最新！山东大学齐鲁医院合作发帖：揭示癌症预测性生物标志物和治疗新靶点
<p style="font-size: 16px; color: black; line-height: 40px; text-align: left; margin-bottom: 15px;"><img src="//q6.itc.cn/q_70/images03/20240427/f01469c5b08a4779b32c14b9c01bc7e7.jpeg" style="width: 50%; margin-bottom: 20px;"></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;">口腔微生物群失调与慢性炎症和癌变<span style="color: black;">关联</span>，具核梭杆菌(Fusobacterium nucleatum,Fn)是口腔微生物群的<span style="color: black;">要紧</span><span style="color: black;">构成</span>部分，可扰乱免疫系统，形成炎性微环境，促进口腔鳞状细胞癌(oral squamous cell carcinoma,OSCC)的<span style="color: black;">出现</span>和<span style="color: black;">发展</span>，但其机制尚不清楚。</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>，山东大学齐鲁医院与山东大学齐鲁医学院&山东省口腔组织再生重点实验室&山东省口腔生物材料与组织再生工程<span style="color: black;">科研</span>中心&山东省口腔<span style="color: black;">疾患</span>临床医学<span style="color: black;">科研</span>中心<span style="color: black;">科研</span>团队合作在期刊《Cell Death&Disease》上<span style="color: black;">发布</span>了题为“The role of CXCL2-mediated crosstalk between tumor cells and macrophages inFusobacterium nucleatum-promoted oral squamous cell carcinoma progression”的<span style="color: black;">科研</span>论文，<strong style="color: blue;">本<span style="color: black;">科研</span><span style="color: black;">显示</span>，Fn<span style="color: black;">经过</span>促进肿瘤细胞增殖、巨噬细胞招募和M2极化，促进OSCC<span style="color: black;">发展</span>。<span style="color: black;">同期</span>，<span style="color: black;">加强</span>的CXCL2介导的OSCC细胞与巨噬细胞之间的相互<span style="color: black;">功效</span>在Fn的促癌<span style="color: black;">功效</span>中发挥着至关<span style="color: black;">要紧</span>的<span style="color: black;">功效</span>。</strong></p>
<p style="font-size: 16px; color: black; line-height: 40px; text-align: left; margin-bottom: 15px;"><img src="//q7.itc.cn/q_70/images03/20240427/e649d5a25cde455294727b42b0945bcd.jpeg" style="width: 50%; margin-bottom: 20px;"></p>
<p style="font-size: 16px; color: black; line-height: 40px; text-align: left; margin-bottom: 15px;">https://www.nature.com/articles/s41419-024-06640-7</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;">01</span></p>
<p style="font-size: 16px; color: black; line-height: 40px; text-align: left; margin-bottom: 15px;">口腔鳞状细胞癌(oral squamous cell carcinoma,OSCC)是一种<span style="color: black;">平常</span>的头颈部恶性肿瘤，发病率高，<span style="color: black;">全世界</span>每年新增病例超过30万例。<span style="color: black;">因为</span>其高侵袭和转移率，OSCC<span style="color: black;">病人</span>的5年<span style="color: black;">存活</span>率仅为50%-60%。多种危险<span style="color: black;">原因</span>已被确定，<span style="color: black;">包含</span>嚼槟榔、过度饮酒、吸烟和人乳头瘤病毒(human papillomavirus,HPV)感染。牙周病原体和其他口腔微生物群最近被认为是独立的危险<span style="color: black;">原因</span>。<span style="color: black;">有些</span>证据<span style="color: black;">显示</span>，口腔微生物群失衡在OSCC的<span style="color: black;">出现</span>、<span style="color: black;">发展</span>和预后中起着<span style="color: black;">重要</span><span style="color: black;">功效</span>，从而为OSCC<span style="color: black;">供给</span>了潜在的生物标志物。口腔微生物群可诱发慢性炎症，产生炎症介质和致癌剂，影响细胞增殖和凋亡。<span style="color: black;">另外</span>，炎症反应可吸引免疫细胞浸润口腔黏膜，调节免疫微环境。</p>
<p style="font-size: 16px; color: black; line-height: 40px; text-align: left; margin-bottom: 15px;">具核梭杆菌(Fusobacterium nucleatum,Fn)是口腔<span style="color: black;">平常</span>的共生微生物，被认为是菌斑生物膜的核心物种和慢性牙周炎的<span style="color: black;">重要</span>致病菌。这种厌氧微生物<span style="color: black;">拥有</span>侵袭性、粘附性和促炎性特性，并能与牙龈卟啉单胞菌相互<span style="color: black;">功效</span>，促进牙周炎的炎症<span style="color: black;">发展</span>。<span style="color: black;">另外</span>，Fn与OSCC密切<span style="color: black;">关联</span>，在OSCC组织中比非癌组织中丰度<span style="color: black;">明显</span><span style="color: black;">上升</span>。然而，Fn在OSCC中的病因学<span style="color: black;">相关</span><span style="color: black;">必须</span><span style="color: black;">经过</span>广泛的<span style="color: black;">科研</span>进一步验证。</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;"><span style="color: black;">科研</span><span style="color: black;">发展</span></span></strong></p>
<p style="font-size: 16px; color: black; line-height: 40px; text-align: left; margin-bottom: 15px;"><span style="color: black;">02</span></p>
<p style="font-size: 16px; color: black; line-height: 40px; text-align: left; margin-bottom: 15px;">为了<span style="color: black;">科研</span>Fn在口腔鳞癌中的潜在促瘤<span style="color: black;">功效</span>，<span style="color: black;">科研</span>人员利用C3H小鼠的SCC7细胞<span style="color: black;">创立</span>了<span style="color: black;">身体</span>皮下移植瘤模型，并<span style="color: black;">经过</span>多点注射Fn进行<span style="color: black;">干涉</span>。FISH检测证实了Fn组中Fn的存在。与对照组相比，Fn组的肿瘤重量和体积<span style="color: black;">增多</span>。流式细胞术分析肿瘤组织<span style="color: black;">表示</span>，与对照组相比，Fn组的M1型巨噬细胞减少，<span style="color: black;">伴同</span>着M2型巨噬细胞的<span style="color: black;">增多</span>。免疫组化结果<span style="color: black;">表示</span>，与对照组相比，Fn组的Ki67、CD206、CXCL2和p65表达更<span style="color: black;">明显</span>，而CD86表达更少。CD86和CD206的IF染色<span style="color: black;">表示</span>，Fn组的CD206/CD86比值<span style="color: black;">明显</span><span style="color: black;">增多</span>。IF染色<span style="color: black;">表示</span>，Fn刺激后p65向核内转移。<span style="color: black;">另外</span>，裂解肿瘤组织，并<span style="color: black;">经过</span>western blot检测p-p65、p65和CXCL2水平。这<span style="color: black;">显示</span>，Fn激活了NF-κB p65信号，并促进了肿瘤组织中CXCL2表达的上调。<strong style="color: blue;">这些<span style="color: black;">发掘</span>进一步<span style="color: black;">显示</span>，Fn促进肿瘤细胞增殖、巨噬细胞招募和M2极化。</strong></p>
<p style="font-size: 16px; color: black; line-height: 40px; text-align: left; margin-bottom: 15px;"><img src="//q2.itc.cn/q_70/images03/20240427/d6760e17e5094cc78b7ac0de8dd7d5ae.jpeg" style="width: 50%; margin-bottom: 20px;"></p>
<p style="font-size: 16px; color: black; line-height: 40px; text-align: left; margin-bottom: 15px;">Fn促进OSCC的<span style="color: black;">发展</span>，并促进小鼠<span style="color: black;">身体</span>M2型巨噬细胞的浸润</p>
<p style="font-size: 16px; color: black; line-height: 40px; text-align: left; margin-bottom: 15px;">为了进一步阐明<span style="color: black;">重要</span>调节因子CXCL2在Fn<span style="color: black;">加强</span>肿瘤生长和巨噬细胞M2极化的<span style="color: black;">功效</span>，<span style="color: black;">科研</span>人员<span style="color: black;">运用</span>了一种<span style="color: black;">选取</span>性<span style="color: black;">控制</span>剂SB225002。<span style="color: black;">科研</span><span style="color: black;">显示</span>SB225002逆转了Fn的促肿瘤<span style="color: black;">功效</span>。<span style="color: black;">另外</span>，它还抵消了Fn诱导的巨噬细胞向M2表型的极化。</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>结论</strong></p>
<p style="font-size: 16px; color: black; line-height: 40px; text-align: left; margin-bottom: 15px;"><span style="color: black;">03</span></p>
<p style="font-size: 16px; color: black; line-height: 40px; text-align: left; margin-bottom: 15px;">综上所述，本<span style="color: black;">科研</span>阐明了由Fn刺激激活的自<span style="color: black;">加强</span>CXCL2信号环路，调控OSCC细胞和巨噬细胞之间的串扰，在驱动OSCC<span style="color: black;">发展</span>中起着至关<span style="color: black;">要紧</span>的<span style="color: black;">功效</span>。<strong style="color: blue;">本<span style="color: black;">科研</span>结果为OSCC趋化因子的潜在治疗靶点和免疫动态平衡<span style="color: black;">供给</span>了新的视角。</strong></p>
<p style="font-size: 16px; color: black; line-height: 40px; text-align: left; margin-bottom: 15px;"><span style="color: black;">参考资料：</span></p>
<p style="font-size: 16px; color: black; line-height: 40px; text-align: left; margin-bottom: 15px;">https://www.nature.com/articles/s41419-024-06640-7</p>
<p style="font-size: 16px; color: black; line-height: 40px; text-align: left; margin-bottom: 15px;"><span style="color: black;">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>治疗方案参考。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。</span></p>
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