Integrative and comparative genomic analyses identify clinically relevant pulmonary carcinoid groups and unveil the supra-carcinoids

International audienceThe worldwide incidence of pulmonary carcinoids is increasing, but little is known about their molecular characteristics. Through machine learning and multi-omics factor analysis, we compare and contrast the genomic profiles of 116 pulmonary carcinoids (including 35 atypical), 75 large-cell neuroendocrine carcinomas (LCNEC), and 66 small-cell lung cancers. Here we report that the integrative analyses on 257 lung neuroendocrine neoplasms stratify atypical carcinoids into two prognostic groups with a 10-year overall survival of 88% and 27%, respectively. We identify therapeutically relevant molecular groups of pulmonary car-cinoids, suggesting DLL3 and the immune system as candidate therapeutic targets; we confirm the value of OTP expression levels for the prognosis and diagnosis of these diseases, and we unveil the group of supra-carcinoids. This group comprises samples with carcinoid-like morphology yet the molecular and clinical features of the deadly LCNEC, further supporting the previously proposed molecular link between the low-and high-grade lung neuroendocrine neoplasms

Incidence and survival of peritoneal malignant mesothelioma between 1989 and 2015: A population-based study

International audienceBACKGROUND:Peritoneal malignant mesothelioma is a rare disease for which few population-based studies are available. The aim of this study was to describe the evolution of the incidence and survival of peritoneal malignant mesothelioma in France between 1989 and 2015, using data derived from the French network of cancer registries.METHODS:Age world-standardized incidence rates and overall survival were calculated using data from 16 French cancer registries. Log-linear Poisson regression analysis was used to estimate the average annual percentage change in incidence rates. Overall survival was performed using age-adjusted Cox proportional hazards model.RESULTS:In French men, the incidence has increased quietly over the reporting period from 0.07 to 0.10 with a maximum of 0.16 per 100,000 persons-years in 2001-2003. For women, the increase in incidence has been lower than for men over the period 1989-2015, ranging from 0.04 to 0.11. A better prognosis was associated with a diagnosis made after 2000 (HR = 1.76; p = 0.013), the epithelioid histological type (p = 0.003), and the fact of being a woman, which has a 5-year risk of death half that of men (HR = 0.55; p = 0.001), regardless of age, diagnosis period or histology.CONCLUSION:Our results are similar to those currently available for other countries. In France, peritoneal mesothelioma remains a rare and fatal cancer with a small increase in the incidence rate since 1989 and a median survival of 1 year; it seemed to develop equally in women and men over this period of time

Nuclear morphology for the detection of alterations in bronchial cells from lung cancer: an attempt to improve sensitivity and specificity.

International audienceOBJECTIVE: To identify which morphologic or densitometric parameters are modified in cell nuclei from bronchopulmonary cancer based on 18 parameters involving shape, intensity, chromatin, texture, and DNA content and develop a bronchopulmonary cancer screening method relying on analysis of sputum sample cell nuclei. STUDY DESIGN: A total of 25 sputum samples from controls and 22 bronchial aspiration samples from patients presenting with bronchopulmonary cancer who were professionally exposed to cancer were used. After Feulgen staining, 18 morphologic and DNA content parameters were measured on cell nuclei, via image cytom- etry. A method was developed for analyzing distribution quantiles, compared with simply interpreting mean values, to characterize morphologic modifications in cell nuclei. RESULTS: Distribution analysis of parameters enabled us to distinguish 13 of 18 parameters that demonstrated significant differences between controls and cancer cases. These parameters, used alone, enabled us to distinguish two population types, with both sensitivity and specificity > 70%. Three parameters offered 100% sensitivity and specificity. When mean values offered high sensitivity and specificity, comparable or higher sensitivity and specificity values were observed for at least one of the corresponding quantiles. CONCLUSION: Analysis of modification in morphologic parameters via distribution analysis proved promising for screening bronchopulmonary cancer from sputum

Digestive cancers and occupational asbestos exposure: incidence study in a cohort of asbestos plant workers

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Preclinical evaluation of CDK4/6 inhibitors in mesothelioma

info:eu-repo/semantics/publishe

Plasma Cell Membrane Localization of c-MET Predicts Longer Survival in Patients with Malignant Mesothelioma: A Series of 157 Cases from the MESOPATH Group

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Role of metal oxide nanoparticles in histopathological changes observed in the lung of welders.

International audienceBACKGROUND: Although major concerns exist regarding the potential consequences of human exposure to nanoparticles (NP), no human toxicological data is currently available. To address this issue, we took welders, who present various adverse respiratory outcomes, as a model population of occupational exposure to NP.The aim of this study was to evaluate if welding fume-issued NP could be responsible, at least partially, in the lung alterations observed in welders. METHODS: A combination of imaging and material science techniques including ((scanning) transmission electron microscopy ((S)TEM), energy dispersive X-ray (EDX), and X-ray microfluorescence (μXRF)), was used to characterize NP content in lung tissue from 21 welders and 21 matched control patients. Representative NP were synthesized, and their effects on macrophage inflammatory secretome and migration were evaluated, together with the effect of this macrophage inflammatory secretome on human lung primary fibroblasts differentiation. RESULTS: Welding-related NP (Fe, Mn, Cr oxides essentially) were identified in lung tissue sections from welders, in macrophages present in the alveolar lumen and in fibrous regions. In vitro macrophage exposure to representative NP (Fe2O3, Fe3O4, MnFe2O4 and CrOOH) induced the production of a pro-inflammatory secretome (increased production of CXCL-8, IL-1ß, TNF-α, CCL-2, -3, -4, and to a lesser extent IL-6, CCL-7 and -22), and all but Fe3O4 NP induce an increased migration of macrophages (Boyden chamber). There was no effect of NP-exposed macrophage secretome on human primary lung fibroblasts differentiation. CONCLUSIONS: Altogether, the data reported here strongly suggest that welding-related NP could be responsible, at least in part, for the pulmonary inflammation observed in welders. These results provide therefore the first evidence of a link between human exposure to NP and long-term pulmonary effects

of welders

Role of metal oxide nanoparticles in histopathological changes observed in the lun