Digestive System Diseases Commons^™

Colorectal Cancer Liver Metastatic Growth Depends On Pad4-Driven Citrullination Of The Extracellular Matrix, A. E. Yuzhalin, A. N. Gordon-Weeks, M. L. Tognoli, K. Jones, B. Markelc, R. Konietzny, R. Fischer, Aaron Muth, E. O'Neill, Paul R. Thompson, P. J. Venables, B. M. Kessler, S. Y. Lim, R. J. Muschel

Open Access Articles

Citrullination of proteins, a post-translational conversion of arginine residues to citrulline, is recognized in rheumatoid arthritis, but largely undocumented in cancer. Here we show that citrullination of the extracellular matrix by cancer cell derived peptidylarginine deiminase 4 (PAD4) is essential for the growth of liver metastases from colorectal cancer (CRC). Using proteomics, we demonstrate that liver metastases exhibit higher levels of citrullination and PAD4 than unaffected liver, primary CRC or adjacent colonic mucosa. Functional significance for citrullination in metastatic growth is evident in murine models where inhibition of citrullination substantially reduces liver metastatic burden. Additionally, citrullination of a key matrix ...

The Dynamic Roles Of Mesenchymal Stem Cells In Colon Cancer, Shan Wang, Zhiguo Miao, Qiyuan Yang, Yimin Wang, Jinzhou Zhang

Open Access Articles

Colon cancer is still one of the most common causes of cancer in human and is characterized by lymphocyte infiltrates and originates from the epithelial cells found in the lining of colon or rectum of the gastrointestinal tract. Mesenchymal stem cells (MSCs) are composed of the multipotent stem cell group of stroma and can be differentiated as various cell lineages, such as fibroblasts, osteoblasts, and adipocytes. MSCs provide mechanical and structural support and have potential functions during tumor growth and metastasis. The efficacy of MSC-based therapies is partly dependent on the migration and homing of MSCs to tumors and metastatic ...

Video Capsule Endoscopy In The Assessment Of Portal Hypertensive Enteropathy, Yasir Al-Azzawai, Lidia Spaho, Mohammed Mahmoud, Joan Kheder, Anne Foley, David R. Cave

Open Access Articles

Background: The features of the portal hypertension enteropathy (PHE) vary from mild mucosal changes to varices with or without bleeding. The prevalence and the development are not fully understood.

Aim: Our aim is to examine the prevalence and the different manifestations of PHE using video capsule endoscopy (VCE).

Methods: It is a single center retrospective study of patients with cirrhosis, who had VCE. Based on the published literature, we divided the PHE lesions into vascular lesions and mucosal lesions.

Results: Of the 100 patients with cirrhosis that had a VCE study, the mean age was 62.82 years. Male gender ...

Implementing Universal Lynch Syndrome Screening (Impulss): Protocol For A Multi-Site Study To Identify Strategies To Implement, Adapt, And Sustain Genomic Medicine Programs In Different Organizational Contexts, Alanna Kulchak Rahm, Mara M. Epstein

Open Access Articles

BACKGROUND: Systematic screening of all colorectal tumors for Lynch Syndrome (LS) has been recommended since 2009. Currently, implementation of LS screening in healthcare systems remains variable, likely because LS screening involves the complex coordination of multiple departments and individuals across the healthcare system. Our specific aims are to (1) describe variation in LS screening implementation across multiple healthcare systems; (2) identify conditions associated with both practice variation and optimal implementation; (3) determine the relative effectiveness, efficiency, and costs of different LS screening protocols by healthcare system; and (4) develop and test in a real-world setting an organizational toolkit for LS ...

Reduced Gut Microbiome Protects From Alcohol-Induced Neuroinflammation And Alters Intestinal And Brain Inflammasome Expression, Patrick P. Lowe, Benedek Gyongyosi, Abhishek Satishchandran, Arvin Iracheta-Vellve, Yeonhee Cho, Aditya Ambade, Gyongyi Szabo

Open Access Articles

BACKGROUND: The end-organ effects of alcohol span throughout the entire body, from the gastrointestinal tract to the central nervous system (CNS). In the intestine, alcohol use changes the microbiome composition and increases gut permeability allowing translocation of microbial components into the circulation. Gut-derived pathogen-associated signals initiate inflammatory responses in the liver and possibly elsewhere in the body. Because previous studies showed that the gut microbiome contributes to alcohol-induced liver disease, we hypothesized that antibiotic administration to reduce the gut microbiome would attenuate alcohol-induced inflammation in the brain and small intestine (SI).

METHODS: Six- to 8-week-old C57BL/6J female mice were ...

Fxr And Tgr5 Agonists Ameliorate Liver Injury, Steatosis, And Inflammation After Binge Or Prolonged Alcohol Feeding In Mice, Arvin Iracheta-Vellve, Charles D. Calenda, Jan Petrasek, Aditya Ambade, Karen Kodys, Luciano Adorini, Gyongyi Szabo

Open Access Articles

Bile acids (BAs) activate various dedicated receptors, including the farnesoid X receptor (FXR) and the Takeda G protein-coupled receptor 5 (TGR5). The FXR agonist obeticholic acid (OCA) is licensed for the treatment of primary biliary cholangitis and has shown promising results in NASH patients, whereas TGR5 agonists target inflammation and metabolism. We hypothesized that FXR and/or TGR5 agonists may be therapeutic in early alcoholic liver disease (ALD) in mice, in which hepatic inflammation plays a major role. OCA, INT-777, and INT-767 are BA derivatives with selective agonist properties for FXR, TGR5, or both, respectively. These compounds were tested in ...

Microrna-96 Promotes Schistosomiasis Hepatic Fibrosis In Mice By Suppressing Smad7, Xufeng Luo, Dongmei Zhang, Jun Xie, Qin Su, Xing He, Ruipu Bai, Guangping Gao, Weiqing Pan

UMass Center for Clinical and Translational Science Supported Publications

Infection with Schistosoma causes aberrant expression of host microRNAs (miRNAs), and normalizing the levels of dysregulated miRNAs can attenuate pathology. Here, we show that the host miRNA, miR-96, is markedly upregulated during the progression of hepatic schistosomiasis. We demonstrate that elevation of miR-96 induces hepatic fibrosis in infected mice by suppressing the expression of its target gene, Smad7. We show that infection with Schistosoma induces the expression of transforming growth factor beta1 (TGF-beta1), which in turn upregulates the expression of miR-96 through SMAD2/3-DROSHA-mediated post-transcriptional regulation. Furthermore, inhibition of miR-96 with recombinant adeno-associated virus 8 (rAAV8)-mediated delivery of Tough ...

Vancomycin Delays Clindamycin-Induced Fatality In The Hamster Model Of Clostridioides [Clostridium] Difficile Infection, Amelia E. Fox-King, Chrisabelle Mefferd, Jacqueline R. Phan, Nancy O. Nou, Ernesto Abel-Santos, Brian P. Hedlund

LSAMP Poster Presentations

Antibiotics can leave the host gut microbiome susceptible to Clostridioides [Clostridium] difficile colonization and lethal toxin production. For instance, clindamycin-induced susceptibility to C. difficile infection (CDI) results in rapid fatality in hamster models, yet vancomycin has been shown to offer increased survival in hamsters challenged with C. difficile. We aim to develop an antibiotic treatment that will facilitate CDI susceptibility without prompt fatality in hamster models. An antibiotic regimen starting with a continuous vancomycin treatment along with a single clindamycin dosage is thought to reduce the major disruption in the indigenous gut microbiome and prevent clindamycin-induced death. Quantitative polymerase chain ...

Association Between Sarcopenia And Functional Status In Liver Transplant Patients, Natasha H. Dolgin, Andrew J. Smith, Samantha G. Harrington, Babak Movahedi, Paulo N.A. Martins, Adel Bozorgzadeh

Open Access Articles

OBJECTIVES: A growing body of evidence shows that frailty and functional performance predict liver transplant outcomes. The Organ Procurement and Transplant Network uses the Karnofsky Performance Status scale to adjust for transplant center case mix in assessing quality measures. This study explores the strength of the relationship between Karnofsky Performance Status scores and objective measures of frailty.

MATERIALS AND METHODS: This observational study includes 136 adult, first-time liver transplant recipients at UMass Memorial (2006-2015) who had 2 abdominal computed tomography scans available (at < /= 90 days pretransplant and > /= 7 days before that). We analyzed the relationship between Karnofsky Performance Status and muscle wasting using absolute ...

Hepatocarcinoma With Tumor Thrombus Occupying The Right Atrium And Portal Vein In A Patient With Hereditary Hemochromatosis And Liver Cirrhosis, Olga Hilda Orasan, Andreea Maria Stefan, Laura Urian, Anca Mihailov, Ovidiu Fabian, Flaviu Muresan, Iulia Breaban, Sorina Cezara Secara, Simina Tarmure Sarlea, Vasile Negrean, Dorel Sampelean, Angela Cozma

Journal of Mind and Medical Sciences

We present the case of a 46-year old patient with Child-Pugh class C cirrhosis with MEDL-Score 16, and hepatocellular carcinoma invading the inferior vena cava and the right atrium. The etiology of cirrhosis is type 1 hereditary hemochromatosis with positive HFE C282Y/C282Y and H63D/H63D mutations. A systematic review of the literature was performed and only 30 cases of hepatocellular carcinoma with tumor thrombosis extending into the right atrium have been described. To our knowledge, this is the first case that evidences the presence in hereditary hemochromatosis of hepatocellular carcinoma with atypical invasion into the right atrium. Screening of ...

Reduced Incidence And Better Liver Disease Outcomes Among Chronic Hcv Infected Patients Who Consume Cannabis, Adeyinka Adejumo, Oluwole Muyiwa Adegbala, Kelechi Lauretta Adejumo, Terence N. Bukong

Open Access Articles

Background and Aim: The effect of cannabis use on chronic liver disease (CLD) from Hepatitis C Virus (HCV) infection, the most common cause of CLD, has been controversial. Here, we investigated the impact of cannabis use on the prevalence of CLD among HCV infected individuals.

Methods: We analyzed hospital discharge records of adults (age > /= 18 years) with a positive HCV diagnosis. We evaluated records from 2007 to 2014 of the Nationwide Inpatient Sample (NIS). We excluded records with other causes of chronic liver diseases (alcohol, hemochromatosis, NAFLD, PBC, HBV, etc.). Of the 188,333 records, we matched cannabis users to ...

Intestinal P-Glycoprotein Exports Endocannabinoids To Prevent Inflammation And Maintain Homeostasis, Rose L. Szabady, Christopher Louissaint, Anneke Lubben, Bailu Xie, Shaun Reeksting, Christine Tuohy, Zachary Demma, Sage Foley, Christina S. Faherty, Alejandro Llanos-Chea, Andrew J. Olive, Randall J. Mrsny, Beth A. Mccormick

Open Access Articles

Neutrophil influx into the intestinal lumen is a critical response to infectious agents, but is also associated with severe intestinal damage observed in idiopathic inflammatory bowel disease. The chemoattractant hepoxilin A3, an eicosanoid secreted from intestinal epithelial cells by the apically restricted efflux pump multidrug resistance protein 2 (MRP2), mediates this neutrophil influx. Information about a possible counterbalance pathway that could signal the lack of or resolution of an apical inflammatory signal, however, has yet to be described. We now report a system with such hallmarks. Specifically, we identify endocannabinoids as the first known endogenous substrates of the apically restricted ...

Heat Stroke As A Cause Of Liver Failure And Evaluation Of Liver Transplant, Paulo N.A. Martins, Isabel M. A. Bruggenwirth, James Mcdaid, Martin Hertl, Tatsuo Kawai, Nahel Elias, Raymond T. Chung, James F. Markmann

Open Access Articles

Heat stroke is a multiple organ dysfunction syndrome of poorly understood pathogenesis. Exertional heat stroke with acute liver failure is a rarely reported condition. Liver transplant has been recommended as treatment in cases of severe liver dysfunction; however, there are only 5 described cases of long-term survival after this procedure in patients with heat stroke. Here, we present 2 cases of young athletes who developed heat stroke. Both patients developed acute liver failure and were listed for liver transplant. Liver function tests of one patient improved, and he was discharged on postoperative day 13. The other patient showed no signs ...

Single-Center Experience With Liver Transplant Using Donors With Very High Transaminase Levels, Paulo N.A. Martins, Amanda Rawson, Babak Movahedi, Isabel M. A. Bruggenwirth, Natasha H. Dolgin, Ann-Britt Martins, Paria Mahboub, Adel Bozorgzadeh

Open Access Articles

OBJECTIVES: Elevation of transaminases has been used as a marker of hepatic ischemic injury and as a crucial parameter for liver graft assessment. However, analysis of serum transaminases has limitations regarding the quantitative assessment of liver necrosis and is not a reliable predictor of outcomes.

MATERIALS AND METHODS: We retrospectively reviewed the medical records of all liver transplants (N = 238) performed at the UMass Memorial Medical Center from 2009 to 2013.

RESULTS: Fourteen liver grafts showed high peak aminotransferases alanine aminotransferase (ALT) and aspartate aminotransferase (AST) at > 1000 U/L. This high aminotransferase group was compared with 224 donors with ...

Video Capsule Endoscopy As A Tool For Evaluation Of Obscure Overt Gastrointestinal Bleeding In The Intensive Care Unit, Shahrad Hakimian, Salmaan Jawaid, Yurima Guilarte-Walker, Jomol Mathew, David R. Cave

Open Access Articles

Background and study aims: Video capsule endoscopy (VCE) is a minimally invasive tool that helps visualize the gastrointestinal tract from the esophagus to the right colon without the need for sedation or preparation. VCE is safe with very few contraindications. However, its role and safety profile in the intensive care unit (ICU) population have not been reported. The aim of this study is to evaluate the safety, efficacy, and feasibility of VCE use in ICU patients. Patients and methods: We conducted a single-center retrospective observational study of patients who underwent VCE for evaluation of obscure overt gastrointestinal bleeding in the ...

Comparing Efficacy Of Lumen-Apposing Stents To Plastic Stents In The Endoscopic Management Of Mature Peripancreatic Fluid Collections: A Single-Center Experience, Matthew J. Fasullo, Yasir Al-Azzawai, Joan Kheder, Jeffrey Abergel, Wahid Y. Wassef

Open Access Articles

Introduction: Mature peripancreatic fluid collection (MPFC) is a known and often challenging consequence of acute pancreatitis and often requires intervention. The most common method accepted is the "step-up approach," which consists of percutaneous drainage followed, if necessary, by minimally invasive retroperitoneal necrosectomy. Our paper aims to distinguish between plastic stents and lumen-apposing stents in the endoscopic management of MPFC in terms of morbidity, mortality, and haste of fluid collection resolution.

Methods: A retrospective analysis was performed at UMass Memorial Medical Center in patients with a diagnosis of MPFC. Utilizing medical records, clinical data, radiology, as well as endoscopic evidence, patients ...

Unique Surgical Approach To A Twisted Ileal-Anal Pouch, Hannah Buettner, Maria X. Kiely, Mengdi Yao, James Yoo, Lilian Chen

Open Access Articles

Total proctocolectomy with ileal pouch-anal anastomosis can restore gastrointestinal continuity in patients requiring colectomy for ulcerative colitis, however, it can be associated with high morbidity. Reoperation for pouch-related complications is technically challenging and often leads to deterioration of pouch function or need for permanent stoma. We report a case of acute on chronic small bowel obstruction secondary to a 360-degree twist in the small bowel introduced during creation of the ileal-anal pouch. Our novel approach at repair has not been reported in past literature which included resection and re-anastomosis of the small bowel proximal to the pouch allowing for pouch ...

Alcohol Consumption Promotes Colorectal Carcinoma Metastasis Via A Ccl5-Induced And Ampk-Pathway-Mediated Activation Of Autophagy, Haodong Zhao, Danlei Chen, Rui Cao, Shiqing Wang, Dandan Yu, Yakun Liu, Yu Jiang, Mei Xu, Jia Luo, Siying Wang

Pharmacology and Nutritional Sciences Faculty Publications

There is a definite relationship between alcohol consumption and colorectal cancer (CRC) development. We investigated effect of alcohol consumption on CRC patients’ progression and prognosis by utilizing epidemiological data and found patients with alcohol consumption increased risks of tumor-node-metastasis (TNM), organ metastasis and poorer prognosis. Because their tumor tissues displayed increased expression of C-C chemokine ligand 5 (CCL5), we hypothesized CCL5 might participate in cancer progression in such patients. Ethanol increased the secretion of CCL5 in two CRC cell lines, HT29 and DLD-1. Treatment with CCL5 directly increased migratory ability of these cells, whereas neutralization or knockdown of CCL5 can ...

Radical Social Ecology As Deep Pragmatism: A Call To The Abolition Of Systemic Dissonance And The Minimization Of Entropic Chaos, Arielle Brender

Student Theses 2015-Present

This paper aims to shed light on the dissonance caused by the superimposition of Dominant Human Systems on Natural Systems. I highlight the synthetic nature of Dominant Human Systems as egoic and linguistic phenomenon manufactured by a mere portion of the human population, which renders them inherently oppressive unto peoples and landscapes whose wisdom were barred from the design process. In pursuing a radical pragmatic approach to mending the simultaneous oppression and destruction of the human being and the earth, I highlight the necessity of minimizing entropic chaos caused by excess energy expenditure, an essential feature of systems that aim ...

In Vivo And In Vitro Studies Of Cry5b And Nicotinic Acetylcholine Receptor Agonist Anthelmintics Reveal A Powerful And Unique Combination Therapy Against Intestinal Nematode Parasites, Yan Hu, Melanie Miller, Bo Zhang, Thanh-Thanh Nguyen, Martin K. Nielsen, Raffi V. Aroian

Open Access Articles

BACKGROUND: The soil-transmitted nematodes (STNs) or helminths (hookworms, whipworms, large roundworms) infect the intestines of ~1.5 billion of the poorest peoples and are leading causes of morbidity worldwide. Only one class of anthelmintic or anti-nematode drugs, the benzimidazoles, is currently used in mass drug administrations, which is a dangerous situation. New anti-nematode drugs are urgently needed. Bacillus thuringiensis crystal protein Cry5B is a powerful, promising new candidate. Drug combinations, when properly made, are ideal for treating infectious diseases. Although there are some clinical trials using drug combinations against STNs, little quantitative and systemic work has been performed to define ...