Gene Therapy of naliguart Glionaly Transfection with sdi-1 gene

sdi-1基因转染naliguart Glonaly的基因治疗

• 批准号: 07671522
• 负责人: KURISU Kaoru
• 金额: $ 1.47万
• 依托单位: HIROSHIMA UNIVERSITY
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Scientific Research (C)
• 财政年份: 1995
• 资助国家: 日本
• 起止时间: 1995 至 1996
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-07671522/
• 关键词: p21; p16; cell cycle regulator; gene transfection; growth inhibition; p21; p16; 悪性脳腫瘍; 遺伝子療法; 老化誘導遺伝子; テロメア

A senescent cell-derived inhibitor of DNA synthetase-1 (sdi-1, p21) which is induced by wild type p53 is a suppressor of cytokinesis. P21 protein forms a complex with cyclin-dependent kinase 2 (cdk-2) and regulates a cell cycle. Also, p16 protein regulates a cell cycle. We investigated the molecular changes of the p21 and p16 gene in human gliomas and studied its effects on growth of glioma cells. DNA and mRNA were extracted from cultured human glioma cells and from clinical samples and analyzed by Southern and northern blotting. Mutations or homozygous deletions of p21 gene were observed in 40% of malignant gliomas, and that of p16 were seen in almost all cell lines and lots of clinical samples.The p21 and p16 gene were transfected into glioma cell lines by a liposome method, and growth inhibitory effects of these transfectants were observed.We constructed of recombinant adenovirus expression vector which were capable of high efficiency, and significant growth inhibitory effects of these transfectants were observed.

由野生型 p53 诱导的衰老细胞衍生的 DNA 合成酶 1 (sdi-1, p21) 抑制剂是胞质分裂的抑制剂。 P21 蛋白与细胞周期蛋白依赖性激酶 2 (cdk-2) 形成复合物并调节细胞周期。此外，p16 蛋白还调节细胞周期。我们研究了人胶质瘤中 p21 和 p16 基因的分子变化，并研究了其对胶质瘤细胞生长的影响。从培养的人神经胶质瘤细胞和临床样本中提取 DNA 和 mRNA，并通过 Southern 和 Northern 印迹进行分析。 40%的恶性胶质瘤中观察到p21基因突变或纯合缺失，几乎所有细胞系和大量临床样本中均观察到p16基因突变或纯合缺失。通过脂质体方法将p21和p16基因转染到胶质瘤细胞系中，观察这些转染子的生长抑制作用。我们构建了能够高效表达的重组腺病毒表达载体。 观察到这些转染子的效率和显着的生长抑制作用。

项目成果

Naoyuki Isobe, Thoru Uozumi, Kaoru Kurisu, Keiichi Kawamoto: "Experimental Studies of the Antitumor Effect of TNP-470 on Malignant Brain Tumor." Neoropediatrics. 27. 136-142 (1996)

Naoyuki Isobe、Thoru Uozumi、Kaoru Kurisu、Keiichi Kawamoto：“TNP-470 对恶性脑肿瘤的抗肿瘤作用的实验研究。”

Kunyu Harada: "Growth inhibition of intracerebral Rat Glioma by transfusion-induced Human Interferon-β" Journal of Surgical Oncology. 59. 105-109 (1995)

Kunyu Harada：“输血诱导的人干扰素-β 抑制大鼠脑内胶质瘤的生长”《肿瘤外科杂志》59. 105-109 (1995)。

Takashi Sadatomo: "New Approach for the Treatment of Medulloblastoma by Transfecucn with Glral Fibrilary Acidic Protin Gene" Journal of Surgicol Oncology. (in print). (1996)

Takashi Sadatomo：“用 Glral 纤维酸性蛋白基因转染治疗髓母细胞瘤的新方法”《外科肿瘤学杂志》。

Naoyuki Isobe: "Antitumor effect of TNP-470 on glial tumors transplanted in rats" Anticancer Research. 16. 71-76 (1996)

Naoyuki Isobe：“TNP-470 对大鼠神经胶质瘤移植的抗肿瘤作用”抗癌研究。

貞友隆: "G-CSF遺伝子導入による脳腫瘍細胞の増殖に及ぼす影響" 神経免疫研究. 8. 267-271 (1995)

Takashi Sadatomo：“G-CSF 基因转移对脑肿瘤细胞增殖的影响”《神经免疫学研究》8. 267-271 (1995)。