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https://www.readbyqxmd.com/read/29777823/updated-efficacy-analysis-including-secondary-population-results-for-oak-a-randomized-phase-iii-study-of-atezolizumab-vs-docetaxel-in-patients-with-previously-treated-advanced-non-small-cell-lung-cancer
#1
L Fehrenbacher, J von Pawel, K Park, A Rittmeyer, D R Gandara, S Ponce Aix, J-Y Han, S M Gadgeel, T Hida, D L Cortinovis, M Cobo, D M Kowalski, F De Marinis, M Gandhi, B Danner, C Matheny, M Kowanetz, P He, F Felizzi, H Patel, A Sandler, M Ballinger, F Barlesi
INTRODUCTION: The efficacy and safety of atezolizumab vs docetaxel as second- or third-line treatment in patients with advanced non-small cell lung cancer in the primary (n=850; ITT850) and secondary (n=1225; ITT1225) efficacy populations of the randomized phase III OAK study at an updated data cutoff were assessed. METHODS: Patients received atezolizumab 1200mg or docetaxel 75mg/m2 intravenously every 3 weeks until loss of clinical benefit or disease progression, respectively...
May 16, 2018: Journal of Thoracic Oncology
https://www.readbyqxmd.com/read/29777016/clinical-utility-of-electronic-alberta-stroke-program-early-computed-tomography-score-software-in-the-enchanted-trial-database
#2
Simon Nagel, Xia Wang, Cheryl Carcel, Thompson Robinson, Richard I Lindley, John Chalmers, Craig S Anderson
BACKGROUND AND PURPOSE: Clinical utility of electronic Alberta Stroke Program Early CT Score (e-ASPECTS), an automated system for quantifying signs of infarction, was evaluated in a large database of thrombolyzed patients with acute ischemic stroke. METHODS: All baseline noncontrast computed tomographic scans of patients with anterior circulation acute ischemic stroke who participated in the alteplase dose arm of the randomized controlled trial ENCHANTED (Enhanced Control of Hypertension and Thrombolysis Stroke Study) were reviewed; poor quality and large (>6 mm) slice thickness were excluded...
May 18, 2018: Stroke; a Journal of Cerebral Circulation
https://www.readbyqxmd.com/read/29776633/molecular-diagnostics-in-colorectal-carcinoma-advances-and-applications-for-2018
#3
REVIEW
Amarpreet Bhalla, Muhammad Zulfiqar, Martin H Bluth
The molecular pathogenesis and classification of colorectal carcinoma are based on the traditional adenomaecarcinoma sequence, serrated polyp pathway, and microsatellite instability (MSI). The genetic basis for hereditary nonpolyposis colorectal cancer is the detection of mutations in the MLH1, MSH2, MSH6, PMS2, and EPCAM genes. Genetic testing for Lynch syndrome includes MSI testing, methylator phenotype testing, BRAF mutation testing, and molecular testing for germline mutations in MMR genes. Molecular makers with predictive and prognostic implications include quantitative multigene reverse transcriptase polymerase chain reaction assay and KRAS and BRAF mutation analysis...
June 2018: Clinics in Laboratory Medicine
https://www.readbyqxmd.com/read/29775807/fir-efficacy-safety-and-biomarker-analysis-of-a-phase-ii-open-label-study-of-atezolizumab-in-pd-l1-selected-patients-with-non-small-cell-lung-cancer
#4
David R Spigel, Jamie E Chaft, Scott Gettinger, Bo H Chao, Luc Dirix, Peter Schmid, Laura Q M Chow, Rodney J Hicks, Larry Leon, Jill Fredrickson, Marcin Kowanetz, Alan Sandler, Roel Funke, Naiyer A Rizvi
INTRODUCTION: The FIR phase II study (NCT01846416) evaluated the efficacy and safety of anti-programmed death-ligand 1 (PD-L1) atezolizumab in advanced non-small-cell lung cancer (NSCLC) selected by tumor cell (TC) or tumor-infiltrating immune cell (IC) PD-L1 expression. METHODS: Patients with PD-L1 TC2/3 (PD-L1 staining on ≥5% of TC) or IC2/3 tumors (PD-L1 staining on ≥5% of IC; determined by SP142 PD-L1 immunohistochemistry assay) with paired fresh and archival histology samples were recruited into Cohort 1 (chemotherapy-naïve/>6 months between adjuvant chemotherapy and recurrence), Cohort 2 (≥ second-line without brain metastases), or Cohort 3 (≥ second-line with treated brain metastases)...
May 15, 2018: Journal of Thoracic Oncology
https://www.readbyqxmd.com/read/29774777/current-research-status-of-palliative-care-in-mainland-china
#5
Tao Wang, Alex Molassiotis, Betty Pui Man Chung, Jing-Yu Tan
OBJECTIVES: This study aimed to obtain an overview of the current research status of palliative care in Mainland China and identify research directions for future studies by characterizing palliative care studies conducted among patients with any life-limiting illness in Mainland China and published in a peer-reviewed journal before November 2016. METHODS: A review guide with 7 categories was initially developed based on existing international palliative care definitions and guidelines through content analysis...
January 1, 2018: Journal of Palliative Care
https://www.readbyqxmd.com/read/29774031/il-10-producing-b-cells-ability-to-induce-regulatory-t-cells-is-maintained-in-rheumatoid-arthritis
#6
Julie Mielle, Rachel Audo, Michael Hahne, Laurence Macia, Bernard Combe, Jacques Morel, Claire Daien
Despite growing evidence highlighting the relevance of increasing IL-10-producing B cells (B10+ cells) in autoimmune diseases, their functions in patients are still unknown. The aim of this study was to evaluate the functions of CpG-induced B10+ cells isolated from healthy controls (HC) and rheumatoid arthritis (RA) patients, on naïve T cell differentiation. We demonstrated that CpG-induced B10+ cells from HC drove naïve T cell differentiation toward regulatory T cells (Treg cells) and IL-10-producing T cells (Tr1) through IL-10 secretion and cellular contacts...
2018: Frontiers in Immunology
https://www.readbyqxmd.com/read/29772681/global-asbestos-disaster
#7
Sugio Furuya, Odgerel Chimed-Ochir, Ken Takahashi, Annette David, Jukka Takala
Introduction : Asbestos has been used for thousands of years but only at a large industrial scale for about 100⁻150 years. The first identified disease was asbestosis, a type of incurable pneumoconiosis caused by asbestos dust and fibres. The latest estimate of global number of asbestosis deaths from the Global Burden of Disease estimate 2016 is 3495. Asbestos-caused cancer was identified in the late 1930's but despite today's overwhelming evidence of the strong carcinogenicity of all asbestos types, including chrysotile, it is still widely used globally...
May 16, 2018: International Journal of Environmental Research and Public Health
https://www.readbyqxmd.com/read/29770915/cytolytic-activity-score-to-assess-anticancer-immunity-in-colorectal-cancer
#8
Sumana Narayanan, Tsutomu Kawaguchi, Li Yan, Xuan Peng, Qianya Qi, Kazuaki Takabe
BACKGROUND: Elevated tumor-infiltrating lymphocytes (TILs) within the tumor microenvironment is a known positive prognostic factor in colorectal cancer (CRC). We hypothesized that since cytotoxic T cells release cytolytic proteins such as perforin (PRF1) and pro-apoptotic granzymes (GZMA) to attack cancer cells, a cytolytic activity score (CYT) would be a useful tool to assess anticancer immunity. METHODS: Genomic expression data were obtained from 456 patients from The Cancer Genome Atlas (TCGA)...
May 16, 2018: Annals of Surgical Oncology
https://www.readbyqxmd.com/read/29770136/cd3%C3%AE%C2%B5-expression-defines-functionally-distinct-subsets-of-v%C3%AE-1-t-cells-in-patients-with-human-immunodeficiency-virus-infection
#9
Pádraic J Dunne, Christina O Maher, Michael Freeley, Katie Dunne, Andreea Petrasca, Judy Orikiiriza, Margaret R Dunne, Derval Reidy, Siobhan O'Dea, Aisling Loy, Jim Woo, Aideen Long, Thomas R Rogers, Fiona Mulcahy, Derek G Doherty
Human γδ T cells expressing the Vδ1 T cell receptor (TCR) recognize self and microbial antigens and stress-inducible molecules in a major histocompatibility complex-unrestricted manner and are an important source of innate interleukin (IL)-17. Vδ1 T cells are expanded in the circulation and intestines of patients with human immunodeficiency virus (HIV) infection. In this study, we show that patients with HIV have elevated frequencies, but not absolute numbers, of circulating Vδ1 T cells compared to control subjects...
2018: Frontiers in Immunology
https://www.readbyqxmd.com/read/29769167/impact-of-sex-on-comparative-outcomes-of-bivalirudin-versus-unfractionated-heparin-in-patients-with-acute-coronary-syndromes-undergoing-invasive-management-a-pre-specified-analysis-of-the-matrix-trial
#10
Giuseppe Gargiulo, Bruno R da Costa, Enrico Frigoli, Cataldo Palmieri, Marco Stefano Nazzaro, Camillo Falcone, Armando Liso, Carlo Vigna, Fabio Abate, Marco Comeglio, Roberto Diletti, Gabriele Gabrielli, Emilio Di Lorenzo, Pietro Mazzarotto, Marco Zimarino, Claudio Moretti, Antonio Colombo, Carlo Penzo, Giampaolo Pasquetto, Salvatore Brugaletta, Fabio Ferrari, Gavino Casu, Vincenzo Guiducci, Antonio Dellavalle, Francesco Liistro, Ciro Mauro, Arnoud W J Van't Hof, Elmir Omerovic, Salvatore Curello, Jose Maria de la Torre Hernandez, Stefano De Servi, Flavia Belloni, Stephan Windecker, Marco Valgimigli
AIMS: To assess whether bivalirudin compared with unfractionated heparin (UFH) is associated with consistent outcomes in male and female patients with acute coronary syndrome (ACS) undergoing invasive management. METHODS AND RESULTS: In the MATRIX program,7213 patients were randomized to bivalirudin or UFH.Patients in bivalirudin group were subsequently assigned to receive or not to receive a post-PCI infusion.The 30-day coprimary outcomes were major adverse cardiovascular and cerebrovascular events (MACE),defined as death,myocardial infarction,or stroke,and net adverse clinical events (NACE),defined as MACE or major bleeding...
May 15, 2018: EuroIntervention
https://www.readbyqxmd.com/read/29769148/current-landscape-and-future-of-dual-anti-ctla4-and-pd-1-pd-l1-blockade-immunotherapy-in-cancer-lessons-learned-from-clinical-trials-with-melanoma-and-non-small-cell-lung-cancer-nsclc
#11
REVIEW
Young Kwang Chae, Ayush Arya, Wade Iams, Marcelo R Cruz, Sunandana Chandra, Jaehyuk Choi, Francis Giles
Immunotherapy is among the most rapidly evolving treatment strategies in oncology. The therapeutic potential of immune-checkpoint inhibitors is exemplified by the recent hail of Food and Drug Administration (FDA) approvals for their use in various malignancies. Continued efforts to enhance outcomes with immunotherapy agents have led to the formulation of advanced treatment strategies. Recent evidence from pre-clinical studies evaluating immune-checkpoint inhibitors in various cancer cell-lines has suggested that combinatorial approaches may have superior survival outcomes compared to single-agent immunotherapy regimens...
May 16, 2018: Journal for Immunotherapy of Cancer
https://www.readbyqxmd.com/read/29769124/knowledge-towards-cervical-cancer-prevention-and-screening-practices-among-women-who-attended-reproductive-and-child-health-clinic-at-magu-district-hospital-lake-zone-tanzania-a-cross-sectional-study
#12
Mabula M Mabelele, John Materu, Faraja D Ng'ida, Michael J Mahande
BACKGROUND: Cervical cancer is a global leading cause of morbidity and mortality, attributable to the death of approximately 266,000 women every year. Majority (87%) of cervical cancer deaths occur in developing countries including Tanzania. Though knowledge of cervical cancer is an important determinant of women's participation in prevention and screening for cervical cancer, little is known about this topic in Tanzania. This study aimed to determine the knowledge of cervical cancer prevention services and screening practices among women who attended Reproductive Child Health clinic at a district hospital in Lake Zone, Tanzania...
May 16, 2018: BMC Cancer
https://www.readbyqxmd.com/read/29767823/the-validity-of-open-source-data-when-assessing-jail-suicides
#13
Amanda L Thomas, Jacqueline Scott, Jeff Mellow
BACKGROUND: The Bureau of Justice Statistics' Deaths in Custody Reporting Program is the primary source for jail suicide research, though the data is restricted from general dissemination. This study is the first to examine whether jail suicide data obtained from publicly available sources can help inform our understanding of this serious public health problem. METHODS: Of the 304 suicides that were reported through the DCRP in 2009, roughly 56 percent (N = 170) of those suicides were identified through the open-source search protocol...
May 9, 2018: Health & Justice
https://www.readbyqxmd.com/read/29767258/pd-l1-mrna-expression-in-egfr-mutant-lung-adenocarcinoma
#14
Kazutoshi Isobe, Atsushi Kakimoto, Tetuo Mikami, Kyohei Kaburaki, Hiroshi Kobayashi, Takahiro Yoshizawa, Yuta Nakano, Takashi Makino, Hajime Otsuka, Go Sano, Keishi Sugino, Susumu Sakamoto, Yujiro Takai, Naobumi Tochigi, Akira Iyoda, Sakae Homma
Molecular mechanisms of programmed death-ligand 1 (PD-L1) mRNA expression and roles of apoptosis and biomarkers are poorly understood in epidermal growth factor receptor (EGFR)-mutant lung adenocarcinoma patients. Thirty-three patients with recurrent postoperative EGFR-mutant lung adenocarcinoma (exon 19 deletion in 16, L858R in 15, G719C in 2 patients) treated with gefitinib were studied. PD-L1 mRNA expression of formalin-fixed paraffin-embedded paratumoral and intratumoral tissues was quantified by PCR. Correlations of PD-L1 mRNA expression with BIM, p53 upregulated modular of apoptosis (PUMA), human epidermal growth factor receptor 2 (HER2), mesenchymal-epithelial transition (MET), EGFR, and vascular endothelial growth factor A (VEGFA) were determined...
May 16, 2018: Oncology Reports
https://www.readbyqxmd.com/read/29766770/mri-guided-thrombolysis-for-stroke-with-unknown-time-of-onset
#15
Götz Thomalla, Claus Z Simonsen, Florent Boutitie, Grethe Andersen, Yves Berthezene, Bastian Cheng, Bharath Cheripelli, Tae-Hee Cho, Franz Fazekas, Jens Fiehler, Ian Ford, Ivana Galinovic, Susanne Gellissen, Amir Golsari, Johannes Gregori, Matthias Günther, Jorge Guibernau, Karl Georg Häusler, Michael Hennerici, André Kemmling, Jacob Marstrand, Boris Modrau, Lars Neeb, Natalia Perez de la Ossa, Josep Puig, Peter Ringleb, Pascal Roy, Enno Scheel, Wouter Schonewille, Joaquin Serena, Stefan Sunaert, Kersten Villringer, Anke Wouters, Vincent Thijs, Martin Ebinger, Matthias Endres, Jochen B Fiebach, Robin Lemmens, Keith W Muir, Norbert Nighoghossian, Salvador Pedraza, Christian Gerloff
Background Under current guidelines, intravenous thrombolysis is used to treat acute stroke only if it can be ascertained that the time since the onset of symptoms was less than 4.5 hours. We sought to determine whether patients with stroke with an unknown time of onset and features suggesting recent cerebral infarction on magnetic resonance imaging (MRI) would benefit from thrombolysis with the use of intravenous alteplase. Methods In a multicenter trial, we randomly assigned patients who had an unknown time of onset of stroke to receive either intravenous alteplase or placebo...
May 16, 2018: New England Journal of Medicine
https://www.readbyqxmd.com/read/29766492/nivolumab-versus-ipilimumab-in-the-treatment-of-advanced-melanoma-a-critical-appraisal
#16
M T Wan, M E Ming
AIM: To show whether either nivolumab in combination with ipilimumab or nivolumab monotherapy vs. ipilimumab monotherapy extends overall survival (OS) or progression-free survival (PFS) in adults with previously untreated, advanced melanoma. SETTING AND DESIGN: The trial was conducted at 137 sites in 21 countries. Randomization (n = 945; 1 : 1 : 1 ratio) was stratified according to metastasis stage, BRAF mutation status and programmed death ligand 1 status. STUDY EXPOSURE: Adults were randomized to one of the following: nivolumab plus ipilimumab every 3 weeks for four doses, followed by nivolumab every 2 weeks; nivolumab every 2 weeks plus placebo; or ipilimumab every 3 weeks for four doses plus placebo...
May 15, 2018: British Journal of Dermatology
https://www.readbyqxmd.com/read/29765155/genetic-transcriptional-and-post-translational-regulation-of-the-programmed-death-protein-ligand-1-in-cancer-biology-and-clinical-correlations
#17
REVIEW
Ioannis Zerdes, Alexios Matikas, Jonas Bergh, George Z Rassidakis, Theodoros Foukakis
The programmed death protein 1 (PD-1) and its ligand (PD-L1) represent a well-characterized immune checkpoint in cancer, effectively targeted by monoclonal antibodies that are approved for routine clinical use. The regulation of PD-L1 expression is complex, varies between different tumor types and occurs at the genetic, transcriptional and post-transcriptional levels. Copy number alterations of PD-L1 locus have been reported with varying frequency in several tumor types. At the transcriptional level, a number of transcriptional factors seem to regulate PD-L1 expression including HIF-1, STAT3, NF-κΒ, and AP-1...
May 16, 2018: Oncogene
https://www.readbyqxmd.com/read/29764856/-tp53-stk11-and-egfr-mutations-predict-tumor-immune-profile-and-the-response-to-anti-pd-1-in-lung-adenocarcinoma
#18
Jerome Biton, Audrey Mansuet-Lupo, Nicolas Pécuchet, Marco Alifano, Hanane Ouakrim, Jennifer Arrondeau, Pascaline Boudou-Rouquette, Francois Goldwasser, Karen Leroy, Jeremy Goc, Marie Wislez, Claire Germain, Pierre Laurent-Puig, Marie-Caroline Dieu-Nosjean, Isabelle Cremer, Ronald Herbst, Hélène F Blons, Diane Damotte
PURPOSE: By unlocking anti-tumor immunity, antibodies targeting programmed cell death 1 (PD-1) exhibit impressive clinical results in non-small cell lung cancer, underlining the strong interactions between tumor and immune cells. However, factors that can robustly predict long-lasting responses are still needed. EXPERIMENTAL DESIGN: We performed in depth immune profiling of lung adenocarcinoma using an integrative analysis based on immunohistochemistry, flow-cytometry and transcriptomic data...
May 15, 2018: Clinical Cancer Research: An Official Journal of the American Association for Cancer Research
https://www.readbyqxmd.com/read/29764752/successful-treatment-by-pembrolizumab-in-a-patient-with-end-stage-renal-disease-with-advanced-non-small-cell-lung-cancer-and-high-pd-l1-expression
#19
Shiho Ishizuka, Shinya Sakata, Chieko Yoshida, Akira Takaki, Sho Saeki, Kazuyoshi Nakamura, Kazuhiko Fujii
We report a 66-year-old Japanese male with end-stage renal disease (ESRD) and advanced non-small cell lung cancer (NSCLC) who was on hemodialysis. The patient harbored high programmed death ligand 1 (PD-L1) expression and was successfully treated with pembrolizumab. Laboratory examination upon diagnosis showed elevated serum creatinine (6.58 mg/dL). We administered pembrolizumab (200 mg/body) and repeated every 3 weeks. His renal dysfunction gradually progressed, hemodialysis was initiated after eight courses of pembrolizumab, and the antitumor effect was maintained at five months after hemodialysis initiation...
May 10, 2018: Respiratory Investigation
https://www.readbyqxmd.com/read/29764494/precision-medicine-becomes-reality-tumor-type-agnostic-therapy
#20
REVIEW
Li Yan, Wei Zhang
Precision medicine just witnessed two breakthroughs in oncology in 2017. Pembrolizumab (Keytruda), Merck's anti-programmed cell death-1 (PD-1) monoclonal antibody (mAb), received accelerated approval in May 2017 by the US Food and Drug Administration for the treatment of adult and pediatric patients with unresectable or metastatic solid tumors that have been identified as having microsatellite instability-high (MSI-H) or deficient DNA mismatch repair (dMMR). Shortly after, nivolumab (Opdivo), Bristol-Myers Squibb's anti-PD-1 mAb, gained an accelerated approval in August 2017 for adult and pediatric patients with MSI-H or dMMR metastatic colorectal cancer that has progressed after standard chemotherapy...
March 31, 2018: Cancer communications
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