Establishment of the novel mouse model of metastatic colorectalcancer and identification of the biomarker for tissue-specific metastasis

• Project/Area Number: 22390257
• Research Category: Grant-in-Aid for Scientific Research (B)
• Allocation Type: Single-year Grants
• Section: 一般
• Research Field: Digestive surgery
• Research Institution: Hiroshima University
• Principal Investigator: HINOI Takao 広島大学, 病院, 講師 (10444689)
• Co-Investigator(Renkei-kenkyūsha): OKAJIMA Masazumi 広島大学, 医歯薬保健学研究院, 教授 (90274068) ; SOTOMARU Yusuke 広島大学, 自然科学研究支援開発センター, 教授 (90309352) ; IKENOUE Tsuneo 東京大学, 医学部附属病院, 助教 (80396712) ; OUE Naohide 広島大学, 医歯薬保健学研究院, 講師 (60346484) ; MIYAMOTO Kazuaki 呉医療センター, 臨床研究部, 室長 (30332373)
• Project Period (FY): 2010 – 2012
• Project Status: Completed (Fiscal Year 2012)
• Budget Amount: ¥19,240,000 (Direct Cost: ¥14,800,000、Indirect Cost: ¥4,440,000); Fiscal Year 2012: ¥4,550,000 (Direct Cost: ¥3,500,000、Indirect Cost: ¥1,050,000); Fiscal Year 2011: ¥5,460,000 (Direct Cost: ¥4,200,000、Indirect Cost: ¥1,260,000); Fiscal Year 2010: ¥9,230,000 (Direct Cost: ¥7,100,000、Indirect Cost: ¥2,130,000)
• Keywords: 小腸大腸肛門外科学 / 大腸癌マウスモデル / バイオマーカー / 大腸癌転移マウスモデル

Research Abstract

We generated novel mouse model with complex mutation of colorectal cancer-related gene. (1) The appropriate condition for tumor development was optimized. (2) Observation of the tumor by micro-endoscope was performed.(3)Effect of the specific medication on the tumor growth was analyzed. (4) Afterestablishment of the mouse model with K-ras mutation, comprehensive gene profiling analysis of K-ras signaling was performed and its target gene was identified. In conclusion, useful mouse model for the individualized medication of colorectal cancer was established.

Research Products

• [Journal Article] Preservation of peritoneal fibrinolysis owing to decreased transcription of plasminogen activator inhibitor-1 in peritoneal mesothelial cells suppresses postoperative adhesion formation in laparoscopic surgery. (2013)
  • Author(s): Shimomura M, Hinoi T, Ikeda S, Adachi T, Kawaguchi Y, Tokunaga M, Sasada T, Egi H, Tanabe K, Okajima M, Ohdan H.
  • Journal Title: Surgery. 2013 Mar Volume: 153(3) Issue: 3 Pages: 344-56
  • DOI: 10.1016/j.surg.2012.07.037
  • Peer Reviewed
• [Journal Article] Primary lung cancer presenting with metastasis to the colon: a case report. (2012)
  • Author(s): Sakai H, Egi H, Hinoi T, Tokunaga M, Kawaguchi Y, Shinomura M, Adachi T, Arihiro K, Ohdan H.
  • Journal Title: World J Surg Oncol Volume: 10 Issue: 1 Pages: 127-127
  • DOI: 10.1186/1477-7819-10-127
  • Peer Reviewed
• [Journal Article] Reg IV is a direct target of intestinal transcriptional factor CDX2 in gastric cancer. (2012)
  • Author(s): Naito Y, Oue N, Hinoi T, Sakamoto N, Sentani K, Ohdan H, Yanagihara K, Sasaki, H, Yasui W.
  • Journal Title: PLoS One Volume: 7(11) Issue: 11 Pages: 47545-47545
  • DOI: 10.1371/journal.pone.0047545
  • Peer Reviewed
• [Journal Article] Submucosal invasive micropapillary carcinoma of the colon with massive lymph node metastases: a case report (2012)
  • Author(s): Mukai S, Takakura Y, Egi H, Hinoi T, Saito Y, Tanimine N, Miguchi M, Adachi T, Shimomura M, Ohdan H.
  • Journal Title: Case Rep Oncol. Volume: 5(3) Issue: 3 Pages: 608-15
  • DOI: 10.1159/000345566
  • Peer Reviewed
• [Journal Article] Liver-intestine cadherin induction by epidermal growth factor receptor is associated with intestinal differentiation of gastric cancer (2012)
  • Author(s): Sakamoto N, Oue N, Sentani K, Anami K, Uraoka N, Naito Y, Oo HZ, Hinoi T, Ohdan H, Yanagihara K, Aoyagi K, Sasaki H, Yasui W.
  • Journal Title: Liver-intestine cadherin induction by epidermal growth factor receptor is associated with intestinal differentiation of gastric cancer Volume: 103(9) Issue: 9 Pages: 1744-50
  • DOI: 10.1111/j.1349-7006.2012.02353.x
  • Peer Reviewed
• [Journal Article] Identification of patients likely to benefit from metastasectomy in stage IV colorectal cancer. (2012)
  • Author(s): Shimomura M, Okajima M, Hinoi T, Egi H, Takakura Y, Kawaguchi Y, Tokunaga M, Adachi T, Tashiro H, Ohdan H.
  • Journal Title: Int J Colorectal Dis. Volume: 27(10) Pages: 1339-46
  • Peer Reviewed
• [Journal Article] Identification of patients likely to benefit from metastasectomy in stage IV colorectal cancer (2012)
  • Author(s): Shimomura M
  • Journal Title: Int J Colorectal Dis Volume: 27 Pages: 1339-1346
• [Journal Article] Identification of patients likely to benefit from metastasectomy in stage IV colorectal cancer (2012)
  • Author(s): Shimomur M
  • Journal Title: International Journal of Colorectal Disease Volume: (In press)
  • Peer Reviewed
• [Journal Article] Adequate lymph node examination is essential to ensure the prognostic value of the lymph node ratio in patients with stage III colorectal cancer. (2011)
  • Author(s): Shimomura M, Ikeda S, Takakura Y, Kawaguchi Y, Tokunaga M, Egi H, Hinoi T, Okajima M, Ohdan H
  • Journal Title: Surg Today Volume: 41(10) Issue: 10 Pages: 1370-9
  • DOI: 10.1007/s00595-010-4446-2
  • NAID: 10030228776
  • Peer Reviewed
• [Journal Article] External Validation of two nomograms for predicting patients survival after hepatic resection for metastatic colorectal cancer (2011)
  • Author(s): Takakura Y, Okajima M, Kanemitsu Y, Kuroda S, Egi H, Hinoi T, Tashiro H, Ohdan H
  • Journal Title: World J Surg Volume: 35 Issue: 10 Pages: 2275-2282
  • DOI: 10.1007/s00268-011-1194-4
  • Peer Reviewed
• [Journal Article] Malignant peripheral nerve sheath tumor arising from the greater omentum: case report. (2011)
  • Author(s): Miguchi M, Takakura Y, Egi H, Hinoi T, Adachi T, Kawaguchi Y, Shinomura M,Tokunaga M, Okajima M, Ohdan H.
  • Journal Title: World J Surg Oncol. Volume: 9 Issue: 1 Pages: 33-33
  • DOI: 10.1186/1477-7819-9-33
  • NAID: 120003692468
  • Peer Reviewed
• [Journal Article] Immunohistochemical analysis of colorectal cancer with gastric phenotype: claudin-18 is associated with poor prognosis. (2010)
  • Author(s): Matsuda M, Sentani K, Noguchi T, Hinoi T, Okajima M, Matsusaki K, Sakamoto N, Anami K, Naito Y, Oue N, Yasui W.
  • Journal Title: Pathol Int. Volume: 60(10) Issue: 10 Pages: 673-80
  • DOI: 10.1111/j.1440-1827.2010.02587.x
  • NAID: 10031123396
  • Peer Reviewed
• [Journal Article] CDX2 regulates multidrug resistance 1 gene expression in malignant intestinal epithelium. (2010)
  • Author(s): Takakura Y, Hinoi T, Oue N, Sasada T, Kawaguchi Y, Okajima M, Akyol A, Fearon ER, Yasui W, Ohdan H.
  • Journal Title: Cancer Res. Volume: 70(17) Issue: 17 Pages: 6767-78
  • DOI: 10.1158/0008-5472.can-09-4701
  • Peer Reviewed
• [Journal Article] Search for transmembrane protein in gastric cancer by the Escherichia coli ampicillin secretion trap: expression of DSC2 in gastric cancer with intestinal phenotype (2010)
  • Author(s): Anami K, Oue N, Noguchi T, Sakamoto N, Sentani K, Hayashi T, Hinoi T, Okajima M, Graff JM, Yasui W.
  • Journal Title: J Pathol. Volume: 221(3) Issue: 3 Pages: 275-84
  • DOI: 10.1002/path.2717
  • Peer Reviewed
• [Journal Article] Gastrointestinal stromal tumors of the small intestine in pediatric populations: a case report and literature review. (2010)
  • Author(s): Shimomura M, Ikeda S, Takakura Y, Kawaguchi Y, Tokunaga M, Takeda H, Sumitani D, Yoshimitsu M, Hinoi T, Okajima M, Ohdan H.
  • Journal Title: Pediatr Surg Int. Volume: 26(6) Issue: 6 Pages: 649-54
  • DOI: 10.1007/s00383-010-2596-3
  • NAID: 120002598772
  • Peer Reviewed
• [Presentation] Oncogenic K-rasmutation associates with GLUT1 expression in mice and human colorectal cancer (2013)
  • Author(s): KawaguchiY, Hinoi T, Sasada T, Adachi T, Saito Y, Miguchi S, Niitsu H, Ohdan H
  • Organizer: AACR Annual Meeting 2013
  • Place of Presentation: Washington DC USA
• [Presentation] ChlorinatedDrinking Water Alters Carcinogenesis in a Mouse Model of Colon Cancer (2012)
  • Author(s): Sasada T, Hinoi T, et al
  • Organizer: AACR Annual Meeting 2012
  • Place of Presentation: Chicago IL USA
• [Presentation] Chlorinated drinking water alters carcinogenesis in a mice model of colon cancer (2012)
  • Author(s): Sasada T, Hinoi T
  • Organizer: American Association for Cancer Research Annual meeting 2012
  • Place of Presentation: Chicago IL, US
• [Presentation] 2種類の遺伝子不安定性大腸癌の新規マウスモデルの作製とその解析 (2012)
  • Author(s): 檜井孝夫
  • Organizer: 日本消化器病学会総会
  • Place of Presentation: 東京
• [Presentation] トランスレーショナルリサーチに有用な右側および左側結腸進行癌マウスモデルの構築:臓器特異的Apcコンディショナル・ノックアウトマウスの作製とその臨床応用 (2011)
  • Author(s): 檜井孝夫
  • Organizer: 日本外科学会
  • Place of Presentation: 東京
  • Year and Date: 2011-05-25
• [Presentation] Chlorinated Drinking Water Alters Carcinogenesis in a Mouse Model of Colon Cancer (2011)
  • Author(s): 佐々田達成、檜井孝夫
  • Organizer: 6th International Society of Gastroenterological Carcinogenesis
  • Place of Presentation: ヒューストン(米国)
  • Year and Date: 2011-01-06
• [Presentation] ChlorinatedDrinking Water Alters Carcinogenesis in a Mouse Model of Colon Cancer (2011)
  • Author(s): Sasada T, Hinoi T, Oue H, Yasui W, et al
  • Organizer: 6thInternational Society of Gastroenterological Carcinogenesis (ISGC)
  • Place of Presentation: Houston TX USA