论坛 › 上海 › 重大突破！中国医学科学院/北京协和医院/北京协和医学院发掘胰腺癌治疗新靶点

l14107cb 发表于 2024-6-27 09:29:37

重大突破！中国医学科学院/北京协和医院/北京协和医学院发掘胰腺癌治疗新靶点

<img src="https://mmbiz.qpic.cn/mmbiz_jpg/pHzHVM2oJO0XoHxKWAY3L5EQD3iadnALckicyQ5l2dHVEJD5DjhZ09icv1NRD2eudm5w6sZ4Y8XpgMNS7S6MYcmzA/640?wx_fmt=jpeg&amp;tp=webp&amp;wxfrom=5&amp;wx_lazy=1&amp;wx_co=1" style="width: 50%; margin-bottom: 20px;"><img src="https://mmbiz.qpic.cn/mmbiz_png/pHzHVM2oJO0j4nwztvicmUVecx5m7j7hHdGicuFLncEGhMjDbMvSRdVUyhGSdE84IMSkPGOUXMVYvkSLKtVd9p8w/640?wx_fmt=png&amp;tp=webp&amp;wxfrom=5&amp;wx_lazy=1&amp;wx_co=1" style="width: 50%; margin-bottom: 20px;">
    <p style="font-size: 16px; color: black; line-height: 40px; text-align: left; margin-bottom: 15px;">&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;本文为转化医学网原创，转载请注明出处&nbsp;</p>
    <p style="font-size: 16px; color: black; line-height: 40px; text-align: left; margin-bottom: 15px;">作者：Jerry</p>
    <p style="font-size: 16px; color: black; line-height: 40px; text-align: left; margin-bottom: 15px;"><strong style="color: blue;">导读：</strong><span style="color: black;">胰腺癌(PC)是一种高度致命的恶性肿瘤，<span style="color: black;">一般</span>表现为代谢重编程，<span style="color: black;">引起</span>治疗漏洞。</span><span style="color: black;">然而，胆固醇代谢<span style="color: black;">反常</span>对胰腺癌<span style="color: black;">生长</span>和<span style="color: black;">发展</span>的影响机制仍不清楚。</span></p>
    <p style="font-size: 16px; color: black; line-height: 40px; text-align: left; margin-bottom: 15px;"><span style="color: black;">近期</span>，中国医学科学院/北京协和医院/北京协和医学院<span style="color: black;">科研</span>人员在国际知名期刊《Cell Death&amp;Disease》上<span style="color: black;">发布</span>了题为“SQLE promotes pancreatic cancer growth by attenuating ER stress and activating lipid rafts-regulated Src/PI3K/Akt signaling pathway”的<span style="color: black;">科研</span>论文，<strong style="color: blue;">该<span style="color: black;">科研</span><span style="color: black;">发掘</span>角鲨烯环氧化酶(SQLE)是胰腺癌生长过程中胆固醇代谢的<span style="color: black;">要紧</span>调节因子。<span style="color: black;">科研</span>人员观察到SQLE在胰腺癌组织中<span style="color: black;">明显</span>上调，其高表达与<span style="color: black;">病人</span>不良预后<span style="color: black;">关联</span>。功能实验<span style="color: black;">显示</span>，SQLE在体外促进细胞增殖，诱导细胞周期<span style="color: black;">发展</span>，<span style="color: black;">控制</span>细胞凋亡，<span style="color: black;">同期</span>在<span style="color: black;">身体</span>促进肿瘤生长。从机制上讲，SQLE<span style="color: black;">拥有</span>双重<span style="color: black;">功效</span>。<span style="color: black;">明显</span>的是，SQLE抑制剂有效地<span style="color: black;">控制</span>了胰腺癌细胞的增殖和异种移植瘤的生长。总之，本<span style="color: black;">科研</span>揭示了SQLE<span style="color: black;">做为</span>一种新的癌基因，<span style="color: black;">经过</span>缓解内质网应激和激活脂筏调节的Src/PI3K/Akt信号通路来促进胰腺癌生长，突显了SQLE<span style="color: black;">做为</span>胰腺癌治疗靶点的<span style="color: black;">潜能</span>。</strong></p><img src="https://mmbiz.qpic.cn/mmbiz_jpg/pHzHVM2oJO0XoHxKWAY3L5EQD3iadnALc4ztyUlqDzpaIiadNGmBH8mIEeYZCZHQgDy7ZMEn9gJkjw3aMTT7LdVg/640?wx_fmt=jpeg&amp;tp=webp&amp;wxfrom=5&amp;wx_lazy=1&amp;wx_co=1" style="width: 50%; margin-bottom: 20px;">
    <p style="font-size: 16px; color: black; line-height: 40px; text-align: left; margin-bottom: 15px;">https://www.nature.com/articles/s41419-023-05987-7#Sec1</p>
    <p style="font-size: 16px; color: black; line-height: 40px; text-align: left; margin-bottom: 15px;"><strong style="color: blue;"><span style="color: black;">科研</span>背景</strong></p>
    <p style="font-size: 16px; color: black; line-height: 40px; text-align: left; margin-bottom: 15px;"><span style="color: black;">&nbsp;01&nbsp;</span></p>
    <p style="font-size: 16px; color: black; line-height: 40px; text-align: left; margin-bottom: 15px;"><strong style="color: blue;">胰腺癌(PC)是一种令人<span style="color: black;">非常</span>苦恼的恶性肿瘤，因死亡人数最多，被认为是<span style="color: black;">全世界</span>癌症致死的第七大<span style="color: black;">重点</span><span style="color: black;">原由</span>，在男性和女性中均如此。</strong><span style="color: black;">另外</span>，预计到2030年，它将<span style="color: black;">作为</span>美国癌症<span style="color: black;">关联</span>死亡的第二大<span style="color: black;">平常</span><span style="color: black;">原由</span>。手术切除<span style="color: black;">日前</span>是该<span style="color: black;">疾患</span>的<span style="color: black;">独一</span>治愈性治疗<span style="color: black;">办法</span>，但术后预后<span style="color: black;">不良</span>，<span style="color: black;">仅有</span>20%的<span style="color: black;">病人</span>能够存活5年以上。虽然在过去的几十年里<span style="color: black;">显现</span>了几种治疗<span style="color: black;">办法</span>，如化疗、放疗、免疫治疗和靶向治疗，但效果仍然<span style="color: black;">不睬</span>想。<span style="color: black;">因此呢</span>，探索<span style="color: black;">引起</span>胰腺癌<span style="color: black;">出现</span>和<span style="color: black;">发展</span>的分子机制，<span style="color: black;">发掘</span>新的靶点并<span style="color: black;">研发</span>有效的治疗策略势在必行。</p>
    <p style="font-size: 16px; color: black; line-height: 40px; text-align: left; margin-bottom: 15px;"><strong style="color: blue;">代谢重编程，<span style="color: black;">做为</span>癌症的一个标志，指肿瘤细胞代谢模式的改变，以适应快速增殖。</strong><span style="color: black;">近期</span>的证据<span style="color: black;">显示</span>，脂肪酸生物合成<span style="color: black;">经过</span>内质网(ER)应激促进了胰腺癌的吉西他滨耐药性。胆固醇是另一种<span style="color: black;">重要</span>的脂质<span style="color: black;">成份</span>，是哺乳动物细胞膜形成不可或缺的一部分，<span style="color: black;">能够</span>产生类固醇激素和胆汁酸。<span style="color: black;">反常</span>胆固醇代谢对肿瘤<span style="color: black;">出现</span>和癌症<span style="color: black;">发展</span><span style="color: black;">亦</span>很<span style="color: black;">要紧</span>。流行病学<span style="color: black;">科研</span><span style="color: black;">发掘</span>血清胆固醇水平<span style="color: black;">上升</span>和膳食胆固醇摄入与胰腺癌<span style="color: black;">危害</span><span style="color: black;">增多</span><span style="color: black;">相关</span>。<span style="color: black;">因此呢</span>，确定与胰腺癌胆固醇代谢<span style="color: black;">关联</span>的<span style="color: black;">重要</span>靶点值得进一步<span style="color: black;">科研</span>。</p>
    <p style="font-size: 16px; color: black; line-height: 40px; text-align: left; margin-bottom: 15px;">近年来，<span style="color: black;">海量</span>证据<span style="color: black;">显示</span>SQLE在<span style="color: black;">区别</span>癌症中的过表达，对细胞的恶性<span style="color: black;">行径</span>至关<span style="color: black;">要紧</span>。<span style="color: black;">因为</span>SQLE在胰腺癌肿瘤<span style="color: black;">出现</span>中的<span style="color: black;">功效</span>尚不<span style="color: black;">知道</span>，本<span style="color: black;">科研</span>致力于阐明SQLE在胰腺癌肿瘤<span style="color: black;">出现</span>中的分子机制。<span style="color: black;">另外</span>，该<span style="color: black;">科研</span>为靶向SQLE<span style="color: black;">做为</span>治疗胰腺癌的潜在<span style="color: black;">办法</span><span style="color: black;">供给</span>了初步证据。</p>
    <p style="font-size: 16px; color: black; line-height: 40px; text-align: left; margin-bottom: 15px;"><strong style="color: blue;"><span style="color: black;">科研</span>过程及<span style="color: black;">发掘</span></strong></p>
    <p style="font-size: 16px; color: black; line-height: 40px; text-align: left; margin-bottom: 15px;"><span style="color: black;">&nbsp;02&nbsp;</span></p>
    <p style="font-size: 16px; color: black; line-height: 40px; text-align: left; margin-bottom: 15px;"><strong style="color: blue;">在本<span style="color: black;">科研</span>中，<span style="color: black;">科研</span>人员确定SQLE是胰腺癌生长中胆固醇代谢的<span style="color: black;">重点</span>调节因子。</strong><span style="color: black;">科研</span>人员<span style="color: black;">发掘</span>，与正常组织相比，SQLE在胰腺癌组织中表达<span style="color: black;">上升</span>，并且SQLE高表达的<span style="color: black;">病人</span>总<span style="color: black;">存活</span>期较短。进一步的功能实验<span style="color: black;">显示</span>，SQLE在体外促进细胞增殖，促进细胞周期<span style="color: black;">发展</span>，<span style="color: black;">控制</span>细胞凋亡，<span style="color: black;">同期</span><span style="color: black;">加强</span><span style="color: black;">身体</span>肿瘤生长。SQLE<span style="color: black;">控制</span>剂可<span style="color: black;">做为</span>潜在的治疗<span style="color: black;">办法</span>，以抑制胰腺癌的生长。</p>
    <p style="font-size: 16px; color: black; line-height: 40px; text-align: left; margin-bottom: 15px;">近年来，多项<span style="color: black;">科研</span><span style="color: black;">显示</span>，胆固醇代谢的改变有助于调节肿瘤的<span style="color: black;">各样</span>生物学过程。<span style="color: black;">另外</span>，还<span style="color: black;">发掘</span><span style="color: black;">操作</span>胆固醇代谢<span style="color: black;">能够</span><span style="color: black;">控制</span>肿瘤生长。<span style="color: black;">科研</span><span style="color: black;">显示</span><span style="color: black;">经过</span>药理学或遗传学<span style="color: black;">控制</span>胆固醇酯化<span style="color: black;">能够</span><span style="color: black;">明显</span><span style="color: black;">控制</span>胰腺癌的生长和转移。在本<span style="color: black;">科研</span>中，<span style="color: black;">科研</span>人员<span style="color: black;">发掘</span>胰腺癌中SQLE的表达上调，且SQLE表达水平高的<span style="color: black;">病人</span><span style="color: black;">存活</span>期较短。<span style="color: black;">科研</span><span style="color: black;">显示</span>SQLE在癌症的<span style="color: black;">区别</span><span style="color: black;">周期</span><span style="color: black;">拥有</span>双重<span style="color: black;">功效</span>，<span style="color: black;">尤其</span>是在结直肠癌中，它在肿瘤<span style="color: black;">出现</span>中<span style="color: black;">拥有</span>促肿瘤功能，但在<span style="color: black;">发展</span>中<span style="color: black;">拥有</span>肿瘤<span style="color: black;">控制</span><span style="color: black;">功效</span>。</p>
    <p style="font-size: 16px; color: black; line-height: 40px; text-align: left; margin-bottom: 15px;"><strong style="color: blue;"><span style="color: black;">科研</span>人员<span style="color: black;">科研</span>了SQLE对胰腺癌细胞促生长<span style="color: black;">功效</span>的机制，<span style="color: black;">发掘</span>SQLE既能促进胰腺癌细胞增殖，又能<span style="color: black;">控制</span>胰腺癌细胞凋亡。</strong><span style="color: black;">科研</span>还<span style="color: black;">发掘</span>，GRP78-PERK-eIF2α-ATF4-CHOP轴在内质网应激途径中的激活，以及SQLE<span style="color: black;">控制</span>后<span style="color: black;">经过</span>脂滴形成诱导胰腺癌细胞死亡。这一结果与<span style="color: black;">近期</span>一项关于乳腺癌和非小细胞肺癌的<span style="color: black;">科研</span>一致。</p>
    <p style="font-size: 16px; color: black; line-height: 40px; text-align: left; margin-bottom: 15px;"><strong style="color: blue;"><span style="color: black;">科研</span>人员还对SQLE敲除和SQLE阴性对照细胞进行RNA测序分析，以<span style="color: black;">科研</span>SQLE在胰腺癌中影响的下游信号通路。</strong><span style="color: black;">另外</span>，<span style="color: black;">科研</span>人员还<span style="color: black;">创立</span>了细胞胆固醇含量变化与SQLE表达水平之间的密切<span style="color: black;">关联</span>性。<span style="color: black;">科研</span>还<span style="color: black;">发掘</span>，基于公开可用的胰腺癌数据集，SQLE和SRC表达水平之间存在正<span style="color: black;">关联</span>。</p>
    <p style="font-size: 16px; color: black; line-height: 40px; text-align: left; margin-bottom: 15px;"><strong style="color: blue;">为了<span style="color: black;">评定</span>SQLE<span style="color: black;">控制</span>剂治疗胰腺癌的有效性，<span style="color: black;">科研</span>人员<span style="color: black;">科研</span>了特比萘芬的疗效。</strong>特比萘芬是一种常用的抗真菌<span style="color: black;">药品</span>，已知对多种癌症<span style="color: black;">拥有</span>生长<span style="color: black;">控制</span><span style="color: black;">功效</span>。在本<span style="color: black;">科研</span>中，<span style="color: black;">科研</span>人员证明了特比萘芬处理<span style="color: black;">能够</span><span style="color: black;">控制</span>细胞增殖，诱导细胞周期阻滞和凋亡，延缓<span style="color: black;">身体</span>肿瘤生长，<span style="color: black;">控制</span>MAPK和Src/PI3K/Akt信号通路。<span style="color: black;">科研</span>还<span style="color: black;">发掘</span>一种特定的哺乳动物SQLE<span style="color: black;">控制</span>剂NB-598在较低剂量下对胰腺癌生长的<span style="color: black;">控制</span><span style="color: black;">功效</span>比特比萘芬更有效。这些结果<span style="color: black;">显示</span>，SQLE<span style="color: black;">控制</span>剂有<span style="color: black;">潜能</span><span style="color: black;">做为</span>一种有效的治疗策略。<span style="color: black;">另外</span>，特比萘芬与化疗<span style="color: black;">药品</span>或靶向治疗的协同抗肿瘤<span style="color: black;">功效</span>已在<span style="color: black;">各样</span>癌症类型中得到证实。</p><img src="https://mmbiz.qpic.cn/mmbiz_jpg/pHzHVM2oJO0XoHxKWAY3L5EQD3iadnALchdvmtFoic40QiabLfwSE2U8Oic1Cv4dqBrPDnlVVPPw947PO1MpPC5QLA/640?wx_fmt=jpeg&amp;tp=webp&amp;wxfrom=5&amp;wx_lazy=1&amp;wx_co=1" style="width: 50%; margin-bottom: 20px;">
    <p style="font-size: 16px; color: black; line-height: 40px; text-align: left; margin-bottom: 15px;">SQLE<span style="color: black;">控制</span>剂<span style="color: black;">控制</span>胰腺癌肿瘤生长</p>
    <p style="font-size: 16px; color: black; line-height: 40px; text-align: left; margin-bottom: 15px;"><strong style="color: blue;"><span style="color: black;">科研</span><span style="color: black;">道理</span></strong></p>
    <p style="font-size: 16px; color: black; line-height: 40px; text-align: left; margin-bottom: 15px;"><span style="color: black;">&nbsp;03&nbsp;</span></p>
    <p style="font-size: 16px; color: black; line-height: 40px; text-align: left; margin-bottom: 15px;">综上，<span style="color: black;">科研</span><span style="color: black;">显示</span>SQLE<span style="color: black;">做为</span>一种<span style="color: black;">要紧</span>的胆固醇代谢调节因子，促进了胰腺癌细胞的生长和肿瘤<span style="color: black;">出现</span>。激励人心的是，在<span style="color: black;">身体</span>外模型中<span style="color: black;">运用</span>SQLE<span style="color: black;">控制</span>剂均能<span style="color: black;">明显</span><span style="color: black;">控制</span>胰腺癌的生长，<span style="color: black;">显示</span>SQLE是一个有前途的胰腺癌治疗靶点。</p>
    <p style="font-size: 16px; color: black; line-height: 40px; text-align: left; margin-bottom: 15px;">参考资料：</p>

    <p style="font-size: 16px; color: black; line-height: 40px; text-align: left; margin-bottom: 15px;">https://www.nature.com/articles/s41419-023-05987-7#Sec1</p>
    <p style="font-size: 16px; color: black; line-height: 40px; text-align: left; margin-bottom: 15px;">注：本文旨在介绍医学<span style="color: black;">科研</span><span style="color: black;">发展</span>，<span style="color: black;">不可</span><span style="color: black;">做为</span>治疗<span style="color: black;">方法</span>参考。如需<span style="color: black;">得到</span>健康<span style="color: black;">指点</span>，请至正规医院就诊。</p>
    <img src="https://mmbiz.qpic.cn/mmbiz_png/pHzHVM2oJO0XoHxKWAY3L5EQD3iadnALc1jcTIbtRwrQDQXO1ckMll7tWZZPY4jldiaw5uFMiahIT6ibKsudZE4kmw/640?wx_fmt=png&amp;tp=webp&amp;wxfrom=5&amp;wx_lazy=1&amp;wx_co=1" style="width: 50%; margin-bottom: 20px;">
    <p style="font-size: 16px; color: black; line-height: 40px; text-align: left; margin-bottom: 15px;">热门·直播/活动</p><a style="color: black;">
      <p style="font-size: 16px; color: black; line-height: 40px; text-align: left; margin-bottom: 15px;">

听听海 发表于 2024-9-2 19:35:20

你的努力一定会被看见，相信自己，加油。

听听海 发表于 2024-9-25 15:08:35

楼主节操掉了，还不快捡起来！

nqkk58 发表于 2024-10-15 05:55:23

你的话深深触动了我，仿佛说出了我心里的声音。

1fy07h 发表于 2024-10-15 12:26:13

你的见解真是独到，让我受益匪浅。

wrjc1hod 发表于 3 天前

“NB”（牛×的缩写，表示叹为观止）‌

查看完整版本: 重大突破！中国医学科学院/北京协和医院/北京协和医学院发掘胰腺癌治疗新靶点