2004 Fiscal Year Final Research Report Summary
Gene Therapy for Ovarian Cancer by Bikunin
| Project/Area Number |
14571553
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| Research Category |
Grant-in-Aid for Scientific Research (C)
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| Allocation Type | Single-year Grants |
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| Section | 一般 |
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| Research Field |
Obstetrics and gynecology
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| Research Institution | Hamamatsu University School of Medicine |
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Principal Investigator |
KOBAYASHI Hiroshi Hamamatsu Univ.Sch.of Med., 医学部, 助教授 (40178330)
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| Co-Investigator(Kenkyū-buntansha) |
NISHIGUCHI Tomizo Hamamatsu Univ.Sch.of Med., 医学部附属病院, 講師 (30198452)
SUZUKI Mitsuaki Jichi Med.Univ., 医学部, 教授 (50110870)
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| Project Period (FY) |
2002 – 2004
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| Keywords | Ovarian Cancer / Gene Therapy / Bikunin |
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| Research Abstract |
A Kunitz-type protease inhibitor, bikunin, is known to suppress the invasion and metastasis of cancer cells. HI8, a carboxyl terminal domain of bikunin, is an active site of this glycoprotein. To increase its affinity for cancer cells, we constructed a chimeric gene, ATF-HI8, and investigated the anti-invasive and anti-migratory activity of ATF-HI8 on ovarian cancer cells. ATF-HI8-expressing plasmid and ATF-expressing plasmid were introduced into the highly invasive and metastatic ovarian cancer cell line HRA. The properties of the established cell line (HRA/ATF-HI8) were compared to those of the HRA/ATF and the HRA/luciferase (HRA/LUC, control) cell lines in terms of cell proliferation, invasion and migration. As a result, (i) there were no differences in cell proliferation between HRA/ATF-HI8 and HRA/LUC ; (ii) the invasion and migration of HRA/ATF-HI8 cells were significantly inhibited compared to those of HRA/LUC cells ; (iii) the migration, but not the invasion, of HRA/ATF cells was significantly inhibited compared to that of HRA/LUC. These results indicate that the overexpression of ATF-HI8 inhibits the invasion and migration of ovarian cancer cells without affecting cell proliferation and suggest that HI8 is involved in the anti-invasive and the anti-migratory activities, and the addition of ATF brought about the increase in the anti-migratory activity of HI8. The above findings suggest the applicability of therapeutic strategies targeting the inhibition of peritoneal invasion and dissemination of ovarian cancer by the use of the chimeric gene ATF-HI8.
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[Journal Article] Bikunin suppresses lipopolysaccharide-induced lethality through down-regulation of tumor necrosis factor-alpha and interleukin-1beta in macrophages.2005
Author(s)
Wakahara K, Kobayashi H, Yagyu T, Matsuzaki H, Kondo T, Kurita N, Sekino H, Inagaki K, Suzuki M, Kanayama N, Terao T.
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Journal Title
J.Infect.Dis. 191
Pages: 930-938
Description
「研究成果報告書概要(欧文)」より
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[Journal Article] A kunitz-type protease inhibitor bikunin disrupts ligand-induced oligomerization of receptors for transforming growth factor (TGF)-β and subsequently suppresses TGF-β signalings.2004
Author(s)
Tatsuo Yagyu, Hiroshi Kobayashi, Kiyoshi Wakahara, Hidenori Matsuzaki, Toshiharu Kondo, Noriyuki Kurita, Hideo Sekino, Kiyokazu Inagaki, Mika Suzuki, Naohiro Kanayama, Toshihiko Terao.
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Journal Title
FEBS Lett. 576
Pages: 408-416
Description
「研究成果報告書概要(欧文)」より
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[Journal Article] Bikunin inhibits lipopolysaccharide-induced tumor necrosis factor alpha induction in macrophages.2004
Author(s)
Matsuzaki H, Kobayashi H, Yagyu T, Wakahara K, Kondo T, Kurita N, Sekino H, Inagaki K, Suzuki M, Kanayama N, Terao T.
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Journal Title
Clin.Diag.Lab.Immunol. 11
Pages: 1140-1147
Description
「研究成果報告書概要(欧文)」より
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[Journal Article] Transforming growth factor-beta1-dependent activation of Smad2/3 and up-regulation of PAI-1 expression is negatively regulated by Src in SKOV-3 human ovarian cancer cells.2004
Author(s)
Wakahara K, Kobayashi H, Yagyu T, Matsuzaki H, Kondo T, Kurita N, Sekino H, Inagaki K, Suzuki M, Kanayama N, Terao T.
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Journal Title
J Cell Biochem. 93(3)
Pages: 437-453
Description
「研究成果報告書概要(欧文)」より
