Rubin S C, Finstad C L, Hoskins W J, Saigo P E, Provencher D M, Federici M G, Hakes T B, Markman M, Reichman B S, Lloyd K O
Memorial Sloan-Kettering Cancer Center, New York, New York.
Am J Obstet Gynecol. 1990 Jul;163(1 Pt 1):69-73. doi: 10.1016/s0002-9378(11)90670-x.
The multidrug-resistance gene, MDR1, encodes a plasma membrane glycoprotein termed P-glycoprotein that mediates active cellular efflux of certain chemotherapeutic agents. P-Glycoprotein expression was evaluated in 98 frozen tumor specimens from 57 patients with epithelial ovarian cancer by the indirect immunoperoxidase technique with monoclonal antibodies C219 and JSB-1 used for detection. Tumor specimens were further characterized antigenically with a panel of monoclonal antibodies representing a variety of epithelial cell antigens. Included were 57 specimens from 33 previously untreated patients; 11 specimens were also available from eight patients in this group after chemotherapy. An additional 30 specimens were studied from 24 other patients after chemotherapy. In only four of the 57 patients with ovarian cancer (7%) did one or more of the specimens express P-glycoprotein. Two of these patients had tumors that were considered clinically drug resistant. No increase in P-glycoprotein expression was noted after exposure to chemotherapy, including the eight individuals for whom specimens were available both before and after treatment. Although drug resistance is a major problem in treatment of ovarian cancer, resistance to the drugs most active against these tumors probably occurs through a mechanism other than expression of the MDR1 gene product.
多药耐药基因MDR1编码一种质膜糖蛋白，称为P - 糖蛋白，它介导某些化疗药物的细胞主动外排。采用间接免疫过氧化物酶技术，用单克隆抗体C219和JSB - 1检测，对57例上皮性卵巢癌患者的98份冷冻肿瘤标本进行了P - 糖蛋白表达评估。用一组代表多种上皮细胞抗原的单克隆抗体对肿瘤标本进行进一步的抗原特性分析。其中包括33例未经治疗患者的57份标本；该组中8例患者化疗后也有11份标本可用。另外对24例其他患者化疗后的30份标本进行了研究。在57例卵巢癌患者中，只有4例（7%）的一份或多份标本表达P - 糖蛋白。其中2例患者的肿瘤被认为具有临床耐药性。化疗后未发现P - 糖蛋白表达增加，包括8例治疗前后均有标本的患者。虽然耐药是卵巢癌治疗中的一个主要问题，但对这些肿瘤最有效的药物的耐药可能是通过MDR1基因产物表达以外的机制发生的。
