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ATP生物发光测定法在选择用于子宫癌细胞系化学敏感性测试的药物筛选面板中的应用。

The use of ATP bioluminescence assays in selecting a drug screen panel for chemosensitivity testing of uterine cancer cell lines.

作者信息

Nguyen H N, Sevin B U, Averette H E, Perras J, Donato D, Penalver M

机构信息

Department of Obstetrics & Gynecology, University of Miami School of Medicine, Florida 33101.

出版信息

Gynecol Oncol. 1992 May;45(2):185-91. doi: 10.1016/0090-8258(92)90283-o.

Abstract

The ATP bioluminescence assay has demonstrated a strong potential to become a clinical assay for chemosensitivity testing. Currently, chemotherapy of gynecologic cancers remains controversial and empirical. To optimize the patient's chance of survival and to justify related toxicities, the chemoregimen should be individualized and based on the patient's chemosensitivity profiles. This study was performed to identify a panel of active drugs against uterine cancer cell lines for possible use in future chemosensitivity testing. We used the ATP chemosensitivity assays to screen 12 common cytotoxic agents against six uterine cancer cell lines. Drug concentrations required for a 50% surviving fraction were defined as IC50s. When using an IC50 of 0.21 PPC (peak plasma concentration) as a cutoff value for sensitivity, the following 8 drugs were considered effective for uterine cancer cell lines: actinomycin D, Adriamycin, vinblastine, etoposide, 5-fluorouracil, methotrexate, cytosine arabinoside, and mitomycin-C. Meanwhile, 4 drugs, cisplatin, 4OH-Cytoxan, bleomycin, and Alkeran with mean IC50s of 2.1 +/- 0.7, 0.8 +/- 0.1, greater than 5.0, and 0.75 +/- 0.36 PPC, respectively, were considered inactive or partially active with higher IC50s than peak plasma concentrations. In conclusion, the above panel of promising drugs can be further tested in animal models or human cancer specimens for possible use in chemosensitivity testing of uterine cancer patients.

摘要

ATP生物发光检测法已显示出成为一种用于化疗敏感性检测的临床检测方法的强大潜力。目前,妇科癌症的化疗仍存在争议且多为经验性治疗。为了优化患者的生存机会并证明相关毒性的合理性,化疗方案应个体化,并基于患者的化疗敏感性概况。本研究旨在确定一组对子宫癌细胞系有活性的药物,以供未来用于化疗敏感性检测。我们使用ATP化疗敏感性检测法,针对六种子宫癌细胞系筛选了12种常见的细胞毒性药物。将50%存活分数所需的药物浓度定义为半数抑制浓度(IC50)。当以0.21倍峰值血浆浓度(PPC)的IC50作为敏感性的临界值时,以下8种药物被认为对子宫癌细胞系有效:放线菌素D、阿霉素、长春碱、依托泊苷、5-氟尿嘧啶、甲氨蝶呤、阿糖胞苷和丝裂霉素C。同时,顺铂、4-羟基环磷酰胺、博来霉素和马法兰这4种药物,其平均IC50分别为2.1±0.7、0.8±0.1、大于5.0和0.75±0.36倍PPC,由于IC50高于峰值血浆浓度,被认为无活性或部分有活性。总之,上述一组有前景的药物可在动物模型或人类癌症标本中进一步测试,以供可能用于子宫癌患者的化疗敏感性检测。

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