Experimental study of gene therapy for malignant brain tumor

恶性脑肿瘤基因治疗的实验研究

• 批准号: 06671392
• 负责人: KURISU Kaoru
• 金额: $ 1.34万
• 依托单位: HIROSHIMA UNIVERSITY
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for General Scientific Research (C)
• 财政年份: 1994
• 资助国家: 日本
• 起止时间: 1994 至 1995
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/en/grant/KAKENHI-PROJECT-06671392/
• 关键词: Malignant brain tumor; Gene therapy; Cytokine

Fundamental experiments of the gene therapy for malignant brain tumor were performed by transfection of cytokine genes, cell regulation genes and cell structure genes. As for cytokine genes we confirmed antitumor effect to the malignant glioma cells both in vitro and in vivo by transfer of TNF-alpha gene or INF-beta gene so far. In addition of these results, We transferd of G-CSF gene into human glioma cells and then transplanted them into subcutaneous space of nude mouse. As a result of this experiment, nude mice that were transplanted G-SCF gene transfected glioma cells did not from solid tumor and histological evaluation of the G-CSF gene transfected tumor revealed intense invasion of granulocytes into the tumor. We revealed delation or mutation of cell regulation genes such as p21 and p16 in human glioma cells. So transfection these cell regulation genes into human glioma cells was performed. As aresult of transfection, growth suppression of human glioma cell was revealed. This result leads to the possibility that transfer of cell regulation genes may be the candidate of the gene therapy for the malignant glioma. GFAP is one of the cell structure component and the expression of GFAP seems to relate to cell differentiation. In this study, we transfected GFAP gene into medulloblastoma cells, resulting in suppressed cell growth and increased sensitivity to anticancer drugs. These results indicate that chemotherapy to medulloblastoma may be much more effective by transferring GFAP gene into tumor cells.

通过细胞因子基因、细胞调控基因和细胞结构基因的导入，进行了恶性脑肿瘤基因治疗的基础实验。在细胞因子基因方面，我们通过转移肿瘤坏死因子-α基因或干扰素-β基因，在体内外证实了其对恶性胶质瘤细胞的抗肿瘤作用。此外，我们还将G-CSF基因导入人脑胶质瘤细胞，并将其移植到裸鼠皮下。本实验的结果是，移植了G-SCF基因的胶质瘤细胞的裸鼠没有实体瘤，组织学检测显示G-CSF基因转染的肿瘤有强烈的粒细胞侵袭。我们揭示了人脑胶质瘤细胞中p21和p16等细胞调控基因的缺失或突变。因此，我们将这些细胞调控基因导入人脑胶质瘤细胞。结果显示，该基因对人脑胶质瘤细胞生长有抑制作用。这一结果表明，细胞调控基因的转移有可能成为恶性胶质瘤基因治疗的候选基因。GFAP是细胞结构成分之一，GFAP的表达可能与细胞分化有关。在本研究中，我们将GFAP基因导入髓母细胞瘤细胞，使细胞生长受到抑制，并增加了对抗癌药物的敏感性。这些结果表明，将GFAP基因导入肿瘤细胞，对髓母细胞瘤的化疗可能更为有效。

项目成果

Takashi Matsuoka: "Antitumor effects of human recombinant macrophage Colony-stimulating factor against rat brain tumors" Biotherapy. 8. 51-62 (1995)

Takashi Matsuoka：“人重组巨噬细胞集落刺激因子对大鼠脑肿瘤的抗肿瘤作用”生物疗法。

Kunyu Harada: "Analysis of sdi-1 Gene Functions in Human Malignant Gliomas" Brain Tumor Researchand Therapy. 435-440 (1996)

Kunyu Harada：“人类恶性胶质瘤中 sdi-1 基因功能的分析”脑肿瘤研究与治疗。

Takashi Sadatomo: "New Approach for the Treatment of Medulloblastoma by Transfection with Glial Fibrillary Acidic protein Gene" Journal of Surgical Oncology. (in print). (1996)

Takashi Sadatomo：“通过转染胶质纤维酸性蛋白基因治疗髓母细胞瘤的新方法”《肿瘤外科杂志》。

Takashi Matsuoka: "Antitumor effects of human recombinant macrophage colony-stimulating factor against rat brain tumor" Biotherapy. 8. 51-62 (1995)

Takashi Matsuoka：“人重组巨噬细胞集落刺激因子对大鼠脑肿瘤的抗肿瘤作用”生物疗法。

松岡隆: "ラット9L gliosarcomaに対するMacrophage Colony-stimulating factor(M-CSF)の抗腫瘍効果の検討" 神経免疫研究. 7. 305-308 (1994)

Takashi Matsuoka：“巨噬细胞集落刺激因子（M-CSF）对大鼠 9L 神经胶质肉瘤的抗肿瘤作用的检查”《神经免疫学研究》7. 305-308（1994）。