Chemopreventive effects of metformin for colon carcinogenesis

• Project/Area Number: 24790714
• Research Category: Grant-in-Aid for Young Scientists (B)
• Allocation Type: Multi-year Fund
• Research Field: Gastroenterology
• Research Institution: Yokohama City University
• Principal Investigator: HOSONO Kunihiro 横浜市立大学, 附属病院, 助教 (50537339)
• Project Period (FY): 2012-04-01 – 2014-03-31
• Project Status: Completed (Fiscal Year 2013)
• Budget Amount: ¥4,160,000 (Direct Cost: ¥3,200,000、Indirect Cost: ¥960,000); Fiscal Year 2013: ¥2,080,000 (Direct Cost: ¥1,600,000、Indirect Cost: ¥480,000); Fiscal Year 2012: ¥2,080,000 (Direct Cost: ¥1,600,000、Indirect Cost: ¥480,000)
• Keywords: メトホルミン / 大腸癌 / 化学予防

Research Abstract

We prospectively randomized nondiabetic patients with ACF to treatment with metformin or no treatment.The metformin group had a significant decrease in the mean number of ACF per patient, whereas the mean ACF number did not change significantly in the control group. We examined the potential direct effects of metformin on ACF via PCNA immunostaining for colorectal cell proliferative activity and TUNEL for apoptosis. The PCNA index decreased significantly following metformin treatment, although the apoptotic index did not change significantly. These data suggest that metformin effects in suppressing cell proliferation mediate suppressive effects on ACF formation. This first reported trial of metformin for inhibiting colorectal carcinogenesis in humans provides preliminary evidence that metformin suppresses colonic epithelial proliferation and rectal ACF formation in humans.

Research Products

• [Journal Article] Covered self-expandable metal stent deployment promises safe neoadjuvant chemoradiation therapy in patients with borderline resectable pancreatic head cancer (2014)
  • Author(s): Kubota K, Sato T, Watanabe S, Hosono K, Kobayashi N, Mori R, Taniguchi K, Matsuyama R, Endo I, Nakajima A
  • Journal Title: Dig Endosc. Volume: 26 Issue: 1 Pages: 77-86
  • DOI: 10.1111/den.12049
  • Peer Reviewed
• [Journal Article] Colon epithelial proliferation and carcinogenesis in diet-induced obesity (2013)
  • Author(s): Takahashi H, Hosono K, Endo H, Nakajima A
  • Journal Title: J Gastroenterol Hepatol. Volume: 28 Issue: S4 Pages: 41-47
  • DOI: 10.1111/jgh.12240
  • Peer Reviewed
• [Journal Article] Diagnosis of biliary cystadenoma by peroral video cholangioscopy (2013)
  • Author(s): Watanabe S, Sato T, Hosono K, Kobayashi N, Endo I, Nakayama T, Inayama Y, Nakajima A, Kubota K
  • Journal Title: Endoscopy Volume: 45 Issue: S 02 Pages: E284-E285
  • DOI: 10.1055/s-0033-1344416
  • Peer Reviewed
• [Journal Article] Diagnosis of biliary cystadenoma by peroral video cholangioscopy. (2013)
  • Author(s): Watanabe S, Sato T, Hosono K, Kobayashi N, Endo I, Nakayama T, Inayama Y, Nakajima A, Kubota K.
  • Journal Title: Endoscopy Volume: 45 Issue: 10 Pages: 835-837
  • DOI: 10.1055/s-0033-1344330
  • Peer Reviewed
• [Journal Article] aPKClambda/iota is a beneficial prognostic marker for pancreatic neoplasms. (2013)
  • Author(s): Kato S, Akimoto K, Nagashima Y, Ishiguro H, Kubota K, Kobayashi N, Hosono K, Watanabe S, Sekino Y, Sato T, Sasaki K, Nakaigawa N, Kubota Y, Inayama Y, Endo I, Ohno S, Maeda S, Nakajima A
  • Journal Title: Pancreatology Volume: 13 Issue: 4 Pages: 360-8
  • DOI: 10.1016/j.pan.2013.05.006
  • Peer Reviewed
• [Journal Article] Inamori MEarly Effect of Single-dose Sitagliptin Administration on Gastric Emptying : Crossover Study Using the (13)C Breath Test (2013)
  • Author(s): Nonaka T, Sekino Y, Iida H, Yamada E, Ohkubo H, Sakai E, Higurashi T, Hosono K, Endo H, Koide T, Takahashi H, Fujita K, Yoneda M, Goto A, Kusakabe A, Kobayashi N, Gotoh E, Maeda S, Nakajima A, Nosaka C
  • Journal Title: J Neurogastroenterol Motil. Volume: 19 Issue: 2 Pages: 227-32
  • DOI: 10.5056/jnm.2013.19.2.227
  • Peer Reviewed
• [Journal Article] A novel scoring system for arterial invasion of pancreatic body and tail cancer based on multidetector row computed tomography and biomarkers (2013)
  • Author(s): Watanabe S, Kobayashi N, Kubota K, Sato T, Kato S, Hosono K, Shimamura T, Inayama Y, Nakajima A, Endo I
  • Journal Title: Pancreatology Volume: 13 Issue: 2 Pages: 161-9
  • DOI: 10.1016/j.pan.2012.12.364
  • Peer Reviewed
• [Journal Article] Tumor diameter and Ki-67 expression in biopsy could be diagnostic markers discriminating from adenoma and early stage cancer in patients with ampullary tumors (2013)
  • Author(s): Kubota K, Fujita Y, Sato T, Watanabe S, Hosono K, Yoneda M, Kirikoshi H, Hisatomi K, Matsuhashi N, Endo I, Inayama Y, Nakajima A
  • Journal Title: J Hepatobiliary Pancreat Sci. Volume: 20 Issue: 5 Pages: 531-7
  • DOI: 10.1007/s00534-013-0594-2
  • NAID: 10031183511
  • Peer Reviewed
• [Journal Article] Factors predicting the presence of small bowel lesions in patients with obscure gastrointestinal bleeding. (2013)
  • Author(s): Sakai E, Endo H, Taniguchi L, Hata Y, Ezuka A, Nagase H, Yamada E, Ohkubo H, Higurashi T, Sekino Y, Koide T, Iida H, Hosono K, Nonaka T, Takahashi H, Inamori M, Maeda S, Nakajima A.
  • Journal Title: Dig Endosc. Volume: 25 Issue: 4 Pages: 412-420
  • DOI: 10.1111/den.12002
  • Peer Reviewed
• [Journal Article] Needle-knife precut papillotomy with a small incision over a pancreatic stent improves the success rate and reduces the complication rate in difficult biliary cannulations (2013)
  • Author(s): Kubota K, Sato T, Kato S, Watanabe S, Hosono K, Kobayashi N, Hisatomi K, Matsuhashi N, Nakajima A.
  • Journal Title: J Hepatobiliary Pancreat Sci. Volume: 20 Issue: 3 Pages: 382-8
  • DOI: 10.1007/s00534-012-0552-4
  • NAID: 10031168235
  • Peer Reviewed
• [Journal Article] Relationship of human rectal aberrant crypt foci and formation of colorectal polyp: One-year following up after polypectomy. (2012)
  • Author(s): Hirokazu Takahashi
  • Journal Title: World J Gastrointest Endosc Volume: 4 Issue: 12 Pages: 561-4
  • DOI: 10.4253/wjge.v4.i12.561
  • Peer Reviewed
• [Journal Article] Increased tumor necrosis factor receptor 1 expression in human colorectal adenomas. (2012)
  • Author(s): Kunihiro Hosono
  • Journal Title: World J Gastroenterol. Volume: 18 Issue: 38 Pages: 5360-8
  • DOI: 10.3748/wjg.v18.i38.5360
  • Peer Reviewed
• [Journal Article] Eicosapentaenoic acid (EPA) efficacy for colorectal aberrant crypt foci (ACF): a double-blind randomized controlled trial. (2012)
  • Author(s): Takuma Higurashi
  • Journal Title: BMC Cancer Volume: 12 Issue: 1 Pages: 413-413
  • DOI: 10.1186/1471-2407-12-413
  • Peer Reviewed
• [Journal Article] Metformin efficacy and safety for colorectal polyps: a double-blind randomized controlled trial. (2012)
  • Author(s): Higurashi T, Takahashi H, Endo H, Hosono K, Uchiyama T, Hata Y,Ezuka A, Yamanaka S, Inayama Y,et.al.
  • Journal Title: BMC Cancer. Volume: 12(1) Issue: 1 Pages: 118-118
  • DOI: 10.1186/1471-2407-12-118
  • Peer Reviewed
• [Presentation] 機能性食品や補助食品の消化器疾患における役割 エイコサペントエン酸(EPA)は大腸上皮の増殖を抑制しACFを減少させる 二重盲検無作為対照試験 (2013)
  • Author(s): 日暮 琢磨, 中島 淳
  • Organizer: 第21回 日本消化器関連学会週間
  • Place of Presentation: グランドプリンスホテル新高輪（東京都港区）