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Yablonski P.,Saint Petersburg State University | Cordos I.,National Institute of Pulmonology | Sokolovich E.,Saint Petersburg State University | Schonfeld N.,HELIOS Klinikum Emil von Behring | And 2 more authors.
European Respiratory Monograph | Year: 2013

Before the introduction of antituberculous drugs, collapse therapy was the dominant surgical treatment for cavitating lung tuberculosis (TB). Today, there is a wide range of indications for surgery in different geographical regions. Most frequently, surgical procedures are indicated for cavernous lesions and tuberculomas in 91.6% of patients, haemoptysis in 58% of patients, and in all patients with multidrug-resistant (MDR) TB. Currently, indications for surgery can be summarised as follows: 1) operations with diagnostic purpose, if it is not possible to rule out TB by other diagnostic methods; 2) elimination of the source of Mycobacterium tuberculosis in patients with cavities persisting under chemotherapy (MDR-TB or destroyed lung); 3) tuberculous pleural empyema; and 4) sequelae of past TB. This overview highlights current controversies in different groups of indications in order to facilitate an optimal therapeutic approach in these patients. © ERS 2013.

Hoda M.A.,Medical University of Vienna | Mohamed A.,Medical University of Vienna | Ghanim B.,Medical University of Vienna | Filipits M.,Medical University of Vienna | And 12 more authors.
Journal of Thoracic Oncology | Year: 2011

Introduction: Human malignant pleural mesothelioma (MPM) is an asbestos-related malignancy characterized by frequent resistance to chemotherapy and radiotherapy. Here, we investigated the feasibility of mammalian target of rapamycin (mTOR) inhibition by temsirolimus as an antimesothelioma strategy. Methods: Phosphorylation of mTOR (p-mTOR) was assessed by immunohistochemistry in MPM surgical specimens (n = 70). Activation of mTOR and impact of mTOR inhibition by temsirolimus was determined in MPM cell lines in vitro (n = 6) and in vivo as xenografts in severe combined immunodeficiency mice (n = 2) either as single agent or in combination with cisplatin. Results: Strong immunoreactivity for p-mTOR was predominantly detected in epitheloid and biphasic but not sarcomatoid MPM specimens while adjacent normal tissues remained widely unstained. Accordingly, all mesothelioma cell lines harbored activated mTOR, which was further confirmed by hyperphosphorylation of the downstream targets pS6K, S6, and 4EBP1. Temsirolimus potently blocked mTOR-mediated signals and exerted a cytostatic effect on mesothelioma cell lines in vitro cultured both as adherent monolayers and as nonadherent spheroids. Mesothelioma cells with intrinsic or acquired cisplatin resistance exhibited hypersensitivity against temsirolimus. Accordingly, cisplatin and temsirolimus exerted synergistic inhibition of the mTOR downstream signals and enhanced growth inhibition and/or apoptosis induction in mesothelioma cell lines. Finally, temsirolimus was highly active against MPM xenograft models in severe combined immunodeficiency mice both as a single agent and in combination with cisplatin. Conclusion: The mTOR inhibitor temsirolimus is active against mesothelioma in vitro and in vivo and synergizes with chemotherapy. These data suggest mTOR inhibition as a promising novel therapeutic strategy against MPM. Copyright © 2011 by the International Association for the Study of Lung Cancer.

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