A5075613958- Angiogenesis and VEGF in Cancer
- Ion channel regulation and function
- Blood disorders and treatments
- Cell Adhesion Molecules Research
- Platelet Disorders and Treatments
- Kruppel-like factors research
- Cancer, Hypoxia, and Metabolism
- Cardiac electrophysiology and arrhythmias
- Cancer Cells and Metastasis
- Neuroscience and Neuropharmacology Research
- Erythrocyte Function and Pathophysiology
- Galectins and Cancer Biology
- TGF-β signaling in diseases
- Neutropenia and Cancer Infections
- Immune Response and Inflammation
- Cancer-related molecular mechanisms research
- Pregnancy and preeclampsia studies
- Connective tissue disorders research
- Renal and related cancers
- PI3K/AKT/mTOR signaling in cancer
- Pharmacology and Obesity Treatment
- Anesthesia and Sedative Agents
- Click Chemistry and Applications
- Injury Epidemiology and Prevention
- Phagocytosis and Immune Regulation
Tokyo Medical and Dental University
2020-2023
The University of Tokyo
2023
Tohoku University
2006-2016
Institute of Aging
2014
Hiroshima University
1990-2013
Hiroshima University Hospital
2007-2011
Hiroshima General Hospital
2011
Funai Electric (Japan)
2009
Abstract The tumor microenvironment (TME) consists of various components including cancer cells, vessels, cancer‐associated fibroblasts (CAFs), and inflammatory cells. These interact with each other via cytokines, which often induce progression. Thus, a greater understanding TME networks is crucial for the development novel therapies. Many types express high levels TGF‐β, induces endothelial‐to‐mesenchymal transition (EndMT), leading to formation CAFs. Although we previously reported that...
HAX1 was identified as the gene responsible for autosomal recessive type of severe congenital neutropenia. However, connection between mutations in and defective granulopoiesis this disease has remained unclear, mainly due to lack a useful experimental model disease. In study, we generated induced pluripotent stem cell lines from patient presenting neutropenia with deficiency, analyzed their vitro neutrophil differentiation potential by using novel serum- feeder-free directed culture system....
Upon stimulation with angiogenic factors, vascular endothelial cells (ECs) secrete a negative-feedback regulator of angiogenesis, vasohibin-1 (VASH1). Because VASH1 lacks classical signal sequence, it is not clear how ECs VASH1. We isolated small vasohibin-binding protein (SVBP) composed 66 amino acids. The level Svbp mRNA was relatively high in the bone marrow, spleen and testes mice. In cultured ECs, Vash1 induced by VEGF, expressed constitutively. interaction between SVBP confirmed using...
During metastasis, cancer cells undergo epithelial-mesenchymal transition (EMT) in response to transforming growth factor-β (TGF-β), which is abundant the tumor microenvironment, and acquire invasive metastatic potentials. Metastasis distant organs requires intravascular invasion extravasation of cells, accompanied by disruption adhesion between vascular endothelial cells. Cancer cell-derived extracellular vesicles (EVs) have been suggested induce destabilization normal blood vessels at...
Background Malignant hyperthermia ( MH ) is a potentially fatal complication of general anesthesia triggered by volatile anesthetics. In animal studies, sevoflurane has been reported to be weak triggering agent. The aim this study was evaluate the clinical severity sevoflurane‐induced compared isoflurane. Methods From J apanese database containing information for 520 cases since 1961, we analyzed 147 classified C linical G rading S cale CGS as ‘very likely’ or ‘almost certain’, accumulated...
Vasohibin-1 (VASH1) is isolated as an endogenous angiogenesis inhibitor produced by the vascular endothelium. We previously reported that tumor growth and were augmented in VASH1 (−/−) mice. Here we examined whether plays any role cancer metastasis. When Lewis lung carcinoma (LLC) cells inoculated footpad to observe spontaneous metastasis, a significant increase metastasis together with inguinal lymph node was evident Histological analyses revealed vessels of mice more immature, having fewer...
Abstract The tumor microenvironment (TME) consists of cancer cells surrounded by stromal components including vessels. Transforming growth factor‐β (TGF‐β) promotes progression inducing epithelial–mesenchymal transition (EMT) in and stimulating angiogenesis the stroma. We previously developed an Fc chimeric TGF‐β receptor containing both type I (TβRI) II (TβRII) receptors (TβRI‐TβRII‐Fc), which trapped all isoforms suppressed growth. However, precise mechanisms underlying this action have...
Vasohibin-1 (VASH1) and vasohibin-2 (VASH2), the 2 members of vasohibin family, have been identified as novel regulators angiogenesis. VASH1 ceases angiogenesis, whereas VASH2 stimulates sprouting. Here we characterized their functional role in placenta. Immunohistochemical analysis human placental tissue clarified distinctive localization; endothelial cells trophoblasts. We then used a mouse model to explore function. Wild-type, Vash1(−/−), Vash2(−/−) mice on C57BL6 background were first...
Abstract Tumor progression and metastasis are regulated by endothelial cells undergoing endothelial–mesenchymal transition (EndoMT), a cellular differentiation process in which lose their properties differentiate into mesenchymal cells. The EndoMT through spectrum of intermediate phases, suggesting that some remain partial state exhibit an endothelial/mesenchymal phenotype. However, detailed analysis has been hampered the lack specific markers. Transforming growth factor‐β (TGF‐β) plays...
Malignant hyperthermia is a pharmacogenetic skeletal muscle disorder of intracellular calcium (Ca 2+ ) homeostasis with an autosomal dominant inheritance. The objective this study was to investigate the safety propofol by investigating its effects on and effect sites in human muscles. Muscle specimens were obtained from 10 individuals predisposition malignant hyperthermia. In skinned fibre experiments, we measured Ca -induced release uptake into sarcoplasmic reticulum. imaging primary...
Malignant hyperthermia is a life-threatening condition caused by autosomal dominant mutations in the ryanodine receptor type 1 gene. Identifying patients predisposed to malignant done through Ca-induced Ca release test Japan. We examined intracellular calcium concentration human cultured muscle cells and compared sensitivity of myotubes activators based on rate. assessed utility this method as an identifying for predisposition hyperthermia. Muscle specimens were obtained from 34 individuals...
Malignant hyperthermia is a pharmacogenetic disorder caused by autosomal dominant mutations in the ryanodine receptor type 1 gene. Propofol has been reported as safe anaesthetic for malignant susceptible patients but not tested on cultured cells from with mutation. The aim of this study was to determine whether propofol could trigger abnormal calcium fluxes human myotubes isolated harbouring native Muscle specimens were obtained diagnose disposition and calcium-induced release test molecular...
Vascular endothelial growth factor receptor 2 (VEGFR2) is a vital target for therapeutic intervention in cancer. We have recently described computer-based drug design small molecule VEGFR2 inhibitor named VH02 (1-((1-(1H-indazol-6-yl)-1H-1,2,3-triazol-4-yl)methyl)-3-(3-chloromethylphenyl)urea). This study aimed to further explore the anti-angiogenic activity of both vitro and vivo. The assays include cell viability, capillary-like tube formation, MMP activity, western blot analyses signaling...
The Japan Soclety of Mechanlcal Englneers 2Al4