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通过磁共振成像和质子磁共振波谱评估重组腺病毒介导单纯疱疹病毒胸苷激酶基因转移后更昔洛韦对实验性颅内胶质瘤的毒性。

Assessment of ganciclovir toxicity to experimental intracranial gliomas following recombinant adenoviral-mediated transfer of the herpes simplex virus thymidine kinase gene by magnetic resonance imaging and proton magnetic resonance spectroscopy.

作者信息

Ross B D, Kim B, Davidson B L

机构信息

Departments of Radiology, Biological Chemistry, and Internal Medicine, University of Michigan, Ann Arbor, Michigan 48109-0553, USA.

出版信息

Clin Cancer Res. 1995 Jun;1(6):651-7.

PMID:9816028
Abstract

Magnetic resonance imaging and in vivo localized H magnetic resonance spectroscopy were used to evaluate a gene therapy approach for treating experimental brain tumors. This approach involved the use of an adenoviral vector to transfer the herpes simplex virus thymidine kinase (HSVtk) gene into intracerebral 9L gliosarcomas in rats followed by systemic administration of the antiherpetic agent ganciclovir. Magnetic resonance imaging quantitation of changes in intracranial 9L tumor doubling times revealed a significant variation in therapeutic response. Localized H magnetic resonance spectra of 9L tumors treated with Ad.RSVtk/ganciclovir revealed a dramatic increase in the resonance intensity at 0.9-1.3 ppm, corresponding to mobile lipids and/or lactate. Changes in intracranial tumor doubling times correlated with changes in H tumor magnetic resonance spectra, suggesting that specific changes in tumor metabolite levels may be predictive of the effectiveness of this gene therapy approach.

摘要

磁共振成像和体内局部氢磁共振波谱被用于评估一种治疗实验性脑肿瘤的基因治疗方法。该方法包括使用腺病毒载体将单纯疱疹病毒胸苷激酶(HSVtk)基因导入大鼠脑内9L胶质肉瘤,随后全身给予抗疱疹药物更昔洛韦。通过磁共振成像对颅内9L肿瘤倍增时间变化进行定量分析,结果显示治疗反应存在显著差异。用Ad.RSVtk/更昔洛韦治疗的9L肿瘤的局部氢磁共振波谱显示,在0.9 - 1.3 ppm处的共振强度显著增加,这与流动脂质和/或乳酸相对应。颅内肿瘤倍增时间的变化与肿瘤氢磁共振波谱的变化相关,这表明肿瘤代谢物水平的特定变化可能预示着这种基因治疗方法的有效性。

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引用本文的文献

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Nonneurotropic adenovirus: a vector for gene transfer to the brain and gene therapy of neurological disorders.非嗜神经性腺病毒:一种用于向脑部进行基因转移及神经系统疾病基因治疗的载体。
Int Rev Neurobiol. 2003;55:3-64. doi: 10.1016/s0074-7742(03)01001-8.
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Applications of magnetic resonance in model systems: cancer therapeutics.磁共振在模型系统中的应用:癌症治疗学
Neoplasia. 2000 Jan-Apr;2(1-2):152-65. doi: 10.1038/sj.neo.7900078.
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Delivery of herpesvirus and adenovirus to nude rat intracerebral tumors after osmotic blood-brain barrier disruption.渗透性血脑屏障破坏后将疱疹病毒和腺病毒递送至裸鼠脑内肿瘤
Proc Natl Acad Sci U S A. 1995 Oct 10;92(21):9829-33. doi: 10.1073/pnas.92.21.9829.