A5054463097- Multiple Myeloma Research and Treatments
- Peptidase Inhibition and Analysis
- Protein Degradation and Inhibitors
- Cell Adhesion Molecules Research
- Cancer therapeutics and mechanisms
- Ubiquitin and proteasome pathways
- Chronic Myeloid Leukemia Treatments
- Acute Myeloid Leukemia Research
- Drug Transport and Resistance Mechanisms
- DNA Repair Mechanisms
- Cancer Mechanisms and Therapy
- HER2/EGFR in Cancer Research
- Endoplasmic Reticulum Stress and Disease
- Myeloproliferative Neoplasms: Diagnosis and Treatment
- Cancer-related Molecular Pathways
- Chemokine receptors and signaling
- Chronic Lymphocytic Leukemia Research
- RNA Interference and Gene Delivery
- Cancer Treatment and Pharmacology
- Monoclonal and Polyclonal Antibodies Research
- Research on Leishmaniasis Studies
- Cytokine Signaling Pathways and Interactions
- Glycosylation and Glycoproteins Research
- Computational Drug Discovery Methods
- HIV/AIDS drug development and treatment
West Virginia University
2016-2025
West Virginia University Hospitals
2020-2025
Modulation Therapeutics (United States)
2013-2024
West Virginia State University
2021-2022
Moffitt Cancer Center
2009-2020
Multiple Sclerosis Society
2020
Molecular Oncology (United States)
2008-2017
University of South Florida
2003-2013
University of Tampa
2012
University of Arizona
1999-2011
The bone marrow microenvironmental components interleukin (IL)-6 and fibronectin (FN) individually influence the proliferation survival of multiple myeloma (MM) cells; however, in vivo, these effectors most likely work together. We examined signaling events, cell cycle progression, levels drug response MM cells either adhered to FN via beta1 integrins, stimulated with IL-6, or treated two combined. Although G(1)-S arrest associated adhesion was overcome when IL-6 added, adhesion-mediated...
Abstract Imatinib mesylate is a potent, molecularly targeted therapy against the oncogenic tyrosine kinase BCR-ABL. Although imatinib has considerable efficacy chronic myeloid leukemia (CML), advanced-stage CML patients frequently become refractory to this agent. The bone marrow predominant microenvironment of and rich source both soluble factors extracellular matrices, which may influence drug response. To address on sensitivity, we used an in vitro stroma model. Our data show culturing...
Abstract The importance of MCL-1 in leukemogenesis has prompted development antagonists e.g., S63845, MIK665. However, their effectiveness acute myeloid leukemia (AML) is limited by compensatory accumulation via the ubiquitin proteasome system. Here, we investigated mechanisms which kinase inhibitors with Src inhibitory activity bosutinib (SKI-606) might circumvent this phenomenon. antagonist/SKI-606 co-administration synergistically induced apoptosis diverse AML cell lines. Consistently, or...
The Fanconi anemia/BRCA (FA/BRCA) DNA damage repair pathway plays a pivotal role in the cellular response to replicative stress induced by alkylating agents and greatly influences drug cancer treatment. We recently reported that FA/BRCA genes are overexpressed causative for resistance human melphalan-resistant multiple myeloma cell lines. However, transcriptional regulation of is not understood. In this report, we describe first time novel function NF-kappaB subunits, RelB/p50, as activators...
Cyclin-dependent kinases (CDKs) are serine/threonine protein that act as key regulatory elements in cell cycle progression. We describe the development of highly potent diaminothiazole inhibitors CDK2 (IC50 = 0.0009-0.0015 μM) from a single hit compound with weak inhibitory activity 15 μM), discovered by high-throughput screening. Structure-based design was performed using 35 cocrystal structures liganded distinct analogues parent compound. The profiling 51 against panel 339 revealed high...
Abstract Cell adhesion to fibronectin is known confer a temporally related cell adhesion–mediated drug resistance (CAM-DR). However, it unknown whether during selection influences the more permanent form of acquired resistance. To examine this question, we compared acquisition mitoxantrone in U937 cells adhered versus selected traditional suspension culture. Our data show that levels are 2- 3-fold greater for with We also mechanism(s) associated fibronectin-adherent cultures. Drug both and...
Abstract Topoisomerase IIα (topo IIα) is exported from the nucleus of human myeloma cells by a CRM1-dependent mechanism at cellular densities similar to those found in patient bone marrow. When topo trafficked cytoplasm, it not contact with DNA; thus, inhibitors are unable induce DNA-cleavable complexes and cell death. Using CRM1 inhibitor or CRM1-specific small interfering RNA (siRNA), we were able block nuclear export as shown immunofluorescence microscopy. Human lines isolated marrow...
Multiple myeloma (MM) remains an incurable disease despite improved treatments, including lenalidomide/pomalidomide and bortezomib/carfilzomib based therapies high-dose chemotherapy with autologous stem cell rescue. New drug targets are needed to further improve treatment outcomes. Nuclear export of macromolecules is misregulated in many cancers, hematological malignancies such as MM. CRM1 (chromosome maintenance protein-1) a ubiquitous protein that exports large proteins (>40 kDa) from the...