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Leclerc J.,University of Lille Nord de France | Tournel G.,University of Lille Nord de France | Courcot-Ngoubo Ngangue E.,University of Lille Nord de France | Pottier N.,University of Lille Nord de France | And 6 more authors.
Biochimie | Year: 2010

Susceptibility to lung diseases, such as lung cancer and chronic obstructive pulmonary disease, is largely influenced by the metabolic capacity of lung tissues. This capacity is partly determined by the expression profile of the cytochromes P450 (CYPs), a superfamily of enzymes that have relevant catalytic properties toward exogenous and endogenous compounds. Using quantitative real-time RT-PCR, we conducted a comprehensive analysis of the expression profile of the 57 human CYP genes in non-tumoral (bronchial mucosa and pulmonary parenchyma) and tumoral lung tissues of 18 patients with non-small cell lung cancer. This study highlights (i) inter-individual variations in lung expression for some CYPs, (ii) different CYP expression patterns between bronchial mucosa and pulmonary parenchyma, that indicate distinctive susceptibility of these tissues toward the deleterious effects of inhaled chemical toxicants and carcinogens, (iii) high intertumoral variability, that could have major implications on lung tumor response to anti-cancer drugs. © 2010 Elsevier Masson SAS.

Jouveshomme S.,Service de Pneumologie et dOncologie Thoracique | Canoui-Poitrine F.,University Paris Est Creteil | Le Thuaut A.,University Paris Est Creteil | Bastuji-Garin S.,University Paris Est Creteil
Medical Oncology | Year: 2013

Recent phase-III trials show that platinum-based chemotherapy (PBCT) for patients with advanced non-small cell lung cancer and poor performance status (PS) improves survival without increasing toxicity, compared to single-agent chemotherapy (CT). The aim of this study was to asses whether these results are transposable in a community population. About 260 consecutive patients with stage IIIB-IV NSCLC (25 % with PS 2) receiving a PBCT were prospectively included in the study and retrospectively analyzed. No difference was observed between PS 0-1 and 2 patients regarding tumor-control rate, symptom relief, and grade III-V toxicity. Median and 1-year survival of PS 2 patients was 6.2 months and 32 %, respectively. PS 1 and PS 2 patients continuing first-line CT beyond the first course shared the same survival. On the other hand, more PS 2 (31.8 vs. 9.3 % of PS 0-1 patients, p < 0.001) discontinued first-line CT after the first course with a poor clinical outcome. They were more likely to have lost weight and to have a high comorbidity score. PBCT in unselected PS 2 patients achieved survival rates similar to those observed in clinical trials, with no increase in toxicity. PS 2 patients continuing CT beyond the first course shared the same prognosis than PS 1 patients. However, almost one-third of PS 2 patients discontinued CT after the first course. Their prognosis was poor. © 2013 Springer Science+Business Media New York.

Vergnon J.-M.,Service de Pneumologie et dOncologie Thoracique
Revue des Maladies Respiratoires Actualites | Year: 2014

Flexible bronchoscopy is the gold standard technique to diagnose central bronchial cancer. Today, 3 new challenges have to be resolved: i) to detect earlier central cancer to allow a curative local treatment; ii) To explore mediastinal lymph node invasion to improve the staging and the treatment; iii) To diagnose peripheral cancer: this situation. is now common with the higher incidence of adenocarcinomas and with the promotion of screening techniques.This paper analyses the main data on early detection of bronchial cancer (fluorescence bronchoscopy and NBI), on mediastinal staging through conventional TBNA or EBUSTBNA and on per-bronchoscopy sampling of peripheral nodules with radial echography or electromagnetic navigation. To obtain the best sensibility in the diagnosis of cancer, pulmonologists should provide adequate samplings to allow gene mutation. Pathologists should also learn the best strategy to optimize these minimal samplings.A larger diffusion of these new expensive bronchoscopic techniques requires an acceptable reimbursement of these fees by the social insurances. © 2013 Elsevier Masson SAS.

Leclerc J.,University of Lille Nord de France | Courcot-Ngoubo Ngangue E.,University of Lille Nord de France | Cauffiez C.,University of Lille Nord de France | Allorge D.,University of Lille Nord de France | And 6 more authors.
Biochimie | Year: 2011

The lung is directly exposed to a wide variety of inhaled toxicants and carcinogens. In order to improve our knowledge of the cellular processing of these compounds in the respiratory tract, we investigated the mRNA expression level of 380 genes encoding xenobiotic-metabolizing enzymes (XME), transporters, nuclear receptors and transcription factors, in pulmonary parenchyma (PP), bronchial mucosa (BM) and tumoral lung tissues from 12 patients with non-small cell lung cancer (NSCLC). Using a high throughput quantitative real-time RT-PCR method, we found that ADH1B, CYP4B1, CES1 and GSTP1 are the major XME genes expressed both in BM and PP. Our results also documented the predominant role played by the xenosensor AhR in human lung. The gene expression profiles were different for BM and PP, with a tendency toward increased mRNA levels of phase I and phase II XME genes in BM, suggesting major differences in the initial stages of xenobiotic metabolism. Some of the significantly overexpressed genes in BM (i.e. CYP2F1, CYP2A13, CYP2W1, NQO1...) encode proteins involved in the bioactivation of procarcinogens, pointing out distinct susceptibility to xenobiotics and their toxic effects between these two tissue types. Additionally, interindividual differences in transcript levels observed for some genes may be of genetic origin and may contribute to the variability in response to environmental exposure and, consequently, in the risk of developing lung diseases. A global decrease in gene expression was observed in tumoral specimens. Some of the proteins are involved in the metabolism or transport of anti-cancer drugs and their influence in the response of tumors to chemotherapy should be considered. In conclusion, the present study provides an overview of the cellular response to toxicants and drugs in healthy and cancerous human lung tissues, and thus improves our understanding of the mechanisms of chemical carcinogenesis as well as cellular resistance to chemotherapy. © 2011 Elsevier Masson SAS. All rights reserved.

Romand P.,Service Route | Kelkel E.,Center Hospitalier | Saint-Raymond C.,Hopital University | Glas N.,Service de Pneumologie et dOncologie Thoracique | And 2 more authors.
Revue des Maladies Respiratoires | Year: 2016

Introduction: With an aging population and an increase in the prevalence of asthma, this disease is becoming more common in the elderly. Nevertheless, the management of severe asthma can be complex, due to an increased risk of uncontrolled disease in patients over 65 years old and partly to the inherent characteristics of old age: comorbidities, underestimation of the role of allergies, poor adherence, difficulties with inhalation devices, etc. Case reports: We report two cases of women over 75 with severe persistent allergic asthma not controlled by high doses of inhaled corticosteroids and long-acting beta-2-agonists in whom treatment with omalizumab was initiated. Following treatment with omalizumab a decrease in the number and severity of exacerbations, improved asthma control and dose reduction or discontinuation of systemic corticosteroids were observed. The tolerance of omalizumab was good in both cases. Conclusions: Omalizumab is to be considered an effective and well-tolerated therapeutic option for elderly patients with inadequately controlled severe allergic asthma. © 2015 SPLF.

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