The action mechanism of thalidomide on the infant cancer in a culture model
| Project/Area Number |
18591958
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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 |
Pediatric surgery
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| Research Institution | Saitama Medical University |
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Principal Investigator |
FUJITA Keiko Saitama Medical University, Faculty of Medicine, Associate Professor (80173425)
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| Project Period (FY) |
2006 – 2007
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| Project Status |
Completed (Fiscal Year 2007)
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| Budget Amount *help |
¥2,370,000 (Direct Cost: ¥2,100,000、Indirect Cost: ¥270,000)
Fiscal Year 2007: ¥1,170,000 (Direct Cost: ¥900,000、Indirect Cost: ¥270,000)
Fiscal Year 2006: ¥1,200,000 (Direct Cost: ¥1,200,000)
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| Keywords | Culture / Thalidomide / Infant cancer / Angiogenesis / DNA Microarray |
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| Research Abstract |
The anti-angiogenic properties of thalidomide have led to the use of the agent as a remedy for malignant tumor, e. g., multiple myeloma, prostatic cancer, hepatoma. Nevertheless, the anti-angiogenic moiety of thalidomide remains unidentified. In 2006, I confirmed anti-angiogenic effects with treatment by thalidomide using three-dimensional collagen gel-cultures of mouse aortae. The results indicated that the anti-angiogenic effects of thalidomide stem from the anti-angiogenic action of apoptosis-inducible active caspase-3. On the basis of these data, I sought in this study to investigate the effects of thalidomide using an in vitro infant cancer model (Hepatoblastoma ; HUH-6 Clone-5) in 2007. I observed morphological and molecular biological changes of hepatoblastoma cells by thalidomide.
Taken together with earlier findings, my new results indicated that the thalidomide-induced directly inhibition of proliferation of hepatoblastoma cells involved apoptosis. I demonstrated by DNA microarray that thalidomide-induced oxidative stress enhanced signaling through bone morphogenetic proteins (Bmps). This lead to up-regulation of the Bmp target gene and Wnt antagonist Dickkopf1 (DKK1) with subsequent inhibition of canonical Wnt/beta-catenin signaling and increased cell death. The apoptosis as a factor important for the mechanism of thalidomide was confirmed. From this, I conclude that perturbing of Bmp/DKK1/Wnt signaling is central to proliferation of hepatoblastoma cells of thalidomide.
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Report
(3 results)
Research Products
(11 results)
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[Presentation] Capillary tube formation in vitro2007
Author(s)
Yamada, K
Organizer
The 48th Congress of Histochem & Cytochem The 39th Annual Meeting of the Japanese Society for Clinical, Molecular Morphology (Joint Meeting)29
Place of Presentation
Kofu City General Auditorium
Description
「研究成果報告書概要(欧文)」より
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