- Cancer Cells and Metastasis
- Digestive system and related health
- Cardiovascular Function and Risk Factors
- Heart Failure Treatment and Management
- Genetic factors in colorectal cancer
- Cardiac pacing and defibrillation studies
- Pediatric Hepatobiliary Diseases and Treatments
- Cardiac Structural Anomalies and Repair
- Cancer Genomics and Diagnostics
- Estrogen and related hormone effects
- Gallbladder and Bile Duct Disorders
- 3D Printing in Biomedical Research
- Pluripotent Stem Cells Research
- Immune Cell Function and Interaction
- Cardiac Arrest and Resuscitation
- Viral Infections and Immunology Research
- Blood Pressure and Hypertension Studies
- Epigenetics and DNA Methylation
- Organ Transplantation Techniques and Outcomes
- Pharmaceutical studies and practices
- Colorectal Cancer Treatments and Studies
- Liver physiology and pathology
- Immunotherapy and Immune Responses
- Mechanical Circulatory Support Devices
- Hemodynamic Monitoring and Therapy
Tokyo Medical and Dental University
2012-2024
Institute of Science Tokyo
2024
Royal Netherlands Academy of Arts and Sciences
2017-2024
University Medical Center Utrecht
2017-2024
The University of Tokyo
2021-2024
Kitasato University
2009-2020
Cancer Genomics Centre
2017-2020
Kitasato Institute Hospital
2016-2020
Oncode Institute
2020
Eindhoven University of Technology
2020
A signature event for organoids Human cancer genomes harbor cryptic mutational signatures that represent the cumulative effects of DNA damage and defects in repair processes. Knowledge how specific originate could have a major impact on diagnosis prevention. One approach to address this question is reproduce experimental systems by genetic engineering then match those found naturally occurring cancers. Drost et al. used CRISPR-Cas9 delete certain enzymes from human colon organoids. In...
Abstract 5-Fluorouracil (5-FU) remains the first-line treatment for colorectal cancer (CRC). Although 5-FU initially de-bulks tumor mass, recurrence after chemotherapy is barrier to effective clinical outcomes CRC patients. Here, we demonstrate that p53 promotes WNT3 transcription, leading activation of WNT/β-catenin pathway in Apc Min/+ /Lgr5 EGFP mice, patient-derived organoids (PDTOs) and cells (PDCs). Through this regulation, induces enrichment stem (CSCs) residual tumors, contributing...
Abstract Background Intraepithelial lymphocytes (IELs) in the intestine play important roles regulation of local immune responses. Although their functions have been studied a variety animal experiments, vitro studies on spatiotemporal behaviors IELs and interaction with intestinal epithelial cells (IECs) hampered due to lack suitable culture system. In this study, we aimed at developing novel co-culture system IECs investigate dynamic between these two populations vitro. Methods We...
To develop stem cell therapy for small intestinal (SI) diseases, it is essential to determine whether SI cells in culture retain their tissue regeneration capabilities. By using a heterotopic transplantation approach, we show that cultured murine epithelial organoids are able reconstitute self-renewing epithelia the colon. When stably integrated, SI-derived grafts many features unique only but distinct from colonic epithelium. Our study provides evidence adult could be source of maintaining...
ATOH1 is a master transcription factor for the secretory lineage differentiation of intestinal epithelial cells (IECs). However, comprehensive contribution ATOH1+ IECs to homeostasis, repair, and tumorigenesis epithelium remains uncertain. Through our cell-lineage tracing, we show here that definite number retain stem cell properties can form ATOH1+IEC-derived clonal ribbons (ATOH1+ICRs) under completely homeostatic conditions. Interestingly, colonic appeared exhibit their function more...
Summary Two genes in the rice genome were identified as those encoding γ subunits, γ1 and γ2, of heterotrimeric G proteins. Using antibodies against recombinant proteins for α, β, γ1, γ2 subunits protein complexes, all proven to be localized plasma membrane rice. Gel filtration solubilized showed that α present large complexes (about 400 kDa) containing other probably also some proteins, whereas amounts β (γ1 γ2) freed from took a 60‐kDa form. A yeast two‐hybrid assay co‐immunoprecipitation...
Estrogen has various effects on adipose tissue. Although the presence of estrogen receptor (ER) been demonstrated in rat tissue and adipocytes, ER not identified human In this study, we existence protein messenger RNA (mRNA) sc adipocytes. The cytosol fraction was partially purified by ammonium sulfate precipitation, analyzed [3H]estradiol (E2) binding assay Western blot analysis. [3H]E2 showed a low specific due to high nonspecific binding, dissociation constant (Kd) maximal sites could be...
Intestinal epithelial cells (IECs) regulate the absorption and secretion of anions, such as HCO3- or Cl-. Bestrophin genes represent a newly identified group calcium-activated Cl- channels (CaCCs). Studies have suggested that, among four human bestrophin-family genes, bestrophin-2 (BEST2) bestrophin-4 (BEST4) might be expressed within intestinal tissue. Consistently, study showed that BEST2 is by colonic goblet cells. However, their precise expression pattern along gastrointestinal tract,...
Intestinal epithelial cells (IECs) play an indispensable role in maintaining body fluid balance partly through their ability to regulate anion/fluid secretion. Yet various inflammatory gastrointestinal diseases, over-secretion of anions results symptoms such as severe diarrhoea. Endogenous mediators, vasoactive intestinal peptide or prostaglandin E2 (PGE2), secretion, but direct effect on purified human IECs has never been described detail. Based a previously organoid swelling model, we...
Double-balloon enteroscopy (DBE) is a novel technique that allows the enteroscope to be inserted deep into small intestine. The procedure has been thought safe, but cases of acute pancreatitis after peroral DBE have recently observed. aim this study was confirm occurrence hyperamylasemia DBE.Peroral carried out in 13 patients from July 2005 February 2006. Blood samples were taken before and 3 h procedure, serum pancreatic amylase levels measured. also evaluated for pancreatic-type abdominal...
Human intestinal organoids (HIOs) derived from human pluripotent stem cells (hPSCs) hold great promise for translational medical applications. A common method to obtain HIOs has been harvest floating hindgut spheroids arising hPSCs. As this technique is elegant but burdensome due the complex protocol and line-to-line variability, a more feasible desired. Here, we establish robust differentiation into suspension-cultured (s-HIOs) by seeding dissociated on spheroid-forming plate. This realizes...
Pleurotus eryngii water extract (PEE), which showed the most significant inhibitory activity against pancreatic lipase in vitro among eight edible mushrooms, was investigated to determine mechanism of its anti-lipase and hypolipidemic effect fat-loaded mice. The effects mushroom extracts on were examined using 4-methylumbelliferyl oleate (4-MUO) or trioleoylglycerol emulsified with lecithin, gum arabic Triton X-100 as a substrate. For vivo experiments, blood samples taken after oral...
The recommended treatment for eosinophilic myocarditis (EM), pathologically defined as myocardial inflammation with eosinophil infiltration, is corticosteroids. Although EM has a wide variety of clinical features including the degree there have been no reports on how patients should be treated corticosteroids irrespective their pathological findings.Thirty-seven consecutive acute hospitalized in our institute between 1996-2009 were enrolled. Excluding those secondary such Loeffler's...
Reports have suggested that the two Notch ligands, Dll1 and Dll4, are indispensable to maintain homeostasis of intestinal epithelium. However, within epithelium, precise distribution cells express those ligands at protein level remains largely unknown. Here, we show a series immunohistochemical analysis through which successfully identified mice epithelial (IECs) endogenously or Dll4. Results showed Dll1-positive (Dll1+ve) IECs reside exclusively crypt, whereas Dll4-positive (Dll4+ve) can...
Background & AimsThe reason why small intestinal cancer is rarer than colorectal not clear. We hypothesized that intraepithelial lymphocytes (IELs), which are enriched in the intestine, closest immune cells to epithelial cells, exclude tumor via cell-to-cell contact.MethodsWe developed DPE-green fluorescent protein (DPE-GFP) × adenomatous polyposis coli; multiple neoplasia (APCmin ) mice, a T-cell–reporter mouse with spontaneous tumors. visualized dynamics of IELs microenvironment and...
Abstract A case of fetal goitrous hypothyroidism associated with high‐output cardiac failure is presented. At 32 weeks gestation, the antenatal diagnosis goiter was made based on ultrasound examination, and thyroid function examined by amniocentesis cordocentesis. Color pulsed Doppler examinations demonstrated a high vascular flow pattern in marked elevation maximum velocity common carotid artery at level neck. It suspected that arteriovenous shunting through large resulted cardiomegaly...
In recent years, primary gastrointestinal follicular lymphoma has been increasingly detected in the duodenum on esophagogastroduodenoscopy (EGD). Primary lymphomas are frequently distributed to multiple sites tract. Therefore, investigation into spread of small bowel is important order determine most appropriate treatment strategy. The performance double-balloon endoscopy (DBE) diagnosis jejunoileal lesions not fully evaluated. We aimed investigate value DBE addition computed tomography (CT)...