A5044701059- Tissue Engineering and Regenerative Medicine
- Epigenetics and DNA Methylation
- Immune cells in cancer
- Acute Myeloid Leukemia Research
- Bladder and Urothelial Cancer Treatments
- Research on Leishmaniasis Studies
- Caveolin-1 and cellular processes
- Endoplasmic Reticulum Stress and Disease
- Microtubule and mitosis dynamics
- Cell Adhesion Molecules Research
- Amino Acid Enzymes and Metabolism
- Cancer, Hypoxia, and Metabolism
- Biochemical and Molecular Research
- Fibroblast Growth Factor Research
- Cancer, Lipids, and Metabolism
- Protein Degradation and Inhibitors
- RNA Research and Splicing
- Myeloproliferative Neoplasms: Diagnosis and Treatment
- Multiple Myeloma Research and Treatments
- Inflammatory mediators and NSAID effects
- RNA modifications and cancer
- Prostate Cancer Treatment and Research
- Photosynthetic Processes and Mechanisms
- Blood disorders and treatments
- Immunotherapy and Immune Responses
Cleveland Clinic
2016-2025
Case Comprehensive Cancer Center
2024
Cancer Institute (WIA)
2021-2023
Cleveland Clinic Lerner College of Medicine
2015
Millennium Engineering and Integration (United States)
2013
Van Andel Institute
2013
Cerner (United States)
2013
Kidney Centre
2013
Here, we show that apolipoprotein A1 (apoA1), the major protein component of high density lipoprotein (HDL), through both innate and adaptive immune processes, potently suppresses tumor growth metastasis in multiple animal models, including aggressive B16F10L murine malignant melanoma model. Mice expressing human apoA1 transgene (A1Tg) exhibited increased infiltration CD11b+ F4/80+ macrophages with M1, anti-tumor phenotype, reduced burden metastasis, enhanced survival. In contrast,...
Multiple myeloma cells secrete more disulfide bond-rich proteins than any other mammalian cell. Thus, inhibition of protein isomerases (PDI) required for folding in the endoplasmic reticulum (ER) should increase ER stress beyond repair this incurable cancer. Here, we report mechanistically unbiased discovery a novel PDI-inhibiting compound with antimyeloma activity. We screened 30,355 small-molecule library using multilayered multiple cell-based cytotoxicity assay that modeled disease niche,...
Despite more than 70,000 new cases of bladder cancer in the United States annually, patients with advanced disease have a poor prognosis due to limited treatment modalities. We evaluated Aurora kinase A, identified as an upregulated candidate molecule cancer, potential therapeutic target.Gene expression human samples was using RNA microarray and quantitative reverse transcriptase PCR. Effects A inhibitor MLN8237 (Millennium) on cell dynamics malignant T24 UM-UC-3 papilloma-derived RT4 cells...
Effective targeting of cancer stem cells (CSCs) requires neutralization self-renewal and chemoresistance, but these phenotypes are often regulated by distinct molecular mechanisms. Here we report the ability to target both via CD55, an intrinsic cell surface complement inhibitor, which was identified in a comparative analysis between CSCs non-CSCs endometrioid models. In this context, CD55 functions complement-independent manner required lipid raft localization for CSC maintenance cisplatin...
Abstract Interplay between tumor cells and host in the microenvironment dictates development of all cancers. In breast cancer, malignant educate macrophages to adopt a protumorigenic phenotype. this study, we show how integrin-regulatory protein kindlin-2 (FERMT2) promotes metastatic progression cancer through recruitment subversion macrophages. Kindlin-2 expression was elevated biopsy tissues where its levels correlated with reduced patient survival. On basis these observations, used...
Abstract Disruption of KDM6A, a histone lysine demethylase, is one the most common somatic alternations in bladder cancer. Insights into how KDM6A mutations affect epigenetic landscape to promote carcinogenesis could help reveal potential new treatment approaches. Here, we demonstrated that loss triggers an switch disrupts urothelial differentiation and induces neoplastic state characterized by increased cell proliferation. In cancer cells with intact FOXA1 interacted activate genes...
Abstract Docetaxel chemotherapy remains a standard of care for metastatic castration-resistant prostate cancer (CRPC). modestly increases survival, yet results in frequent occurrence side effects and resistant disease. An alternate with greater efficacy minimal is needed. Acquisition metabolic aberrations promoting increased survival metastasis CRPC cells includes constitutive activation Akt, loss adenosine monophosphate-activated protein kinase (AMPK) activity due to Ser-485/491...
Abstract TET2 is frequently mutated in myeloid neoplasms. Genetic deficiency leads to skewed differentiation and clonal expansion, but minimal residual TET activity critical for survival of neoplastic progenitor stem cells. Consistent with mutual exclusivity neomorphic IDH1/2 mutations, here we report that mutant–derived 2-hydroxyglutarate synthetically lethal dioxygenase–deficient In addition, a TET-selective small-molecule inhibitor decreases cytosine hydroxymethylation restricted...
Renal cell carcinoma (RCC) patients treated with tyrosine kinase inhibitors (TKI) typically respond initially, but usually develop resistance to therapy. We utilised transcriptome analysis identify gene expression changes during development of sunitinib in a RCC patient-derived xenograft (PDX) model. tumours were harvested pre-treatment, response and escape phases. Direct anti-proliferative effects plus MEK inhibitor assessed. Activation status (phosphorylation) MEK1/2 ERK1/2 was determined,...
Eltrombopag, an FDA-approved non-peptidyl thrombopoietin receptor agonist, is clinically used for the treatment of aplastic anemia, a disease characterized by hematopoietic stem cell failure and pancytopenia, to improve platelet counts function. Eltrombopag results in durable trilineage expansion patients. Some eltrombopag activity has been attributed its off-target effects, including iron chelation properties. However, mechanism action full spectrum clinical effects still poorly understood....
// Shuvojit Banerjee 1 , Geqiang Li 1, * Yize 2 Christina Gaughan Danika Baskar Yvonne Parker 3 Daniel J. Lindner Susan R. Weiss Robert H. Silverman Department of Cancer Biology, Lerner Research Institute, Cleveland Clinic, Cleveland, Ohio, USA Microbiology, Perelman School Medicine, University Pennsylvania, Philadelphia, Translational Hematology and Oncology Research,Taussig Current address: Abpro, 65 Cummings Park Drive, Woburn, MA Correspondence to: Silverman, e-mail: silverr@ccf.org...
Abstract Background: Approximately 15% of high-grade TP53-mutated endometrial cancers (EC) are heterozygous and retain wild-type (WT) signaling. Our previous in vitro findings nominated MDM2 inhibitors as potential radio-sensitizing strategies that leverage TP53 WT Here, we further explore this role for one particular inhibitor, AMG-232, an vivo xenograft model with a EC cell line. Methods: To evaluate the AMG-232 vivo, utilized tumor JHUEM-2 (TP53 WT) Cells (2x106) were injected...
The presence of somatic mutations in splicing factor 3b subunit 1 (SF3B1) patients with Myelodysplastic syndromes ring sideroblasts (MDS-RS) highlights the importance RNA-splicing machinery MDS. We previously reported bone marrow (BM) RS Sf3b1 heterozygous (Sf3b1 (+/-)) mice which are rarely found mouse models (+/-) were originally engineered to study interaction between polycomb genes and other proteins.We used routine blood tests histopathologic analysis BM, spleen, liver evaluate...
ABSTRACT Effective targeting of cancer stem cells (CSCs) requires neutralization self-renewal and chemoresistance, however these phenotypes are often regulated by distinct molecular mechanisms. Here we report the ability to target both via CD55, an intrinsic cell surface complement inhibitor, which was identified in a comparative analysis between CSCs non-CSCs endometrioid models. In this context, CD55 functions complement-independent manner required lipid raft localization for CSC...
Multiple myeloma is a genetically complex hematologic neoplasia in which malignant plasma cells constantly operate at the maximum limit of their unfolded protein response (UPR) due to high secretory burden immunoglobulins and cytokines. The endoplasmic reticulum (ER) resident disulfide isomerase, PDIA1 indispensable for maintaining structural integrity cysteine-rich antibodies cytokines that require accurate intramolecular bond arrangement. expression analysis from RNA-seq multiple patients...
PBRM1, a subunit of the PBAF coactivator complex that transcription factors use to activate target genes, is genetically inactivated in almost all clear cell renal cancers (RCCs). Using unbiased proteomic analyses, we find PAX8, master factor driver proximal tubule epithelial fates, recruits PBRM1/PBAF. Reverse analyses PAX8 interactome confirm recruitment specifically PBRM1/PBAF and not functionally similar BAF. More conspicuous hub RCC cells, however, are corepressors, which oppose...
Graft-versus-host disease (GVHD) is a prevalent and potentially lethal complication of hematopoietic stem cell transplantation. Humanized mouse models xenogeneic GVHD are important tools used to study the human immune response in vivo. Here we NOD-scid IL-2Rynull mice (NSG) transplanted with bone marrow cells evaluate role engraftment production acute GVHD. PRO 140, humanized monoclonal antibody targeting chemokine receptor, CCR5, was its influence on modulation We evaluated kinetics by...
Intermediate and high-risk rhabdomyosarcoma (RMS) patients have poor prognosis with available treatment options, highlighting a clear unmet need for identification of novel therapeutic strategies. Ezrin-radixin-moesin (ERM) family members are membrane-cytoskeleton linker proteins well-defined roles in tumor metastasis, growth, survival. ERM protein activity is regulated by dynamic changes the phosphorylation at conserved threonine residue their C-terminal actin-binding domain. Interestingly,...
Abstract Small cell lung cancer (SCLC) is characterised by high relapse rates. Tumour-initiating cells (TICs) are responsible for drug resistance and recurrence of cancer. Rovalpituzumab tesirine (Rova-T), a potent humanised antibody–drug conjugate, selectively targets delta-like protein 3, which highly expressed in SCLC TICs. The experimental CBL0137 (CBL) inhibits the histone chaperone FACT (facilitates chromatin transcription), required expression transcription factors that essential TIC...
e16507 Background: BC is heterogeneous and associated with high recurrence rate after definitive treatment. Biomarkers to help select patients muscle invasive appropriate for organ preservation chemoradiation are needed. Methods: We characterized 20 primary cell lines, all verified by genomic fingerprinting. Molecular characterization of lines has been reported, including mutation analysis, CNA (high density SNP arrays) gene expression (RNAseq). performed radiosensitivity screening using 2...