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.

在本研究中，作者首先开发了阿霉素结合测定（ABA）体内方法，该方法已被证明能够快速检测培养细胞系中对阿霉素（ADR）和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效果之间的关系。用胶原酶从新鲜活检材料中分离活肿瘤细胞，并与 10ug/ml ADR 一起孵育 30 分钟。然后仅用荧光素二乙酸酯 (FDA) 对活细胞进行染色。荧光显微镜下观察，细胞核内有ADR荧光的活细胞评价为对ADR敏感，无ADR荧光的活细胞为耐药。 %AB 显示所有测量的活细胞中敏感细胞的频率。对四十四名患者进行了分析。大多数原发肿瘤化疗后复发或转移的患者，或原发肿瘤诊断时已发生转移的患者，%AB低于80%。这强烈表明 %AB 较低的肿瘤具有多重耐药性。 11例原发灶无转移且既往接受过任何一种化疗的患者中，4例术前化疗后%AB>80%对化疗组织学敏感，其余7例%AB<80%，除1例耐药外。这也表明%AB与化疗效果有很好的相关性。因此，作者得出结论：ABA 是一种优秀的化疗敏感性试验，值得临床使用，因为它比之前报道的其他化疗敏感性试验能够更快、更准确地预测化疗敏感性。