Read-through transcripts in lung: germline genetic regulation and correlation with the expression of other genes.

Transcripts originating from the transcriptional read through of two adjacent, similarly oriented genes have been identified in normal and neoplastic tissues, but their functional role and the mechanisms that regulate their expression are mostly unknown. Here, we investigated whether the expression of read-through transcripts previously identified in the non-involved lung tissue of lung adenocarcinoma patients was genetically regulated. Data on genome-wide single nucleotide variant genotypes and expression levels of 10 read-through transcripts in 201 samples of lung tissue were combined to identify expression quantitative trait loci (eQTLs).

Outcomes and risk factors identification in urgent lung transplantation: a multicentric study.

Background: In rapidly lung deteriorating patients, urgent lung transplantation (ULT) seems the only definitive therapy. Few publications on this topic report conflicting results, putting a word of caution about ULT programs.

Methods: A national ULT program was introduced in 2010: patients on mechanical support may be transplanted with the first available graft.

Cigarette smoke alters the transcriptome of non-involved lung tissue in lung adenocarcinoma patients.

Alterations in the gene expression of organs in contact with the environment may signal exposure to toxins. To identify genes in lung tissue whose expression levels are altered by cigarette smoking, we compared the transcriptomes of lung tissue between 118 ever smokers and 58 never smokers. In all cases, the tissue studied was non-involved lung tissue obtained at lobectomy from patients with lung adenocarcinoma.

Transplant options for end stage chronic obstructive pulmonary disease in the context of multidisciplinary treatments.

Lung transplantation (LTx) in advanced stage chronic obstructive pulmonary disease (COPD) patients is associated with significant improvement in lung function and exercise capacity. However, demonstration that the procedure also provides a survival benefit has been more elusive compared to other respiratory conditions. Identification of patients with increased risk of mortality is crucial: a low forced expiratory volume in 1 second (FEV) is perhaps the most common reason for referral to a lung transplant center, but in itself is insufficient to identify which COPD patients will benefit from LTx.

Is "lung repair centre" a possible answer to organ shortage?-transplantation of left and right lung at two different centres after ex vivo lung perfusion evaluation and repair: case report.

Ex vivo lung perfusion (EVLP) has become a reality as a technique to evaluate and recondition lungs from marginal donors. We report the first case on the use of EVLP followed by separate transplantation in two different centres. The local organ procurement organization proposed the lungs of a 53-year-old non-smoker donor who died for cerebral haemorrhage.

Prophylactic continuous positive airway pressure after pulmonary lobectomy: a randomized controlled trial.

Background: Despite advances in perioperative care and surgical techniques, patients undergoing pulmonary lobectomy are still at high risk for postoperative complications. Among interventions expected to reduce complications, continuous positive airway pressure (CPAP) is a discussed option. This trial aims to test the hypothesis whether prophylactic application of CPAP following pulmonary lobectomy can reduce postoperative complications.

Ribcage kinematics during exercise justifies thoracoscopic versus postero-lateral thoracotomy lobectomy prompt recovery.

Objectives: The video-assisted thoracic surgery (VATS) approach is encouraged over postero-lateral thoracotomy (PLT) for lobectomy in lung cancer. We compare the ribcage kinematics during exercise before and after both procedures, assuming that VATS, being minimally invasive, could better preserve ribcage expansion.

Methods: Thirty-one patients undergoing lobectomy by means of VATS (n = 20) or PLT (n = 11) were compared presurgery, after chest drainage removal (T1) and 2 months post-surgery (T2) during quiet breathing and incremental exercise.

Multicentric study of endobronchial ultrasound-transbronchial needle aspiration for lung cancer staging in Italy.

Background: Multi-institutional studies of endobronchial-ultrasound transbronchial needle aspiration (EBUS-TBNA) for mediastinal staging in lung cancer are scarce. It is unclear if the high diagnostic performance of EBUS-TBNA reported by experts' guidelines can be generally achieved.

Methods: This is a retrospective study performed in five tertiary referral centers of thoracic surgery in Italy, to assess the EBUS-TBNA diagnostic performance in patients with non-small cell lung cancer (NSCLC).

Genetic susceptibility variants for lung cancer: replication study and assessment as expression quantitative trait loci.

Many single nucleotide polymorphisms (SNPs) have been associated with lung cancer but lack confirmation and functional characterization. We retested the association of 56 candidate SNPs with lung adenocarcinoma risk and overall survival in a cohort of 823 Italian patients and 779 healthy controls, and assessed their function as expression quantitative trait loci (eQTLs). In the replication study, eight SNPs (rs401681, rs3019885, rs732765, rs2568494, rs16969968, rs6495309, rs11634351, and rs4105144) associated with lung adenocarcinoma risk and three (rs9557635, rs4105144, and rs735482) associated with survival.

Human Lung Tissue Transcriptome: Influence of Sex and Age.

Background: Sex and age strongly influence the pathophysiology of human lungs, but scarce information is available about their effects on pulmonary gene expression.

Methods: We followed a discovery-validation strategy to identify sex- and age-related transcriptional differences in lung.

Results: We identified transcriptional profiles significantly associated with sex (215 genes; FDR < 0.

Transcriptional Landscape of Human Tissue Lymphocytes Unveils Uniqueness of Tumor-Infiltrating T Regulatory Cells.

Tumor-infiltrating regulatory T lymphocytes (Treg) can suppress effector T cells specific for tumor antigens. Deeper molecular definitions of tumor-infiltrating-lymphocytes could thus offer therapeutic opportunities. Transcriptomes of T helper 1 (Th1), Th17, and Treg cells infiltrating colorectal or non-small-cell lung cancers were compared to transcriptomes of the same subsets from normal tissues and validated at the single-cell level.

Read-through transcripts in normal human lung parenchyma are down-regulated in lung adenocarcinoma.

Read-through transcripts result from the continuous transcription of adjacent, similarly oriented genes, with the splicing out of the intergenic region. They have been found in several neoplastic and normal tissues, but their pathophysiological significance is unclear. We used high-throughput sequencing of cDNA fragments (RNA-Seq) to identify read-through transcripts in the non-involved lung tissue of 64 surgically treated lung adenocarcinoma patients.

Upregulation of TMEM16A Protein in Bronchial Epithelial Cells by Bacterial Pyocyanin.

Induction of mucus hypersecretion in the airway epithelium by Th2 cytokines is associated with the expression of TMEM16A, a Ca2+-activated Cl- channel. We asked whether exposure of airway epithelial cells to bacterial components, a condition that mimics the highly infected environment occurring in cystic fibrosis (CF), also results in a similar response. In cultured human bronchial epithelial cells, treatment with pyocyanin or with a P.

Preventive analgesia in thoracic surgery: controlled, randomized, double-blinded study.

Objectives: Preventive analgesia is defined as a treatment that is commenced before the surgical procedure in order to diminish the physiological consequences of afferent nociceptive transmission caused by the procedure and prevent central sensitization. The analysis of randomized studies of preventive analgesia is controversial. The aim of this study was to check the analgesic efficacy of preoperative administration of dextromethorphan associated with intercostal nerve block with levobupivacaine in thoracotomy patients who refused or had a contraindication to epidural analgesia.

Do we need to cool the lung graft after ex vivo lung perfusion? A preliminary study.

Background: After normothermic ex vivo lung perfusion (EVLP), pulmonary grafts are usually flush-cooled and stored on ice until implantation although evidence for this practice lacks. We compared outcomes between 2 post-EVLP preservation strategies in a porcine left single-lung transplantation model.

Material And Methods: After cold flush and 2-h EVLP, donor lungs were prepared and split.

Germline polymorphisms and survival of lung adenocarcinoma patients: a genome-wide study in two European patient series.

In lung cancer, the survival of patients with the same clinical stage varies widely for unknown reasons. In this two-phase study, we examined the hypothesis that germline variations influence the survival of patients with lung adenocarcinoma. First, we analyzed existing genotype and clinical data from 289 UK-resident patients with lung adenocarcinoma, identifying 86 single nucleotide polymorphisms (SNPs) that associated with survival (p < 0.

Urgent lung transplant programme in Italy: analysis of the first 14 months.

Objectives: Lung transplantation (LTx) is the only effective treatment for end-stage lung disease. In rapidly deteriorating patients awaiting transplant, supportive strategies for lung function allow only a short period of support and lung transplantation remains the definitive therapy. An urgent transplant programme may reduce the waiting time, allowing lung transplantation in these patients.

Ex vivo lung perfusion to improve donor lung function and increase the number of organs available for transplantation.

This paper describes the initial clinical experience of ex vivo lung perfusion (EVLP) at the Fondazione Ca' Granda in Milan between January 2011 and May 2013. EVLP was considered if donor PaO2 /FiO2 was below 300 mmHg or if lung function was doubtful. Donors with massive lung contusion, aspiration, purulent secretions, pneumonia, or sepsis were excluded.

Does surgery improve survival of patients with malignant pleural mesothelioma?: a multicenter retrospective analysis of 1365 consecutive patients.

Background: Surgery with pleurectomy/decortication (P/D) or extrapleural pneumonectomy (EPP) can be an option for selected patients with resectable malignant pleural mesothelioma (MPM). The aim of this study was to investigate the impact of surgical treatment on the outcome of patients with MPM.

Methods: We retrospectively reviewed data from 1365 consecutive patients with histologically proven MPM, treated from 1982 to 2012 in six Institutions.

Pleural tissue repair with cord blood platelet gel.

Background: Prolonged air leak is the major cause of morbidity after pulmonary resection. In this study we used in vitro and in vivo experiments to investigate an innovative approach based on the use of human umbilical cord blood platelet gel.

Materials And Methods: In vitro, a scratch assay was performed to test the tissue repair capability mediated by cord blood platelet gel compared to the standard culture conditions using human primary mesothelial cells.

Organ allocation waiting time during extracorporeal bridge to lung transplant affects outcomes.

Background: The use of extracorporeal membrane oxygenation (ECMO) as a bridge to lung transplant (LTX) is still being debated.

Methods: We performed a retrospective two-center analysis of the relationship between ECMO bridging duration and survival in 25 patients. Further survival analysis was obtained by dividing the patients according to waiting time on ECMO: up to 14 days (Early group) or longer (Late group).

Multiple isoforms and differential allelic expression of CHRNA5 in lung tissue and lung adenocarcinoma.

CHRNA5 gene expression variation may play a role in individual susceptibility to lung cancer. Analysis of CHRNA5 transcripts expressed in normal lung tissue detected the full-length transcript (isoform-1) and four splicing transcripts (isoform-2 to isoform-5), derived from the recognition of other splice sites in exon 5. Isoforms-2, -3 and -4 were found by protein modeling to form a completely folded, potentially functional extracellular domain and were observed at the protein level, whereas isoform-5 lacked a consistent part of the distorted β sandwich and was not seen at the protein level.

EGFR-targeted therapy for non-small cell lung cancer: focus on EGFR oncogenic mutation.

The two essential requirements for pathologic specimens in the era of personalized therapies for non-small cell lung carcinoma (NSCLC) are accurate subtyping as adenocarcinoma (ADC) versus squamous cell carcinoma (SqCC) and suitability for EGFR molecular testing, as well as for testing of other oncogenes such as EML4-ALK and KRAS. Actually, the value of EGFR expressed in patients with NSCLC in predicting a benefit in terms of survival from treatment with an epidermal growth factor receptor targeted therapy is still in debate, while there is a convincing evidence on the predictive role of the EGFR mutational status with regard to the response to tyrosine kinase inhibitors (TKIs).This is a literature overview on the state-of-the-art of EGFR oncogenic mutation in NSCLC.