A5045095062- Multiple Myeloma Research and Treatments
- Protein Degradation and Inhibitors
- Peptidase Inhibition and Analysis
- Cancer therapeutics and mechanisms
- Ubiquitin and proteasome pathways
- Histone Deacetylase Inhibitors Research
- Monoclonal and Polyclonal Antibodies Research
- Gastric Cancer Management and Outcomes
- HIV/AIDS drug development and treatment
- Cancer Treatment and Pharmacology
- Cancer Mechanisms and Therapy
- Congenital heart defects research
- Immune Cell Function and Interaction
- Chronic Myeloid Leukemia Treatments
- Congenital Heart Disease Studies
- Chemokine receptors and signaling
- Chronic Lymphocytic Leukemia Research
- Cell Adhesion Molecules Research
- PI3K/AKT/mTOR signaling in cancer
- Gastrointestinal Tumor Research and Treatment
- Colorectal Cancer Treatments and Studies
- Synthesis and Biological Evaluation
- Lung Cancer Treatments and Mutations
- Gastrointestinal disorders and treatments
- Synthesis and biological activity
The University of Tokyo
2016-2025
St. Marianna University School of Medicine
2023-2025
Sapporo Medical University
2005-2023
Dana-Farber Cancer Institute
2004-2023
Harvard University
2004-2023
Rakuwakai Otowa Hospital
2008-2023
Multiple Myeloma Research Foundation
2007-2023
University of Tokyo Hospital
2014-2023
Tokyo University of Science
2022
Shizuoka Cancer Center
2009-2020
Summary Thalidomide and immunomodulatory drugs (IMiDs), which target multiple myeloma (MM) cells the bone marrow microenvironment, can overcome drug resistance. These agents also have effects. Specifically, we reported that thalidomide increased serum interleukin‐2 (IL‐2) levels natural killer (NK) cell numbers in peripheral blood of responding MM patients. In this study, investigated mechanisms whereby IMiDs augment NK cytotoxicity. cytotoxicity antibody‐dependent cell‐mediated (ADCC)...
Abstract Bone marrow angiogenesis plays an important role in the pathogenesis and progression multiple myeloma. Recent studies have shown that proteasome inhibitor bortezomib (Velcade, formerly PS-341) can overcome conventional drug resistance vitro vivo; however, its antiangiogenic activity bone milieu has not yet been defined. In present study, we examined effects of on angiogenic phenotype myeloma patient–derived endothelial cells (MMEC). At clinically achievable concentrations, inhibited...
The c-Jun N-terminal kinase (JNK) phosphorylates the glucocorticoid receptor (GR) and inhibits GR-mediated transcription. However, biological effect of GR phosphorylation remains unknown. Here we demonstrate that activated JNK human at Ser226 enhances its nuclear export after withdrawal a ligand for GR, dexamethasone. At 1 h dexamethasone withdrawal, green fluorescent protein-GR molecules were mostly retained nucleus, whereas UV exposure enhanced export, approximately 30-40% cells revealed...
Multiple myeloma (MM) is an invariably fatal form of cancer characterized by clonal proliferation malignant plasma cells in the bone marrow. The canonical Wnt signaling pathway activated MM through constitutively active beta-catenin, a messenger molecule relevant to growth, survival, and migration cells. identification number small molecular compounds, such as PKF115-584, which disrupt interaction transcriptionally beta-catenin/TCF protein complex, provides valuable new therapeutic tools...
A critical role for vascular endothelial factor (VEGF) has been demonstrated in multiple myeloma (MM) pathogenesis. Here, we characterized the effect of small-molecule VEGF receptor inhibitor pazopanib on MM cells bone marrow milieu. Pazopanib inhibits VEGF-triggered signaling pathways both tumor and cells, thereby blocking vitro cell growth, survival, migration, VEGF-induced up-regulation adhesion molecules abrogating cell-MM binding associated proliferation. We show that is first-in-class...
Abstract Purpose: We investigated the antitumor effect of murine/human chimeric CD138-specific monoclonal antibody nBT062 conjugated with highly cytotoxic maytansinoid derivatives against multiple myeloma (MM) cells in vitro and vivo. Experimental Design: examined growth inhibitory BT062-SPDB-DM4, BT062-SMCC-DM1, BT062-SPP-DM1 MM cell lines primary tumor from patients. also vivo activity these agents murine xenograft model human severe combined immunodeficient (SCID) mice bearing implant...
Abstract Cyclin-dependent kinase (CDK) inhibitors have the potential to induce cell-cycle arrest and apoptosis in cancer cells. Seliciclib (CYC202 or R-roscovitine) is a potent CDK inhibitor currently undergoing phase-2 clinical testing lung B-cell malignancies. Here we studied vitro cytotoxic activity of seliciclib against multiple myeloma (MM) Our data demonstrate that has cytotoxicity MM cells are both sensitive resistant conventional therapy as well primary from patients. Cell-cycle...
Abstract In this study, we investigated the cytotoxicity of 5-azacytidine, a DNA methyltransferase inhibitor, against multiple myeloma (MM) cells, and characterized damage–related mechanisms cell death. 5-Azacytidine showed significant both conventional therapy-sensitive therapy-resistant MM lines, as well multidrug-resistant patient-derived with IC50 ∼0.8–3 μmol/L. Conversely, 5-azacytidine was not cytotoxic to peripheral blood mononuclear cells or bone marrow stromal (BMSC) at these doses....
Ehlers-Danlos syndrome (EDS) is a heterogeneous connective tissue disorder involving skin and joint laxity fragility. A new type of EDS, similar to kyphoscoliosis but without lysyl hydroxylase deficiency, has been investigated. We have identified homozygous CHST14 (carbohydrate sulfotransferase 14) mutation in the two familial cases compound heterozygous mutations four sporadic cases. encodes dermatan 4-O-sulfotransferase 1 (D4ST1), which transfers active sulfate from 3'-phosphoadenosine...
The interaction between osteoclasts (OCs) and multiple myeloma (MM) cells plays a key role in the pathogenesis of MM-related osteolytic bone disease (OBD). MM promote OC formation and, turn, OCs enhance cell proliferation. Chemokines are mediators effects on vice versa; particular, CCL3 enhances promotes migration survival. Here, we characterize MLN3897, novel specific antagonist chemokine receptor CCR1, both OC-MM interactions. MLN3897 demonstrates significant impairment (by 40%) function...
Abstract Purpose: The purpose of this study is to delineate the biological significance IκB kinase (IKK) β inhibition in multiple myeloma cells context bone marrow stromal (BMSC) using a novel IKKβ inhibitor MLN120B. Experimental Design: Growth-inhibitory effect MLN120B presence cytokines [interleukin-6 (IL-6) and insulin-like growth factor-I (IGF-1)], conventional agents (dexamethasone, melphalan, doxorubicin), or BMSC was assessed vitro. In vivo anti-multiple activity evaluated severe...
Abstract Purpose: Transforming growth factors (TGFs) have pleiotropic biological effects on tumor cells and their environment. In multiple myeloma (MM), we reported that bone marrow stromal (BMSCs) from MM patients produce more TGF-β1 than BMSCs healthy donors, which in turn induces interleukin (IL)-6 secretion. We show here the TGF-β receptor I kinase inhibitor SD-208 significantly decreases secretion of both IL-6 vascular endothelial factor (VEGF) BMSCs, as well cell triggered by adhesion...
Summary Akt mediates growth and drug resistance in multiple myeloma (MM) cells the bone marrow (BM) microenvironment. We have shown that a novel inhibitor Perifosine induces significant cytotoxicity MM BM milieu. This study further delineated molecular mechanisms whereby triggered cells. Neither intensity of Jun NH 2 ‐terminal kinase phosphorylation nor caspase/poly (ADP‐ribose) polymerase cleavage correlated with Perifosine‐induced MM.1S, INA6, OPM1 OPM2 However, survivin, which regulates...
Abstract The novel immunomodulator FTY720 down-modulates sphingosine-1-phosphate receptor 1 on lymphocytes at low nanomolar concentrations, thereby inhibiting 1–dependent egress of from lymph nodes into efferent lymphatics and blood. At high micromolar concentration, has been shown to induce growth inhibition and/or apoptosis in human cancer cells vitro. In this study, we investigated the biological effects multiple myeloma cells. We found that induces potent cytotoxicity against...
Abstract We previously described two unrelated patients showing characteristic facial and skeletal features, overlapping with the kyphoscoliosis type Ehlers–Danlos syndrome (EDS) but without lysyl hydroxylase deficiency [Kosho et al. (2005) Am J Med Genet Part A 138A:282–287]. After observations of them over time encounter four additional patients, we have concluded that they represent a new clinically recognizable EDS distinct craniofacial characteristics, multiple congenital contractures,...
Epigenetic changes such as DNA methylation play a key role in the development and progression of multiple myeloma. Our aim present study was to use genomic screening identify genes targeted for epigenetic inactivation myeloma assess their resistance dexamethasone.Gene expression examined using microarray screening, reverse transcription-PCR, real-time quantitative PCR. bisulfite PCR, sequencing, pyrosequencing 14 cell lines, 87 specimens, 12 control bone marrow samples. WST-8 assays were...