A5025465098- Esophageal Cancer Research and Treatment
- Cancer Cells and Metastasis
- Epigenetics and DNA Methylation
- Lung Cancer Treatments and Mutations
- Cancer Genomics and Diagnostics
- Cancer-related Molecular Pathways
- Cancer-related gene regulation
- Cancer, Hypoxia, and Metabolism
- Gastric Cancer Management and Outcomes
- Alcohol Consumption and Health Effects
- Ferroptosis and cancer prognosis
- Head and Neck Cancer Studies
- Helicobacter pylori-related gastroenterology studies
- RNA modifications and cancer
- Esophageal and GI Pathology
- Cancer Research and Treatments
- HER2/EGFR in Cancer Research
- Pancreatitis Pathology and Treatment
- Photodynamic Therapy Research Studies
- Pancreatic and Hepatic Oncology Research
- Fibroblast Growth Factor Research
- Cancer, Lipids, and Metabolism
- Cytokine Signaling Pathways and Interactions
- Developmental Biology and Gene Regulation
- Animal Genetics and Reproduction
Kyoto University
2016-2025
University of Pennsylvania
2008-2023
Kyoto University Hospital
2014-2023
UPMC Hillman Cancer Center
2023
Kitano Hospital
2006-2012
Fox Chase Cancer Center
2010-2011
The Wistar Institute
2010-2011
University Gastroenterology
2009-2010
Tokyo Medical University
1996
Tohoku Medical and Pharmaceutical University
1990
The tumor microenvironment (TME) plays a major role in the pathogenesis of multiple cancer types, including upper-gastrointestinal (GI) cancers that currently lack effective therapeutic options. Cancer-associated fibroblasts (CAF) are an essential component TME, contributing to tumorigenesis by secreting growth factors, modifying extracellular matrix, supporting angiogenesis, and suppressing antitumor immune responses. Through unbiased approach, we have established IL-6 mediates cross-talk...
Some patients develop multiple squamous cell carcinomas (SCCs) in the upper aerodigestive tract, attributed to field cancerization; alcohol consumption has been associated with this process. We examined association between areas of dysplastic epithelium development SCC esophagus or head and neck cancer, as well smoking.We 331 early stage esophageal using Lugol chromoendoscopy evaluate esophagus. Patients then were assigned 3 groups, based on number Lugol-voiding lesions: A, no lesion; B, 1-9...
Squamous cell cancers comprise the most common type of human epithelial cancers. One subtype, esophageal squamous carcinoma (ESCC), is an aggressive cancer with poor prognosis due to late diagnosis and metastasis. Factors derived from extracellular matrix (ECM) create environment conducive tumor growth invasion. Specialized cancer-associated fibroblasts (CAFs) in ECM influence tumorigenesis. We have shown previously that nature activation state are critical modulating invasive ability ESCC...
Although autoimmune pancreatitis (AIP) has been recently recognized as a new disease entity of chronic pancreatitis, the clinical diagnosis remains disputed. Autoantibodies against carbonic anhydrase II and lactoferrin are detected in most patients with AIP, but not about 10%. We undertook this study to determine whether additional autoantibodies present serum level AIP patients.We recruited 26 for study. For comparison, we also 53 various pancreatic diseases 12 healthy subjects....
Transforming growth factor-beta (TGF-beta) is a potent inducer of epithelial to mesenchymal transition (EMT). However, it remains elusive about which molecular mechanisms determine the cellular capacity undergo EMT in response TGF-beta. We have found that both epidermal factor receptor (EGFR) overexpression and mutant p53 tumor suppressor genes contribute enrichment an EMT-competent subpopulation among telomerase-immortalized human esophageal cells during malignant transformation. EGFR...
Hypoxia-inducible factors (HIFs), in particular HIF-1α, have been implicated tumor biology. However, HIF target genes the esophageal microenvironment remain elusive. Gene expression profiling was performed upon hypoxia-exposed non-transformed immortalized human epithelial cells, EPC2-hTERT, and comparing with a gene signature of squamous cell carcinoma (ESCC). In addition to known HIF-1α such as carbonic anhydrase 9, insulin-like growth factor binding protein-3 (IGFBP3) cyclooxygenase...
Zinc finger E-box-binding (ZEB) proteins ZEB1 and ZEB2 are transcription factors essential in TGF-β-mediated senescence, epithelial-to-mesenchymal transition (EMT), cancer stem cell functions. ZEBs negatively regulated by members of the miR-200 microRNA family, but precisely how tumor cells expressing emerge during invasive growth remains unknown. Here, we report that NOTCH3-mediated signaling prevents expansion a unique subset ZEB-expressing cells. ZEB expression was associated with lack...
In esophageal squamous cell carcinoma (ESCC), a subset of cells defined by high expression CD44 and low CD24 has been reported to possess characteristics cancer stem-like (CSCs). Novel therapies directly targeting CSCs have the potential improve prognosis ESCC patients. Although fibroblast growth factor-2 (FGF-2) correlates with recurrence poor survival in patients, role FGF-2 regulation yet be elucidated. We report that is significantly upregulated increases CSC content lines inducing...
Insulin-like growth factor-binding protein (IGFBP)-3 is overexpressed frequently in esophageal squamous cell carcinoma. Yet, the role of IGFBP3 tumor biology remains to be elucidated. We find that facilitates transforming factor (TGF)-β1-mediated epithelial-to-mesenchymal transition (EMT) transformed human epithelial cells, EPC2–hTERT–EGFR–p53 R175H . In organotypic 3D culture, a form tissue engineering, laser-capture microdissection revealed concurrent upregulation TGF-β target genes, and...
There exists a highly tumorigenic subset of esophageal squamous cell carcinoma (ESCC) cells defined by high expression CD44. A novel therapy targeting these cancer stem-like (CSCs) is needed to improve prognosis ESCC. CSCs ESCC have mesenchymal phenotype and epithelial-mesenchymal transition (EMT) critical enrich maintain CSCs. EGFR, frequently overexpressed in ESCC, has pivotal roles EMT induced TGF-β invasive fronts. Thus, fronts might be important for EGFR could target eliminating...
Insulin-like growth factor binding protein (IGFBP)-3 regulates cell proliferation and apoptosis in esophageal squamous carcinoma (ESCC) cells. We have investigated how the hypoxic tumor microenvironment ESCC fosters induction of IGFBP3. RNA interference experiments revealed that hypoxia-inducible (HIF)-1α, but not HIF-2α, IGFBP3 mRNA induction. By chromatin immunoprecipitation transfection assays, HIF-1α was found to transactivate through a novel hypoxia responsive element (HRE) located at...
Acetaldehyde is an ethanol-derived definite carcinogen that causes oesophageal squamous cell carcinoma (ESCC). Aldehyde dehydrogenase 2 (ALDH2) a key enzyme eliminates acetaldehyde, and impairment of ALDH2 increases the risk ESCC. produced in various tissues including liver, heart, kidney, but generation functional roles oesophagus remain elusive. Here, we report ethanol drinking increased production wild-type mice. Notably, levels acetaldehyde-derived DNA damage represented by...
Abstract Background Field cancerization defined by multiple development of squamous cell carcinomas (SCCs) in upper aerodigestive tract was explained excessive alcohol intake. A dysfunctional mitochondrial aldehyde dehydrogenase 2 (Aldh2) delays the clearance acetaldehyde, a genotoxic metabolite, and increases SCC risks. TP53 plays key roles carcinogenesis. However, mechanism alcohol-mediated field has not been clearly elucidated. Methods We developed novel genetically engineered mouse...
Severe acute pancreatitis is a disease with high mortality, and infiltration of inflammatory cells reactive oxygen species have crucial role in the pathophysiology this disease. Thioredoxin-1 (TRX-1) an endogenous redox-active multifunctional protein antioxidant anti-inflammatory effects. TRX-1 induced various conditions shows cytoprotective The aim present study was to clarify protective roles host defense mechanism against severe pancreatitis. Experimental by intraperitoneal administration...