A5001700425- Wnt/β-catenin signaling in development and cancer
- Cancer-related gene regulation
- Liver physiology and pathology
- Mitochondrial Function and Pathology
- Epigenetics and DNA Methylation
- CRISPR and Genetic Engineering
- Cancer-related Molecular Pathways
- Cancer, Hypoxia, and Metabolism
- Cancer Research and Treatments
- Pharmacogenetics and Drug Metabolism
- Drug Transport and Resistance Mechanisms
- Glycogen Storage Diseases and Myoclonus
- Fibroblast Growth Factor Research
- Genetic factors in colorectal cancer
- Cholesterol and Lipid Metabolism
- Cell death mechanisms and regulation
- Pluripotent Stem Cells Research
- Genetics and Neurodevelopmental Disorders
- Microtubule and mitosis dynamics
- Virus-based gene therapy research
- Peroxisome Proliferator-Activated Receptors
- Genomics and Chromatin Dynamics
- Advanced Drug Delivery Systems
- vaccines and immunoinformatics approaches
- 3D Printing in Biomedical Research
Taiho Pharmaceutical (Japan)
2014-2023
Nagoya City University
2014
Food Research Institute
1995-2007
Merck (Japan)
1999-2006
G protein-coupled bile acid receptor 1 (Gpbar1/M-Bar) is a novel for acid. Tissue distribution and cell-type specificity of Gpbar1 mRNA suggest potential role the in endocrine system; however, precise physiological still remains to be elucidated. To investigate vivo, gene was disrupted mice. In homozygous mice, total pool size significantly decreased by 21-25% compared with that wild-type suggesting contributes homeostasis. order assess impact deficiency homeostasis more precisely, mice were...
Abstract We have established previously a mouse strain containing mutant β-catenin allele of which exon 3 was sandwiched by loxP sequences [Catnblox(ex3)]. In this strain, Wnt-activating mutation alone is insufficient for hepatocarcinogenesis, but additional mutations or epigenetic changes may be required. Here we report that hepatocellular carcinoma develops at the 100% incidence in mice with simultaneous and H-ras genes are introduced adenovirus-mediated Cre expression. Although rapidly...
An activated form of beta-catenin [Catnb(Delta(ex3))] was expressed in respiratory epithelial cells the developing lung. Although morphogenesis not altered at birth, air space enlargement and cell dysplasia were observed early postnatal period persisted into adulthood. The Catnb(Delta(ex3)) protein caused squamous, cuboidal, goblet intrapulmonary conducting airways. Atypical that stained for surfactant pro C (pro-SP-C) had morphological characteristics alveolar type II bronchioles transgenic...
Acetyl coenzyme A (acetyl-CoA) carboxylase (ACC) catalyzes carboxylation of acetyl-CoA to form malonyl-CoA. In mammals, two isozymes exist with distinct physiological roles: cytosolic ACC1 participates in de novo lipogenesis (DNL), and mitochondrial ACC2 is involved negative regulation beta-oxidation. Since systemic null mice were embryonic lethal, clarify the role hepatic DNL, we generated liver-specific mouse by crossbreeding an Acc1(lox(ex46)) mouse, which exon 46 Acc1 was flanked loxP...
Adult intestinal stem cells (ISCs) possess both a long-term proliferation ability and differentiation capability into enterocytes. As novel in vitro system for the evaluation of drug absorption, we characterized human small epithelial cell (HIEC) monolayer that differentiated from adult ISCs. Continuous proliferation/differentiation ISCs consistently conferred maturation enterocytes to HIECs over 25 passages. The morphologically matured HIEC consisted polarized columnar epithelia with dense...
Hepatocytes of the periportal and perivenous zones liver lobule show marked differences in contents activities many enzymes other proteins. Previous studies from our groups have pointed towards an important role β‐catenin‐dependent signaling regulation expression genes encoding proteins with preferential localization, whereas, contrast, through Ras‐dependent pathway(s) may induce a ‘periportal’ phenotype. We now conducted series experiments to further investigate this hypothesis. In...
Approximately 25–40% of patients with lung cancer show bone metastasis. Bone modifying agents reduce skeletal-related events (SREs), but they do not significantly improve overall survival. Therefore, novel therapeutic approaches are urgently required. In this study, we investigated the anti-tumor effect TAS-115, a VEGFRs and HGF receptor (MET)-targeted kinase inhibitor, in tumor-induced disease model. A549-Luc-BM1 cells, an osteo-tropic clone luciferase-transfected A549 human adenocarcinoma...
Abstract We generated a series of monochain HLA class I knock-in (KI) mouse strains, in which chimeric molecule (α1/α2 domain HLA-A*0201, HLA-A*0301, HLA-A*2402, or HLA-A*3101 and α3 H-2Db) was covalently linked with 15 aa to human β2-microglobulin (β2m) introduced into the endogenous β2m locus. In homozygous KI mice, gene disruption resulted loss H-2 molecules reduction peripheral CD8+ T cell population that partially restored by expression. A dosage-dependent expression HLA, similar PBMCs,...
Plasma thymidine levels in rodents are higher than other mammals including humans, possibly due to a different pattern and lower level of phosphorylase expression. Here, we generated novel knock-in (KI) mouse line with high systemic expression human investigate this difference nucleotide metabolism rodents. The KI mice showed growth retardation around weaning died by 4 weeks age decrease plasma compared the litter-control WT mice. These phenotypes were completely or partially rescued...
To generate a mouse glioblastoma model by genome editing, we introduced Cas9 protein and guide RNAs specific for Nf1, Pten, Trp53 into the neonatal forebrain electroporation. We found high incidence (approximately 90%) of glial tumor development, including glioblastomas, 15 weeks later. The histological features tumors were similar to those diffuse gliomas and, in some cases, human with microvascular proliferation (glomeruloid structure). In addition, unlike fibrillary acidic (GFAP)-positive...
Abstract Background: Invasive bladder cancer frequently shows bone and systemic metastasis. Thus, development of a drug that is effective not only against the primary lesion but also metastatic lesions needed for therapy cancer. The expression level hepatocyte growth factor (HGF) high in invasive patients associated with poor outcomes. Moreover, several recent clinical reports show HGF receptor (MET) was related to grade, stage, tumor size, prognosis patients. Because HGF-MET signaling has...
Abstract <Background> Hepatocyte growth factor (HGF) / HGF receptor (MET) signaling is considered to be involved in chemoresistance cancer treatment. Notably, many reports have described reduced sensitivity vascular endothelial (VEGFR)-targeted inhibitors patients with high serum levels compared those low levels. This study investigated whether directly influenced VEGFR-targeted human clear cell sarcoma (CCS) xenograft models using knock-in (hHGF KI) mice, and evaluated the...