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Translational Respiratory Medicine

Enric Carcereny, Teresa Morán, Laia Capdevila, Sara Cros, Laia Vilà, Maria de Los Llanos Gil, Jordi Remón, Rafael Rosell
In the last decade, important advances have been made in understanding of cancer biology, particularly non-small-cell lung cancer (NSCLC) with the discovery of oncogenic drivers of the disease. The epidermal growth factor receptor (EGFR) gene and its pathways was the first oncogenic driver discovered to be mutated and treatable in lung cancer. Treatment with EGFR tyrosine kinase inhibitors (TKIs) is the standard of care for molecularly selected EGFR-mutant patients, while its role in unselected lung cancer patients is nowadays controversial...
2015: Translational Respiratory Medicine
Erika Rodriguez, Li Chen, Ming-Hui Ao, Susan Geddes, Ed Gabrielson, Frederic Askin, Hui Zhang, Qing Kay Li
BACKGROUND: SALL4 and OCT4 are transcription factors and play essential roles in stem cell development and oncogenesis. However, the expression of these transcription factors has not been well studied in lung cancers. In this study, we evaluated the expression of SALL4 and OCT4 in non-small cell lung carcinomas (NSCLC) by immunochemistry. NSCLC tissue microarrays (TMAs) were constructed with a total of 77 primary lung adenocarcinomas (ADCs) and 90 primary lung squamous cell carcinomas (SqCCs)...
December 2014: Translational Respiratory Medicine
Armine G Minasian, Frank Jj van den Elshout, Pn Richard Dekhuijzen, Petra Je Vos, Frank F Willems, Paul Jpc van den Bergh, Yvonne F Heijdra
BACKGROUND: It is unknown whether serial pulmonary function tests are necessary for the correct diagnosis of chronic obstructive pulmonary disease (COPD) in patients with stable non-congested chronic heart failure (CHF). The aim of this study was to determine the prevalence of COPD in outpatients with stable CHF without pulmonary congestion using initial as well as confirmatory spirometry three months after treatment for COPD. METHODS: Spirometry was performed in 187 outpatients with stable CHF without pulmonary congestion on chest radiograph who had a left ventricular ejection fraction < 40% (mean age 69 ± 10 years, 78% men)...
December 2014: Translational Respiratory Medicine
Cristan Herbert, Qing-Xiang Zeng, Ramesh Shanmugasundaram, Linda Garthwaite, Brian G Oliver, Rakesh K Kumar
BACKGROUND: Respiratory viral infections are the most common trigger of acute exacerbations in patients with allergic asthma. The anti-viral response of airway epithelial cells (AEC) may be impaired in asthmatics, while cytokines produced by AEC may drive the inflammatory response. We investigated whether AEC cultured in the presence of Th2 cytokines associated with an allergic environment exhibited altered responses to double-stranded RNA, a virus-like stimulus. METHODS: We undertook preliminary studies using the MLE-12 cell line derived from mouse distal respiratory epithelial cells, then confirmed and extended our findings using low-passage human AEC...
December 2014: Translational Respiratory Medicine
Inge Hantson, Christophe Dooms, Eric Verbeken, Peter Vandenberghe, Liesbet Vliegen, Tania Roskams, Sara Vander Borght, Kris Nackaerts, Isabelle Wauters, Johan Vansteenkiste
BACKGROUND: ESMO consensus recommends EGFR mutation testing in never/former light smokers (<15 pack-years) or patients with non-squamous NSCLC. The aim of this work was to determine the frequency and clinical predictors of EGFR mutations, and the role of specimen sampling tests, in Caucasian standard practice setting. METHODS: We screened 297 patients according to this consensus. Mutational analysis of EGFR was performed using the Therascreen EGFR RGQ PCR mutation kit...
December 2014: Translational Respiratory Medicine
Peter A Ward, Jamison J Grailer
Acute respiratory distress syndrome (ARDS) in humans involves ≥ 200,000 individuals in the United States, and has a mortality rate (40%) for which no specific drug has been approved for use in humans. We have studied experimental acute lung injury (ALI) in mice following airway deposition of bacterial lipopolysaccharide (LPS) or the recombinant mouse complement anaphylatoxin, C5a. As ALI developed over 6 hr, extracellular histones appeared in bronchoalveolar lavage fluids (BALF). Extracellular histone appearance required both C5a receptors (C5aR, C5L2) as well as neutrophils (PMNs) and lung macrophages, as genetic loss of either C5a receptor or depletion of PMNs or macrophages reduced histone levels found in BALF during ALI...
2014: Translational Respiratory Medicine
Ena Ray Banerjee
This discourse contains three perspectives on various aspects of Stem Cell Biology and tools available to study and translate into Regenerative Medicine. The lung incessantly faces onslaught of the environment, constantly undergoes oxidative stress, and is an important organ of detoxification. In degenerative diseases and inflammation, the lung undergoes irreversible remodeling that is difficult to therapeutically address and/or transplant a dying tissue. The other difficulty is to study its development and regenerative aspects to best address the aforementioned problems...
2014: Translational Respiratory Medicine
Tomoyo Sasaki, Michael Kahn
BACKGROUND: Wnt/β-catenin signaling has been suggested to regulate proximal-distal determination of embryonic lung epithelium based upon genetically modified mouse models. The previously identified and characterized small molecule inhibitor IQ1 can pharmacologically decrease the interaction between β-catenin and its transcriptional coactivator p300, thereby enhancing the β-catenin/CBP interaction. Inhibition of the β-catenin/p300 interaction by IQ1 blocks the differentiation of embryonic stem cells and epicardial progenitor cells; however, whether differential coactivator usage by β-catenin plays a role in proximal-distal determination of lung epithelium is unknown...
2014: Translational Respiratory Medicine
Bruce K Rubin
Chronic airway diseases like cystic fibrosis, chronic bronchitis, asthma, diffuse panbronchiolitis, and bronchiectasis are all associated with chronic inflammation. The airway mucosa responds to infection and inflammation in part by surface mucous (goblet) cell and submucosal gland hyperplasia and hypertrophy with mucus hypersecretion. Products of inflammation including neutrophil derived DNA and filamentous actin, effete cells, bacteria, and cell debris all contribute to mucus purulence and, when this is expectorated it is called sputum...
2014: Translational Respiratory Medicine
Wenping Zhang, Xianliang Chen, Lijun Ma, Jizhen Wu, Limin Zhao, Hongyan Kuang, Taibo Huang, Jianjian Cheng, Luoxian Zhang, Yong Qi, Beibei Sun, Hongyan Niu
BACKGROUND: Prevalence of bronchial asthma, asthma treatment assessment, and estimation of the control level among asthma patients in Henan Province, China are reported in this paper. METHODS: We selected 10 among the 109 cities and districts in Henan province using a multistage stratified cluster random sampling method. A total of 500 households from each city and district were chosen. Approximately 20,000 residents from a total of 5,000 households were randomly selected to answer a questionnaire recommended by the China Asthma Alliance...
2014: Translational Respiratory Medicine
Keith C Meyer
The complex tasks of making a confident diagnosis of a specific form of interstitial lung disease (ILD) and formulating a patient-centered, personalized management plan in an attempt to achieve remission or stabilization of the disease process can pose formidable challenges to clinicians. When patients are evaluated for suspected ILD, an accurate diagnosis of the specific form of ILD that a patient has developed must be made to provide the patient with useful prognostic information and to formulate an appropriate management plan that can relieve symptoms and restore or significantly improve quality of life...
2014: Translational Respiratory Medicine
Beth L Laube
Until the late 1990s, aerosol therapy consisted of beta2-adrenergic agonists, anti-cholinergics, steroidal and non-steroidal agents, mucolytics and antibiotics that were used to treat patients with asthma, COPD and cystic fibrosis. Since then, inhalation therapy has matured to include drugs that: (1) are designed to treat diseases outside the lung and whose target is the systemic circulation (systemic drug delivery); (2) deliver nucleic acids that lead to permanent expression of a gene construct, or protein coding sequence, in a population of cells (gene therapy); and (3) provide needle-free immunization against disease (aerosolized vaccination)...
2014: Translational Respiratory Medicine
Irene Stasi, Federico Cappuzzo
BACKGRUOND: Since their first description, activating epidermal growth factor receptor (EGFR) mutations identify a distinct clinical entity of patients with non-small-cell lung cancer (NSCLC). FINDINGS: New targeted therapies for molecularly selected NSCLC are changing the natural history of the disease, with results superior to standard chemotherapy as demonstrated in large phase III studies with first generation EGFR tyrosine kinase inhibitors (TKIs) erlotinib and gefitinib...
2014: Translational Respiratory Medicine
Hendrik J Harms, Mariëlle C van de Veerdonk, Adriaan A Lammertsma, Anton Vonk Noordegraaf, Harm Jan Bogaard
Whereas the insights into the cellular and molecular mechanisms of pulmonary arterial hypertension (PAH) and associated right heart failure have increased in recent years, there is a lack of clinical tools to assess the pathobiological mechanisms in patients. Positron emission tomography (PET) provides an array of new possibilities to image and quantify relevant disease processes, including proliferation, angiogenesis, matrix remodeling, shifts in metabolism and neurohormonal signaling. Here we describe the first studies which were conducted to image pulmonary vascular remodeling and right heart failure in vivo and discuss additional targets for imaging which hold great promise for future use in PAH patients...
December 2013: Translational Respiratory Medicine
Szu-Jung Chen, Shenq-Shyang Huang, Nan-Shan Chang
It is generally agreed that the pro-inflammatory, pro-survival transcription factor NF-κB is a tumor promoter. Tumor necrosis factor alpha (TNF-α or TNF) mediates NF-κB activation. Tumor suppressor WWOX (FOR or WOX1) is a downstream effector of the TNF signaling. Thus, activation of both WWOX (FOR or WOX1) and NF-κB may occur during TNF signaling and/or under stress conditions. Indeed, the first WW domain of WWOX induces the activation of NF-κB-responsive promoter without TNF participation. It appears that WWOX counteracts with NF-κB in regulating cell survival and death...
December 2013: Translational Respiratory Medicine
Johan Malm, Thomas E Fehniger, Pia Danmyr, Ákos Végvári, Charlotte Welinder, Henrik Lindberg, Paul Upton, Stephanie Carter, Roger Appelqvist, Karin Sjödin, Elisabet Wieslander, Magnus Dahlbäck, Melinda Rezeli, David Erlinge, György Marko-Varga
BACKGROUND: Biobank samples stored in biobanks give researchers and respiratory healthcare institutions access to datasets of analytes valuable for both diagnostic and research practices. The usefulness of these samples in clinical decision-making is highly dependent on their quality and integrity. New procedures that better preserve sample integrity and reduce degradation are being developed to meet the needs of both present and future biobanking. Hereby we present an automatic sample workflow scheme that is designed to handle high numbers of blood samples...
December 2013: Translational Respiratory Medicine
Paul T King, Martin MacDonald, Philip G Bardin
The role of bacterial infection in chronic obstructive pulmonary disease (COPD) and how it should be treated has been an ongoing source of controversy. For many years bacterial infection has not been thought to have an important effect in the pathology of this condition. Recent advances in diagnostic techniques, particularly the use 16S sequencing has demonstrated that there are a large range of bacteria present in the lower respiratory tract, both in terms of exacerbations and chronic colonization. A proportion of the bacteria present in the lower respiratory have also been shown to produce inflammation and hence are likely to be relevant for the pathogenesis of COPD...
December 2013: Translational Respiratory Medicine
Rekha Chaudhuri, Charles McSharry, Mark Spears, Jeffrey Brady, Christal Grierson, C Martina Messow, Gino Miele, Karl Nocka, William MacNee, Martin Connell, John T Murchison, Michael Sproule, Omar Hilmi, Douglas K Miller, Neil C Thomson
BACKGROUND: Matrix-metalloproteinase (MMP)-9 has been implicated in the pathogenesis of COPD, although its link to disease severity is unclear. The purpose of the study was to examine the relationship between disease severity assessed by lung function and computed tomography (CT) and sputum MMP-9 expression, concentration and activity in patients with COPD. FINDINGS: In 53 COPD subjects, smokers and ex-smokers; 46 healthy controls, smokers and never smokers, we measured sputum MMP-9 concentrations (ELISA) and enzyme activity (FRET), sputum MMP-9 mRNA expression, spirometry, diffusing capacity for carbon monoxide (DLco) and CT assessment of emphysema (% low attenuation areas below-950 Hounsfield units)...
December 2013: Translational Respiratory Medicine
Michael A Matthay, Yuanlin Song, Chunxue Bai, Kirk D Jones
Acute lung injury and the acute respiratory distress syndrome are major causes of morbidity and mortality in critically ill patients. This review focuses on new developments in definitions, epidemiology, clinical and basic research, and promising new directions in treatment. There is new information about the potential contribution of environmental factors, especially exposure to cigarette smoke. Pathologic findings in ARDS have been limited to case reports of open lung biopsies and post-mortem studies but there is some new information from a recent pathology study relative to the frequency of diffuse alveolar damage and the severity of arterial hypoxemia...
December 2013: Translational Respiratory Medicine
Y C Gary Lee, Grant W Waterer
Medical advances have failed to arrest the growing morbidity and mortality from lung diseases. COPD, lung cancer and pulmonary infections remain leading causes of death. More than any other time in human history, we need high quality, translatable, patient-focussed respiratory research that will improve clinical practice. Close teamwork of scientists and clinicians are essential. The results of these work need to be disseminated quickly and widely. The creation of an open access journal, such as Translational Respiratory Medicine, dedicated to translational respiratory research can help foster progress...
December 2013: Translational Respiratory Medicine
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