Effect of proton pump inhibitor and COX2 inbitor upon Barrett's intestinal metaplasia.

• Project/Area Number: 15590664
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Single-year Grants
• Section: 一般
• Research Field: Gastroenterology
• Research Institution: First department of internal medicine, Sapporo Medical University
• Principal Investigator: ENDO Takao Sapporo Medical University, First department of internal medicine, Associate professor, 医学部, 助教授 (40191928)
• Co-Investigator(Kenkyū-buntansha): YAMAMOTO Hiroyuki Sapporo Medical University, First department of internal medicine, Assistant professor, 医学部, 助手 (40332910)
• Project Period (FY): 2003 – 2004
• Project Status: Completed (Fiscal Year 2004)
• Budget Amount: ¥3,500,000 (Direct Cost: ¥3,500,000); Fiscal Year 2004: ¥1,700,000 (Direct Cost: ¥1,700,000); Fiscal Year 2003: ¥1,800,000 (Direct Cost: ¥1,800,000)
• Keywords: Barrett's esophagus / PPI / chemo prevention / proton pump inhibitor(PPI) / Barrett粘膜 / 細胞増殖能 / 酸分泌抑制剤

Research Abstract

We examined whether proton pump inhibitor(PPI) may diminish the risk of carcinogenesis. in Barrett's esophagus (BE). In our study, endoscopic biopsy specimens of BE was analyzed for change in the expression of Ki-67, COX-2, CDX-2, sulfo-Lewisa by immunohistochemistry before and after treatment with PPI.
6 months after treatment with PPI, there was a significant decrease in the expression of Ki-76 (cell proliferation maker) and COX-2 (proliferation-related agent). And there was a tendency to decrease in the expression of CDX-2(intestinal transcription factor) and sulfo-Lewisa (intestinal mucin).
In contrast, treatment with histamin2 receptor antagonist (H2RA) showed no significant decrease in the expression of Ki-67, COX-2, CDX-2, sulfo-Le^a.
We evaluated that treatment with PPI would reduce the expression of COX-2 and consequently cell proliferation would decrease.
It was reported that the expression of between COX-2 and CDX-2 would be associated with p38 MAPK pathway. Accordingly, we examined the expression of Phospho-p38 in BE before and after treatment with PPI.
There was a significant decrease in the expression of -Phospho-p38 in both epithelial cells and stromal cells in BE before and-after treatment with- PPL.
Therefore, we concluded- that PPI- would inhibit- the- expression of both COX-2 and CDX-2 via p38. MAPK pathway and that consequently cell proliferation and intestinal metaplasia. would. diminish.

Research Products

• [Journal Article] Aberrant methylation and silencing of the BNIP3 gene in colorectal and gastric cancer. (2005)
  • Author(s): Mural M, Endo T
  • Journal Title: Clin Cancer Res 11 Pages: 1201-1207
• [Journal Article] Interplay of insulin-like growth factor-II, insulin-like growth factor-I, insulin-like growth factor-I receptor, COX-2, and matrix metalloproteinase-7, play key roles in the early stage of colorectal carcinogenesis. (2004)
  • Author(s): Nosho K, et al.
  • Journal Title: Clin Cancer Res 10 Pages: 7850-7957
  • Description: 「研究成果報告書概要(和文)」より
• [Journal Article] Usefulness of narrow-band imaging endoscopy for diagnosis of Barrett's esophagus. (2004)
  • Author(s): Hamamoto Y, et al.
  • Journal Title: J Gastroenterol 39 Pages: 14-20
  • Description: 「研究成果報告書概要(和文)」より
• [Journal Article] Interplay of insulin-like growth factor-II, insulin-like growth factor-I, insulin-like growth factor-I receptor, COX-2, and matrix metalloproteinase-7, play key roles in the early stage of colorectal carcinogenesis (2004)
  • Author(s): Nosho K, Yamamoto H, Taniguchi H, Adachi Y, Yoshida Y, Arimura Y, Endo T, Hinoda Y, Imai K
  • Journal Title: Clin Cancer Res 10 Pages: 7950-7957
  • Description: 「研究成果報告書概要(欧文)」より
• [Journal Article] Epigenetic inactivation of class II transactivator (CHTA) is associated with the absence of interferon-gamma-induced HLA-DR expression in colorectal and gastric cancer cells (2004)
  • Author(s): Satoh A, Toyota M, Ikeda H, Morimoto Y, Akino K, Mita H, Suzuki H, Sasaki Y, Kanaseki T, Takamura Y, Soejima H, Urano T, Yanagihara K, Endo T, Hinoda Y, Fujita M, Hosokawa M, Sato N, Tokino T, Imai K
  • Journal Title: Oncogene 23 Pages: 8876-8886
  • Description: 「研究成果報告書概要(欧文)」より
• [Journal Article] Appearance of enhanced tissue features in narrow-band endoscopic imaging (2004)
  • Author(s): Gono K, Obi T, Yamaguchi M, Ohyama N, Machida H, Sano Y, Yoshida S, Hamamoto Y, Endo T
  • Journal Title: J Biomed Opt. 9 Pages: 568-77
  • Description: 「研究成果報告書概要(欧文)」より
• [Journal Article] Usefulness of narrow-band imaging endoseopy for diagnosis of Barrett's esophagus (2004)
  • Author(s): Hamamoto Y, Endo T, Nosho K, Arimura Y, Sato M, Imai K
  • Journal Title: J Gastroenterol 39 Pages: 14-20
  • Description: 「研究成果報告書概要(欧文)」より
• [Journal Article] Usefulness of narrow-band imaging endoscopy for diagnosis of Barrett's esophgus. (2004)
  • Author(s): Hamamoto Y, Endo T
  • Journal Title: J Gastroenterol 39 Pages: 14-20
• [Journal Article] Appearance of enhanced tissue features in narrow-band endoscopic imaging. (2004)
  • Author(s): Gono K, Obi T, Endo T, et al.
  • Journal Title: Journal of Biomedical Optics 9 Pages: 568-577
• [Journal Article] Interplay of insulin-like growth factor-II, insulin-like growth factor-I, insulin-like growth factor-I receptor, COX-2, and matrix metalloproteinase-7, play key roles in the early stage of colorectal carcinogenesis. (2004)
  • Author(s): Nosho K, Yamamoto H
  • Journal Title: Clin Cancer Res. 10 Pages: 7950-7957
• [Journal Article] Silencing of negative regulator of JAK/STAT in colorectal cancer. (2004)
  • Author(s): Endo T, Toyota M
  • Journal Title: J Gastroenterol 39 Pages: 200-201
  • NAID: 10012674338
• [Journal Article] Endoscopic observation of tissue by narrowband illumination. (2003)
  • Author(s): Gono K, et al.
  • Journal Title: Optical Review 10 Pages: 211-215
  • Description: 「研究成果報告書概要(和文)」より
• [Journal Article] Increased cyclooxygenase-2 expression in large flat colorectal tumors (laterally spreading tumors). (2003)
  • Author(s): Yamashita K, et al.
  • Journal Title: J Gastroenterol 38 Pages: 69-73
  • Description: 「研究成果報告書概要(和文)」より
• [Journal Article] The expression of matrix metalloproteinase matrilysin indicates the degree of inflammation in ulcerative colitis. (2003)
  • Author(s): Matsuno K, et al.
  • Journal Title: J Gastroenterol 38 Pages: 348-354
  • Description: 「研究成果報告書概要(和文)」より
• [Journal Article] Epigenetic inactivation of CHFR and sensitivity to microtubule inhibitors in gastric cancer. (2003)
  • Author(s): Satoh A, et al.
  • Journal Title: Cancer Res 63 Pages: 8606-8613
  • Description: 「研究成果報告書概要(和文)」より
• [Journal Article] Endoscopic observation of tissue by narrowband illumination (2003)
  • Author(s): Gono K, Yamazaki K, Doguchi N, Nonami T, Obi T, Yamaguchi M, Ohyama N, Machida H; Sano Y, Yoshida S, Hamamoto Y, Endo T.
  • Journal Title: Optical Review 10 Pages: 211-215
  • NAID: 10011453060
  • Description: 「研究成果報告書概要(欧文)」より
• [Journal Article] Increased cyclooxygenase-2 expression in large flat colorectal tumors (laterally spreading tumors) (2003)
  • Author(s): Yamashita K, Arimura Y, Shimizu H, Takahashi H, Endo T, Imai K, Yamano H
  • Journal Title: J -Gastroenterol 38 Pages: 69-73
  • NAID: 50000736183
  • Description: 「研究成果報告書概要(欧文)」より
• [Journal Article] The expression of matrix metalloproteinase matrilysin indicates the degree of inflammation in ulcerative colitis (2003)
  • Author(s): Matsuno K, Adachi Y, Yamamoto H, Goto A, Arimura Y, Endo T, Itoh F, Imai K
  • Journal Title: J Gastroenterol 38 Pages: 348-354
  • NAID: 10012737385
  • Description: 「研究成果報告書概要(欧文)」より
• [Journal Article] Differential roles of alterations of p53, p16, and SMAD4 expression in the progression of intraductal papillary-mutinous tumors of the pancreas (2003)
  • Author(s): Sasaki S, Yamamoto H, Kaneto H, Ozeki I, Adachi Y, Takagi H, Matsumoto T, Itoh H, Nagakawa T, Miyakawa H, Muraoka S, Fujinaga A, Suga T, Satoh M, Itoh F, Endo T, Imai K
  • Journal Title: Oncol Rep 10 Pages: 21-25
  • Description: 「研究成果報告書概要(欧文)」より
• [Journal Article] Epigenetic inactivation of CHFR and sensitivity to microtubule inhibitors in gastric cancer (2003)
  • Author(s): Satoh A, Toyota M, Itoh F, Sasaki Y, Suzuki H, Ogi K, Kikuchi T, Mita H, Yamashita T, Kojima T, Kusano M, Fujita M, Hosokawa M, Endo T, Tokino T, Imai K
  • Journal Title: Cancer Res 63 Pages: 8606-8613
  • Description: 「研究成果報告書概要(欧文)」より
• [Book] Barrett食道および下部食道腺癌のApomucinと硫酸化糖鎖の解析(食道胃接合部臨床食道噴門研究会編)(監修 木暮 喬, 星原芳雄) (2003)
  • Author(s): 遠藤高夫
  • Total Pages: 2
  • Description: 「研究成果報告書概要(和文)」より
• [Publications] Hamamoto Y, Endo T: "Usefulness of narrow-band imaging endoscopy for diagnosis of Barrett's esophagus."J Gastroenterol. 39. 14-20 (2004)
• [Publications] Satoh A, Toyota M, Endo T et al.: "Epigenetic inactivation of CHFR and sensitivity to microtubule inhibitors in gastric cancer."Cancer Res. 63. 8606-8613 (2003)
• [Publications] Matsuno K, Adachi Y, Endo T et al.: "The expression of matrix metalloproteinase matrilysin indicates the degree of inflammation in ulcerative colitis."J Gastroenterol. 38. 348-354 (2003)
• [Publications] Yamashita K, Arimura Y, Endo T. et al.: "Increased cyclooxygenase-2 expression in large flat colorectal tumors (laterally spreading tumors)."J Gastroenterol. 38. 69-73 (2003)
• [Publications] Gono K, Yamazaki K, Endo T. et al.: "Endoscopic observation of tissue by Narrow band illumination."Optical rev. 10. 211-215 (2003)
• [Publications] Gono K, Obi T, Endo T, et al.: "Appearance of enhanced tissue features in narrow-band endoscopic imaging."Journal of Biomedical Optics. 9. 568-577 (2004)