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首页> 外文期刊>Journal of drug targeting >Thermosensitive liposomal cisplatin in combination with local hyperthermia results in tumor growth delay and changes in tumor microenvironment in xenograft models of lung carcinoma
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Thermosensitive liposomal cisplatin in combination with local hyperthermia results in tumor growth delay and changes in tumor microenvironment in xenograft models of lung carcinoma

机译：热敏脂质体顺铂与局部热疗组合导致肿瘤生长延迟和肺癌异种血管模型中肿瘤微环境的变化

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摘要

Treatment efficacy of a heat-activated thermosensitive liposome formulation of cisplatin (CDDP), known as HTLC, was determined in xenograft models of non-small-cell lung carcinoma. The short-term impact of local hyperthermia (HT) on tumor morphology, microvessel density and local inflammatory response was also evaluated. The HTLC formulation in combination with local HT resulted in a significant advantage in therapeutic effect in comparison with free drug and a non-thermosensitive liposome formulation of CDDP (i.e. Lipoplatin(TM)) when administered at their maximum tolerated doses. Local HT-induced widespread cell necrosis and a significant reduction in microvessel density in the necrotic regions of tumors. CD11b-expressing innate leukocytes were demonstrated to infiltrate and reside preferentially at the necrotic rim of tumors, likely as a means to phagocytose-damaged tissue. Colocalization of CD11b with a marker of DNA damage (i.e. H2AX) revealed a small portion of CD11b-expressing leukocytes that were possibly undergoing apoptosis as a result of HT-induced damage and/or the short lifespan of leukocytes. Overall, HT-induced tissue damage (i.e. at 24-h post-treatment) alone did not result in significant improvements in treatment effect, rather, the enhancement in tumor drug availability was correlated with improved therapeutic outcomes.
机译：在非小细胞肺癌的异种移植模型中测定了顺铂（CDDP）的热活性热敏脂质体制素的治疗疗效，在非小细胞肺癌的模型中测定。还评估了局部热疗（HT）对肿瘤形态，微血管密度和局部炎症反应的短期影响。与本地HT组合的HTLC制剂在治疗效果中具有显着的优势，与游离药物和在其最大耐受剂量以其施用时CDDP（即脂蛋白（TM））的非热敏脂质体制效果。局部HT诱导的广泛细胞坏死和肿瘤坏死区域中微血管密度的显着降低。表达CD11B的天生白细胞被证明渗透并优先于肿瘤的坏死缘，可能是吞噬细胞损伤组织的手段。 CD11b与DNA损伤标志物的分致化（即H2AX）揭示了一小部分CD11B表达白细胞，其可能经历凋亡，由于HT诱导的损伤和白细胞的短寿命。总体而言，单独的HT诱导的组织损伤（即24小时后）没有导致治疗效果的显着改善，而是与肿瘤药物可用性的增强与改善的治疗结果相关。

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