A genetherapy for the cervical cancer based on its carcinogenesis.

基于宫颈癌致癌作用的基因疗法。

• 批准号: 07671804
• 负责人: SUGIMORI Hajime
• 金额: $ 1.47万
• 依托单位: Saga 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: 1995
• 资助国家: 日本
• 起止时间: 1995 至 1997
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-07671804/
• 关键词: Cervical cancer; p53; genetherapy; p16; HPV; 免疫染色

1.Tne primary culture of squamous epithelial cells and columnar cells from the normal human uteirne cervix was performed. HPV 16 or 18 was transfected to these cells and the imortalized cell lines were established. Furthermore, the malignant transformation was induced by transfection of the carcinogens. Thus, the in-vitro model of multi-step carcinogenesis of the cervical cancer was completed.2.P16, cyclin dependent kinase inhibitor, was examined concerning deletion or point mutation. Although p16 was overexpressed in immortalized cell lines, its deletion was not detected in these in-vitro model. P16 was supposed to be not so important in carcinogenesis of the cervical ancer.3.PMO-hp53 is plasmid that induce wild type p53 by dexamethasone. PMO-hp 53 was transfected to the cervical cancer cell line, TMCC-1 and ME180. By this transfection The cell line showed the following changes.(1) Cell cycle was stopped in M-phase and cell proliferation was disturbed.(2) Cell enlatrgment, multi-nucleation, micro-nucleation and changes in cytoplasm were observed.(3) Proliferation activity in soft agar was dismissed.

1.从正常人uteirne子宫颈进行了鳞状上皮细胞和柱状细胞的原发性培养。将HPV 16或18转染到这些细胞中，并建立了不利的细胞系。此外，通过转染致癌物诱导恶性转化。因此，完成了有关缺失或点突变的细胞周期蛋白依赖激酶抑制剂的多步癌的体外模型。尽管P16在永生的细胞系中过表达，但在这些体外模型中未检测到其缺失。 p16在宫颈Ancer的致癌作用中并不那么重要。3.PMO-HP53是质粒，它诱导地塞米松诱导野生型p53。将PMO-HP 53转染到宫颈癌细胞系TMCC-1和ME180。通过这种转染，细胞系显示了以下变化。（1）在M相中停止细胞周期，并干扰细胞增殖。（2）观察到细胞ENLATRMET，多核核，微核，微核和细胞质的变化。（3）在软araR中的增殖活性被解散。

项目成果

Iwasaka T: "Cytologic changes in two cervical carcinoma cell lines after transfection of the wild-type p53 gene." Acta Obstet Gynecol Scand. 75. 797-803 (1996)

Iwasaka T：“两种宫颈癌细胞系转染野生型 p53 基因后的细胞学变化。”

Iwasaka T: "Outpatient treatment of cervical intra-epithelial neoplasia with laser conization." The Cervix & l.f.g.t.13. 99-103 (1995)

Iwasaka T：“用激光锥切术治疗宫颈上皮内瘤变。”

Uchiyama M: "Correlation between human papilloma virus positivity and p53 gene overexpression in adenocarcinoma of the uterine cervix" Gynecol Oncol. 65. 23-29 (1997)

Uchiyama M：“人乳头瘤病毒阳性与子宫颈腺癌中 p53 基因过度表达之间的相关性”Gynecol Oncol。

Zheng PS: "Telomerase activation in invitro and in vivo cervical carcinogenesis" Gynecol Onol. 66. 222-226 (1997)

郑 PS：“体外和体内宫颈癌发生中的端粒酶激活”Gynecol Onol。

岩坂 剛: "p53遺伝子導入による子宮頚癌治療の試み." 産婦治療. 72. 994-994 (1996)

Tsuyoshi Iwasaka：“尝试通过 p53 基因转移治疗宫颈癌。” 72. 994-994 (1996)