Medical Specialties Commons^™

Pcb126 Exposure During Pregnancy Alters Maternal And Fetal Gene Expression, Cetewayo S. Rashid, Joshua D. Preston, Sara Y. Ngo Tenlep, Marissa K. Cook, Eric M. Blalock, Changcheng Zhou, Hollie I. Swanson, Kevin J. Pearson

Markey Cancer Center Faculty Publications

Polychlorinated biphenyls (PCBs) are organic pollutants that can have lasting impacts on offspring health. Here, we sought to examine maternal and fetal gene expression differences of aryl hydrocarbon receptor (AHR)- regulated genes in a mouse model of prenatal PCB126 exposure. Female mice were bred and gavaged with 1 μmole/kg bodyweight PCB126 or vehicle control on embryonic days 0 and 14, and maternal and fetal tissues were collected on embryonic day 18.5. Total RNAs were isolated, and gene expression levels were analyzed in both maternal and fetal tissues using the NanoString nCounter system. Interestingly, we found that the expression levels of …

Phosphatase And Pseudo-Phosphatase Functions Of Phosphatase Of Regenerating Liver 3 (Prl-3) Are Insensitive To Divalent Metals In Vitro, Jeffery T. Jolly, Ty C. Cheatham, Jessica S. Blackburn

Markey Cancer Center Faculty Publications

Phosphatase of regenerating liver 3 (PRL-3) is associated with cancer metastasis and has been shown to interact with the cyclin and CBS domain divalent metal cation transport mediator (CNNM) family of proteins to regulate the intracellular concentration of magnesium and other divalent metals. Despite PRL-3’s importance in cancer, factors that regulate PRL-3’s phosphatase activity and its interactions with CNNM proteins remain unknown. Here, we show that divalent metal ions, including magnesium, calcium, and manganese, have no impact on PRL-3’s structure, stability, phosphatase activity, or CNNM binding capacity, indicating that PRL-3 does not act as a metal sensor, despite its interaction …

Portable Optical Spectroscopic Assay For Non-Destructive Measurement Of Key Metabolic Parameters On In Vitro Cancer Cells And Organotypic Fresh Tumor Slices, Jing Yan, Carlos Frederico Lima Goncalves, Madison O. Korfhage, Zahid Hasan, Teresa Whei-Mei Fan, Xiaoqin Wang, Caigang Zhu

Markey Cancer Center Faculty Publications

To enable non-destructive metabolic characterizations on in vitro cancer cells and organotypic tumor models for therapeutic studies in an easy-to-access way, we report a highly portable optical spectroscopic assay for simultaneous measurement of glucose uptake and mitochondrial function on various cancer models with high sensitivity. Well-established breast cancer cell lines (MCF-7 and MDA-MB-231) were used to validate the optical spectroscopic assay for metabolic characterizations, while fresh tumor samples harvested from both animals and human cancer patients were used to test the feasibility of our optical metabolic assay for non-destructive measurement of key metabolic parameters on organotypic tumor slices. Our optical …

Structures Of The Insecticidal Toxin Complex Subunit Xpta2 Highlight Roles For Flexible Domains, Cole L. Martin, David W. Chester, Christopher D. Radka, Lurong Pan, Zhengrong Yang, Rachel C. Hart, Elad M. Binshtein, Zhao Wang, Lisa Nagy, Lawrence J. Delucas, Stephen G. Aller

Markey Cancer Center Faculty Publications

The Toxin Complex (Tc) superfamily consists of toxin translocases that contribute to the targeting, delivery, and cytotoxicity of certain pathogenic Gram-negative bacteria. Membrane receptor targeting is driven by the A-subunit (TcA), which comprises IgG-like receptor binding domains (RBDs) at the surface. To better understand XptA2, an insect specific TcA secreted by the symbiont X. nematophilus from the intestine of entomopathogenic nematodes, we determined structures by X-ray crystallography and cryo-EM. Contrary to a previous report, XptA2 is pentameric. RBD-B exhibits an indentation from crystal packing that indicates loose association with the shell and a hotspot for possible receptor binding or a …

Using Artificial Intelligence To Identify Tumor Microenvironment Heterogeneity In Non–Small Cell Lung Cancers, Tanner Ducote, Kassandra J. Naughton, Erika M. Skaggs, Therese J. Bocklage, Derek B. Allison, Christine Fillmore Brainson

Markey Cancer Center Faculty Publications

Lung cancer heterogeneity is a major barrier to effective treatments and encompasses not only the malignant epithelial cell phenotypes and genetics but also the diverse tumor-associated cell types. Current techniques used to investigate the tumor microenvironment can be time-consuming, expensive, complicated to interpret, and often involves destruction of the sample. Here we use standard hematoxylin and eosinestained tumor sections and the HALO AI nuclear phenotyping software to characterize 6 distinct cell types (epithelial, mesenchymal, macrophage, neutrophil, lymphocyte, and plasma cells) in both murine lung cancer models and human lung cancer samples. CD3 immunohistochemistry and lymph node sections were used to …

The Role Of Vaccination Route With An Adenovirus-Vectored Vaccine In Protection, Viral Control, And Transmission In The Sars-Cov-2/K18-Hace2 Mouse Infection Model, Alexandria Dickson, Elizabeth Geerling, E. Taylor Stone, Mariah Hassert, Tara L. Steffen, Taneesh Makkena, Madeleine Smither, Katherine E. Schwetye, Jianfeng Zhang, Bertrand Georges, M. Scot Roberts, John J. Suschak, Amelia K. Pinto, James D. Brien

Markey Cancer Center Faculty Publications

Introduction: Vaccination is the most effective mechanism to prevent severe COVID-19. However, breakthrough infections and subsequent transmission of SARS-CoV-2 remain a significant problem. Intranasal vaccination has the potential to be more effective in preventing disease and limiting transmission between individuals as it induces potent responses at mucosal sites.

Methods: Utilizing a replication-deficient adenovirus serotype 5-vectored vaccine expressing the SARS-CoV-2 RBD (AdCOVID) in homozygous and heterozygous transgenic K18-hACE2, we investigated the impact of the route of administration on vaccine immunogenicity, SARS-CoV-2 transmission, and survival.

Results: Mice vaccinated with AdCOVID via the intramuscular or intranasal route and subsequently challenged with SARS-CoV-2 showed …

The S1p Receptor 1 Antagonist Ponesimod Reduces Tlr4-Induced Neuroinflammation And Increases Aβ Clearance In 5xfad Mice, Zhihui Zhu, Liping Zhang, Ahmed Elsherbini, Simone M. Crivelli, Priyanka Tripathi, Carmen Harper, Zainuddin Quadri, Stefka D. Spassieva, Erhard Bieberich

Markey Cancer Center Faculty Publications

Background Previously, we showed that the sphingosine-1-phosphate (S1P) transporter spinster 2 (Spns2) mediates activation of microglia in response to amyloid β peptide (Aβ). Here, we investigated if Ponesimod, a functional S1P receptor 1 (S1PR1) antagonist, prevents Aβ-induced activation of glial cells and Alzheimer’s disease (AD) pathology.

Methods We used primary cultures of glial cells and the 5XFAD mouse model to determine the effect of Aβ and Ponesimod on glial activation, Aβ phagocytosis, cytokine levels and pro-inflammatory signaling pathways, AD pathology, and cognitive performance.

Findings Aβ42 increased the levels of TLR4 and S1PR1, leading to their complex formation. Ponesimod prevented the …

Weighted Mean Difference Statistics For Paired Data In The Presence Of Missing Values, Yuntong Li, Brent J. Shelton, William St Clair, Heidi L. Weiss, John L. Villano, Arnold Stromberg, Chi Wang, Li Chen

Markey Cancer Center Faculty Publications

Missing data is a common issue in many biomedical studies. Under a paired design, some subjects may have missing values in either one or both of the conditions due to loss of follow-up, insufficient biological samples, etc. Such partially paired data complicate statistical comparison of the distribution of the variable of interest between the two conditions. In this article, we propose a general class of test statistics based on the difference in weighted sample means without imposing any distributional or model assumption. An optimal weight is derived from this class of tests. Simulation studies show that our proposed test with …

The Case For Expanding Visual Assessments During Spaceflight, Ethan Waisberg, Joshua Ong, Mouayad Masalkhi, Nasif Zaman, Sharif Amit Kamran, Prithul Sarker, Alireza Tavakkoli, Andrew G Lee

Faculty, Staff and Student Publications

Spaceflight associated neuro-ocular syndrome (SANS) is one of the potential barriers to human long-duration spaceflight (LDSF), including a manned mission to Mars. While a large barrier, the pathophysiology of SANS is not well understood, and functional and structural findings from SANS continue to be further characterized. Currently on the International Space Station (ISS), scheduled visual assessments are static visual acuity, Amsler grid, and a self-reported survey. Additional visual assessments may help the understanding of this neuro-ophthalmic phenomenon, as well as the effects of spaceflight of overall ocular health. In this paper, a case is made for expanding scheduled visual assessments …

T-Cell Receptor Beta Variable Gene Polymorphism Predicts Immune-Related Adverse Events During Checkpoint Blockade Immunotherapy, Bettzy Stephen, Joud Hajjar, Shrutii Sarda, Dzifa Yawa Duose, Jeffrey M Conroy, Carl Morrison, Anas Alshawa, Mingxuan Xu, Abdulrazzak Zarifa, Sapna P Patel, Ying Yuan, Evan Kwiatkowski, Linghua Wang, Jordi Rodon Ahnert, Siqing Fu, Funda Meric-Bernstam, Geoffrey M Lowman, Timothy Looney, Aung Naing

Faculty, Staff and Student Publications

BACKGROUND: Immune checkpoint inhibitors have revolutionized cancer treatment. However, they are associated with a unique spectrum of side effects, called immune-related adverse events (irAEs), which can cause significant morbidity and quickly progress to severe or life-threatening events if not treated promptly. Identifying predictive biomarkers for irAEs before immunotherapy initiation is therefore a critical area of research. Polymorphisms within the T-cell receptor beta (TCRB) variable (TRBV) gene have been implicated in autoimmune disease and may be mechanistically linked to irAEs. However, the repetitive nature of the TCRB locus and incomplete genome assembly has hampered the evaluation of TRBV polymorphisms in the …

The Development Of Artificial Intelligence-Based To Ols For Expert Peer Review Of Radiotherapy Treatment Plans, Mary Gronberg

Dissertations and Theses (Open Access)

Creating a patient-specific radiation treatment plan is a time-consuming and operator-dependent manual process. The treatment planner adjusts the planning parameters in a trial-and-error fashion in an effort to balance the competing clinical objectives of tumor coverage and normal tissue sparing. Often, a plan is selected because it meets basic organ at risk dose thresholds for severe toxicity; however, it is evident that a plan with a decreased risk of normal tissue complication probability could be achieved. This discrepancy between “acceptable” and “best possible” plan is magnified if either the physician or treatment planner lacks focal expertise in the disease site. …

Auto-Segmentation In Pancreatic And Liver Radiation Therapy, Cenji Yu

Dissertations and Theses (Open Access)

Background

Gastrointestinal cancers exhibit a high mortality rate compared to other cancer types. Among these, pancreatic cancer ranks as the fourth leading cause of cancer-related deaths worldwide. The five-year survival rate remains alarmingly low at a mere 9%. Hepatocellular carcinoma (HCC), another aggressive form of cancer, is rapidly becoming the primary cause of cancer-related deaths in the United States. The treatment of both liver cancer and pancreatic cancer heavily relies on a multidisciplinary approach. Innovative treatment strategies involving dose-escalated regimens, such as stereotactic body radiation therapy (SBRT), are emerging as an important pillar of the management of liver and pancreatic …

Uncertainty In The Physical Basis Of Estimates Of Relative Biological Effectiveness In Carbon Radiotherapy, Shannon Hartzell, Shannon Hartzell Ph.D.

Dissertations and Theses (Open Access)

Carbon ion radiotherapy is a novel modality used for the treatment of tumors that are unresectable, close to critical structures, or resistant to standard radiotherapy. A unique benefit of this therapy is the relative biological effectiveness (RBE) of the beam (i.e., how biologically potent carbon ions are as compared to x-rays), which is significantly elevated. This RBE also varies as a function of many parameters, and there are currently several models implemented in clinical and research-based treatment planning systems with which to predict RBE. These algorithms are computationally expensive and there are currently no means of validating their implementation within …

Risk And Risk Factors For Colorectal Subsequent Malignancies In Survivors Of Childhood Cancer: A Report From The Childhood Cancer Survivor Study, Constance A. Owens

Dissertations and Theses (Open Access)

Survivors of childhood cancer are at risk for colorectal subsequent malignant neoplasms (SMNs); notably, these cancers are amenable to screening. To identify at-risk survivors that may benefit from early screening, descriptive and risk factor analyses were performed to ascertain risk factors for colorectal SMN in childhood cancer survivors. In particular, we explored detailed radiation therapy (RT) data – colorectal and substructure dose-volume metrics – as risk factors for colorectal SMN risk; metrics that have yet to be thoroughly investigated. We developed a novel population-based anatomical colorectal model with substructures for RT dosimetry in late effects studies of childhood cancer survivors; …

The Collaborative National Quality And Efficacy Registry For Scleroderma: Association Of Medication Use On Gastrointestinal Tract Symptoms In Early Disease And The Importance Of Tobacco Cessation, Sarah Luebker, Tracy M Frech, Shervin Assassi, Jessica K Gordon, Elana J Bernstein, Virginia D Steen, Ami A Shah, Laura K Hummers, Carrie Richardson, Dinesh Khanna, Flavia V Castelino, Lorinda Chung, Faye N Hant, Victoria K Shanmugam, John M Vanburen, Jessica Alvey, Monica Harding, Nora Sandorfi

Faculty, Staff and Student Publications

Objectives: Systemic Sclerosis (SSc) is frequently associated with gastrointestinal tract (GIT) involvement. The Collaborative National Quality and Efficacy Registry (CONQUER) is a US-based collaborative study collecting longitudinal follow up data on SSc patients with less than 5-years disease duration enrolled at Scleroderma centres of excellence. This manuscript presents the GIT natural history and outcomes in relation to other scleroderma manifestations and medication exposures.

Methods: CONQUER participants that had completed a minimum of two serial Scleroderma Clinical Trials Consortium GIT Questionnaires (GIT 2.0) were included in this analysis. Patients were categorised by total GIT 2.0 severity at baseline, and by category …

Integrative Prognostic Machine Learning Models In Mantle Cell Lymphoma, Holly A Hill, Preetesh Jain, Chi Young Ok, Koji Sasaki, Han Chen, Michael L Wang, Ken Chen

Faculty, Staff and Student Publications

Patients with mantle cell lymphoma (MCL), an incurable B-cell malignancy, benefit from accurate pretreatment disease stratification. We curated an extensive database of 862 patients diagnosed between 2014 and 2022. A machine learning (ML) gradient-boosted model incorporated baseline features from clinicopathologic, cytogenetic, and genomic data with high predictive power discriminating between patients with indolent or responsive MCL and those with aggressive disease (AUC ROC = 0.83). In addition, we utilized the gradient-boosted framework as a robust feature selection method for multivariate logistic and survival modeling. The best ML models incorporated features from clinical and genomic data types highlighting the need for …

Polypharmacy And Prescription Medication Use In A Population-Based Sample Of Adolescent And Young Adult Cancer Survivors, Andrea C Betts, Caitlin C Murphy, L Aubree Shay, Bijal A Balasubramanian, Christine Markham, Marlyn Allicock

Faculty, Staff and Student Publications

PURPOSE: We examined prescription medication use and identified correlates of polypharmacy-taking multiple medications-in adolescent and young adult cancer survivors (AYAs), who experience early-onset chronic conditions.

METHODS: Our cross-sectional study pooled data (2008-2017) from the national Medical Expenditure Panel Survey. We estimated prevalence of polypharmacy (≥ 5 unique prescription medications over an approximate 1-year period) in AYAs (age 18-39 years with a history of cancer) and age- and sex-matched controls, overall and by sociodemographics, clinical factors, and health indicators. We compared survivors' and controls' medication use across therapeutic classes. To identify correlates of polypharmacy among AYAs, we included factors with p …

An Updated Report On The Prevalence Of Prior Cancer Among Persons Newly Diagnosed With Cancer In The Surveillance, Epidemiology, And End Results Program, Caitlin C Murphy, Guillermo A Tortolero, David E Gerber, Sandi L Pruitt

Faculty, Staff and Student Publications

This cohort study uses population-based data from the National Cancer Institute Surveillance, Epidemiology, and End Results program of cancer registries to estimate prevalence of prior cancer among adults diagnosed with an incident cancer in 2019.

Real-Time 3-D Video Reconstruction For Guidance Of Transventricular Neurosurgery, Prasad Vagdargi, Ali Uneri, Xiaoxuan Zhang, Craig K Jones, Pengwei Wu, Runze Han, Alejandro Sisniega, Junghoon Lee, Patrick Helm, Mark Luciano, William S Anderson, Gregory D Hager, Jeffrey H Siewerdsen

Faculty, Staff and Student Publications

Neuroendoscopic approach to deep-brain targets imparts deformation of the ventricles and adjacent parenchyma, limiting the accuracy of conventional neuronavigation. We report a method for 3D endoscopic reconstruction and registration via simultaneous localization and mapping (SLAM) for real-time guidance with or without robotic assistance. The aim is to permit augmented video overlay of structures registered from preoperative or intraoperative 3D images within and beyond the endoscopic field of view for more accurate targeting in the presence of deep-brain deformation. Phantom studies were performed to evaluate geometric accuracy and uncertainty in distinct scenarios of limited data (feature sparsity and scene occlusion), demonstrating …

Zeb1 Is Regulated By K811 Acetylation To Promote Stability, Nurd Complex Interactions, Emt, And Nsclc Metastasis, Mabel Perez-Oquendo, Roxsan Manshouri, Yanhua Tian, Jared J Fradette, B Leticia Rodriguez, Samrat T Kundu, Don L Gibbons

Faculty, Staff and Student Publications

Epithelial-to-mesenchymal transition results in loss of specialized epithelial cell contacts and acquisition of mesenchymal invasive capacity. The transcription repressor zinc finger E-box-binding homeobox 1 (ZEB1) binds to E-boxes of gene promoter regions to suppress the expression of epithelial genes. ZEB1 has inconsistent molecular weights, which have been attributed to posttranslational modifications (PTM). We performed mass spectrometry and identified K811 acetylation as a novel PTM in ZEB1. To define the role of ZEB1 acetylation in regulating function, we generated ZEB1 acetyl-mimetic (K811Q) and acetyl-deficient (K811R) mutant-expressing non-small cell lung cancer cell lines (NSCLC). We demonstrate that the K811R ZEB1 (125 kDa) …

Interstitial Lung Disease In Patients With Systemic Sclerosis: What Can We Learn From The Senscis Trial?, Shervin Assassi, Sudhakar Tumuluri, Robert W Levin

Faculty, Staff and Student Publications

The SENSCIS trial of nintedanib versus placebo is the largest trial conducted to date in patients with systemic sclerosis-associated interstitial lung disease (SSc-ILD). This trial enrolled 576 patients with an extent of fibrotic ILD on high-resolution computed tomography of >10%. Median time since first non-Raynaud symptom was 3.4 years. Almost half of the patients were receiving a stable dose of mycophenolate at baseline. Key findings of the trial included that at baseline, despite having significant lung fibrosis on HRCT and impairment in lung function, 20% of the patients did not have cough and 30% did not have dyspnoea. Over 52 …

Analysis Of Genomic And Immune Intratumor Heterogeneity In Linitis Plastica Via Multiregional Exome And T-Cell Receptor Sequencing, Jin Huang, Guofeng Zhao, Qiu Peng, Xin Yi, Liyan Ji, Jing Li, Pansong Li, Yanfang Guan, Jie Ge, Ling Chen, Runzhe Chen, Xin Hu, Won-Chul Lee, Alexandre Reuben, P Andrew Futreal, Xuefeng Xia, Jian Ma, Jianjun Zhang, Zihua Chen

Faculty, Staff and Student Publications

The molecular landscape and the intratumor heterogeneity (ITH) architecture of gastric linitis plastica (LP) are poorly understood. We performed whole-exome sequencing (WES) and T-cell receptor (TCR) sequencing on 40 tumor regions from four LP patients. The landscape and ITH at the genomic and immunological levels in LP tumors were compared with multiple cancers that have previously been reported. The lymphocyte infiltration was further assessed by immunohistochemistry (IHC) in LP tumors. In total, we identified 6339 non-silent mutations from multi-samples, with a median tumor mutation burden (TMB) of 3.30 mutations per Mb, comparable to gastric adenocarcinoma from the Cancer Genome Atlas …

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 …

Brief Report: Safety And Antitumor Activity Of Durvalumab Plus Tremelimumab In Programmed Cell Death-(Ligand)1-Monotherapy Pretreated, Advanced Nsclc: Results From A Phase 1b Clinical Trial, Edward B Garon, Alexander I Spira, Sarah B Goldberg, Jamie E Chaft, Vassiliki Papadimitrakopoulou, Tina Cascone, Scott J Antonia, Julie R Brahmer, D Ross Camidge, John D Powderly, Antoinette J Wozniak, Enriqueta Felip, Song Wu, Maria L Ascierto, Nairouz Elgeioushi, Mark M Awad

Faculty, Staff and Student Publications

Introduction: Although first-line immunotherapy approaches are standard, in patients with non-small cell lung cancer (NSCLC) previously treated with programmed cell death protein-1 or programmed death-(ligand)1 (PD-[L]1) inhibitors, the activity of combined CTLA-4 plus PD-(L)1 inhibition is unknown. This phase 1b study evaluated the safety and efficacy of durvalumab plus tremelimumab in adults with advanced NSCLC who received anti-PD-(L)1 monotherapy as their most recent line of therapy.

Methods: Patients with PD-(L)1-relapsed or refractory NSCLC were enrolled between October 25, 2013, and September 17, 2019. Durvalumab 20 mg/kg plus tremelimumab 1 mg/kg was administered intravenously every 4 weeks for four doses, followed …

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 …

Divergent Structures Of Mammalian And Gammaherpesvirus Uracil Dna Glycosylases Confer Distinct Dna Binding And Substrate Activity, Yunxiang Mu, Monika A Zelazowska, Zaowen Chen, Joshua B Plummer, Qiwen Dong, Laurie T Krug, Kevin M Mcbride

Faculty, Staff and Student Publications

Uracil DNA glycosylase (UNG) removes mutagenic uracil base from DNA to initiate base excision repair (BER). The result is an abasic site (AP site) that is further processed by the high-fidelity BER pathway to complete repair and maintain genome integrity. The gammaherpesviruses (GHVs), human Kaposi sarcoma herpesvirus (KSHV), Epstein-Barr virus (EBV), and murine gammaherpesvirus 68 (MHV68) encode functional UNGs that have a role in viral genome replication. Mammalian and GHVs UNG share overall structure and sequence similarity except for a divergent amino-terminal domain and a leucine loop motif in the DNA binding domain that varies in sequence and length. To …

Effect Of Sotagliflozin On Early Mortality And Heart Failure-Related Events: A Post Hoc Analysis Of Soloist-Whf, Bertram Pitt, Deepak L Bhatt, Michael Szarek, Christopher P Cannon, Lawrence A Leiter, Darren K Mcguire, Julia B Lewis, Matthew C Riddle, Adriaan A Voors, Marco Metra, Lars H Lund, Michel Komajda, Jeffrey M Testani, Christopher S Wilcox, Piotr Ponikowski, Renato D Lopes, Justin A Ezekowitz, Franklin Sun, Michael J Davies, Subodh Verma, Mikhail N Kosiborod, Ph Gabriel Steg, Soloist-Whf Investigators

Faculty, Staff and Student Publications

Background: Approximately 25% of patients admitted to hospitals for worsening heart failure (WHF) are readmitted within 30 days.

Objectives: The authors conducted a post hoc analysis of the SOLOIST-WHF (Effect of Sotagliflozin on Cardiovascular Events in Patients With Type 2 Diabetes Post-WHF) trial to evaluate the efficacy of sotagliflozin versus placebo to decrease mortality and HF-related events among patients who began study treatment on or before discharge from their index hospitalization.

Methods: The main endpoint of interest was cardiovascular death or HF-related event (HF hospitalization or urgent care visit) occurring within 90 and 30 days after discharge for the index …

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 …

Open Innovation: The Key To Advancing Brain Health, Harris A Eyre, Jason Searfoss, Malcolm Hopwood, Michael Berk, Shuo Chen, Jeffrey Cummings, Francois Veron, Vicki Zikopoulou, Agustin Ibanez, Kacie Kelly, Jair C Soares, Erin Smith, Barnabas J Gilbert

Faculty, Staff and Student Publications

With the exponential growth in investment attention to brain health-solutions spanning brain wellness to mental health to neurological disorders-tech giants, payers, and biotechnology companies have been making forays into this field to identify technology solutions and pharmaceutical amplifiers. So far, their investments have had mixed results. The concept of open innovation (OI) was first coined by Henry Chesbrough to describe the paradigm by which enterprises allow free flow of ideas, products, and services from the outside to the inside and vice versa in order to remain competitive, particularly in rapidly evolving fields where there is abundant, relevant knowledge outside the …