Tumor-targeting Salmonella typhimurium improves cyclophosphamide chemotherapy at maximum tolerated dose and low-dose metronomic regimens in a murine melanoma model
Tumor-targeting Salmonella typhimurium improves cyclophosphamide chemotherapy at maximum tolerated dose and low-dose metronomic regimens in a murine melanoma model
复制标题
DOI：
10.1002/ijc.22688
复制
发表时间：
2007-08-01
影响因子：
6.4
通讯作者：
Hua, Zi-Chun
中科院分区：
文献类型：
--
作者：
Jia, Li-Jun;Wei, Dong-Ping;Hua, Zi-Chun
癌症的化疗在一定程度上受到药物不能作用于肿瘤血运不良或非血运区域的限制。肿瘤靶向细菌能够在这些灌注度较低的区域优先复制。一些菌株已经与化疗药物联合使用，结果令人振奋。然而，还没有系统的工作来测试细菌对临床化疗模式的影响，如标准最大耐受量(MTD)和新型低剂量节律(LDM)化疗。在这里，鼠伤寒沙门氏菌VNP20009在小鼠黑色素瘤模型中以MTD和LDM方案与环磷酰胺(CTX)联合使用。结果表明，VNP20009显著提高了所有CTX处理的效果。与单独应用VNP20009和CTX相比，VNP20009和CTX联合应用可显著降低肿瘤微血管密度和血清血管内皮生长因子(VEGF)水平。此外，与单独进行细菌治疗相比，联合治疗显著增加了肿瘤内的细菌数量。这些发现表明，肿瘤靶向细菌与标准MTD和LDM方案的CTX联合使用，可能对黑色素瘤的治疗具有临床价值。(C)2007年Wiley-Liss，Inc.
Chemotherapy for cancer is partly limited by the inability of drugs to act on poorly vascularized or avascularized areas of tumors. Tumor-targeting bacteria are capable of preferentially replicating in these poorly perfused regions. Some strains have been combined with chemotherapeutic agents and the results have been promising. However, no systematic work has been carried out to test the effect of bacteria on clinical modes of chemotherapy, such as standard maximum tolerated dose (MTD) and novel low-dose metronomic (LDM) chemotherapy. Here Salmonella typhimutium VNP20009 was combined with cyclophosphamide (CTX) at both MTD and LDM schedules in a murine melanoma model. The results showed that VNP20009 significantly improved the effects of all forms of CTX treatments. The combination of VNP20009 and CTX led to a more significant decrease in tumor microvessel density and serum vascular endothelial growth factor (VEGF) level, compared with either treatment alone. Furthermore, combination therapy remarkably increased the number of bacteria within tumors when compared with bacteria treatment alone. These findings suggest that tumor-targeting bacteria, in conjunction with CTX at standard MTD and LDM regimens, might be of clinical value for the treatment of melanoma. (c) 2007 Wiley-Liss, Inc.