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MRI 监测经导管动脉递送 NK 细胞联合全身给予索拉非尼治疗 HCC

英文原题:MRI monitoring of combined therapy with transcatheter arterial delivery of NK cells and systemic administration of sorafenib for the treatment of HCC.

查看英文原题

MRI monitoring of combined therapy with transcatheter arterial delivery of NK cells and systemic administration of sorafenib for the treatment of HCC.

PubMed 2024/05/15(内容时间) Am J Cancer Res Q2 · IF 3.1(JCR 2025)

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中文摘要

这项临床前研究在大鼠模型中探索索拉非尼联合 NK 细胞化学免疫疗法治疗肝细胞癌(HCC)的协同潜力。研究旨在通过补充 IL-12/18 细胞因子增强 NK 细胞细胞毒性,并阐明协同抗肿瘤作用的潜在分子机制。将 24 只 Sprague-Dawley 大鼠分为不同治疗组,通过灌胃给予索拉非尼,并经肝固有动脉置管给予 NK 细胞。每周采用 MRI 扫描监测肿瘤生长和治疗反应,扫描序列包括 T1 加权、T2 加权、动态对比增强(DCE)和弥散加权成像(DWI)。通过组织学检查评估肿瘤细胞存活、凋亡比例和微血管密度。联合治疗较任一单独治疗均显著抑制肿瘤生长和血管生成,并诱导持久抗肿瘤免疫。DCE-MRI 和 DWI 显示肿瘤微血管发生明显变化,凸显联合疗法的有效性。研究结果显示,索拉非尼增强的 NK 细胞化学免疫疗法有望成为 HCC 治疗策略。靶向递送并补充 IL-12/18 细胞因子可有效增强 NK 细胞在肿瘤微环境中的细胞毒性,从而改善抗肿瘤反应。仍需开展临床试验,以在人类患者中验证这些发现并探索该方法的转化潜力。

展开英文摘要原文

This preclinical study explored the synergistic potential of sorafenib and NK cell chemoimmunotherapy to combat hepatocellular carcinoma (HCC) in a rat model.

We aimed to enhance NK cell cytotoxicity through IL-12/18 cytokines supplementation and elucidate the underlying molecular mechanisms driving this collaborative antitumor action. Twenty-four Sprague-Dawley rats were divided into distinct treatment groups, receiving sorafenib via gavage and NK cells via catheterization of the proper hepatic artery. Tumor growth and treatment response were monitored through weekly MRI scans, including T1w, T2w, DCE, and DWI sequences.

Histological examinations assessed tumor cell viability, apoptosis fraction, and microvessel density. The combined therapy demonstrated significant inhibition of tumor growth, angiogenesis, and induction of durable antitumor immunity compared to either modality alone. DCE-MRI and DWI revealed distinct alterations in tumor microvasculature, highlighting the effectiveness of the combination.

Our findings highlight the promise of sorafenib-augmented NK cell chemoimmunotherapy as a potential therapeutic strategy for HCC management. The targeted delivery of IL-12/18 cytokines supplemented NK cells effectively enhanced cytotoxicity within the tumor microenvironment, leading to improved antitumor responses.

Further investigation in clinical trials is warranted to validate these findings in human patients and explore the translational potential of this approach.

论文信息

作者
Zhang Z、Yu G、Eresen A、Hou Q、Yaghmai V、Zhang Z
单位
Department of Radiological Sciences, University of California Irvine Irvine, CA, USA.United States
期刊
American journal of cancer research2024
原文标识
PubMed 38859849 · DOI 10.62347/IARO1564