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

生殖细胞肿瘤（gct）患者顺铂联合化疗的总有效率有所提高。尽管治愈率很高，但20- 30%的晚期gct患者未能达到持久的完全缓解。这些难治性或复发的gct仍然是目前治疗的主要问题。在临床研究中，我们探讨了紫杉醇联合顺铂衍生物奈达铂和异磷酰胺作为顺铂难治性生殖细胞癌的补救性化疗方案。对14例患者的反应和毒性进行了评估。有效率为57.1% （CR / PR^<m）。>: 8例，NC: 5例，PD: 1例)。7名患者仍然存活，没有疾病。本研究表明紫杉醇联合奈达铂和异磷酰胺化疗对顺铂难治性或复发性生殖细胞癌患者具有显著的抗癌活性。这些结果提示，联合化疗可能是顺铂难治性或复发性生殖细胞癌补救性化疗的选择之一。在这项研究中，为了研究新的gct诊断标记和潜在的治疗靶点，我们使用cDNA微阵列鉴定了347个gct中普遍上调的基因（Int J Oncol, 2003）。此外，我们发现NALP7在gct中显着反激活，并表明NALP7可能是开发gct靶向治疗的有希望的候选者（Cancer Sci, 2004）。

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).