A5059549843- Protein Degradation and Inhibitors
- Peptidase Inhibition and Analysis
- Chromatin Remodeling and Cancer
- Multiple Myeloma Research and Treatments
- Histone Deacetylase Inhibitors Research
- Synthesis and Reactions of Organic Compounds
- Synthesis and Reactivity of Heterocycles
- Epigenetics and DNA Methylation
- Synthesis and Characterization of Heterocyclic Compounds
- Synthesis and Biological Evaluation
- Silkworms and Sericulture Research
- Acute Myeloid Leukemia Research
- Silk-based biomaterials and applications
- Chronic Myeloid Leukemia Treatments
- Phenothiazines and Benzothiazines Synthesis and Activities
- Hematopoietic Stem Cell Transplantation
- Advanced biosensing and bioanalysis techniques
- Ubiquitin and proteasome pathways
- MXene and MAX Phase Materials
- Immune Cell Function and Interaction
- Lymphoma Diagnosis and Treatment
- Insect and Arachnid Ecology and Behavior
- Immunotherapy and Immune Responses
- Viral Infectious Diseases and Gene Expression in Insects
- Lung Cancer Research Studies
Dana-Farber Cancer Institute
2019-2024
Kobe University Hospital
2016-2024
Kobe University
2013-2024
Harvard University
2020-2024
Consorci Institut D'Investigacions Biomediques August Pi I Sunyer
2023
Universitat de Barcelona
2023
Kobe City Medical Center West Hospital
2019
Shimane University
2009
Institute of Vegetable and Floriculture Science
1994-1995
Sericultural Research Institute
1971-1985
Abstract Anti-CD38 monoclonal antibodies like Daratumumab (Dara) are effective in multiple myeloma (MM); however, drug resistance ultimately occurs and the mechanisms behind this poorly understood. Here, we identify, via two vitro genome-wide CRISPR screens probing resistance, KDM6A as an important regulator of sensitivity to Daratumumab-mediated antibody-dependent cellular cytotoxicity (ADCC). Loss leads increased levels H3K27me3 on promoter CD38 , resulting a marked downregulation...
Immunogenic cell death (ICD) is a form of by which cancer treatments can induce clinically relevant antitumor immune response in broad range cancers. In multiple myeloma (MM), the proteasome inhibitor bortezomib an ICD inducer and creates durable therapeutic responses patients. However, eventual relapse resistance to appear inevitable. Here, integrating patient transcriptomic data with analysis calreticulin (CRT) protein interactors, we found that GABA type A receptor-associated (GABARAP)...
Abstract Purpose: BRD9 is a defining component of the noncanonical SWI/SNF complex, which regulates gene expression by controlling chromatin dynamics. Although recent studies have found an oncogenic role for in multiple cancer types including myeloma, its clinical significance and mechanism not yet been elucidated. Here, we sought to identify biological impact may contribute development novel therapeutic strategies. Experimental Design: We performed integrated analyses vitro vivo using...
Abstract Lysine demethylase 5A (KDM5A) is a negative regulator of histone H3 lysine 4 trimethylation (H3K4me3), mark associated with activate gene transcription. We identify that KDM5A interacts the P-TEFb complex and cooperates MYC to control MYC-targeted genes in multiple myeloma cells. develop cell-permeable selective KDM5 inhibitor, JQKD82, increases H3K4me3 but paradoxically inhibits downstream MYC-driven transcriptional output vitro vivo. Using genetic ablation together our we...
Abstract Multiple myeloma (MM) is a plasma cell malignancy characterised by aberrant production of immunoglobulins requiring survival mechanisms to adapt proteotoxic stress. We here show that glutamyl-prolyl-tRNA synthetase (GluProRS) inhibition constitutes novel therapeutic target. Genomic data suggest GluProRS promotes disease progression and associated with poor prognosis, while downregulation in MM cells triggers apoptosis. developed NCP26, ATP-competitive ProRS inhibitor demonstrates...
Abstract Sinusoidal obstruction syndrome/veno-occlusive disease (SOS/VOD) is a life-threatening complication of hematopoietic stem cell transplantation (HSCT). Early diagnosis SOS/VOD associated with improved clinical outcomes. In 2023, the refined European Society for Blood and Marrow Transplantation diagnostic severity criteria (refined EBMT 2023) have been advocated. The revision has introduced new categories, namely; probable, clinical, proven SOS/VOD. addition, Sequential Organ Failure...
Monovalent Omicron XBB.1.5 mRNA vaccines were newly developed and approved by the FDA in Autumn 2023 for preventing COVID-19. However, clinical efficacy these is currently lacking. We previously established quantification of antigen-specific antibody sequence (QASAS) method to assess response severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) vaccination at level using B-cell receptor (BCR) repertoire assay database (CoV-AbDab). Here, we used this evaluate immunogenicity monovalent...
Abstract Bortezomib (BTZ) is a standard-of-care treatment in multiple myeloma (MM); however, adverse side effects and development of resistance limit its long term benefit. To improve target specificity, therapeutic efficacy, overcome resistance, we designed nanoparticles that encapsulate BTZ are surface-functionalized with BCMA antibodies (BCMA-BTZ-NPs). We confirmed efficient cellular internalization the BCMA-BTZ-NPs only BCMA-expressing MM cells, but not BCMA-knockout (KO) cells. In...
A major hurdle in adoptive T-cell therapy is cell exhaustion and failure to maintain antitumor responses. Here, we introduce an induced pluripotent stem (iPSC) strategy for reprogramming revitalizing precursor exhausted B-cell maturation antigen (BCMA)-specific T cells effectively target multiple myeloma (MM). Heteroclitic BCMA72-80 (YLMFLLRKI)-specific CD8+ memory cytotoxic lymphocytes (CTL) were epigenetically reprogrammed a state, developed into hematopoietic progenitor (CD34+ CD43+/CD14-...
Aberrant activation of the Hedgehog (Hh) signaling pathway is involved in maintenance leukemic stem cell (LSCs) populations. PF-0444913 (PF-913) a novel inhibitor that selectively targets Smoothened (SMO), which regulates Hh pathway. Treatment with PF-913 has shown promising results an early phase study acute myeloid leukemia (AML). However, detailed mode action for and relevant biomarkers remain to be elucidated. In this study, we examined bone marrow samples derived from AML patients under...
Reaction of the pyridinium N-ylides with ketenethioacetals in presence triethylamine or potassium carbonate as a base ethanol dimethylformamide gave N-allylides which were readily cyclized to afford indolizine derivatives.
Abstract Background Human herpesvirus 6 (HHV‐6) encephalitis is a known life‐threatening complication following allogeneic hematopoietic stem cell transplantation (allo‐HSCT). However, few studies have focused on the occurrence of HHV‐6 in patients receiving mycophenolate mofetil (MMF) combined with calcineurin inhibitor as prophylaxis for graft‐versus‐host disease (GVHD). This study aimed to investigate impact MMF administered GVHD after allo‐HSCT and characteristics this condition. Methods...
Objective High-dose chemotherapy with autologous hematopoietic stem cell transplantation (auto-HSCT) is an effective treatment option for relapsed and refractory aggressive malignant lymphoma. However, patients frequently experience treatment-induced gastrointestinal symptoms. Synbiotics, including live microorganisms nondigestible food ingredients, reportedly ameliorate chemotherapy-induced mucosal damage. In this study, we assessed the efficacy safety of synbiotics in undergoing auto-HSCT....
Sinusoidal obstruction syndrome (SOS) is a fatal complication of hematopoietic stem cell transplantation (HSCT). Early diagnosis for SOS can improve clinical outcomes significantly. Here, we performed retrospective study to investigate the Cairo diagnostic criteria, in which was defined as development two or more seven events, including transfusion-refractory thrombocytopenia. Among 154 cases allogeneic HSCT, 10 using European Society Blood and Marrow Transplantation criteria (EBMT16)...
Natural killer (NK) cells are a vital component of cancer immune surveillance. They provide rapid and potent response, including direct cytotoxicity mobilization the system, without need for antigen processing presentation. NK may also be better tolerated than T cell therapy approaches susceptible to various gene manipulations. Therefore, have become focus extensive translational research. Gamida Cell's nicotinamide (NAM) platform cultured provides an opportunity enhance therapeutic...
2, 6-Dimethyl-1-ethoxycarbonylmethylpyridinium bromide (Ia) reacted with ketene-thioacetal derivatives (II) in the presence of potassium carbonate to afford 3-ethoxycarbonylindolizine (IV) and 3-vinylindolizine (V). While, 2-aminopyridinium salts (VII) II only give 3-vinylimidazo [1, 2-α] pyridine (VIII). Ia was treated sodium hydride, carbon disulfide then dimethyl sulfate methyl 2-hydroxy-5-methylindolizine-3-dithiocarboxylate (XIII). Also, imidazo pyridine-3-dithiocarboxylate (XVIII, XIX)...