| Project/Area Number |
04454567
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| Research Category |
Grant-in-Aid for General Scientific Research (B)
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| Allocation Type | Single-year Grants |
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| Research Field |
内分泌・代謝学
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| Research Institution | University of Occupational & Environmental Health (U.O.E.H.) |
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Principal Investigator |
ETO Sumiya U.O.E.H., Medicine, Professor, 医学部, 教授 (90010347)
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| Co-Investigator(Kenkyū-buntansha) |
SHIRAKAWA Fumihiko U.O.E.H., Medicine, Lecturer, 医学部, 講師 (10158967)
MISAGO Masahiro U.O.E.H., Medicine, Lecturer, 医学部, 講師 (30157474)
MORIMOTO Isao U.O.E.H., Medicine, Assoc. Professor, 医学部, 助教授 (80145234)
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| Project Period (FY) |
1992 – 1994
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| Project Status |
Completed (Fiscal Year 1994)
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| Budget Amount *help |
¥6,100,000 (Direct Cost: ¥6,100,000)
Fiscal Year 1994: ¥600,000 (Direct Cost: ¥600,000)
Fiscal Year 1993: ¥1,900,000 (Direct Cost: ¥1,900,000)
Fiscal Year 1992: ¥3,600,000 (Direct Cost: ¥3,600,000)
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| Keywords | ATL / hypercalcemia / PTHrP / IL-1 / IL-6 / IL-4 / adhesion molecule / OCT / ATL / 細胞接着分子 / MT2細胞 / PTHγP / MIP1α / IL6 / ビタミンD |
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| Research Abstract |
We have proposed that highly associated hypercalcemia in adult T-cell leukemia (ATL) may be induced by synergetic effects of interleukin-1 production through a vicious cycle and PTHrP production from ATL cells.
In this study, the new following findings were obtained in ATL.
1. PTHrP production, mRNA expression and the growth of ATL cells were rather enhanced in cell culture system under abnormally high levels of calcium condition (up to 4mM) suggesting that there may be another vicious cycle in hypercalcemia of ALT.
2. IL-2 increased PTHrP production in culture nedia. In contrast, IL-4 which is known to be one of bone resorption inhibiting factor decreased mRNA expression of potent bone resorption stimulating factor (BRSF), IL-6, suggesting that various kind of cytokines may be involved in enhancement or inhibition of hypercalcemia of ATL.
3. It was demonstrated that osteoblastic cells adhered to ATL cells, and ATL cells adhered homotypically througha the expression of various kinds of cellular adhesion molecles on the cell surface. Subsequently, these cellular adhesion induced the production of IL-1 and IL-6, very potent BRSF,suggesting that cell-cell adhesion may be involved in the induction of hypercalcemia in ATL as an additional important key.
4. The proliferation of ATL cells and PTHrP production from ATL cells were inhibited by an analog of V.D3 (OCT). Also, it was confirmed that IL-4 inhibited hypercalcemia and decreased the number of osteoclasts in in-vivo experiment. These results suggest that OCT and IL-4 may be usuful candidates for the inhibition of malignant hypercalcemia.
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