Diseases Commons^™

Stat6 Suppression Prevents Bleomycin-Induced Dermal Fibrosis, Hua Sun, Ashish Damania, Megan L Mair, Eniola Otukoya, Yi-Dong Li, Katherine Polsky, Yuying Zeng, Jeremiah A Alt, Martin J Citardi, David B Corry, Amber U Luong, John Morgan Knight

Faculty, Staff and Student Publications

Unified airway disease, including concurrent asthma and chronic rhinosinusitis (CRS), is a common, but poorly understood disorder with no curative treatment options. To establish a murine model of chronic unified eosinophilic airway inflammation, mice were challenged with Aspergillus niger, and sinonasal mucosa and lung tissue were evaluated by immunohistochemistry, flow cytometry, and gene expression. Inhalation of A niger conidia resulted in a Th2-biased lung and sinus inflammation that typifies allergic asthma and CRS. Gene network and pathway analysis correlated with human disease with upregulation of not only the JAK-STAT and helper T-cell pathways, but also less expected pathways governing …

Germline Polymorphisms In Mgmt Associated With Temozolomide-Related Myelotoxicity Risk In Patients With Glioblastoma Treated On Nrg Oncology/Rtog 0825, Michael E Scheurer, Renke Zhou, Mark R Gilbert, Melissa L Bondy, Erik P Sulman, Ying Yuan, Yanhong Liu, Elizabeth Vera, Merideth M Wendland, Emad F Youssef, Volker W Stieber, Ritsuko R Komaki, John C Flickinger, Lawrence C Kenyon, H Ian Robins, Grant K Hunter, Ian R Crocker, Samuel T Chao, Stephanie L Pugh, Terri S Armstrong

Faculty, Staff and Students Publications

BACKGROUND: We sought to identify clinical and genetic predictors of temozolomide-related myelotoxicity among patients receiving therapy for glioblastoma.

METHODS:Patients (n = 591) receiving therapy on NRG Oncology/RTOG 0825 were included in the analysis. Cases were patients with severe myelotoxicity (grade 3 and higher leukopenia, neutropenia, and/or thrombocytopenia); controls were patients without such toxicity. A risk-prediction model was built and cross-validated by logistic regression using only clinical variables and extended using polymorphisms associated with myelotoxicity.

RESULTS: 23% of patients developed myelotoxicity (n = 134). This toxicity was first reported during the concurrent phase of therapy for 56 patients; 30 …

Why Test Results Are Still Getting "Lost" To Follow-Up: A Qualitative Study Of Implementation Gaps, Andrew J Zimolzak, Umber Shahid, Traber D Giardina, Sahar A Memon, Umair Mushtaq, Lisa Zubkoff, Daniel R Murphy, Andrea Bradford, Hardeep Singh

Faculty, Staff and Students Publications

BACKGROUND: Lack of timely follow-up of abnormal test results is common and has been implicated in missed or delayed diagnosis, resulting in potential for patient harm.

OBJECTIVE: As part of a larger project to implement change strategies to improve follow-up of diagnostic test results, this study sought to identify specifically where implementation gaps exist, as well as possible solutions identified by front-line staff.

DESIGN: We used a semi-structured interview guide to collect qualitative data from Veterans Affairs (VA) facility staff who had experience with test results management and patient safety.

SETTING: Twelve VA facilities across the USA.

PARTICIPANTS: Facility staff …

Associations Of Duration, Intensity, And Quantity Of Smoking With Risk Of Gastric Intestinal Metaplasia, Aaron P Thrift, Andre G Jove, Yan Liu, Mimi C Tan, Hashem B El-Serag

Faculty, Staff and Students Publications

GOAL: Determine whether various dimensions of smoking increase risk for gastric intestinal metaplasia.

BACKGROUND: Cigarette smoking has been implicated in the etiology of gastric cancer, but it is not clear if smoking is a risk factor for gastric intestinal metaplasia, a precursor lesion of gastric cancer.

MATERIALS AND METHODS: We compared data from 385 gastric intestinal metaplasia cases and 1577 controls without gastric intestinal metaplasia recruited into a cross-sectional study at the Michael E. DeBakey VA Medical Center in Houston, Texas. All participants completed standardized questionnaires and underwent a study endoscopy with gastric mapping biopsies. Gastric intestinal metaplasia cases included …

An Unusual Case Of Breast Implant-Associated Anaplastic Large Cell Lymphoma, Sarah Premji, Andreia Barbieri, Christine Roth, Eric M Rohren, Gustavo Rivero, Sravanti P Teegavarapu

Faculty, Staff and Students Publications

INTRODUCTION: Breast implant-associated anaplastic large cell lymphoma (BIA-ALCL) is a rare disease entity associated with textured breast implants. Though the clinical course is typically indolent, BIA-ALCL can occasionally invade through the capsule into the breast parenchyma with spread to the regional lymph nodes and beyond including chest wall invasive disease.

CASE: We present the case of a 51-year-old female with a history of bilateral silicone breast implants placed approximately twenty years ago who presented with two months of progressively enlarging right breast mass. Ultrasound-guided biopsy of right breast mass and right axillary lymph node showed CD 30-positive

CONCLUSION: Treatment guidelines …

Mental Health And Access To Medical Care In Patients With Chronic Cardiovascular Conditions: An Analysis Of The Behavior Risk Factor Surveillance System, Riyad Y Kherallah, Mahmoud Al Rifai, Jing Liu, Sina Kianoush, Arunima Misra, Salim S Virani

Faculty, Staff and Students Publications

INTRODUCTION: Poor mental health is associated with worse outcomes for chronic diseases. It is unclear whether mental illness predisposes to difficulties with healthcare access.

METHODS: Using a combined dataset of the 2016-2019 Behavioral Risk Factor Surveillance System, this study focused on individuals who reported a chronic cardiovascular condition. Weighted multivariable logistic regression analyses were used to explore the association between domains of mental health and measures of healthcare access including delaying medical care, more than one year since last routine checkup, lack of a primary care physician, and cost-related medication nonadherence.

RESULTS: Among 1,747,397 participants, 27% had a chronic cardiovascular …

Pcsk9 Inhibitors In The Management Of Cardiovascular Risk: A Practical Guidance, Xiaoming Jia, Mahmoud Al Rifai, Anum Saeed, Christie M Ballantyne, Salim S Virani

Faculty, Staff and Students Publications

Proprotein convertase subtilisin/kexin type 9 (PCSK9) inhibitors are potent medications in the toolkit for treatment of atherosclerotic cardiovascular disease. These agents have been well studied in clinical trials supporting their efficacy in dramatically reducing low-density lipoprotein cholesterol (LDL-C) and impact on cardiovascular outcomes. Since the approval of commercial use for PCSK9 inhibitors in 2015, we have also gained significant experience in the use of these therapeutics in the real-world setting. In this article, we review current guideline recommendations, clinical trial evidence on efficacy and safety as well as data on cost-effectiveness, prescription and adherence. We focus primarily on the monoclonal …

A Steroid Receptor Coactivator Small Molecule "Stimulator" Attenuates Post-Stroke Ischemic Brain Injury, Lisa K Mcclendon, Roberto L Garcia, Tyler Lazaro, Ariadna Robledo, Viren Vasandani, Zean Aaron Evan Luna, Abhijit S Rao, Aditya Srivatsan, David M Lonard, Clifford C Dacso, Peter Kan, Bert W O'Malley

Faculty, Staff and Students Publications

Introduction: Pathologic remodeling of the brain following ischemic stroke results in neuronal loss, increased inflammation, oxidative stress, astrogliosis, and a progressive decrease in brain function. We recently demonstrated that stimulation of steroid receptor coactivator 3 with the small-molecule stimulator MCB-613 improves cardiac function in a mouse model of myocardial ischemia. Since steroid receptor coactivators are ubiquitously expressed in the brain, we reasoned that an MCB-613 derivative (MCB-10-1), could protect the brain following ischemic injury. To test this, we administered MCB-10-1 to rats following middle cerebral artery occlusion and reperfusion.

Methods: Neurologic impairment and tissue damage responses were evaluated on day …

Paraventricular Vitamin D Receptors Are Required For Glucose Tolerance In Males But Not Females, Jessie Beck, Silvania Da Silva Teixeira, Keisha Harrison, Gabrielle Phillips, Yanlin He, Stephanie Sisley

Faculty, Staff and Students Publications

When delivered directly into the brain, vitamin D, can improve glucose levels in male mice. Additionally, the loss of the vitamin D receptor (VDR) in male mice's paraventricular hypothalamus (PVH) results in impaired glucose tolerance. Data in humans shows that low vitamin D levels are detrimental to glucose homeostasis, an effect that may be more prominent in men. However, it is unknown if vitamin D action in the brain is required for normal glucose regulation in female mice. This study shows that in both viral and genetic models, male mice with obesity and PVH VDR loss have impaired glucose tolerance …

Clinical Outcome And Gut Development After Insulin-Like Growth Factor-1 Supplementation To Preterm Pigs, Kristine Holgersen, Martin Bo Rasmussen, Galen Carey, Douglas G Burrin, Thomas Thymann, Per Torp Sangild

Faculty, Staff and Students Publications

BACKGROUND: Elevation of circulating insulin-like growth factor-1 (IGF-1) within normal physiological levels may alleviate several morbidities in preterm infants but safety and efficacy remain unclear. We hypothesized that IGF-1 supplementation during the first 1-2 weeks after preterm birth improves clinical outcomes and gut development, using preterm pigs as a model for infants.

METHODS: Preterm pigs were given vehicle or recombinant human IGF-1/binding protein-3 (rhIGF-1, 2.25 mg/kg/d) by subcutaneous injections for 8 days (Experiment 1, n = 34), or by systemic infusion for 4 days (Experiment 2, n = 19), before collection of blood and organs for analyses.

RESULTS: In both …

Influences Of Disrupted Circadian Rhythms On Stroke Outcome, Jennifer A. Liu

Graduate Theses, Dissertations, and Problem Reports (ETD)

The circadian system is composed of a subset of temporal oscillators that function through a transcriptional and post-translational molecular and functional negative feedback loop cycling approximately every 24 hours. The central clock located in the suprachiasmatic nucleus is responsible for entrainment using light as the key timekeeper (zeitgeber); it is responsible for synchronizing and optimizing physiological behavior and function to the environment. Exogenous information, such as day length and light-dark cycles, provide critical temporal cues for adjusting to environmental conditions. Proper alignment to natural light dark cycles and circadian rhythms is optimal for vital health, fitness, and survival in organisms. …

Proceedings Of The 10th Annual Deep Brain Stimulation Think Tank: Advances In Cutting Edge Technologies, Artificial Intelligence, Neuromodulation, Neuroethics, Interventional Psychiatry, And Women In Neuromodulation, Joshua K Wong, Helen S Mayberg, Doris D Wang, R Mark Richardson, Casey H Halpern, Lothar Krinke, Mattia Arlotti, Lorenzo Rossi, Alberto Priori, Sara Marceglia, Ro'ee Gilron, James F Cavanagh, Jack W Judy, Svjetlana Miocinovic, Annaelle D Devergnas, Roy V Sillitoe, Stephanie Cernera, Carina R Oehrn, Aysegul Gunduz, Wayne K Goodman, Erika A Petersen, Helen Bronte-Stewart, Robert S Raike, Mahsa Malekmohammadi, David Greene, Petra Heiden, Huiling Tan, Jens Volkmann, Valerie Voon, Luming Li, Pankaj Sah, Terry Coyne, Peter A Silburn, Cynthia S Kubu, Anna Wexler, Jennifer Chandler, Nicole R Provenza, Sarah R Heilbronner, Marta San Luciano, Christopher J Rozell, Michael D Fox, Coralie De Hemptinne, Jaimie M Henderson, Sameer A Sheth, Michael S Okun

Faculty, Staff and Students Publications

The deep brain stimulation (DBS) Think Tank X was held on August 17–19, 2022 in Orlando FL. The session organizers and moderators were all women with the theme women in neuromodulation. Dr. Helen Mayberg from Mt. Sinai, NY was the keynote speaker. She discussed milestones and her experiences in developing depression DBS. The DBS Think Tank was founded in 2012 and provides an open platform where clinicians, engineers and researchers (from industry and academia) can freely discuss current and emerging DBS technologies as well as the logistical and ethical issues facing the field. The consensus among the DBS Think …

In Silico Integrative Analysis Of Multi-Omics Reveals Regulatory Layers For Diurnal Gene Expression In Mouse Liver, Chunjie Jiang, Panpan Liu, Cam Mong La, Dongyin Guan

Faculty, Staff and Students Publications

Diurnal oscillation persists throughout the body and plays an essential role in maintaining physiological homeostasis. Disruption of diurnal rhythm contributes to many diseases including type 2 diabetes. The regulatory mechanism of the transcription-translation feedback loop (TTFL) of core clock genes is well-established, while a systematic study across all regulatory layers of gene expression, including gene transcription, RNA translation, and DNA binding protein (DBP) activities, is still lacking. We comprehensively bioinformatics analyzed the rhythmicity of gene transcription, mature RNA abundance, protein abundance and DBP activity using publicly available omic-datasets from mouse livers. We found that the core clock genes,

A Survey On Self-Medication For The Prevention Or Treatment Of Covid-19 And Distrust In Healthcare Of Veterans In A Primary Care Setting In The United States, Eva Amenta, Larissa Grigoryan, Laura Dillon, Casey Hines-Munson, John Van, Barbara Trautner

Faculty, Staff and Students Publications

BACKGROUND: The SARS-CoV-2 (COVID-19) pandemic brought the public overwhelming and conflicting information. Rates of trust in healthcare professionals have been declining among laypersons over the past five decades. In this setting, we sought to evaluate the use of medications, both with or without a prescription, to prevent and treat SARS-CoV-2 as well as trust in healthcare among patients in a primary care clinic.

DESIGN: We surveyed 150 veterans in primary care clinic waiting rooms at a large southwestern tertiary care Veterans Affairs hospital. This survey was performed in March-November 2021.

METHODS: The survey asked about respondents' demographics, use of medications, …

The Transcriptomic Portrait Of Locally Advanced Breast Cancer And Its Prognostic Value In A Multi-Country Cohort Of Latin American Patients, Andrea Sabina Llera, Eliana Saul Furquim Werneck Abdelhay, Nora Artagaveytia, Adrián Daneri-Navarro, Bettina Müller, Carlos Velazquez, Elsa B Alcoba, Isabel Alonso, Daniela B Alves Da Quinta, Renata Binato, Alicia Inés Bravo, Natalia Camejo, Dirce Maria Carraro, Mónica Castro, Juan M Castro-Cervantes, Sandra Cataldi, Alfonso Cayota, Mauricio Cerda, Alicia Colombo, Susanne Crocamo, Alicia Del Toro-Arreola, Raúl Delgadillo-Cisterna, Lucía Delgado, Marisa Dreyer-Breitenbach, Laura Fejerman, Elmer A Fernández, Jorge Fernández, Wanda Fernández, Ramón A Franco-Topete, Carolina Gabay, Fancy Gaete, Adriana Garibay-Escobar, Jorge Gómez, Gonzalo Greif, Thomas G Gross, Marisol Guerrero, Marianne K Henderson, Miguel E Lopez-Muñoz, Alejandra Lopez-Vazquez, Silvina Maldonado, Andrés J Morán-Mendoza, Maria Aparecida Nagai, Antonio Oceguera-Villanueva, Miguel A Ortiz-Martínez, Jael Quintero, Antonio Quintero-Ramos, Rui M Reis, Javier Retamales, Ernesto Rivera-Claisse, Darío Rocha, Robinson Rodríguez, Cristina Rosales, Efrain Salas-González, Verónica Sanchotena, Laura Segovia, Juan Martín Sendoya, Aida A Silva-García, Alejandra Trinchero, Olivia Valenzuela, Vidya Vedham, Livia Zagame, United States-Latin American Cancer Research Network (Us-Lacrn);, Osvaldo L Podhajcer

Faculty, Staff and Students Publications

PURPOSES: Most molecular-based published studies on breast cancer do not adequately represent the unique and diverse genetic admixture of the Latin American population. Searching for similarities and differences in molecular pathways associated with these tumors and evaluating its impact on prognosis may help to select better therapeutic approaches.

PATIENTS AND METHODS: We collected clinical, pathological, and transcriptomic data of a multi-country Latin American cohort of 1,071 stage II-III breast cancer patients of the Molecular Profile of Breast Cancer Study (MPBCS) cohort. The 5-year prognostic ability of intrinsic (transcriptomic-based) PAM50 and immunohistochemical classifications, both at the cancer-specific (OSC) and disease-free survival …

Management Of Perioperative Anticoagulation In A Patient With Antiphospholipid Antibody Syndrome Undergoing Cardiac Surgery: A Case Report, Sanjana A Malviya, Yi Deng, Sayyed O Gilani, Alec A Hendon, Melissa A Nikolaidis, Micah S Moseley

Faculty, Staff and Students Publications

Patients with Antiphospholipid syndrome (APLS) are at high risk for both bleeding and thrombotic complications during cardiac surgery involving cardiopulmonary bypass (CPB). In this case we present a patient with APLS and Immune Thrombocytopenic Purpura who successfully underwent aortic valve replacement (AVR) with CPB despite recent craniotomy for subdural hematoma evacuation. Anticoagulation for CPB was monitored by targeting an Activated Clotting Time (ACT) that was 2× the upper limit of normal. A multidisciplinary approach was essential in ensuring a safe and successful operation.

Metastatic Insulinoma Presenting With Postprandial Hypoglycemia, Monique Debrah Maher, Dimpi Nitin Desai, Mandeep Bajaj

Faculty, Staff and Students Publications

BACKGROUND/OBJECTIVE: Patients with an insulinoma, a type of pancreatic neuroendocrine tumor, typically present with fasting hypoglycemia but can rarely present exclusively with postprandial hypoglycemia.

CASE REPORT: A 69-year-old man presented with episodes of postprandial blurry vision, sweating, and confusion for the last 2 years that were becoming more frequent over the last several weeks. Home blood glucose measurements revealed postprandial hypoglycemia (glucose level, 45-70 mg/dL), and symptoms were consistent with the Whipple triad. Continuous glucose monitoring revealed only postprandial hypoglycemia within 2 hours following meals. An outpatient fast was conducted with detectable insulin (6 μIU/mL) and C-peptide (2.0 ng/mL) levels …

Widening Health Disparities: Increasing Cholangiocarcinoma Incidence In An Underserved Population, Disha Kumar, Varun Bansal, Syed A Raza, Aaron P Thrift, Hoda M Malaty, Robert J Sealock

Faculty, Staff and Students Publications

BACKGROUND AND AIMS: Cholangiocarcinoma is a relatively rare malignancy with high mortality. In the U.S., incidence rates of cholangiocarcinoma have increased, particularly affecting younger age groups and Hispanic and Asian individuals. We investigated the incidence of cholangiocarcinoma in a largely under-represented, minority population.

METHODS: We performed a retrospective cohort study from 2005 to 2017 among adults in a county-funded healthcare system in Harris County, Texas. Incidence rate ratios were computed to compare age-standardized rates using U.S. standard population between 2 time periods: 2005-2011 and 2012-2017.

RESULTS: We identified 139 cholangiocarcinoma cases (64% intrahepatic, 36% extrahepatic). The median age at diagnosis …

Endpoints In Heart Failure Drug Development, Aliza Hussain, Arunima Misra, Biykem Bozkurt

Faculty, Staff and Students Publications

Heart failure (HF) is a major health problem worldwide. The development of effective drug and/or device therapy is crucial to mitigate the significant morbidity, mortality and healthcare costs associated with HF. The choice of endpoint in clinical trials has important practical and clinical implications. Outcomes of interest including mortality and HF hospitalisations provide robust evidence for regulatory approval granted there is sufficiency of safety data. At the same time, it is important to recognise that HF patients experience significant impairments in functional capacity and quality of life, underscoring the need to incorporate parameters of symptoms and patient-reported outcomes in clinical …

Meta-Analysis Comparing Outcomes Of High-Power Short-Duration And Low-Power Long-Duration Radiofrequency Ablation For Atrial Fibrillation, Dibbendhu Khanra, Abdul Hamid, Saurabh Deshpande, Anindya Mukherjee, Sanjiv Petkar, Mohammad Saeed, Indranill Basu-Ray

Faculty, Staff and Students Publications

OBJECTIVE: High power short duration (HPSD) ablation strategy is proposed to be more effective than low power long duration (LPLD) for radiofrequency ablation of atrial fibrillation. Although small trials abound, data from a large cohort are lacking. This meta-analysis compares all the existing studies comparing these two approaches to evaluate perceived advantages of one over the other.

METHODS: A systematic search of PubMed, EMBASE, and Cochrane databases identified studies comparing HPSD to LPLD ablation. All the analyses used the random-effects model.

RESULTS: Ablation settings varied widely across 20 studies comprising 2,136 patients who underwent HPSD and 1,753 patients who underwent …

Adult Memory T Cell Responses To The Respiratory Syncytial Virus Fusion Protein During A Single Rsv Season (2018-2019), Brittani N Blunck, Laura S Angelo, David Henke, Vasanthi Avadhanula, Matthew Cusick, Laura Ferlic-Stark, Lynn Zechiedrich, Brian E Gilbert, Pedro A Piedra

Faculty, Staff and Students Publications

Respiratory Syncytial Virus (RSV) is ubiquitous and re-infection with both subtypes (RSV/A and RSV/B) is common. The fusion (F) protein of RSV is antigenically conserved, induces neutralizing antibodies, and is a primary target of vaccine development. Insight into the breadth and durability of RSV-specific adaptive immune response, particularly to the F protein, may shed light on susceptibility to re-infection. We prospectively enrolled healthy adult subjects (n = 19) and collected serum and peripheral blood mononuclear cells (PBMCs) during the 2018–2019 RSV season. Previously, we described their RSV-specific antibody responses and identified three distinct antibody kinetic profiles associated with infection …

Squamous Cell Carcinoma Arising In An Epidermal Inclusion Cyst, Suzanne Alkul, Christopher N Nguyen, Nisha S Ramani, Mahmud Alkul, Ida Orengo, Ikue Shimizu, Bhuvaneswari Krishnan

Faculty, Staff and Students Publications

Squamous cell carcinoma (SCC) arising from an epidermal inclusion cyst (EIC) is uncommon. We present a case of a 70-year-old man with a scalp nodule with persistent discharge that was resected based on the clinical impression of an EIC. Histopathologic exam showed an infundibular EIC with an epidermal type of squamous epithelium; however, some of the cyst lining and lumen was replaced by squamous proliferation with malignant features. There are 56 cases of SCC arising in EICs reported in the English literature. Though suspected EICs are commonly benign, a thorough pathologic evaluation is required to rule out malignancy.

Unique Challenges To Diagnosing Human Herpesvirus-6 (Hhv-6) Encephalitis Following Post-Hematopoietic Stem Cell Transplant: A Case And Brief Review, Harrison Zhu, Amir Ali, Karrune V Woan, Eric Tam, George Yaghmour, Alan Flores, Preet Chaudhary

Faculty, Staff and Students Publications

A patient with an ultimate diagnosis of human herpesvirus-6 (HHV-6) encephalitis developed central nervous system (CNS) symptoms 13 days after undergoing myeloablative haploidentical allogeneic hematopoietic stem cell transplant (HSCT). Due to the patient's body habitus, magnetic resonance (MR) imaging was not obtained until the onset of retrograde amnesia on day +24. MR imaging and other clinical findings eliminated all skepticism of HHV-6 encephalitis and HHV-6 antivirals were initiated on day +28, leading to gradual recovery. This case demonstrates some of the factors that may complicate the diagnosis of post-alloHSCT HHV-6 encephalitis. Because HHV-6 encephalitis and viremia can occur without warning, …

A Novel Model Of Gestational Diabetes: Acute High Fat High Sugar Diet Results In Insulin Resistance And Beta Cell Dysfunction During Pregnancy In Mice, Akansha Mishra, Simone Hernandez Ruano, Pradip K Saha, Kathleen A Pennington

Faculty, Staff and Students Publications

Gestational diabetes mellitus (GDM) affects 7–18% of all pregnancies. Despite its high prevalence, there is no widely accepted animal model. To address this, we recently developed a mouse model of GDM. The goal of this work was to further characterize this animal model by assessing insulin resistance and beta cell function. Mice were randomly assigned to either control (CD) or high fat, high sugar (HFHS) diet and mated 1 week later. At day 0 (day of mating) mice were fasted and intraperitoneal insulin tolerance tests (ipITT) were performed. Mice were then euthanized and pancreata were collected for histological analysis. Euglycemic …

Sr9009 Improves Heart Function After Pressure Overload Independent Of Cardiac Rev-Erb, Hui Li, Shiyang Song, Chih-Liang Tien, Lei Qi, Andrea Graves, Eleni Nasiotis, Thomas P Burris, Yuanbiao Zhao, Zheng Sun, Lilei Zhang

Faculty, Staff and Students Publications

The core clock component REV-ERB is essential for heart function. Previous studies show that REV-ERB agonist SR9009 ameliorates heart remodeling in the pressure overload model with transverse aortic constriction (TAC). However, it is unknown whether SR9009 indeed works through cardiac REV-ERB, given that SR9009 might target other proteins and that REV-ERB in non-cardiac tissues might regulate cardiac functions indirectly. To address this question, we generated the REV-ERBα/β cardiac-specific double knockout mice (cDKO). We found that REV-ERB cardiac deficiency leads to profound dilated cardiac myopathy after TAC compared to wild-type (WT) control mice, confirming the critical role of REV-ERB in protecting …

Steroid Receptor Coactivators – Their Role In Immunity, Yosi Gilad, David M Lonard, Bert W O'Malley

Faculty, Staff and Students Publications

Steroid Receptor Coactivators (SRCs) are essential regulators of transcription with a wide range of impact on human physiology and pathology. In immunology, SRCs play multiple roles; they are involved in the regulation of nuclear factor-κB (NF-κB), macrophage (MΦ) activity, lymphoid cells proliferation, development and function, to name just a few. The three SRC family members, SRC-1, SRC-2 and SRC-3, can exert their immunological function either in an independent manner or act in synergy with each other. In certain biological contexts, one SRC family member can compensate for lack of activity of another member, while in other cases one SRC can …

Multi-Antigen-Targeted T-Cell Therapy To Treat Patients With Relapsed/Refractory Breast Cancer, Valentina Hoyos, Spyridoula Vasileiou, Manik Kuvalekar, Ayumi Watanabe, Ifigeneia Tzannou, Yovana Velazquez, Matthew French-Kim, Wingchi Leung, Suhasini Lulla, Catherine Robertson, Claudette Foreman, Tao Wang, Shaun Bulsara, Natalia Lapteva, Bambi Grilley, Matthew Ellis, Charles Kent Osborne, Angela Coscio, Julie Nangia, Helen E Heslop, Cliona M Rooney, Juan F Vera, Premal Lulla, Mothaffar Rimawi, Ann M Leen

Faculty, Staff and Students Publications

PURPOSE: Adoptively transferred, ex vivo expanded multi-antigen-targeted T cells (multiTAA-T) represent a new, potentially effective, and nontoxic therapeutic approach for patients with breast cancer (BC). In this first-in-human trial, we investigated the safety and clinical effects of administering multiTAA T cells targeting the tumor-expressed antigens, Survivin, NY-ESO-1, MAGE-A4, SSX2, and PRAME, to patients with relapsed/refractory/metastatic BC.

MATERIALS AND METHODS: MultiTAA T-cell products were generated from the peripheral blood of heavily pre-treated patients with metastatic or locally recurrent unresectable BC of all subtypes and infused at a fixed dose level of 2 × 107/m2. Patients received two infusions of cells 4 …

The Prevalence And Spectrum Of Reported Incidental Adrenal Abnormalities In Abdominal Computed Tomography Of Cancer Patients: The Experience Of A Comprehensive Cancer Center, Aiham Qdaisat, Sara Bedrose, Obadah Ezzeldin, Ahmed W Moawad, Sai-Ching J Yeung, Khaled M Elsayes, Mouhammed Amir Habra

Faculty, Staff and Students Publications

BACKGROUND: The increasing use of computed tomography (CT) has identified many patients with incidental adrenal lesions. Further evaluation of these lesions is often dependent on the language used in the radiology report. Compared to the general population, patients with cancer have a higher risk for adrenal abnormalities, yet data on the prevalence and type of incidental adrenal lesions reported on radiologic reports in cancer patients is limited. In this study, we aimed to determine the prevalence and nature of adrenal abnormalities as an incidental finding reported on radiology reports of cancer patients evaluated for reasons other than suspected adrenal pathology. …

Physical Activity And Diet Quality In Relation To Non-Alcoholic Fatty Liver Disease: A Cross-Sectional Study In A Representative Sample Of Us Adults Using Nhanes 2017–2018, Natalia I Heredia, Xiaotao Zhang, Maya Balakrishnan, Carrie R Daniel, Jessica P Hwang, Lorna H Mcneill, Aaron P Thrift

Faculty, Staff and Students Publications

The association of physical activity (PA) and diet quality with non-alcoholic fatty liver disease (NAFLD) and NAFLD-related fibrosis have never been examined in a representative sample of U.S. adults using a more precise form of measuring NAFLD. The purpose of this study was to assess the associations of PA and diet quality (Healthy Eating Index [HEI]-2015) with NAFLD and a subset with advanced fibrosis (F3-4) as assessed by vibration-controlled transient elastography with controlled attenuation parameter in a representative sample of U.S. adults. This cross-sectional analysis uses data from 2017-2018 National Health and Nutrition Examination Survey. NAFLD was defined as controlled …

Biomarkers Of Response And Resistance To Palbociclib Plus Letrozole In Patients With Er+/Her2- Breast Cancer, Mitch Dowsett, Lucy Kilburn, Mothaffar F Rimawi, C Kent Osborne, Katherine Pogue-Geile, Yuan Liu, Samuel A Jacobs, Melanie Finnigan, Shannon Puhalla, Andrew Dodson, Vera Martins, Maggie Cheang, Sophie Perry, Chris Holcombe, Nick Turner, Claire Swift, Judith M Bliss, Stephen Johnston

Faculty, Staff and Students Publications

PURPOSE: To determine (i) the relationship between candidate biomarkers of the antiproliferative (Ki67) response to letrozole and palbociclib alone and combined in ER

EXPERIMENTAL DESIGN: 307 postmenopausal women with ER+/HER2− primary breast cancer were randomly assigned to neoadjuvant treatment with letrozole for 14 weeks; letrozole for 2 weeks, then letrozole+palbociclib to 14 weeks; palbociclib for 2 weeks, then letrozole+palbociclib to 14 weeks; or letrozole+palbociclib for 14 weeks. Biopsies were taken at baseline, 2 and 14 weeks and surgery at varying times after stopping palbociclib. Immunohistochemical analyses were conducted for Ki67, c-PARP, ER, PgR, RB1, CCNE1, and CCND1.

RESULTS: Higher baselines …