Elucidation of activation mechanism of insulin-like growth factor and development of therapy using neutralizing antibody in the gastrointestinal cancers

• Project/Area Number: 23590939
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: Gastroenterology
• Research Institution: Kyoto University
• Principal Investigator: MIYAMOTO Shin'ichi 京都大学, 医学(系)研究科(研究院), 助教 (90378761)
• Project Period (FY): 2011 – 2013
• Project Status: Completed (Fiscal Year 2013)
• Budget Amount: ¥4,940,000 (Direct Cost: ¥3,800,000、Indirect Cost: ¥1,140,000); Fiscal Year 2013: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000); Fiscal Year 2012: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000); Fiscal Year 2011: ¥2,210,000 (Direct Cost: ¥1,700,000、Indirect Cost: ¥510,000)
• Keywords: がん / シグナル伝達 / 分子標的薬 / インスリン様増殖因子 / 中和抗体 / 分子標的治療 / 腫瘍微小環境 / バイオマーカー / 活性型インスリン様増殖因子 / 肝転移

Research Abstract

It is necessary for the cancer cells to adapt to the tissue microenvironment for the metastasis formation in other ogans. Colon cancer cells highly metastasize to the liver and control of liver metastasis is most important issue in the therapeutic strategy of colon cancer. We clarified that liver-derived insulin-like growth factors (IGFs) activated by cancer-producing protease play an important role for the liver metastasis formation and could be a therapeutic target using neutralizing antibody. Furthermore, we developed the measurement system of activted (bioactive) IGF in the blood and demonstrated that bioactive IGF was increased with progressio of liver metastais and could be a biomarker of IGF neutralizing strategy in the mouse model.

Research Products

• [Journal Article] Multimodal endoscopic treatment for delayed severe esophageal stricture caused by incomplete stent removal (2014)
  • Author(s): Setoyma T, Miyamoto S, Horimatsu T, Morita S, Ezoe Y, Muto M, Watanabe G, Tanaka E, Chiba T
  • Journal Title: Dis Esophagus Volume: 2 Issue: 2 Pages: 7112-115
  • DOI: 10.1111/dote.12041
  • Peer Reviewed
• [Journal Article] Stability of acetaldehyde-derived DNA adduct in vitro. (2012)
  • Author(s): Hori K.
  • Journal Title: Biochem Biophys Res Commun. Volume: 423 Issue: 4 Pages: 642-646
  • DOI: 10.1016/j.bbrc.2012.05.158
  • Peer Reviewed
• [Journal Article] A case of long-term survival of metastatic desmoplastic small round cell tumor treated with multimodal therapy (2012)
  • Author(s): Watanabe T, Miyamoto S, Kitagori K, Horimatsu T, Morita S, Mashimo Y, Ezoe Y, Muto M, Chiba T
  • Journal Title: Oncol Lett Volume: 3(1) Issue: 1 Pages: 30-34
  • DOI: 10.3892/ol.2011.457
  • Peer Reviewed
• [Journal Article] Hemosuccus pancreaticus diagnosed with concurrent endoscopic retrograde pancreatography and selective angiography. (2012)
  • Author(s): Setoyama T.
  • Journal Title: Clin Gastroenterol Hepatol. Volume: 10 Issue: 4 Pages: A28-A28
  • DOI: 10.1016/j.cgh.2011.10.024
  • Peer Reviewed
• [Journal Article] Education and gastrointestinal imaging: case of early-stage squamous cell carcinoma of the anal canal diagnosed using narrow-band imaging system with magnification. (2012)
  • Author(s): Horimatsu T.
  • Journal Title: J Gastroenterol Hepatol. Volume: 27 Issue: 8 Pages: 1468-1468
  • DOI: 10.1111/j.1440-1746.2012.07182.x
  • Peer Reviewed
• [Journal Article] Cerebral air embolism caused by chemoradiotherapy for esophageal cancer. (2012)
  • Author(s): Miyamoto S.
  • Journal Title: J Clin Oncol. Volume: 30 Issue: 25 Pages: e237-e238
  • DOI: 10.1200/jco.2012.41.6156
  • Peer Reviewed
• [Journal Article] Cancer risk and management in a woman with Peutz-Jeghers syndrome. (2012)
  • Author(s): Yasumoto K.
  • Journal Title: Int Canc Conf J Volume: -
  • Peer Reviewed
• [Journal Article] A case of long-term survival of metastatic desmoplastic small round cell tumor treated with multimodal therapy. (2012)
  • Author(s): Watanabe T.
  • Journal Title: Oncol Lett. Volume: 3 Pages: 30-34
  • Peer Reviewed
• [Journal Article] Usefulness of endoscopic radial incision and cutting method for refractory esophagogastric anastomotic stricture (with video). (2012)
  • Author(s): Muto M.
  • Journal Title: Gastrointest Endosc. Volume: 75 Issue: 5 Pages: 965-972
  • DOI: 10.1016/j.gie.2012.01.012
  • Peer Reviewed
• [Journal Article] Tissue damage in the canine normal esophagus by photoactivation with talaporfin sodium (laserphyrin): a preclinical study. (2012)
  • Author(s): Horimatsu T.
  • Journal Title: PLoS One. Volume: 7 Issue: 6 Pages: e38308-e38308
  • DOI: 10.1371/journal.pone.0038308
  • Peer Reviewed
• [Journal Article] Acute Airway Obstruction in a Patient with Achalasia (2011)
  • Author(s): Miyamoto S, Konda Y, Matsui M, Sawada K, Ikeda K, Watanabe N, Kawanami C, Chiba T
  • Journal Title: Internal Medicine Volume: 50 Issue: 20 Pages: 2333-2336
  • DOI: 10.2169/internalmedicine.50.5603
  • NAID: 130001087742
  • ISSN: 0918-2918, 1349-7235
  • Peer Reviewed
• [Journal Article] An unusual cause of dysphagia after endoscopic resection of an early esophageal cancer (2011)
  • Author(s): Nakanishi Y, Miyamoto S, Ishizu S, Seno H, Muto M, Chiba T
  • Journal Title: Endoscopy Volume: 43 Suppl 2 Issue: S 02 Pages: E156-E157
  • DOI: 10.1055/s-0030-1256260
  • Peer Reviewed
• [Journal Article] Pharmacokinetics of oxaliplatin in a hemodialytic patient treated with modified FOLFOX-6 plus bevacizumab therapy (2011)
  • Author(s): Horimatsu T, Miyamoto S, Morita S, Mashimo Y, Ezoe Y, Muto M, Chiba T
  • Journal Title: Cancer Chemother Pharmacol Volume: 68(1) Issue: 1 Pages: 263-6
  • DOI: 10.1007/s00280-011-1633-9
  • Peer Reviewed
• [Journal Article] Umbilical Metastasis (Sister Mary Joseph's Nodule) From Esophageal Squamous Cell Carcinoma (2011)
  • Author(s): Mashimo Y, Horimatsu T, Miyamoto S
  • Journal Title: Clin Gastroenterol Hepatol Volume: 9(8) Issue: 8 Pages: A20-A20
  • DOI: 10.1016/j.cgh.2011.02.023
  • Peer Reviewed
• [Journal Article] Early detection of 5-FU-induced acute leukoencephalopathy on diffusion-weighted MRI (2011)
  • Author(s): Akitake R, Miyamoto S, Nakamura F, Horimatsu T, Ezoe Y, Muto M, Chiba T
  • Journal Title: Jpn J Clin Oncol Volume: 41(1) Issue: 1 Pages: 121-4
  • DOI: 10.1093/jjco/hyq157
  • Peer Reviewed
• [Journal Article] Differences of image enhancement in image-enhanced endoscopy: narrow band imaging versus flexible spectral imaging color enhancement. (2011)
  • Author(s): Muto M, Higuchi H, Ezoe Y, Horimatsu T, Morita S, Miyamoto S, Chiba T.
  • Journal Title: J Gastroenterol. Volume: 46 Issue: 8 Pages: 998-1002
  • DOI: 10.1007/s00535-011-0419-5
  • NAID: 10029563212
  • Peer Reviewed
• [Journal Article] Long-term outcome of transoral organ-preserving pharyngeal endoscopic resection for superficial pharyngeal cancer. (2011)
  • Author(s): Muto M, Satake H, Yano T, Minashi K, Hayashi R, Fujii S, Ochiai A, Ohtsu A, Morita S, Horimatsu T, Ezoe Y, Miyamoto S, Asato R, Tateya I, Yoshizawa A, Chiba T.
  • Journal Title: Gastrointest Endosc. Volume: 74 Issue: 3 Pages: 477-484
  • DOI: 10.1016/j.gie.2011.04.027
  • Peer Reviewed
• [Journal Article] Endoscopic features of sessile serrated adenoma and other serrated colorectal polyps. (2011)
  • Author(s): Yamada A, Notohara K, Aoyama I, Miyoshi M, Miyamoto S, Fujii S, Yamamoto H.
  • Journal Title: Hepatogastroenterology Volume: 58 Pages: 45-51
  • Peer Reviewed
• [Journal Article] Efficacy of preventive endoscopic balloon dilation for esophageal stricture after endoscopic resection. (2011)
  • Author(s): Ezoe Y, Muto M, Horimatsu T, Morita S, Miyamoto S, Mochizuki S, Minashi K, Yano T, Ohtsu A, Chiba T.
  • Journal Title: J Clin Gastroenterol. Volume: 45 Issue: 3 Pages: 222-227
  • DOI: 10.1097/mcg.0b013e3181f39f4e
  • Peer Reviewed
• [Presentation] 食道癌化学放射線療法後の表在性局所遺残・再発病変に対する内視鏡的salvage EMR/ESDの成績 (2012)
  • Author(s): 菊池理.
  • Organizer: 日本消化器内視鏡学会近畿支部第89回支部例会
  • Place of Presentation: 大阪国際会議場(大阪)
• [Presentation] ワークショップ7-2大腸がんに対するインスリン様増殖因子の治療標的としての有用性-発がんから肝転移まで- (2011)
  • Author(s): 宮本心一
  • Organizer: 第7回日本消化管学会総会学術集会
  • Place of Presentation: 京都
  • Year and Date: 2011-02-18
• [Book] Multiple early-stage malignant melanoma of the esophagus with a long follow-up period after endoscopic treatment : report of a case and a literature review. Esophageal Cancer–Cell and Molecular Biology, Biomarkers, Nutrition and Treatment Croatia (2012)
  • Author(s): Miyamoto S, Morita S, Muto M
  • Publisher: INTECH
• [Book] ESOPHAGEAL CANCER CELL AND MOLECULAR BIOLOGY, BIOMARKERS, NUTRITION AND TREATMENT (2012)
  • Author(s): Miyamoto S.
  • Publisher: INTECH(Croatia)
• [Remarks]
  • URL: http://www.kuhp.kyoto-u.ac.jp/~gastro/mmuto/
• [Remarks] 京都大学医学部附属病院 武藤学研究室
  • URL: http://www.kuhp.kyoto-u.ac.jp/~gastro/mmuto/
• [Remarks] 武藤学研究室
  • URL: http://www.kuhp.kyoto-u.ac.jp/~gastro/mmuto/
• [Remarks]
  • URL: http://www.kuhp.kyoto-u.ac.jp/~gastro/mmuto/
• [Remarks] 京都大学 武藤学 研究室