A5036984489- Cancer-related Molecular Pathways
- X-ray Diffraction in Crystallography
- Crystallization and Solubility Studies
- Cancer Research and Treatments
- HIV Research and Treatment
- interferon and immune responses
- RNA modifications and cancer
- Kruppel-like factors research
- Semiconductor materials and devices
- Cell death mechanisms and regulation
- Fibroblast Growth Factor Research
- Cancer, Hypoxia, and Metabolism
- Silicon Nanostructures and Photoluminescence
- Nanowire Synthesis and Applications
- Acute Myeloid Leukemia Research
- Epigenetics and DNA Methylation
- Immune Cell Function and Interaction
- CAR-T cell therapy research
- Ubiquitin and proteasome pathways
- Amino Acid Enzymes and Metabolism
- Virus-based gene therapy research
- Optical Imaging and Spectroscopy Techniques
- Crystallography and molecular interactions
- Thermoregulation and physiological responses
- Chronic Myeloid Leukemia Treatments
Astellas Pharma (Japan)
2015-2025
Columbia University
2023
National Center on Addiction and Substance Abuse at Columbia University
2023
Astellas Pharma (China)
2022
Astellas Pharma (United Kingdom)
2019
Osaka University
1995-2016
National Cancer Centre Japan
2016
Tokyo University of Science
2009-2016
Tokyo Institute of Technology
2000-2014
Tokyo University of Agriculture and Technology
2011-2013
Oncolytic vaccinia virus encoding IL-7 and IL-12 facilitates immune checkpoint blockade in treatment-resistant solid tumors.
Significance Pancreatic neuroendocrine tumors (PanNETs) are a rare pathology, and molecular mechanisms underlying their development have not been well defined. This article shows that two-hit inactivation of the PHLDA3 gene is required for PanNET development: methylation locus loss heterozygosity. functions as suppressor PanNETs via repression Akt activity downstream Akt-regulated biological processes. In addition, tumor-suppressing pathway mediated by MEN1, known PanNETs, dependent on...
// 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...
In order to visualize human skin hemodynamics, we investigated a method that is specifically developed for the visualization of concentrations oxygenated blood, deoxygenated and melanin in tissue from digital RGB color images. Images total blood concentration oxygen saturation can also be reconstructed results blood. Experiments using tissue-like agar gel phantoms demonstrated ability quantitatively transition an dermis. vivo imaging chromophore hand are performed 14 subjects during upper...
The transcription factors HSF1 and p53 both modulate the stress response, thereby protecting facilitating recovery of stressed cells, but have potential to promote tumor development. Here we show that a target gene, IER5, encodes an activator HSF1. IER5 forms ternary complex with phosphatase PP2A, promotes dephosphorylation at numbers serine threonine residues, generating novel, hypo-phosphorylated active form is also transcriptionally upregulated in various cancers, although this...
The tumor suppressor p53 functions by inducing the transcription of a collection target genes. We previously attempted to identify genes microarray expression and Ch IP ‐sequencing analyses. In this study, we describe novel gene, FUCA 1 , which encodes fucosidase. Although fucosidase, α‐ l ‐1 ( 1) has been reported be lysosomal protein, detected it outside lysosomes observed that its activity is highest at physiological pH . As there association between fucosylation tumorigenesis,...
We propose the metal-assisted chemical etching of Ge surfaces in water mediated by dissolved oxygen molecules (O2). First, we demonstrate that around deposited metallic particles (Ag and Pt) are preferentially etched water. When a Ge(100) surface is used, most etch pits shape inverted pyramids. The mechanism this anisotropic proposed to be enhanced formation soluble oxide (GeO2) metals catalytic activity particles, reducing O2 H2O molecules. Secondly, apply nanoscale patterning using...
The PHLDA family (pleckstrin homology‐like domain family) of genes consists 3 members: 1 , 2 and . Both are phosphatidylinositol ( PIP ) binding proteins function as repressors Akt. They have tumor suppressive functions, mainly through Akt inhibition. Several reports suggest that also has a function; however, the precise molecular functions remain to be elucidated. Through comprehensive screen for p53 target genes, we identified novel target, show ability repress in manner similar 2....
Hepatocellular carcinoma is an aggressive cancer with poor prognosis. Fibroblast growth factor 19, a member of the fibroblast family, ligand for receptor 4. Moreover, it plays crucial role in progression hepatocellular carcinoma. ASP5878 novel inhibitor receptors 1, 2, 3, and 4 that under development. It inhibits kinase activity IC50 3.5 nmol/L. potently suppressed 19-expressing cell lines Hep3B2.1-7, HuH-7, JHH-7. In Hep3B2.1-7 line, inhibited phosphorylation its downstream signaling...
Single-cell level analysis is powerful tool to assess the heterogeneity of cellular components in tumor microenvironments (TME). In this study, we investigated immune-profiles using single-cell analyses endoscopically- or surgically-resected tumors, and peripheral blood mononuclear cells from gastric cancer patients. Furthermore, technically characterized two distinct platforms analysis; RNA-seq-based (scRNA-seq), mass cytometry-based (CyTOF), both which are broadly embraced technologies....
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...
The p53 protein exerts its tumor suppressive function mainly by acting as a transcription activator. Two transactivation domains (TADs) located at the amino‐terminus of are required for activation, and activity TADs is tightly regulated post‐translational modifications, such phosphorylation. We attempted to dissect functions two phosphorylation within analyzing target genes induced full‐length (FL‐p53), N‐terminally deleted isoform lacking first TAD (Δ1stTAD) carrying point mutations all...
Abstract Immunotherapy has attracted considerable attention as a therapeutic strategy for cancers including acute myeloid leukemia (AML). In this study, we found that the development of several aggressive subtypes AML is slower in Rag2 −/− mice despite lack B and T lymphocytes, even compared to immunologically normal C57BL/6 mice. Furthermore, an orally active p53-activating drug shows stronger antileukemia effect on than Intriguingly, Natural Killer (NK) cells are increased number, highly...
The common polymorphism of p53 at codon 72, either encoding proline or arginine, has drawn attention as a genetic factor associated with clinical outcome cancer risk for the last 2 decades. We now show that these two polymorphic variants differ in protein structure, especially within N-terminal region and, consequence, post-translational modification N terminus. arginine form (p53-72R) shows significantly enhanced phosphorylation Ser-6 and Ser-20 compared (p53-72P). also diminished...
Abstract Gastric cancer remains one of the leading causes death worldwide. Despite intensive investigations treatments over past three decades, poor prognosis patients with unresectable advanced or recurrent gastric has not significantly changed, and improved therapies are required. Here, we report identification an oncogenic mutation in FGFR4 a human tumour that leads to constitutive activation its product, FGFR4. The G636C-FGFR4 tyrosine kinase domain was found 1 83 primary tumours. G636C...
A new control strategy to realize general-purpose active filters based on voltage detection is proposed as an economical solution harmonic compensation in distribution lines. The method real-time digital simulation of LC filter accomplished by a signal processor. adaptive gain the automatic online adjustment compensating characteristics introduced. This achieves optimum operation according condition AC Thus, can be used filter. In this paper, plural units connected line are investigated....
The authors demonstrate that Ge(100) surfaces containing metallic particles are etched anisotropically in water. This originates from the catalytic reduction of dissolved oxygen (O2) water to molecules (H2O) on particles, which is followed by enhanced oxidation Ge around particles. soluble nature oxide (GeO2) promotes formation inverted pyramidal etch pits composed (111) microfacets. On basis results, propose strategies for avoiding unwanted surface roughening during wet cleaning Ge.
We propose a method to visualize the arterial inflow, vascular resistance, and venous capacitance in skin tissue from red, green, blue (RGB) digital color images. The inflow are visualized based on an increase rate of change total blood concentration during upper limb occlusion at pressure 50 mmHg. resultant with measured mean also provides image resistance human skin. acquired by well correlated those obtained conventional strain-gauge plethysmograph. correlation coefficients R between...