β-Catenin up-regulates Nanog expression through interaction with Oct-3/4 in embryonic stem cells

金沢大学大学院医学系研究科機能再生学It is well known that mouse embryonic stem (ES) cells can be maintained by the presence of leukemia inhibitory factor (LIF). Recent studies have revealed that Wnt also exhibits activity similar to LIF. The molecular mechanism behind the maintenance of ES cells by these factors, however, is not fully understood. In this study, we found that LIF enhances level of nuclear β-catenin, a component of the Wnt signaling pathway. Expression of an activated mutant of β-catenin led to the long-term proliferation of ES cells, even in the absence of LIF. Furthermore, it was found that β-catenin up-regulates Nanog in an Oct-3/4-dependent manner and that β-catenin physically associates with Oct-3/4. These results suggest that up-regulating Nanog through interaction with Oct-3/4 involves β-catenin in the LIF- and Wnt-mediated maintenance of ES cell self-renewal. © 2006 Elsevier Inc. All rights reserved

A stem cell-derived gene (Sddr) negatively regulates differentiation of embryonic stem cells

金沢大学医薬保健研究域医学系Embryonic stem (ES) cells, derived from the inner cell mass of blastocysts, are pluripotent and continue to self-renew. To better understand the molecular mechanisms under-lying self-renewal, we have been searching for a gene(s) which is specifically expressed in self-renewing ES cells. Here we report the isolation and characterization of a novel gene, Sddr (stem cell-derived differentiation regulator). Sddr was highly expressed in undifferentiated ES cells, and its expression was downregulated upon differentiation. In addition to ES cells, Sddr expression was observed strongly in ovary, and weakly in lung. Immunostaining and cellular fractionation analyses suggested that Sddr is a cytoplasmic protein associated with the cytoskeleton. Sddr-null ES cells showed no remarkable abnormalities in their undifferentiated state. In contrast, in differentiating Sddr-null cells, induction of several differentiation-associated markers was enhanced, and downregulation of self-renewal marker genes was accelerated, as compared with wild-type cells. These results suggest that although it is dispensable for ES cell self-renewal, Sddr is a negative regulator of ES cell differentiation. © 2009 UBC Press

β-Catenin up-regulates Nanog expression through interaction with Oct-3/4 in embryonic stem cells

取得学位 : 博士（医学）, 学位授与番号 : 医博甲第1843号, 学位授与年月日 : 平成19年3月22日, 学位授与大学 : 金沢大学, 主査教授 : 平尾 敦, 副査教授 : 金子 周一, 西村 栄

Risk Factors for Oxaliplatin-Induced Hypersensitivity Reactions in Japanese Patients with Advanced Colorectal Cancer

Objective: Previously, we suggested that oxaliplatin (L-OHP)-related grade 3/4 hypersensitivity reactions occurred immediately after the initiation, but grade 1/2 reactions did not. This study was conducted to clarify the risk factors for L-OHP-related hypersensitivity reactions.Methods: Clinical data from 108 Japanese patients with colorectal cancer were analyzed, who were treated with L-OHP-containing regimens, FOLFOX4 and/or mFOLFOX6. The risk factors examined included demographic data, preexisting allergies, laboratory test data, treatment regimen, treatment line of therapy, pretreatment with steroids, total number of cycles and cumulative amount of L-OHP.Results: The incidence of grade 1/2 and grade 3/4 hypersensitivity reactions were found at 13.0% (14/108) and 9.3% (10/108), respectively. Female (P=0.037), preexisting allergies (P=0.004) and lower level of lactate dehydrogenase (P=0.003) were risk factors for grade 1/2 hypersensitivity reactions, and higher neutrophil count (P=0.043) and lower monocyte count (P=0.007) were for grade 3/4 reactions. Total number of cycles were larger in the patients with grade 3/4 reactions than those without reactions (P=0.049).Conclusions: Further extensive examination with a large number of patients is needed to establish a patient management strategy.</p