Abstract:
:The remarkable success of epidermal growth factor receptor (EGFR) and anaplastic lymphoma kinase (ALK) tyrosine kinase inhibitors in patients with EGFR mutations and ALK rearrangements, respectively, introduced the era of targeted therapy in advanced non-small cell lung cancer (NSCLC), shifting treatment from platinum-based combination chemotherapy to molecularly tailored therapy. Recent genomic studies in lung adenocarcinoma identified other potential therapeutic targets, including ROS1 rearrangements, RET fusions, MET amplification, and activating mutations in BRAF, HER2, and KRAS in frequencies exceeding 1%. Lung cancers that harbor these genomic changes can potentially be targeted with agents approved for other indications or under clinical development. The need to generate increasing amounts of genomic information should prompt health-care providers to be mindful of the amounts of tissue needed for these assays when planning diagnostic procedures. In this review, we summarize oncogenic drivers in NSCLC that can be currently detected, highlight their potential therapeutic implications, and discuss practical considerations for successful application of tumor genotyping in clinical decision making.
journal_name
Am J Respir Crit Care Medauthors
Cardarella S,Johnson BEdoi
10.1164/rccm.201305-0843PPsubject
Has Abstractpub_date
2013-10-01 00:00:00pages
770-5issue
7eissn
1073-449Xissn
1535-4970journal_volume
188pub_type
杂志文章,评审abstract:RATIONALE:E-cigarettes vaporize propylene glycol/vegetable glycerin (PG/VG), nicotine, and flavorings. However, the long-term health effects of exposing lungs to vaped e-liquids are unknown. OBJECTIVES:To determine the effects of chronic vaping on pulmonary epithelia. METHODS:We performed research bronchoscopies on h...
journal_title:American journal of respiratory and critical care medicine
pub_type: 杂志文章
doi:10.1164/rccm.201710-2033OC
更新日期:2018-07-01 00:00:00
abstract:RATIONALE:Hyponatremia is associated with decompensated heart failure and poor prognosis in patients with left ventricular systolic dysfunction. OBJECTIVES:We sought to determine if hyponatremia is associated with right heart failure and worse prognosis in patients with pulmonary arterial hypertension (PAH). METHODS:...
journal_title:American journal of respiratory and critical care medicine
pub_type: 杂志文章
doi:10.1164/rccm.200712-1876OC
更新日期:2008-06-15 00:00:00
abstract:RATIONALE:Dysregulation of cellular metabolism has been shown to participate in several pathologic processes. However, the role of metabolic reprogramming is not well appreciated in the pathogenesis of organ fibrosis. OBJECTIVES:To determine if glycolytic reprogramming participates in the pathogenesis of lung fibrosis...
journal_title:American journal of respiratory and critical care medicine
pub_type: 杂志文章
doi:10.1164/rccm.201504-0780OC
更新日期:2015-12-15 00:00:00
abstract:RATIONALE:Sarcoidosis is a granulomatous disease of unknown etiology, although M. tuberculosis may play a role in the pathogenesis. The traditional view holds that inflammation in sarcoidosis is compartmentalized to involved organs. OBJECTIVES:To determine whether whole blood gene expression signatures reflect inflamm...
journal_title:American journal of respiratory and critical care medicine
pub_type: 杂志文章
doi:10.1164/rccm.201106-1143OC
更新日期:2011-11-15 00:00:00
abstract::This study aimed to compare O2 consumption (VO2) determination by the gas-exchange (VO2GE) and Fick (VO2F) methods in cardiac surgical patients. A total of 10 mechanically ventilated postoperative patients were studied prospectively. Thermodilution was performed using three randomly applied techniques: room temperatur...
journal_title:American journal of respiratory and critical care medicine
pub_type: 临床试验,杂志文章,随机对照试验
doi:10.1164/ajrccm.149.5.8173750
更新日期:1994-05-01 00:00:00
abstract::The inflammatory cytokines, tumor necrosis factor-alpha (TNF-alpha) and interleukin-1-beta (IL-1 beta), have been associated with accelerated metabolism and protein turnover following exogenous administration in normal humans. We hypothesized that these inflammatory cytokines might contribute to the weight-losing proc...
journal_title:American journal of respiratory and critical care medicine
pub_type: 杂志文章
doi:10.1164/ajrccm.153.2.8564110
更新日期:1996-02-01 00:00:00
abstract:RATIONALE:Increased thickness of the airway smooth muscle (ASM) layer in asthma may result from hyperplasia or hypertrophy of muscle cells or increased extracellular matrix (ECM). OBJECTIVES:To relate ASM hypertrophy, ASM hyperplasia, and deposition of ECM to the severity and duration of asthma. METHODS:Airways from ...
journal_title:American journal of respiratory and critical care medicine
pub_type: 杂志文章
doi:10.1164/rccm.201110-1849OC
更新日期:2012-05-15 00:00:00
abstract:RATIONALE:Controlled mechanical ventilation (CMV) results in atrophy of the human diaphragm. The autophagy-lysosome pathway (ALP) contributes to skeletal muscle proteolysis, but its contribution to diaphragmatic protein degradation in mechanically ventilated patients is unknown. OBJECTIVES:To evaluate the autophagy pa...
journal_title:American journal of respiratory and critical care medicine
pub_type: 杂志文章
doi:10.1164/rccm.201002-0234OC
更新日期:2010-12-01 00:00:00
abstract::Interleukin (IL)-2 has a central role in regulating T cell responses to Mycobacterium tuberculosis. Adjunctive immunotherapy with recombinant human IL-2 was studied in a randomized, placebo-controlled, double-blinded trial in 110 human immunodeficiency virus-seronegative adults in whom smear-positive, drug-susceptible...
journal_title:American journal of respiratory and critical care medicine
pub_type: 临床试验,杂志文章,随机对照试验
doi:10.1164/rccm.200211-1359OC
更新日期:2003-07-15 00:00:00
abstract::A growing body of evidence suggests that neutrophil-derived proteinases play a major role in lung tissue damage in cystic fibrosis (CF). Most previous studies have focused on serine proteinases such as neutrophil elastase, providing no information on the extent to which metalloproteinases participate in proteolytic pr...
journal_title:American journal of respiratory and critical care medicine
pub_type: 杂志文章
doi:10.1164/ajrccm.152.2.7633740
更新日期:1995-08-01 00:00:00
abstract::POEMS (polyneuropathy, organomegaly, endocrinopathy, monoclonal gammopathy, and skin changes) syndrome is a rare variant of plasma cell dyscrasia with multiple systemic manifestations. We followed the progress of 20 patients with POEMS syndrome in our institution over a 10-yr period. Pulmonary hypertension (PH) was ob...
journal_title:American journal of respiratory and critical care medicine
pub_type: 杂志文章
doi:10.1164/ajrccm.157.3.9707095
更新日期:1998-03-01 00:00:00
abstract::We used three-dimensional reconstructions obtained with spiral computed tomography to measure total diaphragm surface area (Adi), and the surface area of the dome (Ado) and of the zone of apposition (Aap) of the diaphragm in nine patients with single-lung transplantation (SLT) for emphysema and nine normal subjects ma...
journal_title:American journal of respiratory and critical care medicine
pub_type: 杂志文章
doi:10.1164/ajrccm.159.6.9812052
更新日期:1999-06-01 00:00:00
abstract::To investigate the annual decline of lung function in subjects with self-reported asthma, we analyzed data from a longitudinal epidemiologic study. The Copenhagen City Heart Study. The study sample consisted of 10,952 subjects (4,824 men), 20 to 90 yr of age, randomly selected from the city of Copenhagen followed over...
journal_title:American journal of respiratory and critical care medicine
pub_type: 杂志文章
doi:10.1164/ajrccm.150.3.8087330
更新日期:1994-09-01 00:00:00
abstract::Keratinocyte growth factor (KGF) induces transient proliferation of alveolar type II cells (AEII) associated with surfactant alterations. To test the hypothesis that homeostasis of intracellular phospholipid stores is maintained under KGF-induced hyperplasia, we (1) collected tissue from adult rat lungs, fixed for lig...
journal_title:American journal of respiratory and critical care medicine
pub_type: 杂志文章
doi:10.1164/rccm.200112-132OC
更新日期:2003-05-01 00:00:00
abstract:RATIONALE:Obstructive sleep apnea (OSA) is associated with impaired renal function, but uncertainty exists over whether OSA treatment can influence renal outcomes. OBJECTIVES:To determine the effects of continuous positive airway pressure (CPAP) on renal function in subjects with coexisting OSA and cardiovascular dise...
journal_title:American journal of respiratory and critical care medicine
pub_type: 杂志文章,多中心研究
doi:10.1164/rccm.201703-0603OC
更新日期:2017-12-01 00:00:00
abstract::A higher exposure to endotoxin was hypothesized to contribute to lower prevalence of allergic sensitization and hay fever in children growing up on a farm. We studied the association between house dust endotoxin and allergic sensitization. We randomly selected 740 children, aged between 5 and 10 years, from a group of...
journal_title:American journal of respiratory and critical care medicine
pub_type: 杂志文章
doi:10.1164/rccm.200203-256OC
更新日期:2002-10-01 00:00:00
abstract::The relationship between asthma medication and the perception of asthma symptoms is of interest for daily practice. Poor perception of asthma symptoms might influence patients' health care behavior and subsequently might lead to undertreatment and deterioration of their disease. This study investigated the influence o...
journal_title:American journal of respiratory and critical care medicine
pub_type: 临床试验,杂志文章,随机对照试验
doi:10.1164/ajrccm.164.5.9910103
更新日期:2001-09-01 00:00:00
abstract::Infection of the cystic fibrosis (CF) airways elicits an exaggerated, interleukin-8 (IL-8) mediated, neutrophil inflammatory response. Necrosing neutrophils release DNA and actin into the airways, increasing the viscoelasticity of airway secretions. Mucolytics aim to improve airway clearance by reducing this viscoelas...
journal_title:American journal of respiratory and critical care medicine
pub_type: 杂志文章
doi:10.1164/ajrccm.162.5.9908107
更新日期:2000-11-01 00:00:00
abstract:RATIONALE:Obstructive sleep apnea (OSA), a treatable sleep disorder that is associated with alterations in glucose metabolism in individuals without diabetes, is a highly prevalent comorbidity of type 2 diabetes. However, it is not known whether the severity of OSA is a predictor of glycemic control in patients with di...
journal_title:American journal of respiratory and critical care medicine
pub_type: 杂志文章
doi:10.1164/rccm.200909-1423OC
更新日期:2010-03-01 00:00:00
abstract::Although sleep-disordered breathing (SDB) has been shown to be very prevalent in the elderly, little has been done to examine differences between the elderly of different racial groups. It has been well documented that SDB often results in hypertension and that hypertension is more common in African-Americans than in ...
journal_title:American journal of respiratory and critical care medicine
pub_type: 杂志文章
doi:10.1164/ajrccm.152.6.8520760
更新日期:1995-12-01 00:00:00
abstract:RATIONALE:Intensive care unit (ICU) nurses work in a demanding environment where they are repetitively exposed to traumatic situations and stressful events. The psychological effects on nurses as a result of working in the ICU are relatively unknown. OBJECTIVE:To determine whether there is an increased prevalence of p...
journal_title:American journal of respiratory and critical care medicine
pub_type: 杂志文章
doi:10.1164/rccm.200606-735OC
更新日期:2007-04-01 00:00:00
abstract:RATIONALE:Although research supports a sleep-disordered breathing and atrial fibrillation association, prospective data examining sleep-disordered breathing predicting incident atrial fibrillation are lacking. OBJECTIVES:To investigate sleep-disordered breathing indices as predictors of incident atrial fibrillation. ...
journal_title:American journal of respiratory and critical care medicine
pub_type: 杂志文章,多中心研究
doi:10.1164/rccm.201508-1523OC
更新日期:2016-04-01 00:00:00
abstract::During Operation Everest III (Comex '97), to assess the consequences of altitude-induced hypoxia, eight volunteers were decompressed in a hypobaric chamber, with a decompression profile simulating the climb of Mount Everest. Cardiac function was assessed using a combination of M-mode and two-dimensional echocardiograp...
journal_title:American journal of respiratory and critical care medicine
pub_type: 杂志文章
doi:10.1164/ajrccm.161.1.9902096
更新日期:2000-01-01 00:00:00
abstract::We tested the hypothesis that hyperresponsiveness of the upper airway (UAHR) is present in patients with chronic cough of diverse etiology. We determined the frequency of bronchial hyperresponsiveness (BHR), hyperresponsiveness of the upper airway, sputum eosinophilia, pulmonary aspiration, and psychological symptoms ...
journal_title:American journal of respiratory and critical care medicine
pub_type: 杂志文章
doi:10.1164/ajrccm.156.1.9605044
更新日期:1997-07-01 00:00:00
abstract::We evaluated ultrasonic examination as a diagnostic tool for catheter misplacement and pneumothorax after central venous catheter insertion. Physicians in the intensive care unit (ICU) performed the ultrasonic examinations, and the results were compared with those of chest radiography. Eighty-five central venous cathe...
journal_title:American journal of respiratory and critical care medicine
pub_type: 杂志文章
doi:10.1164/ajrccm.164.3.2009042
更新日期:2001-08-01 00:00:00
abstract::Most data about the course of occupational asthma after removal from exposure are based upon the longitudinal assessment of employees exposed to substances inducing late asthmatic reactions in bronchial provocation tests. It was the aim of this study to describe the course of immediate-type occupational asthma after a...
journal_title:American journal of respiratory and critical care medicine
pub_type: 杂志文章
doi:10.1164/ajrccm.150.4.7921450
更新日期:1994-10-01 00:00:00
abstract::Levels of oleic acid (OA) are elevated in plasma and bronchoalveolar lavage fluids of patients with acute respiratory distress syndrome (ARDS). OA is also widely used to provoke edema, by unknown mechanisms, in experimental models of ARDS. We investigated the impact of intravascularly applied OA on epithelial lining f...
journal_title:American journal of respiratory and critical care medicine
pub_type: 杂志文章
doi:10.1164/rccm.200407-954OC
更新日期:2005-03-01 00:00:00
abstract::Asthma is a chronic inflammatory disease that persists even during adequate therapy and asymptomatic episodes. We questioned whether "silent" chronic allergen exposure can induce and maintain airway inflammation and whether this still occurs during regular treatment with inhaled steroids. Twenty-six patients with hous...
journal_title:American journal of respiratory and critical care medicine
pub_type: 临床试验,杂志文章,随机对照试验
doi:10.1164/rccm.2112097
更新日期:2002-08-01 00:00:00
abstract:RATIONALE:Acute respiratory distress syndrome is refractory to pharmacological intervention. Inappropriate activation of alveolar neutrophils is believed to underpin this disease's complex pathophysiology, yet these cells have been little studied. OBJECTIVES:To examine the functional and transcriptional profiles of pa...
journal_title:American journal of respiratory and critical care medicine
pub_type: 杂志文章
doi:10.1164/rccm.201509-1818OC
更新日期:2016-10-15 00:00:00
abstract:RATIONALE:Regional hypoventilation in bronchoconstricted patients with asthma is spatially associated with reduced perfusion, which is proposed to result from hypoxic pulmonary vasoconstriction (HPV). OBJECTIVES:To determine the role of HPV in the regional perfusion redistribution in bronchoconstricted patients with a...
journal_title:American journal of respiratory and critical care medicine
pub_type: 杂志文章
doi:10.1164/rccm.201612-2438OC
更新日期:2017-10-01 00:00:00