Development of new therapy for hormone independent prostate cancer.

开发激素非依赖性前列腺癌的新疗法。

• 批准号: 15591689
• 负责人: USUI Tsuguru
• 金额: $ 2.11万
• 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: 2003
• 资助国家: 日本
• 起止时间: 2003 至 2004
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/en/grant/KAKENHI-PROJECT-15591689/
• 关键词: Hormone independent; FGFR2IIIb; Gene therapy; Apoptosis; Radiotherapy; Chemotherapy; 腫瘍抑制; 遺伝子移入; 上皮・間質相互作用; 分化誘導

The role of FGFR2IIIb in cell proliferation anddifferentiation were studied in hormone independentprostate cancer, and usefulness of combination therapyusing radiation and anticancer agent were also studied in the FGFR2IIIb transfected cell.1)Establishment of FGFR2IIIb transfected PC-3 cell :The growth rate of PC-3 FGFR2IIIb transfected cells was significantly slower than that of the control cells. The growth rate of the PC-3 FGFR2IIIb derived tumors was significantly slower than that of the control. PC-3 FGFR2IIIb cells were morphologically changed from PC-3 neo cells. Immunocytochemical analysis revealed a weak pancytokeratin and lactoferrin-positive staining of the control, whereas PC-3 FGFR2IIIb cells showed strong positive pancytokeratin and lactoferin immunostaining. In the apoptosis assay, most of PC-3 FGFR2IIIb cells were stained with the APOPercentage-dye.2)Signal transduction of FGFR2IIIb :FRS2 was identified as a tyrosine-phosphorylated protein in both PC-3 neo and PC-3 FGFR2IIIb cells stimulated with FGF-1. The signal intensity of FRS2 in PC-3 FGFR2IIIb was much stronger than that of the control. On the stimulation with FGF-7, FRS2 was strongly activated in PC-3 v cells but not in PC-3 neo cells. On stimulation with FGF-1 and FGF-7, the phosphorylation of p44/42 MAP kinase was detected in PC-3 FGFR2IIIb cells, but not in PC-3 neo cells.3)Synergistic effects of radiation and an anticancer agent with the FGFR2IIIbFour and 8 Gy of radiation treatment dramatically decreased the number of colonies in PC3-IIIb cells by 87.7 % and 99.6 %, respectively. The number of colonies in Mock cells bearing an empty vector was reduced by 69.4% and 95.2%, respectively. The mean cell viability on day 3 was 0.34 for PC-IIIb without docetaxel, 0.24 for PC3-IIIb1+0.01μM docetaxel, and 0.20 for PC3-IIIb + 0.1μM of docetaxel. The difference between the groups was statistically significant (p<0.0001).

研究了FGFR2IIIb在激素不依赖型前列腺癌细胞增殖和分化中的作用，并在FGFR2IIIb转染的细胞中研究了放射和抗癌药物联合治疗的有效性。1) FGFR2IIIb转染PC-3细胞的建立：PC-3转染FGFR2IIIb细胞的生长速度明显慢于对照细胞。PC-3 FGFR2IIIb衍生肿瘤的生长速度明显低于对照组。PC-3 FGFR2IIIb细胞与PC-3 neo细胞形态学改变。免疫细胞化学分析显示，对照组的泛细胞角蛋白和乳铁蛋白呈弱阳性染色，而PC-3 FGFR2IIIb细胞的泛细胞角蛋白和乳铁蛋白免疫染色呈强阳性。凋亡实验中，大多数PC-3 FGFR2IIIb细胞用apopercent染色。2) FGFR2IIIb的信号转导：在FGF-1刺激的PC-3 neo和PC-3 FGFR2IIIb细胞中，FRS2被鉴定为酪氨酸磷酸化蛋白。PC-3 FGFR2IIIb中FRS2的信号强度明显强于对照组。在FGF-7刺激下，FRS2在PC-3 v细胞中被强烈激活，而在PC-3 neo细胞中未被激活。在FGF-1和FGF-7刺激下，PC-3 FGFR2IIIb细胞检测到p44/42 MAP激酶磷酸化，但PC-3 neo细胞未检测到p44/42 MAP激酶磷酸化。3)放疗和抗癌药物与fgfr2iiib4和8gy放疗的协同作用使PC3-IIIb细胞的菌落数量分别显著减少87.7%和99.6%。携带空载体的模拟细胞菌落数量分别减少69.4%和95.2%。不含多西他赛的PC-IIIb组第3天的平均细胞活力为0.34,PC3-IIIb +0.01μM多西他赛组为0.24,PC3-IIIb + 0.1μM多西他赛组为0.20。两组间差异有统计学意义（p<0.0001）。

项目成果

IGFBP-rP1の発現回復によるヒト前立腺癌細胞の放射線感受性

通过恢复 IGFBP-rP1 表达来提高人前列腺癌细胞的放射敏感性

• 发表时间: 2004
• 期刊: 日本泌尿器科学会雑誌 95
• 作者: Kubo;N.;Hiroaki Yasumoto;Mituhiro Seki;望月英樹;石 光弘
• 通讯作者: 石 光弘

Tumor Induction by Azoxymethane (AOM) and 2-Amino-1-methyl-6-phenylimidazo[4,5-b]pyridine (PhIP) in F344 Rat Gastric Mucosa Featuring Intestinal Metaplasia Caused by X-irradiation.

氧化偶氮甲烷 (AOM) 和 2-氨基-1-甲基-6-苯基咪唑并[4,5-b]吡啶 (PhIP) 在 F344 大鼠胃粘膜中诱导肿瘤，其特点是 X 射线照射引起的肠化生。

• 期刊: J.Exp.Clin.Cancer Res. (in press)
• 作者: Kashiwabara;S.
• 通讯作者: S.

Protective Effects of a Water-soluble Extract from cultured Medium of Ganoderma Lucidum (Rei-shi) My celia and Agaricus blazei Murill Against X-irradiation in B6C3F1 Mice : Increased Small Intestinal Crypt Survival and Prolongation of Average Time to Anim

灵芝和姬松茸培养基中的水溶性提取物对 B6C3F1 小鼠 X 射线的保护作用：增加小肠隐窝存活并延长平均动物存活时间

• 发表时间: 2005
• 期刊: Int.J.Mol.Med 15・3
• 作者: Kubo;N.
• 通讯作者: N.

Tumor Induction by Azoxymethane(AOM)and 2-Amino-1-methyl-6-phenylmidazo[4,5-b]pyridine (PhP) in F344 Rat Gastric Mucosa Featuring intestinal Metaplasia Caused by X-irradiation.

氧化偶氮甲烷 (AOM) 和 2-氨基-1-甲基-6-苯基咪唑并[4,5-b]吡啶 (PhP) 在 F344 大鼠胃粘膜中诱导肿瘤，其特点是 X 射线照射引起的肠化生。

• 期刊: J.Exp.Clin.Cancer Res. (In press)
• 作者: Kashiwabara;S.
• 通讯作者: S.

Restration of fibroblast growth factor receptor 2 increases radiosensitivity of human prostate cancer.

成纤维细胞生长因子受体 2 的重新抑制会增加人类前列腺癌的放射敏感性。

• 发表时间: 2004
• 期刊: Jpn J Urol 95
• 作者: Inoue K;Chikazawa M;Fukata S;Yoshikawa C;Shuin T.;Nishimura K et al.;Nishimura Kazuo;Nishimura K;Nishimura K et al.;Inoue Hitoshi;Inoue H et al.;Inoue Hitoshi;西村和郎;Nishimura Kazuo;Hiroaki Yasumoto;Hideki Mochizuki;Hideki Mochizuki;Mitsuhiro Seki;望月英樹;石 光弘;Hiroaki Yasumoto;Hideki Mochizuki;Hideki Mochizuki;Mitsuhiro Seki;Mochizuki Hideki
• 通讯作者: Mochizuki Hideki