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Retrospective Analysis Of Retroperitoneal-Abdominal-Pelvic Ganglioneuromas: An International Study By The Transatlantic Australasian Retroperitoneal Sarcoma Working Group (Tarpswg), Sangkyu Noh, Carolyn Nessim, Emily Z Keung, Christina L Roland, Dirk Strauss, Gausihi Sivarajah, Marco Fiore, Davide Biasoni, Stefano Piero Bernardo Cioffi, Winta Mehtsun, Ferdinando Carlo Maria Cananzi, Federico Sicoli, Vittorio Quagliuolo, Jun Chen, Chenghua Luo, Rebecca A Gladdy, Carol Swallow, Wendy Johnston, Samuel J Ford, Caroline Evenden, Fabio Tirotta, Max Almond, Laura Nguyen, Piotr Rutkowski, Maria Krotewicz, Elisabetta Pennacchioli, Kenneth Cardona, Adriana Gamboa, Daphne Hompes, Marleen Renard, Attila Kollár, Christoph O Ryser, Nikolaos Vassos, Chandrajit P Raut, Mark Fairweather, Dagmar Adamkova Krakorova, Sergio Quildrian, Andraz Perhavec, Eran Nizri, Jeffrey M Farma, Stephanie H Greco, Bruno Vincenzi, José Antonio González Lopez, Mireia Solans Solerdecoll, Shintaro Iwata, Suguru Fukushima, Teresa Kim, Francesco Tolomeo, Hayden Snow, Ynez Howlett-Jansen, Dimitri Tzanis, Maxim Nikulin, Alessandro Gronchi, Jason K Sicklick, Transatlantic Australasian Retroperitoneal Sarcoma Working Group

Faculty, Staff and Student Publications

OBJECTIVE: The Transatlantic Australasian Retroperitoneal Sarcoma Working Group conducted a retrospective study on the disease course and clinical management of ganglioneuromas.

BACKGROUND: Ganglioneuromas are rare tumors derived from neural crest cells. Data on these tumors remain limited to case reports and single-institution case series.

METHODS: Patients of all ages with pathologically confirmed primary retroperitoneal, intra-abdominal, and pelvic ganglioneuromas between January 1, 2000, and January 1, 2020, were included. We examined demographic, clinicopathologic, and radiologic characteristics, as well as clinical management.

RESULTS: Overall, 328 patients from 29 institutions were included. The median age at diagnosis was 37 years with 59.1% of …

Definitive Liver Radiotherapy For Intrahepatic Cholangiocarcinoma With Extrahepatic Metastases, Brian De, Rituraj Upadhyay, Kaiping Liao, Tiffany Kumala, Christopher Shi, Grace Dodoo, Joseph Abi Jaoude, Kelsey L Corrigan, Gohar S Manzar, Kathryn E Marqueen, Vincent Bernard, Sunyoung S Lee, Kanwal P S Raghav, Jean-Nicolas Vauthey, Ching-Wei D Tzeng, Hop S Tran Cao, Grace Lee, Jennifer Y Wo, Theodore S Hong, Christopher H Crane, Bruce D Minsky, Grace L Smith, Emma B Holliday, Cullen M Taniguchi, Albert C Koong, Prajnan Das, Milind Javle, Ethan B Ludmir, Eugene J Koay

Faculty, Staff and Student Publications

INTRODUCTION: Tumor-related liver failure (TRLF) is the most common cause of death in patients with intrahepatic cholangiocarcinoma (ICC). Though we previously showed that liver radiotherapy (L-RT) for locally advanced ICC is associated with less frequent TRLF and longer overall survival (OS), the role of L-RT for patients with extrahepatic metastatic disease (M1) remains undefined. We sought to compare outcomes for M1 ICC patients treated with and without L-RT.

METHODS: We reviewed ICC patients that found to have M1 disease at initial diagnosis at a single institution between 2010 and 2021 who received L-RT, matching them with an institutional cohort by …

Smooth Muscle Α-Actin Missense Variant Promotes Atherosclerosis Through Modulation Of Intracellular Cholesterol In Smooth Muscle Cells, Kaveeta Kaw, Abhijnan Chattopadhyay, Pujun Guan, Jiyuan Chen, Suravi Majumder, Xue-Yan Duan, Shuangtao Ma, Chen Zhang, Callie S Kwartler, Dianna M Milewicz

Faculty, Staff and Student Publications

AIMS: The variant p.Arg149Cys in ACTA2, which encodes smooth muscle cell (SMC)-specific α-actin, predisposes to thoracic aortic disease and early onset coronary artery disease in individuals without cardiovascular risk factors. This study investigated how this variant drives increased atherosclerosis.

METHODS AND RESULTS: Apoe-/- mice with and without the variant were fed a high-fat diet for 12 weeks, followed by evaluation of atherosclerotic plaque formation and single-cell transcriptomics analysis. SMCs explanted from Acta2R149C/+ and wildtype (WT) ascending aortas were used to investigate atherosclerosis-associated SMC phenotypic modulation. Hyperlipidemic Acta2R149C/+Apoe-/- mice have a 2.5-fold increase in atherosclerotic plaque burden compared to Apoe-/- mice …

Assessing Cocaine Motivational Value: Comparison Of Brain Reactivity Bias Toward Cocaine Cues And Cocaine Demand, Heather E Webber, Jin H Yoon, Constanza De Dios, Robert Suchting, Vincent Dang, Francesco Versace, Charles E Green, Margaret C Wardle, Scott D Lane, Joy M Schmitz

Faculty, Staff and Student Publications

The behavioral economic measure drug demand and the neural measure late positive potential (LPP) are two measures of motivational value that have been associated with drug relapse risk and treatment outcomes. Despite having overlapping themes, no studies have directly compared drug demand and LPP. Participants (N = 59) included treatment-seeking individuals with cocaine use disorder that had completed both a baseline cocaine demand task and an electroencephalogram (EEG) picture-viewing task of drug-related and pleasant picture cues. Associations between the LPP difference score amplitude (drug-pleasant) and five demand indices (Q₀, essential value [EV], Omax, Pmax, and …

Heterozygous Midnolin Knockout Attenuates Severity Of Nonalcoholic Fatty Liver Disease In Mice Fed A Western-Style Diet High In Fat, Cholesterol, And Fructose, Soo-Mi Kweon, Jose Irimia-Dominguez, Gayeoun Kim, Patrick T Fueger, Kinji Asahina, Keith K Lai, Daniela S Allende, Quincy R Lai, Chih-Hong Lou, Walter M Tsark, Ju Dong Yang, Dominic S Ng, Ju-Seog Lee, Patrick Tso, Wendong Huang, Keane K Y Lai

Faculty, Staff and Student Publications

Although midnolin has been studied for over 20 years, its biological roles in vivo remain largely unknown, especially due to the lack of a functional animal model. Indeed, given our recent discovery that the knockdown of midnolin suppresses liver cancer cell tumorigenicity and that this antitumorigenic effect is associated with modulation of lipid metabolism, we hypothesized that knockout of midnolin in vivo could potentially protect from nonalcoholic fatty liver disease (NAFLD) which has become the most common cause of chronic liver disease in the Western world. Accordingly, in the present study, we have developed and now report on the first …

Multidisciplinary Care Of A Large Brain Metastasis In A Patient With Hormone-Receptor-Positive Breast Cancer With Ataxia-Telangiectasia Mutation, Anca Chelariu-Raicu, Sarina A Piha-Paul, Mariana Chavez-Macgregor, Jason Johnson, Raymond Sawaya, Mary Frances Mcaleer, Alissa Nguyen, Audrey Hartnett, Apostolia M Tsimberidou, Funda Meric-Bernstam, Ecaterina E Dumbrava

Faculty, Staff and Student Publications

Poly (adenosine diphosphate-ribose) polymerase inhibitors (PARP)i are emerging as standard oncology treatments in various tumor types. The indications will expand as PARPi are being investigated in various breast cancer subtypes. Currently, except for BRCA1/2 mutation carriers with human epidermal growth factor receptor 2 (HER2)-negative breast cancer, there is inadequate identification of predictive biomarkers of response. We present a 57-year-old woman with metastatic breast cancer, hormone-receptor-positive, HER2 negative with a germline ataxia-telangiectasia mutation with a large brain metastasis with clinical benefit to talazoparib. This case report exemplifies the importance of the multidisciplinary management of patients with brain metastases and personalized biomarker …

Framework For Quality Assurance Of Ultrahigh Dose Rate Clinical Trials Investigating Flash Effects And Current Technology Gaps, Wei Zou, Rongxiao Zhang, Emil Schüler, Paige A Taylor, Anthony E Mascia, Eric S Diffenderfer, Tianyu Zhao, Ahmet S Ayan, Manju Sharma, Shu-Jung Yu, Weiguo Lu, Walter R Bosch, Christina Tsien, Murat Surucu, Julianne M Pollard-Larkin, Jan Schuemann, Eduardo G Moros, Magdalena Bazalova-Carter, David J Gladstone, Heng Li, Charles B Simone, Kristoffer Petersson, Stephen F Kry, Amit Maity, Billy W Loo, Lei Dong, Peter G Maxim, Ying Xiao, Jeffrey C Buchsbaum

Faculty, Staff and Student Publications

FLASH radiation therapy (FLASH-RT), delivered with ultrahigh dose rate (UHDR), may allow patients to be treated with less normal tissue toxicity for a given tumor dose compared with currently used conventional dose rate. Clinical trials are being carried out and are needed to test whether this improved therapeutic ratio can be achieved clinically. During the clinical trials, quality assurance and credentialing of equipment and participating sites, particularly pertaining to UHDR-specific aspects, will be crucial for the validity of the outcomes of such trials. This report represents an initial framework proposed by the NRG Oncology Center for Innovation in Radiation Oncology …

Image-Based Quantification Of Histological Features As A Function Of Spatial Location Using The Tissue Positioning System, Ruichen Rong, Yonglong Wei, Lin Li, Tao Wang, Hao Zhu, Guanghua Xiao, Yunguan Wang

Faculty, Staff and Student Publications

Background: Tissues such as the liver lobule, kidney nephron, and intestinal gland exhibit intricate patterns of zonated gene expression corresponding to distinct cell types and functions. To quantitatively understand zonation, it is important to measure cellular or genetic features as a function of position along a zonal axis. While it is possible to manually count, characterize, and locate features in relation to the zonal axis, it is labor-intensive and difficult to do manually while maintaining precision and accuracy.

Methods: We addressed this challenge by developing a deep-learning-based quantification method called the "Tissue Positioning System" (TPS), which can automatically analyze zonation …

Brief Report: Clinical Response, Toxicity, And Resistance Mechanisms To Osimertinib Plus Met Inhibitors In Patients With Egfr-Mutant Met-Amplified Nsclc, Kaiwen Wang, Robyn Du, Sinchita Roy-Chowdhuri, Ziping T Li, Lingzhi Hong, Natalie Vokes, Yasir Y Elamin, Celyne Bueno Hume, Ferdinandos Skoulidis, Carl M Gay, George Blumenschein, Frank V Fossella, Anne Tsao, Jianjun Zhang, Niki Karachaliou, Aurora O'Brate, Claudia-Nanette Gann, Jeff Lewis, Waree Rinsurongkawong, J Jack Lee, Don Lynn Gibbons, Ara A Vaporciyan, John V Heymach, Mehmet Altan, Xiuning Le

Faculty, Staff and Student Publications

INTRODUCTION:MET amplification is a known resistance mechanism to EGFR tyrosine kinase inhibitor (TKI) treatment in EGFR-mutant NSCLC. Dual EGFR-MET inhibition has been reported with success in overcoming such resistance and inducing clinical benefit. Resistance mechanisms to dual EGFR-MET inhibition require further investigation and characterization.

METHODS: Patients with NSCLC with both MET amplification and EGFR mutation who have received crizotinib, capmatinib, savolitinib, or tepotinib plus osimertinib (OSI) after progression on OSI at MD Anderson Cancer Center were included in this study. Molecular profiling was completed by means of fluorescence in situ hybridization (FISH) and next-generation sequencing (NGS). Radiological response …

Risk Of Cancer After Diagnosis Of Cardiovascular Disease, Caitlin F Bell, Xiudong Lei, Allen Haas, Richard A Baylis, Hua Gao, Lingfeng Luo, Sharon H Giordano, Mackenzie R Wehner, Kevin T Nead, Nicholas J Leeper

Faculty, Staff and Student Publications

BACKGROUND: Cardiovascular disease (CVD) and cancer share several risk factors. Although preclinical models show that various types of CVD can accelerate cancer progression, clinical studies have not determined the impact of atherosclerosis on cancer risk.

OBJECTIVES: The objective of this study was to determine whether CVD, especially atherosclerotic CVD, is independently associated with incident cancer.

METHODS: Using IBM MarketScan claims data from over 130 million individuals, 27 million cancer-free subjects with a minimum of 36 months of follow-up data were identified. Individuals were stratified by presence or absence of CVD, time-varying analysis with multivariable adjustment for cardiovascular risk factors was …

A Spatially Resolved Single-Cell Genomic Atlas Of The Adult Human Breast, Tapsi Kumar, Kevin Nee, Runmin Wei, Siyuan He, Quy H Nguyen, Shanshan Bai, Kerrigan Blake, Maren Pein, Yanwen Gong, Emi Sei, Min Hu, Anna K Casasent, Aatish Thennavan, Jianzhuo Li, Tuan Tran, Ken Chen, Benedikt Nilges, Nachiket Kashikar, Oliver Braubach, Bassem Ben Cheikh, Nadya Nikulina, Hui Chen, Mediget Teshome, Brian Menegaz, Huma Javaid, Chandandeep Nagi, Jessica Montalvan, Tatyana Lev, Sharmila Mallya, Delia F Tifrea, Robert Edwards, Erin Lin, Ritesh Parajuli, Summer Hanson, Sebastian Winocour, Alastair Thompson, Bora Lim, Devon A Lawson, Kai Kessenbrock, Nicholas Navin

Faculty, Staff and Student Publications

The adult human breast is comprised of an intricate network of epithelial ducts and lobules that are embedded in connective and adipose tissue1-3. Although most previous studies have focused on the breast epithelial system4-6, many of the non-epithelial cell types remain understudied. Here we constructed the comprehensive Human Breast Cell Atlas (HBCA) at single-cell and spatial resolution. Our single-cell transcriptomics study profiled 714,331 cells from 126 women, and 117,346 nuclei from 20 women, identifying 12 major cell types and 58 biological cell states. These data reveal abundant perivascular, endothelial and immune cell populations, and highly diverse luminal epithelial cell states. …

Prmt7 Can Prevent Neurovascular Uncoupling, Blood-Brain Barrier Permeability, And Mitochondrial Dysfunction In Repetitive And Mild Traumatic Brain Injury, Christina H Acosta, Garrett A Clemons, Cristiane T Citadin, William C Carr, Mariana Sayuri Berto Udo, Vesna Tesic, Henry W Sanicola, Anne H Freelin, Jamie B Toms, J Dedrick Jordan, Bharat Guthikonda, Krista M Rodgers, Celeste Yin-Chieh Wu, Reggie Hui-Chao Lee, Hung Wen Lin

Faculty, Staff and Student Publications

Mild traumatic brain injury (TBI) comprises the largest percentage of TBI-related injuries, with pathophysiological and functional deficits that persist in a subset of TBI patients. In our three-hit paradigm of repetitive and mild traumatic brain injury (rmTBI), we observed neurovascular uncoupling via decreased red blood cell velocity, microvessel diameter, and leukocyte rolling velocity 3 days post-rmTBI via intra-vital two-photon laser scanning microscopy. Furthermore, our data suggest increased blood-brain barrier (BBB) permeability (leakage), with corresponding decrease in junctional protein expression post-rmTBI. Mitochondrial oxygen consumption rates (measured via Seahorse XFe24) were also altered 3 days post-rmTBI, along with disrupted mitochondrial dynamics of …

Life-Threatening Hemoptysis In Patients With Metastatic Kidney Cancer, Viral M Patel, Roy Elias, Annapoorani Asokan, Akanksha Sharma, Alana Christie, Ivan Pedrosa, Hsienchang Chiu, Scott Reznik, Raquibul Hannan, Robert Timmerman, James Brugarolas

Faculty, Staff and Student Publications

Hemoptysis is a complication of intrathoracic tumors, both primary and metastatic, and the risk may be increased by procedural interventions as well as Stereotactic Ablative Radiation (SAbR). The risk of hemoptysis with SAbR for lung cancer is well characterized, but there is a paucity of data about intrathoracic metastases. Here, we sought to evaluate the incidence of life-threatening/fatal hemoptysis (LTH) in patients with renal cell carcinoma (RCC) chest metastases with a focus on SAbR. We systematically evaluated patients with RCC at UT Southwestern Medical Center (UTSW) Kidney Cancer Program (KCP) from July 2005 to March 2020. We queried Kidney Cancer …

A Comparison Of Hypofractionated Radiation Therapy Breast Plans For Large Breasted Patients - Hybrid 3d Conformal, And Volumetric Modulated Arc Therapy Vs Standard Hypofractionated 3d Conformal, Kelsie Wentland

Masters Projects

Abstract

Introduction

Patients with a large breast volume are more at risk of adverse skin effects with radiation therapy. Studies concerning these patients are very limited, especially in regard to comparison of planning techniques. While traditional tangent 3D conformal radiation therapy has been the standard of care, recent literature has shown possible benefits of hybrid planning for average breast volume patients. Little has been studied regarding breast cancer patients with large breast volumes and the possible benefits of hybrid planning of this patient demographic. Creating a hybrid plan could have the benefits of both different treatment modalities to provide a …

Potential Toxic Elements And Their Carcinogenic And Non-Carcinogenic Risk Assessment In Some Commercially Important Fish Species From A Ramsar Site, Mohammad Belal Hossain, Md Moudud Ahmed, Yeasmin Nahar Jolly, As-Ad Ujjaman Nur, Salma Sultana, Shirin Akter, Jimmy Yu, Bilal Ahamad Paray, Takaomi Arai

Faculty, Staff and Student Publications

Potentially toxic elements (PTEs) such as Hg, As, and Pb have become concentrated in the aquatic ecosystem as a result of increased human activities. However, these substances frequently have synergistic or antagonistic effects on the human body or other animals. As a result, there are concerns world-wide that commercially available food products, especially fish, may be contaminated with hazardous elements. In this study, samples of four selected fishes, Gutum (Lepidocephalichthys guntea), Baim (Macrognathus pancalus), Baila (Glossogobius giuris), Meni (Nandus nandus) were analyzed from one of the largest freshwater wetlands (designed as a …

A Deep Learning Onion Peeling Approach To Measure Oral Epithelium Layer Number, Xinyi Zhang, Frederico O Gleber-Netto, Shidan Wang, Kevin W Jin, Donghan M Yang, Ann M Gillenwater, Jeffrey N Myers, Renata Ferrarotto, Curtis R Pickering, Guanghua Xiao

Faculty, Staff and Student Publications

Head and neck squamous cell carcinoma (HNSCC), specifically in the oral cavity (oral squamous cell carcinoma, OSCC), is a common, complex cancer that significantly affects patients' quality of life. Early diagnosis typically improves prognoses yet relies on pathologist examination of histology images that exhibit high inter- and intra-observer variation. The advent of deep learning has automated this analysis, notably with object segmentation. However, techniques for automated oral dysplasia diagnosis have been limited to shape or cell stain information, without addressing the diagnostic potential in counting the number of cell layers in the oral epithelium. Our study attempts to address this …

Inhibition Of Microsomal Prostaglandin E2 Synthase Reduces Collagen Deposition In Melanoma Tumors And May Improve Immunotherapy Efficacy By Reducing T-Cell Exhaustion, Yasunari Fukuda, Sun-Hee Kim, Matias A Bustos, Sung-Nam Cho, Jason Roszik, Jared K Burks, Hong Kim, Dave S B Hoon, Elizabeth A Grimm, Suhendan Ekmekcioglu

Faculty, Staff and Student Publications

The arachidonic acid pathway participates in immunosuppression in various types of cancer. Our previous observation detailed that microsomal prostaglandin E2 synthase 1 (mPGES-1), an enzyme downstream of cyclooxygenase 2 (COX-2), limited antitumor immunity in melanoma; in addition, genetic depletion of mPGES-1 specifically enhanced immune checkpoint blockade therapy. The current study set out to distinguish the roles of mPGES-1 from those of COX-2 in tumor immunity and determine the potential of mPGES-1 inhibitors for reinforcing immunotherapy in melanoma. Genetic deletion of mPGES-1 showed different profiles of prostaglandin metabolites from that of COX-2 deletion. In our syngeneic mouse model, mPGES-1-deficient cells exhibited …

Primary Adrenal Angiosarcoma: A Case Report And Review Of The Literature, Zunaira Naeem, Joon Yau Leong, Arianna Morton, Alaa Hrizat, Eric Shiffrin, Andrew Gomella, Peter Mccue, Mark Mann, Li Li

Department of Pathology, Anatomy, and Cell Biology Faculty Papers

Primary adrenal angiosarcoma is an extremely rare malignant tumor with challenging diagnosis. A 66-year-old woman had a 4.3 cm right adrenal mass suspicious for adrenal cortical carcinoma. Pathological examination demonstrated a hemorrhagic adrenal cyst with numerous irregularly shaped anastomosing vascular channels lined by atypical endothelial cells that had frequent atypical mitotic figures (12/10 HPF, Ki67 10%). The tumor cells were positive for CD31, ERG, and FLI-1, but negative for adrenal and other tumor lineage markers by immunohistochemistry. NGS fusion gene testing ruled out epithelioid hemangioendothelioma. Accurate diagnosis and differential inclusion are important for appropriate treatment of this rare tumor.

Association Of Delirium And Depression With Respiratory And Outcome Measures In Covid-19 Inpatients, Alessio Simonetti, Cristina Pais, Vezio Savoia, Maria Camilla Cipriani, Matteo Tosato, Delfina Janiri, Evelina Bernardi, Ottavia Marianna Ferrara, Stella Margoni, Georgios D Kotzalidis, Daniela Chieffo, Massimo Fantoni, Rosa Liperoti, Francesco Landi, Roberto Bernabei, Gabriele Sani

Faculty, Staff and Students Publications

Delirium (DEL) and depression (DEP) may impair the course and severity of acute respiratory illness. The impact of such syndromes on respiratory and outcome parameters in inpatients with COVID-19 needs clarification. To clarify the relationship between DEL and DEP and respiratory outcome measures, we enrolled 100 inpatients from COVID-19 units of the Fondazione Policlinico Universitario Agostino Gemelli IRCCS of Rome. Participants were divided into those with DEL, DEP, or absence of either delirium or depression (CONT). Delirium severity was assessed with the Neelson and Champagne Confusion Scale (NEECHAM). Psychopathology was assessed with the Hamilton Rating Scale for Depression (HAM-D), the …

The Role Of Fas Receptor Methylation In Osteosarcoma Metastasis, Jiayi M Sun, Wing-Yuk Chow, Gufeng Xu, M John Hicks, Manjula Nakka, Jianhe Shen, Patrick Kwok Shing Ng, Aaron M Taylor, Alexander Yu, Jason E Farrar, Donald A Barkauskas, Richard Gorlick, Jaime M Guidry Auvil, Daniela Gerhard, Paul Meltzer, Rudy Guerra, Tsz-Kwong Man, Ching C Lau, On Behalf Of The Target Osteosarcoma Consortium

Faculty, Staff and Students Publications

Osteosarcoma is the most frequent primary malignant bone tumor with an annual incidence of about 400 cases in the United States. Osteosarcoma primarily metastasizes to the lungs, where FAS ligand (FASL) is constitutively expressed. The interaction of FASL and its cell surface receptor, FAS, triggers apoptosis in normal cells; however, this function is altered in cancer cells. DNA methylation has previously been explored as a mechanism for altering FAS expression, but no variability was identified in the CpG island (CGI) overlapping the promoter. Analysis of an expanded region, including CGI shores and shelves, revealed high variability in the methylation of …

The New World Of Rna Diagnostics And Therapeutics, Giovanni Blandino, Roberto Dinami, Marco Marcia, Eleni Anastasiadou, Brid M Ryan, Alina Catalina Palcau, Luigi Fattore, Giulia Regazzo, Rosanna Sestito, Rossella Loria, Ana Belén Díaz Méndez, Maria Chiara Cappelletto, Claudio Pulito, Laura Monteonofrio, George A Calin, Gabriella Sozzi, Jit Kong Cheong, Ranit Aharonov, Gennaro Ciliberto

Faculty, Staff and Student Publications

The 5th Workshop IRE on Translational Oncology was held in Rome (Italy) on 27-28 March at the IRCCS Regina Elena National Cancer Institute. This meeting entitled "The New World of RNA diagnostics and therapeutics" highlightes the significant progress in the RNA field made over the last years. Research moved from pure discovery towards the development of diagnostic biomarkers or RNA-base targeted therapies seeking validation in several clinical trials. Non-coding RNAs in particular have been the focus of this workshop due to their unique properties that make them attractive tools for the diagnosis and therapy of cancer.This report collected the presentations …

Automated Capture And Analysis Of Circulating Tumor Cells In Pediatric, Adolescent And Young Adult Patients With Central Nervous System Tumors, Wafik Zaky, Dristhi Ragoonanan, Izhar Batth, Long Dao, Jian Wang, Xueqing Xia, Najat C Daw, Jonathan B Gill, Soumen Khatua, Shulin Li

Faculty, Staff and Student Publications

Tumors of the central nervous system (CNS) are the most common and lethal childhood malignancy. Detection of residual disease and longitudinal monitoring of treatment response in patients are challenging and rely on serial imaging. This current standard of care fails to detect microscopic disease or provide molecular characteristics of residual tumors. As such, there is dire need for minimally invasive liquid biopsy techniques. We have previously shown the high specificity of using cell surface vimentin (CSV) to identify circulating tumor cells (CTCs) from patients bearing various types of cancers. Here, we describe the first report of CTCs captured from peripheral …

Optimizing The Timing Of Biologic And Surgical Therapy For Patients With Refractory Chronic Rhinosinusitis With Nasal Polyposis (Crswnp), Emily Garvey, Bita Naimi, Alexander Duffy, Paavali Hannikainen, Chase Kahn, Douglas Farquhar, Marc Rosen, Mindy R. Rabinowitz, Elina Toskala, Gurston G. Nyquist

Department of Otolaryngology - Head and Neck Surgery Faculty Papers

INTRODUCTION: Chronic rhinosinusitis with nasal polyposis (CRSwNP) is often treated with endoscopic sinus surgery (ESS); however, patients may require revision surgery due to recurrence. To date, no studies have compared outcomes for combined surgery and biologic therapy for CRSwNP compared with biologic therapy alone.

METHODS: Retrospective case-control study of CRSwNP patients who underwent ESS while on dupilumab or mepolizumab (ESS-biologic cohort) compared with CRSwNP patients on biologic therapy (biologic-only controls). Cohorts were matched according to indication, aspirin-exacerbated respiratory disease (AERD), sinonasal outcome test-22 (SNOT-22), and total polyp scores.

RESULTS: Sixteen patients underwent ESS while on biologic therapy (13 dupilumab and …

Ifit2 Restricts Murine Coronavirus Spread To The Spinal Cord White Matter And Its Associated Myelin Pathology, Madhav Sharma, Debanjana Chakravarty, Afaq Hussain, Ajay Zalavadia, Amy Burrows, Patricia Rayman, Nikhil Sharma, Lawrence C. Kenyon, Cornelia Bergmann, Ganes C. Sen, Jayasri Das Sarma

Department of Pathology, Anatomy, and Cell Biology Faculty Papers

Interferon-induced protein with tetratricopeptide repeats 2, Ifit2, is critical in restricting neurotropic murine-β-coronavirus, RSA59 infection. RSA59 intracranial injection of Ifit2-deficient (-/-) compared to wild-type (WT) mice results in impaired acute microglial activation, reduced CX3CR1 expression, limited migration of peripheral lymphocytes into the brain, and impaired virus control followed by severe morbidity and mortality. While the protective role of Ifit2 is established for acute viral encephalitis, less is known about its influence during the chronic demyelinating phase of RSA59 infection. To understand this, RSA59 infected Ifit2-/- and Ifit2+/+ (WT) were observed for neuropathological outcomes at day 5 (acute phase) and 30 …

Loss Of Metabolic Fitness Drives Tumor Resistance After Car-Nk Cell Therapy And Can Be Overcome By Cytokine Engineering, Li Li, Vakul Mohanty, Jinzhuang Dou, Yuefan Huang, Pinaki P Banerjee, Qi Miao, Jens G Lohr, Tushara Vijaykumar, Julia Frede, Birgit Knoechel, Luis Muniz-Feliciano, Tamara J Laskowski, Shaoheng Liang, Judy S Moyes, Vandana Nandivada, Rafet Basar, Mecit Kaplan, May Daher, Enli Liu, Ye Li, Sunil Acharya, Paul Lin, Mayra Shanley, Hind Rafei, David Marin, Stephan Mielke, Richard E Champlin, Elizabeth J Shpall, Ken Chen, Katayoun Rezvani

Faculty, Staff and Student Publications

Chimeric antigen receptor (CAR) engineering of natural killer (NK) cells is promising, with early-phase clinical studies showing encouraging responses. However, the transcriptional signatures that control the fate of CAR-NK cells after infusion and factors that influence tumor control remain poorly understood. We performed single-cell RNA sequencing and mass cytometry to study the heterogeneity of CAR-NK cells and their in vivo evolution after adoptive transfer, from the phase of tumor control to relapse. Using a preclinical model of noncurative lymphoma and samples from a responder and a nonresponder patient treated with CAR19/IL-15 NK cells, we observed the emergence of NK cell …

The Prevalence Of Diabetes In Juveniles, Tatyana Johnson

Graduate Student Dissertations, Theses, Capstones, and Portfolios

Diabetes mellitus, simply known as diabetes, is a metabolic disorder that impacts how the body makes use of glucose or blood sugar. Glucose is the primary supply of energy for the body’s cells, which is controlled by insulin, a pancreatic hormone. Diabetes results in high blood glucose levels (hyperglycemia), which are caused by either insufficient insulin production by the pancreas or ineffective insulin utilization by the body (Dean & McEntyre, 2004). Although there are several types of diabetes, the two main types are type 1 and type 2. Type 1, also known as juvenile diabetes, is an inflammatory condition in …

Nanoparticle-Mediated Therapy With Mir-198 Sensitizes Pancreatic Cancer To Gemcitabine Treatment Through Downregulation Of Vcp-Mediated Autophagy, Christian Marin-Muller, Dali Li, Jian-Ming Lü, Zhengdong Liang, Osvaldo Vega-Martínez, Sue E Crawford, Mary K Estes, William E Fisher, Changyi Chen, Qizhi Yao

Faculty, Staff and Students Publications

Pancreatic ductal adenocarcinoma (PDAC) remains an extremely aggressive disease characterized by rapidly acquired multi-drug resistance, including to first-line chemotherapeutic agent gemcitabine. Autophagy is a process that is often exploited by cancer and is one of several intrinsic factors associated with resistance to gemcitabine. We have previously found that miR-198 acts as a tumor suppressor in PDAC through the targeting of factors including Valosin-containing protein (VCP). VCP has been reported to play an important role in autophagic flux. In this study, we investigated whether the repression of VCP through miR-198 administration disrupts the autophagy process and sensitizes PDAC cells to gemcitabine …

Perspectives In Melanoma: Meeting Report From The Melanoma Bridge (December 1st–3rd, 2022-Naples, Italy), Paolo A Ascierto, Sanjiv S Agarwala, Allison Betof Warner, Marc S Ernstoff, Bernard A Fox, Thomas F Gajewski, Jérôme Galon, Claus Garbe, Brian R Gastman, Jeffrey E Gershenwald, Pawel Kalinski, Michelle Krogsgaard, Rom S Leidner, Roger S Lo, Alexander M Menzies, Olivier Michielin, Poulikos I Poulikakos, Jeffrey S Weber, Corrado Caracò, Iman Osman, Igor Puzanov, Magdalena Thurin

Faculty, Staff and Student Publications

Outcomes for patients with melanoma have improved over the past decade with the clinical development and approval of immunotherapies targeting immune checkpoint receptors such as programmed death-1 (PD-1), programmed death ligand 1 (PD-L1) or cytotoxic T lymphocyte antigen-4 (CTLA-4). Combinations of these checkpoint therapies with other agents are now being explored to improve outcomes and enhance benefit-risk profiles of treatment. Alternative inhibitory receptors have been identified that may be targeted for anti-tumor immune therapy, such as lymphocyte-activation gene-3 (LAG-3), as have several potential target oncogenes for molecularly targeted therapy, such as tyrosine kinase inhibitors. Unfortunately, many patients still progress and …

Genetics Of Functional Seizures; A Scoping Systematic Review, Ali A. Asadi-Pooya, Mark Hallett, Nafiseh Mirzaei Damabi, Khatereh Fazelian Dehkordi

Department of Neurology Faculty Papers

Background: Evidence on the genetics of functional seizures is scarce, and the purpose of the current scoping systematic review is to examine the existing evidence and propose how to advance the field.

Methods: Web of science and MEDLINE were searched, from their initiation until May 2023. The following key words were used: functional neurological disorder(s), psychogenic neurological disorder(s), functional movement disorder(s), psychogenic movement disorder(s), functional seizures(s), psychogenic seizure(s), nonepileptic seizure(s), dissociative seizure(s), or psychogenic nonepileptic seizure(s), AND, gene, genetic(s), polymorphism, genome, epigenetics, copy number variant, copy number variation(s), whole exome sequencing, or next-generation sequencing.

Results: We identified three original studies. …

Tp53 Induced Glycolysis And Apoptosis Regulator And Monocarboxylate Transporter 4 Drive Metabolic Reprogramming With C-Myc And Nfkb Activation In Breast Cancer, Megan E. Roche, Ying-Hui Ko, Marina Domingo-Vidal, Zhao Lin, Diana Whitaker-Menezes, Ruth C. Birbe, Madalina Tuluc, Balázs Győrffy, Jaime Caro, Nancy J. Philp, Ramon Bartrons, Ubaldo Martinez-Outshoorn

Department of Medical Oncology Faculty Papers

Breast cancer is composed of metabolically coupled cellular compartments with upregulation of TP53 Induced Glycolysis and Apoptosis Regulator (TIGAR) in carcinoma cells and loss of caveolin 1 (CAV1) with upregulation of monocarboxylate transporter 4 (MCT4) in fibroblasts. The mechanisms that drive metabolic coupling are poorly characterized. The effects of TIGAR on fibroblast CAV1 and MCT4 expression and breast cancer aggressiveness was studied using coculture and conditioned media systems and in-vivo. Also, the role of cytokines in promoting tumor metabolic coupling via MCT4 on cancer aggressiveness was studied. TIGAR downregulation in breast carcinoma cells reduces tumor growth. TIGAR overexpression in carcinoma …