The Genes-Stemness-Secretome Interplay in Malignant Pleural Mesothelioma: Molecular Dynamics and Clinical Hints.

MPM has a uniquely poor somatic mutational landscape, mainly driven by environmental selective pressure. This feature has dramatically limited the development of effective treatment. However, genomic events are known to be associated with MPM progression, and specific genetic signatures emerge from the exceptional crosstalk between neoplastic cells and matrix components, among which one main area of focus is hypoxia. Here we discuss the novel therapeutic strategies focused on the exploitation of MPM genetic asset and its interconnection with the surrounding hypoxic microenvironment as well as transcript products and microvesicles representing both an insight into the pathogenesis and promising actionable targets.

Smoking Habit and Respiratory Function Predict Patients' Outcome after Surgery for Lung Cancer, Irrespective of Histotype and Disease Stage.

BACKGROUND: Growing evidence suggests that sublobar resections offer more favorable outcomes than lobectomy in early-stage lung cancer surgery. However, a percentage of cases that cannot be ignored develops disease recurrence irrespective of the surgery performed with curative intent. The goal of this work is thus to compare different surgical approaches, namely, lobectomy and segmentectomy (typical and atypical) to derive prognostic and predictive markers. PATIENTS AND METHODS: Here we analyzed a cohort of 153 NSCLC patients in clinical stage TNM I who underwent pulmonary resection surgery with a mediastinal hilar lymphadenectomy from January 2017 to December 2021, with an average follow-up of 25.5 months. Partition analysis was also applied to the dataset to detect outcome predictors. RESULTS: The results of this work showed similar OS between lobectomy and typical and atypical segmentectomy for patients with stage I NSCLC. In contrast, lobectomy was associated with a significant improvement in DFS compared with typical segmentectomy in stage IA, while in stage IB and overall, the two treatments were similar. Atypical segmentectomy showed the worst performance, especially in 3-year DFS. Quite unexpectedly, outcome predictor ranking analysis suggests a prominent role of smoking habits and respiratory function, irrespective of the tumor histotype and the patient's gender. CONCLUSIONS: Although the limited follow-up interval cannot allow conclusive remarks about prognosis, the results of this study suggest that both lung volumes and the degree of emphysema-related parenchymal damage are the strongest predictors of poor survival in lung cancer patients. Overall, these data point out that greater attention should be addressed to the therapeutic intervention for co-existing respiratory diseases to obtain optimal control of early lung cancer.

The Plastic Interplay between Lung Regeneration Phenomena and Fibrotic Evolution: Current Challenges and Novel Therapeutic Perspectives.

Interstitial lung diseases (ILDs) are a heterogeneous group of pulmonary disorders characterized by variable degrees of inflammation, interstitial thickening, and fibrosis leading to distortion of the pulmonary architecture and gas exchange impairment. Among them, idiopathic pulmonary fibrosis (IPF) displays the worst prognosis. The only therapeutic options consist of the two antifibrotic drugs, pirfenidone and nintedanib, which limit fibrosis progression but do not reverse the lung damage. The shift of the pathogenetic paradigm from inflammatory disease to epithelium-derived disease has definitively established the primary role of type II alveolar cells, which lose their epithelial phenotype and acquire a mesenchymal phenotype with production of collagen and extracellular matrix (EMC) deposition. Some predisposing environmental and genetic factors (e.g., smoke, pollution, gastroesophageal reflux, variants of telomere and surfactant genes) leading to accelerated senescence set a pro-fibrogentic microenvironment and contribute to the loss of regenerative properties of type II epithelial cells in response to pathogenic noxae. This review provides a complete overview of the different pathogenetic mechanisms leading to the development of IPF. Then, we summarize the currently approved therapies and the main clinical trials ongoing. Finally, we explore the potentialities offered by agents not only interfering with the processes of fibrosis but also restoring the physiological properties of alveolar regeneration, with a particular focus on potentialities and concerns about cell therapies based on mesenchymal stem cells (MSCs), whose anti-inflammatory and immunomodulant properties have been exploited in other fibrotic diseases, such as graft versus host disease (GVHD) and COVID-19-related ARDS.