A5015626889- Multiple Myeloma Research and Treatments
- Protein Degradation and Inhibitors
- Ubiquitin and proteasome pathways
- Peptidase Inhibition and Analysis
- Chronic Lymphocytic Leukemia Research
- PI3K/AKT/mTOR signaling in cancer
- Fibroblast Growth Factor Research
- Cancer Mechanisms and Therapy
- Malaria Research and Control
- Cancer-related Molecular Pathways
- Lymphoma Diagnosis and Treatment
- Glycosylation and Glycoproteins Research
- Cancer Genomics and Diagnostics
- Myeloproliferative Neoplasms: Diagnosis and Treatment
- Salivary Gland Tumors Diagnosis and Treatment
- Angiogenesis and VEGF in Cancer
- Ovarian cancer diagnosis and treatment
- Ear and Head Tumors
- Cancer, Hypoxia, and Metabolism
- Kruppel-like factors research
- Cancer therapeutics and mechanisms
- Proteoglycans and glycosaminoglycans research
- RNA modifications and cancer
- Cancer Treatment and Pharmacology
- Ferroptosis and cancer prognosis
Takeda (United States)
2013-2021
Millennium Engineering and Integration (United States)
2011-2020
Merck (Japan)
2011
Merck & Co., Inc., Rahway, NJ, USA (United States)
2008-2011
Osaka City University
2008
Harvard University
2003-2006
Biotechnology Research Institute
2005
McGill University
2005
University College Cork
2000
European Institute of Oncology
1996-1997
Ixazomib is an oral proteasome inhibitor that currently being studied for the treatment of multiple myeloma.
We have identified a critical role for amplified FGFR2 in gastric cancer cell proliferation and survival. In panel of lines, fibroblast growth factor receptor 2 (FGFR2) was overexpressed tyrosine phosphorylated selectively FGFR2-amplified lines KatoIII, Snu16, OCUM-2M. kinase inhibition by specific small-molecule inhibitor resulted selective potent resulting arrest KatoIII cells prominent induction apoptosis both Snu16 OCUM-2M cells. also contained elevated phosphotyrosine EGFR, Her2, Erbb3,...
Posttranslational modification of substrates by the small ubiquitin-like modifier, SUMO, regulates diverse biological processes, including transcription, DNA repair, nucleocytoplasmic trafficking, and chromosome segregation. SUMOylation is reversible, several mammalian homologs yeast SUMO-specific protease Ulp1, termed SENPs, have been identified. We demonstrate here that SENP5, a previously uncharacterized Ulp1 homolog, has SUMO C-terminal hydrolase isopeptidase activities. In contrast to...
Phosphorylation sites on proteins in the phosphatidylinositol 3-kinase pathway that are regulated by candidate drugs can serve as useful biomarkers to predict tumor sensitivity AKT inhibitors.
Experimental studies suggest that angiogenesis plays an important role in the pathogenesis of ascites and progression ovarian cancer. To evaluate association intratumoral microvessel density (IMD) with conventional clinicopathologic features to determine capability these factors predicting responsiveness platinum-based chemotherapy overall survival (OS) we studied 112 carcinomas. IMD was determined using anti-CD31 antibody immunocytochemistry. In entire series, correlated other features....
Treatment of myeloma has benefited from the introduction more effective and better tolerated agents, improvements in supportive care, understanding disease biology, revision diagnostic criteria, new sensitive specific tools for prognostication management. Assessment minimal residual (MRD) response to therapy is one these tools, as longer progression-free survival (PFS) seen consistently among patients who have achieved MRD negativity. Current therapies lead unprecedented frequency depth...
The development of novel agents has transformed the treatment paradigm for multiple myeloma, with minimal residual disease (MRD) negativity now achievable across entire spectrum. Bone marrow-based technologies to assess MRD, including approaches using next-generation flow and sequencing, have provided real-time clinical tools sensitive detection monitoring MRD in patients myeloma. Complementary liquid biopsy-based assays are quickly progressing some, such as mass spectrometry methods, being...
Prior treatment exposure in patients with relapsed/refractory multiple myeloma may affect outcomes subsequent therapies. We analyzed efficacy and safety according to prior the phase 3 TOURMALINE-MM1 study of ixazomib-lenalidomide-dexamethasone (ixazomib-Rd) versus placebo-Rd. Patients received ixazomib-Rd or Efficacy were evaluated subgroups defined type (proteasome inhibitor [PI] immunomodulatory drug) number (1 vs. 2 3) therapies received. Of 722 patients, 503 (70%) had a PI, 397 (55%)...
Ixazomib is an investigational proteasome inhibitor that has shown preclinical activity in lymphoma models. This phase 1 study assessed the safety, tolerability, maximum tolerated dose (MTD), pharmacokinetics, pharmacodynamics and preliminary of intravenous (IV) ixazomib relapsed/refractory patients who had received ⩾2 prior therapies. Thirty with a range histologies 0.125−3.11 mg/m2 on days 1, 8 15 28-day cycles. Patients median two cycles (range 1−36). MTD was determined to be 2.34 mg/m2....
Ixazomib is an investigational proteasome inhibitor with demonstrated antitumor activity in xenograft models of multiple myeloma (MM), lymphoma, and solid tumors. This open-label, phase 1 study investigated intravenous (IV) ixazomib, adult patients advanced non-hematologic malignancies.Patients received IV ixazomib twice-weekly for up to twelve 21-day cycles. The 0.125 mg/m(2) starting dose was doubled (one patient/dose) until 1.0 based on dose-limiting toxicities (DLTs) cycle 1. followed by...
bcl-2 protein and Ki-67 (MIB-1) were studied in 32 acinic cell carcinomas (ACCs), all with a minimum of 5 years' clinical follow-up. Tumour apoptosis was evaluated by TdT dUTP nick end labelling (TUNEL) morphological criteria. Five patients died their disease. Patients stage I tumours had significantly better survival compared other stages (P < 0.05). MIB-1-negative than MIB-1-positive = This study confirms previous report that MIB-1 is an independent prognostic factor for ACC. Stage high...
The cellular repressor of E1A-stimulated genes (CREG) is a secreted glycoprotein that inhibits proliferation and enhances differentiation human embryonal carcinoma cells. CREG binds to the cation-independent mannose 6-phosphate (M6P)/insulin-like growth factor II (IGF2) receptor (IGF2R) (M6P/IGF2R), this has been shown be required for CREG-induced suppression. To better understand function in differentiation, we solved 3D crystal structure protein 1.9-Å resolution. forms tight homodimeric...
Summary Weekly ixazomib with lenalidomide‐dexamethasone (Rd) is feasible and has shown activity in newly diagnosed multiple myeloma ( NDMM ) patients. This phase 1/2 study NCT 01383928) evaluated the recommended 2 dose RP 2D), pharmacokinetics, safety efficacy of twice‐weekly plus Rd ; 64 patients were enrolled across both phases. Patients received oral 3·0 or 3·7 mg lenalidomide 25 dexamethasone 20 (10 cycles 9–16) for up to sixteen 21‐day cycles, followed by maintenance alone. No...
PDK1 activates AKT suggesting that inhibition might suppress tumor development. However, while has been investigated intensively as an oncology target, selective inhibitors suitable for in vivo studies have remained elusive. In this study we present the results of through a universally applicable RNAi approach functional drug target validation oncogenic pathway contexts. This approach, which relies on doxycycline-inducible shRNA expression from Rosa26 locus, is ideal genes like where...