Endometrial carcinoma in vitro chemosensitivity testing of single and combination chemotherapy regimens using the novel microculture kinetic apoptosis assay: implications for endometrial cancer treatment
Endometrial carcinoma in vitro chemosensitivity testing of single and combination chemotherapy regimens using the novel microculture kinetic apoptosis assay: implications for endometrial cancer treatment
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DOI：
10.3802/jgo.2010.21.1.45
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发表时间：
2010-03-01
影响因子：
3.9
通讯作者：
Perree, Mathieu
中科院分区：
文献类型：
--
作者：
Ballard, Karen S.;Homesley, Howard D.;Perree, Mathieu
目的：体外微量培养细胞凋亡动力学（MiCK）分析已被用于预测白血病患者的单药或联合化疗反应。这项可行性研究解决了MiCK在子宫内膜癌samples.Methods：子宫内膜癌标本从全腹子宫切除术在中心实验室进行处理。将活的子宫内膜癌细胞的单细胞悬浮液接种在各个威尔斯孔中。检测了单药和联合治疗方案：多柔比星、顺铂和紫杉醇以及卡铂和紫杉醇的联合治疗（妇科肿瘤组[GOG] 209子宫内膜癌III期试验组）以及紫杉醇、卡铂、多柔比星、顺铂、异环磷酰胺和长春新碱（GOG试验中的活性药物）的单药试验。细胞凋亡测定连续超过48 house.Results：19例患者中有15例成功测定。顺铂、多柔比星和紫杉醇联合用药的平均化疗敏感性最高，卡铂和紫杉醇的平均化疗敏感性较低。联合化疗敏感性高于单药化疗。然而，在25%的患者中，单一药物的化疗敏感性高于联合化疗。作为单一药物，异环磷酰胺，顺铂，紫杉醇具有最高的动力学单位values.Conclusion：使用一组模拟临床剂量方案的药物，MiCK试验是可行的，在子宫内膜癌体外化疗敏感性评估。MiCK测定结果与GOG临床试验结果相关。然而，25%的患者可能最好采用MiCK选择的单药化疗。异环磷酰胺、顺铂和紫杉醇作为单药似乎具有高活性。MiCK可能在未来的新药试验和子宫内膜癌患者的个体化化疗管理中有用。
Objective: The in vitro microculture kinetic (MiCK) apoptosis assay has been used to predict single or combination chemotherapy response in leukemia patients. This feasibility study addressed MiCK in endometrial cancer specimens.Methods: Endometrial cancer specimens from total abdominal hysterectomies were processed at a central laboratory. Single cell suspensions of viable endometrial cancer cells were plated in individual wells. Single and combination regimens were tested: combinations of doxorubicin, cisplatin, and paclitaxel and carboplatin and paclitaxel (Gynecologic Oncology Group [GOG] 209 endometrial cancer phase III trial arms) as well as single agent testing with paclitaxel, carboplatin, doxorubicin, cisplatin, ifosfamide, and vincristine (active agents in GOG trials). Apoptosis was measured continuously over 48 hours.Results: Fifteen of nineteen patients had successful assays. The highest mean chemo sensitivity was noted in the combination of cisplatin, doxorubicin, and paclitaxel with lower mean chemosensitivity for carboplatin and paclitaxel. Combination chemotherapy had higher chemosensitivity than single drug chemotherapy. However, in 25% of patients a single drug had higher chemosensitivity than combination chemotherapy. As single agents, ifosfamide, cisplatin, and paclitaxel had the highest kinetic unit values.Conclusion: Using a panel of agents simulating clinical dose regimens, the MiCK assay was feasible in evaluating in vitro chemosensitivity of endometrial cancer. MiCK assay results correlated with GOG clinical trial results. However, 25% of patients might be best treated with single agent chemotherapy selected by MiCK. Ifosfamide, cisplatin, and paclitaxel appear to have high activity as single agents. MiCK may be useful in future new drug testing and individualizing endometrial cancer patient's chemotherapy management.