Analysis of mechanisms of the resistance of cisplatin in refractory or relapsed germ cell tumors

难治性或复发性生殖细胞肿瘤顺铂耐药机制分析

• 批准号: 16591611
• 负责人: NOMOTO Takeshi
• 金额: $ 1.86万
• 依托单位: Kyoto Prefectural University of Medicine
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Scientific Research (C)
• 财政年份: 2004
• 资助国家: 日本
• 起止时间: 2004 至 2006
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/en/grant/KAKENHI-PROJECT-16591611/
• 关键词: refractory testicular tumor; Salvage chemotherapy; NALP7; cisplatin; Paclitaxel; Salvage Chemotherapy; 救剤化学療法; cDNA microarray; CDDP; CPT-11; Paclitaxal; 遺伝子発現

The overall response rate of cisplatin-based combination chemotherapy of patients with germ cell tumors (GCTs) has improved. Despite the high cure rate, 20-30 percent of patients with advanced GCTs failed to achieve a durable complete response. These refractory or relapsed GCTs remain a major problem in current treatment.In clinical study, we investigated the chemotherapy with paclitaxel in combination with nedaplatin, which is a derivative of cisplatin, and ifosphamide as salvage chemotherapy for cisplatin refractory germ cell cancer. Fourteen patients were evaluated for response and toxicity. Response rate was 57.1 % (CR / PR^<m.> : 8 cases, NC : 5 cases、 PD : 1 cases ).Seven patients remain alive without disease. This study demonstrates that the chemotherapy with paclitaxel in combination with nedaplatin and ifosphamide showed a significant anticancer activity for patients with cisplatin refractory or relapsed germ cell cancer. These findings suggest that the combination chemotherapy may be one of the options of salvage chemotherapy for cisplatin refractory or relapsed germ cell cancer.In this study, to investigate new diagnostic markers and potential therapeutic targets for GCTs, we identified 347 genes that were commonly up-regulated in GCTs by using a cDNA microarray (Int J Oncol, 2003). Furthermore, we identified NALP7 that was significantly transactivated in GCTs and showed that NALP7 may be a promising candidate for development of targeted therapy for GCTs (Cancer Sci, 2004).

以顺铂为基础的联合化疗对生殖细胞肿瘤（GCT）患者的总体缓解率有所提高。尽管治愈率很高，但20- 30%的晚期GCT患者未能获得持久的完全缓解。这些难治或复发的GCT仍然是目前治疗的主要问题，在临床研究中，我们研究了紫杉醇联合奈达铂（顺铂的衍生物）和异环磷酰胺作为顺铂难治性生殖细胞癌的挽救化疗。评估了14名患者的反应和毒性。有效率为57.1%（CR / PR = <m.>8例，NC = 5例，PD = 1例），7例无病生存。本研究表明，紫杉醇联合奈达铂和异环磷酰胺化疗对顺铂难治性或复发性生殖细胞癌患者显示出显著的抗癌活性。这些结果表明，联合化疗可能是顺铂难治性或复发性生殖细胞cancer.In这项研究中，探讨新的诊断标志物和潜在的治疗GCTs的目标之一，我们确定了347个基因，通常上调GCTs通过使用cDNA微阵列（Int J Oncol，2003）。此外，我们鉴定了在GCT中显著反式激活的NALP 7，并表明NALP 7可能是开发GCT靶向治疗的有希望的候选物（Cancer Sci，2004）。

项目成果

The expression of thymidine phosphorylase is a prognostic predictor for the intravesical recurrence of superficial bladder cancer

胸苷磷酸化酶的表达是浅表性膀胱癌膀胱内复发的预后预测因子

• 发表时间: 2006
• 期刊: Int J Clin Oncol 11
• 作者: Nonomura N;Miki T,. et al.
• 通讯作者: Miki T,. et al.

Tunicamycin Enhances Tumor Necrosis Factor-Related Apoptosis-Inducing Ligand-Induced Apoptosis in Human Prostate Cancer Cells

衣霉素增强人前列腺癌细胞中肿瘤坏死因子相关凋亡诱导配体诱导的凋亡

• 发表时间: 2005
• 期刊: Cancer Research 65
• 作者: Shiraishi;T
• 通讯作者: T

Overexpression of XIAP expression in renal cell carcinoma predicts a worse prognosis.

• DOI: 10.1016/s0022-5347(08)60387-0
• 发表时间: 2007-04
• 期刊: International journal of oncology
• 影响因子: 5.2
• 作者: Y. Mizutani;H. Nakanishi;Yong Nan Li;Hiroki Matsubara;Kosuke Yamamoto;N. Sato;T. Shiraishi

Paclitaxal, Ifosphamide, Nedaplatin (TIN療法)を用いた難治性精巣腫瘍に対する救済化学療法

使用紫杉醇、异环磷酰胺、奈达铂对难治性睾丸癌进行挽救性化疗（TIN 疗法）

• 发表时间: 2006
• 期刊: 日本泌尿器科学会雑誌 97
• 作者: Horita S;Yamada H;Inatomi J;Moriyama N;et al.;野本剛史
• 通讯作者: 野本剛史

Salvage Chemotherapy with Paclitaxel, Nedaplatin and Ifosphamide for Relapsed or Refractory Germ Cell Cancer

使用紫杉醇、奈达铂和异环磷酰胺进行挽救性化疗治疗复发或难治性生殖细胞癌

• 发表时间: 2006
• 期刊: Japanese Journal of Urology 97
• 作者: Nomoto;T
• 通讯作者: T