Altered expression of cell-cycle regulatory genes and proteins in malignant bone and soft tissue tumors
| Project/Area Number |
15590304
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| Research Category |
Grant-in-Aid for Scientific Research (C)
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| Allocation Type | Single-year Grants |
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| Section | 一般 |
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| Research Field |
Human pathology
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| Research Institution | KYUSHU UNIVERSITY |
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Principal Investigator |
ODA Yoshinao Kyushu Unviersity, Graduate School of Medical Sciences, Department of Anatomic Pathology, Assistant Professor, 大学院・医学研究院, 講師 (70291515)
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| Co-Investigator(Kenkyū-buntansha) |
TAMIYA Sadafumi Kyushu University, School of Medicine, Department of Health Sciences, Associate Professor, 医学部保健学科, 助教授 (60284486)
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| Project Period (FY) |
2003 – 2005
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| Project Status |
Completed (Fiscal Year 2005)
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| Budget Amount *help |
¥3,500,000 (Direct Cost: ¥3,500,000)
Fiscal Year 2005: ¥700,000 (Direct Cost: ¥700,000)
Fiscal Year 2004: ¥1,000,000 (Direct Cost: ¥1,000,000)
Fiscal Year 2003: ¥1,800,000 (Direct Cost: ¥1,800,000)
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| Keywords | cell-cycle regulatory gene / cell-cycle regulatory protein / malignant bone and soft tissue tumor / p16 / p53 / p21 / RB1 / CHFR / 悪性末梢神経鞘腫瘍 / p14 / メチル化 / チェックポイント機能 / 染色体異常 / Rb遺伝子 / LOH解析 / p16遺伝子 / 遺伝子メチル化 / 粘液型脂肪肉腫 / 脱分化型脂肪肉腫 / マイクロサテライト不安定性 / E2F-1 / 横紋筋肉腫 / 隆起性皮膚線維肉腫 / 線維肉腫 |
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| Research Abstract |
We have carried out extensive investigations concerning altered expression of cell-cycle regulatory genes and proteins in several kinds of malignant bone and soft tissue tumors and the following results have been obtained.
Leiomyosarcoma ; Decreased expression of p16 was significantly poor prognostic factor in both univariate and multivariate analysis. Promoter methylation was shown to have a strong association with inactivation of p16INK4a gene. (Kawaguchi et al. J Pathol 2003) Alveolar soft part sarcoma (ASPS) ; Inactivation of hMLH1/hMSH2 of DNA mismatch repair genes seems to have an important role to play in the mutagenesis of the tumor-suppressor genes in ASPS. (Saito et al. Hum Pathol 2003) Myxofibrosarcoma ; Reduced expression of p21 could be considered a new parameter to be evaluated, along with classical clinicopathologic prognostic factors, for identifying those at high risk for myxofibrosarcoma. (Oda et al. Hum Pathol 2003) Giant cell tumor of bone ; TGF-beta-IIR and p27 expr
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ession were concordantly decreased and this result supports the possibility that these two factors may play an important role in cell proliferation of this tumor. (Kawaguchi et al. Hum Pathol 2004) Dermatofibrosarcoma protuberans (DFSP) ; Microsatellite instability and p53 mutations are involved in tumor progression of DFSP to fibrosarcoma as early and late events, respectively. (Takahira et al. Hum Pathol 2004) Rhabdomyosarcoma ; p53 overexpression may be related to tumor progression because tumors with p53 overexpression have a high proliferative activity. Alveolar type had a significantly higher both mitotic rate and E2F-1 labeling indices when compared with the embryonal type. (Takahashi et al. Mod Pathol 2004) Clear cell sarcoma (CCS) ; All tumors with genetic alterations of the p16INK4a/p14ARF or p53 gene showed a high mitotic rate or tumor necrosis. These alterations were considered to be influential in the poor prognosis of CCS patients. (Takahira et al. Cancer Sci 2004) Dedifferentiated liposarcoma ; Dedifferentiated component more frequently harbored LOH, mutation or promoter methylation of RB1 gene as compared with those in the well-differentiated component. These results suggests that RB protein has a major roel to play in dedifferentiation. (Takahira et al. Mod Pathol 2005) Myxoid/round cell liposarcoma (MLS/RCLS) ; In MLS/RCLS, reduction of p14 protein expression and p53 mutation were related to poor prognosis. These alterations are correlated with the presence of round cell component, which is one of the strong adverse prognostic factors. Accordingly, the p14ARF/p53 pathway may contribute to the presence of round cell component and malignant progression in this tumor. (Oda et al. J Pathol 2005) Malignant peripheral nerve sheath tumor (MPNST) ; Decreased expression of checkpoint with forkhead-associated domain and ring finger (CHFR) was significantly correlated with a high mitotic count, a high ki-67-labeling index and a poor prognosis in MPNST. These results support the assertion that CHFR functions as an inhibitor of tumor proliferation. (Kobayashi et al. Mod Pathol, in press) Less
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Research Products
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