A5035898667- Peptidase Inhibition and Analysis
- Multiple Myeloma Research and Treatments
- Protein Degradation and Inhibitors
- Histone Deacetylase Inhibitors Research
- Ubiquitin and proteasome pathways
- vaccines and immunoinformatics approaches
- Immunotherapy and Immune Responses
- Cancer Mechanisms and Therapy
- Autophagy in Disease and Therapy
- Chronic Myeloid Leukemia Treatments
- MicroRNA in disease regulation
- Chemokine receptors and signaling
- Myeloproliferative Neoplasms: Diagnosis and Treatment
- CAR-T cell therapy research
- Drug-Induced Adverse Reactions
- Immune Cell Function and Interaction
- Amyloidosis: Diagnosis, Treatment, Outcomes
- Chronic Lymphocytic Leukemia Research
- Cancer Treatment and Pharmacology
- Glycosylation and Glycoproteins Research
- Monoclonal and Polyclonal Antibodies Research
- Chemotherapy-related skin toxicity
- Endoplasmic Reticulum Stress and Disease
- Cancer Genomics and Diagnostics
- Cancer-related molecular mechanisms research
Case Western Reserve University
2017-2024
University Hospitals Seidman Cancer Center
2017-2024
Case Comprehensive Cancer Center
2022-2024
University Hospitals of Cleveland
2023-2024
University School
2021-2024
Mayo Clinic in Florida
2023
Dana-Farber Cancer Institute
2006-2023
São Germano Oncologia
2023
Universität Hamburg
2023
University Medical Center Hamburg-Eppendorf
2023
Mammalian cells contain two large proteolytic complexes, the 650-kDa proteasome (or multicatalytic protease) and 1500-kDa (26 S) Ubiquitin-conjugate-degrading enzyme. Since is also required for ATP-dependent degradation of ubiquitinated proteins, we tested whether it may be a component larger complex. The normally soluble in 38% ammonium sulfate. However, after preincubation reticulocyte extracts with ATP, several activities appeared sulfate pellet, including ability to degrade hydrophobic...
Eukaryotic cells contain a 700-kDa proteolytic complex (the "proteasome" or multicatalytic endopeptidase complex), whose role in intracellular protein breakdown is unclear. It has been suggested that the proteasome functions rapid degradation of oxidant-damaged proteins and ATP-dependent pathway. To test these possibilities, hemoglobin albumin were produced by treating with phenylhydrazine, hydroxyl radicals, both superoxide radicals. After oxidant damage, degraded more rapidly erythrocyte...
Although the therapeutic benefit of proteasome inhibition in multiple myeloma remains unchallenged, drug resistance inevitably emerges through mechanisms that remain elusive. Bortezomib provokes unwanted protein accumulation and endoplasmic reticulum stress to activate unfolded response (UPR) autophagy as compensatory restore homeostasis. High-throughput screens detect pharmacologics modulated enhance anti-myeloma effect bortezomib revealed metformin, a widely used antidiabetic agent with...
// Mohamed A.Y. Abdel Malek 1,2,3,* , Sajjeev Jagannathan 1,2,* Ehsan 1,2 Douaa M. Sayed 4 Sahar A. Elgammal 3 Hanan G. Abd El-Azeem Nabila Thabet and James J. Driscoll 1,2,5,6 1 The Vontz Center for Molecular Studies, University of Cincinnati College Medicine, Cincinnati, OH 2 Division Hematology Oncology, Department Clinical Pathology, Faculty Assiut University, Assiut, Egypt South Cancer Institute, 5 Biology, 6 * These authors contributed equally to this work Correspondence: Driscoll,...
Evading apoptosis is a cancer hallmark that remains serious obstacle in current treatment approaches. Although proteasome inhibitors (PIs) have transformed management of multiple myeloma (MM), drug resistance emerges through induction the aggresome+autophagy pathway as compensatory protein clearance mechanism. Genome-wide profiling identified microRNAs (miRs) differentially expressed bortezomib-resistant cells compared with drug-naive cells. The effect individual miRs on proteasomal...
Proteasome inhibitor–based strategies hold promise in transplant but have yielded varying results. Carfilzomib, a second-generation proteasome inhibitor, may possess advantages over bortezomib, the first-generation inhibitors. The purpose of this study was to evaluate safety, toxicity, and preliminary efficacy carfilzomib highly HLA-sensitized kidney candidates. Renal candidates received escalating doses followed by plasmapheresis (group A) or an identical regimen with additional once weekly...
The proteasome (the multicatalytic endoproteinase complex) in mammalian tissues hydrolyzes proteins and several types of peptides. When this structure was isolated rapidly from rabbit skeletal muscle the presence glycerol, its various peptidase protease activities showed a large reversible activation by physiological concentrations ATP (Ka = 0.3-0.5 mM). Hydrolysis succinyl-Leu-Leu-Val-Tyr-(4-methylcoumaryl-7-amide) stimulated up to 12-fold ATP, whereas degradation casein bovine serum...
While clinical benefit of the proteasome inhibitor (PI) bortezomib (BTZ) for multiple myeloma (MM) patients remains unchallenged, dose-limiting toxicities and drug resistance limit long-term utility. The E3 ubiquitin ligase Skp1–Cullin-1–Skp2 (SCFSkp2) promotes proteasomal degradation cell cycle p27 to enhance tumor growth. Increased SKP2 expression reduced levels are frequent in human cancers associated with therapeutic resistance. SCFSkp2 activity is increased by Cullin-1-binding protein...
Functional blockade of the transforming growth factor-beta (TGFβ) signalling pathway improves efficacy cytotoxic and immunotherapies. Here, we conducted a phase 1b study (ClinicalTrials.gov., NCT03143985) to determine primary endpoints safety, tolerability, maximal tolerated dose (200 mg twice daily) for orally-available TGFβ type I receptor kinase inhibitor vactosertib in combination with pomalidomide relapsed and/or refractory multiple myeloma (RRMM) patients who had received ≥2 lines...
Cytotoxic T lymphocytes (CTL) recognize antigenic peptides bound to major histocompatibility complex class I antigens on the cell surface of virus-infected cells. It is believed that majority originate from cytoplasmic degradation proteins assumed be mediated by "20S" proteasome. Cytosolic are then translocated, presumably transporters associated with antigen processing (TAP-1 and -2), into lumen endoplasmic reticulum (ER) where binding formation ternary between heavy chain,...
Purpose . The antitumor activity of a novel alginate (ALG) polymer-based particle that contained paclitaxel (PTX) was evaluated using human primary breast cancer cells. Materials and Methods PTX combined with ALG in nanoparticle as drug delivery system designed to improve tumor cell killing. PTX-ALG nanoparticles were first synthesized by nanoemulsification polymer cross-linking methods improved the aqueous solubility. Structural biophysical properties then determined transmission electron...