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VEGF, Basic-FGF, and TGF-β in Crohn's Disease and Ulcerative Colitis : A Novel Mechanism of Chronic Intestinal Inflammation

Research Project

Project/Area Number13671360
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeSingle-year Grants
Section一般
Research Field Digestive surgery
Research InstitutionKAWASAKI MEDICAL SCHOOL

Principal Investigator

TSUNODA Tsukasa  Kawasaki Medical School, Surgery, Professor, 医学部, 教授 (00110841)

Co-Investigator(Kenkyū-buntansha) URAKAMI Atsushi  Kawasaki Medical School, Surgery, Assistant Professor, 医学部, 講師 (70319979)
HIRAI Toshihiro  Kawasaki Medical School, Surgery, Associate Professor, 医学部, 助教授 (60165149)
KIMOTO Masatoshi  Kawasaki Medical School, Surgery, Associate Professor, 医学部, 助教授 (50153226)
Project Period (FY) 2001 – 2003
Project Status Completed(Fiscal Year 2003)
Budget Amount *help
¥2,900,000 (Direct Cost : ¥2,900,000)
Fiscal Year 2003 : ¥600,000 (Direct Cost : ¥600,000)
Fiscal Year 2002 : ¥700,000 (Direct Cost : ¥700,000)
Fiscal Year 2001 : ¥1,600,000 (Direct Cost : ¥1,600,000)
Keywordsulcerative colitis / Crohn's disease / endothelin-1 / vascular endothelial growth factor / basic fibroblast growth factor / transforming growth factor-β / vasculitis / intestinal ischemia
Research Abstract

Objective : Inflammatory bowel disease(IBD), the precise etiology of which remains unknown, is comprised of two forms of chronic intestinal inflammation ; ulcerative colitis(UC) and Crohn's disease(CD). Recent evidence increasingly suggests that IBD is the result of dysfunctional immunoregulation manifested by inappropriate production of mucosal cytokines. An abnormal microcirculatory system has also been implicated in its pathogenesis. To elucidate the mechanism of ischemic change in IBD, we assessed serum concentration levels of vascular endothelial growth factor(VEGF) and basic fibroblast growth factor(b-FGF), and plasma level of endothelin-1(ET-1). We also investigated the expression of VEGF, b-FGF, and transforming growth factor-β 1,2,3(TGF-β_<1,2,3>) in tissue by immunostaining.
Methods : Blood samples were obtained from 11 patients with UC,11 patients with CD, and 10 patients as controls. Paraffin-embedded samples were used for an immunohistochemicar study.
Results : The concentra … More tion levels(in picograms per milliliter) were as follows : for ET-1,UC:127±47.0,CD:167.3±35.1,and controls(asthma:38.5±23.8 p<0.01;diverticulitis:40.5±25.6, p<0.01), for b-FGF,UC:9.2±1.9,CD:9.1±1.5,and controls(asthma:5.0±0,p<0.01;diverticulitis:5.0±0.p<0.01), for VEGF,UC:659.8±181.0,CD:740.0±182.3,and controls(asthma:193.7±58.7,p<0.01;diverticulitis:199.6±59.7,p<0.01). The levels of VEGF and b-FGF were significantly higher in active IBD than those in the controls. There was a significant positive correlation among the serum levels of VEGF and b-FGF, and the plasma level of ET-1;that is, elevated VEGF,b-FGF, and ET-1 levels correlated well with each other. Immunohistochemical studies showed increased venula in the submucosa and lamina propria. Overexpression of VEGF and b-FGF in endothelial cells was revealed and TGF-β_2 and TGF-β_3 were found in inflammatory cells of active IBD, but no change was observed aroud the vessels in the controls.
Conclusion : It is suggested that the reciprocal reaction of these cytokines may contribute to angibgenesis in IBD by inducing intestinal ischemia through vasoconstriction. Less

Report

(4results)
  • 2003 Annual Research Report   Final Research Report Summary
  • 2002 Annual Research Report
  • 2001 Annual Research Report

Research Products

(70results)

All Other

All Publications

  • [Publications] Katsumichi Iki, et al.: "Case report. Primary adenocarcinoma of the duodenum demonstrated by ultrasonography"J.Gastroenterol.. 36・3. 195-199 (2001)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2003 Final Research Report Summary
  • [Publications] Shigeo Kanazawa, et al.: "VEGF, basic-FGF, and TGF-β in Crohn's disease and ulcerative colitis : A novel mechanism of chronic intestinal inflammation"Am.J.Gastroenterol.. 96・3. 823-828 (2001)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2003 Final Research Report Summary
  • [Publications] Katsumichi Iki, et al.: "Preoperative diagnosis of acute appendiceal diverticulitis by ultrasonography"Surgery. 130・1. 87-89 (2001)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2003 Final Research Report Summary
  • [Publications] 山下和城, 他: "高齢者(75歳以上)大腸癌手術症例の臨床病理学的検討-41歳以上50歳以下の大腸癌症例と比較して-"日臨外会誌. 62・8. 1830-1836 (2001)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2003 Final Research Report Summary
  • [Publications] 垂水研一, 他: "von Recklinghausen病に合併した空腸gastrointestinal stromal tumor(GIT)の1例"胃と腸. 36・7. 934-936 (2001)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2003 Final Research Report Summary
  • [Publications] Kazuki Yamashita, et al.: "Resection of hepatic metastasis from colorectal cancer : Survival, factors influencing prognosis, and follow-up"Kawasaki Med.J.. 27・3-4. 99-112 (2001)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2003 Final Research Report Summary
  • [Publications] Kazuki Yamashita, et al.: "Long-term endoscopic appearances of hand-sewn versus biofragmentable anastomosis ring method"Kawasaki Med.J.. 27・3-4. 113-116 (2001)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2003 Final Research Report Summary
  • [Publications] Kazuki Yamashita, et al.: "Three-dimensional computer images of stomach diseases"Am.J.Surg.. 183. 87-88 (2002)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2003 Final Research Report Summary
  • [Publications] Kazuki Yamashita, et al.: "Gender differences in the dihydropyrimidine dehydrogenase expression of colorectal cancers"Cancer Lett.. 188. 231-236 (2002)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2003 Final Research Report Summary
  • [Publications] 山下和城, 他: "小腸・結腸、結腸・結腸吻合術"消化器外科. 25・7増. 980-989 (2002)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2003 Final Research Report Summary
  • [Publications] 藤倉博之, 他: "原発性十二指腸癌7症例の検討"川崎医会誌. 28・3. 137-142 (2002)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2003 Final Research Report Summary
  • [Publications] 平川克哉, 他: "4型大腸癌の臨床病理学的特徴とX線・内視鏡診断-浸潤様式との関係を中心に-"胃と腸. 37・2. 152-164 (2002)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2003 Final Research Report Summary
  • [Publications] 藤田 穣, 他: "小腸型Crohn病に合併し回腸S状結腸痩からの生検で術前診断しえた回腸癌の1例"胃と腸. 37・8. 1067-1075 (2002)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2003 Final Research Report Summary
  • [Publications] 香川玲奈, 他: "高線量率組織内照射が奏効した直腸癌局所再発の1例"癌の臨床. 48・7. 435-438 (2002)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2003 Final Research Report Summary
  • [Publications] Jiro Hayashi, et al.: "Amyloidosis-induced lower gastrointestinal bleeding in a patient with multiple myeloma"Kawasaki Med.J.. 28・2,3,4. 79-85 (2002)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2003 Final Research Report Summary
  • [Publications] 岡 保夫, 他: "宿便性結腸穿孔の1例"川崎医会誌. 28・4. 297-301 (2002)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2003 Final Research Report Summary
  • [Publications] Kayoko Shimizu, et al.: "Suddenly accelerated growth of gastrointestinal stromal tumor of remnant stomach"Dig.Dis.Sci.. 48・6. 1106-1109 (2002)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2003 Final Research Report Summary
  • [Publications] Hideaki Ueno, et al.: "Quantitative detection of carcinoembryonic antigen messenger RNA in the peritoneal cavity of gastric cancer patients by real-time quantitative reverse transcription polymerase chain reaction"Anticancer Res.. 23. 1701-1708 (2003)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2003 Final Research Report Summary
  • [Publications] Hideaki Ueno, et al.: "Prediction of lymph node metastasis by p53, p21^<Waf1>, and PCNA expression in esophageal cancer patients"J.Exp.Clin.Cancer Res.. 22. 239-245 (2003)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2003 Final Research Report Summary
  • [Publications] 河邉由貴子, 他: "特発性大網捻転症の1例"川崎医会誌. 29・2. 161-165 (2003)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2003 Final Research Report Summary
  • [Publications] Tomoari Kamada, et al.: "Case of early gastric cancer with nodular gastritis."Digestive Endoscopy. 16. 39-43 (2004)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2003 Final Research Report Summary
  • [Publications] Katsumichi Iki, et al.: "Case report. Primary adenocarcinoma of the duodenum demonstrated by ultrasonography."J.Gastroenterol.. 36(3). 195-199 (2001)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2003 Final Research Report Summary
  • [Publications] Shigeo Kanazawa, et al.: "VEGF, basic-FGF, and TGF-β in Crohn's disease and ulcerative colitis : A.novel mechanism of chronic intestinal inflammation."Am.J.Gastroeriterol.. 96(3). 823-828 (2001)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2003 Final Research Report Summary
  • [Publications] Katsumichi Iki, et al.: "Preoperative diagnosis of acute appendiceal diveiticulitis by ultrasonography."Surgery. 130(1). 87-89 (2001)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2003 Final Research Report Summary
  • [Publications] Kazuki Yamashita, et al.: "Resection of hepatic metastasis from colorectal cancer : Survival, factors influencing prognosis, and follow-u"Kawasaki Med.J.. 27(3・4). 99-112 (2001)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2003 Final Research Report Summary
  • [Publications] Kazuki Yamashita, et al.: "Application of different anastomotic methods for a patient with Crohn's disease : Long-term endoscopic appearances of hand-sewn versus biofragmentable anastomosis ring method."Kawasaki Med.J.. 27(3・4). 113-116 (2001)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2003 Final Research Report Summary
  • [Publications] Kazuki Yamashita, et al.: "Three-dimensional computer images of stomach diseases."Am.J.Surg.. 183. 87-88 (2002)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2003 Final Research Report Summary
  • [Publications] Kazuki Yamashita, et al.: "Gender differences in the dihydropyrimidine dehydrogenase expression of colorectal cancers."Cancer Lett.. 188. 231-236 (2002)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2003 Final Research Report Summary
  • [Publications] Jiro Hayashi, et al.: "Amyloidosis-induced lower gastrointestinal bleeding in a patient with multiple myeloma."Kawasaki Med.J.. 28(2・3・4). 79-85 (2002)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2003 Final Research Report Summary
  • [Publications] Kayoko Shimizu, et al.: "Suddenly accelerated growth of gastrointestinal stromal tumor of remnant stomach."Dig.Dis.Sci.. 48(6). 1106-1109 (2003)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2003 Final Research Report Summary
  • [Publications] Hideaki Ueno, et al.: "Quantitative detection of carcinoembryonic antigen messenger RNA in the peritoneal cavity of gastric cancer patients by real-time quantitative reverse transcription polymerase chain reaction."Anticancer Res.. 23. 1701-1708 (2003)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2003 Final Research Report Summary
  • [Publications] Hideaki Ueno, et al.: "Prediction of lymph node metastasis by p53,p21^<Waf1> and PCNA expression in esophageal cancer patients."J.ExClin.Cancer Res.. 22. 239-245 (2003)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2003 Final Research Report Summary
  • [Publications] Tomoari Kamada, et al.: "Case of early gastric cancer with nodular gastritis."Digestive Endoscopy. 16. 39-43 (2004)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2003 Final Research Report Summary
  • [Publications] Hideaki Ueno, Toshihiro Hirai, et al.: "Prediction of lymph node metastasis by p53,p21waf1, and PCNA expression in esophageal cancer patients"J Exp Clin Cancer Res. 22. 239-245 (2003)

    • Related Report
      2003 Annual Research Report
  • [Publications] 宮原栄治, 平井敏弘, 他: "感染を契機に発見され、胸腔鏡補助下に切除した先天性気管支のう胞の1例"日呼吸器外科会誌. 17. 25-29 (2003)

    • Related Report
      2003 Annual Research Report
  • [Publications] 清水克彦, 平井敏弘, 他: "開腹法の違いによる胃癌術後イレウスの発生頻度に関する検討"日臨外会誌. 64・4. 801-804 (2003)

    • Related Report
      2003 Annual Research Report
  • [Publications] 三上佳子, 浦上 淳, 角田 司, 他: "進行・再発大腸癌に対する高用量レボホリナート/フルオロウラシル(LV/5-FU)併用療法の検討"川崎医会誌. 29・2. 99-104 (2003)

    • Related Report
      2003 Annual Research Report
  • [Publications] 岡 保夫, 浦上 淳, 角田 司, 他: "肝転移に対し3回の肝切除を施行し、長期生存を得たZollinger-Ellison症候群の1例"日臨外会誌. 64・12. 3152-3157 (2003)

    • Related Report
      2003 Annual Research Report
  • [Publications] 藤田 穣, 角田 司, 他: "便潜血検査を契機に発見された下行結腸海綿状血管腫の1例"臨牀消化器内科. 19・1. 135-140 (2003)

    • Related Report
      2003 Annual Research Report
  • [Publications] Kazuki Yamashita, Tsukasa Tsunoda: "Three-dimensional computer images of Morgagni hernia"Am J Surg. 187. 109-110 (2004)

    • Related Report
      2003 Annual Research Report
  • [Publications] 浦上 淳: "Pittsburghでの胸腔鏡と腹腔鏡を用いた食道切除手術での教育セミナーに参加して"日本内視鏡外科学会雑誌. 7・1. 80-82 (2002)

    • Related Report
      2002 Annual Research Report
  • [Publications] Kazuki Yamashita, Tsukasa Tsunoda: "Three-dimensional computer images of stomach diseases"Am J Surg. 183. 87-88 (2002)

    • Related Report
      2002 Annual Research Report
  • [Publications] Tadahiko Kubozoe, Tsukasa Tsunoda, et al.: "Possible lack of carcinogenic potential of 9-(4'-aminophenyl)-9H-pyrido[3,4-b] indole (aminophenylnorharman) for the pancreatic duct epithelium in hamsters"J Toxicolog Patholog. 15・1. 7-12 (2002)

    • Related Report
      2002 Annual Research Report
  • [Publications] Atsushi Urakami, Tsukasa Tsunoda, et al.: "Spontaneous fistulization of a pancreatic pseudocyst into the colon and duodenum"Gastrointest Endosc. 55・7. 949-951 (2002)

    • Related Report
      2002 Annual Research Report
  • [Publications] Kazuki Yamashita, Tsukasa Tsunoda, et al.: "Double common bile duct : A case report and a review of the Japanese literature"Surgery. 131・6. 676-681 (2002)

    • Related Report
      2002 Annual Research Report
  • [Publications] Atsushi Urakami, Tsukasa Tsunoda, et al.: "Rupture of a bleeding pancreatic pseudocyst into the stomach"J Hepatobiliary Pancreat Surg. 9. 383-385 (2002)

    • Related Report
      2002 Annual Research Report
  • [Publications] Kazuki Yamashita, Tsukasa Tsunoda, et al.: "Gender differences in the dihydropyrimidine dehydrogenas expression of colorectal cancers"Cancer Lett. 188. 231-236 (2002)

    • Related Report
      2002 Annual Research Report
  • [Publications] 浦上 淳, 角田 司: "閉塞性黄疸に対する減黄術"外科治療. 86・5. 575-576 (2002)

    • Related Report
      2002 Annual Research Report
  • [Publications] 山下和城, 角田 司: "小腸・結腸,結腸・結腸吻合術"消化器外科. 25・7臨増. 980-989 (2002)

    • Related Report
      2002 Annual Research Report
  • [Publications] 浦上 淳, 角田 司, 他: "PTBD後に発生した仮性肝動脈瘤の1例"胆道. 16・4. 331-336 (2002)

    • Related Report
      2002 Annual Research Report
  • [Publications] 藤倉博之, 角田 司, 他: "原発性十二指腸癌7症例の検討"川崎医会誌. 28・3. 137-142 (2002)

    • Related Report
      2002 Annual Research Report
  • [Publications] 平川克哉, 角田 司, 他: "4型大腸癌の臨床病理学的特徴とX線・内視鏡診断-浸潤様式との関係を中心に-"胃と腸. 37・2. 152-164 (2002)

    • Related Report
      2002 Annual Research Report
  • [Publications] 藤田 穣, 角田 司, 他: "小腸型Crohn病に合併し回腸S状結腸瘻からの生検で術前診断しえた回腸癌の1例"胃と腸. 37・8. 1067-1075 (2002)

    • Related Report
      2002 Annual Research Report
  • [Publications] 三井康裕, 角田 司, 他: "リンパ節転移を伴った比較的小さな膵Solid-Pscedopapillary tumorの1例"川崎医会誌. 28・2. 109-113 (2002)

    • Related Report
      2002 Annual Research Report
  • [Publications] 香川玲奈, 浦上 淳, 他: "高線量率組織内照射が奏効した直腸癌局所再発の1例"癌の臨床. 48・7. 435-438 (2002)

    • Related Report
      2002 Annual Research Report
  • [Publications] Tsukasa Tsunoda, et al.: "Pancreaticobiliary Maljunction -Experimental studies on the carcinogenesis of the extrahepatic biliary tree with pancreaticobiliary mailjunction-"Igaku Tosho Shuppan. 12 (2002)

    • Related Report
      2002 Annual Research Report
  • [Publications] 角田 司: "今日の消化器疾患治療指針第2版-膵癌の診断と治療方針・疼痛対策-"医学書院. 5 (2002)

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      2002 Annual Research Report
  • [Publications] 岩本末治, 角田 司: "消化器ナビゲーター-胆道の手術-"メディカルレビュー社. 4 (2002)

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      2002 Annual Research Report
  • [Publications] 岩本末治, 角田 司: "下部胆管癌に対する幽門輪温存膵頭十二指腸切除術"金原出版社. 7 (2002)

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      2002 Annual Research Report
  • [Publications] 伊木勝道, 角田 司: "専門医のための消化器外科学レビュー2002-最新主要文献と解説-6.膵疾患5.膵内分泌腫瘍-"総合医学社. 6 (2002)

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      2002 Annual Research Report
  • [Publications] 浦上淳, 角田司: "アルコール性肝障害"南江堂. 1 (2002)

    • Related Report
      2002 Annual Research Report
  • [Publications] Iki Katsumichi, Tsunoda Tsukasa, et al.: "Primary adenocarcinoma of the duodenun demonstrated by ultrasonography"J. Gastroenterol.. 36・3. 195-199 (2001)

    • Related Report
      2001 Annual Research Report
  • [Publications] Kanazawa Shigeo, Tsunoda Tsukasa, et al.: "Intralobar pulmonary sequestration supplied by multiple anomalous arteries : Report of a case"Surg. Today. 31. 701-704 (2001)

    • Related Report
      2001 Annual Research Report
  • [Publications] Kubozoe Tadahiko, Tsunoda Tsukasa, et al.: "Absence of β-catenin gene mutations in pancreatic duct lesions induced by N-nitrosobis (2-oxopropyl) amine in hamsters"Cancer Letters. 168. 1-6 (2001)

    • Related Report
      2001 Annual Research Report
  • [Publications] Kanazawa Shigeo, Tsunoda Tsukasa, et al.: "VEGF, basic-FGF, and TGF-β in Crohn's disease and ulcerative colitis : a novel mechanism of chronic intestinal inflammation"Am. J. Gastroenterol.. 96・3. 823-828 (2001)

    • Related Report
      2001 Annual Research Report
  • [Publications] Iki Katsumichi, Tsunoda Tsukasa, et al.: "Preoperative diagnosis of acute appendiceal diverticulitis by ultrasonography"Surgery. 130・1. 87-89 (2001)

    • Related Report
      2001 Annual Research Report
  • [Publications] 山下和城, 角田 司, 他: "高齢者(75歳以上)大腸癌手術症例の臨床病理学的検討-41歳以上50歳以下の大腸癌症例と比較して-"日臨外会誌. 62・8. 1830-1836 (2001)

    • Related Report
      2001 Annual Research Report
  • [Publications] 垂水研一, 角田 司, 他: "von Recklinghausen病に合併した空腸gastrointestinal stromal tumor(GIST)の1例"胃と腸. 36・7. 934-936 (2001)

    • Related Report
      2001 Annual Research Report
  • [Publications] 三井 康裕, 角田 司, 他: "急性膵炎を契機に発見された膵管内乳頭腫瘍の1例"川崎医会誌. 27・2. 139-143 (2001)

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  • [Publications] 伊木勝道, 角田 司, 他: "各論6. 膵疾患5. 膵内分泌腫瘍. 専門医のための消化器外科レビュー. -最新主要文献と解説2001-"総合医学社. 5 (2001)

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Published : 2001-04-01   Modified : 2016-04-21  

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