1997 Fiscal Year Annual Research Report

細胞増殖および血管新生抑制分子を発現する組換えアデノウィルスによる癌の遺伝子治療

Research Project

Project/Area Number	09255239
Research Institution	Kyushu University
Principal Investigator	上野光九州大学, 医学部, 講師 (50260378)
Co-Investigator(Kenkyū-buntansha)	田渕和雄佐賀医科大学, 教授 (50116480) 中西洋一九州大学, 医学部, 講師 (20172356) 中野修治九州大学, 医学部, 講師 (40164248)
Keywords	組換えアデノウイルス / 癌 / p53 / p21 WAF1 / Sdi1 / H-Ras / 遺伝子治療 / アポトーシス
Research Abstract	1.Dominant-negative H-Ras発現アデノウイルス(AdCARasY57)を作製し、ヒト膀胱癌由来細胞に感染させたところ、通常倍地での細胞増殖は30%程度抑制したにすぎないものの、Soft agar上での増殖をほとんど完全に抑制した。さらにヌードマウスでの造腫瘍性を観ると腫瘍形成は完全に抑制された。転移や造腫瘍性には増殖信号とは異なるH-Ras-MAP kinase系を介する経路の存在が示唆されるとともに、D/N Rasの導入によりin vivoでの腫瘍形成(とくに転移)を有効に抑える可能性が示された(論文投稿中)。 2.Rac,RhoのDominant-negative form を導入すると培養がん細胞の浸潤能が著しく抑制された。in vivo での抗腫瘍効果を検討中である。 3.がん抑制遺伝子p53,細胞周期進行抑制分子p21WAF1/Sdi1発現ウイルスを作製し、両者のがん細胞増殖に与える抑制効果をin vitro,in vivoで検討した。p53はp21には依存せずにアポトーシスを惹起しがん細胞は死滅した。p21では細胞は増殖を停止し老化に似た形質を示すがアポトーシスは起こらず細胞は残存する。p53は in vivoでもより強い抗腫瘍効果を示した。両者には相加/相乗作用は認めなかった(論文投稿中)。 4.がん細胞に依ってアデノウイルスへの感受性が著しく異なる。細胞表面のある種のインテグリンを定量することで感受性を予測できることを観察した(論文印刷中)。 5.研究計画どおりに数種の新しいベクターの作製に着手した。

Research Products
(11 results)

All Other

All Publications (11 results)

[Publications] Sakamoto T.,et al.: "Transfection of LacZ gene to retina by an adenoviral vector causes retinal dysfunction with no apparent morphological changes." Hum.Gene Ther.(in press).
[Publications] Takayama K.,et al: "The levels of integrin aV and b5 may well predict the susceptibility to adenovirus-mediated gene transfer in human lung cancer cells." Gene Ther.(in press).
[Publications] Li Q,.et al.: "Stretch-induced collagen syntesis in cultured smooth muscle cells from rabbit aortic media and possible involvement of angiotensin II and TGF-b." Vasc.Res..(in press).
[Publications] Ueno H.,et al.: "Adenovirus-mediated expression of secreted form of basic fibroblast growth factor(FGF-2)induces cellular proliferation and angiogenesis in vivo." Arterioscl.Thromb.Vasc.Biol.17. 2453-2460 (1997)
[Publications] Ueno H.,et al.: "Adenovirus-mediated transfer of a dominant-negative H-ras suppresses neointimal formation in balloon-injured arteries in vivo.Arterioscl." Thromb.Vasc.Biol.17. 898-904 (1997)
[Publications] Ueno H.,et al.: "Local expression of C-type natriuretic peptide markedly suppresses neointimal formation in rat injured arteries through an autocrine/paracrine loop." Circulation. 96. 2272-2279 (1997)
[Publications] Ueno H.,et al.: "Adenovirus-mediated transfer of cyclin-dependent kinase inhibitor-p21 suppresses neointimal hyperplasia in balloon-injured arteries in vivo." Ann.NY Acad.Sci.811. 401-411 (1997)
[Publications] Takahashi T.,et al.: "Angiotensin II stimulates mitogen-activated protein kinases ans protein synthesis by a ras-independent pathway in vascular smooth muscle cells." J.Biol.Chem.272. 16018-16022 (1997)
[Publications] Kitamura Y.,et al.: "Interaction of Nck-associated protein 1 with activatied GTP-binding protein" Rac.Biochem.J.3332. 873-878 (1997)
[Publications] Sakaue H.,et al.: "Phosphoinositide 3-kinase is required for insulin-induced but not for growth hormone- or hyperosmolarity-induced glucose uptake in 3T3-L1 adipocytes." Mol.Endocrinol.11. 1551-1562 (1997)
[Publications] Li Q.,et al.: "Stretch-induced proliferation of cultured vascular smooth muscle cells and a possible involvement of local renin-angiotensin system and platelet-derived growth factor." Hypertens.Res.20. 217-223 (1997)

1997 Fiscal Year Annual Research Report

細胞増殖および血管新生抑制分子を発現する組換えアデノウィルスによる癌の遺伝子治療

Principal Investigator

上野 光 九州大学, 医学部, 講師 (50260378)

Research Products

[Publications] Sakamoto T.,et al.: "Transfection of LacZ gene to retina by an adenoviral vector causes retinal dysfunction with no apparent morphological changes." Hum.Gene Ther.(in press).

[Publications] Takayama K.,et al: "The levels of integrin aV and b5 may well predict the susceptibility to adenovirus-mediated gene transfer in human lung cancer cells." Gene Ther.(in press).

[Publications] Li Q,.et al.: "Stretch-induced collagen syntesis in cultured smooth muscle cells from rabbit aortic media and possible involvement of angiotensin II and TGF-b." Vasc.Res..(in press).

[Publications] Ueno H.,et al.: "Adenovirus-mediated expression of secreted form of basic fibroblast growth factor(FGF-2)induces cellular proliferation and angiogenesis in vivo." Arterioscl.Thromb.Vasc.Biol.17. 2453-2460 (1997)

[Publications] Ueno H.,et al.: "Adenovirus-mediated transfer of a dominant-negative H-ras suppresses neointimal formation in balloon-injured arteries in vivo.Arterioscl." Thromb.Vasc.Biol.17. 898-904 (1997)

[Publications] Ueno H.,et al.: "Local expression of C-type natriuretic peptide markedly suppresses neointimal formation in rat injured arteries through an autocrine/paracrine loop." Circulation. 96. 2272-2279 (1997)

[Publications] Ueno H.,et al.: "Adenovirus-mediated transfer of cyclin-dependent kinase inhibitor-p21 suppresses neointimal hyperplasia in balloon-injured arteries in vivo." Ann.NY Acad.Sci.811. 401-411 (1997)

[Publications] Takahashi T.,et al.: "Angiotensin II stimulates mitogen-activated protein kinases ans protein synthesis by a ras-independent pathway in vascular smooth muscle cells." J.Biol.Chem.272. 16018-16022 (1997)

[Publications] Kitamura Y.,et al.: "Interaction of Nck-associated protein 1 with activatied GTP-binding protein" Rac.Biochem.J.3332. 873-878 (1997)

[Publications] Sakaue H.,et al.: "Phosphoinositide 3-kinase is required for insulin-induced but not for growth hormone- or hyperosmolarity-induced glucose uptake in 3T3-L1 adipocytes." Mol.Endocrinol.11. 1551-1562 (1997)

[Publications] Li Q.,et al.: "Stretch-induced proliferation of cultured vascular smooth muscle cells and a possible involvement of local renin-angiotensin system and platelet-derived growth factor." Hypertens.Res.20. 217-223 (1997)

上野光九州大学, 医学部, 講師 (50260378)