A5033262704- Telecommunications and Broadcasting Technologies
- Phagocytosis and Immune Regulation
- Advanced Wireless Communication Techniques
- Advanced MIMO Systems Optimization
- Veterinary Oncology Research
- Millimeter-Wave Propagation and Modeling
- Lung Cancer Treatments and Mutations
- Cancer, Hypoxia, and Metabolism
- PI3K/AKT/mTOR signaling in cancer
- Mast cells and histamine
- Immunotherapy and Immune Responses
- Liver physiology and pathology
- Error Correcting Code Techniques
- MicroRNA in disease regulation
- Virus-based gene therapy research
- Cancer Cells and Metastasis
- Infectious Diseases and Mycology
- RNA Interference and Gene Delivery
- Cancer therapeutics and mechanisms
- Semiconductor Lasers and Optical Devices
- Fibroblast Growth Factor Research
- Wireless Communication Networks Research
- Inflammatory mediators and NSAID effects
- HER2/EGFR in Cancer Research
- Peptidase Inhibition and Analysis
The University of Tokyo
2015-2025
Veterinary Medical Center
2025
Eisai (Japan)
2011-2022
Japan Broadcasting Corporation (Japan)
2009-2021
Kanazawa University
2012-2016
Miyagi Prefectural Hospital Organization
2014
Aichi Cancer Center
2012-2013
Nagoya University
2013
Jichi Medical University
2012
Tokushima University
2012
BIM (BCL2L11) is a BH3-only proapoptotic member of the Bcl-2 protein family. upregulation required for apoptosis induction by EGF receptor (EGFR) tyrosine kinase inhibitors (EGFR-TKI) in EGFR-mutant forms non-small cell lung cancer (NSCLC). Notably, deletion polymorphism occurs naturally 12.9% East Asian individuals, impairing generation isoform EGFR-TKIs gefitinib and erlotinib therefore conferring an inherent drug-resistant phenotype. Indeed, patients with NSCLC, who harbored this host...
Cancer cell microenvironments, including host cells, can critically affect cancer behaviors, drug sensitivity. Although crizotinib, a dual tyrosine kinase inhibitor (TKI) of ALK and Met, shows dramatic effect against EML4-ALK lung these cells acquire resistance to crizotinib by several mechanisms, amplification gatekeeper mutation. We determined whether microenvironmental factors trigger in cells.We tested the effects ligands produced endothelial fibroblasts, themselves, on susceptibility...
c-Met is the cellular receptor for hepatocyte growth factor (HGF) and known to be dysregulated in various types of human cancers. Activation HGF/c-Met pathway causes tumor progression, invasion, metastasis. Vascular endothelial (VEGF) also as a key molecule progression through induction angiogenesis. Because their roles these pathways provide attractive targets therapeutic intervention. We have generated novel, orally active, small compound, E7050, which inhibits both vascular (VEGFR)-2. In...
We investigated the role of prostaglandin D 2 (PGD ) signaling in acute lung injury (ALI), focusing on its producer–effector interaction vivo. Administration endotoxin increased edema and neutrophil infiltration WT mouse lung. Gene disruption hematopoietic PGD synthase (H-PGDS) aggravated all symptoms. Experiments involving bone marrow transplantation between H-PGDS–deficient mice showed that derived from alveolar nonhematopoietic lineage cells (i.e., endothelial epithelial cells) promotes...
Abstract Purpose: Hepatocyte growth factor (HGF) induces resistance to reversible and irreversible epidermal receptor–tyrosine kinase inhibitors (EGFR-TKI) in EGFR mutant lung cancer cells by activating Met the downstream phosphoinositide 3-kinase (PI3K)/Akt pathway. Moreover, continuous exposure HGF accelerates emergence of EGFR-TKI–resistant clones. We assayed whether a new inhibitor, E7050, which is currently being evaluated clinical trials, could overcome these three mechanisms...
Although the EGF receptor tyrosine kinase inhibitors (EGFR-TKI) erlotinib and gefitinib have shown dramatic effects against EGFR mutant lung cancer, patients become resistant by various mechanisms, including gatekeeper EGFR-T790M mutation, Met amplification, HGF overexpression, thereafter relapsing. Thus, it is urgent to develop novel agents overcome EGFR-TKI resistance. We tested of mutant-selective WZ4002 Met-TKI E7050 on 3 cancer cell lines different mechanisms: PC-9/HGF cells with an...
Background Targeting regulatory T cell (Treg) infiltration is an emerging strategy for cancer immunotherapy. However, its efficacy in advanced prostate remains unclear. Here, we showed the therapeutic of anti-Treg treatment a canine model cancer. Methods We used dogs with naturally occurring to study molecular mechanism underlying Treg and effect treatment. Tumor-infiltrating Tregs was evaluated by immunohistochemistry, association prognosis examined spontaneous The explored RNA sequencing...
It is well established that prostaglandins (PGs) are involved in tumor angiogenesis and growth, yet the role of prostaglandin D 2 (PGD ) remains virtually unknown. Here, we show host hematopoietic PGD synthase (H-PGDS) deficiency enhances Lewis lung carcinoma (LLC) progression, accompanied by increased vascular leakage, angiogenesis, monocyte/mast cell infiltration. This can be rescued reconstitution with bone marrow from H-PGDS–naive (WT) mice. In tumors on WT mice, c-kit + mast cells...
Circulating microRNAs in the blood may provide diagnostic and prognostic information about canine neoplastic diseases, their profiles be conserved between human species. We performed RT-qPCR to obtain of circulating plasma microRNA-214 -126 total 181 cases diseases healthy controls. MicroRNA-214 levels were high 2 epithelial tumours (thyroid mammary carcinomas) 4 non-epithelial (osteosarcoma, histiocytic sarcoma, chondrosarcoma, hemangiosarcoma). In contrast, microRNA-126 6 (mammary,...
Mast cell tumour (MCT) is a life-threatening neoplasm commonly found in dogs worldwide. The outcome of treatment for with cutaneous MCT currently poor, mainly because the tumour's aggressiveness and heterogeneity behaviour. This study established novel canine line compared three reference lines (CMMC, VIMC CoMS) terms their characteristics sensitivity to immune cell-mediated cytotoxicity. Of 18 samples, only one derived from high grade was referred as C18 line. could be maintained over 100...
Human epidermal growth factor receptor 2 (HER2) is a known therapeutic target in canine osteosarcoma (OSA); however, the efficacy of anti-HER2 antibody drugs remains unclear. This study aimed to investigate effects including trastuzumab and emtansine (T-DM1) on OSA cell lines vitro vivo. Four (HMPOS, POS, OOS, HOS) were used. Western blotting revealed HER2 protein expression all lines. Although water-soluble tetrazolium salt assays showed inhibitory activity T-DM1 against vitro, was...
Abstract Four new pairs of canine mammary carcinoma cell lines derived from both primary and metastatic lesions were established. The cells cultured in RPMI‐1640 with 10% fetal bovine serum they showed stable growth for more than 120 passages. Using these lines, the expression E‐cadherin was measured by flow cytometry function evaluated aggregation assay results compared statistically. strongly expressed all without a notable difference between origin. In assay, significantly weaker origin (...
Cholangiocarcinoma is an aggressive malignant tumor originating from intrahepatic or extrahepatic bile ducts. Its phenotypes may be assumed by cancer stem cells ( CSC ). Here, we demonstrate that CD 274 PD ‐L1), known as immunomodulatory ligand, has suppressive effects on ‐related of cholangiocarcinoma. Using two human cholangiocarcinoma cell lines, RBE and Hu CCT 1, attempted to isolate the low high each line, xenografted them into immunodeficient NOD ⁄scid⁄γcnull NOG ) mice. We found...
PurposeAlthough EGF receptor tyrosine kinase inhibitors (EGFR-TKI) have shown dramatic effects against EGFR mutant lung cancer, patients ultimately develop resistance by multiple mechanisms. We therefore assessed the ability of combined treatment with Met inhibitor crizotinib and new generation EGFR-TKIs to overcome first-generation EGFR-TKIs. Experimental DesignLung cancer cell lines made resistant gatekeeper EGFR-T790M mutation, amplification, HGF overexpression mice tumors induced these...
Met activation by gene amplification and its ligand, hepatocyte growth factor (HGF), imparts resistance to epidermal receptor (EGFR) tyrosine kinase inhibitors (TKIs) in EGFR-mutant lung cancer. We recently reported that HGF stimulates the production of vascular endothelial (VEGF) facilitates angiogenesis, which indicates induces EGFR-TKI angiogenesis. This study aimed determine effect triple inhibition EGFR, Met, angiogenesis on HGF-triggered cancer.Three clinically approved drugs,...
Almost all cancers show intrinsic and/or evasive resistance to vascular endothelial growth factor ( VEGF ) inhibitors by multiple mechanisms. Serum angiopoietin‐2 (Ang2) level has been proposed as a potential biomarker of inhibitor response in several cancers. From these clinical observations, the Ang2 and Tie2 (its receptor) axis focused on promising target. Here, we novel strategy circumvent combining multi‐tyrosine kinase lenvatinib receptor, fibroblast RET inhibitor) golvatinib (E7050;...
Vascular endothelial growth factor receptor (VEGFR) inhibitors are approved for the treatment of several tumor types; however, some tumors show intrinsic resistance to VEGFR inhibitors, and patients develop acquired these inhibitors. Therefore, a strategy overcome inhibitor is urgently required. Recent reports suggest that activation hepatocyte (HGF) pathway through its cognate receptor, Met, contributes resistance. Here, we explored effect HGF/Met signaling on lenvatinib, inhibitor. In in...
The FGFR signaling pathway has a crucial role in proliferation, survival, and migration of cancer cells, tumor angiogenesis, drug resistance. genetic abnormalities, such as gene fusion, mutation, amplification, have been implicated several types cancer. Therefore, FGFRs are considered potential targets for therapy. E7090 is an orally available selective inhibitor the tyrosine kinase activities FGFR1, -2, -3. In kinetic analyses interaction between FGFR1 kinase, associated more rapidly with...
Mitochondrial electron transport chain complex I (ETCC1) is the essential core of cancer metabolism, yet potent ETCC1 inhibitors capable safely suppressing tumor growth and metastasis in vivo are limited. From a plant extract screening, we identified petasin (PT) as highly inhibitor with chemical structure distinct from conventional inhibitors. PT had at least 1700 times higher activity than that metformin or phenformin induced cytotoxicity against broad spectrum types. administration also...
Resistance to epidermal growth factor receptor tyrosine kinase inhibitors (EGFR-TKIs), gefitinib and erlotinib, is a critical problem in the treatment of EGFR mutant lung cancer. Several mechanisms, including bypass signaling by hepatocyte (HGF)-triggered Met activation, are implicated as mediators resistance. The mammalian target rapamycin (mTOR), downstream conduit MET signaling, thus considered therapeutically attractive various types cancers. purpose this study was examine whether 2...
Crizotinib, a first‐generation anaplastic lymphoma kinase ( ALK ) tyrosine‐kinase inhibitor, is known to be effective against echinoderm microtubule‐associated protein‐like 4 EML )‐ ‐positive non‐small cell lung cancers. Nonetheless, the tumors subsequently become resistant crizotinib and recur in almost every case. The mechanism of acquired resistance needs deciphered. In this study, we established crizotinib‐resistant cells (A925 LPE 3‐ CR via long‐term administration mouse model pleural...