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JCEM:雌激素影响结直肠癌进展的机制或与G蛋白偶联受体的增殖有关

2017-09-29 MedSci MedSci原创

背景:尽管目前缺乏精确的分子机制,但雌激素能影响结直肠癌的发生和发展。目的:本研究旨在探讨雌激素代谢的前受体——人类CRC组织、TCGA Coad数据集、体内外的CRC模型研究中的类固醇硫酸酯酶(STS)和17β-羟类固醇脱氢酶的活性,及随后的非基因组雌激素信号,以及确定和哪种雌激素能改变CRC增殖和进展和其治疗的靶向通路。设计、设置、患者和干预:研究人员从绝经后妇女和根据年龄匹配的男性患者中,收

背景:尽管目前缺乏精确的分子机制,但雌激素能影响结直肠癌的发生和发展。

目的:本研究旨在探讨雌激素代谢的前受体——人类CRC组织、TCGA Coad数据集、体内外的CRC模型研究中的类固醇硫酸酯酶(STS)和17β-羟类固醇脱氢酶的活性,及随后的非基因组雌激素信号,以及确定和哪种雌激素能改变CRC增殖和进展和其治疗的靶向通路。

设计、设置、患者和干预:研究人员从绝经后妇女和根据年龄匹配的男性患者中,收集了人结直肠癌样本及匹配的结直肠正常样本。研究人员测定了雌激素代谢酶和非基因的下游信号转导通路。研究人员使用STS转染的结直肠癌细胞系进行体外培养,以及体内分析。研究人员使用新的超高效液相色谱串联质谱法测定雌激素代谢。

主要结果测量:在异种移植的CRC小鼠中,用BrdU检测法评估雌激素代谢的增殖作用。

结果:人类结直肠癌对雌激素代谢的调节异常,这有利于雌二醇的合成。类固醇硫酸酯酶(STS)是共轭激活雌激素的基本酶,与对照组相比,人CRC样本中它的活性明显升高(P<0.001)。STS过度表达加速了体外和体内的CRC增殖,STS抑制是一种有效的治疗方法。在CRC中,根据结缔组织生长因子(CTGF),研究人员确定了一个G蛋白偶联受体(GPER)增殖的前通路。

结论:人类结直肠癌通过GPER刺激有利于雌二醇合成和增殖。未来需要进一步研究在治疗高危结直肠癌患者时,是否应谨慎使用雌激素替代疗法。

原始出处:

Gilligan LC, Rahman HP,et al.Estrogen Activation by Steroid Sulfatase increases Colorectal Cancer proliferation via GPER.J Clin Endocrinol Metab. 2017 Sep 13. doi: 10.1210/jc.2016-3716. [Epub ahead of print]

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    2018-08-23 achengzhao
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    2018-02-20 smallant2015
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    2017-10-01 大爰

    学习了谢谢分享!!

    0

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    2017-09-30 yfjms

    学习了

    0

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CLIN CANCER RES近期发表了一篇文章,研究结直肠癌切除后循环肿瘤DNA检测是否可以鉴别高复发风险的患者以及循环肿瘤DNA检测是否可以早起发现肿瘤复发以及反映治疗效果。

CSCO 2017全体大会:呋喹替尼三线治疗结直肠癌将引起轰动:FRESCO研究首次亮相中国

长期以来,我国一/二线标准治疗失败的转移性结直肠癌患者,面临无药可选的尴尬局面。然而多数患者体力状态良好治疗意愿强烈。中国自主研发的新药呋喹替尼将填补这一空白。在即将迎来的2017年CSCO全体大会论文交流专场上,我们将会倾听到来自秦叔逵教授带来的呋喹替尼III期FRESCO研究的深度亚组数据分析,值得期待!

Int J Cancer:第二次欧洲筛查报告——欧盟成员国癌症筛查的实施和管理情况

欧洲联盟(欧盟)的癌症筛查执行情况的第二次报告于2017发表。该报告描述了欧盟的乳腺癌、宫颈癌和结直肠癌筛查的实施情况、议定书和组织(更新至2016)和覆盖范围(索引2013年)。

Oncotarget:Beclin 1和LC3可作为预测转移性结直肠癌的生物标志物

自噬是一种高度保守的代谢过程,表现为细胞对不正常的或不需要的细胞成分的“自食”。自噬在癌症转移中扮演著着重要的角色,而转移性疾病是结直肠癌导致相关死亡的主要原因。

Int J Cancer:饮酒、吸烟、体力活动及肥胖对结直肠癌生存的影响

预防结直肠癌首先要改变生活方式,比如说减少高蛋白、高脂肪、精细饮食,增加蔬菜、水果、粗粮,减少吸烟和过量饮酒,加强运动。第二,减少结直肠癌的发病,提高生存的二级预防,通过积极的宣传肠癌的临床表现,使患者积极就诊。积极开展筛查早期发现是最重要的手段,筛查是减少肿瘤提高生存最主要的手段。第三,积极治疗癌前病变。第四,积极治疗,有较佳的疗效。

JAMA SURGERY:转移性结直肠癌原发肿瘤位置与患者死亡率之间的关系

生物治疗(BT)如贝伐单抗或西妥昔单抗在转移性结直肠癌中的应用越来越广泛。有研究表明左侧或右侧原发肿瘤位置会影响患者生存及对生物治疗的反应。JAMA SURGERY近期发表了一篇文章,研究原发肿瘤位置与接受系统化疗联合贝伐单抗或西妥昔单抗的转移性结直肠癌患者死亡率之间的关系。

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