2004 Fiscal Year Final Research Report Summary
Interaction of proinflammatory cytokines and growth factors in gastric carcinogenesis
| Project/Area Number |
14370181
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| Research Category |
Grant-in-Aid for Scientific Research (B)
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| Allocation Type | Single-year Grants |
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| Section | 一般 |
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| Research Field |
Gastroenterology
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| Research Institution | Osaka University |
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Principal Investigator |
SHINOMURA Yasuhisa Osaka University, Graduate School of Medicine, Associate Professor, 医学系研究科, 助教授 (90162619)
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| Co-Investigator(Kenkyū-buntansha) |
KIYOHARA Tatsuya Osaka University, Graduate School of Medicine, Associate Professor, 医学系研究科, 助教授 (50322178)
FUJIMOTO Takashi Osaka University, Medical School, Medical Staff, 医学部附属病院, 医員(臨床研究)
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| Project Period (FY) |
2002 – 2004
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| Keywords | gastric cancer / Helicobacter pylori / gastrin / IL-1 / HB-EGF / gastritis / CD9 |
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| Research Abstract |
We have reported that hypergastrinemia and increased IL-1beta production may contribute to foveolar hyperplasia in Helicobacter pylori-associated enlarged fold gastritis and that gastrin induces heparin binding epidermal growth factor-like growth factor(HB-EGF) and amphiregulin production in the gastric mucosa. The purpose of the present study was to clarify the roles of proinflammatory cytokines and growth factors in gastric carcinogenesis. Gastrin induced IL-8 expression through activation of nuclear factor kappaB in cooperation with IL-1beta. Increased 8-hydroxydeoxyguanosine production and hypermethylation in the region of promoter of tumor suppressor genes were observed in the gastric mucosa of patients with enlarged fold gastritis. HB-EGF expression was associated with CD9 expression in gastric cancer. Anti-CD9 antibody inhibited cell proliferation and induced apoptosis in gastric cancer cells through tyrosine phosphorylation of the p46 Shc isoform. Gastrin and proinflammatory cytokines and growth factors were shown to be involved in gastric carcinogenessis.
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[Journal Article] Gefitinib (‘Iressa', ZD1839) inhibits SN38-triggered EGF signals and IL-8 production in gastric cancer cells.2005
Author(s)
Kishida O, Miyazaki Y, Murayama Y, Ogasa M, Miyazaki T, Yamamoto T, Watabe K, Tsutsui S, Kiyohara T, Shimomura I, Shinomura Y.
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Journal Title
Cancer Chemoth.Pharm. 55(4)
Pages: 393-403
Description
「研究成果報告書概要(欧文)」より
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[Journal Article] CD9-mediated activation of the p46 Shc isoform leads to apoptosis in cancer cells.2004
Author(s)
Murayama Y, Miyagawa J, Oritani K, Yoshida H, Yamamoto K, Kishida O, Miyazaki T, Tsutsui S, Kiyohara T, Miyazaki Y, Higashiyama S, Matsuzawa Y, Shinomura Y
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Journal Title
J Cell Sci. 117(Pt 15)
Pages: 3379-3388
Description
「研究成果報告書概要(欧文)」より
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[Journal Article] c-kit gene mutation at exon 17 or 13 is very rare in sporadic gastrointestinal stromal tumors.2003
Author(s)
Kinoshita K, Isozaki K, Hirota S, Nishida T, Chen H, Nakahara M, Nagasawa Y, Ohashi A, Shinomura Y, Kitamura Y, Matsuzawa Y
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Journal Title
J Gastroenterol Hepatol. 18(2)
Pages: 147-151
Description
「研究成果報告書概要(欧文)」より
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[Journal Article] Gastrin activates nuclear factor kappaB (NFkappaB) through a protein kinase C dependent pathway involving NFkappaB inducing kinase, inhibitor kappaB (IkappaB) kinase, and tumor necrosis factor receptor associated factor 6 (TRAF6) in MKN-28 cells transfected with gastrin receptor.2003
Author(s)
Ogasa M, Miyazaki Y, Hiraoka S, Kitamura S, Nagasawa Y, Kishida O, Miyazaki T, Kiyohara T, Shinomura Y, Matsuzawa Y
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Journal Title
Gut. 52(6)
Pages: 813-819
Description
「研究成果報告書概要(欧文)」より
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[Journal Article] Endoscopic ultrasonography-guided fine needle aspiration biopsy in follow-up patients with gastrointestinal stromal tumors.2003
Author(s)
Kinoshita K, Isozaki K, Tsutsui S, Kitamura S, Hiraoka S, Watabe K, Nakahara M, Nagasawa Y, Kiyohara T, Miyazaki Y, Hirota S, Nishida T, Shinomura Y, Matsuzawa Y
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Journal Title
Eur J Gastroenterol Hepatol. 15(11)
Pages: 1189-1193
Description
「研究成果報告書概要(欧文)」より
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[Journal Article] Helicobacter pylori-induced enlarged-fold gastritis is associated with increased mutagenicity of gastric juice, increased oxidative DNA damage, and an increased risk of gastric carcinoma.2003
Author(s)
Nishibayashi H, Kanayama S, Kiyohara T, Yamamoto K, Miyazaki Y, Yasunaga Y, Shinomura Y, Takeshita T, Takeuchi T, Morimoto K, Matsuzawa Y
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Journal Title
J Gastroenterol Hepatol. 18(12)
Pages: 1384-1391
Description
「研究成果報告書概要(欧文)」より
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[Journal Article] Enhanced carbon tetrachloride-induced liver fibrosis in mice lacking adiponectin.2003
Author(s)
Kamada Y, Tamura S, Kiso S, Matsumoto H, Saji Y, Yoshida Y, Fukui K, Maeda N, Nishizawa H, Nagaretani H, Okamoto Y, Kihara S, Miyagawa J, Shinomura Y, Funahashi T, Matsuzawa Y
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Journal Title
Gastroenterology. 125(6)
Pages: 1796-1807
Description
「研究成果報告書概要(欧文)」より
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[Journal Article] Significance of the association between heparin-binding epidermal growth factor-like growth factor and CD9 in human gastric cancer.2002
Author(s)
Murayama Y, Miyagawa J, Shinomura Y, Kanayama S, Isozaki K, Yamamori K, Mizuno H, Ishiguro S, Kiyohara T, Miyazaki Y, Taniguchi N, Higashiyama S, Matsuzawa Y
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Journal Title
Int.J.Cancer 98(4)
Pages: 505-513
Description
「研究成果報告書概要(欧文)」より
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[Journal Article] Familial gastrointestinal stromal tumors associated with dysphagia and novel type germline mutation of KIT gene.2002
Author(s)
Hirota S, Nishida T, Isozaki K, Taniguchi M, Nishikawa K, Ohashi A, Takabayashi A, Obayashi T, Okuno T, Kinoshita K, Chen H, Shinomura Y, Kitamura Y.
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Journal Title
Gastroenterology 122(5)
Pages: 1493-1499
Description
「研究成果報告書概要(欧文)」より
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[Journal Article] Deficiency of KIT positive cells in the colon of patients with diabetes mellitus.2002
Author(s)
Nakahara M, Isozaki K, Hirota S, Vanderwinden JM, Takakura R, Kinoshita K, Miyagawa J, Chen H, Miyazaki Y, Kiyohara T, Shinomura Y, Matsuzawa Y
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Journal Title
J.Gastroenterol.Hepatol. 17(6)
Pages: 666-670
Description
「研究成果報告書概要(欧文)」より
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[Journal Article] Polyclonal nature of diffuse proliferation of interstitial cells of Cajal in patients with familial and multiple gastrointestinal stromal tumors.2002
Author(s)
Chen H, Hirota S, Isozaki K, Sun H, Ohashi A, Kinoshita K, O'Brien P, Kapusta L, Dardick I, Obayashi T, Okazaki T, Shinomura Y, Matsuzawa Y, Kitamura Y
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Journal Title
Gut. 51(6)
Pages: 793-796
Description
「研究成果報告書概要(欧文)」より
