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walter klepetko

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https://www.readbyqxmd.com/read/28182573/amplified-canonical-transforming-growth-factor-%C3%AE-signalling-via-heat-shock-protein-90-in-pulmonary-fibrosis
#1
Zaneta Sibinska, Xia Tian, Martina Korfei, Baktybek Kojonazarov, Janina Susanne Kolb, Walter Klepetko, Djuro Kosanovic, Malgorzata Wygrecka, Hossein Ardeschir Ghofrani, Norbert Weissmann, Friedrich Grimminger, Werner Seeger, Andreas Guenther, Ralph T Schermuly
Interstitial lung fibroblast activation coupled with extracellular matrix production is a pathological signature of idiopathic pulmonary fibrosis (IPF), and is governed by transforming growth factor (TGF)-β/Smad signalling. We sought to define the role of heat shock protein (HSP)90 in profibrotic responses in IPF and to determine the therapeutic effects of HSP90 inhibition in a murine model of pulmonary fibrosis.We investigated the effects of HSP90 inhibition in vitro by applying 17-AAG (17-allylamino-17-demethoxygeldanamycin) to lung fibroblasts and A549 cells and in vivo by administering 17-DMAG (17-dimethylaminoethylamino-17-demethoxygeldanamycin) to mice with bleomycin-induced pulmonary fibrosis...
December 19, 2016: European Respiratory Journal: Official Journal of the European Society for Clinical Respiratory Physiology
https://www.readbyqxmd.com/read/28093071/spag6-and-l1td1-are-transcriptionally-regulated-by-dna-methylation-in-non-small-cell-lung-cancers
#2
Corinna Altenberger, Gerwin Heller, Barbara Ziegler, Erwin Tomasich, Maximilian Marhold, Thais Topakian, Leonhard Müllauer, Petra Heffeter, György Lang, Adelheid End-Pfützenreuter, Balazs Döme, Britt-Madeleine Arns, Walter Klepetko, Christoph C Zielinski, Sabine Zöchbauer-Müller
BACKGROUND: DNA methylation regulates together with other epigenetic mechanisms the transcriptional activity of genes and is involved in the pathogenesis of malignant diseases including lung cancer. In non-small cell lung cancer (NSCLC) various tumor suppressor genes are already known to be tumor-specifically methylated. However, from the vast majority of a large number of genes which were identified to be tumor-specifically methylated, tumor-specific methylation was unknown so far. Thus, the major aim of this study was to investigate in detail the mechanism(s) responsible for transcriptional regulation of the genes SPAG6 and L1TD1 in NSCLCs...
January 5, 2017: Molecular Cancer
https://www.readbyqxmd.com/read/28051122/kras-mutation-incidence-and-prognostic-value-are-metastatic-site-specific-in-lung-adenocarcinoma-poor-prognosis-in-patients-with-kras-mutation-and-bone-metastasis
#3
Zoltan Lohinai, Thomas Klikovits, Judit Moldvay, Gyula Ostoros, Erzsebet Raso, Jozsef Timar, Katalin Fabian, Ilona Kovalszky, István Kenessey, Clemens Aigner, Ferenc Renyi-Vamos, Walter Klepetko, Balazs Dome, Balazs Hegedus
Current guidelines lack comprehensive information on the metastatic site-specific role of KRAS mutation in lung adenocarcinoma (LADC). We investigated the effect of KRAS mutation on overall survival (OS) in this setting. In our retrospective study, 500 consecutive Caucasian metastatic LADC patients with known KRAS mutational status were analyzed after excluding 32 patients with EGFR mutations. KRAS mutation incidence was 28.6%. The most frequent metastatic sites were lung (45.6%), bone (26.2%), adrenal gland (17...
January 4, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28042343/limited-tumor-tissue-drug-penetration-contributes-to-primary-resistance-against-angiogenesis-inhibitors
#4
Szilvia Torok, Melinda Rezeli, Olga Kelemen, Akos Vegvari, Kenichi Watanabe, Yutaka Sugihara, Anna Tisza, Timea Marton, Ildiko Kovacs, Jozsef Tovari, Viktoria Laszlo, Thomas H Helbich, Balazs Hegedus, Thomas Klikovits, Mir Alireza Hoda, Walter Klepetko, Sandor Paku, Gyorgy Marko-Varga, Balazs Dome
Resistance mechanisms against antiangiogenic drugs are unclear. Here, we correlated the antitumor and antivascular properties of five different antiangiogenic receptor tyrosine kinase inhibitors (RTKIs) (motesanib, pazopanib, sorafenib, sunitinib, vatalanib) with their intratumoral distribution data obtained by matrix-assisted laser desorption ionization mass spectrometry imaging (MALDI-MSI). In the first mouse model, only sunitinib exhibited broad-spectrum antivascular and antitumor activities by simultaneously suppressing vascular endothelial growth factor receptor-2 (VEGFR2) and desmin expression, and by increasing intratumoral hypoxia and inhibiting both tumor growth and vascularisation significantly...
2017: Theranostics
https://www.readbyqxmd.com/read/28026875/the-evidence-for-and-against-different-modes-of-tumour-cell-extravasation-in-the-lung-diapedesis-capillary-destruction-necroptosis-and-endothelialization
#5
Sándor Paku, Viktoria Laszlo, Katalin Dezso, Peter Nagy, Mir Alireza Hoda, Walter Klepetko, Ferenc Renyi-Vamos, Jozsef Timar, Andrew R Reynolds, Balazs Dome
The development of lung metastasis is a significant negative prognostic factor for cancer patients. The extravasation phase of lung metastasis involves interactions of tumour cells with the pulmonary endothelium. These interactions may have broad biological and medical significance, with potential clinical implications ranging from the discovery of lung metastasis biomarkers to the identification of targets for intervention in preventing lung metastases. Because of the potential significance, the mechanisms of tumour cell extravasation require cautious, systematic studies...
December 27, 2016: Journal of Pathology
https://www.readbyqxmd.com/read/28007873/re-excellent-outcome-of-donor-lobectomy-with-various-surgical-techniques-for-the-interlobar-artery
#6
EDITORIAL
Walter Klepetko
No abstract text is available yet for this article.
December 22, 2016: European Journal of Cardio-thoracic Surgery
https://www.readbyqxmd.com/read/27836956/an-association-of-particulate-air-pollution-and-traffic-exposure-with-mortality-after-lung-transplantation-in-europe
#7
David Ruttens, Stijn E Verleden, Esmée M Bijnens, Ellen Winckelmans, Jens Gottlieb, Gregor Warnecke, Federica Meloni, Monica Morosini, Wim Van Der Bij, Erik A Verschuuren, Urte Sommerwerck, Gerhard Weinreich, Markus Kamler, Antonio Roman, Susana Gomez-Olles, Cristina Berastegui, Christian Benden, Are Martin Holm, Martin Iversen, Hans Henrik Schultz, Bart Luijk, Erik-Jan Oudijk, Johanna M Kwakkel-van Erp, Peter Jaksch, Walter Klepetko, Nikolaus Kneidinger, Claus Neurohr, Paul Corris, Andrew J Fisher, James Lordan, Gerard Meachery, Davide Piloni, Elly Vandermeulen, Hannelore Bellon, Barbara Hoffmann, Danielle Vienneau, Gerard Hoek, Kees de Hoogh, Benoit Nemery, Geert M Verleden, Robin Vos, Tim S Nawrot, Bart M Vanaudenaerde
Air pollution from road traffic is a serious health risk, especially for susceptible individuals. Single-centre studies showed an association with chronic lung allograft dysfunction (CLAD) and survival after lung transplantation, but there are no large studies.13 lung transplant centres in 10 European countries created a cohort of 5707 patients. For each patient, we quantified residential particulate matter with aerodynamic diameter ≤10 µm (PM10) by land use regression models, and the traffic exposure by quantifying total road length within buffer zones around the home addresses of patients and distance to a major road or freeway...
January 2017: European Respiratory Journal: Official Journal of the European Society for Clinical Respiratory Physiology
https://www.readbyqxmd.com/read/27641295/a-modified-technique-of-laryngotracheal-reconstruction-without-the-need-for-prolonged-postoperative-stenting
#8
Konrad Hoetzenecker, Thomas Schweiger, Imme Roesner, Matthias Leonhard, Gabriel Marta, Doris M Denk-Linnert, Berit Schneider-Stickler, Wolfgang Bigenzahn, Walter Klepetko
OBJECTIVES: Repair of laryngotracheal stenosis with pronounced side-to-side narrowing and involvement of the glottis is challenging and usually requires laryngotracheal reconstruction with rib cartilage interpositions. This technique, as first described by Couraud, needs prolonged postoperative stabilization with Montgomery T-tubes, imposing significant morbidity and discomfort on patients. We describe our initial experience with a modified laryngotracheal reconstruction technique that avoids the need for prolonged postoperative stenting...
October 2016: Journal of Thoracic and Cardiovascular Surgery
https://www.readbyqxmd.com/read/27619223/management-of-malignant-pleural-mesothelioma%C3%A2-part%C3%A2-1-epidemiology-diagnosis-and-staging-consensus-of-the-austrian-mesothelioma-interest-group-amig
#9
Christian Geltner, Peter Errhalt, Bernhard Baumgartner, Gerhard Ambrosch, Barbara Machan, Josef Eckmayr, Thomas Klikovits, Mir Alireza Hoda, Helmut Popper, Walter Klepetko
Malignant pleural mesothelioma is a rare malignant disease that in the majority of cases is associated with asbestos exposure. The incidence in Europe is about 20 per million inhabitants and it is increasing worldwide. Initial symptoms are shortness of breath, pleural effusion, cough, and chest pain. The typical growth pattern is along the pleural surface; however, infiltration of the lung and/or mediastinal and chest wall structures can occur in a more advanced stage. Ultimately, distant metastases outside the chest can result...
September 2016: Wiener Klinische Wochenschrift
https://www.readbyqxmd.com/read/27540020/docosahexaenoic-acid-causes-rapid-pulmonary-arterial-relaxation-via-kca-channel-mediated-hyperpolarisation-in-pulmonary-hypertension
#10
Chandran Nagaraj, Bi Tang, Bence M Nagy, Rita Papp, Pritesh P Jain, Leigh M Marsh, Andrea L Meredith, Bahil Ghanim, Walter Klepetko, Grazyna Kwapiszewska, E Kenneth Weir, Horst Olschewski, Andrea Olschewski
Cardioprotective benefits of ω-3 fatty acids such as docosahexaenoic acid (DHA) are well established, but the regulatory effect of DHA on vascular tone and pressure in pulmonary hypertension is largely unknown.As DHA is a potent regulator of K(+) channels, we hypothesised that DHA modulates the membrane potential of pulmonary artery smooth muscle cells (PASMCs) through K(+) channels and thus exerts its effects on pulmonary vascular tone and pressure.We show that DHA caused dose-dependent activation of the calcium-activated K(+) (KCa) current in primary human PASMCs and endothelium-dependent relaxation of pulmonary arteries...
October 2016: European Respiratory Journal: Official Journal of the European Society for Clinical Respiratory Physiology
https://www.readbyqxmd.com/read/27512118/trabectedin-is-active-against-malignant-pleural-mesothelioma-cell-and-xenograft-models-and-synergizes-with-chemotherapy-and-bcl-2-inhibition-in-vitro
#11
Mir A Hoda, Christine Pirker, Yawen Dong, Karin Schelch, Petra Heffeter, Kushtrim Kryeziu, Sushilla van Schoonhoven, Thomas Klikovits, Viktoria Laszlo, Anita Rozsas, Judit Ozsvar, Walter Klepetko, Balazs Döme, Michael Grusch, Balazs Hegedüs, Walter Berger
Malignant pleural mesothelioma (MPM) is characterized by widespread resistance to systemic therapy. Trabectedin is an antineoplastic agent targeting both the malignant cells and the tumor microenvironment that has been approved for the treatment of advanced soft tissue sarcoma and ovarian cancer. In this preclinical study, we evaluated the antineoplastic potential of trabectedin as a single agent and in drug combination approaches in human MPM. Therefore, we utilized an extended panel of MPM cell lines (n = 6) and primary cell cultures from surgical MPM specimens (n = 13), as well as nonmalignant pleural tissue samples (n = 2)...
October 2016: Molecular Cancer Therapeutics
https://www.readbyqxmd.com/read/27457873/management-of-malignant-pleural-mesothelioma-part%C3%A2-3-data-from-the-austrian-mesothelioma-interest-group-amig-database
#12
Thomas Klikovits, Mir Alireza Hoda, Yawen Dong, Madeleine Arns, Bernhard Baumgartner, Peter Errhalt, Christian Geltner, Barbara Machan, Wolfgang Pohl, Jörg Hutter, Josef Eckmayr, Michael Studnicka, Martin Flicker, Peter Cerkl, Klaus Kirchbacher, Walter Klepetko
BACKGROUND: Malignant pleural mesothelioma (MPM) is a rare but aggressive tumor originating from the pleural cavity with a strong link to previous asbestos exposure. In order to determine the demographics, diagnostics, therapeutic strategies, and prognosis of MPM patients in Austria, the Austrian Mesothelioma Interest Group (AMIG) was founded in 2011. In this report the data from the AMIG MPM database collected to date are reported. METHODS: A prospective observational registry was initiated, including patients with histologically verified MPM diagnosed and treated at specialized centers in Austria...
September 2016: Wiener Klinische Wochenschrift
https://www.readbyqxmd.com/read/27457872/management-of-malignant-pleural-mesothelioma-part%C3%A2-2-therapeutic-approaches-consensus-of-the-austrian-mesothelioma-interest-group-amig
#13
Mir Alireza Hoda, Thomas Klikovits, Madeleine Arns, Karin Dieckmann, Sabine Zöchbauer-Müller, Christian Geltner, Bernhard Baumgartner, Peter Errhalt, Barbara Machan, Wolfgang Pohl, Jörg Hutter, Josef Eckmayr, Michael Studnicka, Martin Flicker, Peter Cerkl, Walter Klepetko
Treatment of malignant pleural mesothelioma (MPM) depends on performance status of the patient, tumor stage, and histological differentiation. Chemotherapy (CHT) can be administered as first- and second-line treatment in unresectable MPM or as neoadjuvant or adjuvant treatment before or after surgery. A combination of an antifolate and platinum-based CHT is the only approved standard of care. Several targeted and immunotherapies are in evaluation and further studies are warranted to determine the therapeutic value of these new treatment options...
September 2016: Wiener Klinische Wochenschrift
https://www.readbyqxmd.com/read/27457871/malignant-pleural-mesothelioma
#14
EDITORIAL
Walter Klepetko
No abstract text is available yet for this article.
September 2016: Wiener Klinische Wochenschrift
https://www.readbyqxmd.com/read/27449756/tumor-infiltrating-lymphocyte-subsets-and-tertiary-lymphoid-structures-in-pulmonary-metastases-from-colorectal-cancer
#15
Thomas Schweiger, Anna Sophie Berghoff, Christoph Glogner, Olaf Glueck, Orsolya Rajky, Denise Traxler, Peter Birner, Matthias Preusser, Walter Klepetko, Konrad Hoetzenecker
The presence of tumor-infiltrating lymphocytes (TILs) and tertiary lymphoid structures (TLSs) reflects an active inflammatory tumor microenvironment. High density of TILs as well as presence of TLS is associated with improved survival in various solid cancer types. We aimed to describe the density and distribution of TILs and TLS in pulmonary metastases (PMs) from primary colorectal cancer (CRC) and its correlation with clinicopathological variables. Fifty-seven CRC pulmonary metastasectomy specimen (PM) and 31 matched primary CRC specimen were included...
October 2016: Clinical & Experimental Metastasis
https://www.readbyqxmd.com/read/27220108/lung-transplantation-in-patients-with-incidental-early-stage-lung-cancer-institutional-experience-of-a-high-volume-center
#16
Thomas Klikovits, Christopher Lambers, Bahil Ghanim, Balazs Dome, Gabriella Murakoezy, Sabine Zöchbauer-Müller, Ryuichi Waseda, Clemens Aigner, Gyoergy Lang, Shahrokh Taghavi, Walter Klepetko, Peter Jaksch, Mir Alireza Hoda
BACKGROUND: Incidentally discovered lung cancers in lung transplant (LuTX) recipients are rare but may affect outcome. We aim to report our single center experience with incidence, management, and survival of patients with previously unverified primary lung cancer discovered at the time of LuTX. METHODS: A total of 1262 patients undergoing LuTX between 1989 and 2012 were retrospectively analyzed in our prospective database. RESULTS: Patients identified were six men and five women with a mean age of 54...
August 2016: Clinical Transplantation
https://www.readbyqxmd.com/read/27163544/the-lymphatic-phenotype-of-lung-allografts-in-patients-with-bronchiolitis-obliterans-syndrome-and-restrictive-allograft-syndrome
#17
Denise Traxler, Thomas Schweiger, Stefan Schwarz, Magdalena Maria Schuster, Peter Jaksch, Gyoergy Lang, Peter Birner, Walter Klepetko, Hendrik Jan Ankersmit, Konrad Hoetzenecker
BACKGROUND: Chronic lung allograft dysfunction (CLAD), presenting as bronchiolitis obliterans syndrome (BOS) or restrictive allograft syndrome (RAS) is the major limiting factor of long-term survival in lung transplantation. Its pathogenesis is still obscure. In BOS, persistent alloimmune injury and chronic airway inflammation are suggested. One of the main tasks of the lymphatic vessel (LV) system is the promotion of immune cell trafficking. The formation of new LVs has been shown to trigger chronic allograft rejection in kidney transplants...
February 2017: Transplantation
https://www.readbyqxmd.com/read/27106290/functional-and-molecular-factors-associated-with-tapse-in-hypoxic-pulmonary-hypertension
#18
Slaven Crnkovic, Albrecht Schmidt, Bakytbek Egemnazarov, Jochen Wilhelm, Leigh M Marsh, Bahil Ghanim, Walter Klepetko, Andrea Olschewski, Horst Olschewski, Grazyna Kwapiszewska
Adaptation of the right ventricle (RV) to increased afterload is crucial for survival in pulmonary hypertension (PH), but it is challenging to assess RV function and identify associated molecular mechanisms. The aim of the current study was to analyze the relationship between invasive and noninvasive parameters of RV morphology and function and associated molecular changes. The response of mice to normobaric hypoxia was assessed by hechocardiography, invasive hemodynamics, and histological and molecular analyses...
July 1, 2016: American Journal of Physiology. Lung Cellular and Molecular Physiology
https://www.readbyqxmd.com/read/27103380/cd133-cells-in-pulmonary-arterial-hypertension
#19
Vasile Foris, Gabor Kovacs, Leigh M Marsh, Zoltán Bálint, Martin Tötsch, Alexander Avian, Philipp Douschan, Bahil Ghanim, Walter Klepetko, Andrea Olschewski, Horst Olschewski
Circulating mononuclear cells may play an important role for the vascular remodelling in pulmonary arterial hypertension (PAH), but studies addressing multiple progenitor populations are rare and inconsistent.We used a comprehensive fluorescence-activated cell sorting analysis of circulating mononuclear cells in 20 PAH patients and 20 age- and sex-matched controls, and additionally analysed CD133(+) cells in the lung tissue of five PAH transplant recipients and five healthy controls (donor lungs).PAH patients were characterised by increased numbers of circulating CD133(+) cells and lymphopenia as compared with control...
August 2016: European Respiratory Journal: Official Journal of the European Society for Clinical Respiratory Physiology
https://www.readbyqxmd.com/read/27083940/operability-assessment-in-cteph-lessons-from-the-chest-1-study
#20
EDITORIAL
David P Jenkins, Andrzej Biederman, Andrea M D'Armini, Philippe G Dartevelle, Hui-Li Gan, Walter Klepetko, Jaroslav Lindner, Eckhard Mayer, Michael M Madani
Pulmonary endarterectomy is the gold standard treatment for chronic thromboembolic pulmonary hypertension and is potentially curative, although some patients are unsuitable for pulmonary endarterectomy and require alternative management. Lack of standardized assessment of pulmonary endarterectomy eligibility risks suboptimal treatment in some patients. We discuss the implications for future clinical trials and practice of a unique operability assessment in patients who have chronic thromboembolic pulmonary hypertension and were initially screened for inclusion in the CHEST-1 (Chronic Thromboembolic Pulmonary Hypertension Soluble Guanylate Cyclase Stimulator Trial-1) study...
September 2016: Journal of Thoracic and Cardiovascular Surgery
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