Protección frente al enfriamiento intenso por anticongelantes naturales. Modelo ex-vivo de preservación de pulmón de rata.

[spa] Los procedimientos quirúrgicos actualmente disponibles frente a la enfermedad pulmonar avanzada, irreversible y terminal son la cirugía de reducción de volumen pulmonar y el trasplante de pulmón. Expandir la práctica del trasplante de pulmón constituye uno de los grandes retos que la neumología y la cirugía torácica tienen delante. La posibilidad de solucionar los problemas citados constituye el motor de la investigación en transplante de pulmón

Endoplasmic reticulum stress and unfolded protein response in diaphragm muscle dysfunction of patients with stable chronic obstructive pulmonary disease

Respiratory muscle dysfunction is common in patients with chronic obstructive pulmonary disease (COPD). Chronic contractile activity induces endoplasmic reticulum (ER) stress and unfolded protein response (UPR) in animals (animals and humans). We hypothesized that the respiratory muscle dysfunction associated with COPD may upregulate ER stress and UPR expression in diaphragm of stable patients with different degrees of airway obstruction and normal body composition. In diaphragm muscle specimens of patients with mild and moderate-to-severe COPD with preserved body composition and non-COPD controls (thoracotomy because of lung localized neoplasms), expression of protein misfolding (ER stress) and UPR markers, proteolysis and apoptosis (qRT-PCR and immunoblotting), and protein aggregates (lipofuscin, histology) were quantified. All patients and non-COPD controls were also clinically evaluated: lung and muscle functions and exercise capacity. Compared with non-COPD controls, patients exhibited mild and moderate-to-severe airflow limitation and diffusion capacity and impaired exercise tolerance and diaphragm strength. Moreover, compared with the controls, in the diaphragm of the COPD patients, slow-twitch fiber proportions increased, gene expression but not protein levels of protein disulfide isomerase family A member 3 and phosphatidylinositol 3-kinase catalytic subunit type 3 were upregulated, and no significant differences were found in markers of UPR transmembrane receptor pathways (activating transcription factor-6, inositol-requiring enzyme-1α, and protein kinase-like ER kinase), lipofuscin aggregates, proteolysis, or apoptosis. In stable COPD patients with a wide range of disease severity, reduced diaphragm force of contraction, and normal body composition, ER stress and UPR signaling were not induced in the main respiratory muscle. These findings imply that ER stress and UPR are probably not involved in the documented diaphragm muscle dysfunction (reduced strength) observed in all the study patients, even in those with severe airflow limitation. Hence, in stable COPD patients with normal body composition, therapeutic strategies targeted to treat diaphragm muscle dysfunction should not include UPR modulators, even in those with a more advanced disease. NEW & NOTEWORTHY In stable chronic obstructive pulmonary disease patients with a wide range of disease severity, diaphragm muscle weakness, and normal body composition, endoplasmic reticulum stress and unfolded protein response (UPR) signaling were not induced in the main respiratory muscle. These findings imply that endoplasmic reticulum stress and UPR are not involved in the documented diaphragm muscle dysfunction observed in the study patients, even in those with severe airflow limitation. In stable chronic obstructive pulmonary disease patients with normal body composition, therapeutic strategies should not include UPR modulators

Gene expression profile of epithelial-mesenchymal transition in tumours of patients with nonsmall cell lung cancer. The influence of COPD

Epithelial-mesenchymal transition (EMT) is involved in the pathophysiology of lung cancer (LC) and COPD, and the latter is an important risk factor for LC. We hypothesised that the EMT gene expression profile and signalling cascade may differ in LC patients with COPD from those with no respiratory diseases. In lung tumour specimens obtained through video-assisted thoracoscopic surgery from LC (n=20, control group) and LC-COPD patients (n=30), gene expression (quantitative real-time PCR amplification) of EMT markers SMAD3, SMAD4, ZEB2, TWIST1, SNAI1, ICAM1, VIM, CDH2, MMP1 and MMP9 was detected. In lung tumours of LC-COPD compared to LC patients, gene expression of SMAD3, SMAD4, ZEB2 and CDH2 significantly declined, while no significant differences were detected for the other analysed markers. A significant correlation was found between pack-years (smoking burden) and SMAD3 gene expression among LC-COPD patients. LC-COPD patients exhibited mild-to-moderate airway obstruction and a significant reduction in diffusion capacity compared to LC patients. In lung tumour samples of patients with COPD, several markers of EMT expression, namely SMAD3, SMAD4, ZEB2 and CDH2, were differentially expressed suggesting that these markers are likely to play a role in the regulation of EMT in patients with this respiratory disease. Cigarette smoke did not seem to influence the expression of EMT markers in this study. These results have potential clinical implications in the management of patients with LC, particularly in those with underlying respiratory diseases

Markers of stroma in lung cancer: influence of COPD

Background: Stroma, mainly composed by fibroblasts, extracellular matrix (ECM) and vessels, may play a role in tumorigenesis and cancer progression. Chronic Obstructive Pulmonary Disease (COPD) is an independent risk factor for LC. We hypothesized that markers of fibroblasts, ECM and endothelial cells may differ in tumors of LC patients with/without COPD. Methods: Markers of cultured cancer-associated fibroblasts and normal fibroblasts [CAFs and NFs, respectively, vimentin and alpha-smooth muscle actin (SMA) markers, immunofluorescence in cultured lung fibroblasts], ECM, and endothelial cells (type I collagen and CD31 markers, respectively, immunohistochemistry) were identified in lung tumor and non-tumor specimens (thoracotomy for lung tumor resection) from 15 LC-COPD patients and 15 LC-only patients. Results: Numbers of CAFs significantly increased, while those of NFs significantly decreased in tumor samples compared to non-tumor specimens of both LC and LC-COPD patients. Endothelial cells (CD31) significantly decreased in tumor samples compared to non-tumor specimens only in LC patients. No significant differences were seen in levels of type I collagen in any samples or study groups. Conclusions: Vascular endothelial marker CD31 expression was reduced in tumors of non-COPD patients, while type I collagen levels did not differ between groups. A rise in CAFs levels was detected in lung tumors of patients irrespective of airway obstruction. Low levels of CD31 may have implications in the overall survival of LC patients, especially in those without underlying airway obstruction. Identification of CD31 role as a prognostic and therapeutic biomarker in lung tumors of patients with underlying respiratory diseases warrants attention