1998 Fiscal Year Annual Research Report

多角的戦略に基づく組換えアデノウィルスによる固形癌の遺伝子治療法の開発

Research Project

Project/Area Number	10153247
Research Institution	Kyushu University
Principal Investigator	上野光九州大学, 医学部, 講師 (50260378)
Co-Investigator(Kenkyū-buntansha)	中西洋一九州大学, 医学部, 講師 (20172356) 中山敬一九州大学, 生体防御医学研究所, 教授 (80291508)
Keywords	Dominan-negative H-Ras / p53 / VEGF受容体 / 遺伝子治療 / アデノウィルス / NFkB / IKBa / 血管新生
Research Abstract	1. がん抑制遺伝子p53をヒト肺がん由来の癌細胞に導入するとある種の化学療法剤への感受性が亢進することが明らかとなった(論文印刷中)。 2. Dominan-negative H-Ras(RasY57)をヒト膀胱がん由来細胞に導入すると細胞増殖は抑制されないものの寒天培地上での増殖は著しく抑制された。さらにヌードマウスでの腫瘍形成は完全に抑制された。転移や造腫瘍には細胞増殖とは異なる信号伝達系が使われている可能性が示唆されるとともに、D/N Rasのがんの遺伝子治療への応用も示唆された(投稿中)。 3. VEGF受容体(Flt-1)のうち細胞外ドメインのみ(さらに免疫グロブリンIgGのFc部分を付加)の可溶型VEGF受容体発現ウイルス(AdVEGF-ExR)を作製し、可溶型受容体を過剰発現させるとVEGFを吸着しその作用をin vitroでもin vivoでも抑制できた。AdVEGF-ExRを感染させた癌細胞はヌードマウスにおいて腫瘍形成ができなかった。さらにAdVEGF-ExRを筋肉に注入し癌細胞を皮下に植えると腫瘍形成が阻止された。筋肉内で産生された可溶型受容体が血流に乗って癌細胞植え付け部に到達し腫瘍増殖に必須の血管新生を阻害した結果と考えられた(投稿中)。がんの血管新生抑制遺伝子療法としての可能性が示された。 4. IkBa発現ウイルスを作製した。IkBaの過剰発現によりNFkBの活性化を抑制できた。NFkBシグナルを抑制することでがんのアポトーシスが促進される可能性を検討中である。

Research Products
(12 results)

All Other

All Publications (12 results)

[Publications] Mtsumoto T,at al: "Pletelet-derived growth factor activates p38 mito gen activated protein kinase through rasdependent pathway shiech important for actin reorbanization and cell miaration." Journal of Biological Chemistry. in press.
[Publications] Qi Z, et al: "Blockade ofTGF-β signalings prevents liverfibrosis and dysfunction." Proc.Natl.Acad.Sci.USA. in press.
[Publications] Yamamoto H, et al: "Roles of H-ras in signaling by TGF-β:H-ras is essential in activation of MAP kinase,partially involved intranscriptional activation by TGF-β but not in signaling of anti-proliferative response of TGF-β" Eur.J.Biochem.in press.
[Publications] Ohashi,M,et al.: "Adenovirus-mediated p53 tumor suppressor gene therapy of human gastric cancer cells in vitro and in vivo." Gut. in press.
[Publications] Yukawa H,et al.: "In vitro growth suppression of vascular smooth muscle cells using adenovirus-mediated gene tranfer of a truncated form of fibroblast growth factor receptor." Atherosclerosis. in press.
[Publications] Sakamoto T,et al.: "Tranfection of LacZ gene to retina by an adenoviral vector causes retinal dysfunction with no apparent morphological changes." Hum.Gene.Ther.9. 789-799 (1998)
[Publications] Miyamoto T.: "Early viral complications following CD-34-selected autologous peripheral blood stem cell tranplantation for non-Hodgkin's lymphoma." Br.J.Haematol.100. 348-350 (1998)
[Publications] Nagafuji K.: "Donor lymphocyte transfusion for the treatment of Epstein-Barr virus-associated lymphoproliferative disorder of the brain." Bone Marrow Transplant.21. 1155-1158 (1998)
[Publications] Kuroiwa M.: "Interferon-alpha therapy for chronic myelogenous leukemia during pregnancy." Am.J.Hematology. 59・1. 101-102 (1998)
[Publications] Ishikawa F.: "Autoreactive antibodies following autologous peripheral blood stem cell transplantation." Bone Marrow Transplant. 22. 729-731 (1998)
[Publications] Okamura K.: "Identification of a novel bovine serum protein which is involved in human T-cell leukemia virus type I(HTLV-1)-induced syncytium formation." Arch.Virol.144. 1-18 (1999)
[Publications] Asano Y.: "Effect of interleukin-10 on the hematopoietic progenitor cells from patient with aplastic anemia." Stem cells. in press. (1999)

1998 Fiscal Year Annual Research Report

多角的戦略に基づく組換えアデノウィルスによる固形癌の遺伝子治療法の開発

Principal Investigator

上野 光 九州大学, 医学部, 講師 (50260378)

Research Products

[Publications] Mtsumoto T,at al: "Pletelet-derived growth factor activates p38 mito gen activated protein kinase through rasdependent pathway shiech important for actin reorbanization and cell miaration." Journal of Biological Chemistry. in press.

[Publications] Qi Z, et al: "Blockade ofTGF-β signalings prevents liverfibrosis and dysfunction." Proc.Natl.Acad.Sci.USA. in press.

[Publications] Yamamoto H, et al: "Roles of H-ras in signaling by TGF-β:H-ras is essential in activation of MAP kinase,partially involved intranscriptional activation by TGF-β but not in signaling of anti-proliferative response of TGF-β" Eur.J.Biochem.in press.

[Publications] Ohashi,M,et al.: "Adenovirus-mediated p53 tumor suppressor gene therapy of human gastric cancer cells in vitro and in vivo." Gut. in press.

[Publications] Yukawa H,et al.: "In vitro growth suppression of vascular smooth muscle cells using adenovirus-mediated gene tranfer of a truncated form of fibroblast growth factor receptor." Atherosclerosis. in press.

[Publications] Sakamoto T,et al.: "Tranfection of LacZ gene to retina by an adenoviral vector causes retinal dysfunction with no apparent morphological changes." Hum.Gene.Ther.9. 789-799 (1998)

[Publications] Miyamoto T.: "Early viral complications following CD-34-selected autologous peripheral blood stem cell tranplantation for non-Hodgkin's lymphoma." Br.J.Haematol.100. 348-350 (1998)

[Publications] Nagafuji K.: "Donor lymphocyte transfusion for the treatment of Epstein-Barr virus-associated lymphoproliferative disorder of the brain." Bone Marrow Transplant.21. 1155-1158 (1998)

[Publications] Kuroiwa M.: "Interferon-alpha therapy for chronic myelogenous leukemia during pregnancy." Am.J.Hematology. 59・1. 101-102 (1998)

[Publications] Ishikawa F.: "Autoreactive antibodies following autologous peripheral blood stem cell transplantation." Bone Marrow Transplant. 22. 729-731 (1998)

[Publications] Okamura K.: "Identification of a novel bovine serum protein which is involved in human T-cell leukemia virus type I(HTLV-1)-induced syncytium formation." Arch.Virol.144. 1-18 (1999)

[Publications] Asano Y.: "Effect of interleukin-10 on the hematopoietic progenitor cells from patient with aplastic anemia." Stem cells. in press. (1999)

上野光九州大学, 医学部, 講師 (50260378)