P-GLYCOPROTEIN EXPRESSION IN MALIGNANT-MELANOMA

P-GLYCOPROTEIN EXPRESSION IN MALIGNANT-MELANOMA
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DOI:
10.1007/bf01613142
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发表时间:
1991-01-01
影响因子:
3.6
通讯作者:
SUTER, L
SUTER, L
中科院分区:
医学3区
文献类型:
--
作者:
FUCHS, B;OSTMEIER, H;SUTER, L

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在一些人类恶性肿瘤中,对化疗的抗性是由能量依赖性外排系统引起的,该能量依赖性外排系统负责将化疗剂从抗性肿瘤细胞中去除。 这种外排系统的主要成分是依赖于多药耐药基因MDR 1的渗透性糖蛋白(P-糖蛋白)。我们用单克隆抗体C219检测了原发性和转移性黑色素瘤中的P-糖蛋白,仅在1/37的原发性黑色素瘤和1/27的转移性黑色素瘤中观察到大量表达。 无转移的患者对化疗有反应。 此外,在转移显著表达P-糖蛋白的患者中观察到转移生长的完全缓解。 序贯研究显示,化疗期间和化疗后P-糖蛋白阳性细胞无显著增加。 我们的结论是,人类黑色素瘤的耐药性通常不依赖于p-糖蛋白相关的外排系统。 其他机制显然是负责耐药性在这种人类恶性肿瘤。
In some human malignancies resistance to chemotherapy is caused by an energy-dependent efflux system, responsible for the removal of chemotherapeutics out of the resistant tumor cells. A major component of this efflux system is the permeability glycoprotein (p-glycoprotein), which depends on the multidrug-resistance gene MDR1.We have tested p-glycoprotein in primary and metastatic human melanoma by use of the monoclonal antibody C219; a substantial expression was only observed in 1/37 primary melanomas and in 1/27 melanoma metastases. None of the patients with negative metastases responded to chemotherapy. Moreover a complete remission of metastasic growth was observed in the patient with the metastasis significantly expressing the p-glycoprotein. Sequential studies revealed no significant increase of p-glycoprotein-positive cells during and after chemotherapy. We conclude that drug resistance in human melanoma does not usually depend on the p-glycoprotein-related efflux system. Other mechanisms are obviously responsible for drug resistance in this human malignancy.