目的:胶质瘤是一种高侵袭性肿瘤,经常分布在大脑的重要区域,这使得其手术切除极其困难;同时辅助治疗仍然相当无效。
方法:在当前报告中,已经在U87人胶质母细胞瘤模型上进行了一种新的治疗恶性肿瘤的治疗方法.这种方法,称为“卡拉纳汉”,旨在根除癌症干细胞(CSC),最近被证明能够内化细胞外双链DNA的片段。在被内在化之后,这些片段干扰修复由暴露于适当的细胞抑制剂引起的链间交联的过程,并且这种干扰导致CSC的消除或导致其致瘤能力的丧失。该方法的实施需要定期施用细胞抑制剂和复杂的复合双链DNA制剂。
结果:根据Karanahan方法在体外处理的U87细胞完全丧失了它们的致瘤性,并且在脑内移植到免疫缺陷小鼠中时没有产生移植物。在具有发达皮下移植物的SCID小鼠中,治疗后肿瘤生长速度明显减慢(P<0.05)。在脑内移植U87细胞的实验中,然后手术切除发育的移植物并随后进行治疗,Karanahan方法被证明可以可靠地减缓肿瘤生长速度,并使小鼠的中位生存期相对于对照组增加两倍.
结论:Karanahan方法在体外和体内治疗发育的皮下移植物以及手术切除肿瘤后的原位移植物方面的有效性已得到证明。
OBJECTIVE: Glioma is a highly invasive tumor, frequently disposed in essential areas of the brain, which makes its surgical excision extremely difficult; meanwhile adjuvant therapy remains quite ineffective.
METHODS: In the current report, a new therapeutic approach in curing malignant neoplasms has been performed on the U87 human glioblastoma model. This approach, termed \"Karanahan\", is aimed at the eradication of cancer stem cells (CSCs), which were recently shown to be capable of internalizing fragments of extracellular double-stranded DNA. After being internalized, these fragments interfere in the process of repairing interstrand cross-links caused by exposure to appropriate cytostatics, and such an interference results either in elimination of CSCs or in the loss of their tumorigenic potency. Implementation of the approach requires a scheduled administration of cytostatic and complex composite double-stranded DNA preparation.
RESULTS: U87 cells treated in vitro in accordance with the Karanahan approach completely lost their tumorigenicity and produced no grafts upon intracerebral transplantation into immunodeficient mice. In SCID mice with developed subcutaneous grafts, the treatment resulted in reliable slowing down of tumor growth rate (P < 0.05). In the experiment with intracerebral transplantation of U87 cells followed by surgical excision of the developed graft and subsequent therapeutic treatment, the Karanahan approach was shown to reliably slow down the tumor growth rate and increase the median survival of the mice twofold relative to the control.
CONCLUSIONS: The effectiveness of the Karanahan approach has been demonstrated both in vitro and in vivo in treating developed subcutaneous grafts as well as orthotopic grafts after surgical excision of the tumor.