TOPOISOMERASE-I AND TOPOISOMERASE-II ACTIVITY IN HUMAN BREAST, CERVIX, LUNG AND COLON-CANCER
TOPOISOMERASE-I AND TOPOISOMERASE-II ACTIVITY IN HUMAN BREAST, CERVIX, LUNG AND COLON-CANCER
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DOI：
10.1002/ijc.2910590506
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发表时间：
1994-12-01
影响因子：
6.4
通讯作者：
KEITH, WN
中科院分区：
文献类型：
--
作者：
MCLEOD, HL;DOUGLAS, F;KEITH, WN
人类DNA拓扑异构酶作为活性抗癌药物的细胞靶点的鉴定激发了人们对肿瘤生物学中拓扑异构酶功能的进一步兴趣。拓扑异构酶I和II催化活性在许多正常和恶性组织中可检测到。然而，对拓扑异构酶在大多数人类实体瘤中的表达知之甚少。本研究评估了86例乳腺癌、肺癌、宫颈癌或结肠癌患者活检标本中拓扑异构酶I和II的活性。观察到拓扑异构酶表达的显著肿瘤内和肿瘤间变化。与肺癌和乳腺癌相比，宫颈癌和结肠癌的拓扑异构酶I活性相对较高。拓扑异构酶II活性在宫颈癌、结肠癌和肺癌中高于乳腺癌。拓扑异构酶I和II活性在单个结肠肿瘤样品中共分离，但在宫颈、肺或乳腺肿瘤中未观察到相关性。拓扑异构酶I和II活性在肿瘤类型内的大的异质性表明了对拓扑异构酶导向治疗的可变响应的机制。肿瘤组之间的活性差异表明，拓扑异构酶I抑制剂在结肠和宫颈肿瘤中的潜在疗效可能大于肺和乳腺肿瘤。需要进一步进行体内评价，以确定观察到的拓扑异构酶活性异质性的临床相关性。(C)1994 Wiley-Liss，Inc.
The identification of human DNA topoisomerases as cellular targets for active anti-cancer drugs has stimulated further interest in topoisomerase function in tumour biology. Topoisomerase I and II catalytic activity is detectable in many normal and malignant tissues. However, little is known about the expression of topoisomerases in most human solid tumours. The present study evaluated topoisomerase I and II activity in biopsy samples from 86 patients with breast, lung, cervix or colon cancers. Significant intra- and inter-tumour variation in topoisomerase expression was observed. Topoisomerase I activity was relatively high in cervix and colon tumours in comparison to lung and breast cancers. Topoisomerase II activity was high in cervix, colon and lung cancers relative to breast cancer. Topoisomerase I and II activity co-segregated in individual colon tumour samples, but no correlation was observed in cervix, lung or breast tumours. The large heterogeneity in both topoisomerase I and II activity within a tumour type suggests a mechanism for variable response to topoisomerase-directed therapy. The differences in activity between tumour groups suggest that the potential efficacy of inhibitors of topoisomerase I in colon and cervical tumours may be greater than in lung and breast tumours. Future in vivo evaluation is required to establish the clinical relevance of the observed heterogeneity in topoisomerase activity. (C) 1994 Wiley-Liss, Inc.