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病例报告:单纯疱疹病毒胸苷激酶基因介导的基于干细胞的自杀基因疗法可降低多灶性胶质母细胞瘤的肿瘤进展。

Case report: Stem cell-based suicide gene therapy mediated by the herpes simplex virus thymidine kinase gene reduces tumor progression in multifocal glioblastoma.

作者信息

Oraee-Yazdani Saeed, Akhlaghpasand Mohammadhosein, Rostami Fatemeh, Golmohammadi Maryam, Tavanaei Roozbeh, Shokri Gelareh, Hafizi Maryam, Oraee-Yazdani Maryam, Zali Ali-Reza, Soleimani Masoud

机构信息

Functional Neurosurgery Research Center, Shohada Tajrish Comprehensive Neurosurgical Center of Excellence, Shahid Beheshti University of Medical Sciences, Tehran, Iran.

Science and Research Branch, Islamic Azad University, Tehran, Iran.

出版信息

Front Neurol. 2023 Mar 22;14:1060180. doi: 10.3389/fneur.2023.1060180. eCollection 2023.

DOI:10.3389/fneur.2023.1060180
PMID:37034076
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC10075310/
Abstract

INTRODUCTION

The prognosis for glioblastoma multiforme (GBM), a malignant brain tumor, is poor despite recent advancements in treatments. Suicide gene therapy is a therapeutic strategy for cancer that requires a gene to encode a prodrug-activating enzyme which is then transduced into a vector, such as mesenchymal stem cells (MSCs). The vector is then injected into the tumor tissue and exerts its antitumor effects.

CASE PRESENTATION

A 37-year-old man presented to our department with two evident foci of glioblastoma multiforme at the left frontal and left parietal lobes. The patient received an injection of bone marrow-derived MSCs delivering the herpes simplex virus thymidine kinase (HSV-tk) gene to the frontal focus of the tumor, followed by ganciclovir administration as a prodrug for 14 days. For follow-up, the patient was periodically assessed using magnetic resonance imaging (MRI). The growth and recurrence patterns of the foci were assessed. After the injection on 09 February 2019, the patient's follow-up appointment on 19 December 2019 MRI revealed a recurrence of parietal focus. However, the frontal focus had a slight and unremarkable enhancement. On the last follow-up (18 March 2020), the left frontal focus had no prominent recurrence; however, the size of the left parietal focus increased and extended to the contralateral hemisphere through the corpus callosum. Eventually, the patient passed away on 16 July 2020 (progression-free survival (PFS) = 293 days, overall survival (OS) = 513 days).

CONCLUSION

The gliomatous focus (frontal) treated with bone marrow-derived MSCs carrying the HSV-TK gene had a different pattern of growth and recurrence compared with the non-treated one (parietal).

TRIAL REGISTRATION

IRCT20200502047277N2. Registered 10 May 2020-Retrospectively registered, https://eng.irct.ir/trial/48110.

摘要

引言

多形性胶质母细胞瘤(GBM)是一种恶性脑肿瘤,尽管近年来治疗取得了进展,但其预后仍然很差。自杀基因疗法是一种癌症治疗策略,需要一个基因来编码一种前药激活酶,然后将其转导到载体中,如间充质干细胞(MSCs)。然后将载体注入肿瘤组织并发挥其抗肿瘤作用。

病例介绍

一名37岁男性因左额叶和左顶叶有两个明显的多形性胶质母细胞瘤病灶前来我院就诊。患者接受了向肿瘤额叶病灶注射携带单纯疱疹病毒胸苷激酶(HSV-tk)基因的骨髓源性间充质干细胞,随后给予更昔洛韦作为前药治疗14天。为了进行随访,定期使用磁共振成像(MRI)对患者进行评估。评估病灶的生长和复发模式。2019年2月9日注射后,患者在2019年12月19日的MRI随访检查显示顶叶病灶复发。然而,额叶病灶有轻微且不明显的强化。在最后一次随访(2020年3月18日)时,左额叶病灶没有明显复发;然而,左顶叶病灶的大小增加并通过胼胝体扩展到对侧半球。最终,患者于2020年7月16日去世(无进展生存期(PFS)=293天,总生存期(OS)=513天)。

结论

与未治疗的病灶(顶叶)相比,用携带HSV-TK基因的骨髓源性间充质干细胞治疗的胶质瘤病灶(额叶)具有不同的生长和复发模式。

试验注册

IRCT20200502047277N2。2020年5月10日注册 - 追溯注册,https://eng.irct.ir/trial/48110。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/fe55/10075310/c5f17c53bc17/fneur-14-1060180-g0005.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/fe55/10075310/4ce46b513624/fneur-14-1060180-g0001.jpg
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https://cdn.ncbi.nlm.nih.gov/pmc/blobs/fe55/10075310/4ce46b513624/fneur-14-1060180-g0001.jpg
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