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https://www.readbyqxmd.com/read/29351573/multicenter-french-harmonization-study-for-pd-l1-ihc-testing-in-non-small-cell-lung-cancer
#1
J Adam, N Le Stang, I Rouquette, A Cazes, C Badoual, H Pinot-Roussel, L Tixier, C Danel, F Damiola, D Damotte, F Penault-Llorca, S Lantuéjoul
Background: Various PD-L1 immunohistochemistry (IHC) assays have been developed and used in clinical trials in association with different drugs. In order to harmonize and make PD-L1 testing in non-small cell lung cancer (NSCLC) widely available, we conducted a multicenter study comparing PD-L1 standardized assays and laboratory-developed tests (LDT). Methods: IHC with five anti-PD-L1 monoclonal antibodies (28-8, 22C3, E1L3N, SP142 and SP263) was performed concomitantly on 41 NSCLC surgical specimens in 7 centers using Dako Autostainer Link 48 (3 centers), Leica Bond (2 centers) or Ventana BenchMark Ultra (2 centers), platforms...
January 16, 2018: Annals of Oncology: Official Journal of the European Society for Medical Oncology
https://www.readbyqxmd.com/read/29350683/ccat1-stimulation-of-the-symmetric-division-of-nsclc-stem-cells-through-activation-of-the-wnt-signalling-cascade
#2
Chongwen Xu, Guodong Xiao, Boxiang Zhang, Meng Wang, Jichang Wang, Dapeng Liu, Jing Zhang, Hong Ren, Xin Sun
Non-small cell lung cancer (NSCLC) is the leading cause of cancer-related mortalities worldwide, yet this condition remains a poorly understood malignancy, and the subgroup of cancer stem cells (CSCs) leading to therapeutic resistance and adverse prognosis have not been well studied. CSCs frequently undergo symmetric division, which facilitates expansion of the stem cell pool, contributing to long-term relapse and therapy failure. CCAT1 could act as a miRNA sponge to influence downstream genes; however, its roles in NSCLC stem cell are unclear...
January 19, 2018: Gene Therapy
https://www.readbyqxmd.com/read/29348894/the-efficacy-and-safety-of-tivantinib-in-the-treatment-of-solid-tumors-a-systematic-review-and-meta-analysis
#3
Hao Zhang, Zhengqiang Bao, Hongwei Liao, Wen Li, Zhihua Chen, Huahao Shen, Songmin Ying
Background: Tivantinib was designed to kill cancers by targeting the mesenchymal-epithelial transition (MET) protein. Although numerous tivantinib clinical trials are ongoing, tivantinib's efficacy and safety are still not clear. This meta-analysis was done to evaluate tivantinib's efficacy and safety in solid tumor treatment. Materials and Methods: PUBMED, EMBASE, and other databases were searched for eligible tivantinib clinical trials. The hazard ratio (HR) and 95% confidence interval (CI) of progression-free and overall survival (PFS and OS, respectively) were pooled and analyzed to evaluate tivantinib's efficacy...
December 22, 2017: Oncotarget
https://www.readbyqxmd.com/read/29348890/adoptive-immunotherapy-shows-encouraging-benefit-on-non-small-cell-lung-cancer-a-systematic-review-and-meta-analysis
#4
Binghao Zhao, Wenxiong Zhang, Dongliang Yu, Jianjun Xu, Yiping Wei
Although adoptive immunotherapy (AIT) is a novel emerging target treatment for non-small cell lung cancer (NSCLC), its actual efficacy remains controversial. In this meta-analysis, we aimed to evaluate the efficacy of AIT for NSCLC. We systematically searched PubMed, the Cochrane Library, EMBASE, Medline, and Web of Science for relevant parallel randomized controlled trials (RCTs) and high-quality observation studies of AIT without any language restrictions. Two investigators reviewed all the texts and extracted information regarding overall survival rate (OS), progression-free survival rate (PFS), objective response rate (ORR), and disease control rate (DCR) from eligible studies; sensitivity analyses and subgroup analyses were also conducted to reduce heterogeneity Of 319 suitable studies, 15 studies (13 RCTs and 2 observation studies) involving 1684 patients were finally included...
December 22, 2017: Oncotarget
https://www.readbyqxmd.com/read/29348867/pleural-mac30-as-a-prognostic-marker-in-nsclc-with-malignant-pleural-effusion
#5
Yi Shan, Hui Ding, Junjie Lu, Zhijun Ge, Yongfei Tan
Over-expressed meningioma-associate protein (MAC30) in tissues was associated with malignant tumor differentiation, metastasis and poor prognosis. However, the attention of MAC30 in pleural effusion from lung tumor is insufficient. Our retrospective study was prepared to explore the clinical values on diagnosis and prognosis of MAC30 from malignant pleural effusion (MPE) in non-small cell lung cancer (NSCLC). Levels of MAC30 were confirmed in MPE from 48 NSCLC patients and in benign pleural effusion (BPE) from 45 controls via enzyme-linked immunosorbent assay (ELISA)...
December 22, 2017: Oncotarget
https://www.readbyqxmd.com/read/29348853/3d-cultivation-of-nsclc-cell-lines-induce-gene-expression-alterations-of-key-cancer-associated-pathways-and-mimic-in-vivo-conditions
#6
Gabriele Gamerith, Johannes Rainer, Julia M Huber, Hubert Hackl, Zlatko Trajanoski, Stefan Koeck, Edith Lorenz, Johann Kern, Reinhard Kofler, Jens M Kelm, Heinz Zwierzina, Arno Amann
This work evaluated gene expression differences between a hanging-drop 3D NSCLC model and 2D cell cultures and their in-vivo relevance by comparison to patient-derived data from The Cancer Genome Atlas. Gene expression of 2D and 3D cultures for Colo699 and A549 were assessed using Affymetrix HuGene 1.0 ST gene chips. Biostatistical analyses tested for reproducibility, comparability and significant differences in gene expression profiles between cell lines, experiments and culture methods. The analyses revealed a high interassay correlation within specific culture systems proving a high validity...
December 22, 2017: Oncotarget
https://www.readbyqxmd.com/read/29348831/aberrant-expression-of-mir-21-mir-376c-and-mir-145-and-their-target-host-genes-in-merkel-cell-polyomavirus-positive-non-small-cell-lung-cancer
#7
Ismini Lasithiotaki, Eliza Tsitoura, Anastasios Koutsopoulos, Eleni Lagoudaki, Chara Koutoulaki, George Pitsidianakis, Demetrios A Spandidos, Nikolaos M Siafakas, George Sourvinos, Katerina M Antoniou
Merkel Cell Polyoma Virus (MCPyV) infection has been associated with non-small cell lung cancer (NSCLC). Viruses can manipulate cellular miRNAs or have a profound impact on cellular miRNA expression to control host regulatory pathways. In this study, we evaluated the expression profiles of cancer-associated and virally affected host microRNAs miR-21, miR-145, miR-146a, miR-155, miR-302c, miR-367 and miR-376c in a series of NSCLC tissue samples as well as in samples from "healthy" sites, distant from the tumour region that were either positive or negative for MCPyV DNA...
December 22, 2017: Oncotarget
https://www.readbyqxmd.com/read/29348824/kca3-1-channel-inhibition-leads-to-an-icam-1-dependent-increase-of-cell-cell-adhesion-between-a549-lung-cancer-and-hmec-1-endothelial-cells
#8
Etmar Bulk, Nadzeya Kramko, Ivan Liashkovich, Felix Glaser, Hermann Schillers, Hans-Joachim Schnittler, Hans Oberleithner, Albrecht Schwab
Early metastasis leads to poor prognosis of lung cancer patients, whose 5-year survival rate is only 15%. We could recently show that the Ca2+ sensitive K+ channel KCa3.1 promotes aggressive behavior of non-small cell lung cancer (NSCLC) cells and that it can serve as a prognostic marker in NSCLC. Since NSCLC patients die of metastases, we investigated whether KCa3.1 channels contribute to poor patient prognosis by regulating distinct steps of the metastatic cascade. We investigated the extravasation of NSCLC cells and focused on their adhesion to endothelial cells and on transendothelial migration...
December 22, 2017: Oncotarget
https://www.readbyqxmd.com/read/29346833/phase-1b-trial-of-ficlatuzumab-a-humanized-hepatocyte-growth-factor-inhibitory-monoclonal-antibody-in-combination-with-gefitinib-in-asian-patients-with-nsclc
#9
Eng-Huat Tan, Wan-Teck Lim, Myung-Ju Ahn, Quan-Sing Ng, Jin Seok Ahn, Daniel Shao-Weng Tan, Jong-Mu Sun, May Han, Francis C Payumo, Krista McKee, Wei Yin, Marc Credi, Shefali Agarwal, Jaroslaw Jac, Keunchil Park
Hepatocyte growth factor (HGF)/c-Met pathway dysregulation is a mechanism for epidermal growth factor receptor (EGFR) tyrosine kinase inhibitors (TKIs). Ficlatuzumab (AV-299; SCH 900105), a humanized IgG1 κ HGF inhibitory monoclonal antibody, prevents HGF/c-Met pathway ligand-mediated activation. This phase 1b study assessed the safety/tolerability, pharmacokinetics/pharmacodynamics, and antitumor activity of ficlatuzumab plus gefitinib in Asian patients with previously treated advanced non-small cell lung cancer (NSCLC)...
January 18, 2018: Clinical Pharmacology in Drug Development
https://www.readbyqxmd.com/read/29346604/unique-genetic-profiles-from-cerebrospinal-fluid-cell-free-dna-in-leptomeningeal-metastases-of-egfr-mutant-non-small-cell-lung-cancer-a-new-medium-of-liquid-biopsy
#10
Y S Li, B Y Jiang, J J Yang, X C Zhang, Z Zhang, J Y Ye, W Z Zhong, H Y Tu, H J Chen, Z Wang, C R Xu, B C Wang, H J Du, S Chuai, H Han-Zhang, J Su, Q Zhou, X N Yang, W B Guo, H H Yan, Y H Liu, L X Yan, B Huang, M M Zheng, Y L Wu
Background: Leptomeningeal metastases (LM) are more frequent in non-small cell lung cancer (NSCLC) with epidermal growth factor receptor (EGFR) mutations. Due to limited access to leptomeningeal lesions, the purpose of this study was to explore the potential role of cerebrospinal fluid (CSF) as a source of liquid biopsy in patients with LM. Patients and methods: Primary tumor, CSF, and plasma in NSCLC with LM were tested by next-generation sequencing. In total, 45 patients with suspected LM underwent lumbar puncture, and those with EGFR mutations diagnosed with LM were enrolled...
January 15, 2018: Annals of Oncology: Official Journal of the European Society for Medical Oncology
https://www.readbyqxmd.com/read/29346215/challenges-and-perspectives-for-immunotherapy-in-adenocarcinoma-of-the-pancreas-the-cancer-immunity-cycle
#11
Markus Kieler, Matthias Unseld, Daniela Bianconi, Gerald Prager
Pancreatic ductal adenocarcinoma (PDAC) is a lethal disease with a devastating 5-year overall survival of only approximately 7%. Although just 4% of all malignant diseases are accounted to PDAC, it will become the second leading cause of cancer-related deaths before 2030. Immunotherapy has proven to be a promising therapeutic option in various malignancies such as melanoma, non-small cell lung cancer (NSCLC), microsatellite instability-high gastrointestinal cancer, urinary tract cancer, kidney cancer, and others...
February 2018: Pancreas
https://www.readbyqxmd.com/read/29346180/development-of-a-pd-l1-complementary-diagnostic-immunohistochemistry-assay-sp142-for-atezolizumab
#12
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/29346041/post-treatment-mortality-after-surgery-and-stereotactic-body-radiotherapy-for-early-stage-non-small-cell-lung-cancer
#13
William A Stokes, Michael R Bronsert, Robert A Meguid, Matthew G Blum, Bernard L Jones, Matthew Koshy, David J Sher, Alexander V Louie, David A Palma, Suresh Senan, Laurie E Gaspar, Brian D Kavanagh, Chad G Rusthoven
Purpose In early-stage non-small cell lung cancer (NSCLC), post-treatment mortality may influence the comparative effectiveness of surgery and stereotactic body radiotherapy (SBRT), with implications for shared decision making among high-risk surgical candidates. We analyzed early mortality after these interventions using the National Cancer Database. Patients and Methods We abstracted patients with cT1-T2a, N0, M0 NSCLC diagnosed between 2004 and 2013 undergoing either surgery or SBRT. Thirty-day and 90-day post-treatment mortality rates were calculated and compared using Cox regression and propensity score-matched analyses...
January 18, 2018: Journal of Clinical Oncology: Official Journal of the American Society of Clinical Oncology
https://www.readbyqxmd.com/read/29345289/no-erythropoietin-induced-growth-is-observed-in-non-small-cell-lung-cancer-cells
#14
Armin Frille, Katharina Leithner, Andrea Olschewski, Horst Olschewski, Christoph Wohlkönig, Andelko Hrzenjak
Lung cancer patients have the highest incidence of anemia among patients with solid tumors. The use of recombinant human erythropoietin (Epo) has consistently been shown to reduce the need for blood transfusions and to increase hemoglobin levels in lung cancer patients with chemotherapy-induced anemia. However, clinical and preclinical studies have prompted concerns that Epo and the presence of its receptor, EpoR, in tumor cells may be responsible for adverse effects and, eventually, death. The question has been raised whether Epo promotes tumor growth and inhibits the death of cancer cells...
February 2018: International Journal of Oncology
https://www.readbyqxmd.com/read/29344640/over-regulation-of-microrna-133b-inhibits-cell-proliferation-of-cisplatin-induced-non-small-cell-lung-cancer-cells-through-pi3k-akt-and-jak2-stat3-signaling-pathway-by-targeting-egfr
#15
Bin Li, Cui-Min Ding, Yan-Xiao Li, Jing-Cui Peng, Nan Geng, Wen-Wen Qin
The present study determined the anticancer activity and its mechanism of microRNA‑133b on cell proliferation of cisplatin-induced non-small cell lung cancer cells. The expression of microRNA-133b cisplatin‑induced non-small cell lung cancer (NSCLC) tissue was lower than that of para-carcinoma tissue in patients. Overall survival of higher expression in cisplatin-induced NSCLC patients was higher than that of lower expression in cisplatin‑induced NSCLC patients. Over-regulation of microRNA-133b inhibited cell proliferation and LDH activity, induced apoptosis and caspase-3 activity, suppressed the protein expression of EGFR, PI3K, p-Akt, p-JAK2 and p-STAT3, decreased cyclin D1 and increased Bax protein expression in cisplatin‑induced A549 cells...
January 15, 2018: Oncology Reports
https://www.readbyqxmd.com/read/29344346/characterization-and-selective-incorporation-of-small-non-coding-rnas-in-non-small-cell-lung-cancer-extracellular-vesicles
#16
Chuang Li, Fang Qin, Fen Hu, Hui Xu, Guihong Sun, Guang Han, Tao Wang, Mingxiong Guo
Background: Extracellular vesicles (EVs) play important roles in intercellular communication through the delivery of their cargoes, which include proteins, lipids, and RNAs. Increasingly, multiple studies have reported the association between EV small non-coding RNAs and cancer, due to their regulatory functions in gene expression. Hence, analysis of the features of small non-coding RNA expression and their incorporation into EVs is important for cancer research. Results: We performed deep sequencing to investigate the expression of small RNAs in plasma EVs from lung adenocarcinoma (ADC) patients, lung squamous cell carcinoma (SQCC) patients, and healthy controls...
2018: Cell & Bioscience
https://www.readbyqxmd.com/read/29344298/akr1c1-activates-stat3-to-promote-the-metastasis-of-non-small-cell-lung-cancer
#17
Hong Zhu, Lin-Lin Chang, Fang-Jie Yan, Yan Hu, Chen-Ming Zeng, Tian-Yi Zhou, Tao Yuan, Mei-Dan Ying, Ji Cao, Qiao-Jun He, Bo Yang
Metastasis is the leading cause of mortality for human non-small cell lung cancer (NSCLC). However, it is difficult to target tumor metastasis because the molecular mechanisms underlying NSCLC invasion and migration remain unclear. Methods: GEO data analyses and IHC analyses were performed to identify that the expression level of AKR1C1, a member of human aldo-keto reductase family, was highly elevated in patients with metastasis or metastatic foci of NSCLC patients. Functional analyses (in vitro and in vivo) and quantitative genomic analyses were preformed to confirm the pro-metastatic effects of AKR1C1 and the underlying mechanisms...
2018: Theranostics
https://www.readbyqxmd.com/read/29344230/reduced-mir-105-1-levels-are-associated-with-poor-survival-of-patients-with-non-small-cell-lung-cancer
#18
Gaixia Lu, Da Fu, Chengyou Jia, Li Chai, Yang Han, Jin Liu, Tingmiao Wu, Ruting Xie, Zhengyan Chang, Huiqiong Yang, Pei Luo, Zhongwei Lv, Fei Yu, Xiaojun Zhong, Yushui Ma
Altered expression of microRNAs (miRNAs or miRs) contributes to lung carcinogenesis. The present study performed an in silico analysis of differentially expressed miRNAs in different peripheral blood samples from patients with various diseases vs. controls using the Gene Expression Omnibus (GEO) database data, and assessed miR-105-1 expression in 32 normal lung and 142 non-small cell lung cancer (NSCLC) tissue samples using reverse transcription-quantitative polymerase chain reaction. Survival data were calculated using Kaplan-Meier curves and a log-rank test...
December 2017: Oncology Letters
https://www.readbyqxmd.com/read/29344219/upregulation-of-mir-146a-increases-cisplatin-sensitivity-of-the-non-small-cell-lung-cancer-a549-cell-line-by-targeting-jnk-2
#19
Linrong Pang, Jinger Lu, Jia Huang, Caihong Xu, Hui Li, Guangbo Yuan, Xiaochun Cheng, Jun Chen
The aim of the present study was to investigate the effects of microRNA (miR-)146a on the cisplatin sensitivity of the non-small cell lung cancer (NSCLC) A549 cell line and study the underlying molecular mechanism. The differences in expression of miRNAs between A549 and A549/cisplatin (A549/DDP) cells were determined, and miR-146a was selected to study its effect on cisplatin sensitivity of A549/DDP cells. miR-146a mimic and inhibitor transient transfection systems were constructed using vectors, and A549/DDP cells were infected with miR-146a mimic and inhibitor to investigate growth, apoptosis and migration...
December 2017: Oncology Letters
https://www.readbyqxmd.com/read/29344206/impact-of-metastatic-status-on-the-prognosis-of-egfr-mutation-positive-non-small-cell-lung-cancer-patients-treated-with-first-generation-egfr-tyrosine-kinase-inhibitors
#20
Yoshihiko Taniguchi, Akihiro Tamiya, Kenji Nakahama, Yoko Naoki, Masaki Kanazu, Naoki Omachi, Kyoichi Okishio, Takahiko Kasai, Shinji Atagi
The aim of the present study was to analyze the impact of metastatic status on the prognosis of epithelial growth factor receptor (EGFR) mutation-positive patients with non-small cell lung cancer (NSCLC) treated with first-generation EGFR-tyrosine kinase inhibitors (TKIs). A total of 178 EGFR mutation-positive patients with stage IIIB-IV and relapsed NSCLC who were treated with gefitinib or erlotinib as the first-line treatment were enrolled in the present study. Metastatic status, progression-free survival (PFS), overall survival (OS) and treatment-response rates were investigated...
December 2017: Oncology Letters
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