A5012270964- Neuroendocrine Tumor Research Advances
- Pancreatic and Hepatic Oncology Research
- Liver Disease Diagnosis and Treatment
- Hepatitis B Virus Studies
- Neuropeptides and Animal Physiology
- Lung Cancer Research Studies
- Hepatitis C virus research
- Cancer, Stress, Anesthesia, and Immune Response
- Pancreatitis Pathology and Treatment
- Hepatocellular Carcinoma Treatment and Prognosis
- Helicobacter pylori-related gastroenterology studies
- Peptidase Inhibition and Analysis
- Animal Virus Infections Studies
- Cancer Research and Treatments
- Liver physiology and pathology
- Chemokine receptors and signaling
- Drug Transport and Resistance Mechanisms
- Cancer Mechanisms and Therapy
- Allergic Rhinitis and Sensitization
- Advanced Drug Delivery Systems
- Neuroblastoma Research and Treatments
- Phagocytosis and Immune Regulation
- Dermatology and Skin Diseases
- Myasthenia Gravis and Thymoma
- Cancer Cells and Metastasis
Georgetown University
2015-2023
Georgetown University Medical Center
2015-2021
Georgetown-Howard Universities Center for Clinical and Translational Science
2017
SB 9200, an oral prodrug of the dinucleotide 9000, is being developed for treatment chronic hepatitis B virus (HBV) infection and represents a novel class antivirals. 9200 thought to activate viral sensor proteins, retinoic acid-inducible gene 1 (RIG-I) nucleotide-binding oligomerization domain-containing protein 2 (NOD2) resulting in interferon (IFN) mediated antiviral immune responses virus-infected cells. Additionally, binding these proteins could also sterically block ability polymerase...
SB 9200, an orally bioavailable dinucleotide, activates the viral sensor proteins, retinoic acid-inducible gene 1 (RIG-I) and nucleotide-binding oligomerization domain-containing protein 2 (NOD2) causing induction of interferon (IFN) signaling cascade for antiviral defense. The present study evaluated overall response in woodchucks upon immune response, first with 9200 followed by Entecavir (ETV) versus reduction burden ETV immunomodulation. Woodchucks chronically infected woodchuck...
The gastrointestinal peptide cholecystokinin (CCK) is released from the duodenum in response to dietary fat aid digestion, and plasma CCK levels are elevated with consumption of high-fat diets. also a trophic for pancreas has been shown stimulate growth pancreatic cancer. In current investigation, we studied influence diet high saturated on cancer syngeneic murine models before mice became obese exclude confounding factors associated obesity. significantly increased metastasis compared...
RG7834 is a small‐molecule inhibitor of hepatitis B virus (HBV) gene expression that significantly reduces the levels surface antigen (HBsAg) and HBV DNA in humanized liver mouse model. In current study, we evaluated potency woodchuck model chronic infection, alone combination with entecavir (ETV) and/or interferon‐α (wIFN‐α). reduced (WHV) (WHsAg) by mean 2.57 log 10 from baseline WHV 1.71 . ETV + wIFN‐α WHsAg means 2.40 6.70 , respectively. The RG7834, ETV, profoundly 5.00 7.46 However,...
Hepatocellular carcinoma (HCC) is the fastest growing cancer worldwide in part due to obesity epidemic and fatty liver disease, particularly nonalcoholic steatohepatitis (NASH). Chronic inflammation with release of cytokines chemokines activation hepatic stellate cells results changes extracellular matrix (ECM) that predisposes development HCC. Blood levels gastrointestinal peptide cholecystokinin (CCK) are increased humans mice consuming a high-fat diet. We found CCK-B receptor (CCK-BR)...
Parenteral routes of drug administration are often selected to optimize actual dose delivered, assure high bioavailability, bypass first-pass metabolism or harsh gastrointestinal environments, as well maximize the speed onset. Intramuscular (IM) delivery can be preferred intravenous when initiating access is difficult impossible. Drugs injected intramuscularly using a syringe an automated device (autoinjector). Investigation into IM dynamics these methods may guide further improvements in...
Nonalcoholic steatohepatitis (NASH) is a common inflammatory liver condition that may lead to cirrhosis and hepatocellular carcinoma (HCC). Risk factors for NASH include saturated fat diet, altered lipid metabolism, genetic epigenetic factors, including microRNAs. Serum levels of cholecystokinin (CCK) are elevated in mice humans consume high-saturated diet. CCK receptors (CCK-Rs) have been reported on fibroblasts which when activated can induce fibrosis; however, their role hepatic fibrosis...
Growth of pancreatic cancer is stimulated by gastrin in both a paracrine and an autocrine fashion. Traditional therapies have not significantly improved survival, recently has been deemed "cold" tumor due to its poor response immunotherapy. Strategies improve survival are desperately needed. In the current investigation, we studied effects anti-gastrin vaccine, polyclonal antibody stimulator (PAS; formerly called G17DT Gastrimmune), used alone or combination with programmed cell death...
Objectives To analyze whether use of proton pump inhibitors increase the risk for pancreatic cancer in a mouse model and human clinical cohorts. Methods p48-Cre/LSL-Kras G12D mice that develop precancerous intraepithelial neoplasia (PanINs) were treated with low- or high-dose (PPIs) orally 1 4 months. The mechanism cholecystokinin receptor 2 (CCK-2R) activation was investigated vitro. Two resources employed to subjects PPI use. Results Serum gastrin levels increased 8-fold ( P < 0.0001)...
Pancreatic cancer is resistant to chemotherapy in part due the dense desmoplastic fibrosis surrounding tumor, immunosuppressive cells tumor microenvironment (TME), and early rate of metastases. In this study, we examined effects a CCK receptor antagonist, proglumide, alone combination with gemcitabine murine models pancreatic cancer. Tumor growth rate, metastases, survival were assessed mice bearing syngeneic or human tumors treated PBS (control), gemcitabine, proglumide. Excised evaluated...
Nonalcoholic steatohepatitis (NASH) is associated with obesity, metabolic syndrome, and dysbiosis of the gut microbiome. Cholecystokinin (CCK) released by saturated fats plays an important role in bile acid secretion. CCK receptors are expressed on cholangiocytes, CCK-B receptor expression increases livers mice NASH. The farnesoid X (FXR) involved transport a target for novel therapeutics aim this study was to examine proglumide, inhibitor, murine model NASH its interaction at FXR. Mice were...
As current interventions for chronic hepatitis B (CHB) rarely induce cure, more effective drugs are needed. Short-term treatment of woodchucks with the novel immunomodulator AIC649, a parapoxvirus-based stimulator toll-like receptor 9 dependent and independent pathways, has been shown to reduce viral DNA surface antigen via unique, biphasic response pattern. The present study evaluated long-term AIC649 in combination Entecavir potency safety woodchucks. monotreatment induced modest...
Survival from pancreatic cancer is poor because most cancers are diagnosed in the late stages and there no therapies to prevent progression of precancerous intraepithelial neoplasms (PanINs). Inhibiting mutant KRASG12D, primary driver mutation human cancers, has been challenging. The cholecystokinin-B receptor (CCK-BR) absent normal pancreas but becomes expressed high grade PanIN lesions over-expressed making it a prime target for therapy. We developed biodegradable nanoparticle polyplex...
Objective The KRAS gene is the most frequently mutated in pancreatic cancer, and no successful anti-Ras therapy has been developed. Gastrin shown to stimulate cancer an autocrine fashion. We hypothesized that reactivation of peptide gastrin collaborates with during carcinogenesis. Methods LSL-Kras G12D/+ ; P48-Cre (KC) mutant transgenic mice were crossed gastrin-KO (GKO) develop GKO/KC mice. Pancreata examined for 8 months stage intraepithelial neoplasia lesions, inflammation, fibrosis,...
<p>Supplemental Table S1 and Supplemental Figures S1-S3</p>