结合凝和MSC,提供可溶性TRAIL,以向胰腺腺癌及其流体
Giulia Grisendi1, Massimiliano Dall'Ora2, Giulia Casari3
1Laboratory of Cellular Therapy, Department of Medical and Surgical Sciences, University of Modena and Reggio Emilia (UNIMORE), Modena, Italy.
Cell reports. Medicine
|August 21, 2024
概括
这项研究表明,将凝胺化疗与分泌sTRAIL的修饰干细胞结合起来,可以有效地向胰腺癌细胞及其支持性纤维细胞. 这种方法在临床前模型中减少了瘤生长和转移.
科学领域:
- 在瘤学瘤学.
- 癌症生物学 癌症生物学
- 干细胞疗法是一种干细胞疗法.
背景情况:
- 胰腺管道腺癌 (PDAC) 呈现较差的治疗反应,部分归因于与癌症相关的纤维细胞 (CAF).
- 针对癌细胞和瘤微环境对于有效的PDAC治疗至关重要.
研究的目的:
- 为了研究结合基因改造的介质细胞/干细胞 (MSCs) 分泌可溶性 TRAIL (sTRAIL MSCs) 对 PDAC 和 CAF 的协同作用.
- 在胰腺癌的临床前模型中评估这种组合疗法.
主要方法:
- 使用了2D和3D细胞培养模型以及小鼠的正管异种移植模型.
- 作为组合疗法,服用吉姆西塔 (GEM) 和sTRAIL分泌的MSCs (sTRAIL MSCs).
- 评估了瘤细胞存活率,瘤结构,转移和CAF特征.
主要成果:
- 组合疗法在体外和体内显著降低了PDAC细胞存活率.
- 在异种移植模型中观察到瘤结构的破坏,癌细胞标记物的减少 (CK7,CK8/18),以及脏转移的减少.
- 证明了对CAFs的细胞毒性作用,改变了它们的转录组,并减少了脱.
结论:
- 将GEM与sTRAIL MSC结合起来,显示出对PDAC的有希望的治疗策略.
- 这种方法有效地准胰腺癌的瘤和脑膜两部分.
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