9q13nh 发表于 2024-6-27 09:12:35

“靶向药”联合“化疗”！中山大学再发帖：揭示癌症治疗新选取


    <p style="font-size: 16px; color: black; line-height: 40px; text-align: left; margin-bottom: 15px;"><img src="https://q5.itc.cn/q_70/images03/20240405/927f012db9ae470ea2df2e8d17c0e143.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;">晚期鼻咽癌(NPC)<span style="color: black;">病人</span>的<span style="color: black;">存活</span>率不高，化疗效果有限，靶向<span style="color: black;">药品</span>匮乏是NPC治疗的<span style="color: black;">重点</span>挑战，迫切<span style="color: black;">必须</span>寻找新的治疗<span style="color: black;">办法</span>。</span></p>
    <p style="font-size: 16px; color: black; line-height: 40px; text-align: left; margin-bottom: 15px;">3月30日，中山大学<span style="color: black;">科研</span>团队在期刊《Cell Death&amp;Disease》上<span style="color: black;">发布</span>了<span style="color: black;">科研</span>论文，题为“PQR309, a dual PI3K/mTOR inhibitor, synergizes with gemcitabine by impairing the GSK-3β and STAT3/HSP60 signaling pathways to treat nasopharyngeal carcinoma”。本<span style="color: black;">科研</span>中，<span style="color: black;">科研</span>人员探讨了双重PI3K/mTOR<span style="color: black;">控制</span>剂PQR309<span style="color: black;">是不是</span><span style="color: black;">拥有</span>良好的抗肿瘤<span style="color: black;">功效</span>，并使鼻咽癌对吉西他滨的反应<span style="color: black;">敏锐</span>。<strong style="color: blue;"><span style="color: black;">科研</span>人员<span style="color: black;">发掘</span>以PQR309为靶点,应用PI3K/mTOR<span style="color: black;">做为</span>治疗<span style="color: black;">方法</span>，可<span style="color: black;">表率</span>一种促进鼻咽癌对吉西他滨应答的治疗<span style="color: black;">选取</span>。这为鼻咽癌靶向<span style="color: black;">药品</span>联合化疗的<span style="color: black;">科研</span><span style="color: black;">供给</span>了理论<span style="color: black;">基本</span>。</strong></p>
    <p style="font-size: 16px; color: black; line-height: 40px; text-align: left; margin-bottom: 15px;"><img src="//q3.itc.cn/q_70/images03/20240405/773547caf190424eb9bb1eafc86add08.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/s41419-024-06615-8#Sec10</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;">鼻咽癌(NPC)<span style="color: black;">重点</span><span style="color: black;">出现</span>在东亚和东南亚地区，约10%的NPC<span style="color: black;">病人</span>在初诊时已<span style="color: black;">发展</span>至中晚期，<span style="color: black;">引起</span>总<span style="color: black;">存活</span>期(OS)仅为20个月。<span style="color: black;">日前</span>，基于<span style="color: black;">科研</span>，吉西他滨联合铂类<span style="color: black;">方法</span>已被确立为复发或转移性鼻咽癌(RM-NPC)的规范治疗。虽然晚期NPC<span style="color: black;">病人</span>最初对化疗有反应，但耐药性总会<span style="color: black;">显现</span>。近年来，靶向治疗<span style="color: black;">极重</span>地<span style="color: black;">加强</span>了恶性肿瘤<span style="color: black;">病人</span>的治疗效果。然而，美国国家综合癌症网络(NCCN)手册仅<span style="color: black;">意见</span><span style="color: black;">运用</span>表皮生长因子受体靶向<span style="color: black;">控制</span>剂治疗晚期NPC。<span style="color: black;">因此呢</span>，<span style="color: black;">必须</span>针对RM-NPC<span style="color: black;">病人</span>采用新的疗效良好的治疗策略。</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;">评定</span><span style="color: black;">药品</span>组合的<span style="color: black;">身体</span>活性，<span style="color: black;">科研</span>人员将带有CNE1或HNE1皮下异种移植物的BALB/c小鼠分配到四组接受PQR309和/或吉西他滨。<span style="color: black;">科研</span>人员<span style="color: black;">发掘</span>单独<span style="color: black;">运用</span>吉西他滨或PQR309治疗可中度<span style="color: black;">控制</span>皮下肿瘤生长，而与单一治疗相比，PQR309和吉西他滨联合治疗可<span style="color: black;">控制</span>肿瘤生长。<span style="color: black;">科研</span>人员还观察到<span style="color: black;">药品</span>组合治疗对异种移植物生长的高度<span style="color: black;">明显</span><span style="color: black;">控制</span>。在实验过程中，<span style="color: black;">按照</span>苏木精和伊红(H&amp;E)染色，小鼠的内部器官未<span style="color: black;">表示</span><span style="color: black;">显著</span>的病理变化。<span style="color: black;">科研</span>人员进一步比较了PQR309或BYL719与吉西他滨或单独<span style="color: black;">运用</span>时的疗效和毒性。荷瘤小鼠分别接受PQR309、BYL719和吉西他滨单独或联合治疗。与对照组治疗的小鼠相比，单独<span style="color: black;">运用</span>PQR309、BYL719或吉西他滨治疗的小鼠的肿瘤生长得到了有效<span style="color: black;">控制</span>。然而，PQR309和吉西他滨联合治疗<span style="color: black;">引起</span>了最佳的肿瘤消退，优于对照组和单一治疗。<span style="color: black;">要紧</span>的是，<span style="color: black;">没</span>论吉西他滨与PQR309或BYL719联合<span style="color: black;">运用</span>，联合治疗的耐受性良好，这证明了在<span style="color: black;">各样</span>治疗下所有小鼠的体重<span style="color: black;">无</span><span style="color: black;">显著</span>变化。<strong style="color: blue;">数据<span style="color: black;">显示</span>，泛PI3K<span style="color: black;">控制</span>剂PQR309<span style="color: black;">没</span>论是单药治疗还是与吉西他滨联合<span style="color: black;">运用</span>，都<span style="color: black;">能够</span>优化抗肿瘤疗效，而不会<span style="color: black;">引起</span><span style="color: black;">身体</span>毒性<span style="color: black;">增多</span>。</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/images03/20240405/498b63a1bc4a4347afd225f085ec421b.jpeg" style="width: 50%; margin-bottom: 20px;"></p>
    <p style="font-size: 16px; color: black; line-height: 40px; text-align: left; margin-bottom: 15px;">吉西他滨和PQR309在<span style="color: black;">身体</span><span style="color: black;">控制</span>鼻咽癌生长</p>
    <p style="font-size: 16px; color: black; line-height: 40px; text-align: left; margin-bottom: 15px;"><span style="color: black;">另外</span>，p-STAT3、HSP60、p-GSK-3β和Ki67(增殖标志物)阳性细胞百分比在PQR309或吉西他滨治疗下均有所下降，且在联合治疗后进一步下降。蛋白质印迹<span style="color: black;">表示</span>，与对照组和单药治疗组相比，PQR309联合吉西他滨组的cleaved-caspase-3和capase-9水平<span style="color: black;">上升</span>。<span style="color: black;">另一</span>，<span style="color: black;">按照</span>蛋白质印迹分析，PQR309和吉西他滨联合治疗降低了异种移植瘤组织中的p-STAT3、HSP60、p-GSK-3β蛋白水平。<strong style="color: blue;">综上所述，PQR309和吉西他滨联合治疗<span style="color: black;">能够</span>协同<span style="color: black;">控制</span>裸鼠鼻咽癌肿瘤的生长，减少增殖，并诱导细胞凋亡。</strong></p>
    <p style="font-size: 16px; color: black; line-height: 40px; text-align: left; margin-bottom: 15px;"><strong style="color: blue;">为了探索联合治疗中观察到的协同抗肿瘤效应的潜在机制，<span style="color: black;">科研</span>人员还初步<span style="color: black;">评定</span>了其对PI3K/mTOR通路的影响。</strong>这些数据<span style="color: black;">显示</span>，PI3K/mTOR通路可能不参与PQR309和吉西他滨介导的协同抗肿瘤机制。总体而言，结果<span style="color: black;">显示</span>，PQR309和吉西他滨联合应用<span style="color: black;">经过</span>调节GSK-3β、p-STAT3/HSP60轴发挥协同抗NPC活性。</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，本文<span style="color: black;">报告</span>了PQR309，一种双重PI3K/mTOR<span style="color: black;">控制</span>剂，<span style="color: black;">控制</span>了NPC细胞的迁移和侵袭能力，并诱导其凋亡。<span style="color: black;">科研</span>结果<span style="color: black;">显示</span>，PQR309<span style="color: black;">明显</span><span style="color: black;">加强</span>了吉西他滨对NPC的<span style="color: black;">身体</span>外抗侵袭和抗生长活性。<span style="color: black;">另外</span>，PQR309<span style="color: black;">经过</span><span style="color: black;">增多</span>半胱氨酸蛋白酶依赖途径的凋亡，阻断GSK-3β和STAT3/HSP60信号通路，并<span style="color: black;">控制</span>EMT，使NPC对吉西他滨<span style="color: black;">敏锐</span>。这些结果<span style="color: black;">显示</span>，PQR309与吉西他滨<span style="color: black;">拥有</span>协同抗NPC活性，为NPC<span style="color: black;">病人</span><span style="color: black;">供给</span>了一种潜在的治疗<span style="color: black;">选取</span>。这些结果还为后续靶向<span style="color: black;">药品</span>PQR309联合其他化疗<span style="color: black;">药品</span>治疗NPC的转化临床<span style="color: black;">科研</span><span style="color: black;">供给</span>了理论<span style="color: black;">基本</span>。</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/s41419-024-06615-8#Sec10</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<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。</span></p>
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youxijiasuqi 发表于 2024-8-22 17:06:55

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4zhvml8 发表于 2024-10-8 04:40:47

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