Effects of combination chemotherapy on gastric carcinoma using gastric cancer xenografts

• Project/Area Number: 14571242
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Single-year Grants
• Section: 一般
• Research Field: Digestive surgery
• Research Institution: Fujita Health University
• Principal Investigator: NAKAMURA Yasuko Fujita Health Univ., Dept. of Surgery School of Medicine, Assistant Professor, 医学部, 講師 (50308871)
• Co-Investigator(Kenkyū-buntansha): SAKURAI Yoichi Fujita Health Univ., School of Medicine, Associate Professor, 医学部, 助教授 (60170651) ; OCHIAI Masahiro Fujita Health Univ., 医学部, 教授 (00051772) ; 今津 浩喜 藤田保健衛生大学, 医学部, 講師 (50298519) ; 野副 泰智 藤田保健衛生大学, 医学部, 助手
• Project Period (FY): 2002 – 2004
• Project Status: Completed (Fiscal Year 2004)
• Budget Amount: ¥3,400,000 (Direct Cost: ¥3,400,000); Fiscal Year 2004: ¥900,000 (Direct Cost: ¥900,000); Fiscal Year 2003: ¥900,000 (Direct Cost: ¥900,000); Fiscal Year 2002: ¥1,600,000 (Direct Cost: ¥1,600,000)
• Keywords: 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

Research Abstract

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.

Research Products

• [Journal Article] 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 chemotherapy. (2005)
  • Author(s): Yoshida, I., Sakurai, Y., Komori, Y., Tonomura, S., Masui, T., Shoji, M., Nakamura, Y., Imazu, H., Uyama, I., Ochiai, M.
  • Journal Title: Hepatogastroenterology 52 Pages: 977-982
  • Description: 「研究成果報告書概要(和文)」より
• [Journal Article] Orotate phosphoribosyltransferase (OPRT)アッセイ系の確立と胃癌組織におけるOPRT活性 (2005)
  • Author(s): 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
  • Journal Title: 癌と化学療法 32 Pages: 101-106
  • Description: 「研究成果報告書概要(和文)」より
• [Journal Article] Changes in thymidylate synthase and its inhibition rate and changes in dihydropyrimidine dehydrogenase after the administration of 5-fluorouracil with cisplatin to nude mice with gastric cancer xenograft SC-1-NU. (2004)
  • Author(s): Sakurai, Y., Uraguchi, T., Imazu, H., Hasegawa, S., Matsubara, T., Ochiai, M., Funabiki, T.
  • Journal Title: Gastric Cancer 7 Pages: 110-116
  • Description: 「研究成果報告書概要(和文)」より
• [Journal Article] Weekly administration of paclitaxel attenuated rectal stenosis caused by multiple peritoneal recurrence 8 years after the resection of gastric carcinoma (2003)
  • Author(s): Sakurai, Y., Yoshida, I., Tonomura, S., Sakai, W., Nakamura, Y., Imazu, H., Matsubara, T.Ochiai, M.
  • Journal Title: Gastric Cancer 6 Pages: 243-249
  • Description: 「研究成果報告書概要(和文)」より
• [Journal Article] Weekly administration of paclitaxel attenuated rectal stenosis caused by multiple peritoneal recurrence 8 years after the resection of gastric carcinoma (2003)
  • Author(s): Sakurai, Y., Yoshida, I., Tonomura, S., Sakai, W., Nakamura, Y., Imazu, H., Matsubara, T Ochiai, M.
  • Journal Title: Gastric Cancer 6 Pages: 243-249
  • Description: 「研究成果報告書概要(欧文)」より
• [Journal Article] K-ras and p^<53> gene mutations in noncancerous biliary lesions of patients with pancreaticobiliary maljunction. (2002)
  • Author(s): Matsubara, T., Sakurai, Y., Zhi, L., Miura, H., Ochiai, M., Funabiki, T.
  • Journal Title: J Hepatobiliary Pancreat.Surg. 9 Pages: 312-321
  • NAID: 10015742232
  • Description: 「研究成果報告書概要(欧文)」より
• [Journal Article] 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 (2001)
  • Author(s): 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
  • Journal Title: 藤田学園医会誌 25 Pages: 11-13
  • Description: 「研究成果報告書概要(和文)」より
• [Journal Article] Changes in thymidylate synthase and dihydropyrinudine dehydrogenase after the treatment with 5-fluorouracil and cisplatin in human stomach cancer xenograft in nude mice (2001)
  • Author(s): Sakurai, Y., Uraguchi, T., Imazu, H., Hasegawa, S., Matsubara, T., Ochiai, M., Funabiki, T.
  • Journal Title: 4^<th> International Gastric Cancer Congress Pages: 1187-1189
  • Description: 「研究成果報告書概要(欧文)」より