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盘点:近期胃癌重要研究进展一览

2017-06-11 MedSci MedSci原创

胃癌是世界第三大癌症。在中国,每年有超过四十万病人受到胃癌的危害。对于局部晚期胃癌患者来说,目前手术彻底切除仍然是现有治疗方案的基石。胃癌具有起病隐匿、早期常因无明显症状而漏诊、易转移与复发和预后差等特点。胃癌的病因迄今尚未完全阐明。通过对胃癌发病的地理分布以及与移民关系的研究,一般认为外界环境和饮食因素与胃癌的发生关系最为密切,人体还有些利于胃癌发生的条件,也是不容忽视的。这里梅斯小编整理近

胃癌是世界第三大癌症。在中国,每年有超过四十万病人受到胃癌的危害。对于局部晚期胃癌患者来说,目前手术彻底切除仍然是现有治疗方案的基石。胃癌具有起病隐匿、早期常因无明显症状而漏诊、易转移与复发和预后差等特点。胃癌的病因迄今尚未完全阐明。通过对胃癌发病的地理分布以及与移民关系的研究,一般认为外界环境和饮食因素与胃癌的发生关系最为密切,人体还有些利于胃癌发生的条件,也是不容忽视的。这里梅斯小编整理近期关于胃癌的重要研究进展与大家一同分享。

【1】Cancer Cell:日美研究团队发现神经紧张加快胃癌形成机理

日本东京大学与美国哥伦比亚大学的联合研究团队利用转基因技术,使小鼠消化道内负责分泌神经信号传递物质乙酰胆碱的神经细胞发出绿光,从而成功观察到乙酰胆碱从何而来。结果显示,分泌乙酰胆碱的神经细胞环绕于胃干细胞的周围,而且粘膜细胞中的丛细胞也会生成乙酰胆碱。此外,这些神经细胞和丛细胞在小鼠胃癌的发作过程中逐渐增殖,同时在组织内部大量生成乙酰胆碱。

研究人员根据这一发现,怀疑正是这种超量的乙酰胆碱刺激了癌细胞,使其释放出促进神经生长的物质。实验也发现,在胃癌细胞中,一种被称为神经生长因子(NGF)的荷尔蒙,的确由乙酰胆碱的刺激而大量生成。

进而,研究人员制作了胃部神经细胞数量超常的小鼠,发现其胃部出现异常神经并迅速发育,胃癌自然就发作了。另一方面,那些乙酰胆碱受体缺损的小鼠,喂食了NGF受体阻滞剂的小鼠,以及去除了丛细胞的小鼠,则不出现这种因神经信号而加速胃癌进程的现象。因此可以认为,在胃癌的发生过程中,神经紧张是通过乙酰胆碱发挥了作用。(文章详见——Cancer Cell:日美研究团队发现神经紧张加快胃癌形成机理



【2】Ann Surg:胃癌切除术后是Roux-en-Y术式好还是Billroth II术式好?

近期,一项发表在杂志Ann Surg上的文章旨在比较胃癌患者进行远端胃大部切除术(DG)后进行B-II和R-Y重建术后的临床症状。

研究人员将接受DG治疗的162例患者被随机分配到B-II(n = 81)和R-Y(n = 81)手术组。结果显示,B-II手术时间明显短于R-Y。B-II和R-Y组的围手术期发病率分别为28.4%和33.8%;30天死亡率分别为2.5%和1.2%。

R-Y与B-II重建的胃肠道症状评分无显著差异。 R-Y导致的内镜下胃炎相对于B-II的等级较低。此外,两组患者之间的营养状况和1年的生活质量没有差异。(文章详见——Ann Surg:胃癌切除术后是Roux-en-Y术式好还是Billroth II术式好?

【3】Oncotarget:传统中药卡塞平(KSP)通过激发自噬抑制胃癌的生长

卡塞平(KSP)是中国研究者开发的一种新的中药。本研究旨在探讨KSP是否能够抑制胃癌生长,并探究其可能的疗效机制。

通过MFCs(小鼠前胃癌细胞)皮下注射建立裸鼠胃癌异种移植模型。通过MDC染色检测自噬,Lyso-Tracker Red staining和Mito-Traker Green staining检测线粒体和溶酶体。将小鼠MFCs细胞株在加入了KSP的培养液中孵育48小时。结果发现,伴随溶酶体和线粒体的损伤,癌细胞死亡及自噬激活呈KSP浓度依赖性。

研究者同时进行了小鼠胃癌移植瘤模型体内的治疗研究,使用KSP(20毫升/公斤/天)治疗两周后,小鼠胃癌生长受到抑制,而在胃癌MFCs裸鼠异种移植模型肿瘤组织中Beclin-1,Cathepsin L、Bcl-2、p53和Caspase-3水平增加。重要的是,KSP引起的这些效应均能被自噬抑制剂3-MA抑制。(文章详见——Oncotarget:传统中药卡塞平(KSP)通过激发自噬抑制胃癌的生长



【4】Ann Surg Oncol:研究建议早期胃癌行保留幽门胃切除术

据日本研究人员介绍,在早期胃癌患者中,腹腔镜保留幽门切除术提供了“极好”的长期预后和良好的营养状态。

研究人员回顾性研究了2006到2012之间465例行该方法切除胃中部可切除胃癌(cT1 N0)的患者。术前,根据活检结果将内镜标记夹置于癌阴性肿瘤边界,术中胃镜检查验证肿瘤位置,确定合适的切除线。

在短期内,只有14例患者(3%)有严重的并发症,没有院内死亡。15例患者接受辅助化疗。中位随访时间约5年。5年总复发率和无复发生存率均为98%。仅2例术后复发,均不是残胃或区域淋巴结。其中一名患者术后8年后仍未因癌症而死亡。与术前结果比较,术后6个月及术后1、2年时血清总蛋白和白蛋白水平显着升高。经过术后第6个月时的下降后,术后1、2年血红蛋白水平下降,与术前相似。(文章详见——Ann Surg Oncol:研究建议早期胃癌行保留幽门胃切除术

【5】Oncogene:研究发现胃癌发生相关Hippo通路关键转录因子TEAD4特异性结合DNA机制

近日,国际学术权威刊物自然出版集团旗下子刊、肿瘤学重要学术期刊Oncogene杂志在线发表了中国科学院生物化学与细胞生物学研究所/分子细胞科学卓越创新中心周兆才研究组的最新研究成果。研究在原子水平上阐明了Hippo信号通路下游关键转录因子TEAD4特异性识别结合DNA的机制。

研究组此前发现了Hippo-YAP信号通路调控胃癌发生发展的新机制,鉴定了VGLL4作为YAP天然拮抗因子对于胃癌诊疗的潜在应用价值,并发展了治疗性多肽;最近又发现了Hippo与Wnt通路间的互作新模式,并揭示了VGLL4靶向两者核内互作共调控Hippo、Wnt通路从而抑制结肠癌的功能作用。

在此基础上,本项工作主要通过结构生物学、生物化学等技术方法深入解析了Hippo通路下游关键转录因子TEAD4特异性识别结合DNA的机制,发现TEAD4的alpha3螺旋决定了识别DNA的特异性;而其相互作用界面主要由两个位点构成,分别对应于所识别DNA的大沟与小沟;针对其中任一位点的突变则使得TEAD4在靶基因启动子上的占有率显着下降,大大阻碍YAP诱导的TEAD4激活与靶基因转录,抑制胃癌细胞生长。(文章详见——Oncogene:中科院周兆才研究组阐明胃癌发生相关Hippo通路关键转录因子TEAD4特异性结合DNA机制

【6】The Lancet Oncology:曲妥珠单抗不能提高HER2阳性晚期胃癌患者的生存率

曲妥珠单抗联合化疗是治疗HER2阳性进展期胃癌的一线标准,但尚无有效的二线治疗方法。研究人员考察了曲妥珠单抗对HER2阳性晚期胃癌治疗的患者的耐受性和疗效。

试验的第一个阶段,患者随机分配接受曲妥珠单抗(n= 70,3.6 mg/kg 每三周或 2.4 mg/kg每周)或静脉滴注紫杉醇类药物(n= 75, 75mg/m2 多西他赛,每三周一次或者n=37, 80mg/m2 紫杉醇, 每周一次);在第二阶段,患者随机分配接受曲妥珠单抗(n=153,2.4 mg/kg 每周)或者静脉滴注紫杉醇类药物(n=80,剂量同前)。

结果显示,2.4mg/kg曲妥珠单抗组中位随访时间为17.5个月,紫杉醇组为15.4个月;2.4mg/kg曲妥珠单抗组中位生存期为7.9个月,紫杉醇组为8.6个月;2.4mg/kg曲妥珠单抗组发生三级或以上不良事件的概率要低于紫杉醇组;致死性不良事件、严重的不良事件以及导致治疗中断的不良事件发生概率两者相近;2.4mg/kg曲妥珠单抗组最常见的三级或以上不良事件为重度贫血、血小板减少、紫杉醇组为白细胞减少症、重度贫血;2.4mg/kg曲妥珠单抗组最常见严重不良事件为贫血、上消化道出血、肺炎、胃肠道出血,紫杉醇组为肺炎、中性粒细胞减少、白细胞减少。(文章详见——The Lancet Oncology:曲妥珠单抗不能提高HER2阳性晚期胃癌患者的生存率


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    学习了谢谢分享

    0

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    2017-06-13 Jianghuiqin

    最后一个研究没明白!

    0

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    2017-06-12 133****4869

    日美研究团队发现神经紧张加快胃癌形成机理

    0

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    2017-06-12 1771ae4158m

    学习一下很不错

    0

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    2017-06-11 dhzzm

    学习了分享了

    0

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    2017-06-11 cqykthl

    好文章,查看一下原文

    0

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    2017-06-11 cuiyejia

    学习了,谢谢

    0

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    2017-06-11 xiaotaiyang1

    看看了解一下,谢谢

    0

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    2017-06-11 执着追梦

    学习,谢谢分享

    0

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