A5017829721- Crystallization and Solubility Studies
- X-ray Diffraction in Crystallography
- Crystallography and molecular interactions
- Vector-borne infectious diseases
- Asymmetric Synthesis and Catalysis
- Immune Cell Function and Interaction
- Oxidative Organic Chemistry Reactions
- T-cell and Retrovirus Studies
- Herpesvirus Infections and Treatments
- Vector-Borne Animal Diseases
- Immunotherapy and Immune Responses
- Viral Infections and Vectors
- Organic Chemistry Cycloaddition Reactions
- Synthetic Organic Chemistry Methods
- T-cell and B-cell Immunology
- Cytomegalovirus and herpesvirus research
- Animal Disease Management and Epidemiology
- Synthesis and Reactions of Organic Compounds
- Bird parasitology and diseases
- Cancer Immunotherapy and Biomarkers
- Synthesis and Catalytic Reactions
- Veterinary Oncology Research
- Axial and Atropisomeric Chirality Synthesis
- Porphyrin and Phthalocyanine Chemistry
- Animal Virus Infections Studies
Hokkaido University
2016-2025
Advanced Pharma
2019-2025
Murata (United States)
2018
Nara Institute of Science and Technology
2008
Hoshi University
1995-2008
Ebara (Japan)
2008
Tokyo Institute of Technology
2008
Obihiro University of Agriculture and Veterinary Medicine
2008
Seikagaku Corporation (Japan)
1999-2006
Rigaku (Japan)
1999-2006
Abstract Immunotherapy targeting immune checkpoint molecules, programmed cell death 1 (PD-1) and PD-ligand (PD-L1), using therapeutic antibodies has been widely used for some human malignancies in the last 5 years. A costimulatory receptor, PD-1, is expressed on T cells suppresses effector functions when it binds to its ligand, PD-L1. Aberrant PD-L1 expression reported various cancers considered an escape mechanism. Antibodies blocking PD-1/PD-L1 axis induce antitumour responses patients...
Spontaneous cancers are common diseases in dogs. Among these, some malignant such as oral melanoma, osteosarcoma, hemangiosarcoma, and mast cell tumor often recognized clinical problems because, despite their high frequencies, current treatments for these may not always achieve satisfying outcomes. The absence of effective systemic therapies against leads researchers to investigate novel therapeutic modalities, including immunotherapy. Programmed death 1 (PD-1) is a costimulatory receptor...
Programmed death 1 (PD-1), an immunoinhibitory receptor, and programmed ligand (PD-L1), its ligand, together induce the "exhausted" status in antigen-specific lymphocytes are thus involved immune evasion of tumor cells. In this study, canine PD-1 PD-L1 were molecularly characterized, their potential as therapeutic targets for tumors was discussed. The genes conserved among breeds. Based on sequence information obtained, recombinant proteins constructed; they confirmed to bind each other....
Abstract Immunotherapy targeting programmed cell death 1 (PD-1) and PD-ligand (PD-L1) represents promising treatments for human cancers. Our previous studies demonstrated PD-L1 overexpression in some canine cancers, suggested the therapeutic potential of a chimeric anti-PD-L1 monoclonal antibody (c4G12). However, such evidence is scarce, limiting clinical application dogs. In present report, expression was assessed various cancer types, using new mAb, 6C11-3A11, safety efficacy c4G12 were...
Abstract The inhibitory receptor programmed death-1 (PD-1) and its ligand, death-ligand 1 (PD-L1) are involved in immune evasion mechanisms for several pathogens causing chronic infections. Blockade of the PD-1/PD-L1 pathway restores anti-virus responses, with concomitant reduction viral load. In a previous report, we showed that, bovine leukemia virus (BLV) infection, expression PD-1 is closely associated disease progression. However, functions PD-L1 still unknown. To investigate role BLV...
Bovine leukemia virus (BLV), a retrovirus that is widespread worldwide, causes enzootic bovine leukosis (EBL), B-cell leukemia/lymphoma with poor prognosis ultimately results in death. In Japan, the number of cattle infected this increasing, and it estimated more than 35% are currently infected. Since no vaccines or treatments against BLV infection available, important to establish method early diagnosis for EBL reduce economic losses caused by disposal where large expensive beef raised. We...
Abstract Programmed death-1 (PD-1) is a known immunoinhibitory receptor that contributes to immune evasion of various tumor cells and pathogens causing chronic infection, such as bovine leukemia virus (BLV) infection. First, in this study, establish method for the expression functional analysis PD-1, hybridomas producing monoclonal antibodies (mAb) specific PD-1 were established. Treatment with these anti-PD-1 mAb enhanced interferon-gamma (IFN-γ) production peripheral blood mononuclear...
Programmed death-ligand 1 (PD-L1) blockade is accepted as a novel strategy for the reactivation of exhausted T cells that express programmed death-1 (PD-1). However, mechanism PD-L1-mediated inhibitory signalling after PD-L1 cross-linking by anti-PD-L1 monoclonal antibody (mAb) or PD-1-immunogloblin fusion protein (PD-1-Ig) still unknown, although it may induce cell death PD-L1(+) required regular immune reactions. In this study, PD-1-Ig mAb treatment was tested in lines expressed and bovine...
ABSTRACT The CD4 + T-cell response is central for the control of Anaplasma marginale infection in cattle. However, induces a functional exhaustion antigen-specific T cells cattle immunized with A. outer membrane proteins or purified membranes (OMs), which presumably facilitates persistence this rickettsia. In present study, we hypothesize that following induced by upregulation immunoinhibitory receptors on cells, such as programmed death 1 (PD-1) and lymphocyte activation gene 3 (LAG-3)....
Bovine leukemia virus (BLV) infection is a chronic viral of cattle and endemic in many countries, including Japan. Our previous study demonstrated that PGE2, product cyclooxygenase (COX) 2, suppresses Th1 responses contributes to the progression Johne disease, bacterial cattle. However, little information available on association PGE2 with infection. Thus, we analyzed changes plasma concentration during BLV its effects proviral load, gene transcription, responses, disease progression. Both...
Although immune checkpoint inhibitors (ICIs), such as the anti-programmed death-ligand 1 (PD-L1) antibody, have been developed for treatment of canine malignant melanoma, desirable clinical efficacies not achieved. Recent studies in humans suggested that radiation therapy (RT) combined with ICIs induces robust systemic antitumour immunity patients cancer. This study retrospectively examined therapeutic efficacy combination (hypofractionated RT and anti-PD-L1 antibody [c4G12]) dogs pulmonary...
α, α-Trehalose (trehalose) is a nonreducing disaccharide of glucose and accumulated at high concentrations in some anhydrobiotic organisms, which can survive without water for long periods rapidly resume active metabolism upon hydration. Although it has been proposed that the intriguing mechanism bioprotection anhydrobiosis conferred by channel, details such channel have yet to be revealed. We determined crystal structure trehalose anhydrate further understand relationship between channels...
Abstract Introduction Bovine mycoplasma, chiefly Mycoplasma bovis , is a pathogen that causes pneumonia, mastitis, arthritis, and otitis media in cattle. This exerts immunosuppressive effects, such as the inhibition of interferon production. However, mechanisms involved bovine mycoplasmosis have not been fully elucidated. In this study, we investigated role programmed death‐1 (PD‐1)/programmed death‐ligand 1 (PD‐L1) pathway immunosuppression mycoplasmosis. Methods initial experiments, used...
ABSTRACT Johne's disease (paratuberculosis) is a chronic enteritis in cattle that caused by intracellular infection with Mycobacterium avium subsp. paratuberculosis . This characterized the functional exhaustion of T-cell responses to M. antigens during late subclinical and clinical stages, presumably facilitating persistence this bacterium formation lesions. However, mechanisms underlying are poorly understood. Thus, we performed expression analyses immunoinhibitory molecules programmed...
CD4(+)CD25(high)Foxp3(+) T cells suppress excess immune responses that lead to autoimmune and/or inflammatory diseases, and maintain host homeostasis. However, reportedly contribute disease progression by over suppressing in some chronic infections. In this study, kinetic functional analyses of were performed cattle with bovine leukemia virus (BLV) infections, which have reported immunosuppressive characteristics. initial experiments, production the Th1 cytokines IFN-γ TNF-α was reduced...
Programmed death-1 (PD-1), an immunoinhibitory receptor on T cells, is known to be involved in immune evasion through its binding PD-ligand 1 (PD-L1) many chronic diseases. We previously found that PD-L1 expression was upregulated cattle infected with bovine leukemia virus (BLV) and antibody blocked the PD-1/PD-L1 interaction reactivated T-cell function vitro. Therefore, this study assessed antivirus activities vivo. First, we inoculated anti-bovine rat monoclonal 4G12 into a BLV-infected...
Modified-live herpesvirus vaccines are widely used in humans and animals, but field strains can emerge that have a higher virulence break vaccinal protection. Since the introduction of first vaccine 1970s, Marek’s disease virus overcame barrier by acquisition numerous genomic mutations. However, evolutionary adaptations genome responsible for breaks remained elusive. Here, we demonstrate point mutations multifunctional meq gene acquired during evolution significantly alter virulence. Defined...