A5030355011- Cancer Immunotherapy and Biomarkers
- Parathyroid Disorders and Treatments
- Oral and gingival health research
- Protein Degradation and Inhibitors
- Melanoma and MAPK Pathways
- Chronic Kidney Disease and Diabetes
- CAR-T cell therapy research
- Immunotherapy and Immune Responses
- Immune Cell Function and Interaction
- Microtubule and mitosis dynamics
- Epigenetics and DNA Methylation
- Biotin and Related Studies
- Autophagy in Disease and Therapy
- Cell Adhesion Molecules Research
- Nuclear Structure and Function
- PARP inhibition in cancer therapy
- Caveolin-1 and cellular processes
- Cancer-related molecular mechanisms research
- Fibroblast Growth Factor Research
- Cutaneous Melanoma Detection and Management
- T-cell and B-cell Immunology
- Pluripotent Stem Cells Research
- Ubiquitin and proteasome pathways
- Genomics and Chromatin Dynamics
- Sirtuins and Resveratrol in Medicine
Albany Medical Center Hospital
2020-2021
The Wistar Institute
2015-2020
University of the Sciences
2016-2020
Abstract Purpose: We have shown that the aged microenvironment increases melanoma metastasis, and decreases response to targeted therapy, here we queried anti-PD1. Experimental Design: analyzed relationship between age, anti-PD1, prior therapy in 538 patients. used mouse models of melanoma, analyze intratumoral immune young versus mice confirmed our findings human biopsies. Results: Patients over age 60 responded more efficiently anti-PD-1, likelihood anti-PD-1 increased with even when...
The programmed cell death protein 1 (PD-1) limits effector T-cell functions in peripheral tissues, and its inhibition leads to clinical benefit different cancers. To better understand how PD-1 blockade therapy modulates the tumor-host interactions, we evaluated three syngeneic murine tumor models, BRAFV600E-driven YUMM1.1 YUMM2.1 melanomas, carcinogen-induced colon adenocarcinoma MC38. YUMM lines were established from mice with melanocyte-specific BRAFV600E mutation PTEN loss...
Abstract Older patients with melanoma have lower rates of sentinel lymph node (LN) metastases yet paradoxically inferior survival. Patient age correlated an inability to retain Technetium radiotracer during LN biopsy in more than 1,000 patients, and high counts better We hypothesized that loss integrity the lymphatic vasculature due extracellular matrix (ECM) degradation might play a role. implicated HAPLN1 age-dependent ECM dermis. Here, we queried whether could be altered ECM. Lymphatic...
Melanoma accounts for only 5% of all cancers but is the leading cause skin cancer death due to its high metastatic potential. Patients with melanoma have a 10-year survival rate less than 10%. While clinical landscape evolving rapidly, lack response therapies, as well resistance therapy remain critical obstacles treatment this disease. In recent years, myriad mechanisms been unravelled, one which autophagy, focus review. advanced stages malignancy, cells hijack autophagy machinery in order...
Abstract Autophagy mediates resistance to various anticancer agents. In melanoma, targeted therapy has been linked expression of Wnt5A, an intrinsic inhibitor β-catenin, which also promotes invasion. this study, we assessed the interplay between Wnt5A and autophagy by combining studies in human clinical biopsies with functional analyses cell lines mouse models. Melanoma cells high low β-catenin displayed increased basal autophagy. Genetic blockade revealed unexpected feedback loop whereby...
Abstract Purpose: Aging is a poor prognostic factor for melanoma. We have shown that melanoma cells in an aged microenvironment are more resistant to targeted therapy than identical young microenvironment. This dependent on age-related secreted factors. Klotho protein whose serum levels decrease dramatically by age 40. Most studies klotho cancer focused the expression of tumor cell. exogenous inhibits internalization and signaling Wnt5A, which drives metastasis resistance therapy....
Integrin α3β1, a cell adhesion receptor for certain laminins, is known to promote breast tumor growth and invasion. Our previous gene microarray study showed that the RELN gene, which encodes extracellular glycoprotein Reelin, was upregulated in α3β1-deficient (i.e., α3 knockdown) MDA-MB-231 cells. In cancer, reduced expression associated with increased invasion poor prognosis. this we demonstrate α3β1 represses enhance cancer mRNA significantly upon RNAi-mediated knockdown two...
In the current study, we demonstrate that integrin α3β1 promotes invasive and metastatic traits of triple-negative breast cancer (TNBC) cells through induction transcription factor, Brain-2 (Brn-2). We show RNAi-mediated suppression in MDA-MB-231 caused reduced expression Brn-2 mRNA protein activity BRN2 gene promoter. addition, RNAi-targeting decreased invasion vitro lung colonization vivo, exogenous partially restored to which was suppressed. promoted phosphorylation Akt cells, treatment...
Werner syndrome (WS) is an autosomal recessive disorder, the hallmarks of which are premature aging and early onset neoplastic diseases (Orren, 2006; Bohr, 2008). The gene, whose mutation underlies WS phenotype, called WRN. protein encoded by WRN WRNp, has DNA helicase activity (Gray et al., 1997; Orren, 2008; Opresko, Extensive evidence suggests that WRNp plays a role in replication repair (Chen 2003; Hickson, Turaga 2007; However, function not yet fully understood. In this study, we show...
Integrin receptors for the extracellular matrix play critical roles at all stages of carcinogenesis, including tumor growth, progression and metastasis. The laminin-binding integrin α3β1 is expressed in epithelial tissues where it has important cell survival, migration, proliferation, gene expression programs during normal pathological tissue remodeling. signaling adhesion functions promote growth metastasis a number different types cancer cells. Previously, we used RNA interference (RNAi)...
HIV-1-based vectors are widely used in gene therapy. In somatic cells, these mainly integrate within genes. However, no distinct integration site preferences have been observed with regard to large chromosomal regions. The recent emergence of induced pluripotent stem (iPS) similar embryonic (ES) has raised questions about where occurs cells. this work we investigated the a pluripotent, ES-like cell line. We show that approximately 30% integrations occur vicinity telomeres. analyzed sites...
Abstract Melanoma is the most aggressive type of skin cancer and leading cause death from disease. With increasing incidence disease, it crucial to further investigate cellular mechanisms molecular pathways that lead invasion, metastasis, drug resistance. Recent studies have revealed high autophagy correlates with melanoma tumor aggressiveness poor survival in clinical samples, as a common mechanism resistance therapy. Autophagy inhibition leads reduced levels Wnt5A breast model, suggesting...
Abstract Melanoma is an aggressive disease. Although about 13% of melanoma cases are diagnosed at metastatic stage, the 5-year survival rate for these patients 16%. We have previously shown that cells express high levels Wnt5a. Wnt5a a member Wnt family proteins, which play important role during development and tumorigenesis. In melanoma, signaling mediated by autocrine loop also modulates activity midkine. Midkine 16kDa protein elevated in many different cancers. Overexpression midkine...
<p>PDF containing all supplementary figures. Supplementary Figure Legends. Supplemental 1. A, graph indicating the number of patients for which best response data to pembrolizumab was obtained, and from institution. B, various groups treated with pembrolizumab, separated by gender, using 62 years age as most statistically significant cut-off. 2. B Change in mouse weight on final day experiment start female male mice bearing BSC9AJ2 tumors, after treatment 3 doses 300µg rat IgG2AK (N=5)...
<p>Figure Legends for Supplemental Data</p>
<div>Abstract<p><b>Purpose:</b> We have shown that the aged microenvironment increases melanoma metastasis, and decreases response to targeted therapy, here we queried anti-PD1.</p><p><b>Experimental Design:</b> analyzed relationship between age, anti-PD1, prior therapy in 538 patients. used mouse models of melanoma, analyze intratumoral immune young versus mice confirmed our findings human...
<p>Figure Legends for Supplemental Data</p>
<div>Abstract<p><b>Purpose:</b> We have shown that the aged microenvironment increases melanoma metastasis, and decreases response to targeted therapy, here we queried anti-PD1.</p><p><b>Experimental Design:</b> analyzed relationship between age, anti-PD1, prior therapy in 538 patients. used mouse models of melanoma, analyze intratumoral immune young versus mice confirmed our findings human...
<p>PDF containing all supplementary figures. Supplementary Figure Legends. Supplemental 1. A, graph indicating the number of patients for which best response data to pembrolizumab was obtained, and from institution. B, various groups treated with pembrolizumab, separated by gender, using 62 years age as most statistically significant cut-off. 2. B Change in mouse weight on final day experiment start female male mice bearing BSC9AJ2 tumors, after treatment 3 doses 300µg rat IgG2AK (N=5)...