性与日本人群前列腺癌易感性显著相关。(2)遗传多态性与基因型的关联分析 ...更多信息 谷胱甘肽-S-转移酶P1（GSTP 1）对多种内源性或外源性致癌物和抗癌剂如顺铂（CDDP）和阿霉素（ADM）进行解毒。我们研究了GSTP 1多态性与日本尿路上皮癌患者的尿路上皮癌易感性和M-VAC（甲氨蝶呤，长春碱，阿霉素和顺铂）化疗的不良事件之间的关系。GST P1 IIe 105 Val多态性与M-VAC化疗的骨髓抑制不良事件相关。(3)转移性肾细胞癌（RCC）细胞因子治疗预后的预测为预测每个患者的干扰素α治疗预后，对转移性肾细胞癌患者的基因多态性与其治疗预后进行关联分析。因此，STAT 3基因多态性与治疗效果密切相关。这些STAT 3基因多态性可能是该治疗的重要预测指标.非清髓性异基因细胞治疗RCC建立了一种新的非清髓性异基因细胞治疗小鼠模型。使用我们的模型，成功地诱导了抗肿瘤作用，减少了移植物抗宿主病。少

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