| Project/Area Number |
17590792
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| Research Category |
Grant-in-Aid for Scientific Research (C)
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| Allocation Type | Single-year Grants |
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| Section | 一般 |
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| Research Field |
Respiratory organ internal medicine
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| Research Institution | The University of Tokushima |
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Principal Investigator |
YANO Seiji The University of Tokushima, Institute of Health Biosciences, Associate Professor, 大学院ヘルスバイオサイエンス研究部, 助教授 (30294672)
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| Co-Investigator(Kenkyū-buntansha) |
MUGURUMA Hiroaki The University of Tokushima, Institute of Health Biosciences, Assistant Professor, 大学院ヘルスバイオサイエンス研究部, 助手 (30346598)
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| Project Period (FY) |
2005 – 2006
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| Project Status |
Completed (Fiscal Year 2006)
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| Budget Amount *help |
¥3,500,000 (Direct Cost: ¥3,500,000)
Fiscal Year 2006: ¥1,600,000 (Direct Cost: ¥1,600,000)
Fiscal Year 2005: ¥1,900,000 (Direct Cost: ¥1,900,000)
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| Keywords | malignant pleural mesothelioma / orthotopic implantation model / pleural effusion / VEGF / resistance to anticancer drugs / EGF receptor / MYO18B |
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| Research Abstract |
Malignant pleural mesothelioma (MPM) grows aggressively with dissemination in the thoracic cavity and frequently produces malignant pleural effusion. MPM causes respiratory symptoms, including dyspnea, shortness of breath and chest pain, which thus severely limits the quality of life in patients with this disease. Since MPM is refractory to conventional chemotherapy and radiotherapy, the prognosis of MPM patients is extremely poor. To develop a novel therapeutic approach, the cellular and molecular pathogenesis of MPM should be clarified. For such purposes, we established a suitable animal model of MPM that shows patient-like tumor progression. A human MPM cell line (EHMES-10) inoculated orthotopically (thoracic cavity) into SCID mice produced highly vascularized thoracic tumors with pleural dissemination and bloody pleural effusions by 5 weeks.
MYO18B, a novel member of the myosin family, is a tumor suppressor gene isolated from a homozygously deleted region at 22q12.1 in a lung cancer
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cell line. The inactivation of the MYO18B gene plays an important role in several malignant diseases. However, the role of MYO18B in the progression of MPM is still unknown. Six different human MPM cell lines were used in this study. Western blot revealed that none of the cell lines expressed a detectable level of MYO18B protein. One of the MPM cell lines, EHMES-10, was transfected with the MYO18B gene. We found that a restored expression of the MYO18B protein in EHMES-10 cells resulted in the inhibition of their anchorage-independent growth and motility in vitro. In addition, it also inhibited their ectopic (subcutaneous space) and orthotopic (thoracic cavity) growth in SCID mice, in association with an increased degree of cell-apoptosis. Furthermore, it also suppressed the production of bloody pleural effusion after orthotopic injection. These findings suggest that the restored expression of MYO18B may be a useful therapeutic strategy for the treatment of locally advanced MPM in humans. Less
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