Development of novel diagnostic and therapeutic strategies of hepatoblastoma through multicenter cooperative study
Grant-in-Aid for Scientific Research (B)
|Allocation Type||Single-year Grants |
|Research Institution||Chiba University |
OHNUMA Naomi Chiba University, Graduate School of Medicine, Professor, 大学院・医学研究院, 教授 (50125910)
NAKAGAWARA Akira Chiba Cancer Center, Research Institute, Director, 研究所, 所長 (50117181)
SASAKI Fumiaki Hokkaido University, Graduate School of Medicine, Professor, 大学院・医学研究科, 教授 (40178661)
HAYASHI Yutaka Tohoku University, Graduate School of Medicine, Professor, 大学院・医学研究科, 教授 (40125638)
EISO Hiyama Hiroshima University, Natural Science Center for Basic Research and Development, Professor, 自然科学研究支援開発センター, 教授 (00218744)
YOSHIDA Hideo Chiba University, Graduate School of Medicine, Assistant Professor, 大学院・医学研究院, 助教授 (60210712)
橋都 浩平 東京大学, 医学部・附属病院, 教授 (50180815)
|Project Period (FY)
2004 – 2006
Completed(Fiscal Year 2006)
|Budget Amount *help
¥14,100,000 (Direct Cost : ¥14,100,000)
Fiscal Year 2006 : ¥4,100,000 (Direct Cost : ¥4,100,000)
Fiscal Year 2005 : ¥4,800,000 (Direct Cost : ¥4,800,000)
Fiscal Year 2004 : ¥5,200,000 (Direct Cost : ¥5,200,000)
|Keywords||hepatoblastoma / childhood cancer / group study / prognostic factor / microarray / multimodal treatment / Wnt signal / Novel therapeutic strategy / 胚芽腫 / グループスタディー / 造血幹細胞移植 / マクロアレイ / グループスタディ / アレイCGH / cDNAマイクロアレイ / MDR1 / C / EBP|
1.Multimodal treatment of hepatoblasatoma with guideline protocol JPLT-2
Outcome of 126 hepatoblastomas treated with the JPLT-2 protocol was analyzed. Overall 3-year survival was 80%, which was satisfactory, but the outcome of metastatic cases and unrespectable cases were still poor.
2.Hunting hepatoblastoma-related genes by cDNA microarray
Genes responsible for the carcinogenesis and progression of hepatoblastomas were identified through cDNA microarray studies. These genes could be candidates for new prognostic factors of hepatoblastoma. Furthermore, a novel array chip specified for hepatoblastoma was established, which could provide an even more sophisticated profiling of hepatoblastoma.
3.New prognostic factors and multi-drug resistance in hepatoblastoma
C/EBPalpha and beta are important molecules in thedifferentiation and proliferation of fetal hepatocytes. High C/EBPalpha and low C/EBPbeta both predicted a poor prognosis of the patient.
MDR1 expression did not reflect chemoresistance in hepatoblasatoma, and the high expression of MDR1 was rather correlated to a favorable prognosis of the patient.
4.Wnt signaling in hepatocytes
Gne targeting of beta-catenin in mouse hepatocytes showed that by knocking down beta-catenin, canonical pathways become activated and hepatomegaly occurs, although no carcinogenesis was observed.
5.Effect of a novel chemoembolyzation agent on hepatoblastoma
A novel platinum reagent specified for transarterial chemoembolyation (SM-11355) was tested for it efficacy on hepatoblastoma. It did not show prominent antitumor effect in vivo, but the slow-release effect, which is one of the characteristics of this reagent, was confirmed by an intracellular platinum concentration assay. This reagent may have effect on hepatoblastoma in vivo.
Research Products (12results)