B4GALT1 as a New Biomarker of Idiopathic Pulmonary Fibrosis.

Idiopathic pulmonary fibrosis (IPF) is a disease characterized by progressive scarring of the lung that involves the pulmonary interstitium. The disease may rapidly progress, leading to respiratory failure, and the long-term survival is poor. There are no accurate biomarkers available so far. Our aim was to evaluate the expression of the B4GALT1 in patients with IPF. Analysis of B4GALT1 gene expression was performed in silico on two gene sets, retrieved from the Gene Expression Omnibus database. Expression of B4GALT1 was then evaluated, both at the mRNA and protein levels, on lung specimens obtained from lung biopsies of 4 IPF patients, on one IPF-derived human primary cell and on 11 cases of IPF associated with cancer. In silico re-analysis demonstrated that the B4GALT1 gene was overexpressed in patients and human cell cultures with IPF (p = 0.03). Network analysis demonstrated that B4GALT1 upregulation was correlated with genes belonging to the EMT pathway (p = 0.01). The overexpression of B4GALT1 was observed, both at mRNA and protein levels, in lung biopsies of our four IPF patients and in the IPF-derived human primary cell, in other fibrotic non-lung tissues, and in IPF associated with cancer. In conclusion, our results indicate that B4GALT1 is overexpressed in IPF and could represent a novel marker of this disease.

Adenocarcinomas of the Lung and Neurotrophin System: A Review.

Neurotrophins (NTs) represent a group of growth factors with pleiotropic activities at the central nervous system level. The prototype of these molecules is represented by the nerve growth factor (NGF), but other factors with similar functions have been identified, including the brain derived-growth factor (BDNF), the neurotrophin 3 (NT-3), and NT-4/5. These growth factors act by binding specific low (p75) and high-affinity tyrosine kinase (TrkA, TrkB, and TrkC) receptors. More recently, these growth factors have shown effects outside the nervous system in different organs, particularly in the lungs. These molecules are involved in the natural development of the lungs, and their homeostasis. However, they are also important in different pathological conditions, including lung cancer. The involvement of neurotrophins in lung cancer has been detailed most for non-small cell lung cancer (NSCLC), in particular adenocarcinoma. This review aimed to extensively analyze the current knowledge of NTs and lung cancer and clarify novel molecular mechanisms for diagnostic and therapeutic purposes. Several clinical trials on humans are ongoing using NT receptor antagonists in different cancer cell types for further therapeutic applications. The pharmacological intervention against NT signaling may be essential to directly counteract cancer cell biology, and also indirectly modulate it in an inhibitory way by affecting neurogenesis and/or angiogenesis with potential impacts on tumor growth and progression.

Assessing Static Lung Hyperinflation by Whole-Body Plethysmography, Helium Dilution, and Impulse Oscillometry System (IOS) in Patients with COPD.

Purpose: Lung hyperinflation is a feature of chronic obstructive pulmonary disease (COPD) and can determine pivotal consequence on symptoms, exercise tolerance and quality of life. Despite the relevance of assessing lung hyperinflation, there is still no single consensus as to what volume should be taken into account. We investigate which spirometric measurement is more reliable in assessing static lung hyperinflation and which is more related with impulse oscillometry system (IOS) measurements in COPD. Patients and Methods: Fifty-five COPD patients were enrolled. TLC, RV and RV:TLC ratio were obtained both with helium and plethysmography techniques. IOS measurements (X5, Fres and R5-R20) were performed. Pearson and Spearman correlation determined the relationships between the functional parameters that evaluate static hyperinflation (RV: TLC, TLC, RV) and IOS measurements. Results: As expected, we reported a statistically significant difference between these two techniques in terms of mean percentage values of TLC (7.57 ± 3.26 L; p= 0.02) and RV (15.24 ± 7.51 L; p=0.04), while RV:TLC measured with the two methods was similar (5.21 ± 4.69%; p=0.27). The correlation analysis showed that IOS parameters, such as difference in resistance between 5 Hz and 20 Hz (R(5-20)) and resonant frequency (Fres), were positively correlated with RV:TLC ratio, while reactance at 5 Hz (X(5)) was negatively correlated with it. In particular, we pointed out a weak correlation between RV:TLC (%) (Pleth) and R(5-20) (r=0.3, p=0.04), Fres (r=0.3; p=0.03), while X5 had a mild correlation with RV:TLC (%) (r=-0.5;p<0.0001). Moreover, we noticed a strong relationship between RV:TLC (%)(He) and X5 (r=-0.7; p=0.0001) and a mild correlation between RV:TLC (%) (He) and Fres (r=0.4; p=0.003). Between R5-R20 and RV:TLC, there was a weak correlation (r=0.3; p=0.001). No correlation between TLC, RV (L,%) (both helium and Pleth derived) and IOS parameters (R(5-20), X5, Fres) was found. Conclusion: RV:TLC can represent the most reliable parameter in the assessment of hyperinflation, considering the absence of significant difference in its measurement between the two techniques. IOS provides supplementary information in the assessment of static hyperinflation.