Targeting obesity-related metabolic abnormalities for chemoprevention of colorectal cancer and hepatocellular carcinoma

• Project/Area Number: 22790638
• Research Category: Grant-in-Aid for Young Scientists (B)
• Allocation Type: Single-year Grants
• Research Field: Gastroenterology
• Research Institution: Gifu University
• Principal Investigator: SHIMIZU Masahito 岐阜大学, 医学部・附属病院, 助教 (90402198)
• Project Period (FY): 2010 – 2011
• Project Status: Completed (Fiscal Year 2011)
• Budget Amount: ¥3,900,000 (Direct Cost: ¥3,000,000、Indirect Cost: ¥900,000); Fiscal Year 2011: ¥1,820,000 (Direct Cost: ¥1,400,000、Indirect Cost: ¥420,000); Fiscal Year 2010: ¥2,080,000 (Direct Cost: ¥1,600,000、Indirect Cost: ¥480,000)
• Keywords: 肥満 / 発癌予防 / 大腸癌 / 肝細胞癌

Research Abstract

Obesity-and diabetes-related metabolic abnormalities, including insulin resistance, alterations in the IGF-1/IGF-1 receptor axis, state of chronic inflammation, and occurrence of adipokine imbalance, increase the risk of colorectal cancer and hepatocellular carcinoma. Therefore, improvement of these metabolic abnormalities by either pharmaceutical or nutritional intervention, such as supplementation with branched-chain amino acids, may be an effective strategy to prevent the development of colorectal cancer and hepatocellular carcinoma in obese individuals.

Research Products

• [Journal Article] Nutraceutical approach for preventing obesity-related colorectal and liver carcinogenesis (2012)
  • Author(s): Shimizu M, Kubota M, Tanaka T, Moriwaki H.
  • Journal Title: Int J Mol Sci Volume: 13 Pages: 579-595
• [Journal Article] Monosodium glutamate-induced diabetic mice are susceptible to azoxymethane-induced colon tumorigenesis (2012)
  • Author(s): Hata K, Kubota M, Shimizu M, Moriwaki H, Kuno T, Tanaka T, Hara A, Hirose Y.
  • Journal Title: Carcinogenesis Volume: 33 Pages: 702-707
• [Journal Article] Preventive effects of curcumin on the development of azoxymethane-induced colonic preneoplastic lesions in male C57BL/KsJ-db/db obese mice (2012)
  • Author(s): Kubota M, Shimizu M, Sakai H, Yasuda Y, Terakura D, Baba A, Ohno T, Tsurumi H, Tanaka T, Moriwaki H.
  • Journal Title: Nutr Cancer Volume: 64 Pages: 72-79
• [Journal Article] Possible role of visfatin in hepatoma progression and the effects of branched-chain amino acids on visfatin-induced proliferation in human hepatoma cells (2011)
  • Author(s): Ninomiya S, Shimizu M, Imai K, Takai K, Shiraki M, Hara T, Tsurumi H, Ishizaki S, Moriwaki H.
  • Journal Title: Cancer Prev Res Volume: 4 Pages: 2092-2100
• [Journal Article] Increased levels of serum leptin are a risk factor for the recurrence of stage I/II hepatocellular carcinoma after curative treatment (2011)
  • Author(s): Watanabe N, Takai K, Imai K, Shimizu M, Naiki T, Nagaki M, Moriwaki H.
  • Journal Title: J Clin Biochem Nutr Volume: 49 Pages: 153-158
  • NAID: 130004466652
• [Journal Article] C57BL/KsJ-db/db-Apc mice exhibit an increased incidence of intestinal neoplasms (2011)
  • Author(s): Hata K, Kubota M, Shimizu M, Moriwaki H, Kuno T, Tanaka T, Hara A, Hirose Y.
  • Journal Title: Int J Mol Sci Volume: 12 Pages: 8133-8145
• [Journal Article] Acyclic retinoid inhibits diethylnitrosamine-induced liver tumorigenesis in obese and diabetic C57BLKS/J-+(db)/+Lepr(db) mice (2011)
  • Author(s): Shimizu M, Sakai H, Shirakami Y, Iwasa J, Yasuda Y, Kubota M, Takai K, Tsurumi H, Tanaka T, Moriwaki H.
  • Journal Title: Cancer Prev Res Volume: 4 Pages: 128-136
• [Journal Article] Preventive effects of(-)-epigallocatechin gallate on diethylnitrosamine-induced liver tumorigenesis in obese and diabetic C57BL/KsJ-db/db Mice (2011)
  • Author(s): Shimizu M, Sakai H, Shirakami Y, Yasuda Y, Kubota M, Terakura D, Baba A, Ohno T, Hara Y, Tanaka T, Moriwaki H.
  • Journal Title: Cancer Prev Res Volume: 4 Pages: 396-403
• [Journal Article] Pitavastatin suppresses diethylnitrosamine-induced liver preneoplasms in male C57BL/KsJ-db/db obese mice (2011)
  • Author(s): Shimizu M, Yasuda Y, Sakai H, Kubota M, Terakura D, Baba A, Ohno T, Kochi T, Tsurumi H, Tanaka T, Moriwaki H.
  • Journal Title: BMC Cancer Volume: 11 Pages: 281-281
• [Journal Article] Cancer chemoprevention with green tea catechins by targeting receptor tyrosine kinases (2011)
  • Author(s): Shimizu M, Adachi S, Masuda M, Kozawa O, Moriwaki H.
  • Journal Title: Mol Nutr Food Res Volume: 55 Pages: 832-843
• [Journal Article] Chemoprevention of hepatocellular carcinoma by acyclic retinoid (2011)
  • Author(s): Shimizu M, Sakai H, Moriwaki H.
  • Journal Title: Front Biosci Volume: 16 Pages: 759-769
  • NAID: 110009594131
• [Journal Article] Ultraviolet irradiation can induce evasion of colon cancer cells from stimulation of epidermal growth factor (2011)
  • Author(s): Adachi S, Yasuda I, Nakashima M, Yamauchi T, Kawaguchi J, Shimizu M, Itani M, Nakamura M, Nishii Y, Yoshioka T, Hirose Y, Okano Y, Moriwaki H, Kozawa O.
  • Journal Title: J Biol Chem Volume: 286 Pages: 26178-26187
• [Journal Article] Renin-angiotensin system inhibitors suppress azoxymethane-induced colonic preneoplastic lesions in C57BL/KsJ-db/db obese mice (2011)
  • Author(s): Kubota M, Shimizu M, Sakai H, Yasuda Y, Ohno T, Kochi T, Tsurumi H, Tanaka T, Moriwaki H.
  • Journal Title: Biochem Biophys Res Commun Volume: 410 Pages: 108-113
• [Journal Article] Acyclic retinoid inhibits diethylnitrosamine-induced liver tumorigenesis in obese and diabetic C57BLKS/J- +(db)/+Lepr(db) mice (2011)
  • Author(s): Shimizu M, Sakai H, Shirakami Y, Iwasa J, Yasuda Y, Kubota M, Takai K, Tsurumi H, Tanaka T, Moriwaki H
  • Journal Title: Cancer Prev Res Volume: 4 Pages: 128-136
  • Peer Reviewed
• [Journal Article] Preventive effects of (-)-epigallocatechin gallate on diethylnitrosamine-induced liver tumorigenesis in obese and diabetic C57BL/K sJ-db/db Mice (2011)
  • Author(s): Shimizu M, Sakai H, Shirakami Y, Yasuda Y, Kubota M, Terakura D, Baba A, Ohno T, Hara Y, Tanaka T, Moriwaki H
  • Journal Title: Cancer Prev Res Volume: 4 Pages: 396-403
  • Peer Reviewed
• [Journal Article] Pitavastatin suppresses diethylnitrosamine-induced liver preneoplasms in male C57BL/KsJ-db/db obese mice (2011)
  • Author(s): Shimizu M, Yasuda Y, Sakai H, Kubota M, Terakura D, Baba A, Ohno T, Kochi T, Tsurumi H, Tanaka T, Moriwaki H
  • Journal Title: BMC Cancer Volume: 11 Pages: 281-281
  • Peer Reviewed
• [Journal Article] (-)-Epigallocatechin gallate inhibits growth and activation of the VEGF/VEGFR axis in human colorectal cancer cells (2010)
  • Author(s): Shimizu M, Shirakami Y, Sakai H, Yasuda Y, Kubota M, Adachi S, Tsurumi H, Hara Y, Moriwaki H.
  • Journal Title: Chem Biol Interact Volume: 185 Pages: 247-252
• [Journal Article] Pitavastatin inhibits azoxymethane-induced colonic preneoplastic lesions in C57BL/KsJ-db/db obese mice (2010)
  • Author(s): Yasuda Y, Shimizu M, Shirakami Y, Sakai H, Kubota M, Hata K, Hirose Y, Tsurumi H, Tanaka T, Moriwaki H.
  • Journal Title: Cancer Sci Volume: 101 Pages: 1701-1707
  • NAID: 10026594934
• [Journal Article] Dietary supplementation with branched-chain amino acids suppresses diethylnitrosamine-induced liver tumorigenesis in obese and diabetic C57BL/KsJ-db/db mice (2010)
  • Author(s): Iwasa J, Shimizu M, Shiraki M, Shirakami Y, Sakai H, Terakura Y, Takai K, Tsurumi H, Tanaka T, Moriwaki H.
  • Journal Title: Cancer Sci Volume: 101 Pages: 460-467
  • NAID: 10026588190
• [Journal Article] Insulin resistance raises the risk for recurrence of stage I hepatocellularcarcinoma after curative radiofrequency ablation in HCV-positive patiens : A prospective, case-series study (2010)
  • Author(s): Imai K, Takai K, Nishigaki Y, Shimizu S, Naiki T, Hayashi H, Uematsu T, Sugihara J, Tomita E, Shimizu M, Nagaki M, Moriwaki H.
  • Journal Title: Hepatol Res Volume: 40 Pages: 376-382
• [Journal Article] Genetic ablation of Tnfalpha demonstrates no detectable suppressive effect on inflammation-related mouse colon tumorigenesis (2010)
  • Author(s): Sakai H, Yamada Y, Shimizu M, Saito K, Moriwaki H, Hara A.
  • Journal Title: Chem Biol Interact Volume: 184 Pages: 423-430
• [Journal Article] (-)-Epigallocatechin gallate inhibits growth and activation of the VEGF/VEGFR axis in human colorectal cancer cells. (2010)
  • Author(s): Shimizu M, Shirakami Y, Sakai H, Yasuda Y, Kubota M, Adachi S, Tsurumi H, Hara Y, Moriwaki H.
  • Journal Title: Chem Biol Interact Volume: 185 Pages: 247-252
  • Peer Reviewed
• [Journal Article] Pitavastatin inhibits azoxymethane-induced colonic preneoplastic lesions in C57BL/KsJ-db/db obese mice. (2010)
  • Author(s): Yasuda Y, Shimizu M, Shirakami Y, Sakai H, Kubota M, Hata K, Hirose Y, Tsurumi H, Tanaka T, Moriwaki H.
  • Journal Title: Cancer Sci Volume: 101 Pages: 1701-1707
  • NAID: 10026594934
  • Peer Reviewed
• [Journal Article] Dietary supplementation with branched-chain amino acids suppresses diethylnitrosamine-induced liver tumorigenesis in obese and diabetic C57BL/KsJ-db/db mice. (2010)
  • Author(s): Iwasa J, Shimizu M, Shiraki M, Shirakami Y, Sakai H, Terakura Y, Takai K, Tsurumi H, Tanaka T, Moriwaki H.
  • Journal Title: Cancer Sci Volume: 101 Pages: 460-467
  • NAID: 10026588190
  • Peer Reviewed
• [Journal Article] Insulin resistance raises the risk for recurrence of stage I hepato cellularcarcinoma after curative radiofrequency ablation in HCV-positive patiens : A prospective, case-series study. (2010)
  • Author(s): Imai K, Takai K, Nishigaki Y, Shimizu S, Naiki T, Hayashi H, Uematsu T, Sugihara J, Tomita E, Shimizu M, Nagaki M, Moriwaki H.
  • Journal Title: Hepatol Res Volume: 40 Pages: 376-382
  • Peer Reviewed
• [Journal Article] Genetic ablation of Tnfalpha demonstrates no detectable suppressive effect on inflammation-related mouse colon tumorigenesis. (2010)
  • Author(s): Sakai H, Yamada Y, Shimizu M, Saito K, Moriwaki H, Hara A.
  • Journal Title: Chem Biol Interact Volume: 184 Pages: 423-430
  • Peer Reviewed
• [Presentation] ワークショップ18「消化器疾患におけるprobioticsと機能性食品の有用性」緑茶カテキンを用いた肥満関連大腸および肝発癌予防 (2011)
  • Author(s): 清水雅仁、久保田全哉、森脇久隆
  • Organizer: JDDW2011(第53回日本消化器病学会大会)
  • Place of Presentation: 福岡
• [Presentation] シンポジウム「がん予防戦略の最前線」肥満関連分子異常を標的とした肝発癌化学予防 (2011)
  • Author(s): 清水雅仁、森脇久隆
  • Organizer: がん予防大会2011京都
  • Place of Presentation: 京都
• [Presentation] ワークショップ7「Steatohepatitisの病態～その多様性と相同性～」非環式レチノイドによる肥満関連肝腫瘍形成の抑制 (2011)
  • Author(s): 清水雅仁、森脇久隆
  • Organizer: 第97回日本消化器病学会総会
  • Place of Presentation: 新潟
• [Presentation] ワークショップ5「肝発癌・進展とインスリン抵抗性」インスリン抵抗性とIGF/IGF-1受容体シグナルを標的とした肥満関連肝発癌予防 (2010)
  • Author(s): 清水雅仁、岩砂淳平、森脇久隆
  • Organizer: 第46回日本肝臓学会総会
  • Place of Presentation: 山形
• [Presentation] シンポジウム2「消化器癌と栄養療法」分枝鎖アミノ酸製剤(BCAA)を用いた肥満関連肝および大腸発癌の予防 (2010)
  • Author(s): 清水雅仁、白木亮、森脇久隆
  • Organizer: 第96回日本消化器病学会総会
  • Place of Presentation: 新潟