Gene therapy used by p53 of radioresistant tumor for enhancing radiosensitivity

p53基因治疗抗放射肿瘤增强放射敏感性

• 批准号: 11670910
• 负责人: TAKAHASHI Takeo
• 金额: $ 1.73万
• 依托单位: Saitama Medical School
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Scientific Research (C)
• 财政年份: 1999
• 资助国家: 日本
• 起止时间: 1999 至 2001
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-11670910/
• 关键词: NMT-1; NMT-1R; apoptosis; p53; radioseusitivity; gene therapy; p21; bax

Apoptosis is an important mechanism of cell death. P53 oncogene had a relationship with apoptosis. We have previously reported the establishment of two rat yolk sac tumor cell lines(NMT-1, NMT-1R), which were of the same origin and had different radiosensitivity. We reported that radioresistant cell line, NMT-1R, lossed function of p53 gene, and radiation-induced mutation of p53 decreased radiosensitivity. Apoptosis appeared in radiosensitive cell line, NMT-1, 24 h after irradiation in vitro. Expression of p53, p21, and bax proteins were elavated in NMT-1 cells after irradiation. However, there was no epression of p53, p21, and bax proteins in NMT-1. We assessed the status of p53 in two cell lines by PCR-SSCP. NMT-1 cells had wild type of p53 gene, however, mutant p53 was seen in NMT-1R sells. We tried injection of wild type of p53 gene to radioresistant NMT-1R cells. The result was that we failed enhancing radiosensitivity in radioresistant cell line

细胞凋亡是细胞死亡的重要机制。P53癌基因与细胞凋亡有关。我们曾报道建立了两个来源相同但放射敏感性不同的大鼠卵黄囊瘤细胞系（NMT-1，NMT-1 R）。本文报道了放射抗性细胞株NMT-1 R，p53基因功能丧失，放射诱导p53基因突变，放射敏感性降低。体外培养的放射敏感细胞株NMT-1在照射后24 h出现凋亡。照射后NMT-1细胞中p53、p21和bax蛋白表达增强。而NMT-1中p53、p21和bax蛋白均不表达。我们用PCR-SSCP方法检测了两种细胞系中p53的表达情况。NMT-1细胞存在野生型p53基因，而NMT-1 R细胞存在突变型p53基因。我们尝试将野生型p53基因注射到放射抗性NMT-1 R细胞中。结果表明，我们未能提高辐射抗性细胞系的辐射敏感性

项目成果

高橋健夫 他: "エビデンスに基づく放射線治療 インフォームド・コンセントの実践のために 10. 上咽頭癌"臨床放射線. 46・11. 1463-1468 (2001)

Takeo Takahashi 等：“基于证据的放射治疗实践知情同意 10. 鼻咽癌”临床放射学 46・11（2001）。

Hosono M, Machida K, Matsui T, Honda N, Takahashi T et al.: "Non-invasive quantitative monitoring of cerebral blood flow in aneurysmal subarachnoid haemorrhage with 99m-Tc-ECD"Nucleon Medicine Communications. 23. 5-11 (2002)

Hosono M、Machida K、Matsui T、Honda N、Takahashi T 等人：“用 99m-Tc-ECD 对动脉瘤性蛛网膜下腔出血的脑血流进行无创定量监测”Nucleon Medicine Communications。

高橋健夫 他: "エビデンスに基づく放射線治療 インフォームド・コンセントの実践のために 8. 前立腺癌"臨床放射線. 46・8. 985-991 (2001)

Takeo Takahashi 等人：“基于证据的放射治疗实践知情同意 8. 前列腺癌”临床放射学 46・8 (2001)。

Akimoto T, Nonaka T, Ishikawa H, Sakurai H, Saito J, Takahashi T et al.: "Genistein, a tyrosine kinase inhibitor, enhanced radiosensitivity in human esophageal cancer cell lines in vitro : possible involvement of inhibition of survival signal transduction

Akimoto T、Nonaka T、Ishikawa H、Sakurai H、Saito J、Takahashi T 等人：“金雀异黄酮，一种酪氨酸激酶抑制剂，在体外增强人食管癌细胞系的放射敏感性：可能涉及抑制生存信号转导

Matsumoto H, Takahashi T, Mitsuhashi N, Higuchi K, Niibe H: "Modificaiton of tumor-associated antigen(CEA) expression of human Lung cancer cells by irradiation, either alone or in combination with Interferron-γ"Anticancer research. 19. 307-312 (1999)

Matsumoto H、Takahashi T、Mitsuhashi N、Higuchi K、Niibe H：“通过单独或与干扰素-γ 联合照射来改变人肺癌细胞的肿瘤相关抗原 (CEA) 表达”抗癌研究。 19. 307 -312 (1999)