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Studies on the involvement of inflammatory stimuli and immortalization of cells in tongue carcinogenesis and cancer chemoprevention

Research Project

Project/Area Number 10671782
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeSingle-year Grants
Section一般
Research Field 病態科学系歯学(含放射線系歯学)
Research InstitutionKanazawa Medical University

Principal Investigator

TANAKA Takuji  Kanazawa Medical University, Dept.Pathol., Professor, 医学部, 教授 (40126743)

Co-Investigator(Kenkyū-buntansha) MAEDA Masayo  Kanazawa Medical University, Dept.Pathol., Assistant Prof., 医学部, 助手 (30199632)
OTA Takahide  Kanazawa Medical University, Dept.Pathol., Lecturer, 医学部, 講師 (10152141)
TANINO Mikio  Kanazawa Medical University, Dept.Pathol., Associate Prof., 医学部, 助教授 (60135051)
Project Period (FY) 1998 – 2000
Project Status Completed (Fiscal Year 2000)
Budget Amount *help
¥3,100,000 (Direct Cost: ¥3,100,000)
Fiscal Year 2000: ¥500,000 (Direct Cost: ¥500,000)
Fiscal Year 1999: ¥1,100,000 (Direct Cost: ¥1,100,000)
Fiscal Year 1998: ¥1,500,000 (Direct Cost: ¥1,500,000)
KeywordsTongue carcinogenesis / Inhibition of carcinogenesis / Nimesulide / COX-2 inhibitor / COX-2 / 牛ラクトフェリン / フラボノイド / モリン / 炎症性刺激 / 発がん阻止 / 抗酸化作用
Research Abstract

Our previous study indicated that expression of COX-2 protein involves in 4-NQO-induced rat tongue carcinogenesis. In this year, therefore, we investigated possible modifying effect of nimesulide, which specific inhibitor of COX-2, on 4-NQO-induced rat tongue tumorigenesis.
A total of 97 male F344 rats aged 4 weeks were used. Rats were given 4-NQO (20 ppm in drinking water) for 8 weeks to induced tongue squamous cell carcinoma. They were also fed the diets mixed w* nimesulide at a dose of 0.01% or 0.04% during the initiation (10 weeks) or promotion phase (22 weeks). The experiment was terminated 32 weeks after the start. At the end of the study, the incide* of tongue squamous cell carcinoma were 48% (13/27 rats) in the 4-NQO alone group, 20% (3/15 rats) in 4-NQO+0.01% nimesulide group, 13% (2/15 rats) in the 4-NQO+0.04% nimesulide group, 42% (5/12 rats) in the 4-NQO→0.01% nimesulide group, and 8% (1/12 rats) in the 4-NQO→0.04% nimesulide group. Thus, feeding of nemesulide during either the initiation or promotion pahse *tumorirgenesis significantly inhibited the development of tongue carcinoma (P<0.05). No tongue tum* were present in rats of nimesulide alone (0.04%) and untreated control. These results suggest that a COX-2 sepcific inhibitor nimesulide is applicable for human clinical trial for chemoprevention of tongue cancer. The studies on mechanisms of inhibition are ongoing in our laboratory.
It is well known that the treatment of 4-NQO in drinking water specifically prodeces tongue neoplas* However, in the present study, 4-NQO exposure induced squamous cell carcinoma in the palate and gi*of the maxilla as well as tongue carcinoma. Feeding of nimesulide also inhibited the development of th*tumors.

Report

(4 results)
  • 2000 Annual Research Report   Final Research Report Summary
  • 1999 Annual Research Report
  • 1998 Annual Research Report
  • Research Products

    (31 results)

All Other

All Publications (31 results)

  • [Publications] Kawabata,K., et al.: "Suppression of N-nitrosomethylbenzylamine-induced rat esophageal tumorigenesis by dietary feeding of 1'-acetoxychavicol acetate"Japanese Journal of Cancer Research. 91・2. 148-155 (2000)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2000 Final Research Report Summary
  • [Publications] Tanaka,T., et al.: "Colitis-related rat colon carcinogenesis induced by 1-hydroxyanthra-quinone and methylazoxymethanol acetate (review)"Oncology Reports. 7・3. 501-508 (2000)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2000 Final Research Report Summary
  • [Publications] Tanaka,T., et al.: "Prevention of colonic aberrant crypt foci by dietary feeding of garcinol in male F344 rats"Carcinogenesis. 21・6. 1183-1189 (2000)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2000 Final Research Report Summary
  • [Publications] Murakami A., et al.: "Suppression by citrus auraptene of phorbol ester-and endotoxin-induced inflammatory responses : role of attenuation of leukocyte activation."Carcinogenesis. 21・10. 1843-1850 (2000)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2000 Final Research Report Summary
  • [Publications] Murakami,A., et al.: "Inhibitory effect of citrus nobiletin on phorbol ester-induced skin inflammation, oxidative stress, and tumor promotion in mice"Cancer Research. 61・18. 5059-5066 (2000)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2000 Final Research Report Summary
  • [Publications] Tanaka,T., et al.: "Ligands for peroxisome proliterators-activated receptors αand γinhibit chemically-induced colitis and formation of aberrant crypt foci in rats"Cancer Research. 61(in press). (2001)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2000 Final Research Report Summary
  • [Publications] Tanaka,T., et al.: "Lactoferrin : Structure, Function and Application"ELSEVIER. 465 (2000)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2000 Final Research Report Summary
  • [Publications] Tanaka,T., et al.: "Carcinogenic and Anticarcinogenic Factors in Food"WILEY-VCH. 324 (2000)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2000 Final Research Report Summary
  • [Publications] Kunihiro Kawabata, Takuji Tanaka, Tomohiro Yamamoto, Jun Ushida, Akira Hara, Akira Murakami, Koichi Koshimizu, Hajime Ohigashi, Gray D.Stoner, and Hideki Mori: "Suppression of N-nitrosomethylbenzylamine-induced rat esophageal tumorigenesis by dietary feeding of 1'-acetoxychavicol acetate."Japanese Journal of Cancer Research. 91. 148-155 (2000)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2000 Final Research Report Summary
  • [Publications] Takuji Tanaka, Hiroyuki Kohno, Manabu Murakami, Reona Shimada, and Seiko Kagami: "Colitis-associated rat colon carcinogenesis induced by 1-hydroxyanthraquinone and methylazoxymethanol acetate (Review)."Oncology.Reports. 7. 501-508 (2000)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2000 Final Research Report Summary
  • [Publications] Takuji Tanaka, Hiroyuki Kohno, Reona Shimada, Seiko Kagami, Fumio Yamaguchi, Shigehiro Kataoka, Toshiaki Ariga, Akira Murakami, Koichi Koshimizu, and Hajime Ohigashi : Takuji Tanaka, Manabu Murakami, Koichi Koshimizu and Hajime Ohigashi: "Prevention of colonic aberrant crypt foci by dietary feeding of garcinol in male F344 rats."Carcinogenesis. 21. 1183-1189 (2000)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2000 Final Research Report Summary
  • [Publications] Akira Murakami, Yoshimasa Nakamura, Takuji Tanaka, Kyuichi Kawabata, Daisuke Takahashi, Koichi Koshimizu, and Hajime Ohigashi: "Suupression by citrus auraptene of phorbol ester-and endotoxin-induced inflammatory responses ; role of attenuation of leukocyte activation."Carcinogenesis. 21. 1843-1850 (2000)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2000 Final Research Report Summary
  • [Publications] Akira Murakami, Yoshimasa Nakumura, Takuji Tanaka, Harukuni Tokuda, Hoyoku Nishino, Shigeru Kuwahara, Yasuo Takahashi, Kazunori Ogawa, Masamichi Yano, Teruaki Koshiba, Koichi Koshimizu, Koji Torikai, and Hajime Ohigashi: "Inhibitory effect of citrus nobiletin on phorbol ester-induced skin inflammation, oxidative stress, and tumor-promotion in mice."Cancer Research. 60. 5059-5066 (2000)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2000 Final Research Report Summary
  • [Publications] Takuji Tanaka, Hiroyuki Kohno, Shin-ichiro Yoshitani, Shigeki Takashima, Ataru okumura, Akira Murakami, and Masashi Hosokawa: "Ligands for peroxisome proliferator-activated receptor α and γ inhibit chemically-induced colitis and formation of aberrant crypt foci in rats."Cancer Research. 61 : (in press). (2001)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2000 Final Research Report Summary
  • [Publications] Takuji Tanaka, Kunihiro Kawabata, Hiroyuki Kohno, Shiro Honjo, Manabu Murakami, Reona Shimada, Seiko Kagami, and Hiroyuki Tsuda: "Bovine lactoferrin inhibits rat tongue carcinogenesis."Lactoferrin : Structure, Function and Applications, Elvesier Sci., Amsterdam. 401-411 (2000)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2000 Final Research Report Summary
  • [Publications] Takuji Tanaka: "Chemoprevention of colon carcinogenesis by non-nutritive compounds in foods."Sonderdruck aus Deutsche Forschungsgemeinschaft : Carcinogenic and Anticarcinogenic Factors in Food, Senate Commission on Food Safety, SKLM, Wiley-VCH, Weinheim. 365-391 (2000)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2000 Final Research Report Summary
  • [Publications] Kawabata,K., et al.: "Suppression of N-nitrosomethylbenzylamine-induced rat esophagealtumorigenesis by dietaryfeeding of 1'-acetoxychavicol acetate"Japanese Journal of Cancer Research. 91・2. 148-155 (2000)

    • Related Report
      2000 Annual Research Report
  • [Publications] Tanaka,T., et al.: "Colitis-related rat colon carcinogenesis induced by 1-hydroxyanthra-quinone and methylazoxymethanol acetate (review)"Oncology Reports. 7・3. 501-508 (2000)

    • Related Report
      2000 Annual Research Report
  • [Publications] Tanaka,T., et al.: "Prevention of colonic aberrant crypt foci by dietary feeding of garcinol in male F344 rats"Carcinogenesis. 21・6. 1183-1189 (2000)

    • Related Report
      2000 Annual Research Report
  • [Publications] Murakami,A., et al.: "Suppression by citrus auraptene of phorbol ester-and endotoxin-induced inflammatory responses : role of attenuation of leukocyte activation"Carcinogenesis. 21・10. 1843-1850 (2000)

    • Related Report
      2000 Annual Research Report
  • [Publications] Murakami,A., et al.: "Inhibitory effect of citrus nobiletin on phorbol ester-induced skin inflammation, oxidative stress, and tumor promotion in mice"Cancer Research. 60・18. 5059-5066 (2000)

    • Related Report
      2000 Annual Research Report
  • [Publications] Tanaka,T., et al.: "Ligands for peroxisome proliferators-activated receptors α and γ inhibit chemically-induced colitis and formation of aberrant crypt foci in rats"Cancer Research. 61(in press). (2001)

    • Related Report
      2000 Annual Research Report
  • [Publications] Tanaka,T., et al.: "Lactoferrin : Structure, Function and Application"ELSEVIER. 465 (2000)

    • Related Report
      2000 Annual Research Report
  • [Publications] Tanaka,T., et al.: "Carcinogenic and Anticarcinogenic Factors in Food"WILEY-VCH. 324 (2000)

    • Related Report
      2000 Annual Research Report
  • [Publications] Takuji Tanaka,et al.: "Immunomodulatory action of citrus auraptene on macrophage functions and cytokine production of lymphocytes in female BALB/c mice"Carcinogenesis. 20・8. 1471-1476 (1999)

    • Related Report
      1999 Annual Research Report
  • [Publications] Kunihiro Kawabata,et al.: "Chemopreventive effect of dietary flavonoid morin on chemically induced rat tongue carcinogenesis"International Journal of Cancer. 83・3. 381-386

    • Related Report
      1999 Annual Research Report
  • [Publications] Takuji Tanaka,et al.: "Chemopreventive effect of dietary bovine lactoferrin on 4-nitro-quinoline 1-oxide-induced tongue carcinogenesis in male F344 rats"Japanese Journal of Cancer Research. 91・1(印刷中). (2000)

    • Related Report
      1999 Annual Research Report
  • [Publications] Akira Murakami,et al.: "Food for Health in the Pacific Rim"Food&Nutrition Press,Inc.. 9 (1999)

    • Related Report
      1999 Annual Research Report
  • [Publications] Takuji Tanaka: "Chemopre vention of 4-nitroquinaline 1-oxide-induced oral carcinogenesis by citrus auraptene in rats" Carcinogenesis. 19・3. 425-431 (1998)

    • Related Report
      1998 Annual Research Report
  • [Publications] Takuji Tanaka: "Citrus auraptene exerts dose-dependent chemopreventive activity in rat large bowel tumorigenesis : The inhibition correlates with suppression of cell praliferation and lipid peroxidstion and with induction of phase II drug-metabolizing enzymes" Cancer Research. 58・12. 2550-2556 (1998)

    • Related Report
      1998 Annual Research Report
  • [Publications] Yoshimasa Nakamura: "Suppression of tumor promoter-induced oxidative stress and in flammatory responses in mouse skin by a superoxide generation in hibitor 1′-acetoxychavicol acetate" Cancer Research. 58・21. 4832-4839 (1998)

    • Related Report
      1998 Annual Research Report

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Published: 1998-04-01   Modified: 2016-04-21  

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