New biological active substances produced by a human malignant tissue
| Project/Area Number |
61480182
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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 |
内科学一般
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| Research Institution | The First Department of Intrnal Medicine, Medical Center. Saitama Medical School |
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Principal Investigator |
MATSUZAKI Fukashi Professor Saitama Medical School, 医学部・第一内科, 教授 (80010396)
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| Co-Investigator(Kenkyū-buntansha) |
KONDO Ikuo Lecturer Saitama Medical School, 医学部・第一内科, 講師 (70143435)
IMAI Yasuo Associate Professor Saitama Medical School, 医学部・第一内科, 助教授 (30125992)
宮沢 一彦 埼玉医科大学, 総合医療センター第一内科, 助手
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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 |
¥7,200,000 (Direct Cost: ¥7,200,000)
Fiscal Year 1987: ¥1,400,000 (Direct Cost: ¥1,400,000)
Fiscal Year 1986: ¥5,800,000 (Direct Cost: ¥5,800,000)
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| Keywords | human malignat melanoma cell / cachexia / insulin like actiyity / Transforming growth factor / 人悪性黒色腫細胞株 / リポ蛋白リパーゼ活性阻害物質 / カヘキシー |
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| Research Abstract |
We have observed that a human malignant melanoma cell line transplanted to nude mice induced cachexia in the mice. The pathophysiological conditions were very similar to those of cachexia observed in cancer patients. We postulated that the cachexia might be induced by some biological active substances produced and released by the tumor. Since serum glucose levels of the tumor bearing mice decreased and glycogen content of the tumor formed in the nude mice incresed, we tested whether or not the melanoma cells were producing insulin like activity. We found that conditioned media from the cultured melanoma cells contained insulin like activity tested in vitro using rat fat cells. Fractronation by membrane and gel filtration revealed that active substances consisted of at least two components with a molecular weight about 5,000 and 30,000. Hence we could not detect any EGF recepter in the cells, we checked whether the cells were seceting EGF like activity. We could detect high levels of EG
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F like activity in the conditioned media by radiorecepter assay. The physicochemical nature of the EGF like activity was different from those of mouse and human EGF and similar to that of transforming growth factor (TGF)-<alpha>. From various points of view, we concluded that EGF like activity was identical to TGF-<alpha>. We found that the TGF-<alpha> production by the cells was enhanced by retinoic acid. Using collectd dulture media of the cells added tetinoic acid,we succeeded in purification of TGF-<alpha> enough to immunize animals. We could get specific antibodies which did not cross react human and mouse EGF. Using the antibodies, we established a sensitive assay method. By the assay, we could detect TGF-<alpha> in the urine from tumor bearing mice, This suggests that TGF-<alpha> produced by the tumor may be one of causal substances to the cachexia induced by the tumor. We also found that this cell was producing TGF-<bata>. Therefor more than three substances may be related to the induction of cachexia in tumor bearing mice. Less
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Report
(2 results)
Research Products
(7 results)
