Ascending aorta TDI provides wall velocity and strain data differentiating hypertensive from healthy adults and reflecting aortic compliance changes related to age and sex and LV diastolic function.

Autophagy is the main cellular pathway for degradation of long-lived proteins and organelles and regulates cell fate in response to stress. Beclin 1 is a key regulator of this process. In some settings autophagy and apoptosis seem to be interconnected. Recent reports indicate that fibroblasts in idiopathic pulmonary fibrosis (IPF) acquire resistance to apoptosis. Here, we examined the expression of beclin 1, and of the anti apoptotic protein Bcl-2 in human IPF fibroblasts using immunohistochemistry and molecular biology in bioptic sections, in primary cultures of fibroblasts taken from patients with IPF and in fibroblast cell lines. Expression of beclin 1 in fibroblasts from IPF was down-regulated in comparison with fibroblasts from normal lungs while the anti-apoptotic protein Bcl-2 expression was over-expressed. Treatment of fibroblast cell cultures with cisplatin induced a significant increase in beclin 1 and caspase 3 protein levels but a reduction in Bcl-2 expression. These observations were confirmed by the analysis of acid compartments and transmission electron microscopy. Our results demonstrate a modified expression of the apoptotic beclin 1 Bcl-2 proteins in human IPF fibroblasts suggesting the existence of an autophagy/apoptosis system dysfunction.

Real-time three-dimensional (3D) echocardiography allows us to measure right ventricular (RV) end-diastolic volume irrespective of its shape. Tissue Doppler imaging (TDI) and speckle tracking imaging (STI) are new tools to assess myocardial function. We sought to evaluate RV function by 3D echocardiography and myocardial strain imaging in adult patients with atrial septal defect (ASD) before and 6 months after transcatheter closure in order to assess the utility of these new indexes in comparison with standard two-dimensional (2D) and Doppler parameters. Thirty-nine ASD patients and 39 healthy age- and sex-matched controls were studied using a commercially available cardiovascular ultrasound system. 2D-Doppler parameters of RV function (fractional area change, tricuspid annular plane systolic excursion, myocardial performance index) were calculated. 3D RV volumes were also obtained. RV peak-systolic velocities, peak-systolic strain, and peak systolic and diastolic strain-rate were measured in the basal, mid and apical segments of lateral and septal walls in apical 4-chamber view by TDI and STI. In open ASD, RV ejection fraction (3D-RVEF) and global and regional RV longitudinal strain were significantly higher than control group and decreased significantly after closure. By multivariate analysis 3D-RVEF, apical strain and strain rate were independent predictors of functional class. ROC analysis showed 3D-RVEF and apical strain to be more sensitive predictors of unfavorable outcome after defect closure compared to 2D-Doppler indexes. 3D echocardiography and myocardial strain imaging give useful insights in the quantitative assessment of RV function in ASD patients before and after closure.

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Epithelial-to-mesenchymal transition (EMT) is a process in which cells undergo a developmental switch from epithelial to mesenchymal phenotype. This process has been related to embryologic morphogenesis but also to cancer progression and metastasis. The aim of the current study was to investigate the expression of EMT-related markers in adherent and spheroid cell cultures derived from malignant pleural effusions (MPEs) of patients affected by lung adenocarcinoma. On the basis of efficient in vitro propagation, six cases of MPEs were selected and analyzed by immunocytochemistry staining for EMT markers and by RT-PCR for transcription factors known to orchestrate EMT. EMT markers immunostaining showed in spheroids a statistically significant correlation between the loss of E-cadherin immunoreactivity and overexpression of N-cadherin (P < 0.001). Likewise loss of EpCAM epithelial marker was coincident with Vimentin overexpression (P < 0.001). RT-PCR analysis of transcription factors Snail, Slug, and Twist showed a highly variable expression, although a general trend to increase was observed. Importantly, in some selected cases it was possible to establish a precise relationship between spheroid formation, EMT switch and increased upregulation of the marker related to cancer stemness such as ALDH positivity. Therefore, MPE-derived cell cultures, while recapitulating the heterogeneity of lung cancer, are a suitable system to study the mechanisms at the basis of EMT and to understand its relationship with the generation of cancer stem cells.

Abstract. The present study reports two cases of lung cancer with the involvement of the pleura. The diagnosis of adenocarcinoma with epidermal growth factor receptor (EGFR) mutation was made following repeated thoracentesis with cytology of pleural fluid and thoracoscopy with pleural biopsies. Talc pleurodesis was successfully performed in both cases subsequent to diagnosis. Following talc pleurodesis, the first patient (62 years old; male; non-smoker) underwent 3 cycles of cisplatin/vinorelbine chemotherapy, with a poor response. Concurrently, due to the presence of an EGFR mutation, treatment with gefitinib was initiated, with the patient achieving a good response for ~12 months. The residual tumor was treated with stereotactic radiotherapy and the patient continued gefitinib treatment. The patient is presently in good health, has not exhibited any signs of relapse and is continuing gefitinib treatment without side effects. The second patient (53 years old; male ex-smoker) underwent treatment with gefitinib subsequent to talc pleurodesis for a total of 15 months. In addition, radiotherapy (60 Gy) on the residual lesion was performed. Subsequently, second-line therapy with cisplatin/premetrexed was prescribed and followed by maintenance treatment with premetrexed. Three years after diagnosis, the patient did not exhibit any signs of recurrence. These two cases highlight the difficulty in treating advanced stage lung cancer, despite the presence of EGFR mutation. Each lung cancer is different and requires the physician to possess a wide range of knowledge of the therapeutic options available, in addition to careful monitoring in order to adjust the treatment over time. A multidisciplinary approach, involving surgeons, radiation oncologists, pulmonologists and oncologists, is required to optimize the survival and quality of life of patients with lung cancer.

Homeodomain-interacting protein kinase 2 (Hipk2) is an emerging player in cell response to genotoxic agents that contributes to the cell's decision between cell cycle arrest or apoptosis. HIPK2 acts as co-regulator of an increasing number of transcription factors and modulates many different basic cellular processes such as apoptosis, proliferation, DNA damage response, differentiation. Idiopathic pulmonary fibrosis (IPF) is characterized by an anatomical disarrangement of the lung due to fibroblast proliferation, extracellular matrix deposition and lung function impairment. Although the role of inflammation is still debated, attention has been focused on lung cell functions as fibroblast phenotype and activity. Aim of the present study was to analyze the loss of heterozygosity (LOH) at HIPK2 locus 7q32.34 in human lung fibroblasts and the HIPK2 expression in 15 IPF samples and in four primary fibroblast cell cultures isolated from IPF biopsies using semi-quantitative RT-PCR, Western blots and immunohistochemistry. We demonstrated a frequency of LOH in IPF fibroblasts of 46% for the internal D7S6440 microsatellite and 26.6% for the external D7S2468 microsatellite. Furthermore, we demonstrated low HIPK2 protein expression in those fibroblasts from IPF patients that present the HIPK2 LOH. The restoration of HIPK2 expression in IPF derived cells induced a significant reduction of chemoresistance after treatment with cisplatin. The results obtained allow us to hypothesize that HIPK2 dysfunction may play a role in fibroblasts behavior and in IPF pathogenesis. HIPK2 may be considered as a novel potential target for anti-fibrosis therapy.

In the early stages of bronchial asthma, it is frequent to find subjects with a positive history and an FEV1 or FEV1/FVC > 80% of the predicted value. This study investigated if the test of reversibility showed a reversible airway obstruction (RAO) in 291 subjects with the above clinical and functional features. Forced expiratory volume in 1 second (FEV1), forced vital capacity (FVC), and expiratory flows (PEF, MEF50, FEF(25-75)) were registered before and 20 minutes after salbutamol administration (200 mcg by MDI). Of 291 subjects, FEV1 increased in 73 (25%) after bronchodilator > or = 12% compared to baseline; the number of subjects with a > or = 35% increase in MEF50 or FEF(25-75) were similar in terms of percentage (respectively, 29.2% and 29%), whereas those with increases in FVC (> or = 12%) and in PEF (> or = 15%) were significantly lower (respectively, 2.7% and 12.3%). The percentage of subjects with RAO (FEV1 increase after bronchodilator > or = 12%) was lower (12%) in the subgroup (108 subjects), with an MEF50 > or = 70% of the value predicted at the baseline assessment, and higher (36%) in the subjects of the subgroup (183 subjects) with an MEF50 < 70%. In conclusion, it is advisable to carry out reversibility tests in all subjects with symptoms indicative of asthma even if their functional tests are "normal" because in a considerable number of cases the RAO was found to confirm the suspected diagnosis and provided a more reliable classification of the disease.