A5006339979- Cancer-related Molecular Pathways
- Prostate Cancer Treatment and Research
- Advanced Breast Cancer Therapies
- Epigenetics and DNA Methylation
- Cancer Genomics and Diagnostics
- Cancer Mechanisms and Therapy
- Cytokine Signaling Pathways and Interactions
- Cell Adhesion Molecules Research
- Immunotherapy and Immune Responses
- RNA modifications and cancer
- Ocular Oncology and Treatments
- Ubiquitin and proteasome pathways
- RNA Research and Splicing
- Mechanisms of cancer metastasis
- Cancer, Hypoxia, and Metabolism
- Cancer-related molecular mechanisms research
- Peptidase Inhibition and Analysis
- Cancer Cells and Metastasis
- Cancer, Lipids, and Metabolism
- Estrogen and related hormone effects
- Protein Degradation and Inhibitors
- Cancer Research and Treatments
- Protease and Inhibitor Mechanisms
- Radiopharmaceutical Chemistry and Applications
- Lung Cancer Treatments and Mutations
Thomas Jefferson University
2014-2024
Sidney Kimmel Cancer Center
2013-2023
Thomas Jefferson University Hospital
2015-2022
Philadelphia University
2010-2015
Molecular Oncology (United States)
2013
Huazhong University of Science and Technology
2013
Tongji Hospital
2013
University of Manchester
2013
Drexel University
2013
The University of Texas Southwestern Medical Center
2013
Human blood platelets are essential to maintaining normal hemostasis, and platelet dysfunction often causes bleeding or thrombosis. Estimates of genome-wide RNA expression using microarrays have provided insights the transcriptome but were limited by number known transcripts. The goal this effort was deep-sequence from leukocyte-depleted capture complex profile all expressed From each four healthy individuals we generated long (≥40 nucleotides) profiles total ribosomal-RNA depleted...
Recently, we proposed a new mechanism for understanding the Warburg effect in cancer metabolism. In this paradigm, cancer-associated fibroblasts undergo aerobic glycolysis, and extrude lactate to “feed” adjacent cells, which then drives mitochondrial biogenesis oxidative metabolism cells. Thus, there is vectorial transport of energy-rich substrates from fibroblastic tumor stroma anabolic A prediction hypothesis that should express MCT4, mono-carboxylate transporter has been implicated efflux...
Previously, we showed that high-energy metabolites (lactate and ketones) “fuel” tumor growth experimental metastasis in an vivo xenograft model, most likely by driving oxidative mitochondrial metabolism breast cancer cells. To mechanistically understand how these affect cell behavior, here used genome-wide transcriptional profiling. Briefly, human cells (MCF7) were cultured with lactate or ketones, then subjected to analysis (exon-array). Interestingly, our results show treatment increases...
Retinoblastoma (RB; encoded by RB1) is a tumor suppressor that frequently disrupted in tumorigenesis and acts multiple cell types to suppress cycle progression. The role of RB progression, however, poorly defined. Here, we have identified critical for protecting against progression through regulation targets distinct from control. In analyses human prostate cancer samples, loss was infrequently observed primary disease predominantly associated with transition the incurable,...
Summary Macrophage-derived exosomes attenuated complete Freund's adjuvant-induced thermal hyperalgesia in mice. Exosomal microRNA signature from patients with complex regional pain syndrome suggests a potential therapeutic and biomarker utility for exosomes. Exosomes, secreted microvesicles transporting microRNAs (miRNAs), mRNAs, proteins through bodily fluids, facilitate intercellular communication elicit immune responses. contents vary, depending on the source physiological conditions of...
The majority of estrogen receptor (ER)-positive breast cancers are treated with endocrine therapy. While this is effective, acquired resistance to therapies targeted against ER a major clinical challenge. Here, model systems ER-positive differential susceptibility therapy were employed define common nodes for new therapeutic interventions. These analyses revealed that cell cycle progression effectively uncoupled from the activity and functional state in these models. In context, cyclin D1...
We have recently proposed a new mechanism for explaining energy transfer in cancer metabolism. In this scenario, cells behave as metabolic parasites, by extracting nutrients from normal host cells, such fibroblasts, via the secretion of hydrogen peroxide initial trigger. Oxidative stress tumor microenvironment then leads to autophagy-driven catabolism, mitochondrial dys-function, and aerobic glycolysis. This, turn, produces high-energy (such L-lactate, ketones, glutamine) that drive anabolic...
The roles of the chemokine CCL5 and its receptor CCR5 in breast cancer progression remain unclear. Here, we conducted microarray analysis on 2,254 human specimens found increased expression CCR5, but not CCR3, basal HER-2 genetic subtypes. subpopulation cell lines to express displayed a functional response CCL5. In addition, oncogene transformation induced expression, cells that expressed also invasiveness. antagonists maraviroc or vicriviroc, developed block HIV coreceptor function, reduced...
The mechanisms underlying adaptive resistance of melanoma to targeted therapies remain unclear. By combining ChIP sequencing with microarray-based gene profiling, we determined that ERBB3 is upregulated by FOXD3, a transcription factor promotes RAF inhibitors in melanoma. Enhanced signaling promoted pathway cultured cell lines and mouse xenograft models. was dependent on ERBB2; targeting ERBB2 lapatinib combination the inhibitor PLX4720 reduced tumor burden extended latency regrowth vivo...
In breast cancer, inactivation of the RB tumor suppressor gene is believed to occur via multiple mechanisms facilitate tumorigenesis. However, prognostic and predictive value status in disease-specific clinical outcomes has remained uncertain. We investigated pathway deregulation context both ER-positive ER-negative disease using combined microarray datasets encompassing over 900 cancer patient samples. Disease-specific characteristics were this dataset by evaluating correlation among genes...
Anti-PD-1 immunotherapy is the standard of care for treating many patients with non-small cell lung cancer (NSCLC), yet mechanisms treatment failure are emerging. We present a case NSCLC, who rapidly progressed during trial (NCT02318771) combining palliative radiotherapy and pembrolizumab. Planned tumor biopsy demonstrated PD-1 expression by NSCLC cells. validated this observation detecting transcript in cells co-localizing cancer-specific markers resected tissues. further investigated...
Chromosomal instability (CIN) in tumors is characterized by chromosomal abnormalities and an altered gene expression signature; however, the mechanism of CIN poorly understood. CCND1 (which encodes cyclin D1) overexpressed human malignancies has been shown to play a direct role transcriptional regulation. Here, we used genome-wide ChIP sequencing found that DNA-bound form D1 occupied regulatory region genes governing integrity mitochondrial biogenesis. Adding back Ccnd1–/– mouse embryonic...
Abstract The Drosophila Eyes Absent Homologue 1 (EYA1) is a component of the retinal determination gene network and serves as an H2AX phosphatase. cyclin D1 encodes regulatory subunits holoenzyme that phosphorylates inactivates pRb protein. Herein, comparison with normal breast showed EYA1 overexpressed in luminal B cancer subtype. enhanced tumor growth mice vivo, requiring phosphatase domain. cellular proliferation, inhibited apoptosis, induced contact-independent abundance. induction...
Abstract RB loss occurs commonly in neoplasia but its contributions to advanced cancer have not been assessed directly. Here we show that multiple murine models of produces a prometastatic phenotype. Gene expression analyses showed regulation the cell motility receptor RHAMM by RB/E2F pathway was critical for epithelial–mesenchymal transition, motility, and invasion cells. Genetic modulation or pharmacologic inhibition activity sufficient necessary metastatic phenotypes induced prostate...
Breast cancer progression and metastasis are driven by complex reciprocal interactions, between epithelial cells their surrounding stromal microenvironment. We have previously shown that a loss of Cav-1 expression is associated with an increased risk early tumor recurrence, decreased overall survival. To identify characterize the signaling pathways activated in negative stroma, we performed gene profiling using laser microdissected breast cancer-associated stroma. Tumor stroma was capture...
Abstract The epithelial–mesenchymal transition (EMT) enhances cellular invasiveness and confers tumor cells with cancer stem cell–like characteristics, through transcriptional translational mechanisms. mechanisms maintaining repression of EMT invasion are poorly understood. Herein, the cell fate determination factor Dachshund (DACH1), suppressed via cytoplasmic induction Snail by inactivating Y box–binding protein (YB-1). In nucleus, DACH1 antagonized YB-1–mediated oncogenic modules...
Abstract Src family kinases (SFK) integrate signal transduction for multiple receptors, regulating cellular proliferation, invasion, and metastasis in human cancer. Although is rarely mutated prostate cancer, SFK activity increased the majority of cancers. To determine molecular mechanisms governing cancer bone metastasis, FVB murine epithelium was transduced with oncogenic v-Src. The cell lines metastasized mice to brain bone. Gene expression profiling tumors identified activation a CCR5...
Abstract Targeting cyclin-dependent kinases 4/6 (CDK4/6) represents a therapeutic option in combination with BRAF inhibitor and/or MEK (MEKi) melanoma; however, continuous dosing elicits toxicities patients. Using quantitative and temporal vivo reporting, we show that MEKi intermittent CDK4/6 (CDK4/6i) led to more complete tumor responses versus other schedules. Nevertheless, some tumors acquired resistance was associated enhanced phosphorylation of ribosomal S6 protein. These data were...
Metastatic prostate cancer (PCa) inevitably acquires resistance to standard therapy preceding lethality. Here, we unveil a chromosomal instability (CIN) tolerance mechanism as therapeutic vulnerability of therapy-refractory lethal PCa. Through genomic and transcriptomic analysis patient datasets, find that castration chemotherapy-resistant tumors display the highest CIN mitotic kinase levels. Functional genomics screening coupled with quantitative phosphoproteomics identify MASTL survival...
Abstract Introduction Signal transducer and activator of transcripton-5a (Stat5a) its close homologue, Stat5b, mediate key physiological effects prolactin growth hormone in mammary glands. In breast cancer, loss nuclear localized tyrosine phosphorylated Stat5a/b is associated with poor prognosis increased risk antiestrogen therapy failure. Here we quantify for the first time levels Stat5a Stat5b over cancer progression, explore their potential association clinical outcome. Methods protein...
Abstract Purpose: We sought to determine whether dysregulation of the retinoblastoma (RB) tumor suppressor pathway was associated with improved response neoadjuvant chemotherapy in breast cancer. Experimental Design: An RB-loss signature used analyze association between status and pathologic complete gene expression datasets encompassing three different regimens. Parallel immunohistochemical analysis RB conducted on pretreatment biopsies chemotherapy. Results: increased from cancer patients...