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https://www.readbyqxmd.com/read/27909722/expression-of-soluble-programmed-death-1-protein-in-peripheral-blood-regulatory-t-cells-and-its-effects-on-rheumatoid-arthritis-progression
#1
Chun-Feng Ren, Ya-Xin Zhao, Chun-Feng Hou, Luan Luan, Guo-Qing Duan, Shu-Jie Li, Jian-Hong Zhao
The present study aimed to investigate the role of the soluble programmed death‑1 (sPD-1) protein, which is released by peripheral blood regulatory T cells (Treg) during the progression of rheumatoid arthritis (RA). From October 2012 to May 2014, 82 RA patients (RA group) and 90 healthy volunteers (healthy controls; HC) were recruited. Cluster of differentiation (CD)4, CD25 and forkhead/winged helix transcription factor p3 (Foxp3) and expression of cytotoxic T lymphocyte associated antigen 4 (CTLA-4) and Foxp3 were detected by flow cytometry...
November 28, 2016: Molecular Medicine Reports
https://www.readbyqxmd.com/read/27908252/the-combination-of-new-immunotherapy-and-radiotherapy-a-new-potential-treatment-for-locally-advanced-non-small-cell-lung-cancer
#2
Paola Claudia Sacco, Paolo Maione, Cesare Guida, Cesare Gridelli
Lung cancer is the main reason of cancer death worldwide. About 30% of non-small-cell lung cancer (NSCLC) cases are diagnosed with locally advanced disease (stage III). This is a mixed population including patients who have far more extensive and bulky disease than others. Management of these patients continue to be a challenge; frequently, patients have both local recurrence and distant metastases in this stage and the prognosis is very poor with a 5-year overall survival estimated between 3% and 7% for inoperable disease...
December 1, 2016: Current Clinical Pharmacology
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
#3
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/27903604/what-does-pd-l1-positive-or-negative-mean
#4
Antoni Ribas, Siwen Hu-Lieskovan
Expression of the programmed death-1 (PD-1) ligand 1 (PD-L1) is used to select patients and analyze responses to anti-PD-1/L1 antibodies. The expression of PD-L1 is regulated in different ways, which leads to a different significance of its presence or absence. PD-L1 positivity may be a result of genetic events leading to constitutive PD-L1 expression on cancer cells or inducible PD-L1 expression on cancer cells and noncancer cells in response to a T cell infiltrate. A tumor may be PD-L1 negative because it has no T cell infiltrate, which may be reversed with an immune response...
November 30, 2016: Journal of Experimental Medicine
https://www.readbyqxmd.com/read/27903500/primary-resistance-to-pd-1-blockade-mediated-by-jak%C3%A2-mutations
#5
Daniel Sanghoon Shin, Jesse M Zaretsky, Helena Escuin-Ordinas, Angel Garcia-Diaz, Siwen Hu-Lieskovan, Anusha Kalbasi, Catherine S Grasso, Willy Hugo, Salemiz Sandoval, Davis Y Torrejon, Nicolaos Palaskas, Gabriel Abril Rodriguez, Giulia Parisi, Ariel Azhdam, Bartosz Chmielowski, Grace Cherry, Elizabeth Seja, Beata Berent-Maoz, I Peter Shintaku, Dung Thi Le, Drew M Pardoll, Luis A Diaz, Paul C Tumeh, Thomas G Graeber, Roger S Lo, Begoña Comin-Anduix, Antoni Ribas
Loss of function mutations in JAK½ can lead to acquired resistance to anti-programmed death protein 1 (PD-1) therapy. We reasoned they may also be involved in primary resistance to anti-PD-1 therapy. JAK½ inactivating mutations were noted in tumor biopsies of 1 of 23 patients with melanoma and in 1 of 16 patients with mismatch repair deficient colon cancer treated with PD-1 blockade. Both cases had a high mutational load but did not respond to anti-PD-1 therapy. Two out of 48 human melanoma cell lines had JAK½ mutations, which led to lack of PD-L1 expression upon interferon gamma exposure mediated by inability to signal through the interferon gamma receptor pathway...
November 30, 2016: Cancer Discovery
https://www.readbyqxmd.com/read/27900506/arabidopsis-thaliana-methionine-sulfoxide-reductase-b8-influences-stress-induced-cell-death-and-effector-triggered-immunity
#6
Shweta Roy, Ashis Kumar Nandi
Reactive oxygen species (ROS) oxidize methionine to methionine sulfoxide (MetSO) and thereby inactivate proteins. Methionine sulfoxide reductase (MSR) enzyme converts MetSO back to the reduced form and thereby detoxifies the effect of ROS. Our results show that Arabidopsis thaliana MSR enzyme coding gene MSRB8 is required for effector-triggered immunity and containment of stress-induced cell death in Arabidopsis. Plants activate pattern-triggered immunity (PTI), a basal defense, upon recognition of evolutionary conserved molecular patterns present in the pathogens...
November 29, 2016: Plant Molecular Biology
https://www.readbyqxmd.com/read/27896216/recent-advances-in-immunotherapy-in-metastatic-nsclc
#7
REVIEW
Pranshu Bansal, Diaa Osman, Gregory N Gan, George R Simon, Yanis Boumber
Non-small cell lung cancer (NSCLC) is one of most common malignancies and the leading cause of cancer deaths worldwide. Despite advances in targeted therapies, majority of NSCLC patients do not have targetable genomic alterations. Nevertheless, recent discovery that NSCLC is an immunogenic tumor type, and several breakthroughs in immunotherapies have led to rapid expansion of this new treatment modality in NSCLC with recent FDA approvals of programed death receptor-1 inhibitors, such as nivolumab and pembrolizumab...
2016: Frontiers in Oncology
https://www.readbyqxmd.com/read/27895920/pd1-pd-l1-inhibition-as-a-potential-radiosensitizer-in-head-and-neck-squamous-cell-carcinoma-a-case-report
#8
Misako Nagasaka, Mark Zaki, Harold Kim, S Naweed Raza, George Yoo, Ho-Sheng Lin, Ammar Sukari
BACKGROUND: Immunotherapy targeting the checkpoint PD1 (programmed cell death protein 1) or PDL1 (programmed death ligand 1) has led to advances in the treatment of melanoma and non-small cell lung cancer (NSCLC). The use of such therapies has also been introduced into the treatment of other malignancies, including head and neck cancer. The combined effects of checkpoint inhibitors and anti-PD1(L1) antibodies and radiation therapy have not yet been sufficiently investigated. CASE PRESENTATION: We report a case of locally relapsed non-resectable oral cavity squamous cell carcinoma, with excellent local control after pembrolizumab (MK3475) followed by radiotherapy...
2016: Journal for Immunotherapy of Cancer
https://www.readbyqxmd.com/read/27895178/conserved-region-c-functions-to-regulate-pd-1-expression-and-subsequent-cd8-t-cell-memory
#9
Alexander P R Bally, Yan Tang, Joshua T Lee, Benjamin G Barwick, Ryan Martinez, Brian D Evavold, Jeremy M Boss
Expression of programmed death 1 (PD-1) on CD8 T cells promotes T cell exhaustion during chronic Ag exposure. During acute infections, PD-1 is transiently expressed and has the potential to modulate CD8 T cell memory formation. Conserved region C (CR-C), a promoter proximal cis-regulatory element that is critical to PD-1 expression in vitro, responds to NFATc1, FoxO1, and/or NF-κB signaling pathways. Here, a CR-C knockout mouse was established to determine its role on PD-1 expression and the corresponding effects on T cell function in vivo...
November 28, 2016: Journal of Immunology: Official Journal of the American Association of Immunologists
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
#10
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/27891189/variations-in-dna-methylation-of-interferon-gamma-and-programmed-death-1-in-allograft-rejection-after-kidney-transplantation
#11
Karin Boer, L Elly A de Wit, Fleur S Peters, Dennis A Hesselink, Leo J Hofland, Michiel G H Betjes, Caspar W N Looman, Carla C Baan
BACKGROUND: The role of DNA methylation in the regulation of the anti-donor-directed immune response after organ transplantation is unknown. Here, we studied the methylation of two mediators of the immune response: the pro-inflammatory cytokine interferon γ (IFNγ) and the inhibitory receptor programmed death 1 (PD1) in naïve and memory CD8+ T cell subsets in kidney transplant recipients receiving immunosuppressive medication. Both recipients experiencing an episode of acute allograft rejection (rejectors) as well as recipients without rejection (non-rejectors) were included...
2016: Clinical Epigenetics
https://www.readbyqxmd.com/read/27884973/the-emerging-role-of-immune-checkpoint-inhibition-in-malignant-lymphoma
#12
Ida Hude, Stephanie Sasse, Andreas Engert, Paul J Bröckelmann
To evade elimination by the host immune system, tumor cells commonly exploit physiological immune checkpoint pathways, restraining efficient anti-tumor immune cell function. Growing understanding of the complex dialog between tumor cells and their microenvironment contributed to the development of immune checkpoint inhibitors. This innovative strategy has demonstrated paradigm-shifting clinical activity in various malignancies. Antibodies targeting programmed death 1 and cytotoxic T-lymphocyte-associated protein-4 are also being investigated in lymphoid malignancies with varying levels of activity and a favorable toxicity profile...
November 24, 2016: Haematologica
https://www.readbyqxmd.com/read/27879975/metastatic-merkel-cell-carcinoma-response-to-nivolumab
#13
Frances M Walocko, Benjamin Y Scheier, Paul W Harms, Leslie A Fecher, Christopher D Lao
BACKGROUND: Merkel cell carcinoma (MCC) is an aggressive cutaneous neuroendocrine malignancy with limited treatment options. Several lines of evidence support the programmed death-1/programmed death-ligand 1 (PD-1/PD-L1) axis as a likely contributor to immune evasion in MCC. CASE PRESENTATION: We report a case of a patient with metastatic MCC with a significant and durable response to nivolumab, a humanized IgG4 monoclonal anti-PD-1 antibody. CONCLUSION: Immunotherapy with PD-1/PD-L1 inhibitors has become a rational and promising treatment option for MCC in the advanced or metastatic disease...
2016: Journal for Immunotherapy of Cancer
https://www.readbyqxmd.com/read/27879974/nivolumab-dose-selection-challenges-opportunities-and-lessons-learned-for-cancer-immunotherapy
#14
Shruti Agrawal, Yan Feng, Amit Roy, Georgia Kollia, Brian Lestini
BACKGROUND: Immuno-oncology (I-O) therapies target the host immune system, providing the potential to choose a uniform dose and schedule across tumor types. However, dose selection for I-O agents usually occurs early in clinical development and is typically based on tumor response, which may not fully represent the potential for improved overall survival. Here, we describe an integrated approach which incorporates clinical safety and efficacy data with data obtained from analyses of dose-/exposure-response (D-R/E-R) relationships, used to select a monotherapy dose for nivolumab, a programmed death-1 inhibitor, in clinical studies of different tumor types...
2016: Journal for Immunotherapy of Cancer
https://www.readbyqxmd.com/read/27879972/responses-of-metastatic-basal-cell-and-cutaneous-squamous-cell-carcinomas-to-anti-pd1-monoclonal-antibody-regn2810
#15
Gerald S Falchook, Rom Leidner, Elizabeth Stankevich, Brian Piening, Carlo Bifulco, Israel Lowy, Matthew G Fury
BACKGROUND: Basal cell carcinoma (BCC) and cutaneous squamous cell carcinoma (CSCC) share exposure to UV light as the dominant risk factor, and these tumors therefore harbor high mutation burdens. In other malignancies, high mutation burden has been associated with clinical benefit from therapy with antibodies directed against the Programmed Death 1 (PD-1) immune checkpoint receptor. Highly mutated tumors are more likely to express immunogenic tumor neoantigens that attract effector T cells, which can be unleashed by blockade of the PD-1 immune checkpoint...
2016: Journal for Immunotherapy of Cancer
https://www.readbyqxmd.com/read/27876011/nivolumab-associated-acute-glomerulonephritis-a-case-report-and-literature-review
#16
Kyungsuk Jung, Xu Zeng, Marijo Bilusic
BACKGROUND: Immune checkpoint inhibitors are changing the landscape of oncology treatment as they are significantly improving treatment for multiple malignancies. Nivolumab, an anti-programmed death 1 antibody, is a US Food and Drug Administration-approved treatment for melanoma, non-small cell lung cancer, and kidney cancer but can result in a spectrum of autoimmune side effects. Adverse effects can occur within any organ system in the body including the colon, lung, liver, endocrine systems, or kidneys...
November 22, 2016: BMC Nephrology
https://www.readbyqxmd.com/read/27873079/next-generation-predictive-biomarkers-for-immune-checkpoint-inhibition
#17
Yulian Khagi, Razelle Kurzrock, Sandip Pravin Patel
With the advent of targeted therapies, there has been a revolution in the treatment of cancer across multiple histologies. Immune checkpoint blockade has made it possible to take advantage of receptor-ligand interactions between immune and tumor cells in a wide spectrum of malignancies. Toxicity in healthy tissue, however, can limit our use of these agents. Immune checkpoint blockade has been approved in advanced melanoma, renal cell cancer, non-small cell lung cancer, relapsed refractory Hodgkin's lymphoma, and urothelial cancer...
November 21, 2016: Cancer Metastasis Reviews
https://www.readbyqxmd.com/read/27870733/cutaneous-metastatic-melanoma-resembling-a-halo-nevus-in-the-setting-of-pd-1-inhibition
#18
Nathan Tobias Harvey, Michael Millward, Kirstie Macgregor, Robert Paul Bucat, Benjamin Andrew Wood
Malignant melanoma is a common source of cutaneous metastases and can occasionally adopt a histological appearance which mimics a primary melanocytic lesion, either benign or malignant. The authors describe a case of new cutaneous deposits of metastatic melanoma in a 70-year-old woman with a prominent admixed lymphocytic infiltrate, imparting a striking resemblance to a halo nevus. The authors believe this appearance was a direct reflection of treatment with pembrolizumab, a humanized antibody against the immune checkpoint inhibitor programmed death-1...
December 2016: American Journal of Dermatopathology
https://www.readbyqxmd.com/read/27867382/il-1%C3%AE-but-not-programed-death-1-and-programed-death-ligand-pathway-is-critical-for-the-human-th17-response-to-mycobacterium-tuberculosis
#19
Emmanuel Stephen-Victor, Varun Kumar Sharma, Mrinmoy Das, Anupama Karnam, Chaitrali Saha, Maxime Lecerf, Caroline Galeotti, Srinivas V Kaveri, Jagadeesh Bayry
The programed death-1 (PD-1)-programed death ligand-1 (PD-L1) and PD-L2 co-inhibitory pathway has been implicated in the evasion strategies of Mycobacterium tuberculosis. Specifically, M. tuberculosis-induced PD-L1 orchestrates expansion of regulatory T cells and suppression of Th1 response. However, the role of PD pathway in regulating Th17 response to M. tuberculosis has not been investigated. In the present report, we demonstrate that M. tuberculosis and M. tuberculosis-derived antigen fractions have differential abilities to mediate human monocyte- and dendritic cell (DC)-mediated Th17 response and were independent of expression of PD-L1 or PD-L2 on aforementioned antigen-presenting cells...
2016: Frontiers in Immunology
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
#20
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
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