2010 Fiscal Year Final Research Report
Development of novel gene-therapy using IL-12 and DNA nanoassociate bearing hyaluronan-glycocalyx for recurrent hepatocellular carcinoma after liver transplantation
| Project/Area Number |
20591528
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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 |
General surgery
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| Research Institution | Kyushu University |
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Principal Investigator |
SOEJIMA Yuji Kyushu University, 統括診療部, 消化器外科医長 (30325526)
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| Co-Investigator(Kenkyū-buntansha) |
MAEHARA Yoshihiko 九州大学, 教授 (80165662)
TAKETOMI Akinobu 九州大学, 助教 (70363364)
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| Project Period (FY) |
2008 – 2010
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| Keywords | 移植外科学 / 肝細胞癌 / 遺伝子治療 |
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| Research Abstract |
In this project, we investigated the effectiveness of gene therapy using IL-12 and DNA nanoassociate bearing hyaluronan-glycocalyx argeting the sinusoidal endothelial cells for the treatment of recurrent hepatocellular carcinoma after liver transplantation. First of all, mIL-12 plasmid DNA was purified. To develop a system for targeting foreign DNA to SECs, comb-type polycations having HA side chains were prepared by coupling HA to poly(L-lysine) (PLL). The HA-grafted-PLL copolymer (PLL-g-HA) thus formed was mixed with DNA in 154 mM NaCl to form soluble nanoassociates bearing hydrated hyaluronate shells. Agarose gel retardation assays revealed selective interaction of the PLL backbone with DNA despite the presence of polyanionic HA side chains.PLL-g-HA. Polymerization of PLL-g-HA with mIL-12 plasmid DNA was then confirmed. However, stable production and supply of PLL-g-HA/pCAGGS-mIL-12 was difficult due to the lack of PLL-g-HA. C3H mice (H-2(k)) were s.c. implanted with 2.5 x 10(6) MH134 cells (H-2(k)) and we treated the established HCC with electroporation-mediated gene therapy using mIL-12 plasmid DNA. Intratumoral gene transfer of mIL-12 elevated intratumoral mIL-12, IFN-gamma, and IFN-gamma-inducible protein-10, significantly inhibited the growth of HCC, compared with HCC-transferred control pCAGGS plasmid.
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[Journal Article]2008
Author(s)
Soejima Y., Meguro M., Taketomi A., Ikegami T., Yamashita Y., Harada N., Ito S., Uchiyama H., Yoshizumi T., Maehara Y.
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Journal Title
Transpl Int. 21(4)
Pages: 384-389
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[Journal Article] Sequential pancreatoduodenectomy after living donor liver transplantation for cholangiocarcinoma.2008
Author(s)
Soejima Y., Ueda S., Sanefuji K., Kayashima H., Yoshizumi T., Ikegami T., Yamashita Y., Sugimachi K., Iguchi T., Taketomi A., Maehara Y.
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Journal Title
Am J Transplant. 8(10)
Pages: 2158-2162
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