A5019543378- Pancreatic and Hepatic Oncology Research
- Pancreatitis Pathology and Treatment
- Phagocytosis and Immune Regulation
- Pancreatic function and diabetes
- Immune cells in cancer
- Neuroendocrine Tumor Research Advances
- Prostate Cancer Treatment and Research
- Cancer Research and Treatments
- NF-κB Signaling Pathways
- Cancer Cells and Metastasis
- Cancer Immunotherapy and Biomarkers
- Plant Pathogens and Fungal Diseases
- Epigenetics and DNA Methylation
- Mycorrhizal Fungi and Plant Interactions
- Yeasts and Rust Fungi Studies
- Peptidase Inhibition and Analysis
- Chromium effects and bioremediation
- Arsenic contamination and mitigation
- Immune Response and Inflammation
- Biomarkers in Disease Mechanisms
- Trace Elements in Health
- Cancer Genomics and Diagnostics
- Melanoma and MAPK Pathways
- Cancer, Hypoxia, and Metabolism
- Immune Cell Function and Interaction
Clark Atlanta University
2017-2024
Center for Cancer Research
2017-2024
Mayo Clinic in Florida
2011-2023
Atlanta University Center
2018
The University of Texas Health Science Center at San Antonio
2017
University of Pennsylvania
2017
Jacksonville College
2012-2016
WinnMed
2012-2016
Nemours Children’s Clinic
2011-2016
Mayo Clinic
2010-2015
In response to inflammation, pancreatic acinar cells can undergo acinar-to-ductal metaplasia (ADM), a reprogramming event that induces transdifferentiation ductlike phenotype and, in the context of additional oncogenic stimulation, contributes development cancer. The signaling mechanisms underlying pancreatitis-inducing ADM are largely undefined. Our results provide evidence macrophages infiltrating pancreas drive this process. We identify macrophage-secreted inflammatory cytokines RANTES...
The development of pancreatic cancer requires the acquisition oncogenic KRas mutations and upregulation growth factor signaling, but relationship between these is not well established. Here, we show that mutant alters mitochondrial metabolism in acinar cells, resulting increased generation reactive oxygen species (mROS). Mitochondrial ROS then drives dedifferentiation cells to a duct-like progenitor phenotype progression PanIN. This mediated via ROS-receptive kinase protein D1 transcription...
Abstract Purpose: In a previous genome-wide gene expression profiling analysis using an invasion cancer cell lines model, we have identified Slug as selectively overexpressed in the highly invasive cells. Here, investigated clinical significance of lung adenocarcinoma and role process metastasis. Experimental Design: Real-time quantitative reverse transcription-PCR was used to investigate mRNA surgically resected 54 patients its correlation with survival. We line very low levels vitro vivo...
Desmoplasia and an inflammatory environment are defining features of pancreatic cancer. Unclear is how cells that undergo oncogenic transformation can cross-talk with immune this contributes to the development lesions. Here, we demonstrate acinar expressing mutant KRAS expedite their a duct-like phenotype by inducing local inflammation. Specifically, show KRAS(G12D) induces expression intercellular adhesion molecule-1 (ICAM-1), which serves as chemoattractant for macrophages. Infiltrating...
The contributions of the innate immune system to development pancreatic cancer are still ill defined. Inflammatory macrophages can initiate metaplasia acinar cells a duct-like phenotype (acinar-to-ductal [ADM]), which then gives rise intraepithelial neoplasia (PanIN) when oncogenic KRas is present. However, it remains unclear and how this inflammatory macrophage population replaced by tumor-promoting macrophages. Here, we demonstrate presence interleukin-13 (IL-13), convert into Ym1+...
The transdifferentiation of pancreatic acinar cells to a ductal phenotype (acinar-to-ductal metaplasia, ADM) occurs after injury or inflammation the pancreas and is reversible process. However, in presence activating Kras mutations persistent epidermal growth factor receptor (EGF-R) signalling, that underwent ADM can progress intraepithelial neoplasia (PanIN) eventually cancer. In transgenic animal models, PanINs are initiated by high-affinity ligands for EGF-R mutations, but underlying...
Macrophage infiltrations (inflammation) are associated with prostate disorders such as prostatitis, prostatic hyperplasia and cancer. All have elevated cell proliferation, initiated from normal epithelial cells. To date, the mechanism of how macrophages regulate proliferation remains largely unknown. Using a 3D co-culture system, we here show that Raw 264.7 increased PZ-HPV-7 In addition, these expressed higher levels Ym1 CD206. We further identify macrophage-secreted cytokines including...
In this study we have explored the involvement of oxidative stress in Cr(VI)-induced JNK, p38 and ERK signaling pathways their effects on Cr(VI) cytotoxicity human non-small cell lung carcinoma CL3 cells. Exposure to K(2)Cr(2)O(7) markedly activated JNK moderately a dose- (10-80 microM) time-dependent (1-12 h) manner. The decreased rapidly gradually when was removed from medium. Post-incubation Cr(VI)-treated cells with H(2)O(2) increased activities p38, but not ERK. Co-administering...
Background Increased levels of NF-κB are hallmarks pancreatic ductal adenocarcinoma (PDAC) and both classical alternative activation pathways have been implicated. Methodology/Principal Findings Here we show that the pathway is a source for high basal activity in PDAC cell lines. p52/RelB complex mediated through stabilization NF-κB-inducing kinase (NIK). We identify proteasomal downregulation TNF receptor-associated factor 2 (TRAF2) as mechanism by which active NIK increased Such...
Acinar transdifferentiation toward a duct-like phenotype constitutes the defining response of acinar cells to external stress signals and is considered be initial step in pancreatic carcinogenesis. Despite requirement for oncogenic Kras cancer (PDAC) development, not sufficient drive carcinogenesis beyond level premalignancy. Instead, secondary events, such as inflammation-induced signaling activation epidermal growth factor (EGFR) or induction Sox9 expression, are required tumor formation....
Prostate cancer development and progression are associated with increased infiltrating macrophages. is derived from prostatic intraepithelial neoplasia (PIN) lesions. However, the effects macrophages have on PIN remain unclear. Here, we showed that recruited adjacent to expressed M2 macrophage markers. In addition, high levels of Spp1 transcripts, also known as osteopontin, were identified in these Extraneously added accelerated cell proliferation through activation Akt JNK a 3D culture...
In this study we have explored the involvement of oxidative stress in Cr(VI)-induced JNK, p38 and ERK signaling pathways their effects on Cr(VI) cytotoxicity human non-small cell lung carcinoma CL3 cells. Exposure to K 2 Cr O 7 markedly activated JNK moderately a dose- (10–80 μM) time-dependent (1–12 h) manner. The decreased rapidly gradually when was removed from medium. Post-incubation Cr(VI)-treated cells with H increased activities p38, but not ERK. Co-administering...
Acinar-to-ductal metaplasia (ADM) is a reversible epithelial transdifferentiation process that occurs in the pancreas response to acute inflammation. ADM can rapidly progress towards pre-malignant pancreatic intraepithelial neoplasia (PanIN) lesions presence of mutant KRas and ultimately adenocarcinoma (PDAC). In present work, we elucidate role related mechanism glycogen synthase kinase-3beta (GSK-3β) development using vitro 3D cultures genetically engineered mouse models. We show GSK-3β...
During development of pancreatic cancer, alternatively activated macrophages contribute to fibrogenesis, intraepithelial neoplasia (PanIN) lesion growth, and generation an immunosuppressive environment. Here, we show that the immunomodulatory agent pomalidomide depletes areas macrophage populations. Pomalidomide treatment resulted in downregulation interferon regulatory factor 4, a transcription for M2 polarization. Pomalidomide-induced absence led decrease fibrosis at PanIN lesions...
The risk factors for prostate cancer include a high‐fat diet and obesity, both of which are associated with an altered cell environment including increased inflammation. It has been shown that chronic inflammation due to or bacterial infection the potential accelerate as well its precursor, prostatic intraepithelial neoplasia (PIN), development. However, underlying mechanism how promotes development, especially PIN, remains unclear. In this study, we showed more macrophages were present in...
The roles of inflammatory macrophages in pancreatic tissue and the development cancer have not been well characterized. Recently it was shown that macrophages, besides their function clearing dead cells, also initiate acinar cell metaplasia to duct-like progenitor cells. While pancreatitis this is a reversible process, context an oncogenic stimulus process irreversible can lead formation precancerous lesions. Recent work now indicates acquisition activating Kras mutation cells initiates...
The innate immune system has a key role in pancreatic cancer initiation, but the specific contribution of different macrophage populations is still ill-defined. While inflammatory (M1) macrophages have been shown to drive acinar-to-ductal metaplasia (ADM), initiating event, alternatively activated (M2) attributed lesion growth and fibrosis. Here, we determined cytokines chemokines secreted by both subtypes. Then, analyzed their ADM initiation growth, finding that while M1 secrete TNF, CCL5,...
Pancreatic ductal adenocarcinoma (PDAC) can originate from acinar-to-ductal metaplasia (ADM). acini harboring oncogenic Kras mutations are transdifferentiated to a duct-like phenotype that further progresses become pancreatic intraepithelial neoplasia (PanIN) lesions, giving rise PDAC. Although ADM formation is frequently observed in KrasG12D transgenic mouse models of PDAC, the exact mechanisms how regulates this process remain an enigma. Herein, we revealed new downstream target Kras,...