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卵巢透明细胞癌治疗策略的理论模型:聚焦于观点。

Theoretical model of treatment strategies for clear cell carcinoma of the ovary: focus on perspectives.

作者信息

Yoshida Shozo, Furukawa Naoto, Haruta Shoji, Tanase Yasuhito, Kanayama Seiji, Noguchi Taketoshi, Sakata Mariko, Yamada Yoshihiko, Oi Hidekazu, Kobayashi Hiroshi

机构信息

Department of Obstetrics and Gynecology, Nara Medical University, Nara, Japan.

出版信息

Cancer Treat Rev. 2009 Nov;35(7):608-15. doi: 10.1016/j.ctrv.2009.07.002. Epub 2009 Aug 8.

Abstract

OBJECTIVES

Among epithelial ovarian cancer (EOC), clear cell carcinomas (CCC) differ from the other histologic types with respect to their clinical characteristics, carcinogenesis and prognosis. The aim of this review is to summarize the current knowledge and future perspective on the new therapeutic targets and treatment strategies for CCC.

MATERIALS AND METHODS

The present article reviews the English language literature for preclinical and clinical trials and promising molecular targets on CCC of the ovary, based on the gene expression profiling studies.

RESULTS

Here, we show that (1) the expression of the genes involved in transcription, signaling, cell cycle, adhesion, matrix, proteinase, and detoxification was greatly increased in the CCC carcinogenesis; (2) upregulation of hepatocyte nuclear factor-1beta (HNF-1beta) and Polo-like kinase (PLK)-Early mitotic inhibitor-1 (Emi1) as well as their downstream targets are specifically found in most CCC. The promising molecular targeting approach will emerge in the context of HNF-1beta and PLK-Emi1 biology; and 3) several significant common pathways observed in CCC of the ovary overlap the datasets identified in CCC of the kidney. To improve the outcome in CCC therapy, we must learn various adaptive treatment strategies for renal CCC, although it is not supported by any preliminary clinical data.

CONCLUSION

The inhibitors that target HNF-1beta and PLK-Emi1 and their downstream signaling molecules would be evaluated. In addition, the therapy currently used in renal CCC should be considered as an alternative for the present treatments or an attractive therapeutic option for ovarian CCC. The challenges accompanying the recent advance are described in this review article.

摘要

目的

在上皮性卵巢癌(EOC)中,透明细胞癌(CCC)在临床特征、致癌机制和预后方面与其他组织学类型不同。本综述的目的是总结关于CCC新治疗靶点和治疗策略的当前知识及未来前景。

材料与方法

本文基于基因表达谱研究,回顾了关于卵巢CCC的临床前和临床试验以及有前景的分子靶点的英文文献。

结果

在此,我们表明:(1)参与转录、信号传导、细胞周期、黏附、基质、蛋白酶和解毒的基因在CCC致癌过程中表达大幅增加;(2)在大多数CCC中特别发现了肝细胞核因子-1β(HNF-1β)和Polo样激酶(PLK)-早期有丝分裂抑制因子-1(Emi1)及其下游靶点的上调。在HNF-1β和PLK-Emi1生物学背景下将出现有前景的分子靶向方法;以及(3)在卵巢CCC中观察到的几个重要共同途径与在肾CCC中鉴定的数据集重叠。为改善CCC治疗结果,我们必须学习针对肾CCC的各种适应性治疗策略,尽管尚无任何初步临床数据支持。

结论

将评估靶向HNF-1β和PLK-Emi1及其下游信号分子的抑制剂。此外,目前用于肾CCC的治疗应被视为当前治疗的替代方案或卵巢CCC的有吸引力的治疗选择。本文综述了伴随近期进展的挑战。

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