恶性胸膜间皮瘤是肺和胸壁之间的癌症。它一般是由接触石棉引起，尽管罕见，全球的病例数却在不断增加，尽管有些病人对抗有丝分裂的化疗药物长春瑞滨（Vinorelbine）有响应，恶性胸膜间皮瘤的治疗方法依然相当有限。爱尔兰研究人员发现乳腺癌基因BRCA1的变化与恶性胸膜间皮瘤有关。
这项研究的成果发表在《病理学期刊》上，研究人员观察了144例间皮瘤样本，发现近40％没有表达BRCA1蛋白，这与对长春瑞滨较低反应相关。在体外实验中，研究人员能够使间皮瘤细胞重新表达BRCA1基因，从而使其对长春瑞滨敏感。
作为微管毒药，像长春瑞滨这样的药物颇具毒性。检查一个患者的肿瘤基因BRCA1是否表达，可在治疗前预测患者的反应，如果预测出这样的治疗不大可能对他们有效，则可使患者避免遭受痛苦且不必要的副作用的折磨。
总之，BRCA1基因在间皮瘤中起关键作用，能调解由长春瑞滨在间皮瘤细胞凋亡，是值得深入研究的临床预测的生物标志物。（生物谷 Bioon.com）
新闻来源：http://www.fiercebiomarkers.com/story/breast-cancer-gene-triggers-mesothelioma-response/2012-01-04
doi:10.1002/path.3979
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BRCA1 is an essential mediator of vinorelbine induced apoptosis in mesothelioma†
Sara Busacca, Michael Sheaff, Kenneth Arthur,Steven G. Gray, Kenneth J. O'Byrne, Derek J. Richard, Alex Soltermann, Isabelle Opitz, Harvey Pass, D. Paul Harkin, Jennifer E. Quinn, Dean A. Fennell
Therapeutic options for malignant pleural mesothelioma (MPM) are limited despite the increasing incidence globally. The vinca alkaloid, vinorelbine exhibits clinical activity, however, to date, treatment optimization has not been achieved using biomarkers. BRCA1 regulates sensitivity to microtubule poisons, however its role in regulating vinorelbine induced apoptosis in mesothelioma is unknown. Here we demonstrate that BRCA1 plays an essential role in mediating vinorelbine induced apoptosis, as evidenced by: 1) the strong correlation between vinorelbine sensitivity and BRCA1 expression level, 2) induction of resistance to vinorelbine by BRCA1 using siRNA oligonucleotides, 3) dramatic downregulation of BRCA1 following selection for vinorelbine resistance, and 4) the re-activation of vinorelbine induced apoptosis following re-expression of BRCA1 in resistant cells. To determine whether loss of BRCA1 expression in mesothelioma was potentially relevant in vivo, BRCA1 immunohistochemistry was subsequently performed on 144 primary mesothelioma specimens. Loss of BRCA1 protein expression was identified in 38.9% of samples. Together, this data suggests BRCA1 plays a critical role in mediating apoptosis by vinorelbine in mesothelioma, warranting its clinical evaluation as a predictive biomarker. Copyright © 2011 Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd.
