A5005874605- Alzheimer's disease research and treatments
- RNA Research and Splicing
- Immune Cell Function and Interaction
- Dementia and Cognitive Impairment Research
- T-cell and B-cell Immunology
- Cancer Immunotherapy and Biomarkers
- Neuroinflammation and Neurodegeneration Mechanisms
- Cancer Genomics and Diagnostics
- Immunotherapy and Immune Responses
- PI3K/AKT/mTOR signaling in cancer
- Monoclonal and Polyclonal Antibodies Research
- Parkinson's Disease Mechanisms and Treatments
- Diabetes and associated disorders
- Cerebrospinal fluid and hydrocephalus
- Genetic factors in colorectal cancer
- Immune cells in cancer
- Acute Myeloid Leukemia Research
- Health, Environment, Cognitive Aging
- Chronic Myeloid Leukemia Treatments
- Inflammation biomarkers and pathways
- Advanced Glycation End Products research
- Intensive Care Unit Cognitive Disorders
- Neurosurgical Procedures and Complications
- Traumatic Brain Injury and Neurovascular Disturbances
- Amyloidosis: Diagnosis, Treatment, Outcomes
Astellas Pharma (Japan)
2019-2025
National Institute of Technology, Niihama College
2020-2023
Ehime University
2013-2023
Astellas Pharma (China)
2022
Astellas Pharma (United Kingdom)
2019
Eisai (Japan)
2009-2017
Toshiba (Japan)
2017
Brigham and Women's Hospital
2013-2015
Dana-Farber Cancer Institute
2013-2015
Harvard University
2013-2015
Mice deficient in programmed cell death 1 (PD-1, Pdcd1 ), an immunoinhibitory receptor belonging to the CD28/cytotoxic T lymphocyte-associated antigen-4 family, spontaneously develop lupus-like autoimmune disease and dilated cardiomyopathy on C57BL/6 BALB/c backgrounds, respectively. However, how PD-1 deficiency induces different forms of diseases these two strains was unknown. Here, we report that specifically accelerates onset frequency type I diabetes NOD (nonobese diabetic) mice, with...
Stimulatory and inhibitory co-receptors play fundamental roles in the regulation of immune system. We describe a new mouse model spontaneous autoimmune disease. Activation-induced cytidine deaminase–linked autoimmunity (aida) mice harbor loss-of-function mutation gene encoding lymphocyte activation 3 (LAG-3), an co-receptor. Although LAG-3 deficiency alone did not induce nonautoimmune-prone strains, it induced lethal myocarditis BALB/c deficient for co-receptor programmed cell death 1...
The deficiency of programmed cell death 1 (PD-1, Pdcd1), a negative immuno-receptor belonging to the CD28/cytotoxic T lymphocyte antigen 4 (CTLA-4) family, can support various tissue-specific autoimmune conditions. Here, we analyzed effect PD-1 in MRL mice that is genetically predisposed systemic autoimmunity. MRL-Pdcd1−/− developed fatal myocarditis, which reminiscent CTLA-4-deficient (Ctla4−/−) mice. Massive infiltration CD4+ and CD8+ cells myeloid was found hearts concomitant with...
Transplantation of bone marrow cells from nonobese diabetic (NOD) mice, a model for type 1 diabetes mellitus, to C3H/HeN which express I-E alpha molecules and have aspartic acid at residue 57 the I-A beta chain, induced insulitis followed by overt in recipient mice more than 40 weeks after transplantation. When cyclosporin A, perturbs T-cell functions, was injected intraperitoneally into [NOD----C3H/HeN] chimeric daily month, developed within 20 following (NZW x BXSB)F1 develop lupus...
Triple-negative breast cancer (TNBC) is currently the only major tumor subtype without effective targeted therapy and, as a consequence, in general has poor outcome. To identify new therapeutic targets TNBC, we performed short hairpin RNA (shRNA) screen for protein kinases commonly amplified and overexpressed cancer. Using this approach, identified AKT3 gene preferentially required growth of TNBCs. Downregulation Akt3 significantly inhibits TNBC lines three-dimensional (3D) spheroid cultures...
Behavioral and psychological symptoms of dementia (BPSDs) negatively impact the prognosis patients increase caregiver distress. The aims this study were to clarify differences trajectories 12 kinds BPSDs by disease severity in four major dementias develop charts showing frequency, severity, associated distress (ACD) using data a Japan multicenter (J-BIRD).We gathered Neuropsychiatric Inventory (NPI) with Alzheimer's (AD; n = 1091), Lewy bodies (DLB; 249), vascular (VaD; 156), frontotemporal...
Abstract Genetically activated kinases have been attractive therapeutic targets in cancer due to the relative ease of developing tumor-specific treatment strategies for them. To discover novel putative oncogenic kinases, we identified 26 genes commonly amplified and overexpressed breast subjected them a lentiviral shRNA cell viability screen panel lines. Here, report that CLK2, kinase phosphorylates SR proteins involved splicing, acts as an oncogene cancer. Deregulated alternative splicing...
// Tatsuya Kawase 1 , Taisuke Nakazawa Tomohiro Eguchi Hirofumi Tsuzuki Yoko Ueno Yasushi Amano Tomoyuki Suzuki Masamichi Mori and Taku Yoshida Drug Discovery Research, Astellas Pharma, Tsukuba-shi, Ibaraki, Japan Correspondence to: Kawase, email: tatsuya.kawase@astellas.com Keywords: FLT3; FL; FLT3 inhibitor; gilteritinib; antitumor activity Received: June 20, 2019 Accepted: September 10, Published: October 22, ABSTRACT Therapeutic effects of inhibitors have been reported in acute myeloid...
Abstract In recent years, the association between neuroinflammatory markers and dementia, especially Alzheimer’s disease (AD), has attracted much attention. However, evidence for relationship serum-hs-CRP dementia including AD are inconsistent. Therefore, relationships of serum high-sensitivity CRP (hs-CRP) with regions interest brain MRI were investigated. A total 11,957 community residents aged 65 years or older recruited in eight sites Japan (JPSC-AD Study). After applying exclusion...
The development of targeted cancer therapies based on monoclonal antibodies against tumor-associated antigens has progressed markedly over recent decades. This approach is dependent the identification tumor-specific, normal tissue-sparing antigenic targets. transmembrane protein claudin-18 splice variant 2 (CLDN18.2) frequently and preferentially displayed surface primary gastric adenocarcinomas, making it a promising antibody target. Phase 3 studies zolbetuximab, chimeric immunoglobulin G1...
Background Sleep disturbances in Alzheimer disease (AD) may affect behavioral and psychological symptoms of dementia (BPSD). Our aim was to elucidate the associations between sleep other BPSD at different stages AD. Methods This investigation part a multicenter‐retrospective study Japan (J‐BIRD). Eligible for final analyses were 684 AD patients. Global severity estimated using Clinical Dementia Rating (CDR) scale. assessed Neuropsychiatric Inventory (NPI). We analyzed relationships according...
Despite continuing research into Alzheimer's disease (AD), its pathological mechanisms and modulating factors remain unknown. Several genes influence AD pathogenesis by affecting inflammatory pathways. Myocyte-enhancer factor 2C (MEF2C) is one such candidate gene for AD.We examined MEF2C mRNA expression levels methylation rates of CpG on promoter region in peripheral leukocytes from Japanese patients compared with age- sex-matched control subjects.In leukocytes, subjects were significantly...
Microglial dysfunction and inflammation have recently been shown to be related the development of Alzheimer's disease (AD). Inositol polyphosphate-5-phosphatase (INPP5D) functions broadly as a negative regulator immune signaling, its locus was associated with AD in large- scale genome-wide association study. Thus, we examined INPP5D mRNA expression methylation rates CpG sites upstream region exon 1 peripheral leukocytes 50 age- sex-matched control subjects. subjects significantly higher than...
Abstract Studies of diacylglycerol kinase ζ (DGKζ) in DGKζ knockout mice have revealed its role as an intracellular immune checkpoint T cells. Although enhancing antitumor immunity by pharmacological inhibition is desirable, selective inhibitors for clinical use remain largely unexplored. Here, we report a novel, small-molecule, inhibitor, ASP1570, which currently under phase 1 development (NCT05083481), and characterize effect on potential resistance mechanisms against approved multiple...
The efficacy of Fms-like tyrosine kinase 3 (FLT3) inhibitors has been well established against acute myeloid leukemia (AML) with FLT3 internal tandem duplication (FLT3-ITD) mutations. However, comparative data on the available are limited, and drug resistance remains a major concern. This study examined inhibitory effects gilteritinib, quizartinib midostaurin Ba/F3 cells FLT3-ITD mutations, or point mutations in domain (TKD-PM) juxtamembrane (JMD-PM), both vitro vivo. Quizartinib were...
Despite the continuing debate about amyloid hypothesis in Alzheimer's disease (AD), precise pathogenesis is still unclear. Mixed pathology common and multiple different protein aggregates are seen human postmortem brains. Aggregates consisting of alpha-synuclein encoded by Synuclein Alpha gene (SCNA) both dementia with Lewy bodies AD. We examined SNCA mRNA expression methylation rates CpG island at intron 1 peripheral leukocytes 50 AD age- sex-matched control subjects to verify whether...
TREM2 and TYROBP are causal genes for Nasu–Hakola disease (NHD), a rare autosomal recessive characterized by bone lesions early-onset progressive dementia. forms receptor signaling complex with TYROBP, which triggers the activation of immune responses in macrophages dendritic cells, functional polymorphism is reported to be associated neurodegenerative disorders such as Alzheimer's (AD). The objective this study was reveal involvement pathophysiology AD schizophrenia. Methods: We...
Background/Objective: The aim of this study was to examine the blood gene expression and methylation ATP-binding cassette sub-family A member 7 (ABCA7) as a biological marker AD. Methods: AD subjects ( n = 50; 11 males, 77.7±6.05 years old) age- sex-matched healthy controls 50) were recruited. single nucleotide polymorphism in ABCA7 (rs3764650), rates CpG sites promoter region, mRNA levels peripheral examined. Results: distribution rs3764650 not different from that controls. Although...
TOMM40 is located on chromosome 19, in linkage disequilibrium with apolipoprotein E (APOE), andis reported several genome-wide association studies to be associated Alzheimer's disease (AD).Assess APOE and TOM40 mitochondrial genes as blood biomarkers for AD.We examined TOMM40, PTEN-induced putative kinase 1 (PINK1), Parkin RBR E3 ubiquitin protein ligase (PARK2), mRNA expression relation the methylation rates of CpG sites upstream region TOMM40exon peripheral leukocytes TOMM40523 polyT...