| Project/Area Number |
61570181
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| Research Category |
Grant-in-Aid for General Scientific Research (C)
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| Allocation Type | Single-year Grants |
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| Research Field |
Experimental pathology
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| Research Institution | Tokai University, School of Medicine |
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Principal Investigator |
YOSHITO Ueyama @dep. of Pathol. School of Medicine , Tokai University, 医学部・病理, 助教授 (30072408)
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| Co-Investigator(Kenkyū-buntansha) |
NORIKAZU Tamaoki Dep. of Pathol. School of Medicine, Tokai University, 医学部・病理, 教授 (50055860)
MASATO Nakamura Dep. of Pathol. School of Medicine, Tokai University, 医学部・病理, 助手 (00164335)
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| Project Period (FY) |
1986 – 1987
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| Project Status |
Completed (Fiscal Year 1987)
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| Budget Amount *help |
¥1,900,000 (Direct Cost: ¥1,900,000)
Fiscal Year 1987: ¥700,000 (Direct Cost: ¥700,000)
Fiscal Year 1986: ¥1,200,000 (Direct Cost: ¥1,200,000)
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| Keywords | HHM(Humaral Hypercalcemia of Malignancy) / Animal model / 1,25)(OH)_2 Vitamin D / Human tumor / nude rat system / HHM因子の抽出 / 悪性高カルシウム血症 / ヌードマウス / ヌードラット |
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| Research Abstract |
Among hypercalcemia associated with malignant tumor, HHM(Humoral Hypercalcemia of Malignancy) in which humoral factors secreted by malignant tumor cells induce hypercalcemia, is intersted by many researchers becaus HHM is thought to be related with growth of the malignant tumors. But factors related with HHM have not been fully studied yet. One of the reasons is that no ideal animal models have not been found out. Taht is, conventinal models show hypercalcemia and high 1,25(OH)_2 D but human patient show hypercalcemia and low 1,25(OH)_2 D. Herfore, to fins out ideal animal model for HHM, we retransplanted 217 human tumors in nude to nuderate and found out 2( lines which induce hypercalcemia (more than 11 mg/dl) and analyzed thse tumors. most of these lines contain squamous catcinoma elements but adenocarionoma and renal cell catcinomas were also included in this group. Co-relation of human and nude rat's serum calcium levels was apparent. Among these human tumor lines, two lines were further studied. One of which is OCCI-JCK(oral cavity carcinoma) and another one is UCC-8-JCK(uterine catcinoma). Serum calcium , sereum phosphate, renal fubular re-asboorption of phosphate, urinary excretion od cAMP were same between two catcinoma lines but 1,25(OH)_2 D was high in OCC-1JCK but low in UCC-8-JCK. Therefore UCC-8-JCK/nude rat system in thought to be an ideal model for HHM.
The trials to extract the hypercalcemia-inducting factors were also attempted using rat's osteobiast-like osteosarcoma line(UMR106) in which cAMP increases by adding hypercalcemic factors. Two carcinoma lines showed a peak at 30K(molecular weight) but UCC-8-JCK line also showed another peak at 25K. Recently, Dr.Martin et al reorted that they succeeded for cloning DNA of PTHlike factors. Their factor may be compatible with out factor at 30K. Analysis of our factor at 25K. may disclose pathophysiology of hyman HHN.
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