Medical Specialties Commons^™

Chd1, A Multifaceted Epigenetic Remodeler In Prostate Cancer, Haoyan Li, Loraine Gigi, Di Zhao

Faculty, Staff and Student Publications

Chromatin remodeling proteins contribute to DNA replication, transcription, repair, and recombination. The chromodomain helicase DNA-binding (CHD) family of remodelers plays crucial roles in embryonic development, hematopoiesis, and neurogenesis. As the founding member, CHD1 is capable of assembling nucleosomes, remodeling chromatin structure, and regulating gene transcription. Dysregulation of CHD1 at genetic, epigenetic, and post-translational levels is common in malignancies and other human diseases. Through interacting with different genetic alterations, CHD1 possesses the capabilities to exert oncogenic or tumor-suppressive functions in context-dependent manners. In this Review, we summarize the biochemical properties and dysregulation of CHD1 in cancer cells, and then discuss CHD1's …

Editorial: Prion-Like Transmission Of Pathogenic Proteins In Neurodegenerative Diseases: Structural And Molecular Bases, Victor Banerjee, Fei Wang, Daniela Sarnataro, Claudio Soto

Faculty, Staff and Student Publications

No abstract provided.

Targeting T Cell Checkpoints 41bb And Lag3 And Myeloid Cell Cxcr1/Cxcr2 Results In Antitumor Immunity And Durable Response In Pancreatic Cancer, Pat Gulhati, Aislyn Schalck, Shan Jiang, Xiaoying Shang, Chang-Jiun Wu, Pingping Hou, Sharia Hernandez Ruiz, Luisa Solis Soto, Edwin Parra, Haoqiang Ying, Jincheng Han, Prasenjit Dey, Jun Li, Pingna Deng, Emi Sei, Dean Y Maeda, John A Zebala, Denise J Spring, Michael Kim, Huamin Wang, Anirban Maitra, Dirk Moore, Karen Clise-Dwyer, Y Alan Wang, Nicholas E Navin, Ronald A Depinho

Faculty, Staff and Student Publications

Pancreatic ductal adenocarcinoma (PDAC) is considered non-immunogenic, with trials showing its recalcitrance to PD1 and CTLA4 immune checkpoint therapies (ICTs). Here, we sought to systematically characterize the mechanisms underlying de novo ICT resistance and to identify effective therapeutic options for PDAC. We report that agonist 41BB and antagonist LAG3 ICT alone and in combination, increased survival and antitumor immunity, characterized by modulating T cell subsets with antitumor activity, increased T cell clonality and diversification, decreased immunosuppressive myeloid cells and increased antigen presentation/decreased immunosuppressive capability of myeloid cells. Translational analyses confirmed the expression of 41BB and LAG3 in human PDAC. Since …

Targeting Immunosuppressive Ly6c+ Classical Monocytes Reverses Anti-Pd-1/Ctla-4 Immunotherapy Resistance, B Leticia Rodriguez, Limo Chen, Yanli Li, Shucheng Miao, David H Peng, Jared J Fradette, Lixia Diao, Jessica M Konen, Frank R Rojas Alvarez, Luisa M Solis, Xiaohui Yi, Aparna Padhye, Laura A Gibson, Joshua K Ochieng, Xiaofei Zhou, Jing Wang, Don L Gibbons

Faculty, Staff and Student Publications

Introduction: Despite significant clinical advancement with the use of immune checkpoint blockade (ICB) in non-small cell lung cancer (NSCLC) there are still a major subset of patients that develop adaptive/acquired resistance. Understanding resistance mechanisms to ICB is critical to developing new therapeutic strategies and improving patient survival. The dynamic nature of the tumor microenvironment and the mutational load driving tumor immunogenicity limit the efficacy to ICB. Recent studies indicate that myeloid cells are drivers of ICB resistance. In this study we sought to understand which immune cells were contributing to resistance and if we could modify them in a way …

Segmentation Stability Of Human Head And Neck Cancer Medical Images For Radiotherapy Applications Under De-Identification Conditions: Benchmarking Data Sharing And Artificial Intelligence Use-Cases, Jaakko Sahlsten, Kareem A Wahid, Enrico Glerean, Joel Jaskari, Mohamed A Naser, Renjie He, Benjamin H Kann, Antti Mäkitie, Clifton D Fuller, Kimmo Kaski

Faculty, Staff and Student Publications

BACKGROUND: Demand for head and neck cancer (HNC) radiotherapy data in algorithmic development has prompted increased image dataset sharing. Medical images must comply with data protection requirements so that re-use is enabled without disclosing patient identifiers. Defacing, i.e., the removal of facial features from images, is often considered a reasonable compromise between data protection and re-usability for neuroimaging data. While defacing tools have been developed by the neuroimaging community, their acceptability for radiotherapy applications have not been explored. Therefore, this study systematically investigated the impact of available defacing algorithms on HNC organs at risk (OARs).

METHODS: A publicly available dataset …

Tnik Regulation Of Interferon Signaling And Endothelial Cell Response To Virus Infection, Khanh M Chau, Abishai Dominic, Eleanor L Davis, Sivareddy Kotla, Estefani Turcios Berrios, Arsany Fahim, Ashwin Arunesh, Shengyu Li, Dongyu Zhao, Kaifu Chen, Alan R Davis, Minh T H Nguyen, Yongxing Wang, Scott E Evans, Guangyu Wang, John P Cooke, Jun-Ichi Abe, David P Huston, Nhat-Tu Le

Faculty, Staff and Student Publications

BACKGROUND: Traf2 and Nck-interacting kinase (TNIK) is known for its regulatory role in various processes within cancer cells. However, its role within endothelial cells (ECs) has remained relatively unexplored.

METHODS: Leveraging RNA-seq data and Ingenuity Pathway Analysis (IPA), we probed the potential impact of TNIK depletion on ECs.

RESULTS: Examination of RNA-seq data uncovered more than 450 Differentially Expressed Genes (DEGs) in TNIK-depleted ECs, displaying a fold change exceeding 2 with a false discovery rate (FDR) below 0.05. IPA analysis unveiled that TNIK depletion leads to the inhibition of the interferon (IFN) pathway [-log (

SUMMARY: Our findings suggest that …

Early Detection Of Mandible Osteoradionecrosis Risk In A High Comorbidity Veteran Population, David Chamberlayne Wilde, Sagar Kansara, Logan Banner, Rickey Morlen, David Hernandez, Andrew Tsao Huang, Weiyuan Mai, Clifton David Fuller, Stephen Lai, Vlad Constantin Sandulache

Faculty, Staff and Student Publications

OBJECTIVE: Osteoradionecrosis (ORN) of the mandible is a devastating complication of external beam radiation therapy (EBRT) for head and neck squamous cell carcinoma (HNSCC). We sought to ascertain ORN risk in a Veteran HNSCC population treatment with definitive or adjuvant EBRT and followed prospectively.

STUDY DESIGN: Retrospective analysis of prospective cohort.

SETTING: Tertiary care Veterans Health Administration (VHA) medical center.

METHODS: Patients with HNSCC who initiated treatment at the Michael E. DeBakey Veterans Affairs Medical Center (MEDVAMC) are prospectively tracked for quality of care purposes through the end of the cancer surveillance period (5 years post treatment completion). We retrospectively …

Targeting Nuclear Hormone Receptors For The Prevention Of Breast Cancer, Cassandra L Moyer, Powel H Brown

Faculty, Staff and Student Publications

Advancements in research have led to the steady decline of breast cancer mortality over the past thirty years. However, breast cancer incidence has continued to rise, resulting in an undue burden on healthcare costs and highlighting a great need for more effective breast cancer prevention strategies, including targeted chemo preventative agents. Efforts to understand the etiology of breast cancer have uncovered important roles for nuclear receptors in the development and progression of breast cancer. Targeted therapies to inhibit estrogen receptor (ER) and progesterone receptor (PR) signaling (selective ER modulators, aromatase inhibitors and selective PR modulators) have shown great promise for …

Neuroanatomical Correlates Of The Late Positive Potential In Youth With Pediatric Bipolar Disorder, Alessio Simonetti, Marijn Lijffijt, Sherin Kurian, Johanna Saxena, Delfina Janiri, Marianna Mazza, Giulio Carriero, Lorenzo Moccia, Benson Mwangi, Alan C Swann, Jair C Soares

Faculty, Staff and Student Publications

BACKGROUND: The late positive potential (LPP) could be a marker of emotion dysregulation in youth with pediatric bipolar disorder (PBD). However, the neuroanatomical correlates of the LPP are still not clarified.

OBJECTIVE: To provide cortical and deep gray matter correlates of the LPP in youth, specifically, youth with PBD.

METHODS: Twenty-four 7 to 17 years-old children with PBD and 28 healthy controls (HC) underwent cortical thickness and deep gray matter volumes measurements through magnetic resonance imaging and LPP measurement elicited by passively viewing emotional faces through electroencephalography. T-tests compared group differences in LPP, cortical thickness, and deep gray matter volumes. …

Neurocognitive Correlates Of Cerebellar Volumetric Alterations In Youth With Pediatric Bipolar Spectrum Disorders And Bipolar Offspring, Kirti Saxena, Alessio Simonetti, Christopher D Verrico, Delfina Janiri, Marco Di Nicola, Antonello Catinari, Sherin Kurian, Johanna Saxena, Benson Mwangi, Jair C Soares

Faculty, Staff and Student Publications

BACKGROUND: Emerging evidence points towards the involvement of the cerebellum in the processing of emotions and pathophysiology of mood disorders. However, cerebellar and related cognitive alterations in youth with pediatric bipolar disorder (PBD) and those at high risk to develop the disorder, such as bipolar offspring (BD-OFF) are not clearly defined.

OBJECTIVE: To investigate cerebellar gray and white matter volumes, cognition, and their relationship in youth with PBD and BD-OFF.

METHODS: Thirty youth (7 to 17 years, inclusive) with PBD, 30 BD-OFF and 40 healthy controls (HC) were recruited. Study participants underwent a computer-based cognitive battery assessing affective processing, executive …

Development Of A Clinical Prediction Model For Diabetes In Chronic Pancreatitis: The Predict3c Study, Christie Jeon, Phil A Hart, Liang Li, Yunlong Yang, Eleanor Chang, Melena D Bellin, William E Fisher, Evan L Fogel, Christopher E Forsmark, Walter G Park, Stephen K Van Den Eeden, Santhi Swaroop Vege, Jose Serrano, David C Whitcomb, Dana K Andersen, Darwin L Conwell, Dhiraj Yadav, Mark O Goodarzi

Faculty, Staff and Student Publications

Objective: Diabetes that arises from chronic pancreatitis (CP) is associated with increased morbidity and mortality. Methods to predict which patients with CP are at greatest risk for diabetes are urgently needed. We aimed to examine independent risk factors for diabetes in a large cohort of patients with CP.

Research design and methods: This cross-sectional study comprised 645 individuals with CP enrolled in the PROCEED study, of whom 276 had diabetes. We conducted univariable and multivariable regression analyses of potential risk factors for diabetes. Model performance was assessed by area under the receiver operating characteristic curve (AUROC) analysis, and accuracy was …

Editorial: Advances In The Biological Effects Of Ionizing Radiation, Fada Guan, Lina Zhao, Julianna K Bronk, Mirjana Maletic-Savatic, David R Grosshans, David J Carlson

Faculty, Staff and Student Publications

No abstract provided.

Powerful, Scalable And Resource-Efficient Meta-Analysis Of Rare Variant Associations In Large Whole Genome Sequencing Studies, Xihao Li, Corbin Quick, Hufeng Zhou, Sheila M Gaynor, Yaowu Liu, Han Chen, Margaret Sunitha Selvaraj, Ryan Sun, Rounak Dey, Donna K Arnett, Lawrence F Bielak, Joshua C Bis, John Blangero, Eric Boerwinkle, Donald W Bowden, Jennifer A Brody, Brian E Cade, Adolfo Correa, L Adrienne Cupples, Joanne E Curran, Paul S De Vries, Ravindranath Duggirala, Barry I Freedman, Harald H H Göring, Xiuqing Guo, Jeffrey Haessler, Rita R Kalyani, Charles Kooperberg, Brian G Kral, Leslie A Lange, Ani Manichaikul, Lisa W Martin, Stephen T Mcgarvey, Braxton D Mitchell, May E Montasser, Alanna C Morrison, Take Naseri, Jeffrey R O'Connell, Nicholette D Palmer, Patricia A Peyser, Bruce M Psaty, Laura M Raffield, Susan Redline, Alexander P Reiner, Muagututi'a Sefuiva Reupena, Kenneth M Rice, Stephen S Rich, Colleen M Sitlani, Jennifer A Smith, Kent D Taylor, Ramachandran S Vasan, Cristen J Willer, James G Wilson, Lisa R Yanek, Wei Zhao, Nhlbi Trans-Omics For Precision Medicine (Topmed) Consortium, Topmed Lipids Working Group, Jerome I Rotter, Pradeep Natarajan, Gina M Peloso, Zilin Li, Xihong Lin

Faculty, Staff and Student Publications

Meta-analysis of whole genome sequencing/whole exome sequencing (WGS/WES) studies provides an attractive solution to the problem of collecting large sample sizes for discovering rare variants associated with complex phenotypes. Existing rare variant meta-analysis approaches are not scalable to biobank-scale WGS data. Here we present MetaSTAAR, a powerful and resource-efficient rare variant meta-analysis framework for large-scale WGS/WES studies. MetaSTAAR accounts for relatedness and population structure, can analyze both quantitative and dichotomous traits and boosts the power of rare variant tests by incorporating multiple variant functional annotations. Through meta-analysis of four lipid traits in 30,138 ancestrally diverse samples from 14 studies of …

Association Of Hearing Loss And Tinnitus Symptoms With Health-Related Quality Of Life Among Long-Term Oropharyngeal Cancer Survivors, Puja Aggarwal, Marc-Elie Nader, Paul W Gidley, Raj Pratihar, Shirin Jivani, Adam S Garden, Frank E Mott, Ryan P Goepfert, Christopher Wallace Ogboe, Camille Charles, Clifton D Fuller, Stephen Y Lai, G Brandon Gunn, Erich M Sturgis, Ehab Y Hanna, Katherine A Hutcheson, Sanjay Shete

Faculty, Staff and Student Publications

BACKGROUND: This study investigated the association of hearing loss and tinnitus with overall health-related quality of life (HRQoL) among long-term oropharyngeal cancer (OPC) survivors.

METHODS: This study included OPC survivors treated between 2000 and 2013 and surveyed from September 2015 to July 2016. Hearing loss and tinnitus were measured by asking survivors to rate their "difficulty with hearing loss and/or ringing in the ears" from 0 (not present) to 10 (as bad as you can imagine). Hearing loss and tinnitus scores were categorized as follows: 0 for none, 1-4 for mild, and 5-10 for moderate to severe. The primary outcome …

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 …

Influence Of Waist Circumference Measurement Site On Visceral Fat And Metabolic Risk In Youth, Sojung Lee, Yejin Kim, Minsub Han

Faculty, Staff and Student Publications

Although the rate of childhood obesity seems to have plateaued in recent years, the prevalence of obesity among children and adolescents remains high. Childhood obesity is a major public health concern as overweight and obese youth suffer from many co-morbid conditions once considered exclusive to adults. It is now well demonstrated that abdominal obesity as measured by waist circumference (WC) is an independent risk factor for cardiovascular disease and metabolic dysfunction in youth. Despite the strong associations between WC and cardiometabolic risk factors, there is no consensus regarding the optimal WC measurement sites to assess abdominal obesity and obesity-related health …

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.

Cardiac Neural Crest And Cardiac Regeneration, Shannon Erhardt, Jun Wang

Faculty, Staff and Student Publications

Neural crest cells (NCCs) are a vertebrate-specific, multipotent stem cell population that have the ability to migrate and differentiate into various cell populations throughout the embryo during embryogenesis. The heart is a muscular and complex organ whose primary function is to pump blood and nutrients throughout the body. Mammalian hearts, such as those of humans, lose their regenerative ability shortly after birth. However, a few vertebrate species, such as zebrafish, have the ability to self-repair/regenerate after cardiac damage. Recent research has discovered the potential functional ability and contribution of cardiac NCCs to cardiac regeneration through the use of various vertebrate …

Safety And Microbiological Activity Of Phage Therapy In Persons With Cystic Fibrosis Colonized With Pseudomonas Aeruginosa: Study Protocol For A Phase 1b/2, Multicenter, Randomized, Double-Blind, Placebo-Controlled Trial, Pranita D Tamma, Maria Souli, Michael Billard, Joseph Campbell, Douglas Conrad, Damon W Ellison, Beth Evans, Scott R Evans, Kerryl E Greenwood-Quaintance, Andrey A Filippov, Holly S Geres, Toshimitsu Hamasaki, Lauren Komarow, Mikeljon P Nikolich, Thomas P Lodise, Seema U Nayak, Carmelle Norice-Tra, Robin Patel, David Pride, Janie Russell, Daria Van Tyne, Henry F Chambers, Vance G Fowlerjr, Robert T Schooley, Antibacterial Resistance Leadership Group

Faculty, Staff and Student Publications

BACKGROUND: Bacteriophages (phages) are a promising anti-infective option for human disease. Major gaps remain in understanding their potential utility.

METHODS: This is a randomized, placebo-controlled, double-blind study of a single dose of intravenous phage in approximately 72 clinically stable adult cystic fibrosis volunteers recruited from up to 20 US sites with Pseudomonas aeruginosa airway colonization. The single dose of phage consists of a mixture of four anti-pseudomonal phages. Six sentinel participants will be sequentially enrolled with dose escalation of the phage mixture by one log

DISCUSSION: This trial will investigate the activity of phages in reducing P. aeruginosa colony counts …

Clinical Significance Of Glycolytic Metabolic Activity In Hepatocellular Carcinoma, Joann Jung, Sowon Park, Yeonwoo Jang, Sung-Hwan Lee, Yun Seong Jeong, Sun Young Yim, Ju-Seog Lee

Faculty, Staff and Student Publications

High metabolic activity is a hallmark of cancers, including hepatocellular carcinoma (HCC). However, the molecular features of HCC with high metabolic activity contributing to clinical outcomes and the therapeutic implications of these characteristics are poorly understood. We aimed to define the features of HCC with high metabolic activity and uncover its association with response to current therapies. By integrating gene expression data from mouse liver tissues and tumor tissues from HCC patients (n = 1038), we uncovered three metabolically distinct HCC subtypes that differ in clinical outcomes and underlying molecular biology. The high metabolic subtype is characterized by poor …

Comparison Of Machine-Learning And Deep-Learning Methods For The Prediction Of Osteoradionecrosis Resulting From Head And Neck Cancer Radiation Therapy, Brandon Reber, Lisanne Van Dijk, Brian Anderson, Abdallah Sherif Radwan Mohamed, Clifton Fuller, Stephen Lai, Kristy Brock

Faculty, Staff and Student Publications

PURPOSE: Deep-learning (DL) techniques have been successful in disease-prediction tasks and could improve the prediction of mandible osteoradionecrosis (ORN) resulting from head and neck cancer (HNC) radiation therapy. In this study, we retrospectively compared the performance of DL algorithms and traditional machine-learning (ML) techniques to predict mandible ORN binary outcome in an extensive cohort of patients with HNC.

METHODS AND MATERIALS: Patients who received HNC radiation therapy at the University of Texas MD Anderson Cancer Center from 2005 to 2015 were identified for the ML (n = 1259) and DL (n = 1236) studies. The subjects were followed for ORN …

Anti-Cancer Mechanisms Of Action Of Therapeutic Alternating Electric Fields (Tumor Treating Fields [Ttfields]), Shadi Shams, Chirag B Patel

Faculty, Staff and Student Publications

Despite improved survival outcomes across many cancer types, the prognosis remains grim for certain solid organ cancers including glioblastoma and pancreatic cancer. Invariably in these cancers, the control achieved by time-limited interventions such as traditional surgical resection, radiation therapy, and chemotherapy is short-lived. A new form of anti-cancer therapy called therapeutic alternating electric fields (AEFs) or tumor treating fields (TTFields) has been shown, either by itself or in combination with chemotherapy, to have anti-cancer effects that translate to improved survival outcomes in patients. Although the pre-clinical and clinical data are promising, the mechanisms of TTFields are not fully elucidated. Many …

Kidney Proximal Tubule Glut2-More Than Meets The Eye, Majdoleen Ahmad, Ifat Abramovich, Bella Agranovich, Alina Nemirovski, Eyal Gottlieb, Liad Hinden, Joseph Tam

Faculty, Staff and Student Publications

Tubulopathy plays a central role in the pathophysiology of diabetic kidney disease (DKD). Under diabetic conditions, the kidney proximal tubule cells (KPTCs) are exposed to an extensive amount of nutrients, most notably glucose; these nutrients deteriorate KPTCs function and promote the development and progression of DKD. Recently, the facilitative glucose transporter 2 (GLUT2) in KPTCs has emerged as a central regulator in the pathogenesis of DKD. This has been demonstrated by identifying its specific role in enhancing glucose reabsorption and glucotoxicity, and by deciphering its effect in regulating the expression of the sodium-glucose transporter 2 (SGLT2) in KPTCs. Moreover, reduction/deletion …

Mechanical Ventilation In Patients With Cardiogenic Pulmonary Edema: A Sub-Analysis Of The Lung Safe Study, Laura Amado-Rodríguez, Raquel Rodríguez-Garcia, Giacomo Bellani, Tài Pham, Eddy Fan, Fabiana Madotto, John G Laffey, Guillermo M Albaiceta, Lung Safe Investigators

Faculty, Staff and Student Publications

BACKGROUND: Patients with acute respiratory failure caused by cardiogenic pulmonary edema (CPE) may require mechanical ventilation that can cause further lung damage. Our aim was to determine the impact of ventilatory settings on CPE mortality.

METHODS: Patients from the LUNG SAFE cohort, a multicenter prospective cohort study of patients undergoing mechanical ventilation, were studied. Relationships between ventilatory parameters and outcomes (ICU discharge/hospital mortality) were assessed using latent mixture analysis and a marginal structural model.

RESULTS: From 4499 patients, 391 meeting CPE criteria (median age 70 [interquartile range 59-78], 40% female) were included. ICU and hospital mortality were 34% and 40%, …

Glutamine Produces Ammonium To Tune Lysosomal Ph And Regulate Lysosomal Function, Jian Xiong, Thi Thu Trang Luu, Kartik Venkatachalam, Guangwei Du, Michael X Zhu

Faculty, Staff and Student Publications

Glutamine is one of the most abundant amino acids in the cell. In mitochondria, glutaminases 1 and 2 (GLS1/2) hydrolyze glutamine to glutamate, which serves as the precursor of multiple metabolites. Here, we show that ammonium generated during GLS1/2-mediated glutaminolysis regulates lysosomal pH and in turn lysosomal degradation. In primary human skin fibroblasts BJ cells and mouse embryonic fibroblasts, deprivation of total amino acids for 1 h increased lysosomal degradation capacity as shown by the increased turnover of lipidated microtubule-associated proteins 1A/1B light chain 3B (LC3-II), several autophagic receptors, and endocytosed DQ-BSA. Removal of glutamine but not any other amino …

Clinical Cancer And Direct-To-Consumer Genetic Test Result-Sharing Behavior: Findings From Hints 2020, Sukh Makhnoon, Robert Yu, Susan K Peterson, Sanjay Shete

Faculty, Staff and Student Publications

INTRODUCTION: Sharing genetic test results with different stakeholders such as family members, healthcare providers and genetic counselors (HCP/GCs), spouses/partners, and friends is a health behavior of clinical importance in genomic medicine.

METHODS: Using nationally representative population-based data collected from the Health Information National Trends Survey (HINTS 5, cycle 4), we identified the prevalence and factors associated with genetic test result-sharing behavior for high-risk cancer tests, genetic health risk tests, and ancestry tests within four groups: HCP/GCs, first-degree relatives (FDRs), spouse/partner, and friend/other.

RESULTS: Overall, 68.4% of those who underwent high-risk cancer genetic testing shared their results with FDRs, whereas 89.9% …