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  1. Article ; Online: Fatal adverse events in two thymoma patients treated with anti-PD-1 immune check point inhibitor and literature review.

    Konstantina, Thomopoulou / Konstantinos, Rounis / Anastasios, Koutsopoulos / Anastasia, Mala / Eleni, Lagoudaki / Ioannis, Sougklakos / Sofia, Agelaki / Dimitris, Mavroudis

    Lung cancer (Amsterdam, Netherlands)

    2019  Volume 135, Page(s) 29–32

    Abstract: Objectives: Thymomas, as well as thymic carcinomas, are extremely rare tumors that arise from the thymus. The management of these tumors is primarily the complete surgical resection, however when there is tumor progression or metastatic unresectable ... ...

    Abstract Objectives: Thymomas, as well as thymic carcinomas, are extremely rare tumors that arise from the thymus. The management of these tumors is primarily the complete surgical resection, however when there is tumor progression or metastatic unresectable disease, palliative platinum-based chemotherapy is the standard of care. On this setting, alternative options are emerging including immune checkpoints inhibitors. Based on that, PDL-1 expression was measured in thymic tumors as a potential predictive biomarker of response to anti-PD1 and anti-PDL1 immune inhibitors. Our objective is to report the first two cases of fatal toxicity due to anti- PD1 therapy in thymoma patients.
    Materials and methods: Here, we report two cases of metastatic B2/B3 thymomas refractory to initial standard chemotherapy treatment, with high PDL1 expression (>50%), that were treated with the anti-PD1 agent, pembrolizumab.
    Results: The administration of anti- PD1 immune check point inhibitor resulted in a storm of immune related adverse events including myositis, myocarditis and myasthenia gravis and death after administration of the first treatment cycle.
    Conclusion: In thymomas, the administration of PD1 inhibitors seems to be associated with a high percentage of severe immune related adverse events, thus requiring special caution on the usage of these agents in thymomas.
    MeSH term(s) Adult ; Antineoplastic Agents, Immunological/adverse effects ; Antineoplastic Agents, Immunological/therapeutic use ; Drug-Related Side Effects and Adverse Reactions ; Fatal Outcome ; Female ; Humans ; Male ; Middle Aged ; Programmed Cell Death 1 Receptor/antagonists & inhibitors ; Thymoma/drug therapy ; Thymoma/immunology ; Treatment Outcome
    Chemical Substances Antineoplastic Agents, Immunological ; PDCD1 protein, human ; Programmed Cell Death 1 Receptor
    Language English
    Publishing date 2019-07-09
    Publishing country Ireland
    Document type Case Reports ; Journal Article ; Meta-Analysis ; Review
    ZDB-ID 632771-0
    ISSN 1872-8332 ; 0169-5002
    ISSN (online) 1872-8332
    ISSN 0169-5002
    DOI 10.1016/j.lungcan.2019.06.015
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  2. Article ; Online: Phenotypic characterization of circulating tumor cells in the peripheral blood of patients with small cell lung cancer.

    Ippokratis Messaritakis / Eleni Politaki / Athanasios Kotsakis / Eleftheria-Kleio Dermitzaki / Filippos Koinis / Eleni Lagoudaki / Anastasios Koutsopoulos / Galatea Kallergi / John Souglakos / Vassilis Georgoulias

    PLoS ONE, Vol 12, Iss 7, p e

    2017  Volume 0181211

    Abstract: To evaluate the phenotypic heterogeneity of circulating tumor cells (CTCs) based on the expression of proliferative, apoptotic and Epithelial-to-Mesenchymal Transmission (EMT) markers during front-line treatment in patients with small cell lung cancer ( ... ...

    Abstract To evaluate the phenotypic heterogeneity of circulating tumor cells (CTCs) based on the expression of proliferative, apoptotic and Epithelial-to-Mesenchymal Transmission (EMT) markers during front-line treatment in patients with small cell lung cancer (SCLC) and to evaluate their clinical relevance.CTCs from 108 chemotherapy-naïve patients with SCLC were analyzed by double immunofluorescence staining using anti-Ki67, anti-M30, anti-Vimentin along with anti-CKs antibodies. In 83 patients CTCs were also enumerated using the CellSearch.Sequential samples were available from 76 and 48 patients after one-treatment cycle and on disease progression (PD), respectively, for immunofluorescence and from 50 and 36 patients after one-cycle and on PD, respectively, for CellSearch. At baseline, 60.2% of the patients had detectable CTCs by either method. Both proliferative (CK67+) and non-proliferative (Ki67-), apoptotic (M30+) and non-apoptotic (M30-) as well as EMT (Vim+) CTCs were present in the same patient. Among 22 patients without detectable CTCs by CellSearch, CK+/Ki67+ and CK+/Vim+ CTCs could be detected in 6 (27.3%) and 6 (27.3%) patients, respectively. One-chemotherapy cycle reduced both the incidence of detection (p<0.001) and the absolute number (p<0.001) of CTCs; conversely, on PD both the incidence of detection and the number of CTCs were significantly increased (p = 0.002 and p = 0.04, respectively). Multivariate analysis revealed that the increased number of Vim+ CTCs at baseline and of non-apoptotic CTCs on PD could be emerged as independent prognostic factors associated with decreased OS(p = 0.009 and p = 0.023, respectively).CK+/Ki67+, CK+/M30+ and CK+/Vim+ CTCs represent distinct subpopulations of CTCs in patients with SCLC, can be detected even in the absence of detectable CTCs by CellSearch; CK+/Ki67+ and CK+/Vim+ CTCs are associated with unfavorable clinical outcome.
    Keywords Medicine ; R ; Science ; Q
    Subject code 610
    Language English
    Publishing date 2017-01-01T00:00:00Z
    Publisher Public Library of Science (PLoS)
    Document type Article ; Online
    Database BASE - Bielefeld Academic Search Engine (life sciences selection)

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  3. Article ; Online: Predictive value of BRCA1, ERCC1, ATP7B, PKM2, TOPOI, TOPΟ-IIA, TOPOIIB and C-MYC genes in patients with small cell lung cancer (SCLC) who received first line therapy with cisplatin and etoposide.

    Niki Karachaliou / Chara Papadaki / Eleni Lagoudaki / Maria Trypaki / Maria Sfakianaki / Anastasios Koutsopoulos / Dimitris Mavroudis / Efstathios Stathopoulos / Vassilis Georgoulias / John Souglakos

    PLoS ONE, Vol 8, Iss 9, p e

    2013  Volume 74611

    Abstract: BACKGROUND:The aim of the study was to evaluate the predictive value of genes involved in the action of cisplatin-etoposide in Small Cell Lung Cancer (SCLC). METHODS:184 SCLC patients' primary tumour samples were analyzed for ERCCI, BRCA1, ATP7B, PKM2 ... ...

    Abstract BACKGROUND:The aim of the study was to evaluate the predictive value of genes involved in the action of cisplatin-etoposide in Small Cell Lung Cancer (SCLC). METHODS:184 SCLC patients' primary tumour samples were analyzed for ERCCI, BRCA1, ATP7B, PKM2 TOPOI, TOPOIIA, TOPOIIB and C-MYC mRNA expression. All patients were treated with cisplatin-etoposide. RESULTS:The patients' median age was 63 years and 120 (65%) had extended stage, 75 (41%) had increased LDH serum levels and 131 (71%) an ECOG performance status was 0-1. Patients with limited stage, whose tumours expressed high ERCC1 (p=0.028), PKM2 (p=0.046), TOPOI (p=0.008), TOPOIIA (p=0.002) and TOPOIIB (p<0.001) mRNA had a shorter Progression Free Survival (PFS). In limited stage patients, high expression of ERCC1 (p=0.014), PKM2 (p=0.026), TOPOIIA (p=0.021) and TOPOIIB (p=0.019) was correlated with decreased median overall survival (mOS) while in patients with extended stage, only high TOPOIIB expression had a negative impact on Os (p=0.035). The favorable expression signature expression signature (low expression of ERCC1, PKM2, TOPOIIA and TOPOIIB) was correlated with significantly better PFS and Os in both LS-SCLC (p<0.001 and p=0.007, respectively) and ES-SCLC (p=0.007 and (p=0.011, respectively) group. The unfavorable expression signature was an independent predictor for poor PFS (HR: 3.18; p=0.002 and HR: 3.14; p=0.021) and Os (HR: 4.35; p=0.001and HR: 3.32; p=0.019) in both limited and extended stage, respectively. CONCLUSIONS:Single gene's expression analysis as well as the integrated analysis of ERCC1, PKM2, TOPOIIA and TOPOIIB may predict treatment outcome in patients with SCLC. These findings should be further validated in a prospective study.
    Keywords Medicine ; R ; Science ; Q
    Subject code 616
    Language English
    Publishing date 2013-01-01T00:00:00Z
    Publisher Public Library of Science (PLoS)
    Document type Article ; Online
    Database BASE - Bielefeld Academic Search Engine (life sciences selection)

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  4. Article ; Online: Idiopathic Pulmonary Hemosiderosis in Adults

    Argyris Tzouvelekis / Paschalis Ntolios / Anastasia Oikonomou / Anastasios Koutsopoulos / Efthimios Sivridis / George Zacharis / Kostantinos Kaltsas / Panagiotis Boglou / Dimitrios Mikroulis / Demosthenes Bouros

    Case Reports in Medicine, Vol

    A Case Report and Review of the Literature

    2012  Volume 2012

    Abstract: Idiopathic pulmonary hemosiderosis is a very rare condition rarely affecting adults and causing recurrent episodes of diffuse alveolar haemorrhage that may lead to lung fibrosis. Due to lack of pathognomonic findings, IPH diagnosis is established upon ... ...

    Abstract Idiopathic pulmonary hemosiderosis is a very rare condition rarely affecting adults and causing recurrent episodes of diffuse alveolar haemorrhage that may lead to lung fibrosis. Due to lack of pathognomonic findings, IPH diagnosis is established upon exclusion of all other possible causes of DAH in combination with specific pathologic findings revealing bland alveolar haemorrhage with absence of vasculitis and/or accumulation of immune complexes within lung parenchyma. Here we describe a rare case of idiopathic pulmonary hemosiderosis in an otherwise healthy 27-year-old Greek male patient with relapsing episodes of fever accompanied by general fatigue and discomfort. He was at this time point a light smoker and had been hospitalised once in the past for similar symptoms. His iron deficiency anemia coupled with chest high-resolution computed tomography and bronchoalveolar lavage revealed findings compatible with diffuse alveolar hemorrhage. After excluding all other sources of bleeding through extensive gastrointestinal workup and thorough immunologic profile, video-assisted thoracic lung biopsy was performed and the diagnosis of Idiopathic Pulmonary Hemosiderosis was established. Patient was treated with high doses of oral corticosteroids, leading to clinical response. We highlight the need for vigilance by the respiratory physician for the presence of DAH, a challenging, acute condition requiring early recognition along with identification of the underlying syndrome and appropriate treatment to achieve optimal results.
    Keywords Medicine ; R
    Subject code 610
    Language English
    Publishing date 2012-01-01T00:00:00Z
    Publisher Hindawi Limited
    Document type Article ; Online
    Database BASE - Bielefeld Academic Search Engine (life sciences selection)

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  5. Article ; Online: Increased Expression of Epidermal Growth Factor Receptor (EGF-R) in Patients with Different Forms of Lung Fibrosis

    Argyris Tzouvelekis / Paschalis Ntolios / Andreas Karameris / George Vilaras / Panagiotis Boglou / Andreas Koulelidis / Kostas Archontogeorgis / Konstantinos Kaltsas / George Zacharis / Evangelia Sarikloglou / Paschalis Steiropoulos / Dimitrios Mikroulis / Anastasios Koutsopoulos / Marios Froudarakis / Demosthenes Bouros

    BioMed Research International, Vol

    2013  Volume 2013

    Abstract: Introduction. Emerging evidence supports the role of epidermal growth factor-receptor (EGFR) in fibrogenesis. The aim of our study was to investigate the expression profiles of EGFR in three forms of IIPs, including idiopathic pulmonary fibrosis (IPF), ... ...

    Abstract Introduction. Emerging evidence supports the role of epidermal growth factor-receptor (EGFR) in fibrogenesis. The aim of our study was to investigate the expression profiles of EGFR in three forms of IIPs, including idiopathic pulmonary fibrosis (IPF), cryptogenic organizing pneumonia (COP), and nonspecific interstitial pneumonia (NSIP). Patients and Methods. Twenty newly diagnosed patients with IPF, 15 with COP, and 15 with NSIP (cellular, n=4 and fibrotic, n=11) were investigated. Fifteen paraffin blocks obtained from the normal part of lungs removed for benign lesions were used as controls. Immunohistochemistry was carried out using specific monoclonal antibody. Results were verified by qRT-PCR. Results. A significant EGFR upregulation, both in protein and mRNA level, was observed in IPF, COP, and fibrotic NSIP samples compared to controls. EGFR was primarily localized in the hyperplastic alveolar epithelium surrounding areas of fibrosis in IPF, COP, and fibrotic NSIP samples, as assessed by double immunohistochemistry analysis with surfactant protein-A. EGFR mRNA levels were positively associated with indicators of lung fibrosis (type 1 collagen mRNA levels) and negatively correlated with functional prognostic parameters. Conclusions. We conclude that EGFR is upregulated in the hyperplastic alveolar epithelium in all three fibrotic forms of IIPs indicating a potential role during abnormal reepithelization.
    Keywords Medicine ; R
    Subject code 616
    Language English
    Publishing date 2013-01-01T00:00:00Z
    Publisher Hindawi Limited
    Document type Article ; Online
    Database BASE - Bielefeld Academic Search Engine (life sciences selection)

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  6. Article ; Online: Telomerase in pulmonary fibrosis. A link to alveolar cell apoptosis and differentiation

    Argyris Tzouvelekis / Andreas Karameris / Evangelos Tsiambas / Anastasios Koutsopoulos / Rodoula Tringidou / Marios Froudarakis / Dimitrios Mikroulis / George Zacharis / Paschalis Steiropoulos / Ioanna Bazdiara / Constantinos Tsatalas / Ioannis Kotsianidis / Demosthenes Bouros

    Pneumon, Vol 23, Iss 3, Pp 207-

    2010  Volume 239

    Abstract: SUMMARY. Introduction: Telomerase is crucial for extended life span and differentiation and is linked to immortality. Therefore, its role may be crucial in the pathogenesis of pulmonary fibrosis. Our objective was to implicate telomerase in the ... ...

    Abstract SUMMARY. Introduction: Telomerase is crucial for extended life span and differentiation and is linked to immortality. Therefore, its role may be crucial in the pathogenesis of pulmonary fibrosis. Our objective was to implicate telomerase in the pathogenesis of idiopathic fibrotic lung disease. Patients and Methods: Assessment of telomerase activity and expression was carried out using TRAP detection kit and qRT-PCR. Experimental procedure was enhanced by a series of immunostainings and fluorescence in situ hybridization analysis in tissue microarrays constructed with tissue samples from patients with idiopathic pulmonary fibrosis (IPF) and cryptogenic organizing pneumonia (COP). Results: We demonstrated significant downregulation of telomerase expression and activity in patients with fibrotic lung disease compared to controls. Immunolocalization studies coupled by FISH analysis revealed the presence of two subpopulations of type II AECs based on their telomerase expression levels: telomerase positive type II AECs, mainly overlying areas of active fibrosis and telomerase negative type II AECs, mainly localized in areas of established fibrosis. Conclusions: Downregulation of telomerase expression and activity in IPF may indicate a causal relationship between low telomerase expression and disease pathogenesis. The duality phenomenon in telomerase expression suggests that telomerase may regulate the fate of AECs towards either an apoptotic or a mesenchymal phenotype contributing directly to fibrosis. Pneumon 2010, 23(3):207-239.
    Keywords telomerase ; pulmonary fibrosis ; pathogenesis ; interstitial pulmonary fibrosis ; Diseases of the respiratory system ; RC705-779 ; Specialties of internal medicine ; RC581-951 ; Internal medicine ; RC31-1245 ; Medicine ; R ; DOAJ:Internal medicine ; DOAJ:Medicine (General) ; DOAJ:Health Sciences
    Subject code 610
    Language English
    Publishing date 2010-01-01T00:00:00Z
    Publisher Hellenic Thoracic Society & Hellenic Bronchologic Society
    Document type Article ; Online
    Database BASE - Bielefeld Academic Search Engine (life sciences selection)

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  7. Article ; Online: Tumor BRCA1, RRM1 and RRM2 mRNA expression levels and clinical response to first-line gemcitabine plus docetaxel in non-small-cell lung cancer patients.

    Ioannis Boukovinas / Chara Papadaki / Pedro Mendez / Miquel Taron / Dimitris Mavroudis / Anastasios Koutsopoulos / Maria Sanchez-Ronco / Jose Javier Sanchez / Maria Trypaki / Eustathios Staphopoulos / Vassilis Georgoulias / Rafael Rosell / John Souglakos

    PLoS ONE, Vol 3, Iss 11, p e

    2008  Volume 3695

    Abstract: Background Overexpression of RRM1 and RRM2 has been associated with gemcitabine resistance. BRCA1 overexpression increases sensitivity to paclitaxel and docetaxel. We have retrospectively examined the effect of RRM1, RRM2 and BRCA1 expression on outcome ... ...

    Abstract Background Overexpression of RRM1 and RRM2 has been associated with gemcitabine resistance. BRCA1 overexpression increases sensitivity to paclitaxel and docetaxel. We have retrospectively examined the effect of RRM1, RRM2 and BRCA1 expression on outcome to gemcitabine plus docetaxel in advanced non-small-cell lung cancer (NSCLC) patients. Methodology and principal findings Tumor samples were collected from 102 chemotherapy-naïve advanced NSCLC patients treated with gemcitabine plus docetaxel as part of a randomized trial. RRM1, RRM2 and BRCA1 mRNA levels were assessed by quantitative PCR and correlated with response, time to progression and survival. As BRCA1 levels increased, the probability of response increased (Odds Ratio [OR], 1.09: p = 0.01) and the risk of progression decreased (hazard ratio [HR], 0.99; p = 0.36). As RRM1 and RRM2 levels increased, the probability of response decreased (RRM1: OR, 0.97; p = 0.82; RRM2: OR, 0.94; p<0.0001) and the risk of progression increased (RRM1: HR, 1.02; p = 0.001; RRM2: HR, 1.005; p = 0.01). An interaction observed between BRCA1 and RRM1 allowed patients to be classified in three risk groups according to combinations of gene expression levels, with times to progression of 10.13, 4.17 and 2.30 months (p = 0.001). Low BRCA1 expression was the only factor significantly associated with longer time to progression in 31 patients receiving cisplatin-based second-line therapy. Conclusions The mRNA expression of BRCA1, RRM1 and RRM2 is potentially a useful tool for selecting NSCLC patients for individualized chemotherapy and warrants further investigation in prospective studies.
    Keywords Medicine ; R ; Science ; Q
    Subject code 610
    Language English
    Publishing date 2008-01-01T00:00:00Z
    Publisher Public Library of Science (PLoS)
    Document type Article ; Online
    Database BASE - Bielefeld Academic Search Engine (life sciences selection)

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