Development of iPS cells-derived vector cells for antiangiogenic gene therapy for hepatocellular carcinoma.
| Project/Area Number |
22590752
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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 |
Gastroenterology
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| Research Institution | Kurume University |
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Principal Investigator |
TORIMURA Takuji 久留米大学, 先端癌治療研究センター, 教授 (60197986)
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| Co-Investigator(Kenkyū-buntansha) |
NAKAMURA Toru 久留米大学, 医学部, 助教 (30341332)
TANIGUCHI Eitaro 久留米大学, 医学部, 助教 (50341318)
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| Co-Investigator(Renkei-kenkyūsha) |
UENO Takato 久留米大学, 先端癌治療研究センター, 教授 (70176618)
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| Project Period (FY) |
2010 – 2012
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| Project Status |
Completed (Fiscal Year 2012)
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| Budget Amount *help |
¥4,550,000 (Direct Cost: ¥3,500,000、Indirect Cost: ¥1,050,000)
Fiscal Year 2012: ¥1,170,000 (Direct Cost: ¥900,000、Indirect Cost: ¥270,000)
Fiscal Year 2011: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000)
Fiscal Year 2010: ¥2,080,000 (Direct Cost: ¥1,600,000、Indirect Cost: ¥480,000)
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| Keywords | 血管新生抑制遺伝子療法 / 肝細胞癌 / iPS 細胞 / 間葉系幹細胞 / 可用性VEGF レセプター / HIF1-alpha / iPS細胞 / αSMA陽性細胞 / CXCR4遺伝子 / siRNA / 可溶性VEGFレセプター1,2 / 平滑筋細胞 / αSMA / 血管新生抑制療法 / ベクター細胞 / 細胞遊走能 / CXCE4 |
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| Research Abstract |
In the present study, we investigated the anti-tumor effects of anti-angiogenic gene therapy with iPS cell-derived vector cells transfected soluble VEGF receptor-1 and 2 cDNAs. At first, we tried to develop the vector cells from mouse iPS cells. However, mouse iPS cell-derived smooth cells showed less proliferative activity and less homing to tumor tissues than we had expected. So, we changed to construct mesenchymal stem cells from human iPS cells. After constructing mesenchymal stem cells, we transferred CXCR4 cDNA to mesenchymal stem cells to up-regulate the ability of homing to tumor tissues. As vector cells might produce several kinds of growth factors through the activation of HIF signaling under hypoxic condition in tumor tissues, we reduced the expression of HIF1-?? with siRNA technique. Then, we transferred soluble VEGFreceptor-1 and 2 cDNAs with adenovirus vector and injected the vector cells (1x106/week for4 weeks) to tumor-bearing mice of hepatoma cells through the til vein. After 4 weeks of initial treatment, tumor growth was suppressed comparing with non-treated control mice. Injected vector cells mainly located in the stroma of tumor tissues. Some of vector cellsdifferentiated to endothelial cells and smooth muscle cells in tumor tissues. The microvascular density in tumor tissues was decreased comparing with control group. The homing of vector cells to non-cancerous tissues was rarely detected. Severe adverse events such as bone marrow suppression or abnormality of liver function test were not observed.
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Report
(4 results)
Research Products
(35 results)
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[Journal Article] Vandetanib, an inhibitor of VEGF receptor-2 and EGF receptor, suppresses tumor development and improves prognosis of liver cancer in mice2012
Author(s)
Inoue K, Torimura T, Nakamura T,Iwamoto H, Masuda H, Abe M, Hashimoto O, Koga H, Ueno T, Yano H, Sata M.
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Journal Title
Clin Cancer Res.
Volume: 18
Issue: 14
Pages: 3924-3933
DOI
Related Report
Peer Reviewed
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[Journal Article] Serum vascular endothelial growth factor as a predictor of response and survival in patients with advanced hepatocellular carcinoma undergoing hepatic arterial infusionchemotherapy.2012
Author(s)
Niizeki T, Sumie S, Torimura T, Kurogi J, Kuromatsu R, Iwamoto H, Aino H, Nakano M, Kawaguchi A, Kakuma T, Sata M.
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Journal Title
J Gastroenterol.
Volume: 47
Issue: 6
Pages: 686-695
DOI
Related Report
Peer Reviewed
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[Journal Article] Hepatitis C virus core protein upregulates the expression of vascular endothelial growth factor via the nuclearfactor-κB/hypoxia-inducible factor-1α axis under hypoxic conditions.2012
Author(s)
Abe M, Koga H, Yoshida T, Masuda H, Iwamoto H, Sakata M, Hanada S, Nakamura T, Taniguchi E, Kawaguchi T, Yano H, Torimura T, Ueno T, Sata M.
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Journal Title
Hep Res.
Volume: 42
Issue: 6
Pages: 591-600
DOI
NAID
Related Report
Peer Reviewed
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[Journal Article] Interaction of endothelial progenitor cells expressing cytosine deaminase in tumor tissues and 5-fluorocytosine administration suppresses growth of5-fluorouracil-sensitive liver cancer in mice.2012
Author(s)
Torimura T, Ueno T, Taniguchi E, Masuda H, Iwamoto H, Nakamura T, Inoue K, Hashimoto O, Abe M, Koga H, Barresi V, Nakashima E, Yano H, Sata M.
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Journal Title
Cancer Sci.
Volume: 103
Issue: 3
Pages: 542-548
DOI
Related Report
Peer Reviewed
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[Journal Article] Metronomic S-1 chemotherapy and vandetanib: an efficacious and nontoxic treatment for hepatocellular carcinoma2011
Author(s)
Iwamoto H, Torimura T, Nakamura T, Hashimoto O, Inoue K, Kurogi J, Niizeki T, Kuwahara R, Abe M, Koga H, Yano H, Kerbel RS, Ueno T, Sata M.
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Journal Title
Neoplasia.
Volume: 13
Pages: 187-197
Related Report
Peer Reviewed
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[Journal Article] Recent progress in the management of hepatocellular carcinoma detected during a surveillance program in Japan2010
Author(s)
Nakano M, Ando E, Kuromatsu R, Torimura T, Sumie S, Takata A, Fukushima N, Kurogi J, Niizeki T, Iwamoto H, Tanaka M, Sata M.
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Journal Title
HepatolRes.
Volume: 40
Pages: 989-996
NAID
Related Report
Peer Reviewed
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[Journal Article]2010
Author(s)
Nagamatsu H, Hiraki M, Mizukami N, Yoshida H, Iwamoto H, Sumie S, TorimuraT, Sata M.
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Journal Title
Aliment Pharmacol Ther.
Volume: 32
Issue: 4
Pages: 543-550
DOI
Related Report
Peer Reviewed
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