Medicine and Health Sciences Commons^™

Intravenous Aviptadil And Remdesivir For Treatment Of Covid-19-Associated Hypoxaemic Respiratory Failure In The Usa (Tesico): A Randomised, Placebo-Controlled Trial, Samuel M Brown, Christina E Barkauskas, Birgit Grund, Shweta Sharma, Andrew N Phillips, Lindsay Leither, Ithan D Peltan, Michael Lanspa, Daniel L Gilstrap, Ahmad Mourad, Kathleen Lane, Jeremy R Beitler, Alexis L Serra, Ivan Garcia, Eyad Almasri, Mohamed Fayed, Kinsley Hubel, Estelle S Harris, Elizabeth A Middleton, Macy A G Barrios, Kusum S Mathews, Neha N Goel, Samuel Acquah, Jarrod Mosier, Cameron Hypes, Elizabeth Salvagio Campbell, Akram Khan, Catherine L Hough, Jennifer G Wilson, Joseph E Levitt, Abhijit Duggal, Siddharth Dugar, Andrew J Goodwin, Charles Terry, Peter Chen, Sam Torbati, Nithya Iyer, Uriel S Sandkovsky, Nicholas J Johnson, Bryce R H Robinson, Michael A Matthay, Neil R Aggarwal, Ivor S Douglas, Jonathan D Casey, Manuel Hache-Marliere, J Georges Youssef, William Nkemdirim, Brad Leshnower, Omar Awan, Sonal Pannu, Darragh Shane O'Mahony, Prasad Manian, J W Awori Hayanga, Glenn W Wortmann, Bruno M Tomazini, Robert F Miller, Jens-Ulrik Jensen, Daniel D Murray, Nina A Bickell, Jigna Zatakia, Sarah Burris, Elizabeth S Higgs, Ven Natarajan, Robin L Dewar, Adam Schechner, Nayon Kang, Alejandro Arenas-Pinto, Fleur Hudson, Adit A Ginde, Wesley H Self, Angela J Rogers, Cathryn F Oldmixon, Haley Morin, Adriana Sanchez, Amy C Weintrob, Alexandre Biasi Cavalcanti, Anne Davis-Karim, Nicole Engen, Eileen Denning, B Taylor Thompson, Annetine C Gelijns, Virginia Kan, Victoria J Davey, Jens D Lundgren, Abdel G Babiker, James D Neaton, H Clifford Lane

Faculty, Staff and Student Publications

BACKGROUND: There is a clinical need for therapeutics for COVID-19 patients with acute hypoxemic respiratory failure whose 60-day mortality remains at 30-50%. Aviptadil, a lung-protective neuropeptide, and remdesivir, a nucleotide prodrug of an adenosine analog, were compared with placebo among patients with COVID-19 acute hypoxaemic respiratory failure.

METHODS: TESICO was a randomised trial of aviptadil and remdesivir versus placebo at 28 sites in the USA. Hospitalised adult patients were eligible for the study if they had acute hypoxaemic respiratory failure due to confirmed SARS-CoV-2 infection and were within 4 days of the onset of respiratory failure. Participants could be randomly …

Anesthesia Care Provider Sedation Versus Conscious Sedation For Endoscopic Ultrasound-Guided Tissue Acquisition: A Retrospective Cohort Study, Sneha Shaha, Yinglin Gao, Jiahao Peng, Kendrick Che, John J Kim, Wasseem Skef

Faculty, Staff and Students Publications

BACKGROUND/AIMS: We aimed to study the effects of sedation on endoscopic ultrasound-guided tissue acquisition.

METHODS: We conducted a retrospective study evaluating the role of sedation in endoscopic ultrasound-guided tissue acquisition by comparing two groups: anesthesia care provider (ACP) sedation and endoscopist-directed conscious sedation (CS).

RESULTS: Technical success was achieved in 219/233 (94.0%) in the ACP group and 114/136 (83.8%) in the CS group (p=0.0086). In multivariate analysis, the difference in technical success between the two groups was not significant (adjusted odds ratio [aOR], 0.5; 95% confidence interval [CI], 0.234-1.069; p=0.0738). A successful diagnostic yield was present in 146/196 (74.5%) in …

Screening People On Standing Balance With Romberg Testing And Walking Balance With Tandem Walking, Helen S Cohen

Faculty, Staff and Students Publications

The goal of this protocol is to inform readers about the exact procedures to use to perform two screening tests for vestibular disorders: tandem walking (TW) with eyes closed, also known as heel-toe walking, and the Clinical Test of Sensory Integration and Balance (CTSIB), which is also known as the modified Romberg. The study describes the steps for performing each test and each of the three CTSIB subtests so that the reader will be able to replicate the test conditions for use in the clinic, in the clinical laboratory, or in any other situation needing valid and reliable screening for …

Risks Factors And Outcomes For Isolated Catheter-Related Deep Venous Thrombosis In Patients Undergoing Allogeneic Hematopoietic Stem Cell Transplantation, Jonathan Avery, Danielle Guffey, Shengling Ma, Ryan Basom, Stephanie J Lee, David Garcia, Cristhiam M Rojas Hernandez, Ang Li, Kylee L Martens

Faculty, Staff and Students Publications

INTRODUCTION: Patients undergoing allogenic hematopoietic stem cell transplantation (allo-HSCT) require indwelling central venous catheters. The comparative incidence, risk, and outcome of isolated catheter-related deep venous thrombosis (CR-DVT) versus pulmonary embolism/lower-extremity DVT (PE/LE-DVT) remains unclear.

MATERIALS AND METHODS: We conducted a retrospective cohort study for patients undergoing allo-HSCT from 2006 to 2019. CR-DVT and PE/LE-DVT outcomes were screened using ICD codes and radiology reports and confirmed by medical record reviews. Cox regression models were used to assess the association between thrombotic outcomes and pertinent baseline and time-varying covariates. The impact of thrombotic events within 1-year post-transplant (time-varying) on overall mortality was …

Deficiencies With Cage-Aid Questionnaire In Identifying Nonmedical Opioid Use-A Report Of Two Cases, Jaya Amaram-Davila, Patricia Bramati, Laura Gammon, Tarun Mallipeddi, Olivia Jastrzemski, Matthew D Clark, Joseph Arthur, Akhila Reddy, Eduardo Bruera

Faculty, Staff and Students Publications

Background: The CAGE-AID questionnaire (Cut-down, Annoyed, Guilty, Eye-opener scale Adapted to Include Drugs) is used to screen patients for substance use disorder and nonmedical opioid use (NMOU). Major pain guidelines encourage using such screening tools for all patients including cancer patients before initiating opioids. We present two cases where the CAGE-AID results did not accurately identify the risk for NMOU.

Case description: Patient 1 is a male in his 60s with metastatic prostate cancer was admitted for uncontrolled pain. Imaging revealed extensive spinal metastasis, needing initiation of methadone and hydromorphone. The CAGE-AID score was positive, placing him at risk for …

Revision Tracheotomy Complicated By History Of Follicular B-Cell Lymphoma, Sarah Ustrell, Jordan K Simmons, Garrett Henkle, Adam R Szymanowski

Faculty, Staff and Students Publications

This case report presents a 65-year-old woman with multiple complications during a revision tracheotomy including subcutaneous emphysema and a pneumothorax. Management of her airway was complicated by a history of recurrent follicular B-cell lymphoma associated with extensive cervical lymphadenopathy. We detail the importance of heightened clinical awareness and the use of intraoperative safety adjuncts when performing revision tracheostomies.

Immune Infiltration In Tumor And Adjacent Non-Neoplastic Regions Codetermines Patient Clinical Outcomes In Early-Stage Lung Cancer, Chao Cheng, Thinh T Nguyen, Mabel Tang, Xinan Wang, Chongming Jiang, Yanhong Liu, Ivan Gorlov, Olga Gorlova, John Iafrate, Michael Lanuti, David C Christiani, Christopher I Amos

Faculty, Staff and Students Publications

INTRODUCTION: In recent years, the proportion of patients with NSCLC diagnosed at an early stage has increased continuously.

METHODS: In this study, we analyzed samples and data collected from 119 samples from 67 early stage patients with NSCLC, including 52 pairs of tumor and adjacent non-neoplastic samples, and performed RNA-sequencing analysis with high sequencing depth.

RESULTS: We found that immune-related genes were highly enriched among the differentially expressed genes and observed significantly higher inferred immune infiltration levels in adjacent non-neoplastic samples than in tumor samples. In survival analysis, the infiltration of certain immune cell types in tumor, but not adjacent …

Barriers To Human Papillomavirus Vaccine Uptake: Role Of State Religiosity And Healthcare Professionals' Participation In A State Vaccine Program, Monalisa Chandra, Ikponmwosa Osaghae, Rajesh Talluri, Sanjay Shete

Faculty, Staff and Student Publications

BACKGROUND: Despite the known benefits of preventing human papillomavirus (HPV)-related cancers, HPV vaccine coverage is low in the United States. Grounded in Social Ecological theory, we assessed the macro-level (state) and meso-level (organization) factors associated with HPV vaccine initiation and up-to-date.

METHODS: Data from 2020 National Immunization Survey-Teen were used to study a sample of 20 163 US adolescents (aged 13-17 years). The data were collected from each teen's parents or guardians and health-care professionals. Weighted prevalence estimates were calculated, and multivariable regression analyses were conducted.

RESULTS: The prevalence of HPV vaccine initiation was 75.1% and of remaining up-to-date was …

Archival Single-Cell Genomics Reveals Persistent Subclones During Dcis Progression, Kaile Wang, Tapsi Kumar, Junke Wang, Darlan Conterno Minussi, Emi Sei, Jianzhuo Li, Tuan M Tran, Aatish Thennavan, Min Hu, Anna K Casasent, Zhenna Xiao, Shanshan Bai, Lei Yang, Lorraine M King, Vandna Shah, Petra Kristel, Carolien L Van Der Borden, Jeffrey R Marks, Yuehui Zhao, Amado J Zurita, Ana Aparicio, Brian Chapin, Jie Ye, Jianjun Zhang, Don L Gibbons, Ellinor Sawyer, Alastair M Thompson, Andrew Futreal, E Shelley Hwang, Jelle Wesseling, Esther H Lips, Nicholas E Navin

Faculty, Staff and Student Publications

Ductal carcinoma in situ (DCIS) is a common precursor of invasive breast cancer. Our understanding of its genomic progression to recurrent disease remains poor, partly due to challenges associated with the genomic profiling of formalin-fixed paraffin-embedded (FFPE) materials. Here, we developed Arc-well, a high-throughput single-cell DNA-sequencing method that is compatible with FFPE materials. We validated our method by profiling 40,330 single cells from cell lines, a frozen tissue, and 27 FFPE samples from breast, lung, and prostate tumors stored for 3-31 years. Analysis of 10 patients with matched DCIS and cancers that recurred 2-16 years later show that many primary …

Efficacy Of Scalp-Sparing Volumetric-Modulated Arc Therapy Approach In Reducing Scalp Radiation Dose For Patients With Glioblastoma: A Cross-Sectional Study, Muneeb Khan Niazi, Olga Russial, Louis Cappelli, Ryan Miller, Yingxuan Chen, Yelena Vakhnenko, Haisong Lui, Wenyin Shi

Department of Radiation Oncology Faculty Papers

BACKGROUND: Radiation is integral to the treatment of glioblastoma (GBM). However, radiation-induced scalp toxicity can negatively impact patients' quality of life. Volumetric modulated arc therapy (VMAT) optimizes the dose to organs at risk (OARs). We hypothesize that a scalp-sparing VMAT (SSV) approach can significantly reduce undesirable doses to the scalp without compromising the target dose.

METHODS: This is a retrospective cross-sectional study of GBM patients who originally received radiation with non-SSV. We contoured the scalp as a 5 mm rind-like structure beneath the skin above the level of the foramen magnum. We replanned our patients using SSV techniques. We compared …

Pan-Cancer Analysis Of Post-Translational Modifications Reveals Shared Patterns Of Protein Regulation, Yifat Geffen, Shankara Anand, Yo Akiyama, Tomer M Yaron, Yizhe Song, Jared L Johnson, Akshay Govindan, Özgün Babur, Yize Li, Emily Huntsman, Liang-Bo Wang, Chet Birger, David I Heiman, Qing Zhang, Mendy Miller, Yosef E Maruvka, Nicholas J Haradhvala, Anna Calinawan, Saveliy Belkin, Alexander Kerelsky, Karl R Clauser, Karsten Krug, Shankha Satpathy, Samuel H Payne, D R Mani, Michael A Gillette, Saravana M Dhanasekaran, Mathangi Thiagarajan, Mehdi Mesri, Henry Rodriguez, Ana I Robles, Steven A Carr, Alexander J Lazar, François Aguet, Lewis C Cantley, Li Ding, Gad Getz, Clinical Proteomic Tumor Analysis Consortium

Faculty, Staff and Student Publications

Post-translational modifications (PTMs) play key roles in regulating cell signaling and physiology in both normal and cancer cells. Advances in mass spectrometry enable high-throughput, accurate, and sensitive measurement of PTM levels to better understand their role, prevalence, and crosstalk. Here, we analyze the largest collection of proteogenomics data from 1,110 patients with PTM profiles across 11 cancer types (10 from the National Cancer Institute's Clinical Proteomic Tumor Analysis Consortium [CPTAC]). Our study reveals pan-cancer patterns of changes in protein acetylation and phosphorylation involved in hallmark cancer processes. These patterns revealed subsets of tumors, from different cancer types, including those with …

Pan-Cancer Proteogenomics Connects Oncogenic Drivers To Functional States, Yize Li, Eduard Porta-Pardo, Collin Tokheim, Matthew H Bailey, Tomer M Yaron, Vasileios Stathias, Yifat Geffen, Kathleen J Imbach, Song Cao, Shankara Anand, Yo Akiyama, Wenke Liu, Matthew A Wyczalkowski, Yizhe Song, Erik P Storrs, Michael C Wendl, Wubing Zhang, Mustafa Sibai, Victoria Ruiz-Serra, Wen-Wei Liang, Nadezhda V Terekhanova, Fernanda Martins Rodrigues, Karl R Clauser, David I Heiman, Qing Zhang, Francois Aguet, Anna P Calinawan, Saravana M Dhanasekaran, Chet Birger, Shankha Satpathy, Daniel Cui Zhou, Liang-Bo Wang, Jessika Baral, Jared L Johnson, Emily M Huntsman, Pietro Pugliese, Antonio Colaprico, Antonio Iavarone, Milan G Chheda, Christopher J Ricketts, David Fenyö, Samuel H Payne, Henry Rodriguez, Ana I Robles, Michael A Gillette, Chandan Kumar-Sinha, Alexander J Lazar, Lewis C Cantley, Gad Getz, Li Ding

Faculty, Staff and Student Publications

Cancer driver events refer to key genetic aberrations that drive oncogenesis; however, their exact molecular mechanisms remain insufficiently understood. Here, our multi-omics pan-cancer analysis uncovers insights into the impacts of cancer drivers by identifying their significant cis-effects and distal trans-effects quantified at the RNA, protein, and phosphoprotein levels. Salient observations include the association of point mutations and copy-number alterations with the rewiring of protein interaction networks, and notably, most cancer genes converge toward similar molecular states denoted by sequence-based kinase activity profiles. A correlation between predicted neoantigen burden and measured T cell infiltration suggests potential vulnerabilities for immunotherapies. Patterns of …

Wearable Biosensor With Molecularly Imprinted Conductive Polymer Structure To Detect Lentivirus In Aerosol, Jaskirat Singh Batra, Ting-Yen Chi, Mo-Fan Huang, Dandan Zhu, Zheyuan Chen, Dung-Fang Lee, Jun Kameoka

Faculty, Staff and Student Publications

The coronavirus disease (COVID-19) pandemic has increased pressure to develop low-cost, compact, user-friendly, and ubiquitous virus sensors for monitoring infection outbreaks in communities and preventing economic damage resulting from city lockdowns. As proof of concept, we developed a wearable paper-based virus sensor based on a molecular imprinting technique, using a conductive polyaniline (PANI) polymer to detect the lentivirus as a test sample. This sensor detected the lentivirus with a 4181 TU/mL detection limit in liquid and 0.33% to 2.90% detection efficiency in aerosols at distances ranging from 30 cm to 60 cm. For fabrication, a mixture of a PANI monomer …

Car-T Cells Targeting Cd38 And Lmp1 Exhibit Robust Antitumour Activity Against Nk/T Cell Lymphoma, Hongwen Li, Wenting Song, Jiazhuo Wu, Zhuangzhuang Shi, Yuyang Gao, Jiwei Li, Lijuan Han, Jianxiang Zhang, Zhaoming Li, Yong Li, Mingzhi Zhang

Faculty, Staff and Students Publications

BACKGROUND: Natural killer/T cell lymphoma (NKTCL) is an aggressive lymphoma with a poor prognosis. Chimeric antigen receptor-transduced T (CAR-T) cell therapy has become a promising immunotherapeutic strategy against haematologic malignancies.

METHODS: In this study, four CAR-T cell lines (CD38-CAR, LMP1-CAR, CD38-LMP1 tandem CAR 1 and CD38-LMP1 tandem CAR 2) were generated. The effect of CAR-T cells against NKTCL cells was evaluated both in vitro and in vivo. Expression of T cell activation markers and cytokines produced by CAR-T cells were detected by flow cytometry.

RESULTS: The four CAR-T cell lines could effectively eliminate malignant NKTCL cells. They could be activated …

Hypothyroidism Following Radiotherapy For Head And Neck Cancer: A Systematic Review Of The Literature And Opportunities To Improve The Therapeutic Ratio, Michael K Rooney, Lauren M Andring, Kelsey L Corrigan, Vincent Bernard, Tyler D Williamson, Clifton D Fuller, Adam S Garden, Brandon Gunn, Anna Lee, Amy C Moreno, William H Morrison, Jack Phan, David I Rosenthal, Michael Spiotto, Steven J Frank

Faculty, Staff and Student Publications

(1) Background: Radiotherapy (RT) is a central component for the treatment of many head and neck cancers. In this systematic review of the literature, we aimed to characterize and quantify the published evidence on RT-related hypothyroidism, including estimated incidence, clinical risk factors, and dosimetric parameters that may be used to guide clinical decision making. Furthermore, we aimed to identify potential areas of improvement in the prevention and clinical management of RT-induced hypothyroidism, including the role of modern advanced therapeutic techniques. (2) Methods: We conducted a systemic review of the literature in accordance with Preferred Reporting Items for Systematic Reviews and …

An Evolutionarily Nascent Architecture Underlying The Formation And Emergence Of Biomolecular Condensates, Nima Jaberi-Lashkari, Byron Lee, Fardin Aryan, Eliezer Calo

Faculty, Staff and Student Publications

Biomolecular condensates are implicated in core cellular processes such as gene regulation and ribosome biogenesis. Although the architecture of biomolecular condensates is thought to rely on collective interactions between many components, it is unclear how the collective interactions required for their formation emerge during evolution. Here, we show that the structure and evolution of a recently emerged biomolecular condensate, the nucleolar fibrillar center (FC), is explained by a single self-assembling scaffold, TCOF1. TCOF1 is necessary to form the FC, and it structurally defines the FC through self-assembly mediated by homotypic interactions of serine/glutamate-rich low-complexity regions (LCRs). Finally, introduction of TCOF1 …

Mapping The Evolution Of T Cell States During Response And Resistance To Adoptive Cellular Therapy, Pavan Bachireddy, Elham Azizi, Cassandra Burdziak, Vinhkhang N Nguyen, Christina S Ennis, Katie Maurer, Cameron Y Park, Zi-Ning Choo, Shuqiang Li, Satyen H Gohil, Neil G Ruthen, Zhongqi Ge, Derin B Keskin, Nicoletta Cieri, Kenneth J Livak, Haesook T Kim, Donna S Neuberg, Robert J Soiffer, Jerome Ritz, Edwin P Alyea, Dana Pe'er, Catherine J Wu

Faculty, Staff and Student Publications

No abstract provided.

Bcl-2 Inhibition Combined With Pparα Activation Synergistically Targets Leukemic Stem Cell-Like Cells In Acute Myeloid Leukemia, Chendi Xie, Hui Zhou, Dongmei Qin, Huijian Zheng, Yuanfang Tang, Wenjuan Li, Jie Zhou, Long Liu, Xinxin Yu, Hongpeng Duan, Yong Zhou, Zhifeng Li, Zhihong Fang, Yiming Luo, Bing Z Carter, Bing Xu, Jie Zha

Faculty, Staff and Student Publications

Persistence of leukemic stem cells (LSCs) is one of the determining factors to acute myeloid leukemia (AML) treatment failure and responsible for the poor prognosis of the disease. Hence, novel therapeutic strategies that target LSCs are crucial for treatment success. We investigated if targeting Bcl-2 and peroxisome proliferator activated receptor α (PPARα), two distinct cell survival regulating mechanisms could eliminate LSCs. This study demonstrate that the Bcl-2 inhibitor venetoclax combined with the PPARα agonist chiglitazar resulted in synergistic killing of LSC-like cell lines and CD34+ primary AML cells while sparing their normal counterparts. Furthermore, the combination regimen significantly suppressed AML …

Hypothyroidism Following Radiotherapy For Head And Neck Cancer: A Systematic Review Of The Literature And Opportunities To Improve The Therapeutic Ratio, Michael K Rooney, Lauren M Andring, Kelsey L Corrigan, Vincent Bernard, Tyler D Williamson, Clifton D Fuller, Adam S Garden, Brandon Gunn, Anna Lee, Amy C Moreno, William H Morrison, Jack Phan, David I Rosenthal, Michael Spiotto, Steven J Frank

Faculty, Staff and Student Publications

(1) Background: Radiotherapy (RT) is a central component for the treatment of many head and neck cancers. In this systematic review of the literature, we aimed to characterize and quantify the published evidence on RT-related hypothyroidism, including estimated incidence, clinical risk factors, and dosimetric parameters that may be used to guide clinical decision making. Furthermore, we aimed to identify potential areas of improvement in the prevention and clinical management of RT-induced hypothyroidism, including the role of modern advanced therapeutic techniques. (2) Methods: We conducted a systemic review of the literature in accordance with Preferred Reporting Items for Systematic Reviews and …

Inducing Accelerated Lung Toxicity In Mice Using A Partial Arc Sbrt Technique, Andrew Gerry, Charita Kunta, Noelle Francois, Tiziana Deangelis, Anuradha Shastri, Nicole Simone, Reza Taleei

Department of Radiation Oncology Posters

Background

• Radiation-induced pulmonary fibrosis (RIPF) is a frequent outcome of thoracic radiation therapy, constraining safe tumor radiation dosage. Various animal models, such as mice, rats, and pigs, have been devised to study RIPF
• Current methods for inducing lung fibrosis in mice involve whole lung irradiation with doses between 2-20 Gy. These methods used fixed anterior and posterior (AP/PA) x-ray beams at 0º and 180º with analysis typically commencing 24 to 52 weeks post-radiation
• Current methods are unrepresentative of modern radiation therapy techniques and are limited by the associated long latency of RIPF

Mavs Is A Double-Edged Sword, Christina Huang, Jack L. Arbiser

Student Papers, Posters & Projects

No abstract provided.

Non-Coding Rnas: Foes Or Friends For Targeting Tumor Microenvironment, Anna Szymanowska, Cristian Rodriguez-Aguayo, Gabriel Lopez-Berestein, Paola Amero

Faculty, Staff and Student Publications

Non-coding RNAs (ncRNAs) are a group of molecules critical for cell development and growth regulation. They are key regulators of important cellular pathways in the tumor microenvironment. To analyze ncRNAs in the tumor microenvironment, the use of RNA sequencing technology has revolutionized the field. The advancement of this technique has broadened our understanding of the molecular biology of cancer, presenting abundant possibilities for the exploration of novel biomarkers for cancer treatment. In this review, we will summarize recent achievements in understanding the complex role of ncRNA in the tumor microenvironment, we will report the latest studies on the tumor microenvironment …

Racial/Ethnic Disparities In Prostate Cancer 5-Year Survival: The Role Of Health-Care Access And Disease Severity, Christiane J. El Khoury, Sean A.P. Clouston

Department of Medical Oncology Faculty Papers

Introduction: Prostate cancer (PCa) exhibits one of the widest racial and socioeconomic disparities. PCa disparities have also been widely linked to location, as living in more deprived regions was associated with lower healthcare access and worse outcomes. This study aims to examine PCa survival across various USA counties in function of different socioeconomic profiles and discuss the role of potential intermediary factors. Methods: The SEER database linked to county-level SES was utilized. Five-year PCa-specific survival using the Kaplan–Meier method was performed for five racial/ethnic categories in function of SES quintiles. Multilevel Cox proportional hazards regression was performed to assess the …

The Histone Chaperone Function Of Daxx Is Dispensable For Embryonic Development, Chang Sun, Yuan Qi, Natalie Fowlkes, Nina Lazic, Xiaoping Su, Guillermina Lozano, Amanda R Wasylishen

Faculty, Staff and Student Publications

Daxx functions as a histone chaperone for the histone H3 variant, H3.3, and is essential for embryonic development. Daxx interacts with Atrx to form a protein complex that deposits H3.3 into heterochromatic regions of the genome, including centromeres, telomeres, and repeat loci. To advance our understanding of histone chaperone activity in vivo, we developed two Daxx mutant alleles in the mouse germline, which abolish the interactions between Daxx and Atrx (DaxxY130A), and Daxx and H3.3 (DaxxS226A). We found that the interaction between Daxx and Atrx is dispensable for viability; mice are born at the …

Targeting Breast Cancer: The Familiar, The Emerging, And The Uncharted Territories, Hamidreza Montazeri Aliabadi, Arthur Manda, Riya Sidgal, Co Chung

Pharmacy Faculty Articles and Research

Breast cancer became the most diagnosed cancer in the world in 2020. Chemotherapy is still the leading clinical strategy in breast cancer treatment, followed by hormone therapy (mostly used in hormone receptor-positive types). However, with our ever-expanding knowledge of signaling pathways in cancer biology, new molecular targets are identified for potential novel molecularly targeted drugs in breast cancer treatment. While this has resulted in the approval of a few molecularly targeted drugs by the FDA (including drugs targeting immune checkpoints), a wide array of signaling pathways seem to be still underexplored. Also, while combinatorial treatments have become common practice in …

Metastatic Papillary Thyroid Carcinoma Gone Wild, Khulood Talpur, Ambreen Soomro, Afrah Talpur

Abington Jefferson Health Papers

Thyroid cancers account for only 1.5% of all cancers in adults and 3% of all cancers in children. In females, however, thyroid cancers are the fifth most common cancer, comprising 4% of all cases. Of all thyroid cancers, 74-80% of cases are papillary cancer. The prevalence of thyroid cancer is rising worldwide. Although thyroid cancer has a favorable prognosis, up to 20% of patients experienced recurrent disease during the follow-up period. Extra-thyroidal extension occurs in 8% to 32% of cases. Local or regional recurrences occur in 5-15% of patients with papillary thyroid carcinoma (PTC). Distant metastasis occurs in only 1% …

Intrinsic Disorder In Prame And Its Role In Uveal Melanoma, Michael Antonietti, David J. Taylor Gonzalez, Mak Djulbegovic, Guy W. Dayhoff, Vladimir N. Uversky, Carol L. Shields, Carol L. Karp

Wills Eye Hospital Papers

Introduction

The PReferentially expressed Antigen in MElanoma (PRAME) protein has been shown to be an independent biomarker for increased risk of metastasis in Class 1 uveal melanomas (UM). Intrinsically disordered proteins and regions of proteins (IDPs/IDPRs) are proteins that do not have a well-defined three-dimensional structure and have been linked to neoplastic development. Our study aimed to evaluate the presence of intrinsic disorder in PRAME and the role these structureless regions have in PRAME( +) Class 1 UM.

Methods

A bioinformatics study to characterize PRAME’s propensity for the intrinsic disorder. We first used the AlphaFold tool to qualitatively assess the …

Immunotherapy Targeting Different Immune Compartments In Combination With Radiation Therapy Induces Regression Of Resistant Tumors, Nils-Petter Rudqvist, Maud Charpentier, Claire Lhuillier, Erik Wennerberg, Sheila Spada, Caroline Sheridan, Xi Kathy Zhou, Tuo Zhang, Silvia C Formenti, Jennifer S Sims, Alicia Alonso, Sandra Demaria

Faculty, Staff and Student Publications

Radiation therapy (RT) increases tumor response to CTLA-4 inhibition (CTLA4i) in mice and in some patients, yet deep responses are rare. To identify rational combinations of immunotherapy to improve responses we use models of triple negative breast cancer highly resistant to immunotherapy in female mice. We find that CTLA4i promotes the expansion of CD4+ T helper cells, whereas RT enhances T cell clonality and enriches for CD8+ T cells with an exhausted phenotype. Combination therapy decreases regulatory CD4+ T cells and increases effector memory, early activation and precursor exhausted CD8+ T cells. A combined gene signature comprising these three CD8+ …

Cost-Effectiveness Of Ticagrelor Plus Aspirin Versus Aspirin In Acute Ischaemic Stroke Or Transient Ischaemic Attack: An Economic Evaluation Of The Thales Trial, Amarjeet Tank, S Claiborne Johnston, Ritika Jain, Pierre Amarenco, Carl Mellström, Klas Rikner, Hans Denison, Per Ladenvall, Mikael Knutsson, Anders Himmelmann, Scott R Evans, Stefan James, Carlos A Molina, Yongjun Wang, Mario Ouwens

Faculty, Staff and Student Publications

OBJECTIVE: THALES demonstrated that ticagrelor plus aspirin reduced the risk of stroke or death but increased bleeding versus aspirin during the 30 days following a mild-to-moderate acute non-cardioembolic ischaemic stroke (AIS) or high-risk transient ischaemic attack (TIA). There are no cost-effectiveness analyses supporting this combination in Europe. To address this, a cost-effectiveness analysis was performed.

METHODS: Cost-effectiveness was evaluated using a decision tree and Markov model with a short-term and long-term (30-year) horizon. Stroke, mortality, bleeding and EuroQol-5 Dimension (EQ-5D) data from THALES were used to estimate short-term outcomes. Model transitions were based on stroke severity (disabling stroke was defined …

Temporal Dynamics Of Genetically Heterogeneous Extended-Spectrum Cephalosporin-Resistant Escherichia Coli Bloodstream Infections, William C Shropshire, Benjamin Strope, Selvalakshmi Selvaraj Anand, Jordan Bremer, Patrick Mcdaneld, Micah M Bhatti, Anthony R Flores, Awdhesh Kalia, Samuel A Shelburne

Faculty, Staff and Student Publications

Extended-spectrum cephalosporin-resistant Escherichia coli (ESC-R-Ec) is an urgent public health threat with sequence type clonal complex 131 (STc131), phylogroup B2 strains being particularly concerning as the dominant cause of ESC-R-Ec infections. To address the paucity of recent ESC-R-Ec molecular epidemiology data in the United States, we used whole-genome sequencing (WGS) to fully characterize a large cohort of invasive ESC-R-Ec at a tertiary care cancer center in Houston, Texas, collected from 2016 to 2020. During the study time frame, there were 1,154 index E. coli bloodstream infections (BSIs) of which 389 (33.7%) were ESC-R-Ec. …