Medicine and Health Sciences Commons^™

Shared Features Of Metaplasia And The Development Of Adenocarcinoma In The Stomach And Esophagus, Yongji Zeng, Qing K Li, Sujayita Roy, Jason C Mills, Ramon U Jin

Faculty, Staff and Students Publications

Introduction: Plasticity is an inherent property of the normal gastrointestinal tract allowing for appropriate response to injury and healing. However, the aberrancy of adaptable responses is also beginning to be recognized as a driver during cancer development and progression. Gastric and esophageal malignancies remain leading causes of cancer-related death globally as there are limited early disease diagnostic tools and paucity of new effective treatments. Gastric and esophageal adenocarcinomas share intestinal metaplasia as a key precancerous precursor lesion.

Methods: Here, we utilize an upper GI tract patient-derived tissue microarray that encompasses the sequential development of cancer from normal tissues to illustrate …

Emerging Challenges To Cellular Therapy Of Cancer, Premal D Lulla, Malcolm Brenner

Faculty, Staff and Students Publications

Cellular immunotherapy of cancer in the form of chimeric antigen receptor-modified T-cell therapy has become a standard treatment for lymphoid and more recently plasma cell malignancies. Although their successes in these cancers represent a breakthrough for adoptive cell therapy, there are several challenges to their continued growth in the field of cancer medicine. In this review, we discuss the progress made thus far toward achieving "off-the-shelf" accessibility of cell therapies that has the potential to greatly offset the costs associated with the current practice of making patient-specific products. We also review the innovations under investigation that attempt to make cellular …

Role Of Adenosine Deaminase In Prostate Cancer Progression, Christy Charles, Stacy M Lloyd, Danthasinghe Waduge Badrajee Piyarathna, Jie Gohlke, Uttam Rasaily, Vasanta Putluri, Brian W Simons, Alexander Zaslavsky, Srinivas Nallandhighal, George Michailidis, Nallasivam Palanisamy, Nora Navone, Jeffrey A Jones, Michael M Ittmann, Nagireddy Putluri, David R Rowley, Simpa S Salami, Ganesh S Palapattu, Arun Sreekumar

Faculty, Staff and Students Publications

Prostate cancer (PCa) is the second most common cancer and constitutes about 14.7% of total cancer cases. PCa is highly prevalent and more aggressive in African-American (AA) men than in European-American (EA) men. PCa tends to be highly heterogeneous, and its complex biology is not fully understood. We use metabolomics to better understand the mechanisms behind PCa progression and disparities in its clinical outcome. Adenosine deaminase (ADA) is a key enzyme in the purine metabolic pathway; it was found to be upregulated in PCa and is associated with higher-grade PCa and poor disease-free survival. The inosine-to-adenosine ratio, which is a …

Circulating Tumor Dna Sequencing Of Pediatric Solid And Brain Tumor Patients: An Institutional Feasibility Study, Ross Mangum, Jacquelyn Reuther, Koel Sen Baksi, Ilavarasi Gandhi, Ryan C Zabriskie, Alva Recinos, Robin Raesz-Martinez, Frank Y Lin, Samara L Potter, Andrew C Sher, Stephen F Kralik, Carrie A Mohila, Murali M Chintagumpala, Donna Muzny, Jianhong Hu, Richard A Gibbs, Kevin E Fisher, Juan Carlos Bernini, Jonathan Gill, Timothy C Griffin, Gail E Tomlinson, Kelly L Vallance, Sharon E Plon, Angshumoy Roy, D Williams Parsons

Faculty, Staff and Students Publications

The potential of circulating tumor DNA (ctDNA) analysis to serve as a real-time "liquid biopsy" for children with central nervous system (CNS) and non-CNS solid tumors remains to be fully elucidated. We conducted a study to investigate the feasibility and potential clinical utility of ctDNA sequencing in pediatric patients enrolled on an institutional clinical genomics trial. A total of 240 patients had tumor DNA profiling performed during the study period. Plasma samples were collected at study enrollment from 217 patients and then longitudinally from a subset of patients. Successful cell-free DNA extraction and quantification occurred in 216 of 217 (99.5%) …

Intermel: An International Biorepository And Clinical Database To Uncover Predictors Of Survival In Early-Stage Melanoma, Irene Orlow, Keimya D Sadeghi, Sharon N Edmiston, Jessica M Kenney, Cecilia Lezcano, James S Wilmott, Anne E Cust, Richard A Scolyer, Graham J Mann, Tim K Lee, Hazel Burke, Valerie Jakrot, Ping Shang, Peter M Ferguson, Tawny W Boyce, Jennifer S Ko, Peter Ngo, Pauline Funchain, Judy R Rees, Kelli O'Connell, Honglin Hao, Eloise Parrish, Kathleen Conway, Paul B Googe, David W Ollila, Stergios J Moschos, Eva Hernando, Douglas Hanniford, Diana Argibay, Christopher I Amos, Jeffrey E Lee, Iman Osman, Li Luo, Pei-Fen Kuan, Arshi Aurora, Bonnie E Gould Rothberg, Marcus W Bosenberg, Meg R Gerstenblith, Cheryl Thompson, Paul N Bogner, Ivan P Gorlov, Sheri L Holmen, Elise K Brunsgaard, Yvonne M Saenger, Ronglai Shen, Venkatraman Seshan, Eduardo Nagore, Marc S Ernstoff, Klaus J Busam, Colin B Begg, Nancy E Thomas, Marianne Berwick, Intermel Consortium

Faculty, Staff and Students Publications

INTRODUCTION: We are conducting a multicenter study to identify classifiers predictive of disease-specific survival in patients with primary melanomas. Here we delineate the unique aspects, challenges, and best practices for optimizing a study of generally small-sized pigmented tumor samples including primary melanomas of at least 1.05mm from AJTCC TNM stage IIA-IIID patients. We also evaluated tissue-derived predictors of extracted nucleic acids' quality and success in downstream testing. This ongoing study will target 1,000 melanomas within the international InterMEL consortium.

METHODS: Following a pre-established protocol, participating centers ship formalin-fixed paraffin embedded (FFPE) tissue sections to Memorial Sloan Kettering Cancer Center for …

Demographics Of Skin Cancer Knowledge Among Middle And High Schoolers In Texas, Dina H Zamil, Shangyi Fu, Zahra Majd, Emily Powell, Jenna H Zamil, Zeena Y Nawas, Ida F Orengo

Faculty, Staff and Students Publications

INTRODUCTION: Adolescents, an age group that can reduce sun exposure early, may benefit from school-based skin cancer education programs. Literature regarding the demographics of melanoma knowledge is sparse.

OBJECTIVES: This study sought to evaluate melanoma knowledge among students in Texas viewing John Wayne Cancer Foundation Block the Blaze (JWCFBTB) presentations and identify group differences with regard to sociodemographic factors.

METHODS: Before JWCFBTB presentations delivered in Houston and Dallas by health professions students, a pre-presentation melanoma knowledge quiz was distributed. This survey was adapted from a 2000 study evaluating melanoma knowledge in middle and high schoolers in Houston and Dallas. Respondents …

Vaccine-Linked Chemotherapy Improves Cardiac Structure And Function In A Mouse Model Of Chronic Chagas Disease, Kathryn M Jones, Elise N Mangin, Corey L Reynolds, Liliana E Villanueva, Julio Vladimir Cruz, Leroy Versteeg, Brian Keegan, April Kendricks, Jeroen Pollet, Fabian Gusovsky, Maria Elena Bottazzi, Peter J Hotez

Faculty, Staff and Students Publications

INTRODUCTION: Chagas disease, caused by chronic infection with the protozoan parasite Trypanosoma cruzi, affects 6-7 million people worldwide. The major clinical manifestation of Chagas disease is chronic Chagasic cardiomyopathy (CCC), which encompasses a spectrum of symptoms including arrhythmias, hypertrophy, dilated cardiomyopathy, heart failure, and sudden death. Current treatment is limited to two antiparasitic drugs, benznidazole (BNZ) and nifurtimox, but both have limited efficacy to halt the progression of CCC. We developed a vaccine-linked chemotherapy strategy using our vaccine consisting of recombinant Tc24-C4 protein and a TLR-4 agonist adjuvant in a stable squalene emulsion, in combination with low dose benznidazole treatment. …

Sox9 Governs Gastric Mucous Neck Cell Identity And Is Required For Injury-Induced Metaplasia, Spencer G Willet, Nattapon Thanintorn, Helen Mcneill, Sung-Ho Huh, David M Ornitz, Won Jae Huh, Stella G Hoft, Richard J Dipaolo, Jason C Mills

Faculty, Staff and Students Publications

BACKGROUND & AIMS: Acute and chronic gastric injury induces alterations in differentiation within the corpus of the stomach called pyloric metaplasia. Pyloric metaplasia is characterized by the death of parietal cells and reprogramming of mitotically quiescent zymogenic chief cells into proliferative, mucin-rich spasmolytic polypeptide-expressing metaplasia (SPEM) cells. Overall, pyloric metaplastic units show increased proliferation and specific expansion of mucous lineages, both by proliferation of normal mucous neck cells and recruitment of SPEM cells. Here, we identify Sox9 as a potential gene of interest in the regulation of mucous neck and SPEM cell identity in the stomach.

METHODS: We used immunostaining …

Inverse Association Between Gluteofemoral Obesity And Risk Of Non-Cardia Gastric Intestinal Metaplasia, Andre G Jove, Hudson M Holmes, Mimi C Tan, Hashem B El-Serag, Aaron P Thrift

Faculty, Staff and Students Publications

BACKGROUND & AIMS: It is unclear whether obesity confers increased risk of non-cardia gastric adenocarcinoma and its precursor, gastric intestinal metaplasia. Here, we examined whether various dimensions of adiposity independently predispose to the development of non-cardia gastric intestinal metaplasia.

METHODS: We compared data from 409 non-cardia gastric intestinal metaplasia cases and 1748 controls without any gastric intestinal metaplasia from a cross-sectional study at the VA Medical Center in Houston, Texas. Participants completed standardized questionnaires, underwent anthropometric measurements, and underwent a study endoscopy with gastric mapping biopsies. Non-cardia gastric intestinal metaplasia cases included participants with intestinal metaplasia on any non-cardia gastric …

Novel Banana Lectin Car-T Cells To Target Pancreatic Tumors And Tumor-Associated Stroma, Mary K Mckenna, Ada Ozcan, Daniel Brenner, Norihiro Watanabe, Maureen Legendre, Dafydd G Thomas, Christopher Ashwood, Richard D Cummings, Challice Bonifant, David M Markovitz, Malcolm K Brenner

Faculty, Staff and Students Publications

BACKGROUND: Cell therapies for solid tumors are thwarted by the hostile tumor microenvironment (TME) and by heterogeneous expression of tumor target antigens. We address both limitations with a novel class of chimeric antigen receptors based on plant lectins, which recognize the aberrant sugar residues that are a 'hallmark' of both malignant and associated stromal cells. We have expressed in T cells a modified lectin from banana, H84T BanLec, attached to a chimeric antigen receptor (H84T-CAR) that recognizes high-mannose (asparagine residue with five to nine mannoses). Here, we tested the efficacy of our novel H84T CAR in models of pancreatic ductal …

Allogeneic Haematopoietic Cell Transplant In Patients With Relapsed/Refractory Anaplastic Large Cell Lymphoma, Fateeha Furqan, Kwang W Ahn, Yue Chen, Manmeet Kaur, Syed A Abutalib, Nausheen Ahmed, Sairah Ahmed, Mohamed A Kharfan-Dabaja, Johnathan Friedberg, Tara Gregory, Laquisa Hill, Cole Sterling, Stephan K Barta, Mazyar Shadman, Miguel-Angel Perales, Jasmine Zain, Alex F Herrera, Craig Sauter, Mehdi Hamadani

Faculty, Staff and Students Publications

The prognosis of relapsed/refractory (R/R) anaplastic large cell lymphoma (ALCL) is poor. Large studies evaluating outcomes of allogeneic haematopoietic cell transplantation (allo-HCT) in systemic R/R ALCL are not available. Using the Center for International Blood and Marrow Transplant Research (CIBMTR) database, we evaluated outcomes of 182 adults (aged ≥18 years) with R/R ALCL undergoing allo-HCT between 2008 and 2019. Non-relapse mortality (NRM), disease relapse/progression (REL), progression-free survival (PFS), and overall survival (OS) were modelled using Cox proportional hazards models. The median (range) follow-up of survivors was 62 (3-148) months. The 1-year NRM was 18%. The 5-year REL, PFS and OS …

Multiomics In Primary And Metastatic Breast Tumors From The Aurora Us Network Finds Microenvironment And Epigenetic Drivers Of Metastasis, Susana Garcia-Recio, Toshinori Hinoue, Gregory L Wheeler, Benjamin J Kelly, Ana C Garrido-Castro, Tomas Pascual, Aguirre A De Cubas, Youli Xia, Brooke M Felsheim, Marni B Mcclure, Andrei Rajkovic, Ezgi Karaesmen, Markia A Smith, Cheng Fan, Paula I Gonzalez Ericsson, Melinda E Sanders, Chad J Creighton, Jay Bowen, Kristen Leraas, Robyn T Burns, Sara Coppens, Amy Wheless, Salma Rezk, Amy L Garrett, Joel S Parker, Kelly K Foy, Hui Shen, Ben H Park, Ian Krop, Carey Anders, Julie Gastier-Foster, Mothaffar F Rimawi, Rita Nanda, Nancy U Lin, Claudine Isaacs, P Kelly Marcom, Anna Maria Storniolo, Fergus J Couch, Uma Chandran, Michael Davis, Jonathan Silverstein, Alexander Ropelewski, Minetta C Liu, Susan G Hilsenbeck, Larry Norton, Andrea L Richardson, W Fraser Symmans, Antonio C Wolff, Nancy E Davidson, Lisa A Carey, Adrian V Lee, Justin M Balko, Katherine A Hoadley, Peter W Laird, Elaine R Mardis, Tari A King, Charles M Perou

Faculty, Staff and Students Publications

The AURORA US Metastasis Project was established with the goal to identify molecular features associated with metastasis. We assayed 55 females with metastatic breast cancer (51 primary cancers and 102 metastases) by RNA sequencing, tumor/germline DNA exome and low-pass whole-genome sequencing and global DNA methylation microarrays. Expression subtype changes were observed in ~30% of samples and were coincident with DNA clonality shifts, especially involving HER2. Downregulation of estrogen receptor (ER)-mediated cell-cell adhesion genes through DNA methylation mechanisms was observed in metastases. Microenvironment differences varied according to tumor subtype; the ER

Selective Reprogramming Of Regulatory T Cells In Solid Tumors Can Strongly Enhance Or Inhibit Tumor Growth, Rami Alfar, John V Napoleon, Imrul Shahriar, Richard Finnell, Cole Walchle, Austin Johnson, Philip S Low

Faculty, Staff and Students Publications

Folate receptor delta (FRδ) has been used as a biomarker for regulatory T cells (Tregs), because its expression is limited to Tregs and ovum. Although FRδ is unable to bind folate, we have used molecular docking software to identify a folate congener that binds FRδ with high affinity and have exploited this FRδ-specific ligand to target attached drugs (imaging agents, immune activators, and immune suppressors) specifically to Tregs in murine tumor xenografts. Analysis of treated tumors demonstrates that targeting of a Toll-like receptor 7 agonist inhibits Treg expression of FOXP3, PD-1, CTLA4, and HELIOS, resulting in 40-80% reduction in tumor …

The Nr2f2-Hand2 Signaling Axis Regulates Progesterone Actions In The Uterus At Early Pregnancy, Yeongseok Oh, Elvis Quiroz, Tianyuan Wang, Yassmin Medina-Laver, Skylar Montague Redecke, Francisco Dominguez, John P Lydon, Francesco J Demayo, San-Pin Wu

Faculty, Staff and Students Publications

Endometrial function is dependent on a tight crosstalk between the epithelial and stromal cells of the endometrium. This communication is critical to ensure a fertile uterus and relies on progesterone and estrogen signaling to prepare a receptive uterus for embryo implantation in early pregnancy. One of the key mediators of this crosstalk is the orphan nuclear receptor NR2F2, which regulates uterine epithelial receptivity and stromal cell differentiation. In order to determine the molecular mechanism regulated by NR2F2, RNAseq analysis was conducted on the uterus of

The Covert Symphony: Cellular And Molecular Accomplices In Breast Cancer Metastasis, Hongjiang Si, Madelyn Esquivel, Erika Mendoza Mendoza, Kevin Roarty

Faculty, Staff and Students Publications

Breast cancer has emerged as the most commonly diagnosed cancer and primary cause of cancer-related deaths among women worldwide. Although significant progress has been made in targeting the primary tumor, the effectiveness of systemic treatments to prevent metastasis remains limited. Metastatic disease continues to be the predominant factor leading to fatality in the majority of breast cancer patients. The existence of a prolonged latency period between initial treatment and eventual recurrence in certain patients indicates that tumors can both adapt to and interact with the systemic environment of the host, facilitating and sustaining the progression of the disease. In order …

The Fgfr1 Signaling Pathway Upregulates The Oncogenic Transcription Factor Foxq1 To Promote Breast Cancer Cell Growth, Yan Lin, Fengkang Lin, Zhuoran Zhang, Lijia Peng, Wenli Yang, Mao Yang, Bo Luo, Ting Wu, Dabing Li, Xuesen Li, Bing Ran, Songyot Anuchapreeda, Rujirek Chaiwongsa, Pinyaphat Khamphikham, Suwit Duangmano, Jianming Xu, Tao He, Sakorn Pornprasert

Faculty, Staff and Students Publications

FGFR1 is a receptor tyrosine kinase deregulated in certain breast cancers (BCs) with a poor prognosis. Although FGFR1-activated phosphorylation cascades have been mapped, the key genes regulated by FGFR1 in BC are largely unclear. FOXQ1 is an oncogenic transcription factor. Although we found that activation of FGFR1 robustly upregulated FOXQ1 mRNA, how FGFR1 regulates FOXQ1 gene expression and whether FOXQ1 is essential for FGFR1-stimulated cell proliferation are unknown. Herein, we confirmed that activation of FGFR1 robustly upregulated FOXQ1 mRNA and protein in BC cells. Knockdown of FOXQ1 blocked the FGFR1 signaling-stimulated BC cell proliferation, colony formation, and xenograft tumor growth. …

Resveratrol Attenuates Staphylococcal Enterotoxin B-Activated Immune Cell Metabolism, Hasan Alghetaa, Amira Mohammed, Narendra Singh, Kiesha Wilson, Goushuai Cai, Nagireddy Putluri, Mitzi Nagarkatti, Prakash Nagarkatti

Faculty, Staff and Students Publications

Acute Respiratory Distress Syndrome (ARDS) is triggered by a variety of insults, such as bacterial and viral infections, including SARS-CoV-2, leading to high mortality. In the murine model of ARDS induced by Staphylococcal enterotoxin-B (SEB), our previous studies showed that while SEB triggered 100% mortality, treatment with Resveratrol (RES) completely prevented such mortality by attenuating inflammation in the lungs. In the current study, we investigated the metabolic profile of SEB-activated immune cells in the lungs following treatment with RES. RES-treated mice had higher expression of miR-100 in the lung mononuclear cells (MNCs), which targeted mTOR, leading to its decreased expression. …

Ultrahigh Resolution Lipid Mass Spectrometry Imaging Of High-Grade Serous Ovarian Cancer Mouse Models, Xin Ma, Andro Botros, Sylvia R Yun, Eun Young Park, Olga Kim, Soojin Park, Thu-Huyen Pham, Ruihong Chen, Murugesan Palaniappan, Martin M Matzuk, Jaeyeon Kim, Facundo M Fernández

Faculty, Staff and Students Publications

No effective screening tools for ovarian cancer (OC) exist, making it one of the deadliest cancers among women. Considering that little is known about the detailed progression and metastasis mechanism of OC at a molecular level, it is crucial to gain more insights into how metabolic and signaling alterations accompany its development. Herein, we present a comprehensive study using ultra-high-resolution Fourier transform ion cyclotron resonance matrix-assisted laser desorption/ionization (MALDI) mass spectrometry imaging (MSI) to investigate the spatial distribution and alterations of lipids in ovarian tissues collected from double knockout (n = 4) and triple mutant mouse models (n …

Ai-Powered Discovery Of A Novel P53-Y220c Reactivator, Shan Zhou, Dafei Chai, Xu Wang, Praveen Neeli, Xinfang Yu, Aram Davtyan, Ken Young, Yong Li

Faculty, Staff and Students Publications

Introduction

The p53-Y220C mutation is one of the most common mutations that play a major role in cancer progression.

Methods

In this study, we applied artificial intelligence (AI)-powered virtual screening to identify small-molecule compounds that specifically restore the wild-type p53 conformation from p53-Y220C. From 10 million compounds, the AI algorithm selected a chemically diverse set of 83 high-scoring hits, which were subjected to several experimental assays using cell lines with different p53 mutations.

Results

We identified one compound, H3, that preferentially killed cells with the p53-Y220C mutation compared to cells with other p53 mutations. H3 increased the amount of folded …

Risk Stratification For Hepatocellular Cancer Among Patients With Cirrhosis Using A Hepatic Fat Polygenic Risk Score, Aaron P Thrift, Fasiha Kanwal, Yanhong Liu, Saira Khaderi, Amit G Singal, Jorge A Marrero, Nicole Loo, Sumeet K Asrani, Michelle Luster, Abeer Al-Sarraj, Jing Ning, Spiridon Tsavachidis, Xiangjun Gu, Christopher I Amos, Hashem B El-Serag

Faculty, Staff and Students Publications

BACKGROUND: Polygenic risk scores (PRS) hold the promise to refine prognostication in hepatocellular cancer (HCC). The few available HCC PRS include germline risk variants identified among individuals of mostly European ancestry, but data are lacking on the transportability of these PRS in multiethnic U.S patients with cirrhosis from multiple etiologies.

METHODS: We used data from 1644 patients with cirrhosis enrolled in two prospective cohort studies in the U.S. Patients were followed until HCC diagnosis, death, liver transplantation, or last study visit through June 30, 2021. The high-risk variants in PNPLA3-MBOAT7-TM6SF2-GCKR were combined in a PRS and we evaluated its association …

Small Extracellular Vesicle-Mediated Itgb6 Sirna Delivery Downregulates The Αvβ6 Integrin And Inhibits Adhesion And Migration Of Recipient Prostate Cancer Cells, Shiv Ram Krishn, Vaughn Garcia, Nicole M Naranjo, Fabio Quaglia, Christopher D Shields, Maisha A Harris, Andrew V Kossenkov, Qin Liu, Eva Corey, Dario C Altieri, Lucia R Languino

Department of Cancer Biology Faculty Papers

The αVβ6 integrin, an epithelial-specific cell surface receptor absent in normal prostate and expressed during prostate cancer (PrCa) progression, is a therapeutic target in many cancers. Here, we report that transcript levels of ITGB6 (encoding the β6 integrin subunit) are significantly increased in metastatic castrate-resistant androgen receptor-negative prostate tumors compared to androgen receptor-positive prostate tumors. In addition, the αVβ6 integrin protein levels are significantly elevated in androgen receptor-negative PrCa patient derived xenografts (PDXs) compared to androgen receptor-positive PDXs. In vitro, the androgen receptor-negative PrCa cells express high levels of the αVβ6 integrin compared to androgen receptor-positive PrCa cells. Additionally, …

Evaluation Of The Efficacy Of The Anti-Ulcer Oral Mucosal Protective Agent Radoralex® In The Prevention And Treatment Of Radiation-Induced Oral Mucosal Reactions Induced During Treatment Of Nasopharyngeal Carcinoma, Jun Yin, Jirui Xie, Jiawei Lin, Chengyin Weng, Shun Lu, Peng Xu, Shuo Zhang, Cheng Luo, Yecai Huang, Lu Li, Jinyi Lang, Mei Feng

Faculty, Staff and Student Publications

The aim of this study was to evaluate the efficacy and safety of antiulcer oral mucosal protectant-RADoralex® in the prevention and treatment of radiation-induced oral mucosal reactions elicited during intensity-modulated radiation therapy (IMRT). for locally advanced nasopharyngeal carcinoma (NPC). A total of 90 patients with locally advanced NPC who developed post-treatment grade 1 oral mucositis were selected for this study. They were randomly assigned to the experimental group (n = 44) treated by mouth rinsing with the RADoralex® during radiochemotherapy and the control group (n = 43) treated by mouth rinsing with sodium bicarbonate solution, and the patients’ oral mucosal …

Habitat Imaging Biomarkers For Diagnosis And Prognosis In Cancer Patients Infected With Covid-19, Muhammad Aminu, Divya Yadav, Lingzhi Hong, Elliana Young, Paul Edelkamp, Maliazurina Saad, Morteza Salehjahromi, Pingjun Chen, Sheeba J Sujit, Melissa M Chen, Bradley Sabloff, Gregory Gladish, Patricia M De Groot, Myrna C B Godoy, Tina Cascone, Natalie I Vokes, Jianjun Zhang, Kristy K Brock, Naval Daver, Scott E Woodman, Hussein A Tawbi, Ajay Sheshadri, J Jack Lee, David Jaffray, D Code Team, Carol C Wu, Caroline Chung, Jia Wu

Faculty, Staff and Student Publications

OBJECTIVES: Cancer patients have worse outcomes from the COVID-19 infection and greater need for ventilator support and elevated mortality rates than the general population. However, previous artificial intelligence (AI) studies focused on patients without cancer to develop diagnosis and severity prediction models. Little is known about how the AI models perform in cancer patients. In this study, we aim to develop a computational framework for COVID-19 diagnosis and severity prediction particularly in a cancer population and further compare it head-to-head to a general population.

METHODS: We have enrolled multi-center international cohorts with 531 CT scans from 502 general patients and …

Effect Of Neoadjuvant Chemotherapy On Intraoperative Core Temperature In Patients With Breast Cancer: A Retrospective Cohort Study, Daniel D Kim, Sarah M Desnyder, Patrick M Dougherty, Juan P Cata

Faculty, Staff and Student Publications

BACKGROUND: Clinical evidence suggests that chemotherapeutic agents are associated with neuropathy and peripheral autonomic dysfunction. However, the possible effects of neoadjuvant chemotherapy on intraoperative temperature remain poorly characterised.

METHODS: We evaluated patients who underwent a mastectomy for breast cancer between April 2016 and July 2020. Propensity scores were used to match patients who received neoadjuvant chemotherapy with those who did not, and intraoperative core temperature patterns were analysed in the matched cohort. The independent associations between vasopressor use and heart rate during general anaesthesia in the matched cohort were also analysed.

RESULTS: Data from 1764 patients were analysed (882 patients …

Loss Of Ubiquitin-Specific Peptidase 18 Destabilizes 14-3-3Ζ Protein And Represses Lung Cancer Metastasis, Zibo Chen, Lin Zheng, Yulong Chen, Xiuxia Liu, Masanori Kawakami, Lisa Maria Mustachio, Jason Roszik, Katherine V Ferry-Galow, Ralph E Parchment, Xin Liu, Thorkell Andresson, Gerard Duncan, Jonathan M Kurie, Jaime Rodriguez-Canales, Xi Liu, Ethan Dmitrovsky

Faculty, Staff and Student Publications

Cancer metastasis is a major cause of cancer-related mortality. Strategies to reduce metastases are needed especially in lung cancer, the most common cause of cancer mortality. We previously reported increased ubiquitin-specific peptidase 18 (USP18) expression in lung and other cancers. Engineered reduction of USP18 expression repressed lung cancer growth and promoted apoptosis. This deubiquitinase (DUB) stabilized targeted proteins by removing the complex interferon-stimulated gene 15 (ISG15). This study explores if the loss of USP18 reduced lung cancer metastasis. USP18 knock-down in lung cancer cells was independently achieved using small hairpin RNAs (shRNAs) and small interfering RNAs (siRNAs). USP18 knock-down reduced …

Prognostic Model For Predicting Overall And Cancer-Specific Survival Among Patients With Superficial Spreading Melanoma: A Seer Based Study, Qiang Ji, Jun Tang, Shulian Li, Junjie Chen

Faculty, Staff and Student Publications

Skin malignant melanoma is one of the most aggressive skin tumors. Superficial spreading melanoma (SSM) is the most common histological type, which can originate from different body skin sites, and some patients can still accumulate regional lymph nodes and even have distant metastasis in some cases. This study used the relevant data from the monitoring, epidemiology and results database of the National Cancer Institute database to study the overall survival (OS) and cancer-specific survival (CSS) of SSM patients and established an SSM nomogram to evaluate the prognosis of patients. A total of 13,922 patients were collected from the monitoring, epidemiology …

Polycystin-1 Is A Crucial Regulator Of Bin1 Expression And T-Tubule Remodeling Associated With The Development Of Dilated Cardiomyopathy, Magda C Díaz-Vesga, Raúl Flores-Vergara, Jaime A Riquelme, Marcelo Llancaqueo, Gina Sánchez, Cecilia Vergara, Luis Michea, Paulina Donoso, Andrew F G Quest, Ivonne Olmedo, Zully Pedrozo

Faculty, Staff and Student Publications

Cardiomyopathy is commonly observed in patients with autosomal dominant polycystic kidney disease (ADPKD), even when they have normal renal function and arterial pressure. The role of cardiomyocyte polycystin-1 (PC1) in cardiovascular pathophysiology remains unknown. PC1 is a potential regulator of BIN1 that maintains T-tubule structure, and alterations in BIN1 expression induce cardiac pathologies. We used a cardiomyocyte-specific PC1-silenced (PC1-KO) mouse model to explore the relevance of cardiomyocyte PC1 in the development of heart failure (HF), considering reduced BIN1 expression induced T-tubule remodeling as a potential mechanism. PC1-KO mice exhibited an impairment of cardiac function, as measured by echocardiography, but no …

The Impact Of Mutation Of Myelodysplasia-Related Genes In De Novo Acute Myeloid Leukemia Carrying Npm1 Mutation, Yi Wang, Andres E Quesada, Zhuang Zuo, L Jeffrey Medeiros, C Cameron Yin, Shaoying Li, Jie Xu, Gautam Borthakur, Yisheng Li, Chao Yang, Yasmin Abaza, Juehua Gao, Xinyan Lu, M James You, Yizhuo Zhang, Pei Lin

Faculty, Staff and Student Publications

Background: The impact of gene mutations typically associated with myelodysplastic syndrome (MDS) in acute myeloid leukemia (AML) with NPM1 mutation is unclear. Methods: Using a cohort of 107 patients with NPM1-mutated AML treated with risk-adapted therapy, we compared survival outcomes of patients without MDS-related gene mutations (group A) with those carrying concurrent FLT3-ITD (group B) or with MDS-related gene mutations (group C). Minimal measurable disease (MMD) status assessed by multiparameter flow cytometry (MFC), polymerase chain reaction (PCR), and/or next-generation sequencing (NGS) were reviewed. Results: Among the 69 patients treated intensively, group C showed significantly inferior progression-free survival (PFS, p < 0.0001) but not overall survival (OS, p = 0.055) compared to group A. Though groups A and C had a similar MMD rate, group C patients had a higher relapse rate (p = 0.016). Relapse correlated with MMD status at the end of cycle 2 induction (p = 0.023). Survival of group C patients was similar to that of group B. Conclusion: MDS-related gene mutations are associated with an inferior survival in NPM1-mutated AML.

Targeting Myocardial Equilibrative Nucleoside Transporter Ent1 Provides Cardioprotection By Enhancing Myeloid Adora2b Signaling, Jiaojiao Wang, Andre R Jordan, Huabin Zhu, Sarrah L Hasanali, Eric Thomas, Soum D Lokeshwar, Daley S Morera, Sung Alexander, Joseph Mcdaniels, Anuj Sharma, Karina Aguilar, Semih Sarcan, Tianyi Zhu, Mark S Soloway, Martha K Terris, Muthusamy Thangaraju, Luis E Lopez, Vinata B Lokeshwar

Faculty, Staff and Student Publications

BACKGROUND: Hyaluronic acid (HA) promotes cancer metastasis; however, the currently approved treatments do not target HA. Metastatic renal carcinoma (mRCC) is an incurable disease. Sorafenib (SF) is a modestly effective antiangiogenic drug for mRCC. Although only endothelial cells express known SF targets, SF is cytotoxic to RCC cells at concentrations higher than the pharmacological-dose (5-µM). Using patient cohorts, mRCC models, and SF combination with 4-methylumbelliferone (MU), we discovered an SF target in RCC cells and targeted it for treatment.

METHODS: We analyzed HA-synthase (HAS1, HAS2, HAS3) expression in RCC cells and clinical (n = 129), TCGA-KIRC (n = 542), and …

Breast Implant-Associated Anaplastic Large Cell Lymphoma: A Case Report, Jennie Tan, Jamie Johnson-Eddy, Wesley Tang, Yanchun Li

Cooper Rowan Medical Journal

This report aims to review a case of breast implant-associated anaplastic large cell lymphoma (BIA-ALCL) by comparing the patient's course with the current literature.

BIA-ALCL is a specific type of T-cell lymphoma that can develop after breast implantation, but has only recently been recognized within the last decade. Although overall rare, certain types of breast implants have increased association with developing subsequent lymphoma. This case occurred after mastectomy with breast reconstruction for unilateral invasive ductal carcinoma with a textured, saline Allergan breast implant. BIA-ALCL manifested and was symptomatic nine years after implantation.