| Project/Area Number |
23659622
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| Research Category |
Grant-in-Aid for Challenging Exploratory Research
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| Allocation Type | Multi-year Fund |
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| Research Field |
General surgery
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| Research Institution | Wakayama Medical University |
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Principal Investigator |
YAMAUE Hiroki 和歌山県立医科大学, 医学部, 教授 (20191190)
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| Co-Investigator(Kenkyū-buntansha) |
IWAHASHI Makoto 和歌山県立医科大学, 医学部, 博士研究員 (70244738)
TANI Masaji 和歌山県立医科大学, 医学部, 准教授 (60236677)
NAKAMORI Mikihito 和歌山県立医科大学, 医学部, 講師 (10322372)
KAWAI Manabu 和歌山県立医科大学, 医学部, 講師 (40398459)
HIRONO Seika 和歌山県立医科大学, 医学部, 助教 (60468288)
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| Project Period (FY) |
2011 – 2012
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| Project Status |
Completed (Fiscal Year 2012)
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| Budget Amount *help |
¥3,510,000 (Direct Cost: ¥2,700,000、Indirect Cost: ¥810,000)
Fiscal Year 2012: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000)
Fiscal Year 2011: ¥1,820,000 (Direct Cost: ¥1,400,000、Indirect Cost: ¥420,000)
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| Keywords | 癌ウイルス療法 / オートファジー細胞死 / ヘルペスウイルス / 癌治療用ウイルス / ウイルス療法 / 癌に対するウイルス療法 / 腫瘍溶解ウイルス |
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| Research Abstract |
Refractory gastroenterological cancer such as esophageal cancer, scirrhous gastric cancer, and pancreatic cancer is characterized by rapid cancer cell infiltration. Therefore, refractory gastroenterological cancer carries a worse prognosis than other types of cancers. Viral therapy for refractory gastroenterological cancer is a promising strategy. Viral therapy using herpes simplex virus-1 (HSV -1) is especially practical for clinical application when its safety and therapeutic potency are warranted. In our experiments, we developed new type of armed oncolytic herpes simplex viruses using global genetic analysis. In addition, we confirmed that the ICP34.5 protein of HSV -1 is involved in many aspects of viral pathogenesis; promoting neurovirulence, inhibiting interferon-induced shutoff of protein synthesis, inhibiting dendritic cell maturation, and binding to Beclin 1 to interfere with autophagy . Because of its key role in neuropathogenicity, the γ34.5 gene is deleted in all oncolytic HSVs currently in clinical trial for treating malignant tumors. Unfortunately, deletion of γ34.5 attenuates virus replication in cancer cells, especially refractory gastroenterological cancer . To develop new oncolytic HSVs for use in refractory gastroenterological cancer and that replicate in refractory gastroenterological cancer , we have recently explored an armed oncolytic herpes virus expressing SOCS-3 (suppressor of cytokine signaling 3).
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