1995 Fiscal Year Final Research Report Summary
Clinical significance of alpha-fetoprotein as a tumor marker of testicular carcinoma
| Project/Area Number |
06807127
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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 |
Urology
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| Research Institution | Saitama Medical School |
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Principal Investigator |
UENO Munehisa Saitama Med.Sch., Kidney Dis.Med.Cen., Assistant Professor, 医学部, 講師 (60167286)
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| Co-Investigator(Kenkyū-buntansha) |
DEGUCHI Nobuhiro Saitama Med.Sch., Kidney Dis.Med.Cen., Professor, 医学部, 教授 (90118977)
NAKAMURA Kaoru Keio Univ.Sch.of Med., Dpt.of Urology, Assistant Professor, 医学部, 講師 (10146673)
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| Project Period (FY) |
1994 – 1995
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| Keywords | Retinoic acid / Alpha-fetoprotein / Testicular neoplasm / Differentiation / Cyclic AMP / Flowcytometry / RAR-alpha |
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| Research Abstract |
Alpha-fetoprotein (AFP) has been employed as a tumor marker and respond well to the tumor growth. However, this is also true that in some cases, AFP levels increase whereas tumors are reducing, especially when some chemotherapeutic agents are administered. The present study was undertaken to evaluate a clinical significance of AFP as a marker by using our newly established testicular carcinoma cell line, KU-MT,and to determine the role of retinoic acid (RA) and cyclic AMP (cAMP) in differentiating the cells. Testicular carcinoma cells obtained from alung metastasis were transplanted into nude mice. The sera of a tumor bearing mice were positive for AFP (>10,000). Histologically, the xenograft was composed of yolk sac elements and was immunostained positively for AFP.Electron microscopic pictures showed extracellular deposition of a basement membrane-like substance. KU-MT cells grew exponentially with an approximate doubling time of 2 days and produced up to 500 ng/ml of AFP in the culture medium. The cells were recognized by 2D7 and 6E2, the monoclonal antibodies reactive with embryonal carcinoma as well as 2A2 and 2G10 reactive with yolk sac tumor. The percentage of 2G10-positive cells increased from 33% to 57% when incubated with 10^<-7> M all trans RA (ATRA). ATRA decreased the percent S-phase cell of KU-MT which exclusively uptake bromodeoxyuridine (BrdU). ATRA and RA receptor alpha (RAR-alpha) agonist also caused a significant dose related enhancement of AFP production. The enhancement was completely blocked by RAR-alpha antagonist. Forskolin and cholera toxin are well-known to stimulate adenylate cyclase directly, resulting in accumulation of cAMP.Both of them increased the levels of AFP in culture whereas the cell counts and BrdU uptake decreased. In conclusion, the AFP level may be correlated to cell differentiation as well as the growth. Therefore, tumor growth should not be monitored only with marker values.
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Research Products
(2 results)
