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Program death ligand 1/2

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https://www.readbyqxmd.com/read/27907031/in-vitro-pre-clinical-validation-of-suicide-gene-modified-anti-cd33-redirected-chimeric-antigen-receptor-t-cells-for-acute-myeloid-leukemia
#1
Kentaro Minagawa, Muhammad O Jamil, Mustafa Al-Obaidi, Larisa Pereboeva, Donna Salzman, Harry P Erba, Lawrence S Lamb, Ravi Bhatia, Shin Mineishi, Antonio Di Stasi
BACKGROUND: Approximately fifty percent of patients with acute myeloid leukemia can be cured with current therapeutic strategies which include, standard dose chemotherapy for patients at standard risk of relapse as assessed by cytogenetic and molecular analysis, or high-dose chemotherapy with allogeneic hematopoietic stem cell transplant for high-risk patients. Despite allogeneic hematopoietic stem cell transplant about 25% of patients still succumb to disease relapse, therefore, novel strategies are needed to improve the outcome of patients with acute myeloid leukemia...
2016: PloS One
https://www.readbyqxmd.com/read/27893093/ligation-of-cd40-in-human-m%C3%A3-ller-cells-induces-p2x7-receptor-dependent-death-of-retinal-endothelial-cells
#2
Jose-Andres C Portillo, Yalitza Lopez Corcino, George R Dubyak, Timothy S Kern, Shigemi Matsuyama, Carlos S Subauste
Purpose: Cluster of differentiation 40 (CD40) is required for retinal capillary degeneration in diabetic mice, a process mediated by the retinal endothelial cells (REC) death. However, CD40 activates prosurvival signals in endothelial cells. The purpose of this study was to identify a mechanism by which CD40 triggers programmed cell death (PCD) of RECs and address this paradox. Methods: Human RECs and Müller cells were incubated with CD154 and L-N6-(1-Iminoethyl)lysine (L-Nil, nitric oxide synthase 2 inhibitor), α-lipoic acid (inhibitor of oxidative stress), anti-Fas ligand antibody, or A-438079 (P2X7 adenosine triphosphate [ATP] receptor inhibitor)...
November 1, 2016: Investigative Ophthalmology & Visual Science
https://www.readbyqxmd.com/read/27892511/the-clinicopathological-and-prognostic-significance-of-pd-l1-expression-in-gastric-cancer-a-meta-analysis-of-10-studies-with-1-901-patients
#3
Minghui Zhang, Yuandi Dong, Haitao Liu, Yan Wang, Shu Zhao, Qijia Xuan, Yan Wang, Qingyuan Zhang
The prognostic value of programmed death-ligand 1 (PD-L1) in gastric cancer (GC) remains controversial. To clarify this problem, we performed a meta-analysis of research studies identified in the PubMed, EMBASE and the Cochrane Library databases. A total of 1,901 patients in 10 studies were enrolled in this meta-analysis, and the pooled hazard ratio (HR) of 1.64 (95% CI 1.11 to 2.43; P = 0.01) indicated that PD-L1 expression is associated with a shorter overall survival (OS). The pooled odds ratios (ORs) indicated that PD-L1 expression was associated with tumour size (OR = 1...
November 28, 2016: Scientific Reports
https://www.readbyqxmd.com/read/27882863/porphyromonas-gingivalis-suppresses-adaptive-immunity-in-periodontitis-atherosclerosis-and-alzheimer-s-disease
#4
REVIEW
Ingar Olsen, Martin A Taubman, Sim K Singhrao
Porphyromonas gingivalis, a keystone pathogen in chronic periodontitis, has been found to associate with remote body organ inflammatory pathologies, including atherosclerosis and Alzheimer's disease (AD). Although P. gingivalis has a plethora of virulence factors, much of its pathogenicity is surprisingly related to the overall immunosuppression of the host. This review focuses on P. gingivalis aiding suppression of the host's adaptive immune system involving manipulation of cellular immunological responses, specifically T cells and B cells in periodontitis and related conditions...
2016: Journal of Oral Microbiology
https://www.readbyqxmd.com/read/27879653/ellagic-acid-inhibits-bladder-cancer-invasiveness-and-in-vivo-tumor-growth
#5
Claudia Ceci, Lucio Tentori, Maria Grazia Atzori, Pedro M Lacal, Elena Bonanno, Manuel Scimeca, Rosella Cicconi, Maurizio Mattei, Maria Gabriella de Martino, Giuseppe Vespasiani, Roberto Miano, Grazia Graziani
Ellagic acid (EA) is a polyphenolic compound that can be found as a naturally occurring hydrolysis product of ellagitannins in pomegranates, berries, grapes, green tea and nuts. Previous studies have reported the antitumor properties of EA mainly using in vitro models. No data are available about EA influence on bladder cancer cell invasion of the extracellular matrix triggered by vascular endothelial growth factor-A (VEGF-A), an angiogenic factor associated with disease progression and recurrence, and tumor growth in vivo...
November 22, 2016: Nutrients
https://www.readbyqxmd.com/read/27870715/posttranscriptional-control-of-pd-l1-expression-by-17%C3%AE-estradiol-via-pi3k-akt-signaling-pathway-in-er%C3%AE-positive-cancer-cell-lines
#6
Lingyun Yang, Feng Huang, Jiandong Mei, Xun Wang, Qiuyang Zhang, Hongjing Wang, Mingrong Xi, Zongbing You
OBJECTIVE: Estrogen is a well-known oncogenic driver in endometrial (ECs) and breast cancers (BCs). Programmed cell death protein 1 (PD-1) and its ligands PD-1 Ligand 1 (PD-L1) and PD-L2 have been shown to mediate immune evasion of the tumor cells. The purpose of the present study was to assess the effects of estrogen on PD-L1 and PD-L2 expression in EC and BC cell lines. METHODS: 17β-Estradiol (E2)-induced expression of PD-L1 and PD-L2 and possible signaling pathway were investigated in EC and BC cells...
November 17, 2016: International Journal of Gynecological Cancer
https://www.readbyqxmd.com/read/27864219/neoadjuvant-chemotherapy-nact-increases-immune-infiltration-and-programmed-death-ligand-1-pd-l1-expression-in-epithelial-ovarian-cancer-eoc
#7
S J L Mesnage, A Auguste, C Genestie, A Dunant, E Pain, F Drusch, S Gouy, P Morice, E Bentivegna, C Lhomme, P Pautier, J Michels, A Le Formal, B Cheaib, J Adam, A F Leary
BACKGROUND: Lymphocytic infiltration at diagnosis is prognostic in EOC, however the impact of NACT on tumour infiltrating lymphocytes (TILs) or PD-L1 expression remains poorly described. PATIENTS AND METHODS: Patients with EOC and sequential samples (pre-NACT, post-NACT or relapse) were retrospectively identified. TILs were evaluated on whole sections; stromal TILs (sTILs) scored as percentage of stromal area with high sTILs defined as ≥50%; intra-epithelial TILs (ieTILs) scored semi-quantitatively (0-3) with high ieTILs ≥2...
November 17, 2016: Annals of Oncology: Official Journal of the European Society for Medical Oncology
https://www.readbyqxmd.com/read/27863197/programmed-death-ligand-1-expression-and-response-to-the-anti-programmed-death-1-antibody-pembrolizumab-in-melanoma
#8
Adil I Daud, Jedd D Wolchok, Caroline Robert, Wen-Jen Hwu, Jeffrey S Weber, Antoni Ribas, F Stephen Hodi, Anthony M Joshua, Richard Kefford, Peter Hersey, Richard Joseph, Tara C Gangadhar, Roxana Dronca, Amita Patnaik, Hassane Zarour, Charlotte Roach, Grant Toland, Jared K Lunceford, Xiaoyun Nicole Li, Kenneth Emancipator, Marisa Dolled-Filhart, S Peter Kang, Scot Ebbinghaus, Omid Hamid
Purpose Expression of programmed death-ligand 1 (PD-L1) is a potential predictive marker for response and outcome after treatment with anti-programmed death 1 (PD-1). This study explored the relationship between anti-PD-1 activity and PD-L1 expression in patients with advanced melanoma who were treated with pembrolizumab in the phase Ib KEYNOTE-001 study (clinical trial information: NCT01295827). Patients and Methods Six hundred fifty-five patients received pembrolizumab10 mg/kg once every 2 weeks or once every 3 weeks, or 2 mg/kg once every 3 weeks...
December 2016: Journal of Clinical Oncology: Official Journal of the American Society of Clinical Oncology
https://www.readbyqxmd.com/read/27859479/diverse-types-of-dermatologic-toxicities-from-immune-checkpoint-blockade-therapy
#9
REVIEW
Jonathan L Curry, Michael T Tetzlaff, Priyadharsini Nagarajan, Carol Drucker, Adi Diab, Sharon R Hymes, Madeleine Duvic, Wen-Jen Hwu, Jennifer A Wargo, Carlos A Torres-Cabala, Ronald P Rapini, Victor G Prieto
Immunomodulatory drugs that leverages host immune mechanisms to destroy tumor cells has been met with great promise in the treatment of cancer. Immunotherapy, targeting cytotoxic T-lymphocyte-associated antigen 4 (CTLA-4) and the programmed cell death 1 (PD-1) receptor and its ligand (PD-L1) have shown tremendous improvements in the survival of patients with advanced solid tumors. However, the development of dermatologic toxicity (DT) is a consequence to immunotherapy. Review of published reports of the DT to immunotherapy revealed patients receiving anti-CTCLA-4 antibody or anti-PD-1/PD-L1 antibody often develop a DT of any type and grade...
November 10, 2016: Journal of Cutaneous Pathology
https://www.readbyqxmd.com/read/27854242/the-future-prospects-of-immune-therapy-in-gastric-and-esophageal-adenocarcinoma
#10
REVIEW
Walid L Shaib, Jean Paul A Nammour, Harpaul Gill, Mayur Mody, Nabil F Saba
The prognosis of esophageal cancers is poor and novel approaches are urgently needed. Despite improvements in outcomes with transtuzumab and ramucirumab, these improvements added an average of only 2 to 3 months with a median overall survival reported to be around 1 year. Comprehensive genomic sequencing has defined some molecular alterations with potential targets, but the majority of patients still do not benefit from druggable targets. Breakthroughs in immune checkpoint blockade have provided new therapeutic options in many cancers...
November 14, 2016: Journal of Clinical Medicine
https://www.readbyqxmd.com/read/27849650/programmed-cell-death-ligand-1-pd-l1-expression-in-anal-cancer
#11
Rangaswamy Govindarajan, Swetha Gujja, Eric R Siegel, Anu Batra, Anwaar Saeed, Keith Lai, Jennifer D James, Bradley J Fogel, Stephen Williamson
OBJECTIVE: To evaluate the expression of programmed cell death-ligand 1 (PD-L1) in anal cancer. PATIENTS AND METHODS: In a retrospective cohort analysis, subjects with squamous cell carcinoma of the anal canal were tested for PD-L1 expression, then followed for recurrence and survival. Crude recurrence rates (CRRs), crude mortality rates (CMRs), and crude event rates (CERs) were assessed for PD-L1-dependent differences using Poisson regression. All 3 types of crude rate were expressed as the number that occurred per hundred person-years (hPY) of follow-up...
November 15, 2016: American Journal of Clinical Oncology
https://www.readbyqxmd.com/read/27846884/future-perspectives-in-melanoma-research-meeting-report-from-the-melanoma-bridge-napoli-december-1st-4th-2015
#12
Paolo A Ascierto, Sanjiv Agarwala, Gerardo Botti, Alessandra Cesano, Gennaro Ciliberto, Michael A Davies, Sandra Demaria, Reinhard Dummer, Alexander M Eggermont, Soldano Ferrone, Yang Xin Fu, Thomas F Gajewski, Claus Garbe, Veronica Huber, Samir Khleif, Michael Krauthammer, Roger S Lo, Giuseppe Masucci, Giuseppe Palmieri, Michael Postow, Igor Puzanov, Ann Silk, Stefani Spranger, David F Stroncek, Ahmad Tarhini, Janis M Taube, Alessandro Testori, Ena Wang, Jennifer A Wargo, Cassian Yee, Hassane Zarour, Laurence Zitvogel, Bernard A Fox, Nicola Mozzillo, Francesco M Marincola, Magdalena Thurin
The sixth "Melanoma Bridge Meeting" took place in Naples, Italy, December 1st-4th, 2015. The four sessions at this meeting were focused on: (1) molecular and immune advances; (2) combination therapies; (3) news in immunotherapy; and 4) tumor microenvironment and biomarkers. Recent advances in tumor biology and immunology has led to the development of new targeted and immunotherapeutic agents that prolong progression-free survival (PFS) and overall survival (OS) of cancer patients. Immunotherapies in particular have emerged as highly successful approaches to treat patients with cancer including melanoma, non-small cell lung cancer (NSCLC), renal cell carcinoma (RCC), bladder cancer, and Hodgkin's disease...
November 15, 2016: Journal of Translational Medicine
https://www.readbyqxmd.com/read/27836863/checkpoint-proteins-in-pediatric-brain-and-extracranial-solid-tumors-opportunities-for-immunotherapy
#13
Eric K Ring, James M Markert, G Yancey Gillespie, Gregory K Friedman
Pediatric brain and extracranial solid tumors are a diverse group of malignancies that represent almost half of pediatric cancers. Standard therapy includes various combinations of surgery, cytotoxic chemotherapy and radiation, which can be very harmful to a developing child, and survivors carry a substantial burden of long term morbidities. While these therapies have improved survival rates for children with solid tumors, outcomes still remain extremely poor for subsets of patients. Recently, immunosuppressive checkpoint molecules that negatively regulate immune cell function have been described...
November 10, 2016: Clinical Cancer Research: An Official Journal of the American Association for Cancer Research
https://www.readbyqxmd.com/read/27835597/pd-l1-promoter-methylation-is-a-prognostic-biomarker-for-biochemical-recurrence-free-survival-in-prostate-cancer-patients-following-radical-prostatectomy
#14
Heidrun Gevensleben, Emily Eva Holmes, Diane Goltz, Jörn Dietrich, Verena Sailer, Jörg Ellinger, Dimo Dietrich, Glen Kristiansen
BACKGROUND: The rapid development of programmed death 1 (PD-1)/programmed death ligand 1 (PD-L1) inhibitors has generated an urgent need for biomarkers assisting the selection of patients eligible for therapy. The use of PD-L1 immunohistochemistry, which has been suggested as a predictive biomarker, however, is confounded by multiple unresolved issues. The aim of this study therefore was to quantify PD-L1 DNA methylation (mPD-L1) in prostate tissue samples and to evaluate its potential as a biomarker in prostate cancer (PCa)...
November 7, 2016: Oncotarget
https://www.readbyqxmd.com/read/27825958/simultaneous-blockade-of-interacting-ck2-and-egfr-pathways-by-tumor-targeting-nanobioconjugates-increases-therapeutic-efficacy-against-glioblastoma-multiforme
#15
Szu-Ting Chou, Rameshwar Patil, Anna Galstyan, Pallavi R Gangalum, Webster K Cavenee, Frank B Furnari, Vladimir A Ljubimov, Alexandra Chesnokova, Andrei A Kramerov, Hui Ding, Vida Falahatian, Leila Mashouf, Irving Fox, Keith L Black, Eggehard Holler, Alexander V Ljubimov, Julia Y Ljubimova
Glioblastoma multiforme (GBM) remains the deadliest brain tumor in adults. GBM tumors are also notorious for drug and radiation resistance. To inhibit GBMs more effectively, polymalic acid-based blood-brain barrier crossing nanobioconjugates were synthesized that are delivered to the cytoplasm of cancer cells and specifically inhibit the master regulator serine/threonine protein kinase CK2 and the wild-type/mutated epidermal growth factor receptor (EGFR/EGFRvIII), which are overexpressed in gliomas according to The Cancer Genome Atlas (TCGA) GBM database...
November 5, 2016: Journal of Controlled Release: Official Journal of the Controlled Release Society
https://www.readbyqxmd.com/read/27825291/programmed-death-ligand-1-expression-in-papillary-thyroid-cancer-and-its-correlation-with-clinicopathological-factors-and-recurrence
#16
Qinghai Ji, Rongliang Shi, Ning Qu, Tingxian Luo, Jun Xiang, Tian Liao, Guohua Sun, Yu Wang, Yu-Long Wang, Caiping Huang
Background Programmed death ligand 1 (PD-L1) expression has been reported in several malignancies, but the expression of PD-L1 in papillary thyroid cancer (PTC) is has been characterized rarely defined. The aim of this study was to assess the significance of PD-L1 expression and its associations with clinicopathological factors and disease outcome in PTC. Methods Immunohistochemistry staining was conducted retrospectively to evaluate the expression of PD-L1 in a total of 260 PTC tumors and corresponding non-tumor tissues...
November 8, 2016: Thyroid: Official Journal of the American Thyroid Association
https://www.readbyqxmd.com/read/27822406/pd-1-inhibition-and-treatment-of-advanced-melanoma-role-of-pembrolizumab
#17
REVIEW
Ali R Jazirehi, Alexandra Lim, Tam Dinh
Remarkable clinical responses have been seen in patients with metastatic melanoma with targeted therapy (BRAFi vemurafenib, MEKi) and with modern immune cell-based approaches such as TCR engineered adoptive cell transfer (ACT) and earlier experiences with high-dose IL-2. The proximal mediators of these immune therapies are tumor-reactive CTL. Various mechanisms of resistance to immune-mediated apoptotic signals have been described, including phenotypic changes, effector cell exhaustion, functional tolerance, deficiencies in Ag processing and presentation, and mutation or down-regulation of antigenic epitopes...
2016: American Journal of Cancer Research
https://www.readbyqxmd.com/read/27816393/association-of-pd-1-pd-l1-and-ctla-4-gene-expression-and-clinicopathologic-characteristics-in-patients-with-non-small-cell-lung-cancer
#18
Aránzazu Lafuente-Sanchis, Ángel Zúñiga, Miriam Estors, Néstor J Martínez-Hernández, Antonio Cremades, María Cuenca, José M Galbis
INTRODUCTION: Recent studies show a potential benefit of therapies that target programmed death receptor 1 (PD-1)/programmed death-ligand 1 (PD-L1) and cytotoxic T-lymphocyte antigen 4 (CTLA-4) inhibitory checkpoints in a subgroup of patients with non-small-cell lung cancer (NSCLC), without the clinicopathologic characteristics related to positive responses to these treatments being well determined. The aim of this study was to determine PD-1, PD-L1, and CTLA-4 gene expression at the mRNA level in tumoral tissue from patients with NSCLC and analyze their possible relationship with the clinicopathological characteristics and their potential prognostic role...
October 17, 2016: Clinical Lung Cancer
https://www.readbyqxmd.com/read/27816392/assessing-pdl-1-and-pd-1-in-non-small-cell-lung-cancer-a-novel-immunoscore-approach
#19
Erna-Elise Paulsen, Thomas K Kilvaer, Mehrdad Rakaee Khanehkenari, Samer Al-Saad, Sigurd M Hald, Sigve Andersen, Elin Richardsen, Nora Ness, Lill-Tove Busund, Roy M Bremnes, Tom Donnem
INTRODUCTION: Immune checkpoint inhibitors targeting programmed cell death protein 1 (PD-1) or its ligand, PD-L1, have gained momentum in the treatment of non-small cell lung cancer (NSCLC). However, their prognostic significance remains controversial. The present study evaluated the expression of PD-L1 and PD-1 and their potential role in an Immunoscore, supplementing the TNM classification of NSCLC. MATERIALS AND METHODS: Tissue microarrays constructed from tumor tissue samples from 2 cohorts of a total of 536 patients (University Hospital of North Norway, n = 285; Nordland Hospital, n = 251) with primary resected stage I to IIIA NSCLC...
October 5, 2016: Clinical Lung Cancer
https://www.readbyqxmd.com/read/27801735/fading-with-time-of-pd-l1-immunoreactivity-in-non-small-cells-lung-cancer-tissues-a-methodological-study
#20
Francesca Giunchi, Alessio Degiovanni, Niccolò Daddi, Rocco Trisolini, Andrea Dell'Amore, Claudio Agostinelli, Andrea Ardizzoni, Michelangelo Fiorentino
Blockade of inhibitory immune checkpoints is currently arising as a potential immunologic option for tumor therapy. Inhibition of programmed cell death protein 1 and/or its specific ligand programmed death-ligand 1 (PD-L1) was effective in clinical trials in advanced melanoma, non-small cell lung cancer (NSCLC) bladder and kidney cancer. The predictive role of the immunohistochemical (IHC) expression of PD-L1 is highly debated. Different reagents, clones, cutoffs of cell expression and subjective interpretation of PD-L1 immunoreactivity in epithelial cells and lymphocytes are the main issue...
October 31, 2016: Applied Immunohistochemistry & Molecular Morphology: AIMM
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