Hepatology Commons^™

Impact Of Genetic And Non-Genetic Factors On Phenotypic Diversity In Nbas-Associated Disease, Nicole Hammann, Dominic Lenz, Ivo Baric, Ellen Crushell, Carlo Dionisi Vici, Felix Distelmaier, Francois Feillet, Peter Freisinger, Maja Hempel, Anna L. Khoreva, Martin W. Laass, Yves Lacassie, Elke Lainka, Catherine Larson-Nath, Zhongdie Li, Patryk Lipiński, Eberhard Lurz, André Mégarbané, Susana Nobre, Giorgia Olivieri, Bianca Peters, Paolo Prontera, Lea D. Schlieben, Christine M. Seroogy, Cristina Sobacchi, Shigeru Suzuki, Christel Tran, Jerry Vockley

School of Medicine Faculty Publications

Biallelic pathogenic variants in neuroblastoma-amplified sequence (NBAS) cause a pleiotropic multisystem disorder. Three clinical subgroups have been defined correlating with the localisation of pathogenic variants in the NBAS gene; variants affecting the C-terminal region of NBAS result in SOPH syndrome (short stature, optic atrophy, Pelger-Huët anomaly), variants affecting the Sec 39 domain are associated with infantile liver failure syndrome type 2 (ILFS2) and variants affecting the ß-propeller domain give rise to a combined phenotype. However, there is still unexplained phenotypic diversity across the three subgroups, challenging the current concept of genotype-phenotype correlations in NBAS-associated disease. Therefore, besides examining the genetic …

Autoimmune Hepatitis: An Unusual Presentation., Ahmed Ali Aziz, Muhammad Ali Aziz, Deep Mehta, Muhammad Humayoun Rashid

Journal of Community Hospital Internal Medicine Perspectives

Autoimmune hepatitis (AIH) is a chronic inflammatory liver disease that occurs in a bimodal age distribution in the second and fifth-sixth decade of life. The disease is more prevalent in females and presents with variable clinical manifestations ranging from being asymptomatic to acute liver failure. AIH is often overlooked and not worked up in elderly patients who present with liver failure. This can lead to increased morbidity and mortality in elderly patients. AIH should be considered as a differential diagnosis in patients who present with elevated transaminases regardless of age or gender as early recognition and treatment leads to improved …

Role Of Histone Deacetylase (Hdac) In Epithelial To Mesenchymal Transition (Emt) In A Human Cholangiocyte Model Of Ischemic Cholangiopathy, Priyanshi Pragnesh Parikh

Theses and Dissertations

Organ transplants are a vital intervention for many diseases that result in end stage organ failure. Currently, the donation pool is not meeting the demands of the transplant list. Expanding this pool to include donation after cardiac death (DCD) is highly sought-after. However, the use of DCD livers can lead to increased odds of graft failure and ischemic cholangiopathy. The loss of epithelialization and fibrosis that occurs during ischemic cholangiopathy is characteristic of these cells undergoing epithelial-to-mesenchymal transition (EMT). The biological changes the cell experiences enhance migratory capacity, invasiveness, and increased resistance to apoptosis. Our earlier studies have shown differential …

Patient-Specific Genome-Scale Metabolic Models For Individualized Predictions Of Liver Disease, Alexandra Manchel, Jan B. Hoek, Ramon Bataller, Radhakrishnan Mahadevan, Rajanikanth Vadigepalli

Department of Pathology, Anatomy, and Cell Biology Faculty Papers

The prevalence of liver disease is steadily increasing, coupled with the limited availability of therapeutic treatments. Recent literature points to metabolic reprogramming as a key feature of liver failure. Hence, we sought to uncover the metabolic pathways and mechanisms associated with liver disease and acute liver failure. We generated patient-specific genome scale metabolic models by integrating RNA-seq data from patient liver samples with a generalized human metabolic model. Flux balance analysis simulations showed a distinct separation of non-alcohol associated and alcohol-associated disease states. Our analysis suggests that the alcohol associated liver has an increased flux through nucleotide and glycerophospholipid metabolic …

Substance Abuse Relapse Is Not About Willpower But Is The Culmination Of Psychological And Socioeconomic Stress, Paul A. Steffes

Clinical Research in Practice: The Journal of Team Hippocrates

The author reflects on the impact of non-judgmental listening on patient care outcomes.

Urinary Bile Acid Indices As Prognostic Biomarkers For The Complications Of Liver Diseases, Wenkuan Li

Theses & Dissertations

Hepatobilary diseases cause the accumulation of toxic bile acids (BA) in the liver, blood, and other tissues, which may lead to an unfavorable prognosis. In this study, we compared the urinary BA profile in 257 patients with hepatobilary diseases during a 7-year follow-up period. We investigated the use of the urinary BA profile to develop logistic regression models to predict the prognosis of hepatobiliary diseases in terms of developing disease-related complications, especially for ascites. The urinary BA profile was characterized by calculating BA indices, which quantify the composition, metabolism, hydrophilicity, and toxicity of the BA profile. All patients had high …

Urinary Bile Acid Indices As Diagnostic And Prognosic Biomarkers For Liver Diseases, Jawaher Alamoudi

Theses & Dissertations

Hepatobiliary diseases result in the accumulation of toxic bile acids (BA) in the liver, blood, and other tissues which may contribute to an unfavorable prognosis. We compared the urinary BA profile between 300 patients with hepatobiliary diseases vs. 103 healthy controls. Also, we investigated the use of the urinary BA profile to develop survival models to predict the prognosis of hepatobiliary diseases. The urinary BA profile, a set of non-BA parameters, and the adverse events of liver transplant and/or death were monitored in patients with cholestatic liver diseases for up to 7 years. The BA profile was characterized by calculating …

Alternative Splicing Of The Slco1b1 Gene: An Exploratory Analysis Of Isoform Diversity In Pediatric Liver., Bianca D. Van Groen, Chengpeng Bi, Roger Gaedigk, Vincent S. Staggs, Dick Tibboel, Saskia N. De Wildt, J Steven Leeder

Manuscripts, Articles, Book Chapters and Other Papers

The hepatic influx transporter OATP1B1 (SLCO1B1) plays an important role in the disposition of endogenous substrates and drugs prescribed to children. Alternative splicing increases the diversity of protein products from > 90% of human genes and may be triggered by developmental signals. As concentrations of several endogenous OATP1B1 substrates change during growth and development, with this exploratory study we investigated age-dependent alternative splicing of SLCO1B1 mRNA in 97 postmortem livers (fetus-adolescents). Twenty-seven splice variants were detected; 10 were confirmed by additional bioinformatic analyses and verified by quantitative polymerase chain reaction, and selected for detailed analysis based on relative abundance, association with …

Acute Diagnosis Of Wilson’S Disease In A Teenage Patient, Sarah Irvin, Ryan Mccarthy

Marshall Journal of Medicine

Wilson’s Disease, a rare autosomal recessive genetic disease, is caused by a mutation in the ATP7B enzyme gene. Without this enzyme, copper builds up in the brain, liver, and cornea causing a multitude of symptoms. It is important to consider Wilson’s disease because the prognosis is dependent on timely diagnosis. This is an interesting case of a 19-year-old male who presented with suicidal thoughts and rapid weight loss. After many months and an extensive work-up, Wilson’s Disease was diagnosed. Due to his rapid decline, he was transferred to a larger university healthcare center where he is currently enrolled in clinical …

Novel Mechanisms And Biomarkers In Alcohol-Induced Organ Injury., Christine E. Dolin

Electronic Theses and Dissertations

Background. Ethanol (EtOH) consumption is known to affect multiple organs; this is unsurprising, as the concentration of EtOH in the blood at relevant doses reaches the millimolar range. The overarching goal of this dissertation was to elucidate mechanisms of alcohol-induced organ injury, specifically the effects of alcohol on the hepatic extracellular matrix (ECM) proteome, the alcoholic hepatitis (AH) plasma peptidome, and the effects of alcohol on the renal cortex proteome and transcriptome. Methods. Mice were pair-fed ethanol-containing liquid diet chronically, and then some mice were administered lipopolysaccharide (LPS). Liver sections from these mice were processed in a series of increasingly …

Transplanted Adult Human Hepatic Stem/Progenitor Cells Prevent Histogenesis Of Advanced Hepatic Fibrosis In Mice Induced By Carbon Tetrachloride, Yanzhen Bi, Xiyu Liu, Chuanping Si, Ye Hong, Yongke Lu, Pengfei Gao, Yonghong Yang, Xiaobei Zhang, Yibo Wang, Huabao Xiong, Zhongping Duan, Yu Chen, Feng Hong

Pharmacology, Physiology and Toxicology

Transplantation of adult human hepatic stem/progenitor cells (hHSPCs) has been considered as an alternative therapy, replacing donor liver transplantation to treat liver cirrhosis. This study assessed the antifibrotic effects of hHSPCs in mice with fibrosis induced by carbon tetrachloride (CCl₄) and examined the actions of hHSPCs on the fibrogenic activity of human hepatic stellate cells (HSCs) in a coculture system. Isolated hHSPCs expressed stem/progenitor cell phenotypic markers. Mice were given CCl₄ (twice weekly for 7 weeks) and hHSPC transplantation weekly. CCl₄ induced advanced fibrosis (bridging fibrosis and cirrhosis) in mice, which was prevented by hHSPC transplantation. …

Inhibition Of Triggering Receptor Expressed On Myeloid Cells 1 Ameliorates Inflammation And Macrophage And Neutrophil Activation In Alcoholic Liver Disease In Mice, David Tornai, Istvan Furi, Zu T. Shen, Alexander B. Sigalov, Sahin Coban, Gyongyi Szabo

Gyongyi Szabo

Alcoholic liver disease (ALD) is characterized by macrophage and neutrophil leukocyte recruitment and activation in the liver. Damage- and pathogen-associated molecular patterns contribute to a self-perpetuating proinflammatory state in ALD. Triggering receptor expressed on myeloid cells 1 (TREM-1) is a surface receptor that amplifies inflammation induced by toll-like receptors (TLRs) and is expressed on neutrophils and monocytes/macrophages. We hypothesized that TREM-1 signaling contributes to proinflammatory pathway activation in ALD. Using an in vivo ALD model in mice, we tested the effects of ligand-independent TREM-1 inhibitory peptides that were formulated into human high-density lipoprotein (HDL)-mimicking complexes GF9-HDL and GA/E31-HDL. As revealed …

Aortoduodenal Fistula Forms From Primary Aortic Stump Graft In A Two-Time Multi-Visceral Transplant Patient With Presentation Of Gastrointestinal Bleed And Bowel Perforation: A Case Report, Brielle Corrente

Graduate Student Research Symposium

Usually not diagnosed until open laparotomy, aortoduodenalfistulas (ADF) are one of the rarest complications of intestinal transplant surgery. With an incidence rate of only 0.04% at autopsy and only 250 documented cases since the early 1800’s, aortoduodenal fistulas are the most deadly complications of intestinal transplantation with a mortality rate of 100% without surgical intervention. A 39 year old, two-time multi-visceral transplant African American female patient suffered from a primary aortoduodenal fistula formation in a primary modified multi-visceral transplant aortic stump graft site. With emergency open laparotomy repair, revascularization of the secondary multi-visceral transplant was performed, saving the life of …

Identification Of Novel Regulatory Genes In Apap Induced Hepatocyte Toxicity By A Genome-Wide Crispr-Cas9 Screen., Katherine Shortt, Daniel P. Heruth, Nini Zhang, Weibin Wu, Shipra Singh, Ding-You Li, Li Qin Zhang, Gerald J. Wyckoff, Lei S Qi, Craig A. Friesen, Shui Qing Ye

Manuscripts, Articles, Book Chapters and Other Papers

Acetaminophen (APAP) is a commonly used analgesic responsible for more than half of acute liver failure cases. Identification of previously unknown genetic risk factors would provide mechanistic insights and novel therapeutic targets for APAP-induced liver injury. This study used a genome-wide CRISPR-Cas9 screen to evaluate genes that are protective against, or cause susceptibility to, APAP-induced liver injury. HuH7 human hepatocellular carcinoma cells containing CRISPR-Cas9 gene knockouts were treated with 15 mM APAP for 30 minutes to 4 days. A gene expression profile was developed based on the 1) top screening hits, 2) overlap of expression data from APAP overdose studies, …

Progressive Hypoxia-On-A-Chip: An In Vitro Oxygen Gradient Model For Capturing The Effects Of Hypoxia On Primary Hepatocytes In Health And Disease, Young Bok Abraham Kang, Jinsu Eo, Beyza Bulutoglu, Martin L. Yarmush, O. Berk Usta

Faculty Publications - Biomedical, Mechanical, and Civil Engineering

Oxygen is vital to the function of all tissues including the liver and lack of oxygen, that is, hypoxia can result in both acute and chronic injuries to the liver in vivo and ex vivo. Furthermore, a permanent oxygen gradient is naturally present along the liver sinusoid, which plays a role in the metabolic zonation and the pathophysiology of liver diseases. Accordingly, here, we introduce an in vitro microfluidic platform capable of actively creating a series of oxygen concentrations on a single continuous microtissue, ranging from normoxia to severe hypoxia. This range approximately captures both the physiologically relevant oxygen gradient …

Prothrombin Complex Concentrates Or Recombinant Factor Viia Are More Effective Than Fresh-Frozen Plasma At Lowering Inr In Patients With Liver Disease, Abel J. Ignatius

Clinical Research in Practice: The Journal of Team Hippocrates

A critical appraisal and clinical application of Kwon JO, MacLaren R. Comparison of fresh-frozen plasma, four-factor prothrombin complex concentrates, and recombinant factor VIIa to facilitate procedures in critically ill patients with coagulopathy from liver disease: a retrospective cohort study. Pharmacotherapy. 2016;36(10):1047-1054. doi: 10.1002/phar.1827

Metabolic Patterning On A Chip: Towards In Vitro Liver Zonation Of Primary Rat And Human Hepatocytes, Young Bok (Abraham) Kang, Jinsu Eo, Safak Mert, Martin L. Yarmush, O. Berk Usta

Faculty Publications - Biomedical, Mechanical, and Civil Engineering

An important number of healthy and diseased tissues shows spatial variations in their metabolic capacities across the tissue. The liver is a prime example of such heterogeneity where the gradual changes in various metabolic activities across the liver sinusoid is termed as “zonation” of the liver. Here, we introduce the Metabolic Patterning on a Chip (MPOC) platform capable of dynamically creating metabolic patterns across the length of a microchamber of liver tissue via actively enforced gradients of various metabolic modulators such as hormones and inducers. Using this platform, we were able to create continuous liver tissues of both rat and …

Effect Of Stem Cell And Vitamin E For The Reduction Of Liver Fibrosis, Sulaiman Shams, Salman Khan, Muhammad Ayaz, Haider Ali Khan, Hammad Hassan

Centre for Regenerative Medicine & Stem Cell Research

Liver disease is seventh leading cause of death worldwide. In the past, liver transplantation was thought to be the only treatment for the last stage liver disease but currently stem cells therapy is an alternative method for the treatment of liver disease. So mesenchymal stem cells (MSCs) transplantation is one of the best tool for treatment of liver disease. The aim of the current study was to investigate the combined effect of vitamin E (Vit E) and MSCs on liver fibrosis. Liver damage was induced in male albino mice intraperitoneally with carbon tetrachloride (CCl4) twice a week for six weeks. …

Changes In Dietary Patterns And Body Composition Within 12 Months Of Liver Transplantation, Mccoy Simone, Katrina Campbell, Annie-Claude Lassemillante, Matthew P. Wallen, Jonathan Fawcett, Maree Jarrett, Graeme A. Macdonald, Ingrid J. Hickman

Katrina Campbell

Background:

Cardiometabolic risk factors are increasing in liver transplant recipients (LTR). Influencing dietary factors have not been assessed. The aim of this observational study was to assess changes in weight, metabolic function, dietary intake and eating behaviours in the first year after orthotopic liver transplantation (OLT).

Methods:

Consecutive recruitment of 17 patients (14 males) awaiting OLT at a single tertiary hospital. Dietary intake, food behaviours and anthropometry were recorded at baseline, and 6 and 12 months post-transplant.

Results:

By 12 months, patients had gained on average 7.3% of body weight. The prevalence of overweight or obesity increased from baseline 53% …

Nutritional Approaches To Achieve Weight Loss In Nonalcoholic Fatty Liver Disease., Christine C Hsu, Erik Ness, Kris V Kowdley

Articles, Abstracts, and Reports

Nonalcoholic fatty liver disease (NAFLD) can range in spectrum from simple hepatic steatosis to nonalcoholic steatohepatitis (NASH), which is characterized by lipotoxicity, hepatocellular ballooning, and inflammation and can progress to cirrhosis. Weight loss is the cornerstone treatment for NAFLD and NASH. Various randomized controlled trials have shown that weight loss of ≥5-10% leads to significant improvements in hepatic steatosis. Diets high in sodium and fructose have been implicated in the pathogenesis of NAFLD. Although some clinical studies suggest that an isocaloric high-fructose diet does not worsen NAFLD, these clinical studies are often short in duration. More recently, the Dietary Approaches …

The Effect Of Hiv Infection And Hcv Viremia On Inflammatory Mediators And Hepatic Injury-The Women's Interagency Hiv Study., Sheila M Keating, Jennifer L Dodge, Philip J Norris, John Heitman, Stephen J Gange, Audrey L French, Marshall J Glesby, Brian R Edlin, Patricia S Latham, Maria C Villacres, Ruth M Greenblatt, Marion G Peters

Pathology Faculty Publications

Hepatitis C virus infection induces inflammation and while it is believed that HIV co-infection enhances this response, HIV control may reduce inflammation and liver fibrosis in resolved or viremic HCV infection. Measurement of systemic biomarkers in co-infection could help define the mechanism of inflammation on fibrosis and determine if HIV control reduces liver pathology. A nested case-control study was performed to explore the relationship of systemic biomarkers of inflammation with liver fibrosis in HCV viremic and/or seropositive women with and without HIV infection. Serum cytokines, chemokines, growth factors and cell adhesion molecules were measured in HIV uninfected (HIV-, n = …

Lifestyle And Biological Risk Factors For Liver Fibrosis In The Miami Adult Studies On Hiv (Mash) Cohort: An Hiv Infected And Hiv/Hcv Co-Infected Population, Tiffanie S. Stewart

FIU Electronic Theses and Dissertations

Liver disease is now a leading cause of non-AIDS related morbidity and mortality in people living with HIV (PLWH). The present study investigated the interplay between adverse lifestyle factors that are prevalent in PLWH, biological mediators of liver pathogenesis, and a non-invasive measure of liver fibrosis (FIB-4 index) in HIV mono- and HIV/HCV co-infected individuals.

The results of this investigation in the Miami Adult Studies of HIV (MASH) cohort show that the odds of liver fibrosis progression significantly increased over two years for HIV mono-infected participants who drank alcohol hazardously (OR 3.038, P=0.048), and had BMI ≥ 28kg/m^{2 …}

Expression Of The Non-Structural Proteins Ns3/4a Of The Hepatitis C Virus Using A Genetically Modified Vesicular Stomatitis Virus Vector System, Angela Ye Seul Kim

2016 Undergraduate Awards

Hepatitis C virus (HCV) infection is one of the leading causes of chronic liver diseases. Despite advancements in the development of antivirals and efforts to combat HCV infections, there is currently no vaccine for HCV. Adopting traditional approaches to HCV vaccine development has been impractical due to the lack of reproducible cell culture systems that can support HCV replication. In this study, the New Jersey serotype of recombinant vesicular stomatitis virus (rVSVNJ) was used as the vector to express non-structural proteins NS3/4A of genotype 1a HCV for potential vaccine purposes. The rVSVNJ-GMM vector was genetically modified by changing glycine to …

Modulation Of Body Weight By Intestinal Flora In Orphan Nuclear Receptor Shp-/- Mice, Ryan Mifflin

Williams Honors College, Honors Research Projects

The whole-body deletion of small heterodimer partner (SHP) in mice is associated with protection from diet-induced obesity and hepatic steatosis upon feeding of a western diet. This protection was reported to be mediated through decreases in hepatic gene expression for lipogenesis, as well as increases in gene expression for fatty acid oxidation. SHP has been known to regulate the expression of the CYP7A1 gene, encoding the rate-limiting enzyme for bile acid synthesis, thereby altering the bile acid pool. The effects of this altered bile acid profile on the gut microbiome are unknown, as some bacteria in the gut are responsible …

Autophagy Protects Against Cyp2e1/Chronic Ethanol-Induced Hepatotoxicity, Yongke Lu, Arthur I. Cederbaum

Pharmacology, Physiology and Toxicology

Autophagy is an intracellular pathway by which lysosomes degrade and recycle long-lived proteins and cellular organelles. The effects of ethanol on autophagy are complex but recent studies have shown that autophagy serves a protective function against ethanol-induced liver injury. Autophagy was found to also be protective against CYP2E1-dependent toxicity in vitro in HepG2 cells which express CYP2E1 and in vivo in an acute alcohol/CYPE1-dependent liver injury model. The goal of the current report was to extend the previous in vitro and acute in vivo experiments to a chronic ethanol model to evaluate whether autophagy is also protective against CYP2E1-dependent liver …

Inhibition Of Sterile Danger Signals, Uric Acid And Atp, Prevents Inflammasome Activation And Protects From Alcoholic Steatohepatitis In Mice., Arvin Iracheta-Vellve, Jan Petrasek, Abhishek Satishchandran, Benedek Gyongyosi, Banishree Saha, Karen Kodys, Katherine Fitzgerald, Evelyn Kurt-Jones, Gyongyi Szabo

Gyongyi Szabo

Background & Aims: The inflammasome is a well-characterized inducer of inflammation in alcoholic steatohepatitis (ASH). Inflammasome activation requires two signals for mature interleukin (IL)-1β production. Here we asked whether metabolic danger signals trigger inflammasome activation in ASH.

Results:The sterile danger signals, ATP and uric acid, were increased in the serum and liver of alcohol-fed mice. Depletion of uric acid or ATP, or lack of ATP signaling attenuated ASH and prevented inflammasome activation and its major downstream cytokine, IL-1β. Pharmacological depletion of uric acid with allopurinol provided significant protection from alcohol-induced inflammatory response, steatosis and liver damage, and additional protection was …

Liver Sinusoid On A Chip: Long-Term Layered Co-Culture Of Primary Rat Hepatocytes And Endothelial Cells In Microfluidic Platforms, Young Bok (Abraham) Kang, Temitope R. Sodunke, Jason Lamontagne, Joseph Cirillo, Caroline Rajiv, Michael J. Bouchard, Moses Noh

Faculty Publications - Biomedical, Mechanical, and Civil Engineering

We describe the generation of microfluidic platforms for the co-culture of primary hepatocytes and endothelial cells; these platforms mimic the architecture of a liver sinusoid. This paper describes a progressional study of creating such a liver sinusoid on a chip system. Primary rat hepatocytes (PRHs) were co-cultured with primary or established endothelial cells in layers in single and dual microchannel configurations with or without continuous perfusion. Cell viability and maintenance of hepatocyte functions were monitored and compared for diverse experimental conditions. When primary rat hepatocytes were co-cultured with immortalized bovine aortic endothelial cells (BAECs) in a dual microchannel with continuous …

Circulating Microrna Profiles In Human Patients With Acetaminophen Hepatotoxicity Or Ischemic Hepatitis, Jeanine Ward, Chitra Kanchagar, Isana Veksler-Lublinsky, Rosalind C. Lee, Mitchell R. Mcgill, Hartmut Jaeschke, Steven C. Curry, Victor R. Ambros

Victor R. Ambros

We have identified, by quantitative real-time PCR, hundreds of miRNAs that are dramatically elevated in the plasma or serum of acetaminophen (APAP) overdose patients. Most of these circulating microRNAs decrease toward normal levels during treatment with N-acetyl cysteine (NAC). We identified a set of 11 miRNAs whose profiles and dynamics in the circulation during NAC treatment can discriminate APAP hepatotoxicity from ischemic hepatitis. The elevation of certain miRNAs can precede the dramatic rise in the standard biomarker, alanine aminotransferase (ALT), and these miRNAs also respond more rapidly than ALT to successful treatment. Our results suggest that miRNAs can serve as …

Burkitt Lymphoma Presenting As Left Lateral Rectus Palsy, Daniel Tseytlin Do, Usman Shah Md

Department of Medicine

No abstract provided.

Analysis Of The Role Of Astrocyte Elevated Gene-1 In Normal Liver Physiology And In The Onset And Progression Of Hepatocellular Carcinoma, Chadia L. Robertson

Theses and Dissertations

First identified over a decade ago, Astrocyte Elevated Gene-1 (AEG-1) has been studied extensively due to early reports of its overexpression in various cancer cell lines. Research groups all over the globe including our own have since identified AEG-1 overexpression in cancers of diverse lineages including cancers of the liver, colon, skin, prostate, breast, lung, esophagus, neurons and neuronal glia as compared to matched normal tissue. A comprehensive and convincing body of data currently points to AEG-1 as an essential component, critical to the progression and perhaps onset of cancer. AEG-1 is a potent activator of multiple pro-tumorigenic signal transduction …