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Non small cell lung cancer

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https://www.readbyqxmd.com/read/29906817/is-immune-checkpoint-inhibition-part-of-standard-therapy-for-stage-iii-non-small-cell-lung-cancer
#1
Jyoti D Patel, Steven J Chmura
No abstract text is available yet for this article.
June 15, 2018: Cancer
https://www.readbyqxmd.com/read/29906749/long-non-coding-rna-linc00339-facilitates-the-tumorigenesis-of-non-small-cell-lung-cancer-by-sponging-mir-145-through-targeting-foxm1
#2
Yuan Yuan, Gao Haiying, Li Zhuo, Lu Ying, He Xin
Non-small cell lung cancer (NSCLC) is one of leading causes of cancer-related death worldwide. Long noncoding RNAs (lncRNAs) has been identified to modulate the tumorigenesis of NSCLC. However, the precise molecular mechanism of lncRNAs in the course is still unclear. Results showed that LINC00339 was significantly up-regulated in NSCLC tissue and cells, which indicated the poor prognosis of NSCLC patients. Loss-of-function experiments showed that LINC00339 silencing inhibited the proliferation and invasion, accelerated the apoptosis, and suppressed the tumor growth of NSCLC cells in vitro and in vivo...
June 12, 2018: Biomedicine & Pharmacotherapy, Biomédecine & Pharmacothérapie
https://www.readbyqxmd.com/read/29906465/mirna-mediated-apoptosis-activation-through-tmem-48-inhibition-in-a549-cell-line
#3
Feridun Akkafa, İsmail Koyuncu, Ebru Temiz, Hasan Dagli, Fuat Dïlmec, Halit Akbas
Lung has critic function in gas exchange, supplying oxygen to all cells. Rapid metastasis and the high rate of mortality characterises lung cancer. There are two types of this disease, small cell and non-small cell, which differs from each other according to histopathologic features. To date, many therapeutic approaches have been developed to destroy this deadly type of cancer, which one of them is mRNA targeted therapies through miRNA. miRNAs are 19-25 base paired molecules be able to suppress and destruct mRNA and found to be involved in development and progression of lung cancer...
June 12, 2018: Biochemical and Biophysical Research Communications
https://www.readbyqxmd.com/read/29906244/de-novo-lipogenesis-represents-a-therapeutic-target-in-mutant-kras-non-small-cell-lung-cancer
#4
Anju Singh, Christian Ruiz, Kavita Bhalla, John A Haley, Qing Kay Li, George Acquaah-Mensah, Emily Montal, Kuladeep R Sudini, Ferdinandos Skoulidis, Ignacio I Wistuba, Vassiliki Papadimitrakopoulou, John V Heymach, Laszlo G Boros, Edward Gabrielson, Julian Carretero, Kwok-Kin Wong, John D Haley, Shyam Biswal, Geoffrey D Girnun
Oncogenic Kras mutations are one of the most common alterations in non-small cell lung cancer and are associated with poor response to treatment and reduced survival. Driver oncogenes, such as Kras are now appreciated for their ability to promote tumor growth via up-regulation of anabolic pathways. Therefore, we wanted to identify metabolic vulnerabilities in Kras-mutant lung cancer. Using the Kras LSL-G12D lung cancer model, we show that mutant Kras drives a lipogenic gene-expression program. Stable-isotope analysis reveals that mutant Kras promotes de novo fatty acid synthesis in vitro and in vivo...
June 15, 2018: FASEB Journal: Official Publication of the Federation of American Societies for Experimental Biology
https://www.readbyqxmd.com/read/29906114/design-synthesis-and-biological-evaluation-of-pyrimido-4-5-d-pyrimidine-2-4-1-h-3-h-diones-as-potent-and-selective-epidermal-growth-factor-receptor-egfr-inhibitors-against-l858r-t790m-resistance-mutation
#5
Yongjia Hao, Jiankun Lyu, Rong Qu, Yi Tong, Deheng Sun, Fang Feng, Linjiang Tong, Tingyuan Yang, Zhenjiang Zhao, Lili Zhu, Jian Ding, Yufang Xu, Hua Xie, Honglin Li
First-generation epidermal growth factor receptor (EGFR) inhibitors, gefitinib and erlotinib have achieved initially marked clinical efficacy for non-small cell lung cancer (NSCLC) patients with EGFR activating mutations. However, their clinical benefit was limited by the emergence of acquired resistance mutations. In most cases (approximately 60%), the resistance was caused by the secondary EGFR T790M gatekeeper mutation. Thus, it is still desirable to develop novel third-generation EGFR inhibitors to overcome T790M mutation while sparing wild-type (WT) EGFR...
June 15, 2018: Journal of Medicinal Chemistry
https://www.readbyqxmd.com/read/29905882/ercc1-assessment-in-upfront-treatment-with-and-without-cisplatin-based-chemotherapy-in-stage-iiib-iv-non-squamous-non-small-cell-lung-cancer
#6
Matthias Villalobos, Piotr Czapiewski, Niels Reinmuth, Jürgen R Fischer, Stefan Andreas, Cornelius Kortsik, Monika Serke, Martin Wolf, Petra Neuser, Alexander Reuss, Philipp A Schnabel, Michael Thomas
Prior studies have demonstrated an association between excision repair cross-complementation group 1 (ERCC1) expression level and outcomes in patients with advanced non-small cell lung cancer (NSCLC) treated with platinum-based chemotherapy. The aim of this study was to assess the impact of ERCC1 on survival for patients with stage IIIB/IV non-squamous NSCLC (NS-NSCLC) enrolled in the INNOVATIONS trial, thus receiving as treatment either erlotinib/bevacizumab (EB) or cisplatin/gemcitabine/bevacizumab (PGB)...
June 15, 2018: Medical Oncology
https://www.readbyqxmd.com/read/29905778/predictive-biomarkers-for-response-to-egfr-directed-monoclonal-antibodies-for-advanced-squamous-cell-lung-cancer
#7
P D Bonomi, D Gandara, F R Hirsch, K M Kerr, C Obasaju, L Paz-Ares, C Bellomo, J D Bradley, P A Bunn, M Culligan, J R Jett, E S Kim, C J Langer, R B Natale, S Novello, M Pérol, S S Ramalingam, M Reck, C H Reynolds, E F Smit, M A Socinski, D R Spigel, J F Vansteenkiste, H Wakelee, N Thatcher
Background: Upregulated expression and aberrant activation of the epidermal growth-factor receptor (EGFR) are found in lung cancer, making EGFR a relevant target for non-small-cell lung cancer (NSCLC). Treatment with anti-EGFR monoclonal antibodies (mAbs) is associated with modest improvement in overall survival in patients with squamous cell lung cancer (SqCLC) who have a significant unmet need for effective treatment options. While there is evidence that using EGFR gene copy number, EGFR mutation, and EGFR protein expression as biomarkers can help select patients who respond to treatment, it is important to consider biomarkers for response in patients treated with combination therapies that include EGFR mAbs...
June 14, 2018: Annals of Oncology: Official Journal of the European Society for Medical Oncology
https://www.readbyqxmd.com/read/29905018/phase-ii-study-of-carboplatin-pemetrexed-and-bevacizumab-in-advanced-nonsquamous-non-small-cell-lung-cancer
#8
Nicole F Laslett, SuJung Park, Gregory A Masters, David D Biggs, Charles J Schneider, Jamal G Misleh, Kathir Suppiah, Pamela S Simpson, Stephen Grubbs, Timothy F Wozniak, Michael Guarino
Lung cancer remains the leading cause of cancer death throughout the world. Despite new chemotherapeutic, immunomodulating and molecularly targeted agents, patients with locally advanced or metastatic disease still have a poor prognosis. This trial looked to combine antiangiogenic therapy with a first-line cytotoxic chemotherapy doublet, hoping to extend median progression-free survival (PFS) while minimizing toxicity in patients with advanced nonsquamous non-small-cell lung cancer (NSCLC). In this single institution, single-arm study, 51 patients (age >18 yo) were followed from 2007 to 2012...
June 14, 2018: Cancer Medicine
https://www.readbyqxmd.com/read/29904739/internal-dose-escalation-is-associated-with-increased-local-control-for-non-small-cell-lung-cancer-nsclc-brain-metastases-treated-with-stereotactic-radiosurgery-srs
#9
Christopher Abraham, Adam Garsa, Shahed N Badiyan, Robert Drzymala, Deshan Yang, Todd DeWees, Christina Tsien, Joshua L Dowling, Keith M Rich, Michael R Chicoine, Albert H Kim, Eric C Leuthardt, Cliff Robinson
Objective: To identify potentially actionable dosimetric predictors of local control (LC) for non-small cell lung cancer (NSCLC) brain metastases treated with single-fraction stereotactic radiosurgery (SRS). Methods and materials: Patients with NSCLC brain metastases treated with single-fraction SRS were identified. Eligible patients had at least 1 follow-up magnetic resonance imaging scan and were without prior metastasectomy or SRS to the same lesion. LC and overall survival (OS) were estimated using the Kaplan-Meier method...
April 2018: Advances in Radiation Oncology
https://www.readbyqxmd.com/read/29904737/serum-cytokine-profiles-and-metabolic-tumor-burden-in-patients-with-non-small-cell-lung-cancer-undergoing-palliative-thoracic-radiation-therapy
#10
Hanne A Eide, Ingerid Skjei Knudtsen, Vandana Sandhu, Ayca M Løndalen, Ann Rita Halvorsen, Azadeh Abravan, Elin H Kure, Trond V Bogsrud, Odd Terje Brustugun, Jon Amund Kyte, Eirik Malinen, Åslaug Helland
Purpose: Radiation therapy effectively kills cancer cells and elicits local effects in the irradiated tissue. The aim of this study was to investigate the kinetics of cytokines in the serum of patients with lung cancer undergoing radiation therapy and to identify associations with metabolic tumor burden as determined by 2-deoxy-2-fluoro-D-glucose (18 F-FDG) positron emission tomography (PET). Methods and materials: Forty-five patients with advanced non-small cell lung cancer were included in a phase 2 clinical trial and randomized between fractionated thoracic radiation therapy alone or concurrent with an epidermal growth factor receptor inhibitor...
April 2018: Advances in Radiation Oncology
https://www.readbyqxmd.com/read/29904736/lung-cancer-specialists-opinions-on-treatment-for-stage-i-non-small-cell-lung-cancer-a-multidisciplinary-survey
#11
Austin Lammers, Timur Mitin, Drew Moghanaki, Charles R Thomas, Robert Timmerman, Sara E Golden, Sujata Thakurta, Rafal Dziadziuszko, Christopher G Slatore
Purpose: The current standard of care for surgically eligible stage I non-small cell lung cancer (NSCLC) is surgical resection, but emerging data suggest that stereotactic body radiation therapy (SBRT) is potentially as effective as surgery. However, specialist views of the current evidence about SBRT and how they would incorporate a randomized controlled trial (RCT) into practice is unclear. We sought to understand specialist opinions about evidence regarding treatment of stage I NSCLC and how this translates into practice and clinical trial implementation...
April 2018: Advances in Radiation Oncology
https://www.readbyqxmd.com/read/29904349/an-in-vitro-assay-of-herg-k-channel-potency-for-a-new-egfr-inhibitor-fhnd004
#12
Tao Jin, Bingxue Hu, Shanshan Chen, Qiang Wang, Xue Dong, Yin Zhang, Yongqiang Zhu, Zhao Zhang
FHND004 is a newly synthesized epidermal growth factor receptor (EGFR) inhibitor for the treatment of non-small cell lung cancer (NSCLC). The aim of the present study was to investigate the impacts of FHND004 on human ether-à-go-go- related gene (hERG) K+ channels and the molecular mechanisms underlying of its action. Whole-cell patch clamp recording was performed on wild type (WT), mutant hERG channels heterologously expressed in human embryonic kidney (HEK) 293 cells or I Kr endogenously expressed in HL-1 cells, respectively...
2018: Frontiers in Pharmacology
https://www.readbyqxmd.com/read/29904031/immunotherapy-in-non-small-cell-lung-cancer-shifting-prognostic-paradigms
#13
REVIEW
Megan B Barnet, Wendy A Cooper, Michael J Boyer, Steven Kao
Immune checkpoint inhibitors have shown efficacy in the treatment of non-small cell lung cancer (NSCLC) in the adjuvant, first- and subsequent-line settings. In metastatic disease, they provide hope of durable response where “best-case” scenario has long been inadequate. This progress has highlighted the immunogenic nature of NSCLC and invigorated research into immunotherapy in the field. In this review we consider the foundations of immunotherapy in NSCLC, canvass the current research and summarise the evidence guiding clinical practice...
June 14, 2018: Journal of Clinical Medicine
https://www.readbyqxmd.com/read/29903552/quality-adjusted-outcomes-stratified-by-response-in-patients-with-advanced-non-small-cell-lung-cancer-receiving-first-line-nab-paclitaxel-carboplatin-or-paclitaxel-carboplatin
#14
Vera Hirsh, Yin Wan, Fang-Ju Lin, Sandra Margunato-Debay, Teng Jin Ong, Marc Botteman, Corey Langer
BACKGROUND: First-line nab-paclitaxel/carboplatin was associated with a significantly improved overall response rate (primary endpoint) versus paclitaxel/carboplatin in a phase III trial of advanced non-small-cell lung cancer (NSCLC). We report the results of an analysis evaluating the correlation of response and the time to response with survival and quality-adjusted outcomes. PATIENTS AND METHODS: Using a landmark approach, progression-free survival (PFS), overall survival (OS), and quality-adjusted time without symptoms or toxicity (Q-TWiST) were compared between patients with a confirmed partial or complete response at or before 6 weeks (≤ 6-week responders) and those without (≤ 6-week nonresponders)...
May 7, 2018: Clinical Lung Cancer
https://www.readbyqxmd.com/read/29903551/rationale-and-protocol-for-a-canadian-multicenter-phase-ii-randomized-trial-assessing-selective-metabolically-adaptive-radiation-dose-escalation-in-locally-advanced-non-small-cell-lung-cancer-nct02788461
#15
Srinivas Raman, Jean-Pierre Bissonnette, Andrew Warner, Lisa Le, Scott Bratman, Natasha Leighl, Andrea Bezjak, David Palma, Devin Schellenberg, Alexander Sun
We explain the rationale for metabolically adaptive radiation dose escalation in stage III non-small-cell lung cancer and describe the design of a Canadian phase II randomized trial investigating this approach. In the trial, patients are randomized to either conventional chemoradiation treatment (60 Gy in 30 fractions) or metabolically adaptive chemoradiation, where fluorodeoxyglucose-avid tumor sub-volumes receive an integrated boost dose to a maximum of 85 Gy in 30 fractions. The trial sample size is 78 patients, and the target population is patients with newly diagnosed, inoperable stage III non-small-cell lung cancer treated with radical intent chemoradiation...
May 16, 2018: Clinical Lung Cancer
https://www.readbyqxmd.com/read/29902802/relationship-between-paronychia-and-drug-concentrations-of-epidermal-growth-factor-receptor-tyrosine-kinase-inhibitors
#16
Katsuhiro Masago, Kei Irie, Shiro Fujita, Fumiko Imamichi, Yutaka Okada, Nobuyuki Katakami, Shoji Fukushima, Yasushi Yatabe
PURPOSE: The purpose of the study was to evaluate the site of paronychia in patients with non-small cell lung cancer harboring an epidermal growth factor receptor (EGFR) gene activating mutation who were treated with EGFR tyrosine kinase inhibitors (EGFR TKIs). PATIENTS AND METHODS: The study included 55 patients with non-small-cell lung cancer who were treated with an EGFR TKIs. Resulting all toxicities were graded using the Common Terminology Criteria for Adverse Events version 4...
June 14, 2018: Oncology
https://www.readbyqxmd.com/read/29902719/surmounting-the-resistance-against-egfr-inhibitors-through-the-development-of-thieno-2-3-d-pyrimidine-based-dual-egfr-her2-inhibitors
#17
Sandra N Milik, Amal Kamal Abdel-Aziz, Deena S Lasheen, Rabah A T Serya, Saverio Minucci, Khaled A M Abouzid
In light of the emergence of resistance against the currently available EGFR inhibitors, our study focuses on tackling this problem through the development of dual EGFR/HER2 inhibitors with improved enzymatic affinities. Guided by the binding mode of the marketed dual EGFR/HER2 inhibitor, Lapatinib, we proposed the design of dual EGFR/HER2 inhibitors based on the 6-phenylthieno[2,3-d]pyrimidine as a core scaffold and hinge binder. After two cycles of screening aiming to identify the optimum aniline headgroup and solubilizing group, we eventually identified 27b as a dual EGFR/HER2 inhibitor with IC50 values of 91...
June 6, 2018: European Journal of Medicinal Chemistry
https://www.readbyqxmd.com/read/29902067/biomarkers-for-alk-and-ros1-in-lung-cancer-immunohistochemistry-and-fluorescent-in-situ-hybridization
#18
Peter P Luk, Christina I Selinger, Annabelle Mahar, Wendy A Cooper
CONTEXT: - A small proportion of non-small cell lung cancers harbor rearrangements of ALK or ROS1 genes, and these tumors are sensitive to targeted tyrosine kinase inhibitors. It is crucial for pathologists to accurately identify tumors with these genetic alterations to enable patients to access optimal treatments and avoid unnecessary side effects of less effective agents. Although a number of different techniques can be used to identify ALK- and ROS1-rearranged lung cancers, immunohistochemistry and fluorescence in situ hybridization are the mainstays...
June 14, 2018: Archives of Pathology & Laboratory Medicine
https://www.readbyqxmd.com/read/29902012/tumor-targeted-nanoparticles-deliver-a-vitamin-d-based-drug-payload-for-treatment-of-egfr-tyrosine-kinase-inhibitor-resistant-lung-cancer
#19
Chang Liu, Tatiana Shaurova, Suzanne Shoemaker, Martin Petkovich, Pamela A Hershberger, Yun Wu
Mutation in the tyrosine kinase (TK) domain of the epidermal growth factor receptor (EGFR) gene drives the development of lung cancer. EGFR tyrosine kinase inhibitors (EGFR TKI) including erlotinib and afatinib are initially effective in treating EGFR mutant non-small cell lung cancer (NSCLC). However, drug resistance quickly develops due to several mechanisms, including induction of the epithelial-mesenchymal transition (EMT). No effective therapies are currently available for patients who develop EMT-associated EGFR TKI resistance...
June 14, 2018: Molecular Pharmaceutics
https://www.readbyqxmd.com/read/29901571/indoleamine-2-3-dioxygenase-in-non-small-cell-lung-cancer-a-targetable-mechanism-of-immune-resistance-frequently-coexpressed-with-pd-l1
#20
Ashley Volaric, Ryan Gentzler, Richard Hall, James H Mehaffey, Edward B Stelow, Timothy N Bullock, Linda W Martin, Anne M Mills
The immune regulatory enzyme indoleamine-2,3-dioxygenase (IDO-1) suppresses T cell responses and may reduce efficacy of therapies targeting immune checkpoints such as programmed death receptor-1/programmed death ligand-1 (PD-1/PD-L1). Early phase clinical trials combining IDO-1 and PD-1/PD-L1 inhibitors have shown some promise in non-small cell lung cancers (NSCLCs). However, the coexpression of IDO-1 and PD-L1 has not been thoroughly investigated, and the potential for IDO-1 immunohistochemical expression as a therapeutic biomarker is unknown...
June 12, 2018: American Journal of Surgical Pathology
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