Apoptosis-based evaluation of chemosensitivity in ovarian cancer patients
Apoptosis-based evaluation of chemosensitivity in ovarian cancer patients
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DOI：
10.1016/j.jsgi.2003.11.003
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发表时间：
2004-05-01
期刊：
影响因子：
--
通讯作者：
Mor, G
中科院分区：
文献类型：
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作者：
Flick, MB;O'Malley, D;Mor, G
目的：诱导靶细胞凋亡是化疗诱导细胞杀伤的关键机制。我们已经建立了一个体外系统，用于确定上皮性卵巢癌细胞对卡铂和紫杉醇（泰素）的化疗敏感性。需要预测个体肿瘤敏感性可能性的实用测定来促进适当治疗的选择。我们试图确定是否上皮性卵巢癌细胞（EOC）收集的腹水中已知的临床化疗敏感或化疗耐药的卡铂和紫杉醇的患者将显示出类似的反应化疗药物后，在体外treatment.METHODS：13例III期和IV期卵巢癌治疗卡铂和紫杉醇进行了研究。半胱天冬酶-3活化被用作化疗诱导的程序性细胞死亡活化的替代标志物。我们比较了体外细胞凋亡反应与分离肿瘤细胞的患者的临床反应。临床敏感性被定义为没有证据表明疾病复发后6个月最佳减积手术和完成chemotherapy.Results：7个化疗敏感的患者，5个细胞样本在体外治疗增加了caspase-3活性的卡铂和紫杉醇。六个化疗耐药的情况下，没有表现出caspase-3的活性，只有一个或两个agent.CONCLUSION：可量化的凋亡标志物，如caspase-3的激活有可能预测化疗的临床反应。在临床实验室中应用该测定法可以优化有效治疗的潜力，并避免无效药物的毒性。版权所有（C）2004由妇科调查协会。
OBJECTIVE: Induction of apoptosis in target cells is a key mechanism by which chemotherapy induces cell killing. We have established an in vitro system for determining the chemosensitivity of epithelial ovarian cancer cells to carboplatin and paclitaxel (Taxol). Practical assays to predict the likelihood of individual tumor sensitivity are needed to facilitate the choice of adequate treatment. We sought to determine whether epithelial ovarian cancer cells (EOC) collected from the ascites fluid of patients known to be clinically chemosensitive or chemoresistant to carboplatin and paclitaxel would show a similar response to chemotherapeutic drugs after in vitro treatment.METHODS: Thirteen patients with stage III and IV ovarian cancer treated with carboplatin and paclitaxel were studied. Caspase-3 activation was used as a surrogate marker for activation of chemotherapy-induced programmed cell death. We compared the in vitro apoptotic response to the clinical response of the patients from whom the tumor cells were isolated. Clinical sensitivity was defined as no evidence of disease recurrence for 6 months after optimal debulking surgery and completion of chemotherapy.RESULTS: Of seven chemosensitive patients, five cell samples treated in vitro had increased caspase-3 activity in response to both carboplatin and paclitaxel. Five of six chemoresistant cases did not show caspase-3 activity in response to only one or to neither agent.CONCLUSION: Quantifiable markers of apoptosis such as caspase-3 activation have the potential to predict the clinical response to chemotherapy. Application of this assay in clinical laboratories could optimize the potential for efficient treatment and avoid the toxicities of ineffective drugs. Copyright (C) 2004 by the Society for Gynecologic Investigation.