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睾丸癌中的肺耐药蛋白分析

[Lung resistance protein analysis in testicular cancer].

作者信息

Mándoky László, Géczi Lajos, Doleschall Zoltán, Csuka Orsolya, Bodrogi István, Bak Mihály

机构信息

Országos Onkológiai Intézet, Cytopathologiai osztály, Budapest, Hungary.

出版信息

Magy Onkol. 2002;46(4):339-45. Epub 2003 Feb 1.

Abstract

Germ cell testicular cancers are well-curable neoplasms, because total remission can be achieved in about 80% of the cases. However, 15-20% of the patients die due to drug resistance (DR). A number of mechanisms of the multidrug resistance phenotype are known, including MDR/P-glycoprotein (P-gp) and the so-called multidrug resistance associated protein (MRP). Lung Resistance Protein (LRP) is an ATP dependent membrane transporter protein associated with MDR. In our present work we studied the expression of LRP in testicular cancers. LRP expression was determined by immunohistochemistry (IH), Western blot (WB) and RT-PCR techniques. Clinical resistance was defined in accordance with the clinical oncologic rules. In 29 (41%) of 70 primary testicular tumours and in 22 (63%) of 35 cases, elevated LRP levels were established by IH and WB, respectively. In the latter 63%, the LRP mRNA levels were elevated as well. Six cases of the 15 seminomas and 23 cases of the nonseminomatous germ cell tumours (NSGCT) proved to be positive. No relationship was demonstrated between LRP expression and the stage of the disease. Despite the LRP positivity of 6 tumour samples, all of the seminomas proved sensitive. Of the 39 sensitive NSGCT, 27 cases were LRP-negative, whereas 11 tumour samples of 16 patients belonging to the resistant group proved LRP-positive (p=0.04). The authors concluded that the expression of LRP is responsible for clinical drug resistance in non-seminomatous testicular cancer patients.

摘要

睾丸生殖细胞癌是可治愈的肿瘤,因为约80%的病例可实现完全缓解。然而,15 - 20%的患者因耐药性(DR)死亡。已知多种多药耐药表型的机制,包括MDR/P - 糖蛋白(P - gp)和所谓的多药耐药相关蛋白(MRP)。肺耐药蛋白(LRP)是一种与多药耐药相关的ATP依赖性膜转运蛋白。在我们目前的研究中,我们研究了LRP在睾丸癌中的表达。通过免疫组织化学(IH)、蛋白质印迹法(WB)和逆转录 - 聚合酶链反应(RT - PCR)技术测定LRP表达。根据临床肿瘤学规则定义临床耐药性。在70例原发性睾丸肿瘤中的29例(41%)以及35例中的22例(63%),分别通过IH和WB确定LRP水平升高。在后者的63%中,LRP mRNA水平也升高。15例精原细胞瘤中的6例和23例非精原细胞性生殖细胞肿瘤(NSGCT)被证明为阳性。未发现LRP表达与疾病分期之间存在关联。尽管6个肿瘤样本LRP呈阳性,但所有精原细胞瘤均被证明敏感。在39例敏感的NSGCT中,27例LRP为阴性,而在16例耐药组患者的11个肿瘤样本中LRP为阳性(p = 0.04)。作者得出结论,LRP的表达是导致非精原细胞性睾丸癌患者临床耐药的原因。

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