Project/Area Number |
07457312
|
Research Category |
Grant-in-Aid for Scientific Research (B)
|
Allocation Type | Single-year Grants |
Section | 一般 |
Research Field |
Cerebral neurosurgery
|
Research Institution | Nagoya University |
Principal Investigator |
YOSHIDA Jun Nagoya University, School of Medicine Neurosurgery, Professor, 医学部, 教授 (40158449)
|
Co-Investigator(Kenkyū-buntansha) |
HAGIWARA Masatoshi Tokyo medical and dental university, Medical Research Institute, Professor, 難治疾患研究所, 教授 (10208423)
WAKABAYASHI Toshihiko Nagoya University, School of Medicine Neurosurgery, Assistant Professor, 医学部, 講師 (50220835)
|
Project Period (FY) |
1995 – 1997
|
Project Status |
Completed (Fiscal Year 1997)
|
Budget Amount *help |
¥7,500,000 (Direct Cost: ¥7,500,000)
Fiscal Year 1997: ¥2,100,000 (Direct Cost: ¥2,100,000)
Fiscal Year 1996: ¥1,600,000 (Direct Cost: ¥1,600,000)
Fiscal Year 1995: ¥3,800,000 (Direct Cost: ¥3,800,000)
|
Keywords | BRAIN TUMOR / INTERFERON / TNF / GENE / LIPOSOME / NF-kappaB / PHOSPHORYLATION / SIGNAL TRANSDUCTION / NF-κB |
Research Abstract |
Our aim is analysis of mechanisms of antitumor activity induced by cytokine gene transfection into human glioma cells. To clarify the underlying mechanisms involved in the different susceptibility to cytokines, we examined the degrees of phosphorylation or NF-kappaB complex when cytokines (interferon-beta (IFN-beta) or tumor necrosis factor-alpha (TNF-alpha)) were exogenously added to human glioma cells. These results suggest that the different NF-kB complex induced by cytokines in human glioma cells might be related to the varying degrees of susceptibility of tumor cells to cytokines. To elucidate the mechanisms underlying the antitumor activity of cytokine gene transfection using cationic liposomes, we observed morphological changes under video-enhanced contrast differential interference contrast microscopy. Cells harboring the intranuclear human IFN-beta gene underwent morphological changes characterized by bled formation and cytoplasmic boiling such as apoptosis. On the other hand, exogenously added cytokines did not induce the changes at all. In in vivo experiments using C57BL/6 mouse, we confirmed the activation of cellular immunity when liposomes, containing mouse IFN-beta gene were injected into the experimental glioma.
|