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Comparable effectiveness and immunomodulatory actions of oxaliplatin and cisplatin in electrochemotherapy of murine melanoma
Bioelectrochemistry ( IF 4.8 ) Pub Date : 2017-10-03 , DOI: 10.1016/j.bioelechem.2017.09.009
Katja Ursic , Spela Kos , Urska Kamensek , Maja Cemazar , Janez Scancar , Simon Bucek , Simona Kranjc , Barbara Staresinic , Gregor Sersa

Interest in platinum-based chemotherapeutics such as oxaliplatin (OXA) and cisplatin (CDDP) has been reinvigorated by their newly described impacts on tumor-specific immune responses. In addition to CDDP, OXA is frequently used to treat cancers. Based on the characteristics of OXA, which are similar to those of CDDP, and the presumably more pronounced immunomodulatory effect of OXA, OXA is a candidate for electrochemotherapy (ECT). We compared the effectiveness of intratumoral ECT with OXA to that of ECT with CDDP in murine B16F10 melanoma to determine the equieffective dose. Special attention was given to the elicitation of immunogenic cell death and local immune response. Based on the in vitro and in vivo results pertaining to effectiveness and drug uptake in cells and tumors, ECT with OXA is as effective as ECT with CDDP when the OXA dose is increased 1.6-fold. Exposure of melanoma cells to ECT induces immunogenic cell death when either OXA or CDDP is used, which correlates with a comparable increase in lymphocyte infiltration into tumors after ECT with either OXA or CDDP. Based on these results, OXA is a valid platinum-based drug for use with ECT, and the effectiveness of ECT with OXA is comparable to that of the well-established ECT with CDDP. Furthermore, both drugs display equal and specific immune responses following ECT.



中文翻译:

奥沙利铂和顺铂在小鼠黑色素瘤电化学治疗中的可比功效和免疫调节作用

对基于铂的化学疗法(例如奥沙利铂(OXA)和顺铂(CDDP))的兴趣已因其对肿瘤特异性免疫反应的最新描述而受到鼓舞。除CDDP外,OXA还经常用于治疗癌症。基于与CDDP相似的OXA特性,以及OXA可能更明显的免疫调节作用,OXA是电化学疗法(ECT)的候选者。我们比较了在小鼠B16F10黑色素瘤中瘤内ECT与OXA的效果与ECT与CDDP的效果,以确定等效剂量。特别注意引起免疫原性细胞死亡和局部免疫应答。基于体外体内有关细胞和肿瘤中有效性和药物吸收的结果,OXA剂量增加1.6倍时,OXA的ECT效果与CDDP的ECT效果相同。当使用OXA或CDDP时,黑素瘤细胞暴露于ECT会诱导免疫原性细胞死亡,这与使用OXA或CDDP的ECT后淋巴细胞浸润进入肿瘤的相对增加有关。基于这些结果,OXA是可与ECT一起使用的有效的铂基药物,并且OXA的ECT的有效性可与CDDP完善的ECT的有效性相媲美。此外,两种药物在ECT后均表现出相同且特异性的免疫反应。

更新日期:2017-10-03
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