Digital Commons Network^™

Serinc5 Restricts Hiv Membrane Fusion By Altering Lipid Order And Heterogeneity In The Viral Membrane, Amanda E Ward, Daria Sokovikova, Melvin Neal Waxham, Frederick A Heberle, Ilya Levental, Kandice R Levental, Volker Kiessling, Judith M White, Lukas K Tamm

Faculty, Staff and Student Publications

The host restriction factor, Serinc5, incorporates into budding HIV particles and inhibits their infection by an incompletely understood mechanism. We have previously reported that Serinc5 but not its paralogue, Serinc2, blocks HIV cell entry by membrane fusion, specifically by inhibiting fusion pore formation and dilation. A body of work suggests that Serinc5 may alter the conformation and clustering of the HIV fusion protein, Env. To contribute an additional perspective to the developing model of Serinc5 restriction, we assessed Serinc2 and Serinc5's effects on HIV pseudoviral membranes. By measuring pseudoviral membrane thickness via cryo-electron microscopy and order via the fluorescent dye, …

Mek Inhibition Synergizes With Tyk2 Inhibitors In Nf1-Associated Malignant Peripheral Nerve Sheath Tumors, Dana C Borcherding, Neha V Amin, Kevin He, Xiaochun Zhang, Yang Lyu, Carina Dehner, Himanshi Bhatia, Angad Gothra, Layla Daud, Peter Ruminski, Christine A Pratilas, Kai Pollard, Taylor Sundby, Brigitte C Widemann, Angela C Hirbe

2020-Current year OA Pubs

PURPOSE: Malignant peripheral nerve sheath tumors (MPNST) are aggressive sarcomas with limited treatment options and poor survival rates. About half of MPNST cases are associated with the neurofibromatosis type 1 (NF1) cancer predisposition syndrome. Overexpression of TYK2 occurs in the majority of MPNST, implicating TYK2 as a therapeutic target.

EXPERIMENTAL DESIGN: The effects of pharmacologic TYK2 inhibition on MPNST cell proliferation and survival were examined using IncuCyte live cell assays in vitro, and downstream actions were analyzed using RNA-sequencing (RNA-seq), qPCR arrays, and validation of protein changes with the WES automated Western system. Inhibition of TYK2 alone and in combination …

Targeting Of Epigenetic Co-Dependencies Enhances Anti-Aml Efficacy Of Menin Inhibitor In Aml With Mll1-R Or Mutant Npm1, Warren Fiskus, Christopher P Mill, Christine Birdwell, John A Davis, Kaberi Das, Steffen Boettcher, Tapan M Kadia, Courtney D Dinardo, Koichi Takahashi, Sanam Loghavi, Michael J Soth, Tim Heffernan, Gerard M Mcgeehan, Xinjia Ruan, Xiaoping Su, Christopher R Vakoc, Naval Daver, Kapil N Bhalla

Faculty, Staff and Student Publications

Monotherapy with Menin inhibitor (MI), e.g., SNDX-5613, induces clinical remissions in patients with relapsed/refractory AML harboring MLL1-r or mtNPM1, but most patients either fail to respond or eventually relapse. Utilizing single-cell RNA-Seq, ChiP-Seq, ATAC-Seq, RNA-Seq, RPPA, and mass cytometry (CyTOF) analyses, present pre-clinical studies elucidate gene-expression correlates of MI efficacy in AML cells harboring MLL1-r or mtNPM1. Notably, MI-mediated genome-wide, concordant, log2 fold-perturbations in ATAC-Seq and RNA-Seq peaks were observed at the loci of MLL-FP target genes, with upregulation of mRNAs associated with AML differentiation. MI treatment also reduced the number of AML cells expressing the stem/progenitor cell signature. A …

The Role Of Extracellular Vesicles In Cancer, Raghu Kalluri, Kathleen M Mcandrews

Faculty, Staff and Student Publications

Intercellular communication is a key feature of cancer progression and metastasis. Extracellular vesicles (EVs) are generated by all cells, including cancer cells, and recent studies have identified EVs as key mediators of cell-cell communication via packaging and transfer of bioactive constituents to impact the biology and function of cancer cells and cells of the tumor microenvironment. Here, we review recent advances in understanding the functional contribution of EVs to cancer progression and metastasis, as cancer biomarkers, and the development of cancer therapeutics.

One Population, Multiple Lifestyles: Commensalism And Pathogenesis In The Human Mycobiome, Diana M Proctor, Rebecca A Drummond, Michail S Lionakis, Julia A Segre

Faculty, Staff and Student Publications

Candida auris and Candida albicans can result in invasive fungal diseases. And yet, these species can stably and asymptomatically colonize human skin and gastrointestinal tracts. To consider these disparate microbial lifestyles, we first review factors shown to influence the underlying microbiome. Structured by the damage response framework, we then consider the molecular mechanisms deployed by C. albicans to switch between commensal and pathogenic lifestyles. Next, we explore this framework with C. auris to highlight how host physiology, immunity, and/or antibiotic receipt are associated with progression from colonization to infection. While treatment with antibiotics increases the risk an individual will succumb …

Blood Pressure Surge With Alarm Is Reduced After Exercise And Diet Intervention In Firefighters, Deborah L Feairheller, Macie Smith, Megan Carty, Emily H Reeve

College of Population Health Faculty Papers

BACKGROUND: Cardiac-related incidents are a public health concern for tactical occupations, and cardiovascular disease rates are higher in these populations compared with civilians. Research is needed to examine blood pressure (BP) responses in firefighters. The pager alert is one occupational hazard, and it is unknown if lifestyle change can reduce the systolic surge response.

PURPOSE: To measure BP surge with alarm in firefighters to determine whether the magnitude is lower after a 6-week tactical exercise and Mediterranean-diet intervention.

METHODS: SBP and DBP and BP surge levels, circulating markers, vascular health, and fitness were analyzed. BP surge with alarm was captured …

Molecular Mechanisms Of Ferroptosis And Updates Of Ferroptosis Studies In Cancers And Leukemia, Hiroki Akiyama, Bing Z Carter, Michael Andreeff, Jo Ishizawa

Faculty, Staff and Student Publications

Ferroptosis is a mode of cell death regulated by iron-dependent lipid peroxidation. Growing evidence suggests ferroptosis induction as a novel anti-cancer modality that could potentially overcome therapy resistance in cancers. The molecular mechanisms involved in the regulation of ferroptosis are complex and highly dependent on context. Therefore, a comprehensive understanding of its execution and protection machinery in each tumor type is necessary for the implementation of this unique cell death mode to target individual cancers. Since most of the current evidence for ferroptosis regulation mechanisms is based on solid cancer studies, the knowledge of ferroptosis with regard to leukemia is …

Toward Quantification Of Hypoxia Using Fluorinated Euii/Iii-Containing Ratiometric Probes, S A Amali S Subasinghe, Caitlyn J Ortiz, Jonathan Romero, Cassandra L Ward, Alexander G Sertage, Lyazat Kurenbekova, Jason T Yustein, Robia G Pautler, Matthew J Allen

Faculty, Staff and Students Publications

Hypoxia is a prognostic biomarker of rapidly growing cancers, where the extent of hypoxia is an indication of tumor progression and prognosis; therefore, hypoxia is also used for staging while performing chemo- and radiotherapeutics for cancer. Contrast-enhanced MRI using EuII-based contrast agents is a noninvasive method that can be used to map hypoxic tumors, but quantification of hypoxia using these agents is challenging due to the dependence of signal on the concentration of both oxygen and EuII. Here, we report a ratiometric method to eliminate concentration dependence of contrast enhancement of hypoxia using fluorinated EuII/III-containing probes. We studied three different …

Factor Xa Cleaves Sars-Cov-2 Spike Protein To Block Viral Entry And Infection, Wenjuan Dong, Sean P J Whelan, Et Al.

2020-Current year OA Pubs

Serine proteases (SP), including furin, trypsin, and TMPRSS2 cleave the SARS-CoV-2 spike (S) protein, enabling the virus to enter cells. Here, we show that factor (F) Xa, an SP involved in blood coagulation, is upregulated in COVID-19 patients. In contrast to other SPs, FXa exerts antiviral activity. Mechanistically, FXa cleaves S protein, preventing its binding to ACE2, and thus blocking viral entry and infection. However, FXa is less effective against variants carrying the D614G mutation common in all pandemic variants. The anticoagulant rivaroxaban, a direct FXa inhibitor, inhibits FXa-mediated S protein cleavage and facilitates viral entry, whereas the indirect FXa …

A Distinct Pattern Of Growth And Rac1 Signaling In Melanoma Brain Metastasis Cells, Ioana Stejerean-Todoran, Phyllis A Gimotty, Andrea Watters, Patricia Brafford, Clemens Krepler, Tetiana Godok, Haiyin Li, Zuriñe Bonilla Del Rio, Anke Zieseniss, Dörthe M Katschinski, Sinem M Sertel, Silvio O Rizzoli, Bradley Garman, Katherine L Nathanson, Xiaowei Xu, Qing Chen, Jack H Oswald, Michal Lotem, Gordon B Mills, Michael A Davies, Michael P Schön, Ivan Bogeski, Meenhard Herlyn, Adina Vultur

Faculty, Staff and Student Publications

Background: Melanoma, the deadliest of skin cancers, has a high propensity to form brain metastases that are associated with a markedly worsened prognosis. In spite of recent therapeutic advances, melanoma brain lesions remain a clinical challenge, biomarkers predicting brain dissemination are not clear and differences with other metastatic sites are poorly understood.

Methods: We examined a genetically diverse panel of human-derived melanoma brain metastasis (MBM) and extracranial cell lines using targeted sequencing, a Reverse Phase Protein Array, protein expression analyses, and functional studies in vitro and in vivo.

Results: Brain-specific genetic alterations were not detected; however, MBM cells in vitro …

Evaluation Of Focal Adhesion Mediated Subcellular Curvature Sensing In Response To Engineered Extracellular Matrix, Daniel T Bowers, Mary Elizabeth Mcculloch, Justin L Brown

Faculty, Staff and Student Publications

Fibril curvature is bioinstructive to attached cells. Similar to natural healthy tissues, an engineered extracellular matrix can be designed to stimulate cells to adopt desired phenotypes. To take full advantage of the curvature control in biomaterial fabrication methodologies, an understanding of the response to fibril subcellular curvature is required. In this work, we examined morphology, signaling, and function of human cells attached to electrospun nanofibers. We controlled curvature across an order of magnitude using nondegradable poly(methyl methacrylate) (PMMA) attached to a stiff substrate with flat PMMA as a control. Focal adhesion length and the distance of maximum intensity from the …

Swi/Snf Blockade Disrupts Pu1-Directed Enhancer Programs In Normal Hematopoietic Cells And Acute Myeloid Leukemia, Courtney Chambers, Katerina Cermakova, Yuen San Chan, Kristen Kurtz, Katharina Wohlan, Andrew Henry Lewis, Christiana Wang, Anh Pham, Milan Dejmek, Michal Sala, Mario Loeza Cabrera, Rogelio Aguilar, Radim Nencka, H Daniel Lacorazza, Rachel E Rau, H Courtney Hodges

Faculty, Staff and Students Publications

UNLABELLED: In acute myeloid leukemia (AML), SWI/SNF chromatin remodeling complexes sustain leukemic identity by driving high levels of MYC. Previous studies have implicated the hematopoietic transcription factor PU.1 (SPI1) as an important target of SWI/SNF inhibition, but PU.1 is widely regarded to have pioneer-like activity. As a result, many questions have remained regarding the interplay between PU.1 and SWI/SNF in AML as well as normal hematopoiesis. Here we found that PU.1 binds to most of its targets in a SWI/SNF-independent manner and recruits SWI/SNF to promote accessibility for other AML core regulatory factors, including RUNX1, LMO2, and MEIS1. SWI/SNF inhibition …

On-The-Go Adaptation Of Implementation Approaches And Strategies In Health: Emerging Perspectives And Research Opportunities, Elvin H Geng, Aaloke Mody, Byron J Powell

2020-Current year OA Pubs

In many cases, implementation approaches (composed of one or more strategies) may need to change over time to work optimally. We use a literature review to inform a mechanistic analysis of such on-the-go adaptations. We suggest that such adaptations of implementation strategies consist of three necessary steps. The first component is the initial effect of the implementation approach on intended implementation, service delivery, or clinical outcomes. Second, these initial effects must in turn be used to modify, alter, intensify, or otherwise change the implementation approach. Third, the modified approach itself has effects. Conceiving of adaptation as all three steps implies …

Rapid Profiling Of Dna Replication Dynamics Using Mass Spectrometry-Based Analysis Of Nascent Dna, Mohamed E Ashour, Andrea K Byrum, Alice Meroni, Jun Xia, Saurabh Singh, Roberto Galletto, Susan M Rosenberg, Alessandro Vindigni, Nima Mosammaparast

Faculty, Staff and Students Publications

The primary method for probing DNA replication dynamics is DNA fiber analysis, which utilizes thymidine analog incorporation into nascent DNA, followed by immunofluorescent microscopy of DNA fibers. Besides being time-consuming and prone to experimenter bias, it is not suitable for studying DNA replication dynamics in mitochondria or bacteria, nor is it adaptable for higher-throughput analysis. Here, we present mass spectrometry-based analysis of nascent DNA (MS-BAND) as a rapid, unbiased, quantitative alternative to DNA fiber analysis. In this method, incorporation of thymidine analogs is quantified from DNA using triple quadrupole tandem mass spectrometry. MS-BAND accurately detects DNA replication alterations in both …

Inhibition Of Stat6 With Antisense Oligonucleotides Enhances The Systemic Antitumor Effects Of Radiotherapy And Anti-Pd-1 In Metastatic Non-Small Cell Lung Cancer, Kewen He, Hampartsoum B Barsoumian, Nahum Puebla-Osorio, Yun Hu, Duygu Sezen, Mark D Wasley, Genevieve Bertolet, Jie Zhang, Carola Leuschner, Liangpeng Yang, Claudia S Kettlun Leyton, Natalie Wall Fowlkes, Morgan Maureen Green, Lisa Hettrick, Dawei Chen, Fatemeh Masrorpour, Meidi Gu, Hadi Maazi, Alexey S Revenko, Maria Angelica Cortez, James W Welsh

Faculty, Staff and Student Publications

Diverse factors contribute to the limited clinical response to radiotherapy (RT) and immunotherapy in metastatic non-small cell lung cancer (NSCLC), among which is the ability of these tumors to recruit a retinue of suppressive immune cells-such as M2 tumor-associated macrophages (TAM)-thereby establishing an immunosuppressive tumor microenvironment that contributes to tumor progression and radio resistance. M2 TAMs are activated by the STAT6 signaling pathway. Therefore, we targeted STAT6 using an antisense oligonucleotide (ASO) along with hypofractionated RT (hRT; 3 fractions of 12 Gy each) to primary tumors in three bilateral murine NSCLC models (Lewis lung carcinoma, 344SQ-parental, and anti-PD-1-resistant 344SQ lung …

Dna Damage Repair Kinase Dna-Pk And Cgas Synergize To Induce Cancer-Related Inflammation In Glioblastoma, Clara Taffoni, Johanna Marines, Hanane Chamma, Soumyabrata Guha, Mathilde Saccas, Amel Bouzid, Ana-Luiza Chaves Valadao, Clément Maghe, Jane Jardine, Mi Kyung Park, Katarzyna Polak, Mara De Martino, Claire Vanpouille-Box, Maguy Del Rio, Celine Gongora, Julie Gavard, Nicolas Bidère, Min Sup Song, Donovan Pineau, Jean-Philippe Hugnot, Karima Kissa, Laura Fontenille, Fabien P Blanchet, Isabelle K Vila, Nadine Laguette

Faculty, Staff and Student Publications

Cytosolic DNA promotes inflammatory responses upon detection by the cyclic GMP-AMP (cGAMP) synthase (cGAS). It has been suggested that cGAS downregulation is an immune escape strategy harnessed by tumor cells. Here, we used glioblastoma cells that show undetectable cGAS levels to address if alternative DNA detection pathways can promote pro-inflammatory signaling. We show that the DNA-PK DNA repair complex (i) drives cGAS-independent IRF3-mediated type I Interferon responses and (ii) that its catalytic activity is required for cGAS-dependent cGAMP production and optimal downstream signaling. We further show that the cooperation between DNA-PK and cGAS favors the expression of chemokines that promote …

Lecanemab For Patients With Early Alzheimer Disease: Bayesian Analysis Of A Phase 2b Dose-Finding Randomized Clinical Trial, Donald A Berry, Shobha Dhadda, Michio Kanekiyo, David Li, Chad J Swanson, Michael Irizarry, Lynn D Kramer, Scott M Berry

Faculty, Staff and Student Publications

IMPORTANCE: Bayesian clinical trial designs are increasingly common; given their promotion by the US Food and Drug Administration, the future use of the bayesian approach will only continue to increase. Innovations possible when using the bayesian approach improve the efficiency of drug development and the accuracy of clinical trials, especially in the context of substantial data missingness.

OBJECTIVE: To explain the foundations, interpretations, and scientific justification of the bayesian approach in the setting of lecanemab trial 201, a bayesian-designed phase 2 dose-finding trial; to demonstrate the efficiency of using a bayesian design; and to show how it accommodates innovations in …

Il6 Mediates Suppression Of T- And Nk-Cell Function In Emt-Associated Tki-Resistant Egfr-Mutant Nsclc, Sonia A Patel, Monique B Nilsson, Yan Yang, Xiuning Le, Hai T Tran, Yasir Y Elamin, Xiaoxing Yu, Fahao Zhang, Alissa Poteete, Xiaoyang Ren, Li Shen, Jing Wang, Seyed Javad Moghaddam, Tina Cascone, Michael Curran, Don L Gibbons, John V Heymach

Faculty, Staff and Student Publications

Purpose: Patients with advanced non-small cell lung cancer (NSCLC) harboring activating EGFR mutations are initially responsive to tyrosine kinase inhibitors (TKI). However, therapeutic resistance eventually emerges, often via secondary EGFR mutations or EGFR-independent mechanisms such as epithelial-to-mesenchymal transition. Treatment options after EGFR-TKI resistance are limited as anti-PD-1/PD-L1 inhibitors typically display minimal benefit. Given that IL6 is associated with worse outcomes in patients with NSCLC, we investigate whether IL6 in part contributes to this immunosuppressed phenotype.

Experimental design: We utilized a syngeneic genetically engineered mouse model (GEMM) of EGFR-mutant NSCLC to investigate the effects of IL6 on the tumor microenvironment and …

Dysregulation And Epigenetic Reprogramming Of Nrf2 Signaling Axis Promote Acquisition Of Cisplatin Resistance And Metastasis In Head And Neck Squamous Cell Carcinoma, Abdullah A Osman, Emre Arslan, Mason Bartels, Chieko Michikawa, Antje Lindemann, Katarzyna Tomczak, Wangjie Yu, Vlad Sandulache, Wencai Ma, Li Shen, Jing Wang, Anand K Singh, Mitchell J Frederick, Nakia D Spencer, Jeffery Kovacs, Timothy Heffernan, William F Symmans, Kunal Rai, Jeffrey N Myers

Faculty, Staff and Student Publications

PURPOSE: Cisplatin (CDDP)-based chemotherapy is a first-line treatment for patients with advanced head and neck squamous cell carcinomas (HNSCC), despite a high rate of treatment failures, acquired resistance, and subsequent aggressive behavior. The purpose of this study was to study the mechanism of CDDP resistance and metastasis in HNSCC. We investigated the role of NRF2 pathway activation as a driven event for tumor progression and metastasis of HNSCC.

EXPERIMENTAL DESIGN: Human HNSCC cell lines that are highly resistant to CDDP were generated. Clonogenic survival assays and a mouse model of oral cancer were used to examine the impact of NRF2 …

Rapid Profiling Of Dna Replication Dynamics Using Mass Spectrometry-Based Analysis Of Nascent Dna, Mohamed E Ashour, Andrea K Byrum, Alice Meroni, Jun Xia, Saurabh Singh, Roberto Galletto, Susan M Rosenberg, Alessandro Vindigni, Nima Mosammaparast

2020-Current year OA Pubs

The primary method for probing DNA replication dynamics is DNA fiber analysis, which utilizes thymidine analog incorporation into nascent DNA, followed by immunofluorescent microscopy of DNA fibers. Besides being time-consuming and prone to experimenter bias, it is not suitable for studying DNA replication dynamics in mitochondria or bacteria, nor is it adaptable for higher-throughput analysis. Here, we present mass spectrometry-based analysis of nascent DNA (MS-BAND) as a rapid, unbiased, quantitative alternative to DNA fiber analysis. In this method, incorporation of thymidine analogs is quantified from DNA using triple quadrupole tandem mass spectrometry. MS-BAND accurately detects DNA replication alterations in both …

Discerning Conversational Context In Online Health Communities For Personalized Digital Behavior Change Solutions Using Pragmatics To Reveal Intent In Social Media (Prism) Framework, Tavleen Singh, Kirk Roberts, Trevor Cohen, Nathan Cobb, Amy Franklin, Sahiti Myneni

Faculty, Staff and Student Publications

BACKGROUND: Online health communities (OHCs) have emerged as prominent platforms for behavior modification, and the digitization of online peer interactions has afforded researchers with unique opportunities to model multilevel mechanisms that drive behavior change. Existing studies, however, have been limited by a lack of methods that allow the capture of conversational context and socio-behavioral dynamics at scale, as manifested in these digital platforms.

OBJECTIVE: We develop, evaluate, and apply a novel methodological framework, Pragmatics to Reveal Intent in Social Media (PRISM), to facilitate granular characterization of peer interactions by combining multidimensional facets of human communication.

METHODS: We developed and applied …

Transferrin Receptor-Mediated Iron Uptake Promotes Colon Tumorigenesis, Hyeoncheol Kim, Luke B. Villareal, Zhaoli Liu, Mohammad Haneef, Daniel M. Falcon, David R. Martin, Ho-Joon Lee, Michael K. Dame, Durga Attili, Ying Chen, James Varani, Jason R. Spence, Olga Kovbasnjuk, Justin A. Colacino, Costas A. Lyssiotis, Henry C. Lin, Yatrik M. Shah, Xiang Xue

Pathology Research and Scholarship

Transferrin receptor (TFRC) is the major mediator for iron entry into a cell. Under excessive iron conditions, TFRC is expected to be reduced to lower iron uptake and toxicity. However, the mechanism whereby TFRC expression is maintained at high levels in iron-enriched cancer cells and the contribution of TFRC to cancer development are enigmatic. Here the work shows TFRC is induced by adenomatous polyposis coli (APC) gene loss-driven β-catenin activation in colorectal cancer, whereas TFRC-mediated intratumoral iron accumulation potentiates β-catenin signaling by directly enhancing the activity of tankyrase. Disruption of TFRC leads to a reduction of colonic iron levels and …

Probenecid Slows Disease Progression In A Murine Model Of Autosomal Dominant Polycystic Kidney Disease, Sergey N. Arkhipov, D'Anna L. Potter, Regina F. Sultanova, Daria V. Ilatovskaya, Peter C. Harris, Tengis S. Pavlov

Hypertension and Vascular Research Articles

Development of autosomal dominant polycystic kidney disease (ADPKD) involves renal epithelial cell abnormalities. Cystic fluid contains a high level of ATP that, among other effects, leads to a reduced reabsorption of electrolytes in cyst-lining cells, and thus results in cystic fluid accumulation. Earlier, we demonstrated that Pkd1(RC/RC) mice, a hypomorphic model of ADPKD, exhibit increased expression of pannexin-1, a membrane channel capable of ATP release. In the current study, we found that human ADPKD cystic epithelia have higher pannexin-1 abundance than normal collecting ducts. We hypothesized that inhibition of pannexin-1 function with probenecid can be used to attenuate ADPKD development. …

Using Multiple Imputation Of Real-World Data To Estimate Clinical Remission In Pediatric Inflammatory Bowel Disease, Nanhua Zhang, Chunyan Liu, Steven J. Steiner, Richard B. Colletti, Robert Baldassano, Shiran Chen, Stanley Cohen, Michael D. Kappelman, Shehzad Saeed, Laurie S. Conklin, Richard Strauss, Sheri Volger, Eileen King, Kim Hung Lo

Pediatrics Faculty Publications

Aim: To evaluate the performance of the multiple imputation (MI) method for estimating clinical effectiveness in pediatric Crohn's disease in the ImproveCareNow registry; to address the analytical challenge of missing data. Materials & methods: Simulation studies were performed by creating missing datasets based on fully observed data from patients with moderate-to-severe Crohn's disease treated with non-ustekinumab biologics. MI was used to impute sPCDAI remission statuses in each simulated dataset. Results: The true remission rate (75.1% [95% CI: 72.6%, 77.5%]) was underestimated without imputation (72.6% [71.8%, 73.3%]). With MI, the estimate was 74.8% (74.4%, 75.2%). Conclusion: MI reduced nonresponse bias and …

Logistical, Technical, And Radiation Safety Aspects Of Establishing A Radiopharmaceutical Therapy Program: A Case In Lutetium-177 Prostate-Specific Membrane Antigen (Psma) Therapy, Jacqueline E Zoberi, Jose Garcia-Ramirez, David Luechtefeld, Nichole M Maughan, Maxwell Amurao, Reiko Oyama, Brian C Baumann, Hiram A Gay, Jeff M Michalski

2020-Current year OA Pubs

Prostate-specific membrane antigen (PSMA) is a cell surface protein highly expressed in nearly all prostate cancers, with restricted expression in some normal tissues. The differential expression of PSMA from tumor to non-tumor tissue has resulted in the investigation of numerous targeting strategies for therapy of patients with metastatic prostate cancer. In March of 2022, the FDA granted approval for the use of lutetium-177 PSMA-617 (Lu-177-PSMA-617) for patients with PSMA-positive metastatic castration-resistant prostate cancer (mCRPC) who have been treated with androgen receptor pathway inhibition and taxane-based chemotherapy. Therefore, the use of Lu-177-PSMA-617 is expected to increase and become more widespread. Herein, …

Addressing The Surgical Workplace: An Opportunity To Create A Culture Of Belonging, Carla M. Pugh, Orlando C. Kirton, J. E. Betsy Tuttle, Ronald V. Maier, Yue-Yung Hu, John H. Stewart, Julie Ann Freischlag, Julie Ann Sosa, Selwyn M Vickers, Mary T. Hawn, Timothy J. Eberlein, Diana L. Farmer, Robert S. Higgins, Carlos A. Pellegrini, Sanziana A. Roman, Marie L. Crandall, Christian M. De Virgilio, Allan Tsung, L. D. Britt

Abington Jefferson Health Papers

No abstract provided.

Community Health Workers To Increase Cancer Screening: 3 Community Guide Systematic Reviews, Devon L Okasako-Schmucker, Yinan Peng, Jamaicia Cobb, Leigh R Buchanan, Ka Zang Xiong, Shawna L Mercer, Susan A Sabatino, Stephanie Melillo, Patrick L Remington, Shiriki K Kumanyika, Beth Glenn, Erica S Breslau, Cam Escoffery, Maria E Fernandez, Gloria D Coronado, Karen Glanz, Patricia D Mullen, Sally W Vernon

Faculty, Staff and Student Publications

INTRODUCTION: Many in the U.S. are not up to date with cancer screening. This systematic review examined the effectiveness of interventions engaging community health workers to increase breast, cervical, and colorectal cancer screening.

METHODS: Authors identified relevant publications from previous Community Guide systematic reviews of interventions to increase cancer screening (1966 through 2013) and from an update search (January 2014-November 2021). Studies written in English and published in peer-reviewed journals were included if they assessed interventions implemented in high-income countries; reported screening for breast, cervical, or colorectal cancer; and engaged community health workers to implement part or all of the …

Associations Between Perceived Racial Discrimination, Racial Residential Segregation, And Cancer Screening Adherence Among Low-Income African Americans: A Multilevel, Cross-Sectional Analysis, Lynn N Ibekwe, Maria Eugenia Fernández-Esquer, Sandi L Pruitt, Nalini Ranjit, Maria E Fernández

Faculty, Staff and Student Publications

OBJECTIVES: African Americans suffer disproportionately from cancer compared to their White counterparts. Racism may be an important determinant, but the literature on its association with cancer screening is limited. We examine associations between racism and cancer screening among a sample of African Americans.

DESIGN: Guided by the Public Health Critical Race Praxis and the Behavioral Model of Health Services Use, we conducted a multilevel, cross-sectional study using cancer risk assessment data collected from 405 callers to the 2-1-1 Texas helpline. We merged these data with contextual data from the U.S. Census Bureau. We assessed perceived racial discrimination using the Experiences …

Naive T Cells Inhibit The Outgrowth Of Intractable Antigen-Activated Memory T Cells: Implications For T-Cell Immunotherapy, Sandhya Sharma, Mae Woods, Naren U Mehta, Tim Sauer, Kathan S Parikh, Michael Schmuck-Henneresse, Huimin Zhang, Birju Mehta, Malcolm K Brenner, Helen E Heslop, Cliona M Rooney

Faculty, Staff and Students Publications

BACKGROUND: The wider application of T cells targeting viral tumor-antigens via their native receptors is hampered by the failure to expand potent tumor-specific T cells from patients. Here, we examine reasons for and solutions to this failure, taking as our model the preparation of Epstein-Barr virus (EBV)-specific T cells (EBVSTs) for the treatment of EBV-positive lymphoma. EBVSTs could not be manufactured from almost one-third of patients, either because they failed to expand, or they expanded, but lacked EBV specificity. We identified an underlying cause of this problem and established a clinically feasible approach to overcome it.

METHODS: CD45RO+CD45RA- memory compartment …

Contribution Of Adaptive Immunity To Human Copd And Experimental Models Of Emphysema, Farrah Kheradmand, Yun Zhang, David B Corry

Faculty, Staff and Students Publications

The pathophysiology of chronic obstructive pulmonary disease (COPD) and the undisputed role of innate immune cells in this condition have dominated the field in the basic research arena for many years. Recently, however, compelling data suggesting that adaptive immune cells may also contribute to the progressive nature of lung destruction associated with COPD in smokers have gained considerable attention. The histopathological changes in the lungs of smokers can be limited to the large or small airways, but alveolar loss leading to emphysema, which occurs in some individuals, remains its most significant and irreversible outcome. Critically, however, the question of why …