Development of a novel therapy for hormone-refractory prostate cancer

开发激素难治性前列腺癌的新疗法

• 批准号: 17591679
• 负责人: MATSUBARA Akio
• 金额: $ 2.37万
• 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: 2005
• 资助国家: 日本
• 起止时间: 2005 至 2006
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/en/grant/KAKENHI-PROJECT-17591679/
• 关键词: Fibroblast growth factor; Fibroblast growth factor receptor; Tyrosine kinase; Prostate cancer; Hormone refractory; Radiation; Gene therapy; 遺伝子治療; 線維芽細胞成長因子受容体

RESEARCH RESULTS Fibroblast growth factor receptor 2 (FGFR2) is a receptor-type tyrosine kinase that has a growth inhibitory effect on hormone-refractory prostate cancer. To investigate the synergistic effects of radiation and an anticancer agent with FGFR2 in hormone-refractory human prostate cancer cells, a hormone-refractory human prostate cancer cell line, PC3, was transfected with FGFR2. The effects of radiation or docetaxel on cell cycle and apoptosis were evaluated by flowcytometry and Annexin affinity assay, respectively.Expression of FGFR2 in PC3 cells resulted in growth suppression in vitro and reduced tumor formation in vivo concurrent with increased cellular differentiation and apoptosis. Four to 8 Gy of radiation further decreased the number of colonies in transfected PC3 cells. Annexin affinity assay revealed that 8 Gy of radiation caused significant apoptosis for transfected PC3 cells. Also, at 24 hours after 8 Gy of radiation, proportion of G2/M phase was significantly higher in the transfected PC3 cells than in Mock cell. Docetaxel showed similar effects on the transfected PC3 cells.These results indicate that radiation and docetaxel enhance the growth-suppressive activity of FGFR2 in hormone-refractory human prostate cancer cells. Combination of FGFR2 with radiation or docetaxel may provide a new avenue for gene therapy of hormone-refractory prostate cancer.

研究结果成纤维细胞生长因子受体2（FGFR2）是一种受体型酪氨酸激酶，对激素难治性前列腺癌具有生长抑制作用。为了研究辐射和FGFR2抗癌剂在激素难治性的人前列腺癌细胞中的协同作用，用FGFR2转染了一种激素 - 难治性的人类前列腺癌细胞PC3。辐射或多西他赛对细胞周期和凋亡的影响分别通过流环术和膜联蛋白亲和力测定进行了评估。PC3细胞中FGFR2的表达导致体外抑制生长，并减少体内肿瘤形成，体内与细胞分化和凋亡的增加相关。四到8 GY的辐射进一步减少了转染的PC3细胞中的菌落数量。膜联蛋白亲和力测定表明8 Gy的辐射引起了转染的PC3细胞的显着凋亡。同样，在8 Gy辐射后24小时，转染的PC3细胞中G2/m期的比例明显高于模拟细胞。多西他赛对转染的PC3细胞显示出相似的影响。这些结果表明，辐射和多西他赛在激素难治性的人前列腺癌细胞中增强了FGFR2的生长抑制活性。 FGFR2与辐射或多西他赛的组合可以为激素难治性前列腺癌的基因治疗提供新的途径。

项目成果

総説 会陰式前立腺全摘除術

审查会阴根治性前列腺切除术

• 发表时间: 2005
• 期刊: 西日本泌尿器科 67・7
• 作者: Furuya;Nagakawa;Fuse et al.;Yoshimasa Ishida;Yasuhisa Hasegawa;Yasuhisa Hasegawa;松原昭郎;亭島淳;Akio Matsubara;Jun Teishima;亭島淳;Shunichi Namiki;松原昭郎;Akio Matsubara;松原昭郎
• 通讯作者: 松原昭郎

前立腺癌検診におけるAge-specific Reference Range of PSAの有用性

PSA 年龄特异性参考范围在前列腺癌筛查中的作用

• 发表时间: 2005
• 期刊: 臨床泌尿器科 18・8
• 作者: Furuya;Nagakawa;Fuse et al.;Yoshimasa Ishida;Yasuhisa Hasegawa;Yasuhisa Hasegawa;松原昭郎;亭島淳;Akio Matsubara;Jun Teishima;亭島淳;Shunichi Namiki;松原昭郎;Akio Matsubara;松原昭郎;石光広
• 通讯作者: 石光広

前立腺癌のホルモン依存性消失におけるFGFレセプターの関わりと治療への応用

FGF受体参与前列腺癌激素依赖性消失及其治疗应用

• 发表时间: 2006
• 期刊: 日本内分泌学会雑誌 82・2
• 作者: Furuya;Nagakawa;Fuse et al.;Yoshimasa Ishida;Yasuhisa Hasegawa;Yasuhisa Hasegawa;松原昭郎
• 通讯作者: 松原昭郎

Changes in quality of life in first year after radical prostatectomy by retropubic, Laparoscopic and perineal approach : Malti- institutional longitudinal study in Japan

耻骨后、腹腔镜和会阴入路根治性前列腺切除术后第一年生活质量的变化：日本马耳他机构纵向研究

• 发表时间: 2006
• 期刊: Urology 67・2
• 作者: Furuya;Nagakawa;Fuse et al.;Yoshimasa Ishida;Yasuhisa Hasegawa;Yasuhisa Hasegawa;松原昭郎;亭島淳;Akio Matsubara;Jun Teishima;亭島淳;Shunichi Namiki
• 通讯作者: Shunichi Namiki

前立腺癌切除標本の取り扱い方

如何处理前列腺癌切除标本

• 发表时间: 2005
• 期刊: 臨床泌尿器科 59・12
• 作者: Furuya;Nagakawa;Fuse et al.;Yoshimasa Ishida;Yasuhisa Hasegawa;Yasuhisa Hasegawa;松原昭郎;亭島淳;Akio Matsubara;Jun Teishima;亭島淳;Shunichi Namiki;松原昭郎;Akio Matsubara;松原昭郎;石光広;安本博晃
• 通讯作者: 安本博晃