Study for the development of molecular therapy targeting the signal transduction pathway through epidermal growth factor receptor
| Project/Area Number |
17390445
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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 |
Obstetrics and gynecology
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| Research Institution | Yamagata University |
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Principal Investigator |
KURACHI Hirohisa Yamagata University, Faculty of Medicine, Professor and chairman (40153366)
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| Co-Investigator(Kenkyū-buntansha) |
NAKAHARA Kenji Yamagata University, Faculty of Medicine, Associate Professor (80250934)
TAKAHASHI Kazuhiro Yamagata University, Faculty of Medicine, Associate Professor (20292427)
HAYASAKA Tadashi Yamagata University, Faculty of Medicine, Associate Professor (10375339)
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| Project Period (FY) |
2005 – 2007
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| Project Status |
Completed (Fiscal Year 2007)
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| Budget Amount *help |
¥16,750,000 (Direct Cost: ¥15,400,000、Indirect Cost: ¥1,350,000)
Fiscal Year 2007: ¥5,850,000 (Direct Cost: ¥4,500,000、Indirect Cost: ¥1,350,000)
Fiscal Year 2006: ¥5,300,000 (Direct Cost: ¥5,300,000)
Fiscal Year 2005: ¥5,600,000 (Direct Cost: ¥5,600,000)
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| Keywords | ovanan cancer / molecular tareeted therapy / EGF receptor / sienal transduction / anti cancer drug / EGF受容体(EGFR) / DNA損傷 |
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| Research Abstract |
Treatment with gefitinib increased the efficacy of the cisplatin-induced inhibition in the intraabdominal dissemination and production of ascites in athymic nude mice inoculated intraperitoneally with cisplatin-resistant Caov-3cells. Immunofluorescent reactivity for phosphorylated EGFR in tumors treated with gefitinib alone and combination of cisplatin + gefitinib was clearly reduced compared with that in tumors treated with vehicle and cisplatin alone. Similar Results were found for the phosphorylation of ERK and Akt.
We next investigated the expression of DNA-PK by immunofluorescent staining with anti-DNA-PK antibody. Treatment with cisplatin significantly increased the expression of DNA-PK in nuclei compared with that in tumors treated with vehicle. Treatment with combination of cisplatin + gefitinib significantly reduced the expression of DNA-PK compared with treatment with cisplatin alone. These results suggested that inhibition of DNA repair by gefitinib enhanced the efficacy of cisplatin.
Moreover, we investigated the effects of platinum-based chemotherapy on the signaling cascades and apoptosis before and after chemotherapy in patients with ovarian cancers using specimens obtained during surgical procedures. The increase in ERK phosphorylation was more consistent than that of Akt. Increases in apoptotic marker expression were observed in all patients exposed to chemotherapy. Activation of ERK by chemotherapy may be associated with apoptosis of tumor cells in patients with ovarian cancers.
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Report
(4 results)
Research Products
(21 results)
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[Journal Article] Raloxifene increases proliferation and upregulates telomerase activity in human umbilical vein endothelial cells.2006
Author(s)
Doshida M, Ohmichi M, Tsutsumi S, Kawagoe J, Takahashi T, Du B, Mori-Abe A, Ohta T, Saitoh-Sekiguchi M, Takahashi K, Kurachi H.
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Journal Title
J Biol Chem 281(34)
Pages: 24270-24278
Related Report
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[Journal Article] Clinical outcome and risk factors for recurrence in borderline ovarian tumours.2006
Author(s)
Yokoyama Y, Moriya T, Takano T, Shoji T, Takahasi O, Nakahara K, Yamada H, Yaegashi N, Okamura K, Izutsu T, Sugiyama T, Tanaka T, Kurachi H, Sato A, Tase T, Mizunuma H.
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Journal Title
Br J Cancer 94(11)
Pages: 1586-1591
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[Journal Article] Inhibition of phosphatidylinositol 3-kinase increases efficacy of cisplatin in in vivo ovarian cancer models.2006
Author(s)
Ohta T, Ohmichi M, Hayasaka T, Mabuchi S, Saitoh M, Kawagoe J, Takahashi K, Igarashi H, Du B, Doshida M, Ishida GM, Motoyama T, Tasaka K, Kurachi H.
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Journal Title
Endocrinology 147(4)
Pages: 1761-1769
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[Journal Article] Inhibitition of phosphatidy linostitol 3-kinase increase efficacy of cisplatinin in vivo ovarian cancer models.2006
Author(s)
Ohta T, Ohmichi M, Hayasaka T, Mabuchi S, Saitoh M, Kawagoe J, Takahashi K, Igarashi H, Du B, Doshida M, Mirei IG, Motoyama T, Tasaka K, Kurachi H.
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