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NAT GENET :揭示儿童脑癌根源

2013-07-11 何嫱 生物通

由德国癌症研究中心领导的一个科学家小组证实,一个过度活跃的信号通路是最常见的儿童脑癌——毛细胞型星形细胞瘤(pilocytic astrocytoma)的致病原因。通过研究96个病例,研究人员发现一些基因缺陷与一条特殊信号通路有关联。因此,可以利用药物来阻断这一信号级联反应的组成元件,帮助治疗疾病儿童。研究结果发布在最新一期的《自然遗传学》(Nature Genetic

由德国癌症研究中心领导的一个科学家小组证实,一个过度活跃的信号通路是最常见的儿童脑癌——毛细胞型星形细胞瘤(pilocytic astrocytoma)的致病原因。通过研究96个病例,研究人员发现一些基因缺陷与一条特殊信号通路有关联。因此,可以利用药物来阻断这一信号级联反应的组成元件,帮助治疗疾病儿童。研究结果发布在最新一期的《自然遗传学》(Nature Genetics)杂志上。

脑癌是儿童癌症死亡的首要原因。即便是癌症得到治愈,年轻的患者所经受的治疗压力,也会对发育中的大脑造成损害。为了找到新的靶结构以开发出更温和的治疗方案,癌症研究人员系统地分析了这些肿瘤的所有遗传改变。PedBrain协会于2010年启动这一项目。在德国癌症研究中心Stefan Pfister教授的领导下,现在PedBrain协会的研究人员发布了第一批毛细胞型星形细胞瘤基因组的分析结果。

毛细胞型星形细胞瘤是最常见的儿童脑肿瘤。这些肿瘤通常生长缓慢。然而,由于手术往往很难触及到它们,使得肿瘤无法完全切除,治疗后可能再度复发,对患儿造成长期的、破坏性的影响。

在以往的研究工作中,Stefan Pfister教授和David Jones博士领导的研究小组已经确定了大部分毛细胞型星形细胞瘤的特征性突变,并发现所有的遗传改变均与一条称作为MAPK(丝裂原活化蛋白激酶)的重要细胞信号通路有关。这一信号通路调控了许多基础的生物学过程,例如胚胎发育、分化、细胞生长与死亡等。

论文的第一作者David Jones 说:“几年前我们已经猜测出,毛细胞型星形细胞瘤普遍是由于MAPK信号缺陷性激活所引起。然而有五分之一的病例,我们最初没有发现这些突变。在针对96个肿瘤的全基因组分析中,我们现在发现了此前从未在星形细胞瘤中描述过的另外3种基因,其激活缺陷与MAPK信号通路有关。”

“除了MAPK突变,我们没有找到其他可以促进肿瘤生长的常见突变。这明确地表明了,过度激活的MAPK信号是毛细胞型星形细胞瘤形成的必要条件,” Stefan Pfister说。

总的来说,相比于更加恶性的儿童脑瘤——髓母细胞瘤,毛细胞型星形细胞瘤基因组中的突变要少得多。这一研究发现与星形细胞瘤较良性的生长行为相符。研究人员发现随着患病个体的年龄增大,突变数量逐渐增加。

大约一半的毛细胞型星形细胞瘤形成于小脑中,其余50%存在于其他各个大脑区域。相比于其他的病例,小脑毛细胞型星形细胞瘤的遗传同质性(genetically homogeneous)更高。

Stefan Pfister说:“从研究结果中我们得出了一个重要的结论:能够从不同位点来阻断过度活跃MAPK信号级联反应的药物,都有可能成为所有毛细胞型星形细胞瘤的靶向性药物。因此,未来我们或许能够帮助到那些难以接受手术治疗的患者。”   


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    2014-01-19 liye789132251
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    2013-09-16 canlab
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    2013-09-24 cy0324
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Lancet Oncol:脑瘤治疗的新遗传标记物

近日,英国诺丁汉大学研究人员发现脑癌3套遗传标记物,可能为致命的脑瘤诊断带来新的希望。 这项最新研究由Richard Grundy教授率领,发表在权威杂志Lancet Oncology最新一期上。 尽管需要新的、更有效的治疗手段,早些年也已经开展了一系列研究,但取得的成绩并不如人意。这项诺丁汉大学完成的研究旨在筛选出可用来提高癌症治疗功效和开展治疗的分子标记物。 诺丁汉大学与加拿大多伦多病童

Nature Genet:儿童侵袭性神经母细胞瘤致病基因被发现

  来自约翰霍普金斯大学Kimmel癌症中心和费城儿童医院(CHOP)的科学家们发表在12月2日的《自然·遗传学》(Nature Genetics)杂志上的一项研究结果表明:在对74个儿童神经母细胞瘤进行全基因组测序后,ARID1A和ARID1B两个基因发生改变的患儿相比无此基因改变的患儿生存期缩短了四分之三。这一发现有可能最终导致早期确认患有侵袭性神经母细胞瘤的儿童,他们或许需要接受其他的治疗。

MOL CANCER THER:CFAK-Y15可治疗神经胶质瘤

Vita M. Golubovskaya, PhD   美国罗斯维尔帕克癌症研究所(RPCI)近日发表报告称,他们在前临床研究中对一种被称为CFAK-Y15的小分子抑制剂治疗某些脑瘤的有效性进行了评估。这项被发表在《肿瘤分子治疗学》杂志上的研究首次证实,利用CFAK-Y15来抑制黏着斑激酶(FAK)的功能可有效控制胶质母细胞瘤的生长,尤其是当与标准化疗药物替莫唑胺(Temodar)联合使用

手机或增脑癌风险

    频繁长时间使用手机、喜欢把手机放在枕头边上等可能增加患脑肿瘤风险。在举行的第六届上海国际神经外科大会上,中国工程院院士、复旦大学附属华山医院神经外科主任周良辅教授披露,我国每年因为脑胶质瘤死亡人数达到十万人。   第六届上海国际神经外科大会上,来自国内外200多名脑神经外科专家汇聚一堂,就中国首部《中国中枢神经系统胶质瘤诊断和治疗指南》进行了深入探讨。  

PLoS ONE:禁食让脑瘤对化疗更加敏感

在一项新研究中,来自美国南加州大学的研究人员首次证实控制性禁食(controlled fasting)改善在癌症治疗中的化疗疗效,延长患有侵袭性脑瘤的小鼠的预期寿命。 在这项刊登在PLoS ONE期刊上的最新研究中,研究人员首次证实禁食时间似乎提高化疗在治疗神经胶质瘤上的疗效。神经胶质瘤是一种最为常见被诊断出来的脑瘤。患有神经胶质瘤的病人平均存活期限小于两年。 论文通信作者Valter Lon

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