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表达单纯疱疹病毒胸苷激酶的间充质干细胞对宫颈癌模型具有抑制作用。

HSV-TK Expressing Mesenchymal Stem Cells Exert Inhibitory Effect on Cervical Cancer Model.

作者信息

Kenarkoohi Azra, Bamdad Taravat, Soleimani Masoud, Soleimanjahi Hoorieh, Fallah Ali, Falahi Shahab

机构信息

Department of Virology, Faculty of Medical Sciences, Tarbiat Modares University, Tehran, Iran.

Department of Microbiology, Faculty of Medicine, Ilam University of Medical Sciences, Ilam, Iran.

出版信息

Int J Mol Cell Med. 2020 Spring;9(2):146-154. doi: 10.22088/IJMCM.BUMS.9.2.146. Epub 2020 Aug 10.

Abstract

A growing area of research is focused on cancer therapy, and new therapeutic approaches are welcomed. Mesenchymal stem cell (MSC)-based gene therapy is a promising strategy in oncology. Intrinsic tropism and migration to tumor microenvironment with off lights are attractive features of this type of cell carrier. In this way, suicide genes have also found a good platform for better performance and have shown a stronger anti-tumor mechanism by riding on mesenchymal cells. In this study, we investigated the anti-tumor activity of intratumoral injected MSCs transduced with a lentivector expressing the HSV/TK in a mouse cervical cancer model. Following the injection of MSCs transduced with lentivector carrying TK, MSCs alone or PBS into the mice tumor, ganciclovir was administered intraperitoneally during 14 days, and tumor size, survival time, natural killer (NK) cells and cytotoxic T lymphocyte (CTL) activities were assessed. We demonstrated that combination of suicide therapy and cell therapy leading m,to successful tumor inhibition. Significant reduction in tumor size was detected in test group in comparison with controls. Also, potent antitumor NK and CTL activity was seen in treatment group in comparison with controls. Our data demonstrated that the mesenchymal cells expressing TK had inhibitory effect on cervical cancer model.

摘要

一个不断发展的研究领域聚焦于癌症治疗,新的治疗方法受到欢迎。基于间充质干细胞(MSC)的基因治疗是肿瘤学中一种有前景的策略。这种类型的细胞载体具有内在的嗜性以及向肿瘤微环境迁移的特性,这很有吸引力。通过这种方式,自杀基因也找到了一个能更好发挥作用的良好平台,并且通过搭载在间充质细胞上展现出更强的抗肿瘤机制。在本研究中,我们在小鼠宫颈癌模型中研究了经慢病毒载体转导表达单纯疱疹病毒胸苷激酶(HSV/TK)的肿瘤内注射间充质干细胞的抗肿瘤活性。在向小鼠肿瘤内注射携带胸苷激酶的慢病毒载体转导的间充质干细胞、单纯间充质干细胞或磷酸盐缓冲液(PBS)后,连续14天腹腔注射更昔洛韦,并评估肿瘤大小、生存时间、自然杀伤(NK)细胞和细胞毒性T淋巴细胞(CTL)活性。我们证明自杀疗法和细胞疗法的联合导致成功的肿瘤抑制。与对照组相比,试验组检测到肿瘤大小显著减小。此外,与对照组相比,治疗组观察到强大的抗肿瘤NK和CTL活性。我们的数据表明,表达胸苷激酶的间充质细胞对宫颈癌模型具有抑制作用。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/2f35/7489112/382ada8fc23a/ijmcm-9-146-g001.jpg

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