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https://www.readbyqxmd.com/read/28332624/effects-of-icotinib-with-and-without-radiation-therapy-on-patients-with-egfr-mutant-non-small-cell-lung-cancer-and-brain-metastases
#1
Yun Fan, Yanjun Xu, Lei Gong, Luo Fang, Hongyang Lu, Jing Qin, Na Han, Fajun Xie, Guoqin Qiu, Zhiyu Huang
EGFR-TKIs and radiation therapy (RT) are the principal treatment for patients with brain metastases (BM) and EGFR mutant NSCLC. However, the optimal use of brain RT for patients with asymptomatic BM remains undefined. A total of 152 patients were identified. 58 patients were excluded. Of the remaining 97 patients, 56 patients received upfront RT followed by icotinib, including WBRT or SRS. 41 patients received icotinib therapy alone. The mOS from diagnosis of BM was 27.0 months for the whole cohort (95% CI, 23...
March 23, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28332584/akt-targeting-as-a-strategy-to-boost-chemotherapy-efficacy-in-non-small-cell-lung-cancer-through-metabolism-suppression
#2
Marion Le Grand, Raphael Berges, Eddy Pasquier, Marie-Pierre Montero, Laurence Borge, Alice Carrier, Sophie Vasseur, Veronique Bourgarel, Duje Buric, Nicolas André, Diane Braguer, Manon Carré
Metabolic reprogramming is a hallmark of cancer development, mediated by genetic and epigenetic alterations that may be pharmacologically targeted. Among oncogenes, the kinase Akt is commonly overexpressed in tumors and favors glycolysis, providing a rationale for using Akt inhibitors. Here, we addressed the question of whether and how inhibiting Akt activity could improve therapy of non-small cell lung cancer (NSCLC) that represents more than 80% of all lung cancer cases. First, we demonstrated that Akt inhibitors interacted synergistically with Microtubule-Targeting Agents (MTAs) and specifically in cancer cell lines, including those resistant to chemotherapy agents and anti-EGFR targeted therapies...
March 23, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28332580/clinical-impact-of-single-nucleotide-polymorphism-in-pd-l1-on-response-to-nivolumab-for-advanced-non-small-cell-lung-cancer-patients
#3
Takashi Nomizo, Hiroaki Ozasa, Takahiro Tsuji, Tomoko Funazo, Yuto Yasuda, Hironori Yoshida, Yoshitaka Yagi, Yuichi Sakamori, Hiroki Nagai, Toyohiro Hirai, Young Hak Kim
This study was intended to determine the efficacy of nivolumab, we evaluated treatment response with respect to PD-1/PD-L1 SNPs among patients with NSCLC. A total of 50 patients with NSCLC were treated with nivolumab and were also evaluated for PD-1/PD-L1 single nucleotide polymorphisms (SNPs) from plasma DNA. We investigated the association among PD-1/PD-L1 SNPs, objective response rate (ORR) and progression-free survival (PFS). Two of seven SNPs studied showed association with ORR and PFS, with maximum evidence at the marker rs2282055...
March 23, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28332433/the-cost-effectiveness-of-alectinib-in-anaplastic-lymphoma-kinase-positive-alk-advanced-nsclc-previously-treated-with-crizotinib
#4
J J Carlson, W Canestaro, A Ravelo, W Wong
Introduction Anaplastic lymphoma kinase (ALK) targeting drugs provide an important option for advanced non-small cell lung cancer patients with this distinct tumor type; however, there is considerable uncertainty as to which drug provides the optimal value after crizotinib treatment. This study estimated the cost-utility of alectinib vs ceritinib from a US payer perspective. Methods A cost-utility model was developed using partition survival methods and three health states: progression-free (PF), post-progression (PP), and death...
March 23, 2017: Journal of Medical Economics
https://www.readbyqxmd.com/read/28332364/potential-antitumor-activity-of-sim-89-in-non-small-cell-lung-cancer-cells
#5
Jun Pei, Tianqing Chu, Minhua Shao, Jiajun Teng, Huifang Sha, Aiqing Gu, Rong Li, Jialin Qian, Weifeng Mao, Ying Li, Baohui Han
PURPOSE: c-Met and its ligand, hepatocyte growth factor (HGF), play a critical role in oncogenesis and metastatic progression. The aim of this study was to identify inhibited enzymogram and to test the antitumor activity of SIM-89 (a c-Met receptor tyrosine kinase inhibitor) in non-small cell lung cancer. MATERIALS AND METHODS: Z'-LYTE kinase assay was employed to screen the kinase enzymogram, and mechanism of action (MOA) analysis was used to identify the inhibited kinases...
May 2017: Yonsei Medical Journal
https://www.readbyqxmd.com/read/28332225/molecular-dynamics-validation-of-crizotinib-resistance-to-alk-mutations-l1196m-and-g1269a-and-identification-of-specific-inhibitors
#6
Nagasundaram Nagarajan, Carlton Ranjith Wilson Alphonse, Prakash Vincent Samuel Gnana, Rajesh Kannan Rajaretinam
Anaplastic lymphoma kinase (ALK) positive non-small cell lung cancer (NSCLC) patients are mostly treated with ALK tyrosine kinase inhibitors (TKIs). Crizotinib is the first generation ALK inhibitor practiced as a primary chemo to combat cancer cells followed by second generation inhibitor ceritinib which are effective against crizotinib resistant ALK mutations. However, patients treated with these drugs invariably relapsed because of the development of new drug resistance mutations. In this study we explored the crizotinib resistance in the presence of ALK mutations L1196M and G1269A through molecular dynamics simulation studies...
March 23, 2017: Journal of Cellular Biochemistry
https://www.readbyqxmd.com/read/28332047/mechanisms-of-resistance-to-target-therapies-in-non-small-cell-lung-cancer
#7
Francesco Facchinetti, Claudia Proto, Roberta Minari, Marina Garassino, Marcello Tiseo
Targeted therapies are revolutionizing the treatment of advanced non-small cell lung cancer (NSCLC). The discovery of key oncogenic events mainly in lung adenocarcinoma, like EGFR mutations or ALK rearrangements, has changed the treatment landscape while improving the prognosis of lung cancer patients. Inevitably, virtually all patients initially treated with targeted therapies develop resistance because of the emergence of an insensitive cellular population, selected by pharmacologic pressure. Diverse mechanisms of resistance, in particular to EGFR, ALK and ROS1 tyrosine-kinase inhibitors (TKIs), have now been discovered and may be classified in three different groups: (1) alterations in the target (such as EGFR T790M and ALK or ROS1 mutations); (2) activation of alternative pathways (i...
March 23, 2017: Handbook of Experimental Pharmacology
https://www.readbyqxmd.com/read/28331830/prognostic-significance-of-%C3%AE-catenin-expression-in-patients-with-non-small-cell-lung-cancer-a-meta-analysis
#8
Jiajia Jin, Ping Zhan, Masaru Katoh, Susumu S Kobayashi, Kevin Phan, Hong Qian, Huijuan Li, Xiaoxia Wang, Xihua Wang, Yong Song
BACKGROUND: β-catenin is a key component of the canonical Wnt pathway, which plays pivotal roles in malignant transformation and cancer progression. Several studies have reported the clinical significance of the expression level of β-catenin in different subcellular locations. This meta-analysis aimed to assess the prognostic value of β-catenin expression patterns in patients with non-small cell lung cancer (NSCLC). METHODS: PubMed and Embase databases were searched to identify all articles referring to the association between β-catenin expression level and outcomes of patients of NSCLC up to November 2016...
February 2017: Translational Lung Cancer Research
https://www.readbyqxmd.com/read/28331811/proteomic-analysis-of-bronchoalveolar-lavage-fluid-balf-from-lung-cancer-patients-using-label-free-mass-spectrometry
#9
Abduladim Hmmier, Michael Emmet O'Brien, Vincent Lynch, Martin Clynes, Ross Morgan, Paul Dowling
BACKGROUND: Lung cancer is the leading cause of cancer-related mortality in both men and women throughout the world. The need to detect lung cancer at an early, potentially curable stage, is essential and may reduce mortality by 20%. The aim of this study was to identify distinct proteomic profiles in bronchoalveolar fluid (BALF) and plasma that are able to discriminate individuals with benign disease from those with non-small cell lung cancer (NSCLC). METHODS: Using label-free mass spectrometry analysis of BALF during discovery-phase analysis, a significant number of proteins were found to have different abundance levels when comparing control to adenocarcinoma (AD) or squamous cell lung carcinoma (SqCC)...
June 2017: BBA Clinical
https://www.readbyqxmd.com/read/28331612/utility-of-pd-l1-immunohistochemistry-assays-for-predicting-pd-1-pd-l1-inhibitor-response
#10
REVIEW
Laurence P Diggs, Eddy C Hsueh
We have seen a notable increase in the application of PD-1/PD-L1 inhibitors for the treatment of several solid and hematogenous malignancies including metastatic melanoma, non-small-cell lung cancer and lymphoma to name a few. The need for biomarkers for identification of a suitable patient population for this type of therapy is now pressing. While specific biomarker assays have been developed for these checkpoint inhibitors based on their respective epitopes, the available studies suggested the clinical utility of these biomarker assays is for response stratification and not patient selection...
2017: Biomarker Research
https://www.readbyqxmd.com/read/28331416/dna-pk-inhibition-by-nu7441-enhances-chemosensitivity-to-topoisomerase-inhibitor-in-non-small-cell-lung-carcinoma-cells-by-blocking-dna-damage-repair
#11
Masaaki Yanai, Haruhiko Makino, Bingqiong Ping, Kenichi Takeda, Natsumi Tanaka, Tomohiro Sakamoto, Kosuke Yamaguchi, Masahiro Kodani, Akira Yamasaki, Tadashi Igishi, Eiji Shimizu
BACKGROUND: DNA double-strand breaks (DSBs) are the most cytotoxic form of DNA damage and are induced by ionizing radiation and specific chemotherapeutic agents, such as topoisomerase inhibitors. Cancer cells acquire resistance to such therapies by repairing DNA DSBs. A major pathway for the repair of DNA DSBs is non-homologous end-joining (NHEJ), which requires DNA-dependent protein kinase (DNA-PK) activity. In this study, we investigated the effect of NU7441, a synthetic small-molecule compound, as a specific inhibitor of DNA-PK on the chemosensitization of non-small cell lung carcinoma (NSCLC) A549 cells...
March 2017: Yonago Acta Medica
https://www.readbyqxmd.com/read/28331344/adverse-prognostic-impact-of-tgfb1-t869c-polymorphism-in-non-small-cell-lung-cancer
#12
Yulan Sang, Xin Bi, Yan Liu, Wei Zhang, Dongjie Wang
Previously, several polymorphisms in TGFB1 have been identified in non-small-cell lung cancer (NSCLC), and the variants, C-509T, T869C, and G915C, have been demonstrated to associate with higher circulating levels of TGF-β1. However, little is known about the prognostic value of TGF-β1 polymorphisms in cancers. In this study, by genotyping the TGF-β1 T869C polymorphism in a total of 261 patients with NSCLC using DNA from blood lymphocytes, we first found that NSCLC patients, especially those with allele C carriers, had significantly higher serum TGF-β1 levels than healthy individuals...
2017: OncoTargets and Therapy
https://www.readbyqxmd.com/read/28330997/igfbp3-modulates-lung-tumorigenesis-and-cell-growth-through-igf1-signaling
#13
Yong A Wang, Yunguang Sun, Joshua D Palmer, Charalambos Solomides, Li-Ching Huang, Yu Shyr, Adam P Dicker, Bo Lu
Insulin-like growth factor binding protein 3 (IGFBP3) modulates cell growth through IGF-dependent and -independent mechanisms. Reports suggest that the serum levels of IGFBP3 are associated with various cancers and that IGFBP3 expression is significantly decreased in cisplatin (CDDP)-resistant lung cancer cells. Based on these findings, we investigated whether Igfbp3 deficiency accelerates mouse lung tumorigenesis and if expression of IGFBP3 enhances CDDP response by focusing on the IGF1 signaling cascade. To this end, an Igfbp3-null mouse model was generated in combination with KrasG12D to compare the tumor burden...
March 22, 2017: Molecular Cancer Research: MCR
https://www.readbyqxmd.com/read/28330089/discovery-of-potential-alk-inhibitors-by-virtual-screening-approach
#14
Anish Kumar, V Shanthi, K Ramanathan
Crizotinib is an anticancer drug used for the treatment of non-small cell lung cancer. Evidences available suggest that there is a development of an acquired resistance against crizotinib action due to the emergence of several mutations in the ALK gene. It is therefore necessary to develop potent anti-cancer drugs for the treatment of crizotinib resistance non-small cell lung cancer types. In the present study, a novel class of lead molecule was identified using virtual screening, molecular docking and molecular dynamic approach...
June 2016: 3 Biotech
https://www.readbyqxmd.com/read/28329255/resection-rate-and-operability-of-elderly-patients-with-non-small-cell-lung-cancer-nationwide-study-from-1991-to-2014
#15
Kristjan Baldvinsson, Gudrun Nina Oskarsdottir, Andri Wilberg Orrason, Hannes Halldorsson, Hunbogi Thorsteinsson, Martin Ingi Sigurdsson, Steinn Jonsson, Tomas Gudbjartsson
OBJECTIVES: An increasing number of elderly patients are diagnosed with non-small cell lung cancer (NSCLC). We compared the surgical resection rate, operability and survival in this age group (≥75 years) to younger patients using centralized databases in Iceland. METHODS: The study population comprised all patients diagnosed with NSCLC in Iceland from 1991 to 2014. A total of 140 elderly patients (≥75 years) with NSCLC underwent pulmonary resection and were compared with 550 surgically resected patients less than 75 years, with respect to resection rate, short and long-term survival and complications of surgery...
January 31, 2017: Interactive Cardiovascular and Thoracic Surgery
https://www.readbyqxmd.com/read/28329143/epidermal-growth-factor-receptor-mutations-are-linked-to-skip-n2-lymph-node-metastasis-in-resected-non-small-cell-lung-cancer-adenocarcinomas%C3%A2
#16
Francesco Guerrera, Stéphane Renaud, Fabrizio Tabbó, Anne-Claire Voegeli', Pier Luigi Filosso, Michèle Legrain, Monica Boita, Mickaël Schaeffer, Michèle Beau-Faller, Enrico Ruffini, Pierre-Emmanuel Falcoz, Giorgio Inghirami, Alberto Oliaro, Gilbert Massard
OBJECTIVES: The impact of skip N2 metastases (i.e. N2 lymph node metastases without N1) on survival in surgically resected non-small lung cancer remains an intriguing and rarely investigated topic. The goal of our study was to elucidate (i) skip N2 influence on overall survival (OS) and time to recurrence (TTR) in patients with resected lung adenocarcinoma and (ii) its link with epidermal growth factor receptor ( EGFR ) and v-Ki-ras2 Kirsten rat sarcoma viral oncogene homolog ( KRAS ) mutations...
December 15, 2016: European Journal of Cardio-thoracic Surgery
https://www.readbyqxmd.com/read/28327984/more-valuable-than-platinum-first-line-pembrolizumab-in-advanced-stage-non-small-cell-lung-cancer
#17
T Zou, M M Awad
No abstract text is available yet for this article.
February 27, 2017: Annals of Oncology: Official Journal of the European Society for Medical Oncology
https://www.readbyqxmd.com/read/28327934/pazopanib-or-placebo-in-completely-resected-stage-i-nsclc-patients-results-of-the-phase-ii-ifct-0703-trial
#18
B Besse, J Mazières, L Ribassin-Majed, F Barlesi, J Bennouna, R Gervais, L Moreau, H Berard, D Debieuvre, O Molinier, D Moro-Sibilot, P J Souquet, S Jacquot, L Petit, H Lena, J P Pignon, B Lacas, F Morin, B Milleron, G Zalcman, J C Soria
Background: Adjuvant treatment in resected stage I non-small cell lung cancer (NSCLC) is generally not recommended. Pazopanib is an oral tyrosine kinase inhibitor of VEGFR-1/2/3 and PDGFR-α/β. We explored the feasibility and efficacy of adjuvant pazopanib in this population. Patients and methods: In this double-blind phase II/III trial, patients with resected stage I NSCLC were randomized to placebo or pazopanib 800 mg/d (P800) for 6 months with a two-step Fleming design...
February 23, 2017: Annals of Oncology: Official Journal of the European Society for Medical Oncology
https://www.readbyqxmd.com/read/28327923/heart-dose-exposure-as-prognostic-marker-after-radiotherapy-for-resectable-stage-iiia-b-non-small-cell-lung-cancer-secondary-analysis-of-a-randomised-trial
#19
M Guberina, W Eberhardt, M Stuschke, T Gauler, F Heinzelmann, D Cheufou, M Kimmich, G Friedel, H Schmidberger, K Darwiche, V Jendrossek, M Schuler, G Stamatis, C Pöttgen
BACKGROUND: Heart exposure to ionizing irradiation can cause ischemic heart disease. The partial heart volume receiving ≥5 Gy (heartV5) was supposed to be an independent prognostic factor for survival after radiochemotherapy for locally advanced non-small cell lung cancer (NSCLC). But validation of the latter hypothesis is needed under the concurrent risks of lung cancer patients. PATIENTS AND METHODS: The ESPATUE phase III trial recruited patients with potentially operable IIIA(N2)/selected IIIB NSCLC between 01/2004 and 01/2013...
February 21, 2017: Annals of Oncology: Official Journal of the European Society for Medical Oncology
https://www.readbyqxmd.com/read/28327735/reverse-micelle-based-water-soluble-nanoparticles-for-simultaneous-bioimaging-and-drug-delivery
#20
Ying Chen, Yong Liu, Yongchao Yao, Shiyong Zhang, Zhongwei Gu
With special confined water pools, reverse micelles (RMs) have shown potential for a wide range of applications. However, the inherent water-insolubility of RMs hinders their further application prospects, especially for applications related to biology. We recently reported the first successful transfer of RMs from organic media to an aqueous phase without changing the smart water pools by the hydrolysis of an arm-cleavable interfacial cross-linked reverse micelles. Herein, we employed another elaborate amphiphile 1 to construct new acrylamide-based cross-linked water-soluble nanoparticles (ACW-NPs) under much gentler conditions...
March 22, 2017: Organic & Biomolecular Chemistry
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