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腾讯登录新型化合物结合放疗可保护正常细胞且靶向杀灭癌细胞
| 导读 | 近些年来尽管放射疗法已经变得非常先进，但是当肿瘤细胞扩散到周围组织后，如何进行足够剂量的放疗依然是一大挑战；近日，刊登在国际杂志Molecular Cancer Therapeutics上的一篇研究报道中，来自托马斯杰斐逊大学的研究人员开发了一种新型抗癌药物，其或许可以通过保护正常细胞免于放疗影响来标记癌症扩散的组织，相关研究或为有效治疗辐射引发的意外暴露伤害提供帮助。 |
近些年来尽管放射疗法已经变得非常先进，但是当肿瘤细胞扩散到周围组织后，如何进行足够剂量的放疗依然是一大挑战；近日，刊登在国际杂志Molecular Cancer Therapeutics上的一篇研究报道中，来自托马斯杰斐逊大学的研究人员开发了一种新型抗癌药物，其或许可以通过保护正常细胞免于放疗影响来标记癌症扩散的组织，相关研究或为有效治疗辐射引发的意外暴露伤害提供帮助。
Ulrich Rodeck博士表示，这种新型药物可以保护正常细胞和组织免于辐射伤害，而且还具有抗癌特性，可以潜在增加放疗的治疗效应。早期研究中，研究人员检测了5种化合物抵御辐射保护的效应；这项研究中，科学家们在放射疗法前一天给予小鼠5种化合物的一种，同时在放射疗法后数天再继续给予小鼠这种化合物，结果显示，一种名为RTA408的化合物表现出了较强的免辐射保护效应，而且其同FDA批准的药物氨磷汀的治疗保护效应相当。
利用生长小鼠机体中的前列腺癌细胞进行研究，研究者们表示，RTA408并不会赋予癌细胞免于辐射的保护效应，实际上当RTA408在未放疗下单独给予小鼠时，其也会减缓人类胰腺癌移植小鼠机体中肿瘤的生长，当RTA408结合放疗后就可以明显放大辐射对肿瘤生长的抑制效应。
研究者Rodeck说道，相比单独使用其中一种单一疗法，将RTA408同放疗结合将可以有效抑制肿瘤的生长；研究人员计划继续揭开放疗保护效应背后的分子机制，目的在于理解化合物RTA408的工作机理以及其如何更好地应用于临床中。（转化医学网360zhyx.com）
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Radiation Protection of the Gastrointestinal Tract and Growth Inhibition of Prostate Cancer Xenografts by a Single Compound
Molecular Cancer Therapeutics doi: 10.1158/1535-7163.MCT-14-0354
Vitali Alexeev1, Elizabeth Lash1, April Aguillard1, Laura Corsini1, Avi Bitterman1, Keith Ward2, Adam P. Dicker3, Alban Linnenbach1, and Ulrich Rodeck1,3,*
Normal tissue toxicity markedly reduces the therapeutic index of genotoxic anticancer agents, including ionizing radiation. Countermeasures against tissue damage caused by radiation are limited by their potential to also protect malignant cells and tissues. Here, we tested a panel of signal transduction modifiers for selective radioprotection of normal but not tumor tissues. These included three inhibitors of GSK3 (LiCl, SB216763, and SB415286) and two inhibitors of NF-κB (ethyl pyruvate and RTA 408). Among these, the thiol-reactive triterpenoid RTA 408 emerged as a robust and effective protector of multiple organ systems (gastrointestinal, skin, and hemopoietic) against lethal doses of radiation. RTA 408 preserved survival and proliferation of intestinal crypt cells in lethally irradiated mice while reducing apoptosis incidence in crypts and villi. In contrast, RTA 408 uniformly inhibited growth of established CWR22Rv1, LNCaP/C4-2B, PC3, and DU145 xenografts either alone or combined with radiation. Antitumor effects in vivo were associated with reduced proliferation and intratumoral apoptosis and with inhibition of NF-κB–dependent transcription in PC3 cells. Selective protection of normal tissue compartments by RTA 408 critically depended on tissue context and could not be replicated in vitro. Collectively, these data highlight the potential of RTA 408 as a cytoprotective agent that may be safely used in chemoradiation approaches.
Molecular Cancer Therapeutics doi: 10.1158/1535-7163.MCT-14-0354
Vitali Alexeev1, Elizabeth Lash1, April Aguillard1, Laura Corsini1, Avi Bitterman1, Keith Ward2, Adam P. Dicker3, Alban Linnenbach1, and Ulrich Rodeck1,3,*
Normal tissue toxicity markedly reduces the therapeutic index of genotoxic anticancer agents, including ionizing radiation. Countermeasures against tissue damage caused by radiation are limited by their potential to also protect malignant cells and tissues. Here, we tested a panel of signal transduction modifiers for selective radioprotection of normal but not tumor tissues. These included three inhibitors of GSK3 (LiCl, SB216763, and SB415286) and two inhibitors of NF-κB (ethyl pyruvate and RTA 408). Among these, the thiol-reactive triterpenoid RTA 408 emerged as a robust and effective protector of multiple organ systems (gastrointestinal, skin, and hemopoietic) against lethal doses of radiation. RTA 408 preserved survival and proliferation of intestinal crypt cells in lethally irradiated mice while reducing apoptosis incidence in crypts and villi. In contrast, RTA 408 uniformly inhibited growth of established CWR22Rv1, LNCaP/C4-2B, PC3, and DU145 xenografts either alone or combined with radiation. Antitumor effects in vivo were associated with reduced proliferation and intratumoral apoptosis and with inhibition of NF-κB–dependent transcription in PC3 cells. Selective protection of normal tissue compartments by RTA 408 critically depended on tissue context and could not be replicated in vitro. Collectively, these data highlight the potential of RTA 408 as a cytoprotective agent that may be safely used in chemoradiation approaches.
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