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眼部黑色素瘤中的多药耐药性。

Multidrug resistance in ocular melanoma.

作者信息

McNamara M, Clynes M, Dunne B, NicAmhlaoibh R, Lee W R, Barnes C, Kennedy S M

机构信息

Research Foundation, Royal Victoria Eye and Ear Hospital, Dublin, Ireland.

出版信息

Br J Ophthalmol. 1996 Nov;80(11):1009-12. doi: 10.1136/bjo.80.11.1009.

DOI:10.1136/bjo.80.11.1009
PMID:8976731
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC505681/
Abstract

AIMS/BACKGROUND: Metastatic disease in patients with ocular melanoma is resistant to chemotherapy. One of the main mechanisms of modulating multidrug resistance is the expression of the multidrug resistance gene 1 (MDR1) product (p-glycoprotein) by tumour cells. The purpose of this study was to evaluate the frequency of expression of the MDR1 gene in ocular melanoma whose primary treatment was surgical excision or enucleation.

METHODS

Twelve recent ocular melanomas were received fresh, snap frozen and cryostat sections of tumour were analysed for expression of MDR1 by immunohistochemistry using a well characterised monoclonal antibody to MDR1. Tumour explants were established in short term tissue culture from four tumours and cell blocks were examined by immunohistochemistry.

RESULTS

MDR1 expression was present in five of 12 ocular melanomas. Upregulation of protein expression was found in four cell lines established in short term culture from tumour explants. A recurrent tumour, initially treated by local excision and radioactive plaque, showed overexpression of MDR1 mRNA.

CONCLUSIONS

These results suggest that significant level of MDR1 may be intrinsically present in ocular melanomas before exposure to drugs involved in multidrug resistance, and indicate the possible importance of MDR1 in modulating chemoresistance in ocular melanoma. Chemosensitisation may be of potential value in planning adjuvant chemotherapy for patients with metastatic disease.

摘要

目的/背景：眼黑色素瘤患者的转移性疾病对化疗耐药。调节多药耐药的主要机制之一是肿瘤细胞表达多药耐药基因1（MDR1）产物（P-糖蛋白）。本研究的目的是评估原发性治疗为手术切除或眼球摘除的眼黑色素瘤中MDR1基因的表达频率。

方法

收集12例近期眼黑色素瘤新鲜标本，速冻后制成冰冻切片，用一种针对MDR1的特异性良好的单克隆抗体，通过免疫组化分析肿瘤组织中MDR1的表达。从4个肿瘤组织中建立短期组织培养的肿瘤外植体，并通过免疫组化检查细胞块。

结果

12例眼黑色素瘤中有5例存在MDR1表达。在从肿瘤外植体建立的4个短期培养细胞系中发现蛋白表达上调。1例复发性肿瘤，最初接受局部切除和放射性敷贴治疗，显示MDR1 mRNA过表达。

结论

这些结果表明，在接触与多药耐药相关的药物之前，眼黑色素瘤中可能固有存在显著水平的MDR1，并提示MDR1在调节眼黑色素瘤化疗耐药中的可能重要性。化学增敏在为转移性疾病患者规划辅助化疗时可能具有潜在价值。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/7813/505681/178784bc291d/brjopthal00011-0079-b.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/7813/505681/f65d721b092b/brjopthal00011-0078-a.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/7813/505681/2f0a23d7153d/brjopthal00011-0079-a.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/7813/505681/178784bc291d/brjopthal00011-0079-b.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/7813/505681/f65d721b092b/brjopthal00011-0078-a.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/7813/505681/2f0a23d7153d/brjopthal00011-0079-a.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/7813/505681/178784bc291d/brjopthal00011-0079-b.jpg

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