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DETECTION OF MULTI-DRUG RESISTANCY IN MALIGNANT BONE AND SOFT TISSUE TUMORS BY ADRIAMYCIN BINDING ASSAY

阿霉素结合试验检测恶性骨和软组织肿瘤的多药耐药性

基本信息

批准号：
05671224
负责人：
KUSUZAKI Katsuyuki
金额：
$ 1.02万
依托单位：
KYOTO PREFECTURAL UNIVERSITY OF MEDICINE
依托单位国家：
日本
项目类别：
Grant-in-Aid for General Scientific Research (C)
财政年份：
1993
资助国家：
日本
起止时间：
1993 至 1994
项目状态：
已结题

项目摘要

In this study, the author first, developed in vivo method of adriamycine Binding Assay (ABA) which has been proved to be able to quickly detect sensitivity not only to adriamycine (ADR) also to multi-anticancer drugs in cultured cell lines and secondly, investigated relationship between adriamycin binding ratio and clinical or histological effect of chemotherapy in human bone nad soft tissue tumors. Living tumor cells were isolated from fresh biopsied materials with collagenase and incubated with 10ug/ml ADR for 30 min. Only living cells were then stained with fluorescein diacetate (FDA). Under observation with fluorescence microscope, the living cells with ADR fluorescence in nucleus were evaluated to be sensitive to ADR,but ones without ADR were resistant. %AB showed frequency of sensitive cells in all of the living cells measured. Fourty-four patients were analyzed. In most of the patients with recurrence or metastasis after chemotherapy to primary tumor, or with metastatic disease at diagnosis of primary tumor, %AB was less than 80%. This strongly suggests that tumors with low %AB are multi-drug resistant. Of 11 patients with primary tumor lesion without metastasis and any kind of previous chemotherapy, 4 with %AB more than 80% were histologically sensitive to chemotherapy after preoperative chemotherapy, whereas remaining 7 with %AB less than 80% except one were resistant. It also shows that %AB is correlated with chemotherapy effect well. The author, therefore concluded that ABA is one of the excellent chemosensitivity tests and avalable to clinical usage, because it is able to predict sensitivity to chemotherapy more quickly and accurately than other chemosensitivity tests previously reported.

本研究首先建立了体内阿霉素结合试验（阿坝）方法，该方法已被证明不仅能快速检测培养细胞系对阿霉素（ADR）的敏感性，而且能快速检测培养细胞系对多种抗癌药物的敏感性;其次，研究了阿霉素结合率与人骨和软组织肿瘤化疗的临床或组织学疗效的关系。用胶原酶从新鲜活检材料中分离活肿瘤细胞，并与10 μ g/ml ADR孵育30分钟。在荧光显微镜下观察，细胞核内有ADR荧光的活细胞对ADR敏感，而无ADR荧光的活细胞对ADR耐药。%AB显示在所有测量的活细胞中敏感细胞的频率。分析了44例患者。在原发肿瘤化疗后复发或转移的患者中，或在原发肿瘤诊断时有转移性疾病的患者中，大多数%AB小于80%。这强烈表明具有低%AB的肿瘤是多药耐药的。11例原发灶无转移且既往接受过任何化疗的患者中，4例术前化疗后%AB> 80%的患者组织学上对化疗敏感，7例术前化疗后%AB <80%的患者除1例外均为耐药。%AB与化疗效果有较好的相关性。因此，作者认为阿坝是一种优良的化疗敏感性试验，可用于临床，因为它能够比以前报道的其他化疗敏感性试验更快，更准确地预测化疗敏感性。