A5068897558- Cholangiocarcinoma and Gallbladder Cancer Studies
- Cancer-related molecular mechanisms research
- Cancer Cells and Metastasis
- Cancer-related gene regulation
- Pancreatic and Hepatic Oncology Research
- Ubiquitin and proteasome pathways
- Liver physiology and pathology
- MicroRNA in disease regulation
- Intraperitoneal and Appendiceal Malignancies
- RNA modifications and cancer
- Cancer-related Molecular Pathways
- Cancer Mechanisms and Therapy
- Gastric Cancer Management and Outcomes
- Pluripotent Stem Cells Research
- Organ Transplantation Techniques and Outcomes
- RNA Research and Splicing
- Gallbladder and Bile Duct Disorders
- Ovarian cancer diagnosis and treatment
- Layered Double Hydroxides Synthesis and Applications
- CRISPR and Genetic Engineering
- Helicobacter pylori-related gastroenterology studies
- Pancreatic function and diabetes
- Wnt/β-catenin signaling in development and cancer
Kanazawa University
2019-2021
The University of Tokyo
2015-2018
Tokyo Medical University
2016
Abstract Intrahepatic cholangiocarcinoma (ICC) is an aggressive malignancy with poor prognosis and its incidence increasing worldwide. Recently, several types of cells have been considered as the origin ICC, namely cholangiocytes, liver progenitor cells, hepatocytes. Here, we established a novel mouse model ICC by liver-specific Kras activation Pten deletion. An activating mutation in combination deletion was introduced embryonic hepatic bipotential (so-called hepatoblasts) mature...
Abstract Pseudomyxoma peritonei ( PMP ) is a rare disease exhibiting distinct clinical feature caused by cancerous cells that produce mucinous fluid in the abdominal cavity. s originate most frequently from appendix and less ovary. This can range benign to malignant, histologically, classified into two types: disseminated peritoneal adenomucinosis DPAM representing milder phenotype, adenocarcinomas PMCA aggressive phenotype. Although histological classification clinically useful,...
Significance Wnt activation is critically important during both early development and throughout adulthood for the maintenance regeneration of tissue-resident stem cells. However, underlying mechanism regulating Wnt-dependent epithelial renewal differentiation in stomach remains poorly understood. Here we apply genome-scale CRISPR-Cas9 knockout screening to three-dimensional ex vivo organoids reveal mechanistic insight into mouse gastric epithelia. Our organoid-based strategy can be readily...
Biliary tract cancer (BTC) is one of the most devastating types malignant neoplasms worldwide. However, mechanisms underlying development and progression BTC remain unresolved. includes extrahepatic bile duct carcinoma (EBDC), gallbladder (GBC) ampulla Vater (AVC), named according to location tumor. Although genetic alterations intrahepatic cholangiocarcinoma have been investigated, those EBDC, GBC AVC not yet fully understood. The present study analyzed somatic mutations 50...
Hepatocyte growth factor (HGF) is secreted as an inactive single-chain HGF (scHGF); however, only proteolytically processed two-chain (tcHGF) can activate the MET receptor. We investigated localization of tcHGF and activated/phosphorylated (pMET) using a tcHGF-specific antibody. In day 16.5 mouse embryos, total (scHGF + tcHGF) was mainly localized in smooth muscle cells close to, but separate from, MET-positive epithelial endodermal organs, including stomach. adult stomach, cells, glandular...
Abstract F-box and WD40 domain protein 7 (FBXW7) is a component of the SKP1-CUL1-F-box (SCF) complex that mediates ubiquitination diverse oncogenic target proteins. The exploration FBXW7 mutations in human primary cancer has revealed three mutation hotspots at conserved arginine residues (Arg 465 , Arg 479 505 ) domain, which are critical for substrate recognition. To study function R465C most frequent malignancies, we generated novel conditional knockin mouse line murine Fbxw7 R468C...
Deregulation of the canonical Wnt signaling pathway plays an important role in human tumorigenesis through accumulation β‐catenin and subsequent transactivation TCF 7L2. Although some consequences associated with accumulated have been clarified, comprehensive effect activated β‐catenin/ 7L2 transcriptional complex on remains to be elucidated. To understand precise molecular mechanisms underlying colorectal cancer, we searched for genes regulated by tumors. We performed expression profile...
Abstract Regarding the carcinogenesis of intrahepatic cholangiocarcinoma (ICC), growing interest has been focused on its cellular origin, namely cholangiocytes, progenitor cells, or hepatocytes. We have recently established a novel mouse model ICC by introducing liver-specific Kras activation and Pten deletion using Alb-Cre mice, in which Cre/loxP-mediated gene recombination was achieved hepatoblasts mature To elucidate origin this model, we utilized hepatocyte cholangiocyte-lineage specific...
Abstract Deregulated Wnt signaling is one of the earliest steps in colorectal tumorigenesis. The impairment results most frequently from APC mutations, which leads to accumulation β-catenin and subsequent activation TCF7L2. Although previous studies have identified a number target genes activated β-catenin/TCF7L2 transcriptional complex such as cMYC CCND1, comprehensive effect on tumorigenesis remains be elucidated. To understand precise molecular mechanisms underlying cancer, we searched...
Abstract The mitogen-activated protein kinase (MAPK) pathway and the phosphoinositide 3-kinase (PI3K) are intracellular signaling pathways that involved in carcinogenesis. Various studies suggest these important for development of liver tumors. To investigate effect coactivation MAPK PI3K tumorigenesis, we generated three types mouse models by crossbreeding conditional KrasG12D knockin mice and/or Pten knockout with Alb-Cre (Alb-Cre KrasG12D/+ flox/flox mice, flox/+ mice). Among models,...
Abstract Pseudomyxoma peritonei (PMP) is a rare disease occurring in 1-2 / 1000,000 and shows distinct clinical feature caused by cancerous cells that produce mucin or gelatinous fluid the abdominal cavity. Tumor are most frequently originated from appendiceal mucinous cancer, less tumors of ovary. PMP histologically classified into two types; disseminated peritoneal adenomucinosis (DPAM) showing milder phenotype, adenocarcinomas (PMCA) exhibiting more aggressive phenotype. Several molecular...
ABSTRACT An ability to safely harness the powerful regenerative potential of adult stem cells for clinical applications is critically dependent on a comprehensive understanding underlying mechanisms regulating their activity. Epithelial organoid cultures accurately recapitulate many features in vivo cell-driven epithelial regeneration, providing an excellent ex platform interrogation key regulatory mechanisms. Here, we employed Genome-Scale CRISPR Knock-Out (GeCKO) screening assay using...