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Comparison Of Human Cytokine Array, Cytokine Bead Arrays, And Protein Elisa In Determining Cytokine Production In Media Supernatant From In Vitro Strain Of Human Dermal Fibroblasts, Aric Anloague, Jonathan W. Lowery Ph.D. 2019 Marian University - Indianapolis

Comparison Of Human Cytokine Array, Cytokine Bead Arrays, And Protein Elisa In Determining Cytokine Production In Media Supernatant From In Vitro Strain Of Human Dermal Fibroblasts, Aric Anloague, Jonathan W. Lowery Ph.D.

Student Publications and Research

This experiment analyzes three different techniques used in literature to detect cytokine release from cells in vitro: the Human Cytokine Array (HCA) by R&D Systems, the BD Cytometric Bead Array (CBA) assay, and protein enzyme-linked immunosorbent assay (ELISA). The model used to test these assays was a human dermal fibroblast cell culture that was subjected to strain profiles by the Flexcell FX-6000 that include a repetitive motion injury, a profile with the injury strain as well as a strain representing myofascial release, and a control that was not strained. Each of these techniques analyzed the conditioned media of the ...


Alzheimer's Disease Microbiome Is Associated With Dysregulation Of The Anti-Inflammatory P-Glycoprotein Pathway, John P. Haran, Shakti K. Bhattarai, Sage Foley, Protiva Dutta, Doyle V. Ward, Vanni Bucci, Beth A. McCormick 2019 University of Massachusetts Medical School

Alzheimer's Disease Microbiome Is Associated With Dysregulation Of The Anti-Inflammatory P-Glycoprotein Pathway, John P. Haran, Shakti K. Bhattarai, Sage Foley, Protiva Dutta, Doyle V. Ward, Vanni Bucci, Beth A. Mccormick

Open Access Articles

The microbiota-gut-brain axis is a bidirectional communication system that is poorly understood. Alzheimer's disease (AD), the most common cause of dementia, has long been associated with bacterial infections and inflammation-causing immunosenescence. Recent studies examining the intestinal microbiota of AD patients revealed that their microbiome differs from that of subjects without dementia. In this work, we prospectively enrolled 108 nursing home elders and followed each for up to 5 months, collecting longitudinal stool samples from which we performed metagenomic sequencing and in vitro T84 intestinal epithelial cell functional assays for P-glycoprotein (P-gp) expression, a critical mediator of intestinal homeostasis. Our ...


Transcriptional Regulation Of Nlrc4 Inflammasome By Irf8, Ein Lee 2019 University of Tennessee Health Science Center

Transcriptional Regulation Of Nlrc4 Inflammasome By Irf8, Ein Lee

Theses and Dissertations (ETD)

The NLRC4 inflammasome is a crucial part of the innate immune response against bacterial infections. We found that NLRC4 inflammasome activation in bone marrow-derived macrophages (BMDMs) is greatly dependent on interferon regulatory factor 8 (IRF8). NLRC4-mediated caspase-1 activation and subsequent production of the inflammasome-dependent cytokines IL-1β and IL-18 and cell death were impaired in IRF8-deficient cells. IRF8 mediated the transcription of genes encoding NAIPs, the receptors for NLRC4 inflammasome, which recognize bacterial flagellin and type III secretion system (T3SS) proteins. IRF8 was critical for host survival following infection with Salmonella Typhimurium or Burkholderia thailandensis. Furthermore, mice deficient in IRF8 were ...


Identification Of Anaerobes In Clinical Specimens Comparison Between The Rapid Ana Ii System And The Bruker Maldi-Tof Ms System Utilized In The Clinical Laboratory, Raymond Chow 2019 Dominican University of California

Identification Of Anaerobes In Clinical Specimens Comparison Between The Rapid Ana Ii System And The Bruker Maldi-Tof Ms System Utilized In The Clinical Laboratory, Raymond Chow

Natural Sciences and Mathematics | Clinical Laboratory Sciences Culminating Projects

Matrix-Assisted Laser Desorption and Ionization Time-of-Flight Mass Spectrometry (MALDI-TOF MS) has been revealed as an invaluable platform for identifying anaerobic bacteria in the clinical laboratory over traditional methods such as the RapID ANA II System.

A qualitative comparison is made, through the analysis of methodologies and specifications, to determine whether the RapID ANA II system or Bruker MALDI-TOF MS is more suitable for identifying anaerobic organism in the clinical laboratory. Based on the data reviewed, the MALDI-TOF MS is a more intuitive platform within the clinical laboratory due to its increased specificity, cost-effectiveness, and shorten turnaround time for the identification ...


Potential Role Of Extracellular Atp Released By Bacteria In Bladder Infection And Contractility, Behnam Abbasian 2019 The University of Western Ontario

Potential Role Of Extracellular Atp Released By Bacteria In Bladder Infection And Contractility, Behnam Abbasian

Electronic Thesis and Dissertation Repository

Urgency urinary incontinence (UUI), the result of conditions such as overactive bladder (OAB), could potentially be influenced by both commensal and urinary tract infection-associated bacteria. The sensing of bladder filling involves interplay between various parts of the nervous system eventually resulting in contraction of the detrusor muscle during micturition. Here we model host responses to various urogenital bacteria, firstly by using urothelial bladder cell lines and then with myofibroblast contraction assays. To measure responses, we examined calcium influx, gene expression and alpha smooth muscle actin deposition assays. We found that organisms such as Escherichia coli IA2 and Gardnerella vaginalis ATCC ...


Rabies-Based Vaccine Induces Potent Immune Responses Against Nipah Virus., Rohan Keshwara, Thomas Shiels, Elena Postnikova, Drishya Kurup, Christoph Wirblich, Reed F. Johnson, Matthias J. Schnell 2019 Thomas Jefferson University

Rabies-Based Vaccine Induces Potent Immune Responses Against Nipah Virus., Rohan Keshwara, Thomas Shiels, Elena Postnikova, Drishya Kurup, Christoph Wirblich, Reed F. Johnson, Matthias J. Schnell

Department of Microbiology and Immunology Faculty Papers

Nipah Virus (NiV) is a re-emerging zoonotic pathogen in the genus Henipavirus of the Paramyxoviridae family of viruses. NiV is endemic to Bangladesh and Malaysia and is highly fatal to both livestock and humans (human case fatality rate = 74.5%). Currently, there is no approved vaccine against NiV on the market. The goal of this study was to use a recombinant RABV vector expressing NiV glycoprotein (NiV G) to develop a bivalent candidate vaccine against NiV disease and rabies virus (RABV) disease, which is also a significant health burden in the regions where NiV is endemic. The rabies vector is ...


Role Of Ribosome Recycling Factor As A Ribosome Releasing Factor, Yoshio Inokuchi, Fabio Quaglia, Akikazu Hirashima, Yoshihiro Yamamoto, Hideko Kaji, A. Kaji 2019 Teikyo University

Role Of Ribosome Recycling Factor As A Ribosome Releasing Factor, Yoshio Inokuchi, Fabio Quaglia, Akikazu Hirashima, Yoshihiro Yamamoto, Hideko Kaji, A. Kaji

Department of Biochemistry and Molecular Biology Posters

The objective of this presentation is to study the in vivo actions of ribosome recycling factor (RRF) and compare them with those found in vitro. RRF is known to catalyze three separate reactions: release of tRNA and mRNA from the post-termination complex (PoTC), and splitting of the ribosome of the PoTC. To study the mechanism of RRF reaction in vivo, we used E. coli harboring temperature sensitive (ts) RRF and assayed by following downstream reading of translationally coupled ORF. At the non-permissive temperature, ribosomes remain on the termination codon of the junction sequence of coupled ORFs and translate downstream ORF ...


Dynamic Molecular Changes During The First Week Of Human Life Follow A Robust Developmental Trajectory., Amy H. Lee, Casey P. Shannon, Nelly Amenyogbe, Tue B. Bennike, Joann Diray-Arce, Olubukola T. Idoko, Erin E. Gill, Rym Ben-Othman, William S. Pomat, Simon D. van Haren, Kim-Anh Lê Cao, Momoudou Cox, Alansana Darboe, Reza Falsafi, Davide Ferrari, Daniel J. Harbeson, Daniel He, Cai Bing, Samuel J. Hinshaw, Jorjoh Ndure, Jainaba Njie-Jobe, Matthew A. Pettengill, Peter C. Richmond, Rebecca Ford, Gerard Saleu, Geraldine Masiria, John Paul Matlam, Wendy Kirarock, Elishia Roberts, Mehrnoush Malek, Guzmán Sanchez-Schmitz, Amrit Singh, Asimenia Angelidou, Kinga K. Smolen, Diana Vo, Ken Kraft, Kerry McEnaney, Sofia Vignolo, Arnaud Marchant, Ryan R. Brinkman, Al Ozonoff, Robert E.W. Hancock, Anita H.J. van den Biggelaar, Hanno Steen, Scott J. Tebbutt, Beate Kampmann, Ofer Levy, Tobias R. Kollmann 2019 University of British Columbia

Dynamic Molecular Changes During The First Week Of Human Life Follow A Robust Developmental Trajectory., Amy H. Lee, Casey P. Shannon, Nelly Amenyogbe, Tue B. Bennike, Joann Diray-Arce, Olubukola T. Idoko, Erin E. Gill, Rym Ben-Othman, William S. Pomat, Simon D. Van Haren, Kim-Anh Lê Cao, Momoudou Cox, Alansana Darboe, Reza Falsafi, Davide Ferrari, Daniel J. Harbeson, Daniel He, Cai Bing, Samuel J. Hinshaw, Jorjoh Ndure, Jainaba Njie-Jobe, Matthew A. Pettengill, Peter C. Richmond, Rebecca Ford, Gerard Saleu, Geraldine Masiria, John Paul Matlam, Wendy Kirarock, Elishia Roberts, Mehrnoush Malek, Guzmán Sanchez-Schmitz, Amrit Singh, Asimenia Angelidou, Kinga K. Smolen, Diana Vo, Ken Kraft, Kerry Mcenaney, Sofia Vignolo, Arnaud Marchant, Ryan R. Brinkman, Al Ozonoff, Robert E.W. Hancock, Anita H.J. Van Den Biggelaar, Hanno Steen, Scott J. Tebbutt, Beate Kampmann, Ofer Levy, Tobias R. Kollmann

Department of Pathology, Anatomy, and Cell Biology Faculty Papers

Systems biology can unravel complex biology but has not been extensively applied to human newborns, a group highly vulnerable to a wide range of diseases. We optimized methods to extract transcriptomic, proteomic, metabolomic, cytokine/chemokine, and single cell immune phenotyping data fromblood, a volume readily obtained from newborns. Indexing to baseline and applying innovative integrative computational methods reveals dramatic changes along a remarkably stable developmental trajectory over the first week of life. This is most evident in changes of interferon and complement pathways, as well as neutrophil-associated signaling. Validated across two independent cohorts of newborns from West Africa and Australasia ...


Pnaktide Inhibits Na/K-Atpase Reactive Oxygen Species Amplification And Attenuates Adipogenesis, Komal Sodhi, Kyle Maxwell, Yanling Yan, Jiang Liu, Muhammad Chaudhry, Morgan Getty, Zijian Xie, Nader G. Abraham, Joseph I. Shapiro MD 2019 Marshall University

Pnaktide Inhibits Na/K-Atpase Reactive Oxygen Species Amplification And Attenuates Adipogenesis, Komal Sodhi, Kyle Maxwell, Yanling Yan, Jiang Liu, Muhammad Chaudhry, Morgan Getty, Zijian Xie, Nader G. Abraham, Joseph I. Shapiro Md

Muhammad Chaudhry

Obesity has become a worldwide epidemic and is a major risk factor for metabolic syndrome. Oxidative stress is known to play a role in the generation and maintenance of an obesity phenotype in both isolated adipocytes and intact animals. Because we had identified that the Na/K-ATPase can amplify oxidant signaling, we speculated that a peptide designed to inhibit this pathway, pNaKtide, might ameliorate an obesity phenotype. To test this hypothesis, we first performed studies in isolated murine preadipocytes (3T3L1 cells) and found that pNaKtide attenuated oxidant stress and lipid accumulation in a dose-dependent manner. Complementary experiments in C57Bl6 mice ...


Ripk1 Can Mediate Apoptosis In Addition To Necroptosis During Embryonic Development., Xuhua Zhang, John P. Dowling, Jianke Zhang 2019 Thomas Jefferson University

Ripk1 Can Mediate Apoptosis In Addition To Necroptosis During Embryonic Development., Xuhua Zhang, John P. Dowling, Jianke Zhang

Department of Microbiology and Immunology Faculty Papers

RIPK1 has emerged as a key effector in programmed necrosis or necroptosis. This function of RIPK1 is mediated by its protein serine/threonine kinase activity and through the downstream kinase RIPK3. Deletion of RIPK1 prevents embryonic lethality in mice lacking FADD, a signaling adaptor protein required for activation of Caspase 8 in extrinsic apoptotic pathways. This indicates that FADD-mediated apoptosis inhibits RIPK1-dependent necroptosis to ensure successful embryogenesis. However, the molecular mechanism for this critical regulation remains unclear. In the current study, a novel mouse model has been generated, by disrupting a potential caspase cleavage site at aspartic residue (D)324 ...


Wave 2 Strains Of Atypical Vibrio Cholerae El Tor Caused The 2009-2011 Cholera Outbreak In Papua New Guinea, Andrew R. Greenhill, Ankur Mutreja, Dieter Bulach, Matthew J. Belousoff, Marinjho H. Jonduo, Deirdre A. Collins, Monalisa P. Kas, Johanna Wapling, Torsten Seemann, Alice Lafana, Gordon Dougan, Mark V. Brown, Paul F. Horwood 2019 Edith Cowan University

Wave 2 Strains Of Atypical Vibrio Cholerae El Tor Caused The 2009-2011 Cholera Outbreak In Papua New Guinea, Andrew R. Greenhill, Ankur Mutreja, Dieter Bulach, Matthew J. Belousoff, Marinjho H. Jonduo, Deirdre A. Collins, Monalisa P. Kas, Johanna Wapling, Torsten Seemann, Alice Lafana, Gordon Dougan, Mark V. Brown, Paul F. Horwood

ECU Publications Post 2013

Vibrio cholerae is the causative agent of cholera, a globally important human disease for at least 200 years. In 2009-2011, the first recorded cholera outbreak in Papua New Guinea (PNG) occurred. We conducted genetic and phenotypic characterization of 21 isolates of V. cholerae, with whole-genome sequencing conducted on 2 representative isolates. The PNG outbreak was caused by an atypical El Tor strain harbouring a tandem repeat of the CTX prophage on chromosome II. Whole-genome sequence data, prophage structural analysis and the absence of the SXT integrative conjugative element was indicative that the PNG isolates were most closely related to strains ...


Osteoblasts Are "Educated" By Crosstalk With Metastatic Breast Cancer Cells In The Bone Tumor Microenvironment., Alexus D. Kolb, Alison B. Shupp, Dimpi Mukhopadhyay, Frank C. Marini, Karen M. Bussard 2019 Thomas Jefferson University

Osteoblasts Are "Educated" By Crosstalk With Metastatic Breast Cancer Cells In The Bone Tumor Microenvironment., Alexus D. Kolb, Alison B. Shupp, Dimpi Mukhopadhyay, Frank C. Marini, Karen M. Bussard

Department of Cancer Biology Faculty Papers

INTRODUCTION: In a cancer-free environment in the adult, the skeleton continuously undergoes remodeling. Bone-resorbing osteoclasts excavate erosion cavities, and bone-depositing osteoblasts synthesize osteoid matrix that forms new bone, with no net bone gain or loss. When metastatic breast cancer cells invade the bone, this balance is disrupted. Patients with bone metastatic breast cancer frequently suffer from osteolytic bone lesions that elicit severe bone pain and fractures. Bisphosphonate treatments are not curative. Under ideal circumstances, osteoblasts would synthesize new matrix to fill in erosion cavities caused by osteoclasts, but this is not what occurs. Our prior evidence demonstrated that osteoblasts are ...


Tradd Regulates Perinatal Development And Adulthood Survival In Mice Lacking Ripk1 And Ripk3., John P. Dowling, Mohamed Alsabbagh, Christina Del Casale, Zheng-Gang Liu, Jianke Zhang 2019 Thomas Jefferson University

Tradd Regulates Perinatal Development And Adulthood Survival In Mice Lacking Ripk1 And Ripk3., John P. Dowling, Mohamed Alsabbagh, Christina Del Casale, Zheng-Gang Liu, Jianke Zhang

Department of Microbiology and Immunology Faculty Papers

TRADD is an adaptor for TNFR1-induced apoptosis and NFκB activation. However, TRADD-deficient mice undergo normal development and contain normal lymphoid populations, which contrasts with an embryonic defect in mice lacking FADD, the shared adaptor mediating apoptosis. Recent studies indicate FADD suppresses embryonic necroptosis mediated by RIPK1. TRADD was suggested to also mediate necroptosis. Here we report that targeting TRADD fails to rescue Fadd −/− embryos from necroptosis, and ablation of TRADD rescues Ripk1 −/− mice from perinatal lethality when RIPK3-mediated necroptosis is disabled. The resulting Ripk1 −/− Ripk3 −/− Tradd −/− mice survive until early adulthood, but die thereafter. A single allele of Tradd is ...


Cyclin D1 Integrates G9a-Mediated Histone Methylation., Zhiping Li, Xuanmao Jiao, Gabriele Di Sante, Adam Ertel, Mathew C. Casimiro, Min Wang, Sanjay Katiyar, Xiaoming Ju, D. V. Klopfenstein, Aydin Tozeren, William Dampier, Iouri Chepelev, Albert Jeltsch, Richard G. Pestell 2019 Baruch S. Blumberg Institute

Cyclin D1 Integrates G9a-Mediated Histone Methylation., Zhiping Li, Xuanmao Jiao, Gabriele Di Sante, Adam Ertel, Mathew C. Casimiro, Min Wang, Sanjay Katiyar, Xiaoming Ju, D. V. Klopfenstein, Aydin Tozeren, William Dampier, Iouri Chepelev, Albert Jeltsch, Richard G. Pestell

Department of Cancer Biology Faculty Papers

Lysine methylation of histones and non-histone substrates by the SET domain containing protein lysine methyltransferase (KMT) G9a/EHMT2 governs transcription contributing to apoptosis, aberrant cell growth, and pluripotency. The positioning of chromosomes within the nuclear three-dimensional space involves interactions between nuclear lamina (NL) and the lamina-associated domains (LAD). Contact of individual LADs with the NL are dependent upon H3K9me2 introduced by G9a. The mechanisms governing the recruitment of G9a to distinct subcellular sites, into chromatin or to LAD, is not known. The cyclin D1 gene product encodes the regulatory subunit of the holoenzyme that phosphorylates pRB and NRF1 thereby governing ...


Severity Of Disease And Mortality For Hospitalized Patients With Community-Acquired Viral Pneumonia Compared To Patients With Community-Acquired Bacterial Pneumonia, Richard Y. Kim, Thomas Chandler, Stephen P. Furmanek, Timothy Lee Wiemken, Rodrigo Cavallazzi 2019 University of Louisville

Severity Of Disease And Mortality For Hospitalized Patients With Community-Acquired Viral Pneumonia Compared To Patients With Community-Acquired Bacterial Pneumonia, Richard Y. Kim, Thomas Chandler, Stephen P. Furmanek, Timothy Lee Wiemken, Rodrigo Cavallazzi

The University of Louisville Journal of Respiratory Infections

Background: There exists a large body of literature to help identify, diagnose, treat, and manage community-acquired pneumonia (CAP). Despite this, there is little data that directly compares the clinical syndromes and complications of pure bacterial pneumonia to pure viral pneumonia. Our study compares the clinical presentation, morbidity and mortality of viral vs. bacterial etiologies of CAP.

Methods: This was a secondary data analysis of the Community-Acquired Pneumonia Organization (CAPO) international study database. Data was collected concerning patient demographics, physical examination findings, laboratory findings, radiological findings, severity of illness, and clinical outcomes and stratified according to the two study groups, CAVP ...


Conjugated Bile Acid And Sphingosine 1-Phosophate Prompt Cholangiocarcinoma Cell Growth Via Releasing Exosomes, Waad A. Alruwaili 2019 Virginia Commonwealth University

Conjugated Bile Acid And Sphingosine 1-Phosophate Prompt Cholangiocarcinoma Cell Growth Via Releasing Exosomes, Waad A. Alruwaili

Theses and Dissertations

Cholangiocarcinoma (CCA) is a fatal primary malignancy that is formed in the bile ducts. Cancer-associated myofibroblasts play a crucial role in CCA proliferation and invasion. Furthermore, there is a growing interest in the role of the exosome in the interaction between the cancer-associated myofibroblasts and cholangiocarcinoma which lead to CCA growth. However how cholangiocarcinoma-derived exosome affect the cancer-associated myofibroblasts in the tumor microenvironment remain unknown. In this study, we examined whether exosome produced by cholangiocarcinoma could involve in the prompt of CCA cells growth by regulation of myofibroblast. We found that cholangiocarcinoma-derived exosome could prompt elevated α-smooth muscle actin and ...


Characterization Of Protein Involved In Hemolysis Expressed By Sneathia Amnii, A Pathogen Of The Female Urogenital Tract, Gabriella Gentile, Lizette Carrasco, Amy Stanford, Kimberly Jefferson 2019 Virginia Commonwealth University

Characterization Of Protein Involved In Hemolysis Expressed By Sneathia Amnii, A Pathogen Of The Female Urogenital Tract, Gabriella Gentile, Lizette Carrasco, Amy Stanford, Kimberly Jefferson

Graduate Research Posters

Sneathia amnii is a poorly characterized gram-negative anaerobe that commonly colonizes the vagina. It has been linked to many obstetric disorders, including preterm labor, preeclampsia, and chorioamnionitis. S. amnii lyses human red blood cells, and we aimed to identify the hemolysin. We identified two genes that appear to encode transporter and effector components of a two-partner secretion system. The putative effector, which we refer to as SaFHA, contains a domain with amino acid similarity to the filamentous hemagglutinin (FHA) of Bordetella pertussis and its predicted structure suggests it may form a transmembrane channel or pore. Thus, we hypothesized that SaFHA ...


Urease Is An Essential Component Of The Acid Response Network Of Staphylococcus Aureus And Is Required For A Persistent Murine Kidney Infection, Chunyi Zhou, Fatema Bhinderwala, McKenzie K. Lehman, Vinai Chittezham Thomas, Sujata S. Chaudhari, Kelsey J. Yamada, Kirk W. Foster, Robert Powers, Tammy Kielian, Paul D. Fey 2019 University of Nebraska Medical Center

Urease Is An Essential Component Of The Acid Response Network Of Staphylococcus Aureus And Is Required For A Persistent Murine Kidney Infection, Chunyi Zhou, Fatema Bhinderwala, Mckenzie K. Lehman, Vinai Chittezham Thomas, Sujata S. Chaudhari, Kelsey J. Yamada, Kirk W. Foster, Robert Powers, Tammy Kielian, Paul D. Fey

Journal Articles: Pathology and Microbiology

Staphylococcus aureus causes acute and chronic infections resulting in significant morbidity. Urease, an enzyme that generates NH3 and CO2 from urea, is key to pH homeostasis in bacterial pathogens under acidic stress and nitrogen limitation. However, the function of urease in S. aureus niche colonization and nitrogen metabolism has not been extensively studied. We discovered that urease is essential for pH homeostasis and viability in urea-rich environments under weak acid stress. The regulation of urease transcription by CcpA, Agr, and CodY was identified in this study, implying a complex network that controls urease expression in response to changes in metabolic ...


Protease-Mediated Growth Of Staphylococcus Aureus On Host Proteins Is Opp3 Dependent, McKenzie K. Lehman, Austin S. Nuxoll, Kelsey J. Yamada, Tammy Kielian, Steven D. Carson, Paul D. Fey 2019 University of Nebraska Medical Center

Protease-Mediated Growth Of Staphylococcus Aureus On Host Proteins Is Opp3 Dependent, Mckenzie K. Lehman, Austin S. Nuxoll, Kelsey J. Yamada, Tammy Kielian, Steven D. Carson, Paul D. Fey

Journal Articles: Pathology and Microbiology

Staphylococcus aureus has the ability to cause infections in multiple organ systems, suggesting an ability to rapidly adapt to changing carbon and nitrogen sources. Although there is little information about the nutrients available at specific sites of infection, a mature skin abscess has been characterized as glucose depleted, indicating that peptides and free amino acids are an important source of nutrients for the bacteria. Our studies have found that mutations in enzymes necessary for growth on amino acids, including pyruvate carboxykinase (ΔpckA) and glutamate dehydrogenase (ΔgudB), reduced the ability of the bacteria to proliferate within a skin abscess ...


Reanalysis Of The Nccn Pd-L1 Companion Diagnostic Assay Study For Lung Cancer In The Context Of Pd-L1 Expression Findings In Triple-Negative Breast Cancer, David L. Rimm, Gang Han, Janis M. Taube, Eunhee S. Yi, Julia A. Bridge, Douglas B. Flieder, Robert Homer, Anja C. Roden, Fred R. Hirsch, Ignacio I. Wistuba, Lajos Pusztai 2019 Yale University

Reanalysis Of The Nccn Pd-L1 Companion Diagnostic Assay Study For Lung Cancer In The Context Of Pd-L1 Expression Findings In Triple-Negative Breast Cancer, David L. Rimm, Gang Han, Janis M. Taube, Eunhee S. Yi, Julia A. Bridge, Douglas B. Flieder, Robert Homer, Anja C. Roden, Fred R. Hirsch, Ignacio I. Wistuba, Lajos Pusztai

Journal Articles: Pathology and Microbiology

The companion diagnostic test for checkpoint inhibitor immune therapy is an immunohistochemical test for PD-L1. The test has been shown to be reproducible for expression in tumor cells, but not in immune cells. Immune cells were used in the IMpassion130 trial which showed PD-L1 expression was associated with a better outcome. Two large studies have been done assessing immune cell PD-L1 expression in lung cancer. Here, we reanalyze one of those studies, to show that, even with an easier scoring method, there is still only poor agreement between assays and pathologist for immune cell PD-L1 expression.


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