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Anti pd1

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https://www.readbyqxmd.com/read/29149031/anti-inflammatory-and-antinociceptive-effects-of-ethyl-acetate-fraction-of-an-edible-red-macroalgae-sarcodia-ceylanica
#1
Chieh-Chih Shih, Hwong-Ru Hwang, Chi-I Chang, Huei-Meei Su, Pei-Chin Chen, Hsiao-Mei Kuo, Pei-Jyuan Li, Hui-Min David Wang, Kuan-Hao Tsui, Yu-Chi Lin, Shi-Ying Huang, Zhi-Hong Wen
Research so far has only shown that edible red macroalgae, Sarcodia ceylanica has the ability to eliminate free radicals and anti-diabetic, anti-bacterial properties. This study was conducted both in vitro and in vivo on the ethyl acetate extract (PD1) of farmed red macroalgae in order to explore its anti-inflammatory properties. In order to study the in vitro anti-inflammatory effects of PD1, we used lipopolysaccharide (LPS) to induce inflammatory responses in murine macrophages. For evaluating the potential in vivo anti-inflammatory and antinociceptive effects of PD1, we used carrageenan-induced rat paw edema to produce inflammatory pain...
November 17, 2017: International Journal of Molecular Sciences
https://www.readbyqxmd.com/read/29134678/systemic-immune-checkpoint-blockade-with-anti-pd1-antibodies-does-not-alter-cerebral-amyloid-%C3%AE-burden-in-several-amyloid-transgenic-mouse-models
#2
Martine Latta-Mahieu, Bradford Elmer, Alexis Bretteville, Yaming Wang, Mati Lopez-Grancha, Philippe Goniot, Nicolas Moindrot, Paul Ferrari, Véronique Blanc, Nathalie Schussler, Emmanuel Brault, Valérie Roudières, Véronique Blanchard, Zhi-Yong Yang, Pascal Barneoud, Philippe Bertrand, Bart Roucourt, Sofie Carmans, Astrid Bottelbergs, Liesbeth Mertens, Cindy Wintmolders, Peter Larsen, Caroline Hersley, Tyler McGathey, Margaret M Racke, Ling Liu, Jirong Lu, Michael J O'Neill, David R Riddell, Andreas Ebneth, Gary J Nabel, Laurent Pradier
Chronic inflammation represents a central component in the pathogenesis of Alzheimer's disease (AD). Recent work suggests that breaking immune tolerance by Programmed cell Death-1 (PD1) checkpoint inhibition produces an IFN-γ-dependent systemic immune response, with infiltration of the brain by peripheral myeloid cells and neuropathological as well as functional improvements even in mice with advanced amyloid pathology (Baruch et al., (): Nature Medicine, 22:135-137). Immune checkpoint inhibition was therefore suggested as potential treatment for neurodegenerative disorders when activation of the immune system is appropriate...
November 14, 2017: Glia
https://www.readbyqxmd.com/read/29130342/nivolumab-in-recurrent-metastatic-head-and-neck-cancers
#3
Andy Karabajakian, Thibaut Reverdy, Max Gau, Jérôme Fayette
Head and neck cancer is an immunosuppressive disease, with a high proportion expressing PD-L1. Until recently, options were lacking in second line. Prognosis is poor especially for patients who progress during chemotherapy with survival often inferior to 6 months. Nivolumab is the only anti-PD1 agent to prolong survival in the second-line setting and is now the standard option since the CheckMate-141 trial. Treatment is generally well tolerated, patients seem to have a better quality of life when compared with chemotherapy...
November 13, 2017: Future Oncology
https://www.readbyqxmd.com/read/29126088/in-the-immuno-oncology-era-is-anti-pd-1-or-anti-pd-l1-immunotherapy-modifying-the-sensitivity-to-conventional-cancer-therapies
#4
Sandrine Aspeslagh, Margarida Matias, Virginia Palomar, Laurent Dercle, Emilie Lanoy, Jean-Charles Soria, Sophie Postel-Vinay
INTRODUCTION: The advent of anti-programmed death receptor-1/ligand-1 antibodies (anti-PD(L)1) is profoundly changing the therapeutic strategy of oncology. As anti-PD(L)1 modulate tumour microenvironment, it might impact sensitivity to conventional cancer therapy (CCT). Therefore, we explored whether sensitivity to CCT was different before and after anti-PD(L)1 therapy. METHODS: Patients who started anti-PD(L)1 treatment at Gustave Roussy Cancer Centre between February 2012 and December 2015, and who received at least one line of CCT immediately before and immediately after anti-PD(L)1, were eligible...
November 7, 2017: European Journal of Cancer
https://www.readbyqxmd.com/read/29116432/seom-clinical-guideline-for-the-management-of-malignant-melanoma-2017
#5
A Berrocal, A Arance, V E Castellon, L de la Cruz, E Espinosa, M G Cao, J L G Larriba, I Márquez-Rodas, A Soria, S M Algarra
All melanoma suspected patients must be confirmed histologically and resected. Sentinel node biopsy must be done when tumor is over 1 mm or if less with high-risk factors. Adjuvant therapy with interferon could be offered for patients with high-risk melanoma and in selected cases radiotherapy can be added. Metastatic melanoma treatment is guided by mutational BRAF status. BRAF wild type patients must receive anti-PD1 containing therapy and BRAF mutated patients BRAF/MEK inhibitors or anti-PD1 containing therapy...
November 7, 2017: Clinical & Translational Oncology
https://www.readbyqxmd.com/read/29114543/molecular-mechanisms-of-programmed-cell-death-1-dependent-t-cell-suppression-relevance-for-immunotherapy
#6
REVIEW
Miren Zuazo, Maria Gato-Cañas, Noelia Llorente, María Ibañez-Vea, Hugo Arasanz, Grazyna Kochan, David Escors
Programmed cell death-1 (PD1) has become a significant target for cancer immunotherapy. PD1 and its receptor programmed cell death 1 ligand 1 (PDL1) are key regulatory physiological immune checkpoints that maintain self-tolerance in the organism by regulating the degree of activation of T and B cells amongst other immune cell types. However, cancer cells take advantage of these immunosuppressive regulatory mechanisms to escape T and B cell-mediated immunity. PD1 engagement on T cells by PDL1 on the surface of cancer cells dramatically interferes with T cell activation and the acquisition of effector capacities...
October 2017: Annals of Translational Medicine
https://www.readbyqxmd.com/read/29097495/ebv-associated-primary-nodal-t-nk-cell-lymphoma-shows-distinct-molecular-signature-and-copy-number-changes
#7
Siok-Bian Ng, Tae-Hoon Chung, Seiichi Kato, Shigeo Nakamura, Emiko Takahashi, Young-Hyeh Ko, Joseph D Khoury, C Cameron Yin, Richie Soong, Anand D Jeyasekharan, Michal Marek Hoppe, Viknesvaran Selvarajan, Soo-Yong Tan, Soon-Thye Lim, Choon-Kiat Ong, Maarja-Liisa Nairismägi, Priyanka Maheshwari, Shoa-Nian Choo, Shuangyi Fan, Chi-Kuen Lee, Shih-Sung Chuang, Wee-Joo Chng
The molecular biology of primary nodal T- and NK-cell lymphoma and its relationsihp with extranodal NK/T-cell lymphoma, nasal type is poorly understood. In this study, we assessed the relationship between nodal and extranodal EBV-positive T/NK-cell lymphomas using gene expression profiling and copy number aberration analyses. We performed GEP and CNA analysis on 66 cases of EBV-associated T/NK-cell lymphoma from nodal and extranodal sites, and correlated the molecular signatures with clinicopathologic features...
November 2, 2017: Haematologica
https://www.readbyqxmd.com/read/29096940/anti-pd1-pdl1-induced-psoriasis
#8
Dimitra Voudouri, Vasiliki Nikolaou, Konstantinos Laschos, Andriani Charpidou, Nikolaos Soupos, Ioanna Triantafyllopoulou, Ioanna Panoutsopoulou, Gerasimos Aravantinos, K Syrigos, A Stratigos
BACKGROUND: Immune checkpoint inhibitors are novel agents approved for the treatment of late-stage malignancies. Despite its important clinical benefits, checkpoint inhibition is associated with a unique spectrum of side effects known as immune-related adverse events. Skin toxicities are the most frequent immune-related adverse events during anti-PD1 blockade therapies. Among them, rare cases of psoriasis exacerbation have been reported. METHODS: We present the clinical characteristics of exacerbated psoriasis in 5 patients under anti-PD1/PDL1 therapy...
October 18, 2017: Current Problems in Cancer
https://www.readbyqxmd.com/read/29089645/identification-and-characterization-of-hla-a24-specific-xbp1-cd138-syndecan-1-and-cs1-slamf7-peptides-inducing-antigens-specific-memory-cytotoxic-t-lymphocytes-targeting-multiple-myeloma
#9
J Bae, T Hideshima, G L Zhang, J Zhou, D B Keskin, N C Munshi, K C Anderson
XBP1 (X-box binding protein 1), CD138 (Syndecan-1), and CS1 (SLAMF7) are highly expressed antigens in cancers including multiple myeloma (MM). Here we identify and characterize immunogenic HLA-A24 peptides derived from these antigens for potential vaccination therapy of HLA-A24+ patients with MM. The identified immunogenic HLA-A24-specific XBP1 unspliced (UN)185-193 (I S P W I L A V L), XBP1 spliced (SP)223-231 (V Y P E G P S S L), CD138265-273 (I F A V C L V G F) and CS1240-248 (L F V L G L F L W) peptides induced antigen-specific CTL with anti-MM activity in an HLA-A24 restricted manner...
November 1, 2017: Leukemia: Official Journal of the Leukemia Society of America, Leukemia Research Fund, U.K
https://www.readbyqxmd.com/read/29082853/cancer-gene-profiling-in-non-small-cell-lung-cancers-reveals-activating-mutations-in-jak2-and-jak3-with-therapeutic-implications
#10
Shuyu D Li, Meng Ma, Hui Li, Aneta Waluszko, Tatyana Sidorenko, Eric E Schadt, David Y Zhang, Rong Chen, Fei Ye
BACKGROUND: Next-generation sequencing (NGS) of cancer gene panels are widely applied to enable personalized cancer therapy and to identify novel oncogenic mutations. METHODS: We performed targeted NGS on 932 clinical cases of non-small-cell lung cancers (NSCLCs) using the Ion AmpliSeq™ Cancer Hotspot panel v2 assay. RESULTS: Actionable mutations were identified in 65% of the cases with available targeted therapeutic options, including 26% of the patients with mutations in National Comprehensive Cancer Network (NCCN) guideline genes...
October 30, 2017: Genome Medicine
https://www.readbyqxmd.com/read/29081991/severe-steroid-resistant-anti-pd1-t-cell-checkpoint-inhibitor-induced-hepatotoxicity-driven-by-biliary-injury
#11
Gary Joseph Doherty, Adam M Duckworth, Susan E Davies, George F Mells, Rebecca Brais, Susan V Harden, Christine A Parkinson, Pippa G Corrie
INTRODUCTION: Hepatotoxicity from T-cell checkpoint blockade is an increasingly common immune-related adverse event, but remains poorly characterised and can be challenging to manage. Such toxicity is generally considered to resemble autoimmune hepatitis, although this assumption is extrapolated from limited clinicopathological reports of anti-cytotoxic T-lymphocyte-associated protein 4-induced hepatotoxicity. METHODS: Here we report, with full clinicopathological correlation, three cases of T-cell checkpoint inhibitor-induced hepatotoxicity associated with anti-programmed cell death protein 1 agents...
2017: ESMO Open
https://www.readbyqxmd.com/read/29077601/live-threatening-autoimmune-cardiomyopathy-reproducibly-induced-in-a-patient-by-checkpoint-inhibitor-therapy
#12
Azadeh Tajmir-Riahi, Tanja Bergmann, Michael Schmid, Abbas Agaimy, Gerold Schuler, Lucie Heinzerling
Checkpoint inhibitors induce a plethora of immune-related adverse events (irAEs) including autoimmune colitis, hepatitis, endocrinopathies, and rarer side effects like neuritis. Here, a case of autoimmune cardiomyopathy (grade 3 CTCAE) and myocarditis under combination therapy with nivolumab plus ipilimumab in a 72-year-old melanoma patient is reported. Treatment induced a partial response for 14 months. However, after 10 infusions the patient developed dyspnea, edema of the legs, ascites and a weight gain of 10 kg because of a decompensated heart insufficiency with a reduced ejection fraction from formerly 48%-50% to 15%...
October 26, 2017: Journal of Immunotherapy
https://www.readbyqxmd.com/read/29074426/survival-of-the-fittest-cancer-challenges-t-cell-metabolism
#13
Davide G Franchina, Feng He, Dirk Brenner
T cells represent the major contributors to antitumor-specific immunity among the tumor-infiltrating lymphocytes. However, tumors acquire ways to evade immunosurveillance and anti-tumor responses are too weak to eradicate the disease. T cells are often functionally impaired as a result of interaction with, or signals from, transformed cells and the tumor microenvironment, including stromal cells. Among these, nutrients use and consumption is critically important for the control of differentiation and effector mechanisms of T cells...
October 24, 2017: Cancer Letters
https://www.readbyqxmd.com/read/29070816/resistance-to-checkpoint-blockade-therapy-through-inactivation-of-antigen-presentation
#14
Moshe Sade-Feldman, Yunxin J Jiao, Jonathan H Chen, Michael S Rooney, Michal Barzily-Rokni, Jean-Pierre Eliane, Stacey L Bjorgaard, Marc R Hammond, Hans Vitzthum, Shauna M Blackmon, Dennie T Frederick, Mehlika Hazar-Rethinam, Brandon A Nadres, Emily E Van Seventer, Sachet A Shukla, Keren Yizhak, John P Ray, Daniel Rosebrock, Dimitri Livitz, Viktor Adalsteinsson, Gad Getz, Lyn M Duncan, Bo Li, Ryan B Corcoran, Donald P Lawrence, Anat Stemmer-Rachamimov, Genevieve M Boland, Dan A Landau, Keith T Flaherty, Ryan J Sullivan, Nir Hacohen
Treatment with immune checkpoint blockade (CPB) therapies often leads to prolonged responses in patients with metastatic melanoma, but the common mechanisms of primary and acquired resistance to these agents remain incompletely characterized and have yet to be validated in large cohorts. By analyzing longitudinal tumor biopsies from 17 metastatic melanoma patients treated with CPB therapies, we observed point mutations, deletions or loss of heterozygosity (LOH) in beta-2-microglobulin (B2M), an essential component of MHC class I antigen presentation, in 29...
October 26, 2017: Nature Communications
https://www.readbyqxmd.com/read/29069958/pd-l1-immunohistochemistry-for-non-small-cell-lung-carcinoma-which-strategy-should-be-adopted
#15
Paul Hofman
PD-L1 detection with immunohistochemistry (IHC) is the only predictive biomarker available to date for PD-L1/PD1 immunotherapy in thoracic oncology. While many studies have been published on this biomarker, they raise a number of questions concerning mainly, i) the type of antibody for use and its condition of utilization, ii) the threshold to be used, iii) the message and information to communicate to the thoracic oncologist and, iv) the adoption of this methodology as part of the daily practices of a pathology laboratory...
October 26, 2017: Expert Review of Molecular Diagnostics
https://www.readbyqxmd.com/read/29069740/blockage-of-foxp3-transcription-factor-dimerization-and-foxp3-aml1-interaction-inhibits-t-regulatory-cell-activity-sequence-optimization-of-a-peptide-inhibitor
#16
Teresa Lozano, Marta Gorraiz, Aritz Lasarte-Cía, Marta Ruiz, Obdulia Rabal, Julen Oyarzabal, Sandra Hervás-Stubbs, Diana Llopiz, Pablo Sarobe, Jesús Prieto, Noelia Casares, Juan José Lasarte
Although T regulatory cells (Treg) are essential for the prevention of autoimmune diseases, their immunoregulatory function restrains the induction of immune responses against cancer. Thus, development of inhibitors of FOXP3, a key transcription factor for the immunosuppressive activity of Treg, might give new therapeutic opportunities. In a previous work we identified a peptide (named P60) able to enter into the cells, bind to FOXP3, and impair Treg activity in vitro and in vivo. Here we show that P60 binds to the intermediate region of FOXP3 and inhibits its homodimerization as well as its interaction with the transcription factor AML1...
September 22, 2017: Oncotarget
https://www.readbyqxmd.com/read/29061560/bitter-melon-prevents-the-development-of-4-nqo-induced-oral-squamous-cell-carcinoma-in-an-immunocompetent-mouse-model-by-modulating-immune-signalling
#17
Ratna B Ray, Subhayan Sur, Robert Steele, Rajeev Aurora, Mark Vavares, Katherine E Schwetye
Head and neck squamous cell carcinoma (HNSCC) is the sixth most common cancer worldwide, and tobacco is one of the most common factors for HNSCC of the oral cavity. We have previously observed that bitter melon (Momordica charantia) extract (BME) exerts anti-proliferative activity against several cancers including HNSCC. In this study, we investigated the preventive role of BME in 4-nitroquinoline 1-oxide (4-NQO) carcinogen-induced HNSCC. We observed that BME feeding significantly reduced the incidence of 4-NQO induced oral cancer in a mouse model...
October 23, 2017: Cancer Prevention Research
https://www.readbyqxmd.com/read/29059149/targeting-immunosuppressive-adenosine-in-cancer
#18
REVIEW
Dipti Vijayan, Arabella Young, Michele W L Teng, Mark J Smyth
Despite the success of anti-programmed cell death protein 1 (PD1), anti-PD1 ligand 1 (PDL1) and anti-cytotoxic T lymphocyte antigen 4 (CTLA4) therapies in advanced cancer, a considerable proportion of patients remain unresponsive to these treatments (known as innate resistance). In addition, one-third of patients relapse after initial response (known as adaptive resistance), which suggests that multiple non-redundant immunosuppressive mechanisms coexist within the tumour microenvironment. A major immunosuppressive mechanism is the adenosinergic pathway, which now represents an attractive new therapeutic target for cancer therapy...
October 23, 2017: Nature Reviews. Cancer
https://www.readbyqxmd.com/read/29045547/safety-of-resuming-anti-pd-1-in-patients-with-immune-related-adverse-events-iraes-during-combined-anti-ctla-4-and-anti-pd1-in-metastatic-melanoma
#19
M H Pollack, A Betof, H Dearden, K Rapazzo, I Valentine, A S Brohl, K K Ancell, G V Long, A M Menzies, Z Eroglu, D B Johnson, A N Shoushtari
Background: Combined CTLA-4 and PD-1 blockade induces high rates of immune-related adverse events (irAEs). The safety of resuming anti-PD-1 in patients who discontinue combination therapy due to irAEs is not known. Patients and Methods: We assessed patients who experienced clinically significant irAEs from combined CTLA-4 and PD-1 blockade leading to treatment discontinuation at four academic centers. We assessed the safety of resuming anti-PD-1 in terms of recurrent and distinct irAEs...
October 11, 2017: Annals of Oncology: Official Journal of the European Society for Medical Oncology
https://www.readbyqxmd.com/read/29045514/exploratory-analysis-of-the-association-of-depth-of-response-and-survival-in-patients-with-metastatic-non-small-cell-lung-cancer-treated-with-a-targeted-therapy-or-immunotherapy
#20
C E McCoach, G M Blumenthal, L Zhang, A Myers, S Tang, R Sridhara, P Keegan, R Pazdur, R C Doebele, D Kazandjian
Background: Response Evaluation Criteria in Solid Tumors (RECIST) permits rapid evaluation of new therapeutic strategies in cancer. However, RECIST does not capture the heterogeneity of response in highly active therapies. Depth of tumor response may provide a more granular view of response. We explored the association between, depth of response (DepOR), with overall survival (OS) and progression-free survival (PFS) for patients with NSCLC being treated with an ALK inhibitor (ALKi) or an anti-PD-1 antibody (Ab)...
November 1, 2017: Annals of Oncology: Official Journal of the European Society for Medical Oncology
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