Effects of combination chemotherapy on gastric carcinoma using gastric cancer xenografts

胃癌异种移植联合化疗对胃癌的影响

• 批准号: 14571242
• 负责人: NAKAMURA Yasuko
• 金额: $ 2.18万
• 依托单位: Fujita Health University
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Scientific Research (C)
• 财政年份: 2002
• 资助国家: 日本
• 起止时间: 2002 至 2004
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/en/grant/KAKENHI-PROJECT-14571242/
• 关键词: Gastric cancer; Anticancer chemotherapy; Taxanes; Apoptosis; Nude mice; タキサン系薬; thymidine phosphorylase; パクリタキセル; 5'DFUR; ヌードマウス可移植性ヒト胃癌株; タキソール

Experimental anticancer chemotherapy was performed on human gastric cancer xenografts, MKN-45 and TMK-1, serially transplanted in nude mice. Anticancer effects and toxic efcts were examined after the oral administration of 5'fluorodeoxyuridine (5'dFUrd) and intravenous administration of weekly paclitaxel and their combination. The tumor growth curve and tumor five body weight were evaluated.. Gene expressions of thymidine phosphorylase (TP), thymidylate synthase (TS), dihydropyrimidine dehydrogenase (DPD), orotate phosphribisyltransferase (OPRT), and uridine phosphorylase (UP) were examined after the administrations of 5'dFUrd, paclitaxel and their combination. Apoptosis occurred after these chemnotherapeutic regimens were also examined using TUNEL method and irmmnunohistochemical reactivity of cleaved cytokeratin 18. Combined chemotherapy of dihydropyrimidine dehydrogenase-inhibitory fluoropyrimidine, S-1, and paclitaxel was likewise per-fonned..The combined administration of 5'dFUrd and paclitaxel elicited the most effective anticancer effects, compared with 5'dFUrd alone and/or paclitaxel alone in both gastric cancer xenografts. There was no difference of the tumor free body weight, used as a reflection of toxic effects, between each getup. The administration of paclitaxel upregulated the gene expression of TP The expression of TP mRNA peaked 2 clays after the administration of paclitaxel. The administration of S-1 upregulated the gene expressions of TP, DPD. The gene expressions of TS, OPRT, UP did not changed after the administrations of these agents. Apoptosis index was significantly increased after the administration of paclitaxel.

对人胃癌异种移植物MKN-45和TMK-1进行实验性抗癌化疗，连续移植到裸鼠体内。研究口服5'氟脱氧尿苷(5'dFUrd)和静脉注射每周一次紫杉醇及其组合后的抗癌作用和毒性作用。评价肿瘤生长曲线和肿瘤五重。 术后检测胸苷磷酸化酶（TP）、胸苷酸合酶（TS）、二氢嘧啶脱氢酶（DPD）、乳清酸磷酸三酯转移酶（OPRT）、尿苷磷酸化酶（UP）基因表达量。 5'dFUrd、紫杉醇及其组合的施用。使用TUNEL法和裂解细胞角蛋白18的免疫组织化学反应性检查这些化疗方案后发生细胞凋亡。同样进行二氢嘧啶脱氢酶抑制性氟嘧啶、S-1和紫杉醇的联合化疗。5'dFUrd和5'dFUrd的联合给药紫杉醇产生最有效的抗癌作用，在两种胃癌异种移植物中与单独使用 5'dFUrd 和/或单独使用紫杉醇进行比较。每种组合之间用作毒性作用反映的无肿瘤体重没有差异。紫杉醇给药上调TP基因表达 TP mRNA表达在紫杉醇给药后2个粘土达到峰值。 S-1的施用上调了TP、DPD的基因表达。施用这些药物后TS、OPRT、UP的基因表达没有变化。给予紫杉醇后细胞凋亡指数显着增加。

项目成果

消化器癌における化学療法剤感受性決定因子としてのp53発現性

p53 表达作为胃肠道癌症化疗药物敏感性决定因素

• 发表时间: 2001
• 期刊: 藤田学園医会誌 25
• 作者: 庄司光孝;桜井洋二;松原俊樹;智立柱;殿村周平;増井利彦;吉田郁男;野副泰智;小林栄孝;三浦弘剛;神保康子;菅沼正司;今津浩喜;長谷川茂;落合正宏;船曵孝彦
• 通讯作者: 船曵孝彦

Changes in thymidylate synthase and dihydropyrinudine dehydrogenase after the treatment with 5-fluorouracil and cisplatin in human stomach cancer xenograft in nude mice

5-氟尿嘧啶和顺铂处理人胃癌裸鼠移植瘤后胸苷酸合成酶和二氢吡啶脱氢酶的变化

• 发表时间: 2001
• 期刊: 4^<th> International Gastric Cancer Congress
• 作者: Sakurai;Y.;Uraguchi;T.;Imazu;H.;Hasegawa;S.;Matsubara;T.;Ochiai;M.;Funabiki;T.
• 通讯作者: T.

Successful downstaging by S-1-based chemotherapy followed by surgical resections for gastric carcinoma with extensive distant lymph node metastasis -Report of two cases and a review of cases with surgical resection after downstaging by S-1-based chemother

远处淋巴结广泛转移的胃癌经S-1化疗成功降期并手术切除-附S-1化疗降期后手术切除病例2例报告及回顾

• 发表时间: 2005
• 期刊: Hepatogastroenterology 52
• 作者: Yoshida;I.;Sakurai;Y.;Komori;Y.;Tonomura;S.;Masui;T.;Shoji;M.;Nakamura;Y.;Imazu;H.;Uyama;I.;Ochiai;M.
• 通讯作者: M.

Orotate phosphoribosyltransferase (OPRT)アッセイ系の確立と胃癌組織におけるOPRT活性

乳清酸磷酸核糖转移酶（OPRT）测定体系的建立及胃癌组织中OPRT活性

• 发表时间: 2005
• 期刊: 癌と化学療法 32
• 作者: 桜井洋一;坂本一樹;杉本芳一;吉田郁男;増井利彦;殿村周平;稲葉一樹;庄司光孝;中村康子;宇山一朗;小森義之;落合正宏;松浦司郎;田中英之;岡 俊範;福島正和
• 通讯作者: 福島正和