Project/Area Number |
12470372
|
Research Category |
Grant-in-Aid for Scientific Research (B)
|
Allocation Type | Single-year Grants |
Section | 一般 |
Research Field |
Pediatric surgery
|
Research Institution | CHIBA UNIVERSITY |
Principal Investigator |
OHNUMA Naomi Chiba University, Graduate School of Medicine, Professor, 大学院・医学研究院, 教授 (50125910)
|
Co-Investigator(Kenkyū-buntansha) |
HASHIZUME Kohei Tokyo University, Graduate School of Medicine, Professor, 大学院・医学系研究科, 教授 (50180815)
HAYASI Yutaka Tohoku University, Graduate School of Medicine, Professor, 大学院・医学系研究科, 教授 (40125638)
SASAKI Fumiaki Hokkaido University, Graduate School of Medicine, Professor, 大学院・医学研究科, 教授 (40178661)
NAKAGAWARA Akira Chiba Cancer Center, Division of Biochemistry, Director, 生化学研究部, 部長 (50117181)
HIYAMA Eiso Hiroshima University Hospital, Assistant Professor, 医学部・歯学部附属病院, 助教授 (00218744)
|
Project Period (FY) |
2000 – 2003
|
Project Status |
Completed (Fiscal Year 2003)
|
Budget Amount *help |
¥14,000,000 (Direct Cost: ¥14,000,000)
Fiscal Year 2003: ¥3,400,000 (Direct Cost: ¥3,400,000)
Fiscal Year 2002: ¥3,400,000 (Direct Cost: ¥3,400,000)
Fiscal Year 2001: ¥3,400,000 (Direct Cost: ¥3,400,000)
Fiscal Year 2000: ¥3,800,000 (Direct Cost: ¥3,800,000)
|
Keywords | HEPATOBLASTOMA / BETA-CATENIN / cDNA PROJECT / TELOMERASE / MDR1 / P-gp / MRP / cMOAT / Real time PCR / 肝悪性腫瘍 / 薬剤耐性 / CMOAT / cDNA / hTERT / P-glycoprotein / APC / サイクリンD1 |
Research Abstract |
We analyzed beta-catenin abnormality in 68 childhood hepatoblastomas. The high frequency of the beta-catenin abnormality (44/68=65%) indicates an important role in the pathogenesis of hepatoblastoma. The beta-catenin abnormalities do not correlated with patient's outcome. These data suggest that disregulation of the Wnt/beta-catenin pathway is an obligatory step in hepatoblastoma pathogenesis. To identify novel hepatoblastoma (HBL)-related genes as biological markers, we have performed a cDNA project of HBL. Expression profile from HBL was very similar to that from a normal liver, and most genes were related to metabolism in liver. Seven novel genes and 33 novel genes were identified to be expressed at high levels in HBLs and normal livers, respectively. On the other hand, 4 known genes and 43 known genes were identified to be expressed at high levels in HBLs and normal livers, respectively. We examined the levels of hTERT mRNA expression and telomerase activity in 48 hepatoblastoma mRNA samples and 28 frozen tumor samples, respectively. The outcomes of the patients with high hTERT expression or high telomerase activity were significantly worse when compared to other patients (p<0.01). These results indicate that high levels of hTERT mRNA expression as well as telomerase activity may be an independent prognosis-predicting factors in the patients with hepatoblastoma.
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