Gastroenterology Commons^™

Site-Specific Immunomodulator: A Novel Treatment For Crohn's Disease, Brian Bressler, Kevin P. Bethel, Ralf Kleef, Sophie L. Reynolds, Simon Sutcliffe, David W. Mullins, Hal Gunn

Dartmouth Scholarship

We investigated the mechanism of action, safety, and efficacy of the Site-Specific Immunomodulator (SSI) QBECO, a novel immunotherapy for Crohn’s disease (CD). Using human monocytic THP-1 cells, we demonstrate that SSI QBECO (derived from the common colon bacteria E. coli) activates macrophages to an M1 phenotype (associated with enhanced capacity to eliminate bacteria and activate innate immune responses). We assessed SSI QBECO in a compassionate use protocol of ten adult patients with active CD. Patients with moderate to severe clinical symptoms receiving conventional CD treatments and/or complementary therapies were included, except patients receiving anti-TNF medications. SSI QBECO was self-administered subcutaneously …

Total Pancreatectomy With Islet Autologous Transplantation: The Cure For Chronic Pancreatitis?, Samuel J. Kesseli, Kerrington A. Smith, Timothy B. Gardner

Dartmouth Scholarship

Chronic pancreatitis (CP) is a debilitating disease that leads to varying degrees of pancreatic endocrine and exocrine dysfunction. One of the most difficult symptoms of CP is severe abdominal pain, which is often challenging to control with available analgesics and therapies. In the last decade, total pancreatectomy with autologous islet cell transplantation has emerged as a promising treatment for the refractory pain of CP and is currently performed at approximately a dozen centers in the United States. While total pancreatectomy is not a new procedure, the endocrine function-preserving autologous islet cell isolation and re-implantation have made the prospect of total …

Sessile Serrated Adenomas In The Proximal Colon Are Likely To Be Flat, Large And Occur In Smokers, Tarun Rustagi, Priya Rangasamy, Matthew Myers, Melinda Sanders, Haleh Vaziri, George Y. Wu, John W. Birk, Petr Protiva, Joseph C. Anderson

Dartmouth Scholarship

Aim: To examine the epidemiology and the morphology of the proximal sessile serrated adenomas (SSAs).

Methods: We conducted a retrospective study to identify patients with SSAs using a university-based hospital pathology database query from January 2007 to April 2011. Data collected included: age, gender, ethnicity, body mass index, diabetes, smoking, family history of colorectal cancer, aspirin, and statin use. We collected data on morphology of SSAs including site (proximal or distal), size, and endoscopic appearance (flat or protuberant). We also compared proximal SSAs to proximal tubular adenomas detected during same time period.

Deletion Of Rb Accelerates Pancreatic Carcinogenesis By Oncogenic Kras And Impairs Senescence In Pre-Malignant Lesions, Catherine Carrière, A. Jesse Gore, Alixanna M. Norris, Jason R. Gunn, Alison Young, Daniel Longnecker, Murray Korc

Dartmouth Scholarship

Rb1 encodes a cell-cycle regulator that is functionally disrupted in most human cancers. Pancreatic ductal adenocarcinomas (PDACs) have a high frequency of mutations in KRAS and INK4A/CDKN2A that might allow cells to bypass the regulatory actions of retinoblastoma (RB). To determine the role of loss of RB function in PDAC progression, we investigated the effects of Rb disruption during pancreatic malignant transformation initiated by oncogenic Kras.We generated mice with pancreas-specific disruption of Rb, in the absence or presence of oncogenic Kras, to examine the role of RB in pancreatic carcinogenesis.

Clinical Features And Management Of Autoimmune Hepatitis, Edward L. Krawitt

Dartmouth Scholarship

Autoimmune hepatitis (AIH) is a chronic hepatitis of unknown etiology which can progress to cirrhosis. Its clinical manifestations are highly variable and sometimes follow a fluctuating course. Diagnosis is based on characteristic histologic, clinical, biochemical and serological findings. Anti-inflammatory/immunosuppressive treatment frequently induces remission but long-term maintenance therapy is often required. Liver transplantation is generally successful in patients with decompensated cirrhosis unresponsive to or intolerant of medical therapy.

Inhibition Of Signal Transducer And Activator Of Transcription 3 Expression By Rna Interference Suppresses Invasion Through Inducing Anoikis In Human Colon Cancer Cells, Yu Fan, You-Li Zhang, Ying Wu, Wei Zhang, Yin-Huan Wang, Zhao-Ming Cheng, Hua Li

Dartmouth Scholarship

AIM: To investigate the roles and mechanism of signal transducer and activator of transcription 3 (STAT3) in invasion of human colon cancer cells by RNA interference.

The Nestin Progenitor Lineage Is The Compartment Of Origin For Pancreatic Intraepithelial Neoplasia, Catherine Carriere, Elliot S. Seeley, Tobias Goetze, Daniel S. Longnecker, Murray Korc

Dartmouth Scholarship

To determine the cell compartment in which initial oncogenic mutations occur in pancreatic ductal adenocarcinoma (PDAC), we generated a mouse model in which endogenous expression of mutated Kras (Kras(G12D)) was initially directed to a population of pancreatic exocrine progenitors characterized by the expression of Nestin. Targeting of oncogenic Kras to such a restricted cell compartment was sufficient for the formation of pancreatic intraepithelial neoplasias (PanINs), putative precursors to PDAC. PanINs appeared with the same grade and frequency as observed when Kras(G12D) was targeted to the whole pancreas by a Pdx1-driven Cre recombinase strategy. Thus, the Nestin cell lineage is highly …

A Novel Triterpenoid Induces Transforming Growth Factor Β Production By Intraepithelial Lymphocytes To Prevent Ileitis, Laurie A. Minns, Dominique Buzoni-Gatel, Kenneth H. Ely, Nicolas Rachinel, Souphalone Luangsay, Lloyd H. Kasper

Dartmouth Scholarship

The loss of homeostasis is a hallmark of inflammatory bowel disease. Oral infection of susceptible mice with Toxoplasma gondii results in an acute lethal ileitis characterized by increased interferon γ, tumor necrosis factor α, and inducible nitric oxide synthase; homeostasis results from transforming growth factor β production by intraepithelial lymphocytes. The synthetic oleanane triterpenoid 2-cyano-3,12-dioxooleana-1,9-dien-28-oic acid (CDDO) is a potent anti-inflammatory molecule previously shown in vitro to suppress the de novo synthesis of inducible nitric oxide synthase and to induce the transcription and activation of genes from the transforming growth factor β signaling pathway. We evaluated the immune response in …

Ccr5 Mediates Specific Migration Of Toxoplasma Gondii—Primed Cd8+ Lymphocytes To Inflammatory Intestinal Epithelial Cells, Souphalone Luangsay, Lloyd H. Kasper, Nicolas Rachinel, Laurie A. Minns

Dartmouth Scholarship

Toxoplasma gondii, an obligate intracellular parasite, can invade intestinal epithelial cells and elicit a robust Th1 immune response. In this model of intestinal inflammation, CD8⁺ intraepithelial lymphocytes (IELs) secrete transforming growth factor (TGF)-β, which appears necessary for the maintenance of homeostasis in the intestine. However, the mechanism responsible for the IEL migration to the inflamed intestine is still unclear.An in vitro coculture cell system was used to quantify the IEL attraction by an infected intestinal epithelial cell line (m-IC_cl2). We used CCR5-deficient mice to determine which chemokine receptor—chemokine interaction could be responsible for the recruitment of …

Adenoma Characteristics At First Colonoscopy As Predictors Of Adenoma Recurrence And Characteristics At Follow-Up, Rosalind U. Van Stolk, Gerald J. Beck, John A. Baron, Robert Haile, Robert Summers

Dartmouth Scholarship

All patients with colorectal adenomas may not require identical follow-up. We aimed to determine if adenoma characteristics at initial colonoscopy could predict adenoma recurrence or characteristics at follow-up. The number of adenomas and the size, type, and degree of atypia in 479 patients in a polyp prevention trial were evaluated as predictors of the same characteristics at follow-up using odds ratios (ORs) with 95% confidence intervals (CIs). Multiple logistic regression analysis was performed to determine if several baseline characteristics were simultaneously associated with outcome.