Sensitivity of short-term cultures derived from human malignant glioma to the anti-cancer drug temozolomide
Sensitivity of short-term cultures derived from human malignant glioma to the anti-cancer drug temozolomide
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DOI：
10.1097/00001813-199902000-00006
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发表时间：
1999-02-01
影响因子：
2.3
通讯作者：
Darling, JL
中科院分区：
文献类型：
--
作者：
Sankar, A;Thomas, DGT;Darling, JL
已显示出对恶性神经胶质瘤的临床活性的替莫唑胺的活性已在体外针对源自这些肿瘤的短期培养物进行了评估，所述短期培养物使用以MTT减少为终点的中间持续时间微量滴定测定。该试验先前已显示与单层克隆形成试验密切相关。在15个来自WHO III级和IV级星形细胞瘤的短期培养物（传代水平3-9）中评估了敏感性。这些培养物中替莫唑胺的ID（50）中值为258 μ M，CCNU的ID（50）中值为16.13 μ M。替莫唑胺的最大血清浓度为75 μ M，但15种培养物中只有3种（20%）的ID（50）低于此值。15个培养物中有14个（93%）显示替莫唑胺和CCNU之间的交叉耐药，尽管对CCNU极度耐药的一个株系保留了对替莫唑胺的敏感性。已发表的克隆形成生存曲线的比较研究表明，本研究中使用的短期胶质瘤细胞系具有与已建立的胶质瘤细胞系相似的敏感性，而结肠癌细胞系和膀胱癌通常对这些药物更具耐药性。来自睾丸畸胎瘤细胞系的细胞系可能对替莫唑胺表现出极高的敏感性，这种敏感性水平仅偶尔见于恶性神经胶质瘤的短期培养物中[（C）1999 Lippincott威廉姆斯& Wilkins.]。
The activity of temozolomide, which has shown clinical activity against malignant glioma, has been assessed in vitro against short-term cultures derived from these tumors using an intermediate duration microtitration assay with MTT reduction as the end-point. This assay has previously been shown to correlate closely with a monolayer clonogenic assay. Sensitivity was assessed in 15 short-term cultures (passage levels 3-9) derived from WHO grade III and IV astrocytomas. These cultures had a median ID(50) value of 258 mu M for temozolomide and 16.13 mu M for CCNU. Maximum serum concentrations of temozolomide are of the order of 75 mu M but only three of 15 (20%) cultures had ID(50)s below this value. Fourteen of 15 (93%) cultures displayed cross-resistance between temozolomide and CCNU, although one line which was extremely resistant to CCNU retained sensitivity to temozolomide. Comparative studies of published clonogenic survival curves indicate that the shortterm glioma cell lines used in this study have similar sensitivities to established glioma cell lines, whilst colon carcinoma cell lines and bladder carcinoma are often more resistant to these drugs. Cell lines from testicular teratoma cell lines may show exquisite sensitivity to temozolomide and this level of sensitivity is seen only occasionally in shortterm cultures derived from malignant glioma, [(C) 1999 Lippincott Williams & Wilkins.].