Project/Area Number |
15591536
|
Research Category |
Grant-in-Aid for Scientific Research (C)
|
Allocation Type | Single-year Grants |
Section | 一般 |
Research Field |
Cerebral neurosurgery
|
Research Institution | Kagoshima University |
Principal Investigator |
TAKESHIMA Hideo Kagoshima University, University Hospital, Faculty of Medicine and Dentistry, Assistant professor, 医学部・歯学部附属病院, 講師 (70244134)
|
Co-Investigator(Kenkyū-buntansha) |
HIRANO Hirofumi Kagoshima University, University Hospital, Faculty of Medicine and Dentistry, Assistant professor, 医学部・歯学部附属病院, 講師 (00264416)
倉津 純一 鹿児島大学, 大学院・医歯学総合研究科, 教授 (20145296)
|
Project Period (FY) |
2003 – 2004
|
Project Status |
Completed (Fiscal Year 2004)
|
Budget Amount *help |
¥3,500,000 (Direct Cost: ¥3,500,000)
Fiscal Year 2004: ¥1,100,000 (Direct Cost: ¥1,100,000)
Fiscal Year 2003: ¥2,400,000 (Direct Cost: ¥2,400,000)
|
Keywords | germ cell tumor / germinoma / tumor marker / c-kir / s-kit / SCF / Stem cell factor |
Research Abstract |
In certain subgroupes of central nervous system(CNS) germ cell tumors(GCTs) such as yolk sac tumors and choriocarcinomas, clinical diagnosis could be determined by detecting specific oncoproteins, e.g. alpha-fetoprotein or HCG. So called "neoadjuvant therapy" can be immediatelyapplied without histological verification by craniotomy. Although germinomas are the most common CNS GCTs, no specific tumor marker(s) has been identified. In the absence of such a marker, effective treatment planning requires surgical intervention to obtain a histologic diagnosis. The aim of this study was to establish specific marker(s) for germinomas. In the present work, we focused on c-kit and its ligand, stem cell factor(SCF). The proto-oncogene c-kit is a transmembrane tyrosine kinase receptor that plays a crucial role in the development of germ cells and is aberrantly expressed in a variety of neoplasms. A soluble form of the c-kit(s-kit), composed of only the extracellular domain, has been identified as a
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functional molecule. We immunohistochemically analyzed the distribution of c-kit and SCF to determine its expression profile in various histologic subtypes of CNS GCTs. To examine whether s-kit or SCF represents a novel clinical marker, its concentration in cerebrospinal fluid(CSF) was assayed by sandwich enzyme-linked immunosorbent assay(ELISA). On the cell surface of germinomas, c-kit and SCF was diffusely positive. Some mature teratoma components were weakly immunoreactive for c-kit and SCF ; syncytiotrophoblastic giant cells were negative. The level of s-kit was significantly higher in germinoma-containing tumors. The CSF concentration of s-kit was correlated with the clinical course ; it was markedly higher in patients with subarachnoid dissemination. Meanwhile, the level of SCF also increased in germinoma even in CSF samples with low s-kit concentration. However, specificity of SCF was lower than s-kit, since level of SCF increased in other types of tumors such as medulloblastoma. Therefore, combination of s-kit and SCF seems to be useful for the diagnosis of germinoma at this point. Less
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