Studies on a novel gene therapy of glioma using antisense oligonucletide for microtubule-associated protein mRNA

利用反义寡核苷酸针对微管相关蛋白mRNA进行胶质瘤新型基因治疗的研究

• 批准号: 09671450
• 负责人: MATSUNO Akira
• 金额: $ 2.05万
• 依托单位: Teikyo University
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Scientific Research (C)
• 财政年份: 1997
• 资助国家: 日本
• 起止时间: 1997 至 1998
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-09671450/
• 关键词: antisense oligonucleotide; glioma; gene therapy; Microtubule-associated protein; growth suppression

Microtubule-associated protein (MAP) lA, one of the well-known MAPs that are essential for the various bioactivities, is known to be expressed in cultured glioma cells such as rat C6 glioma cells. The antisense oligodeoxynucleotide for MAP lA is demonstrated, by colony forming assay, to have significantly suppressed the in vitro proliferation of rat 6 glioma cells. The effect of antisense oligodeoxynucleotide on the expression of MAP lA has been demonstrated by immunohistochemical staining. This report will be the first one describing the efficiency of antisense oligodeoxynucleotide for MAP lA on the growth suppression of rat C6 glioma cells. The effect of antisense oligodeoxynucleotide for MAP 1A on the cell cycle of rat C6 glioma cells has also been shown by the flow cytometrical analysis. The suppression of MAP IA resulted in GL arrest of C6 glioma cells, and this result strongly suggests the important role of MAP IA in the cell cycle. The suppression of MAP lA using antisense oligodeoxynudeotide strategy can be established as a novel antitumor therapy for gliomas.

微管相关蛋白(MAP)1A是众所周知的MAP之一，其对于各种生物活性是必需的，已知其在培养的神经胶质瘤细胞例如大鼠C6神经胶质瘤细胞中表达。通过集落形成测定证明MAP 1A的反义寡脱氧核苷酸显着抑制了大鼠6神经胶质瘤细胞的体外增殖。反义寡脱氧核苷酸对MAP1A表达的影响已通过免疫组织化学染色证实。该报告将是第一篇描述MAP 1A反义寡脱氧核苷酸对大鼠C6神经胶质瘤细胞生长抑制的效率的报告。流式细胞术分析也显示了 MAP 1A 反义寡脱氧核苷酸对大鼠 C6 神经胶质瘤细胞细胞周期的影响。 MAP IA 的抑制导致 C6 神经胶质瘤细胞的 GL 停滞，这一结果强烈表明 MAP IA 在细胞周期中的重要作用。使用反义寡脱氧核苷酸策略抑制MAP1A可被确立为神经胶质瘤的新型抗肿瘤疗法。

项目成果

松野彰ら: "Growth hormone releasing hormone (GHRH) による、成長ホルモン (GH) のautocrine or paracrine regulation : 血漿GHRHが高値を示したGHRH-GH産生下垂体腺腫" ホルモンと臨床46巻 '98秋季増刊号 内分泌病理学 最近の進歩1998. 46. 19-25 (1998)

Akira Matsuno 等人：“生长激素释放激素 (GHRH) 对生长激素 (GH) 的自分泌或旁分泌调节：产生 GHRH-GH 的垂体腺瘤伴高血浆 GHRH”激素临床卷 46 98 秋季特刊内分泌病理学最新进展 1998. 46. 19-25 (1998)

Matsuno A,Sasaki T,Kirino T: "Plurihormonal Pituitary Tumor : Letter to the editor" J Neurosurg. (in press).

Matsuno A、Sasaki T、Kirino T：“多激素垂体瘤：致编辑的信”J Neurosurg。

Matsuno A et al.: "Electron microscopic and confocal laser scanning microscopic obsenotion of subcellular orgenelles and pituitary hormone mRNA" Endocrine Pathology. (in press).

Matsuno A 等人：“亚细胞器和垂体激素 mRNA 的电子显微镜和共焦激光扫描显微观察”内分泌病理学。

Matsuno A et al.: "Silent somatotroph adenoma, detected by catalyzed signal amplification and non-radioisotopic in situ hybridization" EndocrineJ. (in press).

Matsuno A 等人：“通过催化信号放大和非放射性同位素原位杂交检测到的沉默生长激素细胞腺瘤”EndocrineJ。

Matsuno A et Al.: "Application of ultrastructural in situ hybridization combined with immuno histochemistry to pathephysis logical studies of pituitary cell:Technical Review" Acta Histochem Cytochem. 31. 259-265 (1998)

Matsuno A 等人：“超微结构原位杂交与免疫组织化学相结合在垂体细胞病理生理逻辑研究中的应用：技术评论”Acta Histochem Cytochem。