1995 Fiscal Year Annual Research Report

悪性グリオーマの分子生物学と新しい治療体系への応用

Research Project

Project/Area Number	06454419
Research Institution	KUMAMOTO UNIVERSITY
Principal Investigator	生塩之敬熊本大学, 医学部, 教授 (20028583)
Co-Investigator(Kenkyū-buntansha)	竹島秀雄熊本大学, 医学部, 助手 (70244134) 西徹熊本大学, 医学部・附属病院, 助手 (00264309) 濱田潤一郎熊本大学, 医学部・附属病院, 助手 (40253752) 倉津純一熊本大学, 医学部, 助教授 (20145296)
Keywords	PDGF / グリオーマ細胞 / トラピジ-ル / MCP-1 / Neurofibromatosis
Research Abstract	すでに私たちは血小板由来増殖因子(platelet-derived growth factor : PDGF)に依存性に増殖するグリオーマ細胞に対してPDGF阻害剤であるトラピジ-ルが増殖抑制をきたし、その機序としてグリオーマ細胞のシグナル伝達系を抑制し、細胞の分化を誘導することを明かにした。さらにグリオーマ細胞からmonocyte chemoattractant protein-1 : MCP-1)が産生され、グリオーマ局所の免疫反応に関与することを明かにしている。今回、私たちはPDGF阻害剤がグリオーマ細胞からのMCP-1産生を抑制することを明かにした。さらにTNFやinterleukin-1などのサイトカインがグリオーマ細胞からMCP-1の産生を調節していることも明らかにしたが、この調節機構に増殖因子の阻害剤が抑制的に作用するものと考えられる。今後、増殖因子のグリオーマに対する免疫反応の調節機序について検討を進める予定である。また、グリオーマの発生・増殖に重要な役割を示すNeurofibromatosis (NF)蛋白の機能についてさらに検討する目的でNF蛋白の抗体を作製した。方法としてグリオーマNF1,NF2蛋白をglutathion-S-transferaseとの融合蛋白質として大腸菌に大量に発現させGSH affinty columnを用いて精製した後、この融合蛋白を用いてラットに免疫しそれぞれの特異抗体を作製した。この結果、NF2蛋白質と結合する細胞内85kDa蛋白質はNF2の癌抑制機能に重要な役割を示すことが示唆された。現在、この85kDa蛋白の精製および解析が進行中である。

Research Products
(13 results)

All Other

All Publications (13 results)

[Publications] Yoshiki Saitoh: "Expression of osteopontin in human glioma. Its correlation with the malignancy." Laboratory Investigation. 72(1). 55-63 (1995)
[Publications] Youichi Itoyama: "Treatment of intracranial nongerminomatous malignant germ cell tumors producing α-fetoprotein." Neurosurgery. 36. 456-466 (1995)
[Publications] Kiminori Sato: "Immunohistochemical expression of inducible nitric oxide synthase (iNOS) in reversible endotoxic shock studied by a novel monoclonal antibody against rat iNOS." Journal of Leukocyte Biology. 57. 36-44 (1995)
[Publications] Satoshi Goto: "Immunostaining calcineurin,a Ca^<2+>/Calmodulin-regulated protein phosphatase,in the diagnostic tumor pathology" Brain Tumor Pathology. 12. 23-30 (1995)
[Publications] Kyoichi Sato: "Expression of monocyte chemoattractant protein-1 in meningioma." Journal of Neurosurgery. 82. 874-878 (1995)
[Publications] Jun-ichi Kuratsu: "The mechanism of growth-regulation of glioma cells by trapidil." Journal of Neuro-Oncology. 23. 201-206 (1995)
[Publications] Jun-ichi Kuratsu: "Stimulatory effect of suramin on the proliferation of human glioma cells." Anticancer Research. 15. 1263-1268 (1995)
[Publications] Yukitaka Ushio: "p16 in the oncogenesis of malignant glomas." Critical Reviw of Neurosurgery. 5. 347-352 (1995)
[Publications] Kazuya Hamada: "Expression and alternative splicing of Pit-1 messenger Ribonucleic acid in pituitary adenomas." Neurosurgery. 38(2). 362-366 (1995)
[Publications] Jun-ichi Kuratsu: "Epidemiologic study of primary intracranial tumors. A regional survey in Kumamoto prefecture in the southern part of Japan." Journal of Neurosurgery. (in press).
[Publications] Toru Nishi: "High-efficiency in vivo gene transfer using intra-arterial plasmid DNA injection following in vivo electroporationl." Cancer Research. (in press).
[Publications] Kazuya Hamada: "Expression of tissue factor correlates with grade of melignancy in human gioma." Cancer. (in press).
[Publications] Kimio Yoshizato: "Increased monocyte chemoattractant protein-1 expression by tumor necrosis factor-α can mediate macrophage infiltration in gliomas." International Journal of Oncology. (in press).

1995 Fiscal Year Annual Research Report

悪性グリオーマの分子生物学と新しい治療体系への応用

Principal Investigator

生塩 之敬 熊本大学, 医学部, 教授 (20028583)

Research Products

[Publications] Yoshiki Saitoh: "Expression of osteopontin in human glioma. Its correlation with the malignancy." Laboratory Investigation. 72(1). 55-63 (1995)

[Publications] Youichi Itoyama: "Treatment of intracranial nongerminomatous malignant germ cell tumors producing α-fetoprotein." Neurosurgery. 36. 456-466 (1995)

[Publications] Kiminori Sato: "Immunohistochemical expression of inducible nitric oxide synthase (iNOS) in reversible endotoxic shock studied by a novel monoclonal antibody against rat iNOS." Journal of Leukocyte Biology. 57. 36-44 (1995)

[Publications] Satoshi Goto: "Immunostaining calcineurin,a Ca^<2+>/Calmodulin-regulated protein phosphatase,in the diagnostic tumor pathology" Brain Tumor Pathology. 12. 23-30 (1995)

[Publications] Kyoichi Sato: "Expression of monocyte chemoattractant protein-1 in meningioma." Journal of Neurosurgery. 82. 874-878 (1995)

[Publications] Jun-ichi Kuratsu: "The mechanism of growth-regulation of glioma cells by trapidil." Journal of Neuro-Oncology. 23. 201-206 (1995)

[Publications] Jun-ichi Kuratsu: "Stimulatory effect of suramin on the proliferation of human glioma cells." Anticancer Research. 15. 1263-1268 (1995)

[Publications] Yukitaka Ushio: "p16 in the oncogenesis of malignant glomas." Critical Reviw of Neurosurgery. 5. 347-352 (1995)

[Publications] Kazuya Hamada: "Expression and alternative splicing of Pit-1 messenger Ribonucleic acid in pituitary adenomas." Neurosurgery. 38(2). 362-366 (1995)

[Publications] Jun-ichi Kuratsu: "Epidemiologic study of primary intracranial tumors. A regional survey in Kumamoto prefecture in the southern part of Japan." Journal of Neurosurgery. (in press).

[Publications] Toru Nishi: "High-efficiency in vivo gene transfer using intra-arterial plasmid DNA injection following in vivo electroporationl." Cancer Research. (in press).

[Publications] Kazuya Hamada: "Expression of tissue factor correlates with grade of melignancy in human gioma." Cancer. (in press).

[Publications] Kimio Yoshizato: "Increased monocyte chemoattractant protein-1 expression by tumor necrosis factor-α can mediate macrophage infiltration in gliomas." International Journal of Oncology. (in press).

生塩之敬熊本大学, 医学部, 教授 (20028583)