A5004563285- Pancreatic and Hepatic Oncology Research
- Pancreatitis Pathology and Treatment
- Cancer, Hypoxia, and Metabolism
- Phagocytosis and Immune Regulation
- Pancreatic function and diabetes
- Cancer, Lipids, and Metabolism
- Cardiovascular Disease and Adiposity
- Liver Disease Diagnosis and Treatment
- Cancer, Stress, Anesthesia, and Immune Response
- Diet and metabolism studies
- Adipokines, Inflammation, and Metabolic Diseases
- Cancer Research and Treatments
- Cell Adhesion Molecules Research
- Growth Hormone and Insulin-like Growth Factors
- Esophageal Cancer Research and Treatment
- Acute Kidney Injury Research
- Anesthesia and Neurotoxicity Research
- Nutrition and Health in Aging
- Gastrointestinal disorders and treatments
- Metabolism, Diabetes, and Cancer
- Diabetes and associated disorders
- Nutritional Studies and Diet
- Cancer Cells and Metastasis
- Lung Cancer Diagnosis and Treatment
- RNA modifications and cancer
The Ohio State University Wexner Medical Center
2016-2025
The Ohio State University
2016-2024
Crowell & Moring (United States)
2024
Medical University of South Carolina
2024
The Ohio State University Comprehensive Cancer Center – Arthur G. James Cancer Hospital and Richard J. Solove Research Institute
2017-2023
National Cancer Institute
2003-2019
National Institutes of Health
2003-2019
Frederick National Laboratory for Cancer Research
2003-2019
The University of Texas MD Anderson Cancer Center
2011-2018
Emory University
2018
Objective Limited efficacy of immune checkpoint inhibitors in pancreatic ductal adenocarcinoma (PDAC) has prompted investigation into combination therapy. We hypothesised that interleukin 6 (IL-6) blockade would modulate immunological features PDAC and enhance the anti-programmed death-1-ligand 1 (PD-L1) inhibitor Design Transcription profiles IL-6 secretion from primary patient-derived stellate cells (PSCs) were analyzed via Nanostring immunohistochemistry, respectively. In vivo mechanistic...
Genetic mutations that give rise to active mutant forms of Ras are oncogenic and found in several types tumor. However, such not clear biomarkers for disease, since they frequently detected healthy individuals. Instead, it has become elevated levels activity critical Ras-induced tumorigenesis. the mechanisms underlying production pathological unclear. Here, we show presence Ras, inflammatory stimuli initiate a positive feedback loop involving NF-κB further amplifies levels. Stimulation...
Abstract The mechanisms that allow cancer cells to adapt the typical tumor microenvironment of low oxygen and glucose high lactate are not well understood. GPR81 is a receptor recently identified in adipose muscle has been investigated cancer. In current study, we examined expression function cells. We found was present colon, breast, lung, hepatocellular, salivary gland, cervical, pancreatic carcinoma cell lines. Examination tumors resected from patients with indicated 94% (148 158)...
Lipocalin-2 (LCN2) promotes malignant development in many cancer types. LCN2 is upregulated patients with pancreatic ductal adenocarcinoma (PDAC) and obese individuals, but whether it contributes to PDAC unclear. In this study, we investigated the effects of Lcn2 depletion on diet-induced obesity, inflammation, development. Mice acinar cell-specific expression KrasG12D were crossed Lcn2-depleted animals fed isocaloric diets varying amounts fat content. Pancreas collected analyzed for...
A significant challenge to overcome in pancreatic ductal adenocarcinoma (PDAC) is the profound systemic immunosuppression that renders this disease non-responsive immunotherapy. Our supporting data provide evidence CD200, a regulator of myeloid cell activity, expressed PDAC microenvironment. Additionally, myeloid-derived suppressor cells (MDSC) isolated from patients with express elevated levels CD200 receptor (CD200R). Thus, we hypothesize expression microenvironment limits responses...
Pancreatic ductal adenocarcinoma (PDAC) is the fourth leading cause of cancer death in USA, accounting for ~40,000 deaths annually. The dismal prognosis PDAC largely due to its late diagnosis. Currently, most sensitive diagnosis requires invasive procedures, such as endoscopic ultrasonography, which has inherent risks and accuracy that highly operator dependent. Here we took advantage a general characteristic solid tumors, acidic microenvironment generated by-product metabolism, develop...
Pancreatic ductal adenocarcinoma (PDAC) is often accompanied by weight loss. We sought to characterize factors associated with loss and observed nutritional interventions, as well define the effect of on survival.Consecutive subjects diagnosed PDAC (N = 123) were retrospectively evaluated. Univariate analysis was used compare without substantial (>5%) Multivariate logistic regression performed identify loss, survival analyses using Kaplan-Meier curves Cox models.Substantial at diagnosis...
The empirical dietary index for hyperinsulinemia (EDIH) and inflammatory pattern (EDIP) scores assess the insulinemic potentials of habitual patterns, irrespective macronutrient content, are based on plasma insulin response or biomarkers, respectively. glycemic (GI) load (GL) postprandial potential carbohydrate content. We tested hypothesis that patterns promoting hyperinsulinemia, chronic inflammation, hyperglycemia may influence type 2 diabetes risk. calculated from baseline (1993-1998)...
Obesity is a risk factor for pancreatic ductal adenocarcinoma (PDAC), deadly disease with limited preventive strategies. Lifestyle interventions to decrease obesity represent potential approach prevent obesity-associated PDAC. In this study, we examined whether decreasing through physical activity (PA) and/or dietary changes could inflammation in humans and PDAC mice. Comparison of circulating inflammatory-associated cytokines subjects (overweight obese) before after PA intervention revealed...
The marine ascidian <i>Diazona angulata</i> was the source organism for complex cytotoxic peptide diazonamide A. molecular structure of this recently revised after synthesis a biologically active analog A in which single nitrogen atom replaced by an oxygen atom. Diazonamide causes cells to arrest mitosis, and, exposure drug, treated lose both interphase and spindle microtubules. Both are potent inhibitors microtubule assembly, equivalent activity dolastatin 10 therefore far more than 15....
<h3>Background and Aims</h3> Pancreatic ductal adenocarcinoma (PDAC) is the fourth leading cause of cancer death in USA. Surgical resection only effective treatment; however, 20% patients are candidates for surgery. The ability to detect early PDAC would increase availability surgery improve patient survival. This study assessed feasibility using enzymatic activity cathepsin E (Cath E), a protease highly specifically expressed PDAC, as novel biomarker detection pancreas-bearing pancreatic...
Chronic inflammation (CI) is a risk factor for pancreatic cancer (PC) including the most common type, ductal adenocarcinoma (PDAC), but its role and mechanisms involved are unclear. To investigate of CI in PC, we generated genetic mouse models with specific presence or absence TP53. Mice were engineered to express either cyclooxygenase-2 (COX-2) IκB kinase-2 (IKK2), TP53+/+ TP53f/f specifically adult acinar cells by using full-length elastase promoter-driven Cre. Animals followed >80 weeks...
A workshop on "The Interface of Pancreatic Cancer with Diabetes, Obesity, and Inflammation: Research Gaps Opportunities" was held by the National Institute Diabetes Digestive Kidney Diseases October 12, 2017. The purpose to explore relationship possible mechanisms increased risk pancreatic ductal adenocarcinoma (PDAC) related diabetes, role altered intracellular energy metabolism in PDAC, biomarkers diabetes caused PDAC associated obesity, inflammatory events mediators as contributing causes...
Pancreatic ductal adenocarcinoma (PDAC) is associated with significant fibrosis. Recent findings have highlighted the profibrotic activity of tissue-resident macrophages in pancreatic cancer microenvironment. Here, we show that neoplastic epithelium, as well a subset macrophages, expresses prolactin-receptor (PRLR). High mobility group box 1-induced prolactin expression pancreas maintained FAK1 and STAT3 phosphorylation within epithelium stroma. Gain-of-function loss-of-function experiments...
The lethality of pancreatic adenocarcinoma stems from an elevated incidence tumor cell invasion and metastasis that are mediated by mechanisms not yet understood. Recent studies indicate the proinvasive integrin alpha 6 beta 4 is highly upregulated in adenocarcinomas. To assess importance this cancer migration invasion, lines were screened for expression immunoblotting fluorescence-activated sorting their ability to migrate invade toward hepatocyte growth factor (HGF). We found surface...
Abstract Previous studies in our laboratory identified that 3-deazaneplanocin A (DZNep), a carbocyclic adenosine analog and histone methyl transferase inhibitor, suppresses TGFβ-induced epithelial-to-mesenchymal (EMT) characteristics. In addition, DZNep epigenetically reprograms miRNAs to regulate endogenous TGFβ1 levels via miR-663/4787-mediated RNA interference (Mol Cancer Res. 2016 Sep 13. pii: molcanres.0083.2016) (1). Although also attenuates exogenous EMT response, the mechanism of...
Blood is an ideal body fluid for the discovery or monitoring of diagnostic and prognostic protein biomarkers. However, discovering robust biomarkers requires analysis large numbers samples to appropriately represent interindividual variability. To address this analytical challenge, we established a high-throughput cost-effective proteomics workflow accurate comprehensive at depth applicable clinical studies. For validation, processed 1 μL each from 62 plasma in 96-well plates analyzed...