A5068991114- interferon and immune responses
- Cytokine Signaling Pathways and Interactions
- Cancer Immunotherapy and Biomarkers
- Synthetic Organic Chemistry Methods
- Mesoporous Materials and Catalysis
- Catalytic C–H Functionalization Methods
- Crystallization and Solubility Studies
- T-cell and B-cell Immunology
- X-ray Diffraction in Crystallography
- Asymmetric Synthesis and Catalysis
- Coordination Chemistry and Organometallics
- Bacteriophages and microbial interactions
- Zeolite Catalysis and Synthesis
- Ferroptosis and cancer prognosis
- CAR-T cell therapy research
- Immunotherapy and Immune Responses
- Catalytic Cross-Coupling Reactions
- Cancer Mechanisms and Therapy
- Porphyrin and Phthalocyanine Chemistry
- Chemical synthesis and alkaloids
- Immune cells in cancer
- Immune Cell Function and Interaction
- Studies on Chitinases and Chitosanases
- Geological and Geochemical Analysis
- Alkaloids: synthesis and pharmacology
Takeda (United States)
2021-2024
The University of Tokyo
1993-2021
AstraZeneca (United States)
2021
Millennium Engineering and Integration (United States)
2021
Takeda (Japan)
2017-2018
Asahi Glass (Japan)
2017
Tohoku University
2010-2011
Nagaoka University of Technology
2010-2011
Nagaoka University
2010
Institute of Particle and Nuclear Studies
2004
Immune checkpoint inhibitors can stimulate antitumor immunity but also induce toxicities termed immune-related adverse events (irAEs). Colitis is a common and severe irAE that lead to treatment discontinuation. Mechanistic understanding of gut irAEs has been hampered because robust colitis not observed in laboratory mice treated with inhibitors. We report here this limitation be overcome by using harboring the microbiota wild-caught mice, which develop overt following anti-CTLA-4 antibodies....
A palladium-catalyzed asymmetric synthesis of silicon-stereogenic 5,10-dihydrophenazasilines was developed that proceeds via an unprecedented enantioselective 1,5-palladium migration. High enantioselectivity achieved by employing 4,4'-bis(trimethylsilyl) (R)-Binap as the chiral ligand, and a series mechanistic investigations were carried out to probe catalytic cycle this process.
Immune checkpoint blockade (ICB) therapies have changed the paradigm of cancer therapies. However, anti-tumor response ICB is insufficient for many patients and limited to specific tumor types. Despite preclinical clinical studies understand mechanism efficacy ICB, not completely understood. Harnessing models one way treatment response.In order delineate mechanisms activity in syngeneic models, we selected two murine colorectal based on vivo screening sensitivity with anti-PD-1 therapy. We...
Oncology therapies targeting the immune system have improved patient outcomes across a wide range of tumor types, but resistance due to an inadequate T-cell response in suppressive microenvironment (TME) remains significant problem. New that activate innate and relieve this suppression may be beneficial overcome hurdle. TAK-676 is synthetic novel stimulator interferon genes (STING) agonist designed for intravenous administration. Here we demonstrate dose-dependently triggers activation STING...
Stimulator of Interferon Genes (STING) plays an important role in innate immunity by inducing type I interferon production upon infection with intracellular pathogens. STING activation can promote increased T-cell and inflammation the tumor microenvironment, resulting antitumor immunity. Natural synthetic cyclic dinucleotides (CDNs) are known to activate STING, several CDN molecules being investigated clinic using intratumoral administration route. Here, we describe identification agonist...
Abstract A palladium‐catalyzed asymmetric synthesis of silicon‐stereogenic 5,10‐dihydrophenazasilines was developed that proceeds via an unprecedented enantioselective 1,5‐palladium migration. High enantioselectivity achieved by employing 4,4′‐bis(trimethylsilyl) ( R )‐Binap as the chiral ligand, and a series mechanistic investigations were carried out to probe catalytic cycle this process.
Ipilimumab, a monoclonal antibody that recognizes cytotoxic T-lymphocyte associated protein 4 (CTLA-4), was the first immune checkpoint inhibitor approved by FDA to treat metastatic melanoma patients. Multiple preclinical studies have proposed Fc effector functions of anti-CTLA-4 therapy are required for anti-tumor efficacy, in part, through depletion intratumoral regulatory T cells (Tregs). However, contribution Fc-independent antibodies observed efficacy is not fully understood. H11,...
Abstract A double helicene with a spiro‐Si linker ( 4 ) was synthesized by four successive nucleophilic substitutions on SiCl . Its P,P ), M,M and P,M isomers were isolated characterized single crystal X‐ray analysis. Due to the central spirosilabi[fluorene] moiety, two units in are symmetrically nearly perpendicularly arranged. )‐ exhibit unique optical properties attributable LUMO spiro‐conjugation between sila[7]helicene units.
Scleroderma has clinical characteristics including skin and other tissue fibrosis, but there is an unmet need for anti-fibrotic therapy. Halofuginone (HF) a well-known anti-fibrosis agent in preclinical studies which exerts its effect via inhibition of TGF-β/Smad3 signaling pathway. Recently, prolyl-tRNA synthetase (PRS) was elucidated as target protein HF that binds to the proline binding site catalytic domain PRS. Here, we characterized new class PRS inhibitor (T-3833261) carefully...
The enantio-and diastereocontrolled total synthesis of (-)-salinosporamide A, a potent 20S proteasome inhibitor, was accomplished through organocatalytic aldolization, diastereoselective Claisen condensation, Rh-catalyzed Reformatsky reaction, and an AZADO-catalyzed oxidative -lactonization reaction as the key reactions.Salinosporamide A (1, aka NPI-0052, marizobnib) discovered by Fenical coworkers cytotoxic principle produced marine actinomycete Salinosopra tropicana. 1
Molecular dynamics (MD) simulations were applied to construct a plasticity model, which enables one simulate deformations of soda-lime silica glass (SLSG) by using continuum methods. To model the plasticity, stress induced uniaxial and variety biaxial was measured MD simulations. We found that surfaces yield maximum stresses, are evaluated from equivalent stress-strain curves, reasonably represented Mohr-Coulomb ellipsoid. Comparing finite element constructed large scale atomistic on...
Anti–tumor necrosis factor alpha (anti-TNFα) therapy has become the mainstay of for Crohn's disease (CD). However, post-therapy, recurrence rate is still high. The aim this study was to dissect molecular mechanism CD treated with anti-TNFα and investigate novel therapeutic options that could induce complete remission. We re-analyzed publicly available mucosal gene expression data from patients pre– post–infliximab extract transcriptional differences between responders healthy controls. used...
Abstract Robust interferon (IFN) signaling is integral for productive immune-mediated anti-tumor responses; however, impaired IFN has been linked to checkpoint inhibitor (CPI) resistance. The cyclic GMP-AMP Synthase (cGAS)-STimulator of InterferoN Genes (STING) pathway an essential regulator in response aberrant cytosolic DNA, including from tumors, and emerged as attractive therapeutic target. TAK-676 a systemically delivered novel synthetic STING agonist that binds activates along with...
We measured the energy and angular distributions (7 eV–10 keV 20°–160°) of secondary electrons produced in collisions 6.0 MeV/u He2+ ions with water vapor. Binary‐encounter collision peaks were clearly observed at calculated energies angles <90°, as well K‐LL Auger peak oxygen about 500 eV for all angles. From these measurements, doubly differential cross sections (DDCS) electron emissions deduced an estimated uncertainty ±13%. The distribution (SDCS) was also obtained by integrating DDCS...
A rare case of bilateral fat necrosis the breast is reported. The patient was a 50-year-old unmarried woman having no history trauma, disease or surgery breast. In breasts, ill-defined, firm masses with skin retraction were noted. Bilateral cancer diagnosed clinically. However, both lesions showed histologically chronic granulomatous inflammation foci fatty necrosis, infiltration lymphocytes, plasma cells, lipid containing foamy foreign body giant cells engurfing choresterol-crystals, and...
<div><p>Oncology therapies targeting the immune system have improved patient outcomes across a wide range of tumor types, but resistance due to an inadequate T-cell response in suppressive microenvironment (TME) remains significant problem. New that activate innate and relieve this suppression may be beneficial overcome hurdle. TAK-676 is synthetic novel stimulator interferon genes (STING) agonist designed for intravenous administration. Here we demonstrate dose-dependently...
<p>Supplementary methods and results: The supplementary describe: 1) the chemical synthesis characterization of TAK-676, inclusive TAK-676 structure, purification chromatogram NMR characterization; 2) details regarding STING DNA cloning (recombinant E. coli expression utilizing an N-terminal His tag C-terminal Avi tag) for binding assays (time-resolved fluorescence resonance energy transfer assay); 3) description pathway activation (inclusive cell culture methods) in THP1-Dual™,...