A5072337663- Pancreatic and Hepatic Oncology Research
- Cancer Cells and Metastasis
- Cancer Mechanisms and Therapy
- Cancer Immunotherapy and Biomarkers
- Advanced Breast Cancer Therapies
- Pancreatitis Pathology and Treatment
- Immune cells in cancer
- Ferroptosis and cancer prognosis
- Phagocytosis and Immune Regulation
- Lung Cancer Research Studies
- Cytokine Signaling Pathways and Interactions
- Cancer-related Molecular Pathways
- Cancer Genomics and Diagnostics
- Lung Cancer Treatments and Mutations
- Cancer Research and Treatments
- Colorectal Cancer Treatments and Studies
- Neuroendocrine Tumor Research Advances
- Galectins and Cancer Biology
- Kruppel-like factors research
- Apelin-related biomedical research
- Wnt/β-catenin signaling in development and cancer
- Cancer, Hypoxia, and Metabolism
- Cancer-related cognitive impairment studies
- Chemical Reactions and Isotopes
University of Miami
2016-2023
Sylvester Comprehensive Cancer Center
2016-2021
// Nagaraj S. Nagathihalli 1 , Jason A. Castellanos 2 Michael N. VanSaun Xizi Dai Mahogany Ambrose 3 Qiaozhi Guo 4 Yanhua Xiong Nipun B. Merchant Division of Surgical Oncology, Department Surgery, University Miami Miller School Medicine, Sylvester Comprehensive Cancer Center, Miami, Florida, USA Vanderbilt Nashville, Tennessee, Meharry Medical College, Yale New Haven, Connecticut, Correspondence to: Merchant, email: nmerchant@med.miami.edu Keywords: pancreatic stellate cells, IL-6, STAT3,...
Abstract Major contributors to therapeutic resistance in pancreatic ductal adenocarcinoma (PDAC) include Kras mutations, a dense desmoplastic stroma that prevents drug delivery the tumor, and activation of redundant signaling pathways. We have previously identified mechanistic rationale for targeting STAT3 overcome PDAC. In this study, we investigate molecular mechanisms underlying heterogeneous response RAS pathway inhibition Effects JAK/STAT3 (STAT3i) or MEK (MEKi) were established...
Abstract A hallmark of pancreatic ductal adenocarcinoma (PDAC) is the presence a dense, desmoplastic stroma and consequent altered interactions between cancer cells their surrounding tumor microenvironment (TME) that promote disease progression, metastasis, chemoresistance. We have previously shown IL6 secreted from stellate (PSC) stimulates activation STAT3 signaling in cells, an established mechanism therapeutic resistance PDAC. now identified cell–derived cytokine IL1α as upstream...
Lack of durable response to cytotoxic chemotherapy is a major contributor the dismal outcomes seen in pancreatic ductal adenocarcinoma (PDAC). Extensive tumor desmoplasia and poor vascular supply are two predominant characteristics which hinder delivery chemotherapeutic drugs into PDAC tumors mediate resistance therapy. Previously, we have shown that STAT3 key biomarker therapeutic gemcitabine treatment PDAC, can be overcome by combined inhibition Src EGFR pathways. Although it...
Activating KRAS mutations, a defining feature of pancreatic ductal adenocarcinoma (PDAC), promote tumor growth in part through the activation cyclin-dependent kinases (CDK) that induce cell-cycle progression. p16INK4a (p16), encoded by gene CDKN2A, is potent inhibitor CDK4/6 and serves as critical checkpoint cell proliferation. Mutations subsequent loss p16 occur PDAC at rate higher than reported any other type results Rb inactivation unrestricted cellular growth. Therefore, strategies...
Heavy alcohol consumption is the dominant risk factor for chronic pancreatitis (CP); however, treatment and prevention strategies alcoholic (ACP) remains limited. The present study demonstrates that ACP induction in C57BL/6 mice causes significant acinar cell injury, pancreatic stellate (PSC) activation, exocrine function insufficiency, an increased fibroinflammatory response when compared with or CP alone. Although withdrawal of during recovery led to reversion damage, continued established...
The Src family of non-receptor tyrosine kinases are frequently activated in pancreatic ductal adenocarcinoma (PDAC), contributing to disease progression through downregulation E-cadherin and induction epithelial-to-mesenchymal transition (EMT). purpose this study was examine the efficacy kinase inhibition restoring levels PDAC. Immunohistochemical analysis human PDAC samples showed activation is inversely correlated with levels. Protein mRNA E-cadherin, gene expression its various...
<div>Abstract<p>A hallmark of pancreatic ductal adenocarcinoma (PDAC) is the presence a dense, desmoplastic stroma and consequent altered interactions between cancer cells their surrounding tumor microenvironment (TME) that promote disease progression, metastasis, chemoresistance. We have previously shown IL6 secreted from stellate (PSC) stimulates activation STAT3 signaling in cells, an established mechanism therapeutic resistance PDAC. now identified cell–derived cytokine IL1α...
ABSTRACT Pancreatic ductal adenocarcinoma (PDAC) is characterized by immune exclusion, pro-inflammatory polarization of cancer-associated fibroblasts (CAF), and resistance to checkpoint inhibition (ICI). We have previously demonstrated that reciprocally activated RAS/MEK/ERK JAK/STAT3 pathways mediate therapeutic resistance, while combined MEK STAT3 (MEKi+STAT3i) overcomes such in preclinical models. now show MEKi+STAT3i not only alters stromal architecture but also uncovers plasticity...
Abstract Introduction: Cell survival after DNA damage relies on repair processes to protect the integrity of genome. The process involves homologous recombination system that requires numerous factors including recombinase RAD51 and BRCA2, which co-localize replication centers within damaged cell nucleus. defective mechanisms in cancer cells can be exploited for therapy, when abrogated double-strand breaks (DSB) causes genomic instability increase sensitivity consequential cellular...
Abstract Introduction: Activating KRAS mutations are commonly found in PDAC and lead to constitutive downstream activation of MEK, which results uncontrolled proliferation. We have previously shown that MEK inhibition STAT3 signaling confers drug resistance continued cancer cell growth while combined overcomes this resistance. Since is a critical mediator cytokine production, we sought determine the effects on immune tumor microenvironment (TME). Tumor infiltrating immune/inflammatory cells,...
<p>Supplementary Fig. S1-S4 and figure legends.</p>
<div>Abstract<p>A hallmark of pancreatic ductal adenocarcinoma (PDAC) is the presence a dense, desmoplastic stroma and consequent altered interactions between cancer cells their surrounding tumor microenvironment (TME) that promote disease progression, metastasis, chemoresistance. We have previously shown IL6 secreted from stellate (PSC) stimulates activation STAT3 signaling in cells, an established mechanism therapeutic resistance PDAC. now identified cell–derived cytokine IL1α...
<p>Supplementary Fig. S1-S4 and figure legends.</p>
<p>Supplementary Figures</p>
<p>Supplementary Figures</p>
<div>Abstract<p>Activating <i>KRAS</i> mutations, a defining feature of pancreatic ductal adenocarcinoma (PDAC), promote tumor growth in part through the activation cyclin-dependent kinases (CDK) that induce cell-cycle progression. p16<sup>INK4a</sup> (p16), encoded by gene <i>CDKN2A</i>, is potent inhibitor CDK4/6 and serves as critical checkpoint cell proliferation. Mutations subsequent loss p16 occur PDAC at rate higher than reported any...
<div>Abstract<p>Activating <i>KRAS</i> mutations, a defining feature of pancreatic ductal adenocarcinoma (PDAC), promote tumor growth in part through the activation cyclin-dependent kinases (CDK) that induce cell-cycle progression. p16<sup>INK4a</sup> (p16), encoded by gene <i>CDKN2A</i>, is potent inhibitor CDK4/6 and serves as critical checkpoint cell proliferation. Mutations subsequent loss p16 occur PDAC at rate higher than reported any...
<p>MALDI-IMS analysis of treated xenograft tissues.</p>