A5012867231- Peptidase Inhibition and Analysis
- Histone Deacetylase Inhibitors Research
- Protein Degradation and Inhibitors
- Cancer-related gene regulation
- Ubiquitin and proteasome pathways
- Multiple Myeloma Research and Treatments
- vaccines and immunoinformatics approaches
- RNA Interference and Gene Delivery
- Carbohydrate Chemistry and Synthesis
- Acute Myeloid Leukemia Research
- Immunotherapy and Immune Responses
- CAR-T cell therapy research
- Cancer Mechanisms and Therapy
- Retinoids in leukemia and cellular processes
- Cancer Immunotherapy and Biomarkers
- Chemokine receptors and signaling
- Chronic Myeloid Leukemia Treatments
- Immune Cell Function and Interaction
- NF-κB Signaling Pathways
- Bladder and Urothelial Cancer Treatments
- Click Chemistry and Applications
- Epigenetics and DNA Methylation
- Genomics and Chromatin Dynamics
- Melanoma and MAPK Pathways
- Nuclear Receptors and Signaling
University Hospitals Seidman Cancer Center
2021-2025
Case Western Reserve University
2014-2025
University Hospitals of Cleveland
2022-2024
University School
2016-2024
Case Comprehensive Cancer Center
2023-2024
Dana-Farber Cancer Institute
2023
Harvard University
2023
São Germano Oncologia
2023
University Hospital Foundation
2023
Universität Hamburg
2023
Inflammatory bowel disease (IBD) is characterized by damage to the gut mucosa and systemic inflammation. We sought evaluate role of chronic inflammation on circulating T-cell activation in human subjects with Crohn's ulcerative colitis. studied 54 patients IBD 28 healthy controls. cycling were assessed whole blood samples flow cytometry. Levels lipopolysaccharide (LPS) measured serum Limulus amoebocyte lysate assay, plasma levels inflammatory markers LPS-binding proteins ELISA. The...
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...
1,25-dihydroxyvitamin D3 (1,25D), the biologically active form of vitamin D, is widely considered a promising therapy for acute myeloid leukemia (AML) based on its ability to drive differentiation leukemic cells. However, clinical trials have been disappointing in part dose-limiting hypercalcemia. Here we show how inhibiting glycogen synthase kinase 3 (GSK3) can improve response AML cells 1,25D-mediated differentiation. GSK3 inhibition enhanced differentiating effects low concentrations...
Standard therapies used for the treatment of acute myeloid leukemia (AML) are cytotoxic agents that target rapidly proliferating cells. Unfortunately, this therapeutic approach has limited efficacy and significant toxicity majority AML patients still die their disease. In contrast to poor prognosis most patients, individuals with a rare subtype AML, promyelocytic leukemia, can be cured by differentiation therapy using regimens containing all-trans retinoic acid. GSK3 been previously...
Proteasomes degrade intracellular proteins to generate antigenic peptides that are recognized by the adaptive immune system and promote anticancer immunity. However, tumors subvert antigen presentation machinery escape immunosurveillance. We hypothesized proteasome activation could concomitantly increase abundance diversity in multiple myeloma cells. High-throughput screens revealed histone deacetylase 6 (HDAC6) inhibitors activated proteasomes unmask neoantigens amplify tumor-specific...
Urothelial cell carcinoma (UCC, bladder cancer) remains a difficult to treat malignancy with rising incidence worldwide. In the U.S., UCC is sixth most incident neoplasm and ~90% of diagnoses are made in those >55 years age, ~four times more commonly observed men than women. The important risk factor for developing cancer tobacco smoking, which accounts ∼50% cases followed by occupational exposure aromatic amines ionizing radiation. standard care advanced includes platinum-based...
ABSTRACT Recently, a new lineage of CD4 + T cells in humans and mice has been reported. This helper cell secretes interleukin-17 (IL-17) defined as 17 (Th17). Th17 express the IL-23 receptor (IL-23R) play an important pathogenic role different inflammatory conditions. In this study, our aim was to characterize optimum conditions for isolation propagation human peripheral blood vitro clones. To isolate cells, two steps were taken. Initially, we negatively isolated from mononuclear normal...
Proteasomes generate antigenic peptides that are presented on the tumor surface to cytotoxic T-lymphocytes. Immunoproteasomes highly specialized proteasome variants expressed at higher levels in antigen-presenting cells and contain replacements of three constitutive catalytic subunits with a hydrophobic C-terminus fit within groove MHC class I (MHC-I) molecules. A hallmark cancer is ability evade immunosurveillance by disrupting antigen presentation machinery downregulating MHC-I...
Glycogen synthase kinase-3 (GSK3) inhibitors induce differentiation and growth inhibition of acute myeloid leukemia (AML) cells. Our pre-clinical studies showed GSK3 leads to sensitization AML cells tretinoin-mediated differentiation. We conducted a phase I trial lithium, inhibitor, plus tretinoin for relapsed, refractory non-promyelocytic AML. Nine patients with median (range) age 65 (42-82) years were enrolled. All subjects had relapsed after prior therapy, 3 (1-3) therapies. Oral lithium...
Functional blockade of the transforming growth factor-beta (TGF-β) signaling pathway improves efficacy cytotoxic and immunotherapies. We conducted a phase 1b study to determine safety, efficacy, maximal tolerated dose (200 mg po bid) potent, orally-available TGF-β type I receptor kinase inhibitor vactosertib in relapsed and/or refractory multiple myeloma patients who had received ≥2 lines chemoimmunotherapy. Vactosertib combined with pomalidomide was well-tolerated at all doses, manageable...
Abstract A hallmark of cancer is the ability to evade immunosurveillance mechanisms and thwart efficacy immunotherapeutic agents. The proteasome functions as an essential component by generating peptides from intracellular proteins that are then presented T-cells. Antigens generated promote infiltration immune cells into tumors improve tumor regression in response immunotherapy. Cancer can elimination system deregulating antigen presentation machinery downregulate expression recognized...
7557 Background: Despite significant therapeutic advancements, Multiple Myeloma (MM) remains an incurable disease. Autologous stem cell transplantation (ASCT) is a standard treatment for eligible patients, with high-dose melphalan (MEL200) as the preferred conditioning regimen. Reduced-dose (MEL140) used older or less fit patients. However, this was not prospectively studied and there has been ongoing debate about efficacy of reduced dosing. This study aimed to investigate impact dose on...