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https://www.readbyqxmd.com/read/28818609/multicenter-comparison-of-22c3-pharmdx-agilent-and-sp263-ventana-assays-to-test-pd-l1-expression-for-nsclc-patients-to-be-treated-with-immune-checkpoint-inhibitors
#1
Antonio Marchetti, Massimo Barberis, Renato Franco, Graziano De Luca, Maria Vittoria Pace, Stefania Staibano, Marco Volante, Fiamma Buttitta, Elena Guerini-Rocco, Luisella Righi, Tommaso D'antuono, Giorgio V Scagliotti, Carmine Pinto, Gaetano De Rosa, Mauro Papotti
INTRODUCTION: Among the several agents targeting the programmed cell death 1 (PD-1) pathway, pembrolizumab is currently the only one approved for the treatment of non-small cell lung cancer patients in association with a companion diagnostic assay, the anti-programmed cell death ligand 1 (PD-L1) immunohistochemical (IHC) 22C3 PharmDx (Agilent) using the Dako Autostainer. However, the Dako platform is not present in each pathology department and this technical limitation is a major problem for the diffusion of the PD-L1 IHC predictive test for pembrolizumab...
August 14, 2017: Journal of Thoracic Oncology
https://www.readbyqxmd.com/read/28817118/altered-marginal-zone-and-innate-like-b-cells-in-aged-senescence-accelerated-samp8-mice-with-defective-igg1-responses
#2
Isabel Cortegano, Mercedes Rodríguez, Isabel Martín, Maria Carmen Prado, Carolina Ruíz, Rafael Hortigüela, Mario Alía, Marçal Vilar, Helena Mira, Eva Cano, Mercedes Domínguez, Belén de Andrés, María Luisa Gaspar
Aging has a strong impact on the activity of the immune system, enhancing susceptibility to pathogens and provoking a predominant pre-inflammatory status, whereas dampening responses to vaccines in humans and mice. Here, we demonstrate a loss of marginal zone B lymphocytes (MZ, CD19(+)CD45R(+)CD21(++)CD23(lo)) and a decrease of naive B cells (CD19(+)IgD(+)), whereas there is an enhancement of a CD19(+)CD45R(lo) innate-like B cell population (B1REL) and the so-called aged B cell compartment (ABC, CD45R(+)CD21(lo)CD23(lo)CD5(-)CD11b(-)) in aged senescence-accelerated (SAMP8) mice but not in aged senescence-resistant (SAMR1) mice...
August 17, 2017: Cell Death & Disease
https://www.readbyqxmd.com/read/28808299/gut-homing-%C3%AE-42pd1-v%C3%AE-2-t-cells-promote-innate-mucosal-damage-via-tlr4-during-acute-hiv-type-1-infection
#3
Allen Ka Loon Cheung, Hau-Yee Kwok, Yiru Huang, Min Chen, Yufei Mo, Xilin Wu, Ka-Shing Lam, Hoi-Kuan Kong, Terrence Chi Kong Lau, Jingying Zhou, Jingjing Li, Lin Cheng, Boon Kiat Lee, Qiaoli Peng, Xiaofan Lu, Minghui An, Hui Wang, Hong Shang, Boping Zhou, Hao Wu, Aimin Xu, Kwok-Yung Yuen, Zhiwei Chen
The innate immune cells underlying mucosal inflammatory responses and damage during acute HIV-1 infection remain incompletely understood. Here, we report a Vδ2 subset of gut-homing γδ T cells with significantly upregulated Δ42PD1 (a PD1 isoform) in acute (~20%) HIV-1 patients compared to chronic HIV-1 patients (~11%) and healthy controls (~2%). The frequency of Δ42PD1(+)Vδ2 cells correlates positively with plasma levels of pro-inflammatory cytokines and fatty-acid-binding protein before detectable lipopolysaccharide in acute patients...
August 14, 2017: Nature Microbiology
https://www.readbyqxmd.com/read/28803721/conditioning-neoadjuvant-therapies-for-improved-immunotherapy-of-cancer
#4
REVIEW
Zachary Benson, Saeed H Manjili, Mehran Habibi, Georgi Guruli, Amir A Toor, Kyle K Payne, Masoud H Manjili
Recent advances in the treatment of melanoma and non-small cell lung cancer (NSCLC) by combining conventional therapies with anti-PD1/PD-L1 immunotherapies, have renewed interests in immunotherapy of cancer. The emerging concept of conventional cancer therapies combined with immunotherapy differs from the classical concept in that it is not simply taking advantage of their additive anti-tumor effects, but it is to use certain therapeutic regimens to condition the tumor microenvironment for optimal response to immunotherapy...
August 10, 2017: Biochemical Pharmacology
https://www.readbyqxmd.com/read/28783540/survival-of-melanoma-patients-treated-with-targeted-therapy-and-immunotherapy-after-systematic-upfront-control-of-brain-metastases-by-radiosurgery
#5
C Gaudy-Marqueste, A S Dussouil, R Carron, L Troin, N Malissen, A Loundou, S Monestier, S Mallet, M A Richard, J M Régis, J J Grob
BACKGROUND: Targeted therapy (TT) and immunotherapies (ITs) have dramatically improved survival in metastatic melanoma (MM). However, their efficacy on brain metastasis (BM) remains limited and poorly documented. PATIENTS AND METHODS: Retrospective cohort of consecutive MM patients (pts) with BMs, all systematically upfront treated by Gamma-Knife (GK) at first BM and retreated in case of new BMs, from 2010 to 2015 at the time when ipilimumab BRAF ± MEK inhibitors and anti-PD1 were introduced in practice...
August 4, 2017: European Journal of Cancer
https://www.readbyqxmd.com/read/28776778/eruptive-keratoacanthomas-arising-in-the-setting-of-lichenoid-toxicity-after-pd1-inhibition-with-nivolumab
#6
Stephanie I Feldstein, Forum Patel, Larissa Larsen, Edward Kim, Samuel Hwang, Maxwell A Fung
We were fascinated to read the observations of Bandino et al. who described two patients who developed keratoacanthomas and squamous cell carcinoma in association with bullous pemphigoid-like lesions after treatment with PD-1 inhibitors, nivolumab or pembrolizumab, in a recent issue of the Journal. Herein we report two patients with no prior history of skin cancer who developed eruptive keratoacanthomas in the setting of lichenoid skin toxicity after starting nivolumab. This article is protected by copyright...
August 3, 2017: Journal of the European Academy of Dermatology and Venereology: JEADV
https://www.readbyqxmd.com/read/28770269/the-pd-1-pd-l1-inhibitory-pathway-is-altered-in-primary-glomerulonephritides
#7
Ewelina Grywalska, Iwona Smarz-Widelska, Ewelina Krasowska-Zajac, Izabela Korona-Glowniak, Karolina Zaluska-Patel, Michal Mielnik, Martyna Podgajna, Anna Malm, Jacek Rolinski, Wojciech Zaluska
The pathogenesis of primary proliferative and non-proliferative glomerulonephritides (PGN and NPGN) is still not fully understood, however, current evidence suggests that most cases of PGN and NPGN are the results of immunologic response to different etiologic agents that activates various biological processes leading to glomerular inflammation and injury. Programmed cell death protein 1 (PD-1) is the major inhibitory receptor regulating T cell exhaustion. The aim of this study was to evaluate the frequencies of PD-1-positive and PD-ligand 1 (PD-L1)-positive T and B lymphocytes in patients with NPGN and PGN in relation to clinical parameters for the first time...
August 2, 2017: Archivum Immunologiae et Therapiae Experimentalis
https://www.readbyqxmd.com/read/28755050/glutamate-neonatal-excitotoxicity-modifies-vegf-a-vegf-b-vegfr-1-and-vegfr-2-protein-expression-profiles-during-postnatal-development-of-the-cerebral-cortex-and-hippocampus-of-male-rats
#8
Jose Luis Castañeda-Cabral, Carlos Beas-Zarate, Graciela Gudiño-Cabrera, Monica E Ureña-Guerrero
Vascular endothelial growth factor (VEGF) exerts both neuroprotective and proinflammatory effects in the brain, depending on the VEGF (A-E) and VEGF receptor (VEGFR1-3) types involved. Neonatal monosodium glutamate (MSG) treatment triggers an excitotoxic degenerative process associated with several neuropathological conditions, and VEGF messenger RNA (mRNA) expression is increased at postnatal day (PD) 14 in rat hippocampus (Hp) following the treatment. The aim of this work was to establish the changes in immunoreactivity to VEGF-A, VEGF-B, VEGFR-1 and VEGFR-2 proteins induced by neonatal MSG treatment (4 g/kg, subcutaneous, at PD1, 3, 5 and 7) in the cerebral motor cortex (CMC) and Hp...
July 29, 2017: Journal of Molecular Neuroscience: MN
https://www.readbyqxmd.com/read/28753231/pd-1-inhibitor-associated-lichenoid-inflammation-with-incidental-suprabasilar-acantholysis-or-vesiculation-report-of-four-cases
#9
Shaun Chou, Cathy Zhao, Shelley Ji Eun Hwang, Pablo Fernandez-Penas
BACKGROUND: Immune checkpoint agents targeting Programmed cell death-1 protein (PD1) or Cytotoxic T-Lymphocyte Associated Protein-4 (CTLA-4) receptors are increasingly utilised in treatment of advanced malignancies. However, these immunotherapies are commonly associated with idiosyncratic cutaneous adverse reactions. Thus, recognition and awareness of these reactions are necessary. METHODS: We reviewed the skin biopsies of all patients on anti-PD1 therapy with or without ipilimumab who developed lichenoid inflammation and included those with microscopic suprabasal or intraepidermal clefts...
July 28, 2017: Journal of Cutaneous Pathology
https://www.readbyqxmd.com/read/28739716/clinical-significance-of-pd1-and-pdl1-in-human-breast-cancer
#10
Michal Uhercik, Andrew J Sanders, Sioned Owen, Eleri L Davies, Anup K Sharma, Wen G Jiang, Kefah Mokbel
BACKGROUND/AIM: Programmed death 1 (PD1) and its ligand programmed death ligand 1 (PDL1) form a pathway which when activated is thought to result in suppression of antitumor adaptive responses, influencing antitumor immunity. With potential targeted therapies emerging against PDL1, we investigated the clinical significance of mRNA expression levels of PD1 and PDL1 in our breast cancer cohort to explore its association with disease progression and prognosis. Previous studies evaluating the expression of PD1 and PDL1 (mRNA or protein) and its association with prognosis in breast cancer showed both positive and negative correlations and hence remain controversial...
August 2017: Anticancer Research
https://www.readbyqxmd.com/read/28739711/adrenal-insufficiency-related-to-anti-programmed-death-1-therapy
#11
Ryo Ariyasu, Atsushi Horiike, Takahiro Yoshizawa, Yosuke Dotsu, Junji Koyama, Masafumi Saiki, Tomoaki Sonoda, Shingo Nishikawa, Satoru Kitazono, Noriko Yanagitani, Makoto Nishio
BACKGROUND/AIM: Adrenal insufficiency is one of the adverse events (AEs) associated with anti-programmed death-1 (PD1) therapy. Delaying diagnoses can lead to serious conditions. It is necessary to elucidate detailed clinical features of these AEs. PATIENTS AND METHODS: Patients treated with anti-PD-1 monotherapy or in combination with anti-cytotoxic T cell lymphocyte-4 therapy at our hospital from January 2013 to December 2016 were identified. The patients' clinical characteristics and laboratory and radiologic findings were collected...
August 2017: Anticancer Research
https://www.readbyqxmd.com/read/28735186/development-of-a-robust-reporter-gene-assay-to-measure-the-bioactivity-of-anti-pd-1-anti-pd-l1-therapeutic-antibodies
#12
Lan Wang, Chuanfei Yu, Yalan Yang, Kai Gao, Junzhi Wang
Being regarded as the 'cancer panacea', the anti-PD-1/anti-PD-L1 monoclonal antibodies (mAbs) have become the R&D focus of biopharmaceutical industries. Several marketed such mAbs have been proved particularly effective in treating various cancers. However, the cell-based bioassay to measure the biological activities of the anti-PD-1/anti-PD-L1 mAbs as the lot release or stability test has been a great challenge to quality control laboratories due to the immunomodulating nature of the mAbs. Here, we describe the development and validation of a reporter gene assay consisting of two-cell systems to measure the bioactivity of the anti-PD-1/anti-PD-L1 mAbs...
May 8, 2017: Journal of Pharmaceutical and Biomedical Analysis
https://www.readbyqxmd.com/read/28734141/new-dinuclear-palladium-ii-complexes-studies-of-the-nucleophilic-substitution-reactions-dna-bsa-interactions-and-cytotoxic-activity
#13
Dušan Ćoćić, Snežana Jovanović, Marija Nišavić, Dejan Baskić, Danijela Todorović, Suzana Popović, Živadin D Bugarčić, Biljana Petrović
Six new dinuclear Pd(II) complexes, [{Pd(2,2'-bipy)Cl}2(μ-pz)](ClO4)2 (Pd1), [{Pd(dach)Cl}2(μ-pz)](ClO4)2 (Pd2), [{Pd(en)Cl}2(μ-pz)](ClO4)2 (Pd3), [{Pd(2,2'-bipy)Cl}2(μ-4,4'-bipy)](ClO4)2 (Pd4), [{Pd(dach)Cl}2(μ-4,4'-bipy)](ClO4)2 (Pd5) and [{Pd(en)Cl}2(μ-4,4'-bipy)](ClO4)2 (Pd6) (where 2,2'-bipy=2,2'-bipyridyl, pz=pyrazine, dach=trans-(±)-1,2-diaminocyclohexane, en=ethylenediamine, 4,4'-bipy=4,4'-bipyridyl) have been synthesized and characterized by elemental microanalysis, IR, (1)H NMR and MALDI-TOF mass spectrometry...
July 16, 2017: Journal of Inorganic Biochemistry
https://www.readbyqxmd.com/read/28733529/immunotherapy-of-wap-tnp-mice-with-early-stage-mammary-gland-tumors
#14
Michael Bruns, Wolfgang Deppert
The SV40 transgenic BALB/c mouse based WAP-T/WAP-TNP model for triple-negative breast cancer allows the analysis of parameters influencing immunotherapeutic approaches. Except for WAP-TNP tumors expressing the immune-dominant LCMV NP-epitope within SV40 T-antigen (T-AgNP) which is not expressed by T-Ag of WAP-T tumors, the tumors are extremely similar. Comparative anti-PD1/PD-L1 immunotherapy of WAP-T and WAP-TNP mice supported the hypothesis that the immunogenicity of tumor antigen T-cell epitopes strongly influences the success of immune checkpoint blockade therapy, with highly immunogenic T-cell epitopes favoring rapid CTL exhaustion...
June 29, 2017: Oncotarget
https://www.readbyqxmd.com/read/28733528/analyses-of-selected-safety-endpoints-in-phase-1-and-late-phase-clinical-trials-of-anti-pd-1-and-pd-l1-inhibitors-prediction-of-immune-related-toxicities
#15
Ricardo Costa, Rubens B Costa, Sarah M Talamantes, Irene Helenoswki, Benedito A Carneiro, Young Kwang Chae, William J Gradishar, Razelle Kurzrock, Francis J Giles
PURPOSE: Anti-PD1 and PD-L1 antibodies are associated with immune-related adverse effects (irAEs). This analysis aims to assess the discrepancies between frequencies of irAEs observed in phase 1 trials with those seen in late-phase trials and to evolve the field of drug development. METHODS: PubMed search was conducted for articles published until December of 2016. Trials needed to have at least one of the study arms consisting of nivolumab, pembrolizumab or atezolizumab monotherapy...
June 29, 2017: Oncotarget
https://www.readbyqxmd.com/read/28733197/extrafollicular-pd1-and-intrafollicular-cd3-expression-are-associated-with-survival-in-follicular-lymphoma
#16
Kedmi Meirav, Schiby Ginette, Tadmor Tamar, Barshack Iris, Nagler Arnon, Avigdor Abraham
INTRODUCTION: Both microenvironment and tumor biomarkers impact outcome in follicular lymphoma (FL). We aimed to study the effect of Ki-67, CD3, CD68, and PD1 expression on outcome of FL. MATERIALS AND METHODS: Forty-eight patients were included. Stained slides were visually assessed and marker expression was correlated with outcome. Both intra- and extrafollicular expression of Ki-67, CD68, and PD1 were evaluated. CD3 was evaluated only in the intrafollicular area...
June 23, 2017: Clinical Lymphoma, Myeloma & Leukemia
https://www.readbyqxmd.com/read/28729032/a-novel-model-of-autosomal-recessive-polycystic-kidney-questions-the-role-of-the-fibrocystin-c-terminus-in-disease-mechanism
#17
Patricia Outeda, Luis Menezes, Erum A Hartung, Stacey Bridges, Fang Zhou, Xianjun Zhu, Hangxue Xu, Qiong Huang, Qin Yao, Feng Qian, Gregory G Germino, Terry Watnick
Autosomal recessive polycystic kidney disease (OMIM 263200) is a serious condition of the kidney and liver caused by mutations in a single gene, PKHD1. This gene encodes fibrocystin/polyductin (FPC, PD1), a large protein shown by in vitro studies to undergo Notch-like processing. Its cytoplasmic tail, reported to include a ciliary targeting sequence, a nuclear localization signal, and a polycystin-2 binding domain, is thought to traffic to the nucleus after cleavage. We now report a novel mouse line with a triple HA-epitope "knocked-in" to the C-terminus along with lox P sites flanking exon 67, which encodes most of the C-terminus (Pkhd1(Flox67HA))...
July 17, 2017: Kidney International
https://www.readbyqxmd.com/read/28725344/complete-response-of-mediastinal-clear-cell-sarcoma-to-pembrolizumab-with-radiotherapy
#18
Samuel Marcrom, Jennifer F De Los Santos, Robert M Conry
BACKGROUND: Clear cell sarcoma (CCS) is a rare, aggressive soft tissue sarcoma thought to derive from neural crest and characterized by a 12;22 translocation. The resulting fusion protein directly activates expression of the melanocyte master transcription factor and drives the same down-stream pathways in CCS and melanoma leading to significant clinical parallels between these malignancies. Striking success of immune checkpoint blockade in melanoma has promoted interest in immunotherapy of CCS...
2017: Clinical Sarcoma Research
https://www.readbyqxmd.com/read/28716652/toxicity-profiles-of-immunotherapy
#19
REVIEW
Sophie Cousin, Antoine Italiano
Immunotherapies are changing the landscape of advanced solid tumor treatment. These therapies have different mechanisms of action and include oncolytic viruses, checkpoint inhibitors, such as CTLA-4 or PD1/PD-L1 monoclonal antibodies, and CSF-1R antibodies. Given the growing therapeutic impact of these agents in oncology, it is important to better understand their properties. Immunotherapies generate new toxicity profiles that are called immune-related adverse events and require specific management. This review focuses on the mechanisms of action of such side effects, as well as their description and their general management...
July 15, 2017: Pharmacology & Therapeutics
https://www.readbyqxmd.com/read/28714780/atezolizumab-for-the-treatment-of-non-small-cell-lung-cancer
#20
Fernando C Santini, Charles M Rudin
The immune system can restrain or promote cancer development and growth. Antibodies targeting immune checkpoints have revolutionized cancer treatment. Among the best responses have been in non-small cell lung cancer (NSCLC) which is largely caused by chronic exposure to carcinogens; associated with high neoantigen creation and sensitization to immune recognition. Atezolizumab was the first approved antibody that targets the PD-1 ligand (PD-L1). Areas covered: This drug profile article covers the basics of the cancer-immunity cycle and reviews some aspects of innate and adaptive immunology...
July 27, 2017: Expert Review of Clinical Pharmacology
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