惡性胸膜間皮瘤是肺和胸壁之間的癌癥,。它一般是由接觸石棉引起，盡管罕見,，全球的病例數(shù)卻在不斷增加,，盡管有些病人對抗有絲分裂的化療藥物長春瑞濱（Vinorelbine）有響應，惡性胸膜間皮瘤的治療方法依然相當有限,。愛爾蘭研究人員發(fā)現(xiàn)乳腺癌基因BRCA1的變化與惡性胸膜間皮瘤有關,。
這項研究的成果發(fā)表在《病理學期刊》上，研究人員觀察了144例間皮瘤樣本,，發(fā)現(xiàn)近40％沒有表達BRCA1蛋白,，這與對長春瑞濱較低反應相關。在體外實驗中,，研究人員能夠使間皮瘤細胞重新表達BRCA1基因,，從而使其對長春瑞濱敏感。
作為微管毒藥,，像長春瑞濱這樣的藥物頗具毒性,。檢查一個患者的腫瘤基因BRCA1是否表達，可在治療前預測患者的反應,，如果預測出這樣的治療不大可能對他們有效,，則可使患者避免遭受痛苦且不必要的副作用的折磨。
總之,，BRCA1基因在間皮瘤中起關鍵作用,，能調(diào)解由長春瑞濱在間皮瘤細胞凋亡，是值得深入研究的臨床預測的生物標志物,。（生物谷 Bioon.com）
新聞來源：http://www.fiercebiomarkers.com/story/breast-cancer-gene-triggers-mesothelioma-response/2012-01-04
doi:10.1002/path.3979
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PMID:
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.
