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https://www.readbyqxmd.com/read/28811082/correlation-between-molecular-analysis-diagnosis-according-to-the-2015-who-classification-of-unresected-lung-tumours-and-ttf1-expression-in-small-biopsies-and-cytology-specimens-from-344-non-small-cell-lung-carcinoma-patients
#1
Prudence A Russell, Toni-Maree Rogers, Benjamin Solomon, Naveed Alam, Stephen A Barnett, Vivek Rathi, Richard A Williams, Gavin M Wright, Matthew Conron
We investigated correlations between diagnosis according to the 2015 World Health Organization (WHO) classification of unresected lung tumours, molecular analysis and TTF1 expression in small biopsy and cytology specimens from 344 non-small cell lung carcinoma (NSCLC) patients. One case failed testing for EGFR, KRAS and ALK abnormalities and six had insufficient tumour for ALK testing. Overall mutation rate in 343 cases was 48% for the genes tested, with 19% EGFR, 33% KRAS and 4% BRAF mutations, and 5% ALK rearrangements detected...
August 12, 2017: Pathology
https://www.readbyqxmd.com/read/28810650/glutathione-s-transferase-a1-mediates-nicotine-induced-lung-cancer-cell-metastasis-by-promoting-epithelial-mesenchymal-transition
#2
Wei Wang, Feiyu Liu, Chaoyang Wang, Chengde Wang, Yijun Tang, Zhongmin Jiang
The present study aimed to investigate the effect of glutathione S-transferase A1 (GSTA1) on lung cancer cell viability, invasion and adhesion in the presence of nicotine in vitro. Furthermore, the effect of GSTA1 on the epithelial-mesenchymal transition (EMT), a process strongly associated with lung cancer metastasis, was examined. Human lung carcinoma A549 cells were treated with various concentrations of nicotine (0.01, 0.1, 1 and 10 µM) and levels of GSTA1 mRNA and protein were measured by reverse transcription-quantitative polymerase chain reaction and western blot analysis, respectively...
August 2017: Experimental and Therapeutic Medicine
https://www.readbyqxmd.com/read/28809490/electrophilic-zinc-homoenolates-synthesis-of-cyclopropylamines-from-cyclopropanols-and-amines
#3
L Reginald Mills, Luis Miguel Barrera Arbelaez, Sophie A L Rousseaux
Metal homoenolates, produced via C-C bond cleavage of cyclopropanols, have been extensively investigated as nucleophiles for the synthesis of β-substituted carbonyl derivatives. Herein, we demonstrate that zinc homoenolates can react as carbonyl-electrophiles in the presence of nucleophilic amines to yield highly valuable trans-cyclopropylamines in good yields and high diastereoselectivities. GSK2879552, a lysine demethylase 1 inhibitor currently in clinical trials for the treatment of small cell lung carcinoma, was synthesized using this strategy...
August 15, 2017: Journal of the American Chemical Society
https://www.readbyqxmd.com/read/28807337/evaluation-of-cd43-expression-in-non-hematopoietic-malignancies
#4
Bjorn H Batdorf, Steven H Kroft, Paul R Hosking, Alexandra M Harrington, Alexander C Mackinnon, Horatiu Olteanu
OBJECTIVES: CD43 is normally expressed only on the surface of leukocytes, and is considered a sensitive and specific marker for hematologic malignancies. As such, it may have diagnostic utility in confirming hematolymphoid lineage in cases that are negative for CD45. Aberrant CD43 expression has been described in non-hematopoietic tumors, although literature data on this topic is variable and sometimes contradictory. To clarify and expand on existing literature findings, we evaluated CD43 expression by immunohistochemistry (IHC) in a large cohort (307) of non-hematopoietic neoplasms, including poorly differentiated malignancies...
August 2017: Annals of Diagnostic Pathology
https://www.readbyqxmd.com/read/28806116/systemic-therapy-for-stage-iv-non-small-cell-lung-cancer-american-society-of-clinical-oncology-clinical-practice-guideline-update
#5
Nasser Hanna, David Johnson, Sarah Temin, Sherman Baker, Julie Brahmer, Peter M Ellis, Giuseppe Giaccone, Paul J Hesketh, Ishmael Jaiyesimi, Natasha B Leighl, Gregory J Riely, Joan H Schiller, Bryan J Schneider, Thomas J Smith, Joan Tashbar, William A Biermann, Gregory Masters
Purpose Provide evidence-based recommendations updating the 2015 ASCO guideline on systemic therapy for patients with stage IV non-small-cell lung cancer (NSCLC). Methods The ASCO NSCLC Expert Panel made recommendations based on a systematic review of randomized controlled trials from February 2014 to December 2016 plus the Cancer Care Ontario Program in Evidence-Based Care's update of a previous ASCO search. Results This guideline update reflects changes in evidence since the previous guideline update. Fourteen randomized controlled trials provide the evidence base; earlier phase trials also informed recommendation development...
August 14, 2017: Journal of Clinical Oncology: Official Journal of the American Society of Clinical Oncology
https://www.readbyqxmd.com/read/28805682/alk-in-non-small-cell-lung-cancer-nsclc-pathobiology-epidemiology-detection-from-tumor-tissue-and-algorithm-diagnosis-in-a-daily-practice
#6
REVIEW
Paul Hofman
Patients with advanced-stage non-small cell lung carcinoma (NSCLC) harboring an ALK rearrangement, detected from a tissue sample, can benefit from targeted ALK inhibitor treatment. Several increasingly effective ALK inhibitors are now available for treatment of patients. However, despite an initial favorable response to treatment, in most cases relapse or progression occurs due to resistance mechanisms mainly caused by mutations in the tyrosine kinase domain of ALK. The detection of an ALK rearrangement is pivotal and can be done using different methods, which have variable sensitivity and specificity depending, in particular, on the quality and quantity of the patient's sample...
August 12, 2017: Cancers
https://www.readbyqxmd.com/read/28805673/alk-status-assessment-with-liquid-biopsies-of-lung-cancer-patients
#7
REVIEW
Paul Hofman
Patients with advanced stage non-small cell lung carcinoma (NSCLC) harboring an anaplastic lymphoma kinase ALK gene rearrangement, detected from a tissue sample, can benefit from targeted ALK inhibitor treatment. However, while treatment is initially effective in most cases, relapse or progression occurs due to different resistance mechanisms including mutations in the tyrosine kinase domain of echinoderm microtubule-associated protein-like 4 (EML44)-ALK. The liquid biopsy concept has recently radically changed the clinical care of NSCLC patients, in particular for those harboring an epidermal growth factor receptor (EGFR) gene mutation...
August 12, 2017: Cancers
https://www.readbyqxmd.com/read/28804548/overexpression-of-pten-suppresses-non-small-cell-lung-carcinoma-metastasis-through-inhibition-of-integrin-%C3%AE-v%C3%AE-6-signaling
#8
Yan Xia Yu, Yi Wang, Hong Liu
Studies have demonstrated that the abnormal expression of phosphatase and tensin homolog deleted on chromosome 10 (PTEN) is associated with multiple malignancies, but its functional role in non-small-cell lung carcinoma (NSCLC) metastasis remains to be elucidated. In the present study, we investigated the role of PTEN in regulating proliferation, migration, and invasion of NSCLC cells by establishing NSCLC cell strains with constitutively silenced or elevated PTEN expression. We demonstrated that ectopic expression of PTEN inhibits migration and invasion of NSCLC cells in vitro through wound healing and Transwell invasion assays...
2017: American Journal of Translational Research
https://www.readbyqxmd.com/read/28802998/on-the-sulfation-of-o-desmethyltramadol-by-human-cytosolic-sulfotransferases
#9
Mohammed I Rasool, Ahsan F Bairam, Katsuhisa Kurogi, Ming-Cheh Liu
BACKGROUND: Previous studies have demonstrated that sulfate conjugation is involved in the metabolism of the active metabolite of tramadol, O-desmethyltramadol (O-DMT). The current study aimed to systematically identify the human cytosolic sulfotransferases (SULTs) that are capable of mediating the sulfation of O-DMT. METHODS: The sulfation of O-DMT under metabolic conditions was demonstrated using HepG2 hepatoma cells and Caco-2 human colon carcinoma cells. O-DMT-sulfating activity of thirteen known human SULTs and four human organ specimens was examined using an established sulfotransferase assay...
February 16, 2017: Pharmacological Reports: PR
https://www.readbyqxmd.com/read/28802669/studies-on-the-dynamic-resolution-of-crizotinib-intermediate
#10
Alexandre da S de França, Marcus V M Silva, Rebeca V Neves, Stefania P de Souza, Raquel A C Leão, Carlos M Monteiro, Ângelo Rocha, Carlos A M Afonso, Rodrigo O M A de Souza
Crizotinib is an anti-cancer agent approved for treatment of non-small cell lung carcinoma. Retrosynthetic analysis revels 1-(2,6-dichloro-3-fluorophenyl)ethanol as an important intermediate, which can be made available by different biocatalytic approaches. Herein we report our results on the kinetic and dynamic resolution towards the desired chiral intermediate for Crizotinib synthesis. The results obtained show that very good conversions and high selectivity could be obtained for the kinetic resolution (45% conv...
July 21, 2017: Bioorganic & Medicinal Chemistry
https://www.readbyqxmd.com/read/28801308/egfr-mutations-compromise-hypoxia-associated-radiation-resistance-through-impaired-replication-fork-associated-dna-damage-repair
#11
Mohammad Saki, Haruhiko Makino, Prashanthi Javvadi, Nozomi Tomimatsu, Lianghao Ding, Jennifer E Clark, Elaine Gavin, Kenichi Takeda, Joel Andrews, Debabrata Saha, Michael D Story, Sandeep Burma, Chaitanya Nirodi
Epidermal growth factor receptor (EGFR) signaling has been implicated in hypoxia-associated resistance to radiation or chemotherapy. Non-small cell lung carcinomas (NSCLC) with activating L858R or ΔE746-E750 EGFR mutations exhibit elevated EGFR activity and downstream signaling. Here, relative to wild type (WT) EGFR, mutant (MT) EGFR expression significantly increases radiosensitivity in hypoxic cells. Gene expression profiling in human bronchial epithelial cells (HBEC) revealed that MT-EGFR expression elevated transcripts related to cell cycle and replication in aerobic and hypoxic conditions and down-regulated RAD50, a critical component of non-homologous end-joining (NHEJ) and homologous recombination (HR) DNA repair pathways...
August 11, 2017: Molecular Cancer Research: MCR
https://www.readbyqxmd.com/read/28801183/paired-phase-ii-studies-of-erlotinib-bevacizumab-for-advanced-bronchioloalveolar-carcinoma-or-never-smokers-with-advanced-non-small-cell-lung-cancer-swog-s0635-and-s0636-trials
#12
Howard L West, James Moon, Antoinette J Wozniak, Philip Mack, Fred R Hirsch, Martin J Bury, Myron Kwong, Dorothy D Nguyen, Dennis F Moore, Jieling Miao, Mary Redman, Karen Kelly, David R Gandara
BACKGROUND: Before mutation testing of the epidermal growth factor receptor (EGFR) gene was recognized as highly associated with the activity of EGFR tyrosine kinase inhibitors (TKIs), clinically defined patient populations with bronchioloalveolar carcinoma (BAC) and never smokers were identified as likely to benefit from EGFR TKIs. From preclinical and clinical data suggesting potentially improved efficacy with a combination of an EGFR TKI and the antiangiogenic agent bevacizumab, the Southwestern Oncology Group (SWOG) initiated paired phase II trials to evaluate the combination of erlotinib/bevacizumab in patients with advanced BAC (SWOG S0635) or never smokers with advanced lung adenocarcinoma (SWOG S0636)...
July 6, 2017: Clinical Lung Cancer
https://www.readbyqxmd.com/read/28795418/cd274-pdl1-and-jak2-genomic-amplifications-in-pulmonary-squamous-cell-and-adenocarcinoma-patients
#13
Sergi Clavé, Lara Pijuan, David Casadevall, Álvaro Taus, Javier Gimeno, Sílvia Hernández-Llodrà, María Rodríguez-Rivera, Marta Lorenzo, Sílvia Menéndez, Joan Albanell, Blanca Espinet, Edurne Arriola, Marta Salido
AIMS: CD274 (PDL1) and JAK2 (9p24.1) gene amplifications have been recently described in pulmonary carcinomas in association with PD-L1 protein expression. Also, PTEN loss have been explored preclinically in relation with PD-L1 expression. It remains to be determined if these genomic alterations may affect PD-L1 expression levels in non-small cell lung cancer. METHODS AND RESULTS: PD-L1 and PTEN protein expression by IHC, and CD274, JAK2 and PTEN gene copy number alterations (CNAs) by FISH were studied in 171 pulmonary carcinoma specimens...
August 10, 2017: Histopathology
https://www.readbyqxmd.com/read/28795312/treatment-of-lung-carcinosarcoma-and-other-rare-histologic-subtypes-of-non-small-cell-lung-cancer
#14
REVIEW
Han Yang, Yongbin Lin, Ying Liang
Lung carcinosarcoma (PCS) and other histological subtypes of non-small cell lung cancer, such as primary pulmonary lymphoma (PPL), pulmonary carcinoid (PC), and primary pulmonary lymphoepithelioma-like carcinoma (LELC), are rare. For their low incidence, the diagnosis and treatment are still controversial. Some patients only need surgery, while others may need chemotherapy, radiotherapy, or targeted therapy. In this paper, we retrospectively reviewed the literature of some rare histological subtype of NSCLC for the recent 20 years, and try to get some conclusions...
August 10, 2017: Current Treatment Options in Oncology
https://www.readbyqxmd.com/read/28794826/incidental-extravascular-findings-in-computed-tomographic-angiography-for-planning-or-monitoring-endovascular-aortic-aneurysm-repair-smoker-patients-increased-lung-cancer-prevalence
#15
Maria Antonietta Mazzei, Susanna Guerrini, Francesco Gentili, Giuseppe Galzerano, Francesco Setacci, Domenico Benevento, Francesco Giuseppe Mazzei, Luca Volterrani, Carlo Setacci
AIM: To validate the feasibility of high resolution computed tomography (HRCT) of the lung prior to computed tomography angiography (CTA) in assessing incidental thoracic findings during endovascular aortic aneurysm repair (EVAR) planning or follow-up. METHODS: We conducted a retrospective study among 181 patients (143 men, mean age 71 years, range 50-94) referred to our centre for CTA EVAR planning or follow-up. HRCT and CTA were performed before or after 1 or 12 mo respectively to EVAR in all patients...
July 28, 2017: World Journal of Radiology
https://www.readbyqxmd.com/read/28794639/kiaa1522-overexpression-promotes-tumorigenicity-and-metastasis-of-esophageal-cancer-cells-through-potentiating-the-erk-activity
#16
Zhi-Hui Xie, Jing Yu, Li Shang, Yi-Qing Zhu, Jia-Jie Hao, Yan Cai, Xin Xu, Yu Zhang, Ming-Rong Wang
Esophageal squamous cell carcinoma (ESCC) is a highly malignant tumor associated with a poor prognosis, and the molecular mechanisms underlying its formation and progression remain poorly understood. KIAA1522 is upregulated in various tumor tissues, but its function is unknown. Alterations in KIAA1522 expression and its implication in ESCC are currently unclear. In this study, an immunohistochemical analysis of ESCC tissues showed that KIAA1522 was highly expressed in 46% (157/342) of ESCC specimens and that its expression was inversely correlated with the degree of differentiation (P=0...
2017: OncoTargets and Therapy
https://www.readbyqxmd.com/read/28793041/experimental-study-of-peripheral-blood-pro-surfactant-protein-b-for-screening-non-small-cell-lung-cancer
#17
Yong He, Zhenjie Jiang, Fengzhi Tong, Mingwu Li, Xingru Yin, Shixin Hu, Linlin Wang
Purpose: To evaluate the possibility of using peripheral-blood presurfactant protein B (Pro-SFTPB) for screening non-small cell lung cancer (NSCLC). Methods: A total of 873 healthy volunteers and 165 lung cancer patients hospitalized in the Fifth People's Hospital of Dalian were tested Pro-SFTPB once every half year from January 2014 to September 2015. The healthy volunteers were also conducted spiral computed tomography (CT) examination once every year. The data were then com-pared and statistically analyzed...
July 2017: Acta Cirúrgica Brasileira
https://www.readbyqxmd.com/read/28792981/hyperphosphorylation-of-rps6kb1-rather-than-overexpression-predicts-worse-prognosis-in-non-small-cell-lung-cancer-patients
#18
Bojiang Chen, Lan Yang, Rui Zhang, Yuncui Gan, Wen Zhang, Dan Liu, Hong Chen, Huairong Tang
RPS6KB1 is the kinase of ribosomal protein S6 which is 70 kDa and is required for protein translation. Although the abnormal activation of RPS6KB1 has been found in types of diseases, its role and clinical significance in non-small cell lung cancer (NSCLC) has not been fully investigated. In this study, we identified that RPS6KB1 was over-phosphorylated (p-RPS6KB1) in NSCLC and it was an independent unfavorable prognostic marker for NSCLC patients. In spite of the frequent expression of total RPS6KB1 and p-RPS6KB1 in NSCLC specimens by immunohistochemical staining (IHC), only p-RPS6KB1 was associated with the clinicopathologic characteristics of NSCLC subjects...
2017: PloS One
https://www.readbyqxmd.com/read/28790845/clinical-efficacy-evaluation-of-tyrosine-kinase-inhibitors-for-non-adenocarcinoma-lung-cancer-patients-harboring-egfr-sensitizing-mutations
#19
REVIEW
Xinyu Song, Zhehai Wang
Epidermal growth factor receptor (EGFR) tyrosine kinase inhibitors (TKIs) as a standard therapy have been used in EGFR-mutated adenocarcinoma of non-small-cell lung cancer (NSCLC) patients in recent years. But in current randomized prospective clinical trials, due to few cases of non-adenocarcinoma patients having been found, the efficacy of TKIs for EGFR-mutated non-adenocarcinoma and the relationship with clinicopathological characteristics remained debatable. The results of retrospective studies showed that the frequency of EGFR mutation was significantly associated with nationality, gender, smoking history, and histology type...
2017: OncoTargets and Therapy
https://www.readbyqxmd.com/read/28783173/synergistic-activity-and-heterogeneous-acquired-resistance-of-combined-mdm2-and-mek-inhibition-in-kras-mutant-cancers
#20
A N Hata, S Rowley, H L Archibald, M Gomez-Caraballo, F M Siddiqui, F Ji, J Jung, M Light, J S Lee, L Debussche, S Sidhu, R I Sadreyev, J Watters, J A Engelman
There are currently no effective targeted therapies for KRAS mutant cancers. Therapeutic strategies that combine MEK inhibitors with agents that target apoptotic pathways may be a promising therapeutic approach. We investigated combining MEK and MDM2 inhibitors as a potential treatment strategy for KRAS mutant non-small cell lung cancers (NSCLC) and colorectal carcinomas that harbor wild-type TP53. The combination of pimasertib (MEK inhibitor) and SAR405838 (MDM2 inhibitor) was synergistic and induced the expression of PUMA and BIM, led to apoptosis and growth inhibition in vitro, and tumor regression in vivo...
August 7, 2017: Oncogene
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