Development of HB-EGF-CTF related therapy and biomarker for gastrointestinal cancer

• Project/Area Number: 24590923
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: Gastroenterology
• Research Institution: Nagoya City University
• Principal Investigator: Shimura Takaya 名古屋市立大学, 医学(系)研究科(研究院), 講師 (90405192)
• Co-Investigator(Kenkyū-buntansha): EBI Masahide 愛知医科大学, 医学部, 講師 (40611629) ; YOSHIDA Michihiro 名古屋市立大学, 医学研究科, 研究員 (20636328)
• Co-Investigator(Renkei-kenkyūsha): HIGASHIYAMA Shigeki 愛媛大学, 大学院医学系研究科, 教授 (60202272)
• Project Period (FY): 2012-04-01 – 2016-03-31
• Project Status: Completed (Fiscal Year 2015)
• Budget Amount: ¥5,330,000 (Direct Cost: ¥4,100,000、Indirect Cost: ¥1,230,000); Fiscal Year 2014: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000); Fiscal Year 2013: ¥1,950,000 (Direct Cost: ¥1,500,000、Indirect Cost: ¥450,000); Fiscal Year 2012: ¥1,820,000 (Direct Cost: ¥1,400,000、Indirect Cost: ¥420,000)
• Keywords: HB-EGF / 胃癌 / 大腸癌 / EGFR / Amphiregulin

Outline of Final Research Achievements

HB-EGF expression, not intracellular localization of HB-EGF-CTF, in the tumor was one of the predictive factor for anti-EGFR therapy against KRAS wild type metastatic ｃolorectal cancer, as well as other EGFR ligands including amphiregulin, TGF-a, epiregulin (Yoshida M, Shimura T, et al. J Cancer Res Clin Oncol.2013: 367-78).
Urinary level and tumor expression of ADAM12, which regulates HB-EGF-CTF nuclear translocation, is a useful biomarker for early diagnosis of gastric cancer(Yoshida M, Shimura T, et al. J Cancer Res Clin Oncol.2013: 367-78).

Research Products

• [Int'l Joint Research] ハーバード大学医学部(米国)
• [Journal Article] Urinary ADAM12 and MMP-9/NGAL complex detect the presence of gastric cancer. (2015)
  • Author(s): Shimura T, Dagher A, Sachdev M, Ebi M, Yamada T, Yamada T, Joh T, Moses MA.
  • Journal Title: Cancer Prevention Research Volume: 8(3) Issue: 3 Pages: 240-248
  • DOI: 10.1158/1940-6207.capr-14-0229
  • Peer Reviewed / Int'l Joint Research / Acknowledgement Compliant
• [Journal Article] Multicenter, prospective trial of white-light imaging alone versus white-light imaging followed by magnifying endoscopy with narrow-band imaging for the real-time imaging and diagnosis of invasion depth in superficial esophageal squamous cell carcinoma. (2015)
  • Author(s): Ebi M, Shimura T, Yamada T, Mizushima T, Itoh K, Tsukamoto H, Tsuchida K, Hirata Y, Murakami K, Kanie H, Nomura S, Iwasaki H, Kitagawa M, Takahashi S, Joh T.
  • Journal Title: Gastrointestinal Endoscopy Volume: 81(6) Issue: 6 Pages: 1355-1361
  • DOI: 10.1016/j.gie.2014.11.015
  • Peer Reviewed / Acknowledgement Compliant
• [Journal Article] Subset Analysis of a Multicenter, Randomized Controlled Trial to Compare Magnifying Chromoendoscopy with Endoscopic Ultrasonography for Stage Diagnosis of Early Stage Colorectal Cancer. (2015)
  • Author(s): Yamada T, Shimura T, Ebi M, Hirata Y, Nishiwaki H, Mizushima T, Asukai K, Togawa S, Takahashi S, Joh T.
  • Journal Title: PLoS One Volume: 10(8) Issue: 8 Pages: e0134942-e0134942
  • DOI: 10.1371/journal.pone.0134942
  • Peer Reviewed / Open Access / Acknowledgement Compliant
• [Journal Article] Magnifying Chromoendoscopy and Endoscopic Ultrasonography Measure Invasion Depth of Early-Stage Colorectal Cancer with Equal Accuracy, Based on a Prospective Trial. (2014)
  • Author(s): Shimura T, Ebi M, Yamada T, Hirata Y, Nishiwaki H, Mizushima T, Asukai K, Togawa S, Takahashi S, Joh T
  • Journal Title: Clinilcal Gastroenterology and Hepatology Volume: 12(4) Issue: 4 Pages: 662-668
  • DOI: 10.1016/j.cgh.2013.06.022
  • Peer Reviewed
• [Journal Article] Management of systolic blood pressure after endoscopic submucosal dissection is crucial for prevention of postgastric bleeding. (2014)
  • Author(s): Ebi M, Shimura T, Nishiwaki H, Tanaka M, Tsukamoto H, Ozeki K, Sawada T, Mizoshita T, Mori Y, Kubota E, Tanida S, Kataoka H, Joh T.
  • Journal Title: Eur J Gastroenterol Hepatol Volume: 26(5) Issue: 5 Pages: 504-9
  • DOI: 10.1097/meg.0000000000000072
  • Peer Reviewed
• [Journal Article] Preoperative drainage using a transanal tube enables elective laparoscopic colectomy for obstructive distal colorectal cancer. (2013)
  • Author(s): Yamada T, Shimura T, Sakamoto E, Kurumiya Y, Komatsu S, Iwasaki H, Nomura S, Kanie H, Hasegawa H, Orito E, Joh T
  • Journal Title: Ｅｎｄｏｓｃｏｐｙ Volume: 45(4) Issue: 04 Pages: 265-71
  • DOI: 10.1055/s-0032-1326030
  • Peer Reviewed
• [Journal Article] Telmisartan inhibits cell proliferation by blocking nuclear translocation of ProHB-EGF C-terminal fragment in colon cancer cells. (2013)
  • Author(s): Ozeki K, Tanida S, Morimoto C, Inoue Y, Mizoshita T, Tsukamoto H, Shimura T, Kataoka H, Kamiya T, Nishiwaki E, Ishiguro H, Higashiyama S, Joh T.
  • Journal Title: PLoS One Volume: 8(2) Issue: 2 Pages: e56770-e56770
  • DOI: 10.1371/journal.pone.0056770
  • URL: http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3579940/
  • Peer Reviewed
• [Journal Article] Novel nasogastric tube-related criteria for urgent endoscopy in nonvariceal upper gastrointestinal bleeding (2013)
  • Author(s): Iwasaki H, Shimura T, Yamada T, Aoki M, Nomura S, Kusakabe A, Kanie H, Ban T, Hayashi K, Joh T, Orito E
  • Journal Title: Dig Dis Sci. Volume: Sep;58(9) Issue: 9 Pages: 2564-71
  • DOI: 10.1007/s10620-013-2706-x
  • Peer Reviewed
• [Journal Article] Annexin A2 regulates a disintegrin and metalloproteinase 17-mediated ectodomain shedding of pro-tumor necrosis factor-α in monocytes and colon epithelial cells. (2013)
  • Author(s): Tsukamoto H, Tanida S, Ozeki K, Ebi M, Mizoshita T, Shimura T, Mori Y, Kataoka H, Kamiya T, Fukuda S, Higashiyama S, Joh T.
  • Journal Title: Inflamm Bowel Dis. Volume: 19 Issue: 7 Pages: 1365-1373
  • DOI: 10.1097/mib.0b013e318281f43a
  • Peer Reviewed
• [Journal Article] Infliximab salvage therapy for patients with ulcerative colitis who failed to respond to tacrolimus. (2013)
  • Author(s): Tsukamoto H, Tanida S, Mizoshita T, Ozeki K, Ebi M, Shimura T, Mori Y, Kataoka H, Kamiya T, Joh T
  • Journal Title: Eur J Gastroenterol Hepatol. Volume: Jun;25(6) Issue: 6 Pages: 714-8
  • DOI: 10.1097/meg.0b013e32835eb999
  • Peer Reviewed
• [Journal Article] A novel predictive strategy by immunohistochemical analysis of four EGFR ligands in metastatic colorectal cancer treated with anti-EGFR antibodies. (2013)
  • Author(s): Yoshida M, Shimura T, Sato M, Ebi M, Nakazawa T, Takeyama H, Joh T.
  • Journal Title: J Cancer Res Clin Oncol. Volume: Mar;139(3) Issue: 3 Pages: 367-78
  • DOI: 10.1007/s00432-012-1340-x
  • Peer Reviewed
• [Journal Article] Nuclear translocation of the cytoplasmic domain of HB-EGF induces gastric cancer invasion (2012)
  • Author(s): Shimura T, Yoshida M, Fukuda S, Ebi M, Hirata Y, Mizoshita T, Tanida S, Kataoka H, Kamiya T, Higashiyama S, Joh T
  • Journal Title: BMC Cancer Volume: 12 Issue: 1 Pages: 205-205
  • DOI: 10.1186/1471-2407-12-205
  • Peer Reviewed
• [Journal Article] Nuclear translocation of pro-amphiregulin induces chemoresistance in gastric cancer (2012)
  • Author(s): Yoshida Michihiro
  • Journal Title: Cancer Science Volume: 103 Issue: 4 Pages: 708-715
  • DOI: 10.1111/j.1349-7006.2012.02204.x
  • Peer Reviewed
• [Journal Article] C-reactive protein is a potential prognostic factor for metastatic gastric cancer. (2012)
  • Author(s): Shimura T, Kitagawa M, Yamada T, Ebi M, Mizoshita T, Tanida S, Kataoka H, Kamiya T, Joh T.
  • Journal Title: Anticancer Res. Volume: Feb;32(2) Pages: 491-6
  • Peer Reviewed
• [Journal Article] The impact of cross-resistance between paclitaxel and docetaxel for metastatic gastric cancer (2012)
  • Author(s): Shimura T, et al
  • Journal Title: Onkologie Volume: 35 Issue: 4 Pages: 176-183
  • DOI: 10.1159/000337400
  • Peer Reviewed
• [Journal Article] Comparison of staging diagnosis by two magnifying endoscopy classification for superficial oesophageal cancer. (2012)
  • Author(s): Ebi M, Shimura T, Murakami K, Yamada T, Hirata Y, Tsukamoto H, Mizoshita T, Tanida S, Kataoka H, Kamiya T, Joh T.
  • Journal Title: Dig Liver Dis. Volume: Nov;44(11) Issue: 11 Pages: 940-9
  • DOI: 10.1016/j.dld.2012.05.007
  • Peer Reviewed
• [Journal Article] The relationship between antitumor effects and relative dose intensity of S-1 plus cisplatin treatment for metastatic gastric cancer. (2012)
  • Author(s): Kitagawa M, Shimura T, Yamada T, Ebi M, Hirata Y, Mizoshita T, Tanida S, Kataoka H, Kamiya T, Joh T.
  • Journal Title: Anticancer Res. Volume: May;32(5) Pages: 1763-8
  • Peer Reviewed
• [Presentation] Urinary ADAM12 and MMP-9/NGAL complex detect the presence of gastric cancer. (2015)
  • Author(s): 志村 貴也
  • Organizer: Digestive Disease Week 2015
  • Place of Presentation: ワシントンD.C.(アメリカ）
  • Year and Date: 2015-05-16
  • Int'l Joint Research
• [Presentation] Potential of urinary MMP-9/NGAL complex as a novel non-invasive biomarker for the early detection of gastric cancer. (2014)
  • Author(s): Shimura T, Dagher A, Ebi M, Yamada T, Yamada T, Joh T, Moses MA
  • Organizer: AACR Annual Meeting 2014
  • Place of Presentation: San Diego (USA)
  • Year and Date: 2014-04-05 – 2014-04-09
• [Presentation] Multicenter, Prospective, Ccomparative Trial of magnifying chromoendoscopy and endoscopic ultrasonography for stage diagnosis of early colorectal cancer. (2013)
  • Author(s): Ebi M, Shimura T, Yamada T, Hirata Y, Nishiwaki H, Mizushima T, Asukai K, Togawa S, Takahashi S, Joh T
  • Organizer: 21th UEG Week Berlin 2013
  • Place of Presentation: ICC Berlin - Internationales Congress-Centrum Berlin (Berlin)
• [Presentation] 大腸癌抗EGFR抗体療法の効果予測における4 種類のEGFRリガンド(AR，HB-EGF，TGF-α，EREG)解析の有用性 (2013)
  • Author(s): 吉田 道弘、志村 貴也、城 卓志
  • Organizer: 第99回 日本消化器病学会総会
  • Place of Presentation: 城山観光ホテル（鹿児島）
• [Presentation] A promising strategy for predictive marker by immunohistochemical analysis of four EGFR ligands in anti-EGFR antibody for metastatic colorectal cancer (2012)
  • Author(s): Michihiro Yoshida, Takaya Shimura, Mikinori Sato, Masahide Ebi, Takahiro Nakazawa, Hiromitsu Takeyama, Takashi Joh
  • Organizer: 20th UEG Week Amsterdam 2012
  • Place of Presentation: The Amsterdam RAI Exhibition & Convention Centre (Amsterdam)
• [Presentation] A novel predictive strategy by immunohistochemical analysis of four EGFR ligands in anti-EGFR antibody for mCRC (2012)
  • Author(s): Michihiro Yoshida, Takaya Shimura, Mikinori Sato, Masahide Ebi, Hiromitsu Takeyama, Takashi Joh
  • Organizer: 第71回日本癌学会学術総会
  • Place of Presentation: ホテルロイトン札幌（札幌）