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We investigated antibody responses to hepatitis C virus (HCV) antigens E1 and E2 and the relevance of animal models for vaccine development. We compared antibody responses to vaccination with recombinant E1E2 complex in heathy volunteers, non-human primates (NHPs), and mice METHODS: We analyzed 519 serum samples from participants in a phase 1 vaccine trial (NCT00500747) and compared them with serum or plasma samples from C57BL/6J mice (n=28) and rhesus macaques (n=4) immunized with the same HCV E1E2 antigen...
Prolactin (PRL) signaling is upregulated in hormone-responsive cancers. The PRL receptor (PRLR) is class I cytokine receptor that signals via the JAK-STAT and MAPK pathways to regulate cell proliferation, migration, stem-cell features, and apoptosis. Patients with pancreatic ductal adenocarcinoma (PDAC) have high plasma levels of PRL. We investigated whether PRLR signaling contributes to growth of pancreatic tumors in mice.
Barrett's esophagus (BE) is the only known precursor to esophageal adenocarcinoma (EAC), a cancer associated with a dismal 5-year survival rate (Am J Gastroenterol 2017;112(7):1032-1048). Despite all the advances in this field, we have had minimal impact on the incidence, morbidity and mortality related to this lethal cancer. This has provided the impetus for major gastroenterology societies to propose quality indicators to guide diagnostic, surveillance and treatment strategies including endoscopic eradica...
Functions of intestinal stem cells (ISCs) are regulated by diet and metabolic pathways. Hepatocyte nuclear factor 4 (HNF4) are transcription factors that bind fatty acids. We investigated how HNF4 transcription factors regulate metabolism and their functions in ISCs in mice METHODS: We performed studies with Villin-Cre, Lgr5-EGFP-IRES-Cre, Hnf4a, and Hnf4g mice. Villin-Cre; Lgr5-EGFP-IRES-Cre; Hnf4a; Hnf4g mice are hereafter referred to Hnf4ag. Mice were given tamoxifen to induce Cre recombinase. Mice trans...
Approximately 35% of patients with colorectal cancer (CRC) have a family history of the disease, due to genetic factors, common exposures, or both. Some families with a history of CRC carry genetic variants that cause CRC with high or moderate penetrance, but these account for only 5%-10% of CRC cases. Most families with a history of CRC and/or adenomas do not carry genetic variants associated with cancer syndromes-this is called common familial CRC. Our understanding of familial predisposition to CRC and c...
We aimed to develop and validate a deep-learning computer-aided detection (CAD) system, suitable for use in real time in clinical practice, to improve endoscopic detection of early neoplasia in patients with Barrett's esophagus (BE).
Liver regeneration is impaired in mice with hepatocyte-specific deficiencies in microRNA (miRNA) processing, but it is not clear which miRNAs regulate this process. We developed a high-throughput screen to identify miRNAs that regulate hepatocyte repopulation following toxic liver injury using Fah-/- mice.
Screening, followed by colonoscopic polypectomy (or surgery for malignant lesions), prevents incident colorectal cancer and mortality. However, there are variations in effective application of nearly every aspect of the screening process. Screening is a multistep process, and failure in any of single step could result in unnecessary morbidity and mortality. Awareness of variations in operator- and system-dependent performance has led to detailed, comprehensive recommendations in the United States and Europe...
Mutations in the human serine protease 1 gene (PRSS1), which encodes cationic trypsinogen, can accelerate its autoactivation and cause hereditary or sporadic chronic pancreatitis. Disruption of the locus that encodes cationic trypsinogen in mice (T7) causes loss of expression of the protein, but only partially decreases the severity of secretagogue-induced acute pancreatitis and has no effect on chronic pancreatitis. We investigated whether trypsinogen becomes pathogenic only when it is activated by mutatio...
Mutations in the tetratricopeptide repeat domain 7A gene (TTC7A) cause intestinal epithelial and immune defects. Patients can become immune deficient and develop apoptotic enterocolitis, multiple intestinal atresia, and recurrent intestinal stenosis. The intestinal disease in patients with TTC7A deficiency is severe, untreatable, and recurs despite resection or allogeneic hematopoietic stem cell transplant. We screened drugs for those that prevent apoptosis of in cells with TTC7A deficiency and tested their...