Gastroenterology Commons^™

Spectral Characterization Of Colorectal Cancer Using Excitation-Scanning Hyperspectral Imaging, Natalie Hadad

Honors Theses

Colorectal cancer is one of the most common and deadly cancers worldwide, with a lifetime risk of approximately one in twenty-three for men and one in twenty-five for women. Although early detection significantly improves survival, current diagnostic approaches such as tissue biopsy are invasive, reliant on subjective interpretation, have extended turnaround times, and risk missing flat or depressed lesions that are more difficult to detect than raised polyps. These limitations highlight the need for objective, minimally invasive technologies capable of detecting early tissue changes. This study investigates excitation-scanning hyperspectral imaging (Ex-HSI) as a label-free optical approach for identifying colorectal cancer–associated …

Gastrointestinal Symptoms Associated With Sodium Bicarbonate Supplementation Protocols: A Systematic Review, Ian P. Winter, Paul Sarac, Patrick B. Wilson

Exercise Science Faculty Publications

Sodium bicarbonate positively impacts performance, but its associated gastrointestinal symptoms (GIS) may limit use. This systematic review synthesized literature that has evaluated GIS with sodium bicarbonate supplementation. Literature searches were performed from February 2024-March 2026. Eligible studies provided ≥ 5 g of sodium bicarbonate within a 24-h period or, if a multi-day protocol, at least one day involving ≥ 5 g. Included studies had a placebo group/condition or a comparison group/condition that created a contrast related to delivery method, form, or dose. In total, 101 investigations were summarized in six categories: acute single dosing (n = 35); acute spread dosing …

Metagenomic Characterization Of Gut Microbiota In Children With Autism Spectrum Disorder: Microbial Signatures And Modulation By Anti-Inflammatory Diet And Probiotics, Marysol Valencia-Buitrago, Rodrigo Dias Oliveira-Carvalho, Valbert Cardoso, Jessica Triviño-Valencia, Luisa Matilde Salamanca-Duque, Vanessa Martínez-Díaz, Jovanny Zabaleta, Narmer Fernando Galeano-Vanegas, Carlos Andrés Naranjo-Galvis

School of Medicine Faculty Publications

Background: Autism Spectrum Disorder (ASD) is increasingly associated with alterations in gut microbiota, intestinal permeability, and immune dysregulation. However, integrative studies exploring these mechanisms in Latin American populations are lacking. Objective: To characterize gut microbiota profiles in Colombian children with ASD and evaluate the effects of two microbiota-targeted interventions, an anti-inflammatory diet and a probiotic formulation, on microbial diversity and taxonomic composition. Methods: In a two-phase study, shotgun metagenomic sequencing was performed on fecal samples from 23 children with ASD and 7 typically developing (TD) controls. In the second phase, 17 children with ASD were randomized to receive a 12-week …

The Colonic Crypt: Cellular Dynamics And Signaling Pathways In Homeostasis And Cancer, Anh L. Nguyen, Molly A. Lausten, Bruce M. Boman

College of Life Sciences Faculty Papers

The goal of this review is to expand our understanding of how the cellular organization of the normal colonic crypt is maintained and elucidate how this intricate architecture is disrupted during tumorigenesis. Additionally, it will focus on implications for new therapeutic strategies targeting Epithelial-Mesenchymal Transition (EMT). The colonic crypt is a highly structured epithelial unit that functions in maintaining homeostasis through a complex physiological function of diverse cell types: SCs, transit-amplifying (TA) progenitors, goblet cells, absorptive colonocytes, Paneth-like cells, M cells, tuft cells, and enteroendocrine cells. These cellular subpopulations are spatially organized and regulated by multiple crucial signaling pathways, including …

The Brescia International Multidisciplinary Consensus Guidelines On The Optimal Pathology Assessment And Multidisciplinary Pathways Of Non-Pancreatic Neoplasms In And Around The Ampulla Of Vater (Peripan), Mohammad Abu Hilal, Bas A Uijterwijk, Daniël H L Lemmers, Boris V Janssen, Marc G Besselink, Denise Bianchi, Arantza Fariña, Noriyoshi Fukushima, Anthony J Gill, Seung-Mo Hong, Alyssa Krasinskas, Claudio Luchini, Laura Melocchi, Giulio Rossi, Aldo Scarpa, Olca Basturk, Deyali Chatterjee, Angela Chou, Irene Esposito, Roger Feakins, Bas Groot Koerkamp, Ralph H Hruban, Stefano La Rosa, Chanjuan Shi, Aatur Singhi, Joanne Verheij, Huamin Wang, Sergio Alfieri, Fabio Ausania, Adnan Alseidi, Marco J Bruno, Ugo Boggi, Claudio Bnà, Christos Dervenis, Massimo Falconi, Michele Ghidini, Jakob W Kist, Giovanni Marchegiani, Michele Milella, Roberto Salvia, Ajith Siriwardena, Hanneke Wilmink, Alberto Zaniboni, Shaimaa Al-Janabi, Maia Blomhoff Holm, Eva Roos, Naoki Sano, In Hye Song, Zeynep Tarcan, Gianpaolo Balzano, Isabella Frigerio, Alfredo Guglielmi, Giuseppe Malleo, Horacio Asbun, Volkan Adsay, Caroline Verbeke

Faculty, Staff and Student Publications

IMPORTANCE: The lack of multidisciplinary workflow guidelines and clear definitions and classifications for neoplasms in and around the ampulla of Vater results in inconsistencies affecting patient care and research.

OBJECTIVE: The PERIPAN international multidisciplinary consensus group aimed to standardize the multidisciplinary diagnostic workflow and achieve consensus on definitions and classifications in order to ensure proper classification and optimal diagnostic assessment and consequently to improve patient care and future research.

DESIGN: An international team of 43 experts (pathologists, surgeons, radiologists, gastroenterologists, oncologists) from 12 countries identified knowledge gaps, reviewed 37061 articles, and proposed recommendations using the Scottish Intercollegiate Guidelines Network methodology …

Egg White Hydrolysate In Hypertension: A Mechanistic Investigation Of Gut Microbiota Dependent And Independent Pathways, Emerson David Nolasco

Dissertations and Doctoral Documents, University of Nebraska-Lincoln, 2023–

Cardiovascular diseases are one of the leading causes of mortality worldwide in which hypertension is a risk factor. Present pharmacological interventions require long-term adherence to the therapy and are often associated with undesirable side effects. Moreover, treatments have overlooked the role of the microbiome in the development of hypertension. Egg white hydrolysate (EWH) has exhibited antihypertensive properties with potential to be used as a natural alternative for the prevention and management of hypertension. However, EWH peptide’s effect on the gut microbiome remains yet to be elucidated. Studies have described that a portion of the ingested protein can remain undigested as …

In Silico Prediction Of Cytotoxic T-Cell Epitopes From Helicobacter Pylori Virulence Factors Using An Immunoinformatics Approach, Demy Valerie Chacon, Kiana Alika Co, Daphne Noreen Enriquez, Aubrey Love Labarda, Reanne Eden Manongsong, Edward Kevin B. Bragais

Biology Faculty Publications

Background: Helicobacter pylori infects approximately half of the global population, leading to gastric and duodenal ulcers. Despite the availability of antibiotics, challenges such as patient reluctance, high treatment costs, and antibiotic resistance limit their effectiveness, making vaccination a promising alternative. This study used immunoinformatics to identify candidate epitopes for a multiepitope vaccine construct against H. pylori.

Material and methods: The protein variability server was utilized for conservation analysis. The epitopes were screened for antigenicity, allergenicity, toxicity, cross-reactivity, and population coverage. Selected epitopes were docked with their corresponding human leukocyte antigen (HLA) alleles, and thermodynamic quantities were determined. Five virulence …

Longitudinal Analysis Of Gut Microbiome And Metabolome Correlates Of Response And Toxicity With Idecabtagene Vicleucel, Satabdi Saha, Lubna Rehman, Abdur Rehman, Faezeh Darbaniyan, Donna M Weber, Melody Becnel, Mahmoud Gaballa, Sheeba K Thomas, Hans C Lee, Chia-Chi Chang, Reetakshi Arora, Meghan Menges, Salvatore Corallo, Marco L Davila, Frederick L Locke, Mark R Tanner, Sattva S Neelapu, Elizabeth J Shpall, Christopher R Flowers, Robert Z Orlowski, Robert R Jenq, Michael D Jain, Christine Peterson, Doris K Hansen, Neeraj Y Saini, Krina K Patel

Faculty, Staff and Student Publications

Increasing evidence suggests that the gut microbiome may influence the responses and toxicities associated with chimeric antigen receptor T-cell (CAR-T) therapy. We conducted whole-genome shotgun sequencing on stool samples (N = 117) collected at various times from patients with multiple myeloma (n = 33) who underwent idecabtagene vicleucel (ide-cel) anti-B-cell maturation antigen CAR-T therapy. We observed a significant decrease in bacterial diversity after ide-cel infusion, along with significant differences in the bacterial composition linked to therapy response and toxicities. Specifically, we found significant enrichment of Flavonifractor plautii, Bacteroides thetaiotaomicron, Blautia fecis, and Dysosmobacter species in ide-cel responders. A notable finding …

Risk Of Pancreatic Cancer In Glycemically Defined New-Onset Diabetes: A Prospective Cohort Study, Suresh T Chari, Bechien Wu, Camden Lopez, Eva Lustigova, Qiaoling Chen, Stephen K Van Den Eeden, Amethyst D Leimpeter, William Fisher, Amy Wood, Ashley S Alexander, John Valenta, Santhi Swaroop Vege, Erin E Carlson, Kari G Rabe, Phil A Hart, Lu Qian, Ying-Qi Zhao, Nadia Yosuf, Lynn Matrisian, Barbara Kenner, Jo Ann Rinaudo, Anirban Maitra, Ziding Feng

Faculty, Staff and Student Publications

Background & aims: The increased 3-year incidence of pancreatic cancer after new-onset diabetes observed in retrospective studies needs prospective validation. It is unknown whether incidence varies by race and ethnicity.

Methods: In a prospective, observational study using active real-time surveillance of electronic health records, we identified 18,838 adults 50 years or older with glycemically defined new-onset diabetes (GNOD). In this interim analysis, we report 3-year Kaplan-Meier estimates of the proportion diagnosed with pancreatic cancer after GNOD (absolute incidence [95% CI]) and associated standardized incidence ratio (SIR) by race and ethnicity, overall 3-year incidence of pancreatic cancer adjusting for racial distribution …

Trem2 Depletion In Pancreatic Cancer Elicits Pathogenic Inflammation And Accelerates Tumor Progression Via Enriching Il-1Β+ Macrophages, Daowei Yang, Xinlei Sun, Hua Wang, Ignacio I Wistuba, Huamin Wang, Anirban Maitra, Yang Chen

Faculty, Staff and Student Publications

Background & aims: Pancreatic ductal adenocarcinoma (PDAC) has a complex tumor microenvironment enriched with tumor-associated macrophages. Triggering receptor expressed on myeloid cells 2 (TREM2) is highly expressed by a subset of macrophages in PDAC. However, the functional role of TREM2 in PDAC progression remains elusive.

Methods: We generated a novel transgenic mouse model (KPPC;Trem2-/-) that enables the genetic depletion of TREM2 in the context of spontaneous PDAC development. Single-cell RNA-sequencing analysis was used to identify changes in the tumor immune microenvironment on TREM2 depletion. We evaluated the impacts of TREM2 depletion on the tumor immune microenvironment to elucidate the functions …

Efficacy And Safety Of Larotrectinib In Patients With Trk Fusion Gastrointestinal Cancer, Changsong Qi, Lin Shen, Thierry Andre, Hyun Cheol Chung, Timothy L Cannon, Elena Garralda, Antoine Italiano, Damian T Rieke, Tianshu Liu, Domnita-Ileana Burcoveanu, Natascha Neu, Chiara E Mussi, Rui-Hua Xu, David S Hong, Alexander Drilon, Jordan Berlin

Faculty, Staff and Student Publications

Background: Larotrectinib is the first-in-class, highly selective TRK inhibitor with demonstrated efficacy in various TRK fusion solid tumours. We report the efficacy and safety of larotrectinib in patients with TRK fusion gastrointestinal (GI) cancer.

Methods: Patients with TRK fusion GI cancer from NAVIGATE (NCT02576431) were included. Response was independent review committee (IRC)-assessed per RECIST v1.1.

Results: As of July 2023, 44 patients were enrolled. Tumour types included colorectal (CRC; n = 26), pancreatic (n = 7), cholangiocarcinoma (n = 4), gastric (n = 3), and one each of appendiceal, duodenal, oesophageal and hepatic cancers. Of the 26 patients …

Rising Use Of Immune Checkpoint Inhibitors And The Escalating Burden Of Gastrointestinal And Hepatic Toxicities: A Nine-Year Analysis, Donghyun Ko, Do Han Kim Md, Pedro Palacios Argueta Md, Wilhelm S. Basegoda Md, Jose A. Porres, Francis F. Fadi, Jana G. Hashash, Francis A. Farraye, Paul T. Kroner Md

Posters

The advent of immune checkpoint inhibitors (ICIs), including programmed death 1 (PD-1), PD-L1, and cytotoxic T-lymphocyte-associated antigen 4 (CTLA-4) inhibitors, has revolutionized cancer therapeutics, markedly improving survival in various malignancies. However, their expanding utilization has been paralleled by the emergence of immune-related adverse events (irAEs), particularly gastrointestinal (GI) and hepatic toxicities, which pose significant challenges in clinical practice. These toxicities can manifest as a spectrum of conditions, from mild transient symptoms to severe, life-threatening complications, necessitating a better understanding of their prevalence and trends. This study aims to evaluate the temporal changes in ICI use and associated GI and hepatic …

Effects Of Social Isolation On Cecum Opioid Receptor Expression And Affective Behavior, Jordan Riser, John Tkaczynski, Nicole Shellenbarger, Maya Patel, Daniel Chandler, Daniel Manvich

Rowan-Virtua Research Day

BACKGROUND

Psychological stress can induce gastrointestinal symptoms and exacerbate existing gastrointestinal disorders, indicating an interaction between the central and enteric nervous systems. Central nervous system activation of opioid receptors stimulates sympathetic outflow to the enteric nervous system, delaying motility and reducing gastrointestinal secretions, producing a similar clinical presentation to IBS.

HYPOTHESIS

We hypothesize that social isolation induces anxiety states, disrupting homeostatic noradrenergic activity in the brain and gut, leading to neurophysiological changes in the cecum characterized by altered expression of opioid receptors.

METHODS

Sprague-Dawley rats were housed in either group (control) or socially isolated conditions. Affective behavior was assessed using …

Elucidating The Multi-Omics Of Early-Onset Colorectal Cancer, Jumanah Alshenaifi

Dissertations and Theses (Open Access)

The incidence and mortality rates of sporadic early-onset colorectal cancer have increased in recent decades, but there is no clear etiological basis for this trend. EOCRC is commonly defined as colon and rectal cancers diagnosed before the age of 50 years. The rising incidence of EOCRC has made it the second most common cancer and the third leading cause of cancer death in this age group. The rising incidence of EOCRC is also documented internationally in more than 20 countries across different continents. Clinically, EOCRC has a distinct, more aggressive clinical profile than LOCRC. While approximately 15% of EOCRC cases …

Toward The Application Of Natural Language Processing In Electronic Health Record Analysis For Taxonomy Development, Latoya Mcdonald

All Dissertations

Electronic health records (EHRs) are pivotal resources for nurse practice because they increase the timeliness and reliability of patient information at the point of care and support access by multiple healthcare providers and the individual patients themselves. However, it is widely recognized that data extraction from EHRs is challenging due to the variability in the language used in clinical care notes and the lack of standardized terminology across healthcare systems. The broad objective of this dissertation is to develop taxonomy-based classification models for nursing care by applying feature engineering approaches to EHRs that include nursing care of ostomy patients following …

Multiparametric Mri Scoring System Of The Pancreas For The Diagnosis Of Chronic Pancreatitis, Temel Tirkes, Dhiraj Yadav, Darwin L Conwell, Xuandong Zhao, Anil K Dasyam, Vivek Gowdra Halappa, Aashish Patel, Zarine K Shah, Jordan Swensson, Naoki Takahashi, Sudhakar Venkatesh, Ashley Wachsman, Liang Li, Kristofer Jennings, Yunlong Yang, Phil A Hart, Stephen J Pandol, Walter G Park, Santhi Swaroop Vege, Mark Topazian, Paul R Territo, Scott A Persohn, Dana K Andersen, Evan L Fogel, Consortium For The Study Of Chronic Pancreatitis, Diabetes, And Pancreatic Cancer (Cpdpc)

Faculty, Staff and Student Publications

Background: Ductal features alone may not offer high diagnostic sensitivity or most accurate disease severity of chronic pancreatitis (CP).

Purpose: Diagnose CP based on multiparametric MRI and MRCP features.

Study type: Prospective.

Population: Between February 2019 and May 2021, 46 control (23 males, 49.3 ± 14.1 years), 45 suspected (20 males, 48.7 ± 12.5 years), and 46 definite (20 males, 53.7 ± 14.6 years) CP patients were enrolled at seven hospitals enrolled in the MINIMAP study. CP classification was based on imaging findings and clinical presentation.

Field strength and sequences: 1.5 T. T1-weighted (T1W) spoiled gradient echo, T1 map with …

Fecal Immunochemical Test Positivity Thresholds: An International Survey Of Population-Based Screening Programs, Graeme P Young, Sally C Benton, Robert S Bresalier, Han-Mo Chiu, Evelien Dekker, Callum G Fraser, Marieke A M Frasa, Stephen P Halloran, Michael Hoffmeister, Susan Parry, Kevin Selby, Carlo Senore, Harminder Singh, Erin L Symonds

Faculty, Staff and Student Publications

Background: The fecal immunochemical test for hemoglobin (FIT) is now a widely used non-invasive test in population-based organized screening programs for colorectal neoplasia. The positivity thresholds of tests currently in use are based on the fecal hemoglobin concentration (f-Hb), but the rationale for the adopted thresholds are not well documented. To understand current global usage of FIT in screening programs we conducted an international survey of the brands of FIT used, the f-Hb positivity threshold applied and the rationale for the choice.

Methods: All members of the World Endoscopy Organization CRC Screening Committee were invited to complete an eight-element initial …

Prevalence And Patterns Of Opioid Use In Chronic Pancreatitis, Anna Evans Phillips, Darwin L Conwell, Shuang Li, Jami L Saloman, Phil A Hart, Evan L Fogel, Santhi Swaroop Vege, Dana K Andersen, William E Fisher, Christopher E Forsmark, Stephen Pandol, Walter G Park, Mark D Topazian, Stephen K Van Den Eeden, Jose Serrano, Liang Li, Dhiraj Yadav

Faculty, Staff and Student Publications

Introduction: Opioids are used to treat pain in chronic pancreatitis (CP), but little is known about current use patterns. The aim of this study was to characterize the utilization of opioids and associations with clinical characteristics in adult patients with CP.

Methods: This cross-sectional analysis used baseline data from participants with definite CP enrolled in a cohort study in the United States (PROspective Evaluation of CP for EpidEmiologic and Translational StuDies). Data on demographics, pain medication use, healthcare utilization, disability, and pain patterns were systematically collected in case report forms while quality of life was assessed with patient-reported outcome instruments. …

Effects Of Prebiotic Phytocompound Administration In Gestational Diabetic Dams And Its Influence On Offspring Cognitive Outcomes, Gayathri Jagadeesan, Tushar K Das, Jennifer M Mendoza, Ghalya Alrousan, Maria P Blasco-Conesa, Parimelazhagan Thangaraj, Bhanu Priya Ganesh

Faculty, Staff and Student Publications

Gestational diabetes mellitus (GD)-induced gut dysbiosis in pregnant mothers may increase the risk of cognitive impairment and neurological disorders in both the mother and offspring as they age. Restoring gut balance could improve cognitive outcomes for both. Despite advancements in GD treatment, side effects have increased, and long-term neurocognitive impacts on offspring born to GD mothers remain underexplored. This study uses a GD mouse model, inducing pancreatic dysfunction in 3-month-old pregnant C57BL/6J mice with Streptozotocin. The efficacy and mechanism of the prebiotic phytocompound green leaf extract (

A Deep Learning-Based System For Automatic Detection Of Emesis With High Accuracy In Suncus Murinus, Zengbing Lu, Yimeng Qiao, Xiaofei Huang, Dexuan Cui, Julia Y H Liu, Man Piu Ngan, Luping Liu, Zhixin Huang, Zi-Tong Li, Lingqing Yang, Aleena Khalid, Yingyi Deng, Sze Wa Chan, Longlong Tu, John A Rudd

Children’s Nutrition Research Center Staff Publications

Quantifying emesis in Suncus murinus (S. murinus) has traditionally relied on direct observation or reviewing recorded behaviour, which are laborious, time-consuming processes that are susceptible to operator error. With rapid advancements in deep learning, automated animal behaviour quantification tools with high accuracy have emerged. In this study, we pioneere the use of both three-dimensional convolutional neural networks and self-attention mechanisms to develop the Automatic Emesis Detection (AED) tool for the quantification of emesis in S. murinus, achieving an overall accuracy of 98.92%. Specifically, we use motion-induced emesis videos as training datasets, with validation results demonstrating an accuracy of 99.42% for …

Dysregulated Klf4 Expression Plays A Pivotal Role In The Pathogenesis Of Pancreatic Intraductal Papillary Mucinous Neoplasms, Xiangsheng Zuo, Liang Wang, Yi Liu, Huamin Wang, Margarete Hafley, Mihai Gagea, Ru Chen, Yun Xiong, Sheng Pan, Imad Shureiqi, Robert S Bresalier, Daoyan Wei

Faculty, Staff and Student Publications

No abstract provided.

Light-Dark Shift Promotes Colon Carcinogenesis Through Accelerated Colon Aging, Deepak Sharma, Phillip A Engen, Abu Osman, Darbaz Adnan, Maliha Shaikh, Mostafa K Abdel-Reheem, Ankur Naqib, Stefan J Green, Bruce Hamaker, Christopher B Forsyth, Lin Cheng, Ali Keshavarzian, Khashayarsha Khazaie, Faraz Bishehsari

Faculty, Staff and Student Publications

Colorectal cancer (CRC) is the third most common cancer worldwide, with rising prevalence among younger adults. Several lifestyle factors, particularly disruptions in circadian rhythms by light-dark (LD) shifts, are known to increase CRC risk. Epidemiological studies previously showed LD-shifts are associated with increased risk of CRC. To explore the mechanisms and interactions between LD-shift and intestinal aging, we investigated how the combination of LD-shifts and aging impacts colon carcinogenesis development. Our data showed that LD-shifts and aging increased colon tumorigenesis. Notably, LD-shift accelerated intestinal aging by altering aging-related pathways, such as intestinal barrier damage, accompanied by dysbiotic changes in the …

Nucleus-Translocated Gclm Promotes Chemoresistance In Colorectal Cancer Through A Moonlighting Function, Jin-Fei Lin, Ze-Xian Liu, Dong-Liang Chen, Ren-Ze Huang, Fen Cao, Kai Yu, Ting Li, Hai-Yu Mo, Hui Sheng, Zhi-Bing Liang, Kun Liao, Yi Han, Shan-Shan Li, Zhao-Lei Zeng, Song Gao, Huai-Qiang Ju, Rui-Hua Xu

Faculty, Staff and Student Publications

Metabolic enzymes perform moonlighting functions during tumor progression, including the modulation of chemoresistance. However, the underlying mechanisms of these functions remain elusive. Here, utilizing a metabolic clustered regularly interspaced short palindromic repeats (CRISPR)-Cas9 knockout library screen, we observe that the loss of glutamate-cysteine ligase modifier subunit (GCLM), a rate-limiting enzyme in glutathione biosynthesis, noticeably increases the sensitivity of colorectal cancer (CRC) cells to platinum-based chemotherapy. Mechanistically, we unveil a noncanonical mechanism through which nuclear GCLM competitively interacts with NF-kappa-B (NF-κB)-repressing factor (NKRF), to promote NF-κB activity and facilitate chemoresistance. In response to platinum drug treatment, GCLM is phosphorylated by P38 …

Limosilactobacillus Reuteri Ameliorates Maternal Separation Stress In Newborn Mice And Alters Subsequent Adult Behaviour, Z. M. Saleh, B. Okeugo, V. R. Venna, F. W. Blixt, V. A. Quaicoe, E. S. Park, S. Giorgberidze, Meng Luo, Christopher M. Taylor, J. M. Rhoads, Y. Liu

School of Medicine Faculty Publications

Maternal separation (MS) in mice results in behavioral deficits and gut microbiota dysbiosis that all persist into adulthood. Limosilactobacillus reuteri DSM 17938 modulates gut microbiota, alters systemic metabolites, and facilitates immune regulation. To assess the effect of DSM 17938 on biochemical and behavioural stress-associated changes, newborn mice were exposed to unpredictable MS (MSU) daily from day 7 to day 20 of life, with intragastric administration of DSM 17938 or PBS as control. Body weight, brain levels of cholecystokinin (CCK), glial fibrillary acidic protein (GFAP), corticosterone, and stool microbiota were assessed at day 21. Behaviour tests including Y-maze (YMT), Tail Suspension …

Systematic Review Of Immune Checkpoint Inhibitor-Related Gastrointestinal, Hepatobiliary, And Pancreatic Adverse Events, Malek Shatila, Hao Chi Zhang, Anusha Shirwaikar Thomas, Antonio Pizuorno Machado, Sidra Naz, Nitish Mittal, Christine Catinis, Krishnavathana Varatharajalu, Carolina Colli Cruz, Eric Lu, Deanna Wu, Julie R Brahmer, Franck Carbonnel, Stephen B Hanauer, Bret Lashner, Bryan Schneider, John A Thompson, Michel Obeid, David P Farris, Yinghong Wang

Faculty, Staff and Student Publications

Gastrointestinal immune-related adverse events (GI irAEs) are common manifestations of immune checkpoint inhibitor (ICI) toxicity. We present a comprehensive systematic review of the incidence, management, and clinical course of irAEs across the entire GI system, including the luminal GI tract, liver, and pancreas. MEDLINE, Embase, Web of Science Core Collection, and Cochrane Library were used to conduct this review. All studies pertaining to GI irAEs were included. Both abstracts and full manuscripts were eligible if they included human subjects and were written in the English language. Articles not available in English, animal studies, or research not specific to GI toxicity …

Circulating Galectin-3: A Prognostic Biomarker In Hepatocellular Carcinoma, Shadi Chamseddine, Betul Gok Yavuz, Yehia I Mohamed, Sunyoung S Lee, James C Yao, Zishuo Ian Hu, Michael Lapelusa, Lianchun Xiao, Ryan Sun, Jeffrey S Morris, Rikita I Hatia, Manal Hassan, Dan G Duda, Maria Diab, Amr Mohamed, Ahmed Nassar, Hesham M Amin, Ahmed Omar Kaseb

Faculty, Staff and Student Publications

INTRODUCTION: Galectin-3 plays critical roles in the adhesion, proliferation, and differentiation of tumor cells. Recent data have suggested that galectin-3 plays a role in the development of hepatocellular carcinoma (HCC); however, its prognostic value has not been validated. The aim of our study was to evaluate the clinical and prognostic value of galectin-3 in patients with HCC.

METHODS: We prospectively enrolled and collected clinicopathologic data and serum samples from 767 patients with HCC between 2001 and 2014 at The University of Texas MD Anderson Cancer Center. Two hundred patients without HCC were also enrolled and had data collected. The Kaplan-Meier …

Molecular And Clinical Features Of Pancreatic Acinar Cell Carcinoma: A Single-Institution Case Series, Ashwathy Balachandran Pillai, Mahmoud Yousef, Abdelrahman Yousef, Kristin D Alfaro-Munoz, Brandon G Smaglo, Jason Willis, Robert A Wolff, Shubham Pant, Mark W Hurd, Anirban Maitra, Huamin Wang, Matthew Harold G Katz, Laura R Prakash, Ching-Wei D Tzeng, Rebecca Snyder, Luca F Castelnovo, Anthony Chen, Andrey Kravets, Kseniia Kudriavtseva, Artem Tarasov, Kirill Kryukov, Haoqiang Ying, John Paul Shen, Dan Zhao

Faculty, Staff and Student Publications

Objectives: Acinar cell carcinoma (ACC) accounts for about 1% of pancreatic cancers. The molecular and clinical features of ACC are less characterized than those of pancreatic ductal adenocarcinoma. Methods: We retrospectively evaluated the clinical and molecular features of ACC patients who underwent germline and/or somatic molecular testing at The University of Texas MD Anderson Cancer Center from 2008 to 2022 and two cases from 2023-2024 who underwent RNA and TME analysis by Boston Gene. Patient information was extracted from our institutional database with the approval of the Institutional Review Board. Results: We identified 16 patients with available molecular testing …

Rotavirus Vaccine Effectiveness Against Severe Acute Gastroenteritis: 2009-2022, Alpha Oumar Diallo, Mary E Wikswo, Iddrisu Sulemana, Leila C Sahni, Julie A Boom, Sasirekha Ramani, Rangaraj Selvarangan, Mary E Moffatt, Christopher J Harrison, Natasha Halasa, James Chappell, Laura Stewart, Mary Allen Staat, Elizabeth Schlaudecker, Christina Quigley, Eileen J Klein, Janet A Englund, Danielle M Zerr, Geoffrey A Weinberg, Peter G Szilagyi, Christina Albertin, Samantha H Johnston, John V Williams, Marian G Michaels, Robert W Hickey, Aaron T Curns, Michelle Honeywood, Slavica Mijatovic-Rustempasic, Mathew D Esona, Michael D Bowen, Umesh D Parashar, Rashi Gautam, Sara A Mirza, Jacqueline E Tate

Faculty, Staff and Students Publications

Background: Rotavirus was the leading cause of acute gastroenteritis among US children until vaccine introduction in 2006, after which, substantial declines in severe rotavirus disease occurred. We evaluated rotavirus vaccine effectiveness (VE) over 13 years (2009-2022).

Methods: We analyzed data from the New Vaccine Surveillance Network using a test-negative case-control design to estimate rotavirus VE against laboratory-confirmed rotavirus infections among children seeking care for acute gastroenteritis (≥3 diarrhea or ≥1 vomiting episodes within 24 hours) in the emergency department (ED) or hospital. Case-patients and control-patients were children whose stool specimens tested rotavirus positive or negative, respectively, by enzyme immunoassay or …

Barriers And Opportunities In Pancreatic Cancer Immunotherapy, Yixin Ju, Dongzhi Xu, Miao-Miao Liao, Yutong Sun, Wen-Dai Bao, Fan Yao, Li Ma

Faculty, Staff and Student Publications

Pancreatic ductal adenocarcinoma (PDAC) presents a fatal clinical challenge characterized by a dismal 5-year overall survival rate, primarily due to the lack of early diagnosis and limited therapeutic efficacy. Immunotherapy, a proven success in multiple cancers, has yet to demonstrate significant benefits in PDAC. Recent studies have revealed the immunosuppressive characteristics of the PDAC tumor microenvironment (TME), including immune cells with suppressive properties, desmoplastic stroma, microbiome influences, and PDAC-specific signaling pathways. In this article, we review recent advances in understanding the immunosuppressive TME of PDAC, TME differences among various mouse models of pancreatic cancer, and the mechanisms underlying resistance to …

Parp-1 Selectively Impairs Kras-Driven Phenotypic And Molecular Features In Intrahepatic Cholangiocarcinoma, Friederike L Keggenhoff, Darko Castven, Diana Becker, Stojan Stojkovic, Jovana Castven, Carolin Zimpel, Beate K Straub, Tiemo Gerber, Harald Langer, Patricia Hähnel, Thomas Kindler, Jörg Fahrer, Colm J O'Rourke, Ursula Ehmer, Anna Saborowski, Lichun Ma, Xin Wei Wang, Timo Gaiser, Matthias S Matter, Christian Sina, Stefanie Derer, Ju-Seog Lee, Stephanie Roessler, Bernd Kaina, Jesper B Andersen, Peter R Galle, Jens U Marquardt

Faculty, Staff and Student Publications

Objective: Intrahepatic cholangiocarcinoma (iCCA) is the second most common primary liver cancer with limited therapeutic options. KRAS mutations are among the most abundant genetic alterations in iCCA associated with poor clinical outcome and treatment response. Recent findings indicate that Poly(ADP-ribose)polymerase1 (PARP-1) is implicated in KRAS-driven cancers, but its exact role in cholangiocarcinogenesis remains undefined.

Design: PARP-1 inhibition was performed in patient-derived and established iCCA cells using RNAi, CRISPR/Cas9 and pharmacological inhibition in KRAS-mutant, non-mutant cells. In addition, Parp-1 knockout mice were combined with iCCA induction by hydrodynamic tail vein injection to evaluate an impact on phenotypic and molecular …