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Background: Calretinin is the most widespread positive marker for the immunohistochemical identification of malignant mesothelioma (MM) and was proposed to serve as a blood-based biomarker. Functionally, evidence has accumulated that calretinin might be implicated in MM tumorigenesis. We aimed to identify calretinin (CR; Calb2 ) in murine MM and reactive mesothelial cells in granuloma from asbestos-exposed NF2 +/- mice, a line heterozygous for the tumor suppressor merlin (NF2), used as a mouse MM model. Additionally, we sought to ascertain the presence of calretinin in MM cell lines from other mouse strains. We also intended to investigate the role of calretinin in mesotheliomagenesis by comparing the survival of asbestos-exposed NF2 +/- and NF2 +/- CR -/- mice., Methods: NF2 +/- and NF2 +/- CR -/- mice, both lines on a C57Bl/6J background, were exposed to asbestos following an established protocol. Tumor histology and asbestos-induced mortality were assessed. MM and granuloma from NF2 +/- mice were analyzed with immunohistochemical methods for calretinin expression. Levels of Calb2 mRNA and calretinin expression in tumors and MM cell lines of various mouse strains were determined by RT-qPCR and Western blot analysis, respectively., Results: No expression of calretinin at the protein level was detected, neither in MM from NF2 +/- mice, NF2 +/- MM-derived cell lines nor immortalized mesothelial cells of mouse origin. At the mRNA level we detected Calb2 expression in MM cell lines from different mouse strains. Survival of NF2 +/- and NF2 +/- CR -/- mice exposed to asbestos showed no significant difference in a log-rank (Kaplan-Meier) comparison., Conclusions: The concomitant determination of calretinin and mesothelin blood levels has been proposed for early detection of human MM. Mouse MM models based on asbestos exposure are assumed to yield helpful information on the time course of appearance of mesothelin and calretinin in the blood of asbestos-treated mice determining the earliest time point for interventions. However, the observed absence of calretinin in MM from NF2 +/- mice and derived cell lines, as well as from MM cells from Balb/c and C3H mice likely precludes the use of calretinin as a biomarker for mouse MM. The results also indicate possible species differences with respect to an involvement of calretinin in the formation of MM., Competing Interests: Human embryonic lung tissue came from the specimen collection of the Unit of Anatomy, Section of Medicine, University of Fribourg, where donators had approved the use of tissue for teaching and research purposes. All experiments requiring mouse tissue (embryos) were performed with permission of the local animal care committee (Canton of Fribourg, Switzerland) and according to the present Swiss law and the European Communities Council Directive of 24 November 1986 (86/609/EEC).The authors declare that they have no competing interests.Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

Background: Sarcoidosis presents with typical clinic-radiological findings and shows histologically non-caseating granulomas. Pulmonary manifestations of sarcoidosis can be diverse, involving the intrathoracic lymph nodes and pulmonary parenchyma., Case Presentation: We here describe a case of a 35-year-old patient who presented with a history of exertion dyspnoea and coughing for the past 20 years. At the age of 15, she was exposed to smoke emanating from a fire. Later, she had exposure to mold for two years, and during her childhood, she had animals such as a cockatiel, dog, cat, gecko, and turtle. Computed tomography of the chest revealed symmetrical apical giant bullous lesions. Histology of the resected bullae showed prominent peribronchial fibrosis with non-necrotizing, non-caseating granulomas and collaps of pulmonary lobules adjacent to the bulla. The absence of granulomatous infection and a markedly elevated CD4:CD8 ratio in bronchoalveolar lavage analysis suggested that the underlying process was sarcoidosis., Conclusion: In very rare cases, sarcoidosis can be associated with bilateral symmetrical apical giant bullous disease due to fibrotic and granulomatous changes resulting in a restriction of lung tissue.

Background: Malignant pleural mesothelioma (MPM) is an aggressive cancer with short overall survival. Long non-coding RNAs (lncRNA) are a class of RNAs more than 200 nucleotides long that do not code for protein and are part of the 90% of the human genome that is transcribed. Earlier experimental studies in mice showed GAS5 (growth arrest specific transcript 5) gene deletion in asbestos driven mesothelioma. GAS5 encodes for a lncRNA whose function is not well known, but it has been shown to act as glucocorticoid receptor decoy and microRNA "sponge". Our aim was to investigate the possible role of the GAS5 in the growth of MPM., Methods: Primary MPM cultures grown in serum-free condition in 3% oxygen or MPM cell lines grown in serum-containing medium were used to investigate the modulation of GAS5 by growth arrest after inhibition of Hedgehog or PI3K/mTOR signalling. Cell cycle length was determined by EdU incorporation assay in doxycycline inducible short hairpinGAS5 clones generated from ZL55SPT cells. Gene expression was quantified by quantitative PCR. To investigate the GAS5 promoter, a 0.77 kb sequence was inserted into a pGL3 reporter vector and luciferase activity was determined after transfection into MPM cells. Localization of GAS5 lncRNA was identified by in situ hybridization. To characterize cells expressing GAS5, expression of podoplanin and Ki-67 was assessed by immunohistochemistry., Results: GAS5 expression was lower in MPM cell lines compared to normal mesothelial cells. GAS5 was upregulated upon growth arrest induced by inhibition of Hedgehog and PI3K/mTOR signalling in in vitro MPM models. The increase in GAS5 lncRNA was accompanied by increased promoter activity. Silencing of GAS5 increased the expression of glucocorticoid responsive genes glucocorticoid inducible leucine-zipper and serum/glucocorticoid-regulated kinase-1 and shortened the length of the cell cycle. Drug induced growth arrest was associated with GAS5 accumulation in the nuclei. GAS5 was abundant in tumoral quiescent cells and it was correlated to podoplanin expression., Conclusions: The observations that GAS5 levels modify cell proliferation in vitro, and that GAS5 expression in MPM tissue is associated with cell quiescence and podoplanin expression support a role of GAS5 in MPM biology.