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卵巢癌中线粒体超微结构与化疗反应的关系

Mitochondrial ultrastructure-associated chemotherapy response in ovarian cancer.

作者信息

Saitou Motoaki, Isonishi Seiji, Hamada Tomomi, Kiyokawa Takako, Tachibana Toshiaki, Ishikawa Hiroshi, Yasuda Makoto

机构信息

Department of Obstetrics/Gynecology, Jikei University School of Medicine, Tokyo 105, Japan.

出版信息

Oncol Rep. 2009 Jan;21(1):199-204.

PMID:19082462
Abstract

We developed mitochondrial (MT) scoring system based on MT ultrastructural findings in association with response to chemotherapy in ovarian cancer (OC). Ultrathin sections of MT prepared from 28 OC patients before chemotherapy were examined by electron microscopy. Platinum-sensitive ovarian carcinoma cell line 2008 and its resistant variant C13 were used as control cells. Seven independent MT features including, diameter, pattern of cresta structure, electron density, distribution-density and -pattern, ratio of minimal/maximal diameter and MT architecture were examined and were assigned a score between 0 and 2. Twenty-eight cases were primary advanced OC, including 4 recurrent cases. Nine cases were chemosensitive while 19 were resistant. Univariate and multivariate analysis in each factor showed good correlation to chemosensitivity for 2 factors of electron density, distribution pattern. Total score of these 2 factors in 9 sensitive cells was 1.44+/-0.41 (M +/- SE) and was 3.58+/-0.18 in 19 resistant cells (P<0.001). Receptor operative characteristics (ROC) analysis revealed that total 'cut-off' score was 3 point (P<0.05; AUC=0.84). In conclusion, this MT scoring system was excellently correlated to response regardless of histopathologic findings and this strongly suggests that the system is deemed to be of great value as biomarker for the chemosensitivity in OC.

摘要

我们基于线粒体(MT)超微结构 findings 并结合卵巢癌(OC)对化疗的反应,开发了线粒体评分系统。对 28 例 OC 患者化疗前制备的 MT 超薄切片进行电子显微镜检查。铂敏感的卵巢癌细胞系 2008 及其耐药变体 C13 用作对照细胞。检查了七个独立的 MT 特征,包括直径、嵴结构模式、电子密度、分布密度和模式、最小/最大直径比以及 MT 结构,并给予 0 到 2 分。28 例为原发性晚期 OC,包括 4 例复发病例。9 例对化疗敏感,19 例耐药。对每个因素进行单变量和多变量分析显示,电子密度、分布模式这两个因素与化疗敏感性具有良好的相关性。9 个敏感细胞中这两个因素的总分是 1.44±0.41(平均值±标准误),19 个耐药细胞中为 3.58±0.18(P<0.001)。受试者工作特征(ROC)分析显示,总“临界”评分为 3 分(P<0.05;AUC=0.84)。总之,无论组织病理学结果如何,该 MT 评分系统与反应都具有极好的相关性,这强烈表明该系统被认为作为 OC 化疗敏感性的生物标志物具有很大价值。

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