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https://www.readbyqxmd.com/read/29352857/combining-chemotherapy-with-pd-1-blockade-in-nsclc
#1
REVIEW
Matthen Mathew, Thomas Enzler, Catherine A Shu, Naiyer A Rizvi
Antitumor immunity relies on the ability of the immune system to recognize tumor cells as foreign and eliminate them. An effective immune response in this setting is due to surveillance of tumor-specific antigens that induce an adaptive immune response resulting in T-cell mediated cytotoxicity. Immune checkpoint inhibitors, specifically those targeting the programmed cell death-1 (PD-1)/programmed cell death ligand-1 (PD-L1) axis, have demonstrated promising activity in non-small cell lung cancer (NSCLC). However, there remains a crucial need for better treatment strategies for the majority of patients with advanced NSCLC, particularly in the frontline setting...
January 17, 2018: Pharmacology & Therapeutics
https://www.readbyqxmd.com/read/29352490/oral-lichenoid-reaction-showing-multiple-ulcers-associated-with-anti-programmed-death-cell-receptor-1-treatment-a-report-of-two-cases-and-published-work-review
#2
Koya Obara, Mamiko Masuzawa, Yasuyuki Amoh
Anti-programmed cell death receptor-1 (PD-1) antibodies represent an effective treatment opinion for advanced melanoma and non-small-cell lung cancer, as well as other cancerous entities. Immune checkpoint inhibitors such as anti-PD-1 antibody result in a unique side-effect profile, commonly described as immune-related adverse events (irAE). These irAE affect the skin, gastrointestinal tract, liver, endocrine system and other organ systems. We report two cases of oral lichenoid reaction showing multiple ulcers associated with nivolumab treatment...
January 20, 2018: Journal of Dermatology
https://www.readbyqxmd.com/read/29352166/epstein-barr-virus-encoded-latent-membrane-protein-1-suppresses-necroptosis-through-targeting-ripk1-3-ubiquitination
#3
Xiaolan Liu, Yueshuo Li, Songling Peng, Xinfang Yu, Wei Li, Feng Shi, Xiangjian Luo, Min Tang, Zheqiong Tan, A M Bode, Ya Cao
Necroptosis is an alternative programmed cell death pathway that is unleashed in the absence of apoptosis and mediated by signaling complexes containing receptor-interating protein kinase 1 (RIPK1) and RIPK3. This form of cell death has recently been implicated in host defense system to eliminate pathogen-infected cells. However, only a few viral species such as herpes simplex virus (HSV) and cytomegalovirus (CMV) have evolved mechanisms inhibiting necroptosis to overcome host antiviral defense, which is important for successful pathogenesis...
January 19, 2018: Cell Death & Disease
https://www.readbyqxmd.com/read/29350470/specific-expression-of-pd-l1-in-rela-fusion-supratentorial-ependymoma-implications-for-pd-1-targeted-therapy
#4
Davis A Witt, Andrew M Donson, Vladimir Amani, Daniel C Moreira, Bridget Sanford, Lindsey M Hoffman, Michael H Handler, Jean M Mulcahy Levy, Kenneth L Jones, Anandani Nellan, Nicholas K Foreman, Andrea M Griesinger
BACKGROUND: A desperate need for novel therapies in pediatric ependymoma (EPN) exists, as chemotherapy remains ineffective and radiotherapy often fails. EPN have significant infiltration of immune cells, which correlates with outcome. Immune checkpoint inhibitors provide an avenue for new treatments. This study characterizes tumor-infiltrating immune cells in EPN and aims at predicting candidates for clinical trials using checkpoint inhibitors targeting PD-L1/PD-1 (programmed death ligand 1/programmed death 1)...
January 19, 2018: Pediatric Blood & Cancer
https://www.readbyqxmd.com/read/29350327/hypermutated-tumors-and-immune-checkpoint-inhibition
#5
Kristen K Ciombor, Richard M Goldberg
Microsatellite instability-high/DNA mismatch repair deficient tumors are found across the cancer spectrum and often harbor markedly increased numbers of mutations when compared to microsatellite stable/DNA mismatch repair proficient tumors. As a result of this high mutational load, tumor-infiltrating lymphocyte density is increased and more immunogenic neoepitopes are expressed, leading to upregulation of immune checkpoints in these tumors. Checkpoint inhibitors such as pembrolizumab and nivolumab, both immunoglobulin G4 (IgG4) monoclonal antibodies that block interactions between the programmed cell death receptor-1 and its ligands, have significant activity in this tumor class...
January 19, 2018: Drugs
https://www.readbyqxmd.com/read/29349927/treatment-related-toxicities-of-immune-checkpoint-inhibitors-in-advanced-cancers-a-meta-analysis
#6
Johnathan Man, Georgia Ritchie, Matthew Links, Sally Lord, Chee Khoon Lee
BACKGROUND: We performed a meta-analysis to quantify toxic death, adverse events (AEs) and treatment discontinuation due to AEs from checkpoint inhibitors (CI). METHODS: We searched for randomized trials with adequate reporting for toxicity outcomes. Pooled risk ratios were estimated for CI versus chemotherapy or different combinations of these agents. RESULTS: Twenty trials of five different cancers with 10 794 patients with performance status 0 or 1 were identified...
January 19, 2018: Asia-Pacific Journal of Clinical Oncology
https://www.readbyqxmd.com/read/29349789/postmarketing-cases-of-eluxadoline-associated-pancreatitis-in-patients-with-or-without-a-gallbladder
#7
L Harinstein, E Wu, A Brinker
BACKGROUND: Cases of pancreatitis were identified in the eluxadoline clinical development program, reflected in initial product labelling, and the subject of postmarketing reports. AIM: To analyse postmarketing cases of eluxadoline-associated pancreatitis. METHODS: We retrospectively analysed all US adverse event reports of pancreatitis associated with eluxadoline reported to the FDA Adverse Event Reporting System (FAERS) database from May 27, 2015 through February 15, 2017...
January 19, 2018: Alimentary Pharmacology & Therapeutics
https://www.readbyqxmd.com/read/29349763/immune-checkpoint-blockade-for-breast-cancer
#8
April Swoboda, Rita Nanda
An effective antitumor immune response requires interaction between cells of the adaptive and innate immune system. Three key elements are required: generation of activated tumor-directed T cells, infiltration of activated T cells into the tumor microenvironment, and killing of tumor cells by activated T cells. Tumor immune evasion can occur as a result of the disruption of each of these three key T cell activities, resulting in three distinct cancer-immune phenotypes. The immune inflamed phenotype, characterized by the presence of a robust tumor immune infiltrate, suggests impaired activated T cell killing of tumor cells related to the presence of inhibitory factors...
2018: Cancer Treatment and Research
https://www.readbyqxmd.com/read/29349707/piperazine-clubbed-with-2-azetidinone-derivatives-suppresses-proliferation-migration-and-induces-apoptosis-in-human-cervical-cancer-hela-cells-through-oxidative-stress-mediated-intrinsic-mitochondrial-pathway
#9
Rashmin Khanam, Raj Kumar, Iram Iqbal Hejazi, Syed Shahabuddin, Ramovatar Meena, Vikrant Jayant, Prabhat Kumar, Abdul Roouf Bhat, Fareeda Athar
Piperazine scaffolds or 2-azetidinone pharmacophores have been reported to show anti-cancer activities and apoptosis induction in different types of cancer cells. However, the mechanistic studies involve in induction of apoptosis addressing these two moieties for human cervical cancer cells remain uncertain. The present study emphasizes on the anti-proliferating properties and mechanism involved in induction of apoptosis for these structurally related azoles derivatives in HeLa cancer cells. 1-Phenylpiperazine clubbed with 2-azetidione derivatives (5a-5h) were synthesized, characterized using various spectroscopic techniques and evaluated for their in-vitro anti-proliferative activities and induction of apoptosis...
January 18, 2018: Apoptosis: An International Journal on Programmed Cell Death
https://www.readbyqxmd.com/read/29349487/lay-first-responder-training-in-eastern-uganda-leveraging-transportation-infrastructure-to-build-an-effective-prehospital-emergency-care-training-program
#10
Peter G Delaney, Richard Bamuleke, Yang Jae Lee
BACKGROUND: Though road traffic injuries (RTIs) are a major cause of mortality in East Africa, few countries have emergency medical services. The aim was to create a sustainable and efficient prehospital lay first responder program, creating a system with lay first responders spread through the 53 motorcycle taxi stages of Iganga Municipality. METHODS: One hundred and fifty-four motorcycle taxi riders were taught a first aid curriculum in partnership with a local Red Cross first aid trainer and provided with a first aid kit following WHO guidelines for basic first aid...
January 18, 2018: World Journal of Surgery
https://www.readbyqxmd.com/read/29348907/microsatellite-stability-and-mismatch-repair-proficiency-in-nasopharyngeal-carcinoma-may-not-predict-programmed-death-1-blockade-resistance
#11
Xiyi Liao, Liang Zhao, Sangang Wu, Hua Zheng, Haojun Chen, Huan Zhang, ZiJing Wang, Qin Lin
The US FDA granted accelerated approval to pembrolizumab for microsatellite instability-high and mismatch repair deficient cancers. The response of programmed death-1 blockade in mismatch repair proficiency (pMMR) colorectal cancer is very poor, however, whether such treatment is effective in pMMR nasopharyngeal carcinoma (NPC) remains unknown. We report a case of a 51-year-old man with NPC. PET-CT scan revealed a space-occupying lesion in the left lung, and the pathologic result confirmed the occupying lesion originated from NPC...
December 22, 2017: Oncotarget
https://www.readbyqxmd.com/read/29348848/pd-l1-expression-in-tumor-tissue-and-peripheral-blood-of-patients-with-oral-squamous-cell-carcinoma
#12
Manuel Weber, Falk Wehrhan, Christoph Baran, Abbas Agaimy, Maike Büttner-Herold, Raimund Preidl, Friedrich W Neukam, Jutta Ries
Background: Immune checkpoints like programmed cell death-1 (PD-1) and its ligand PD-L1 are involved in immune escape mechanisms of solid tumors including oral squamous cell carcinoma (OSCC). Inhibitors of the pathway are successfully used for treating especially advanced disease. However, the physiological relevance of PD-1/PD-L1-signaling in OSCC is insufficiently understood. The aim of the study was to analyze if PD-L1 expression in tumor tissue and peripheral blood samples of OSCC patients is associated with histomorphological tumor parameters and if PD-L1 expression in patients is different from controls...
December 22, 2017: Oncotarget
https://www.readbyqxmd.com/read/29348830/inactivation-deficiency-of-dhodh-induces-cell-cycle-arrest-and-programed-cell-death-in-melanoma
#13
Lichao Liu, Zhen Dong, Qian Lei, Jie Yang, Huanrong Hu, Qian Li, Yacong Ji, Leiyang Guo, Yanli Zhang, Yaling Liu, Hongjuan Cui
Malignant melanoma (MM) is one of the most malignant tumors and has a very poor prognosis. However, there are no effective drugs to treat this disease. As a kind of iron flavin dependent enzyme, dihydroorotate dehydrogenase (DHODH, EC 1.3.3.1) is the fourth and a key enzyme in the de novo biosynthesis of pyrimidines. Herein, we found that DHODH inactivation/deficiency inhibited melanoma cell proliferation, induced cell cycle arrest at S phase and lead to autophagy in human melanoma cells. Meanwhile, leflunomide treatment induced cell apoptosis and deficiency of DHODH sensitized cells to drug-induced apoptosis in BCL-2 deficient melanoma cells, while not in BCL-2 abundant melanoma cells...
December 22, 2017: Oncotarget
https://www.readbyqxmd.com/read/29347993/updated-efficacy-of-avelumab-in-patients-with-previously-treated-metastatic-merkel-cell-carcinoma-after-%C3%A2-1%C3%A2-year-of-follow-up-javelin-merkel-200-a-phase-2-clinical-trial
#14
Howard L Kaufman, Jeffery S Russell, Omid Hamid, Shailender Bhatia, Patrick Terheyden, Sandra P D'Angelo, Kent C Shih, Céleste Lebbé, Michele Milella, Isaac Brownell, Karl D Lewis, Jochen H Lorch, Anja von Heydebreck, Meliessa Hennessy, Paul Nghiem
BACKGROUND: Merkel cell carcinoma (MCC) is a rare, aggressive skin cancer associated with poor survival outcomes in patients with distant metastatic disease (mMCC). In an initial analysis from JAVELIN Merkel 200, a phase 2, prospective, open-label, single-arm trial in mMCC, avelumab-a human anti-programmed death-ligand 1 (PD-L1) monoclonal antibody-showed promising efficacy and a safety profile that was generally manageable and tolerable. Here, we report the efficacy of avelumab after ≥1 year of follow-up in patients with distant mMCC that had progressed following prior chemotherapy for metastatic disease...
January 19, 2018: Journal for Immunotherapy of Cancer
https://www.readbyqxmd.com/read/29347890/disproportionately-higher-unintentional-injury-mortality-among-alaska-native-people-2006-2015
#15
Gretchen Day, Peter Holck, Hillary Strayer, Kathryn Koller, Timothy Thomas
We compared rates of unintentional injury (UI) deaths (total and by injury category) among Alaska Native (AN) people to rates of U.S. White (USW) and Alaska White (AKW) populations during 2006-2015. The mortality data for AN and AKW populations were obtained from Alaska Bureau of Vital Statistics and USW mortality data were obtained from WISQARS, the Center for Disease Control and Prevention online injury data program. AN and AKW rates were age-adjusted to the U.S. 2000 Standard Population and rate ratios (RR) were calculated...
December 2018: International Journal of Circumpolar Health
https://www.readbyqxmd.com/read/29346540/blood-and-lymphatic-vessels-contribute-to-the-impact-of-the-immune-microenvironment-on-clinical-outcome-in-non-small-cell-lung-cancer
#16
Giovanna Armani, Denise Madeddu, Giulia Mazzaschi, Giovanni Bocchialini, Francesco Sogni, Caterina Frati, Bruno Lorusso, Angela Falco, Costanza Annamaria Lagrasta, Stefano Cavalli, Chiara Mangiaracina, Rocchina Vilella, Gabriella Becchi, Letizia Gnetti, Emilia Corradini, Eugenio Quaini, Konrad Urbanek, Matteo Goldoni, Paolo Carbognani, Luca Ampollini, Federico Quaini
OBJECTIVES: Lymphangiogenesis plays a critical role in the immune response, tumour progression and therapy effectiveness. The aim of this study was to determine whether the interplay between the lymphatic and the blood microvasculature, tumour-infiltrating lymphocytes and the programmed death 1 (PD-1)/programmed death ligand 1 (PD-L1) immune checkpoint constitutes an immune microenvironment affecting the clinical outcome of patients with non-small-cell lung cancer. METHODS: Samples from 50 squamous cell carcinomas and 42 adenocarcinomas were subjected to immunofluorescence to detect blood and lymphatic vessels...
January 15, 2018: European Journal of Cardio-thoracic Surgery
https://www.readbyqxmd.com/read/29346340/disparities-in-preconception-health-indicators-%C3%A2-behavioral-risk-factor-surveillance-system-2013-2015-and-pregnancy-risk-assessment-monitoring-system-2013-2014
#17
Cheryl Robbins, Sheree L Boulet, Isabel Morgan, Denise V D'Angelo, Lauren B Zapata, Brian Morrow, Andrea Sharma, Charlan D Kroelinger
PROBLEM/CONDITION: Preconception health is a broad term that encompasses the overall health of nonpregnant women during their reproductive years (defined here as aged 18-44 years). Improvement of both birth outcomes and the woman's health occurs when preconception health is optimized. Improving preconception health before and between pregnancies is critical for reducing maternal and infant mortality and pregnancy-related complications. The National Preconception Health and Health Care Initiative's Surveillance and Research work group suggests ten prioritized indicators that states can use to monitor programs or activities for improving the preconception health status of women of reproductive age...
January 19, 2018: MMWR. Surveillance Summaries: Morbidity and Mortality Weekly Report. Surveillance Summaries
https://www.readbyqxmd.com/read/29346180/development-of-a-pd-l1-complementary-diagnostic-immunohistochemistry-assay-sp142-for-atezolizumab
#18
Bharathi Vennapusa, Brian Baker, Marcin Kowanetz, Jennifer Boone, Ina Menzl, Jean-Marie Bruey, Gregg Fine, Sanjeev Mariathasan, Ian McCaffery, Simonetta Mocci, Sandra Rost, Dustin Smith, Eslie Dennis, Szu-Yu Tang, Bita Damadzadeh, Espen Walker, Priti S Hegde, J Andrew Williams, Hartmut Koeppen, Zachary Boyd
Cancer immunotherapies, such as atezolizumab, are proving to be a valuable therapeutic strategy across indications, including non-small cell lung cancer (NSCLC) and urothelial cancer (UC). Here, we describe a diagnostic assay that measures programmed-death ligand 1 (PD-L1) expression, via immunohistochemistry, to identify patients who will derive the most benefit from treatment with atezolizumab, a humanized monoclonal anti-PD-L1 antibody. We describe the performance of the VENTANA PD-L1 (SP142) Assay in terms of specificity, sensitivity, and the ability to stain both tumor cells (TC) and tumor-infiltrating immune cells (IC), in NSCLC and UC tissues...
January 16, 2018: Applied Immunohistochemistry & Molecular Morphology: AIMM
https://www.readbyqxmd.com/read/29345842/pd-l1-is-a-promising-blood-marker-for-predicting-tumor-progression-and-prognosis-in-patients-with-gastric-cancer
#19
Masahiko Amatatsu, Takaaki Arigami, Yoshikazu Uenosono, Shigehiro Yanagita, Yasuto Uchikado, Yuko Kijima, Hiroshi Kurahara, Yoshiaki Kita, Shinichiro Mori, Ken Sasaki, Itaru Omoto, Kosei Maemura, Sumiya Ishigami, Shoji Natsugoe
Immune checkpoint inhibitor therapy has been clinically introduced for several malignancies, and its effectiveness has been confirmed by clinical trials. In particular, programmed cell death protein 1 (PD-1) and programmed death-ligand 1 (PD-L1) are widely known as important immune checkpoint molecules associated with the mechanisms of immune escape by malignant tumor cells. On the other hand, liquid biopsy of blood specimens has the clinical benefit of providing a simple, repeatable sampling tool. Non-invasive liquid biopsy has recently been spotlighted as a promising approach to predicting tumor progression and prognosis...
January 18, 2018: Cancer Science
https://www.readbyqxmd.com/read/29345283/regulation-of-programmed-death-ligand-in-the-human-head-and-neck-squamous-cell-carcinoma-microenvironment-is-mediated-through-matrix-metalloproteinase-mediated-proteolytic-cleavage
#20
Mayuko Hira-Miyazawa, Hiroyuki Nakamura, Mariko Hirai, Yutaka Kobayashi, Hiroko Kitahara, George Bou-Gharios, Shuichi Kawashiri
Recurrent and/or metastatic head and neck squamous cell carcinoma (R/M HNSCC) is a devastating malignancy with a poor prognosis. According to recent clinical studies, tumour growth can be effectively reduced and survival can be improved by blocking the programmed death receptor-1 (PD-1)/programmed death-ligand 1 (PD‑L1) pathway. PD-L1 expression has been proposed as a potential causative mechanism, as HNSCC is highly immunosuppressive. However, anti-PD-1 treatment is beneficial only for certain patients...
February 2018: International Journal of Oncology
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