National Institute of Tuberculosis and Lung Diseases

Warsaw, Poland

National Institute of Tuberculosis and Lung Diseases

Warsaw, Poland
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Florczuk M.,National Institute of Tuberculosis and Lung Diseases | Szpechcinski A.,National Institute of Tuberculosis and Lung Diseases | Chorostowska-Wynimko J.,National Institute of Tuberculosis and Lung Diseases
Targeted Oncology | Year: 2017

Lung cancer is the most common cancer worldwide. Up to 85% of lung cancer cases are diagnosed as non-small cell lung cancer (NSCLC). The effectiveness of NSCLC treatment is expected to be improved through the implementation of robust and specific biomarkers. MicroRNAs (miRNAs) are small, non-coding molecules that play a key role in the regulation of basic cellular processes, including differentiation, proliferation and apoptosis, by controlling gene expression at the post-transcriptional level. Deregulation of miRNA activity results in the loss of homeostasis and the development of a number of pathologies, including lung cancer. During lung carcinogenesis, miRNAs exhibit dual regulatory function: they act as oncogenes to promote cancer development or as tumour suppressors. Unique miRNA sequences have been detected in malignant tissues and corresponding healthy tissues. Furthermore, stable forms of tumour-related miRNAs are detectable in the peripheral blood of patients with NSCLC. The potential benefits of using extracellular miRNAs present in body fluids as part of the diagnostic evaluation of cancer include low invasiveness (compared with tumour cell/tissue sampling), and the repeatability and ease of obtaining the specimens. Apart from the diagnostic applications of altered miRNA expression profiles, the dual regulatory role of miRNA in cancer might drive the further development of personalised therapies in NSCLC. The clinical usefulness of miRNA expression analysis to predict the efficacy of various treatment strategies including surgery, radio- and chemotherapy, and targeted therapies has been evaluated in NSCLC. Also, the capacity of a single miRNA to regulate the expression of multiple genes simultaneously presents an opportunity to use these small molecules in personalised therapy as individualised therapeutic tools.[Figure not available: see fulltext.] © 2017, The Author(s).

Skirecki T.,Medical University of Warsaw | Kawiak J.,Polish Academy of Sciences | Dziedzic D.,National Institute of Tuberculosis and Lung Diseases | Domagala-Kulawik J.,Medical University of Warsaw
Archivum Immunologiae et Therapiae Experimentalis | Year: 2014

Lung tumors are characterized by their high metastatic potential, which is the main cause of therapeutic failure. However, the exact cellular origin of metastasis remains unknown. Since the introduction of the cancer stem cell theory, lung cancer stem cells (LCSCs) have been thought to represent metastasis-founding cells. The current study aimed to evaluate whether LCSCs could be found in the circulation. Expression of the stem cell markers CD133 and EpCAM was confirmed in tumor and normal lung tissue by flow cytometry. Then, this technique was further used to investigate the expression of CD133 and EpCAM in the peripheral blood of 41 patients with primary lung cancer. Putative LCSCs (CD133+EpCAM+) were present in 6/7 tumor samples, and CD133+EpCAM+ cells were identified in the blood samples of 15 patients at a median level of 40/ml of blood. EpCAM+ cells were detected in 60 % of the patients, and the number of these cells was higher in patients with adenocarcinoma than patients with squamous cell carcinoma and was also higher in patients with less advanced disease. Moreover, the frequency of this subpopulation significantly correlated with the circulating level of SSEA-4+ cells. Additionally, CD133+EpCAM- cells were found in 87 % of the patients, and the numbers of these cells were significantly higher in patients with distant metastases and correlated with disease stage. This study confirmed the presence of an LCSC subpopulation with a CD133+EpCAM+ phenotype in the tumors and blood of patients with lung cancer, and these results suggest an important role for CD133 and EpCAM in lung cancer progression and their potential application as novel biomarkers of the disease. © 2013 The Author(s).

Chorostowska-Wynimko J.,National Institute of Tuberculosis and Lung Diseases | Struniawski R.,National Institute of Tuberculosis and Lung Diseases | Sliwinski P.,National Institute of Tuberculosis and Lung Diseases | Wajda B.,University of Gdansk
COPD: Journal of Chronic Obstructive Pulmonary Disease | Year: 2015

The alpha-1 antitrypsin deficiency (AATD) targeted screening program, together with the National Registry, were established in Poland in 2010 soon after the AATD diagnostics became available. Between 2010 and 2014 a total of 2525 samples were collected from respiratory patients countrywide; 55 patients with severe AAT deficiency or rare mutations were identified and registered, including 36 PiZZ subjects (65%). The majority of AATD patients were diagnosed with COPD (40%) or emphysema (7%), but also with bronchial asthma (16%) and bronchiectasis (13%). Therefore, the registry has proved instrumental in setting-up the AATD-dedicated network of respiratory medical centres in Poland. Since augmentation therapy is not reimbursed in our country, the smoking cessation guidance, optimal pharmacotherapy of respiratory symptoms as well the early detection, and effective treatment of exacerbations is absolutely essential. © Informa Healthcare USA, Inc.

Kopinski P.,Nicolaus Copernicus University | Gizycka A.,National Institute of Tuberculosis and Lung Diseases | Chorostowska-Wynimko J.,National Institute of Tuberculosis and Lung Diseases
Polski Merkuriusz Lekarski | Year: 2014

Recent reports prove the necessity to modify the classical definitions of cell death. The canonical distinction between apoptosis (defined as programed cell death - PCD) and necrosis (gene independent) in no longer scientifically valid. Furthermore, more than one process mediated by intracellular genetic program has been documented, for example programmed necrosis. Diversity in definitions leads to confusion, particularly regarding specific terminology. Here we present the new unified criteria for the evaluation of cell death mechanisms as proposed by the Nomenclature Committee on Cell Death in recommendations from 2009 and 2012.

Szpechcinski A.,National Diagnostics | Chorostowska-Wynimko J.,National Diagnostics | Kupis W.,National Institute of Tuberculosis and Lung Diseases | Maszkowska-Kopij K.,National Institute of Tuberculosis and Lung Diseases | And 3 more authors.
Expert Opinion on Biological Therapy | Year: 2012

Objective: Minute amounts of free-circulating DNA are present in plasma of healthy individuals, whereas its increased concentration was observed in patients with malignant tumors including non-small cell lung cancer (NSCLC). This study aimed at demonstrating the potential usefulness of plasma DNA concentration monitoring in NSCLC patients for therapy effectiveness assessment throughout the treatment and follow-up period. Methods: Plasma DNA concentration was assessed in 50 NSCLC patients (stage I IIIA) prior and following the radical treatment using real-time quantitative PCR method. 10 orthopedic patient undergoing hip joint surgery and 40 healthy volunteers comprised control groups. Results: NSCLC patients (8.02 ng/ml) demonstrated significantly higher mean plasma DNA concentration with respect to healthy controls (2.27 ng/ml; p < 0.0000). Drastic increase in plasma DNA levels up to mean 68.74 ng/ml was detected a week after primary tumor resection. Still, similar phenomenon was observed in patients subjected to orthopedic surgical treatment (from 3.00 to 28.38 ng/ml, p < 0.0015). Most resected NSCLC patients with no disease recurrence during 3- to 6-month follow-up demonstrated reduced plasma DNA levels (mean 2.77 ng/ml) with respect to their presurgical values, whereas in relapsed subjects plasma DNA levels were significant higher. Conclusion: Free-circulating DNA concentration in plasma was significantly higher in NSCLC patients versus healthy controls. Its drastic increase following radical NSCLC treatment was most likely due to the surgical trauma. Importantly, the kinetics of plasma free-circulating DNA seems to be a promising marker of long-term effects of radical surgery in NSCLC. © 2012 Informa UK, Ltd.

Radzikowska E.,National Institute of Tuberculosis and Lung Diseases | Roszkowski-Sliz K.,National Institute of Tuberculosis and Lung Diseases | Chabowski M.,National Institute of Tuberculosis and Lung Diseases | Glaz P.,National Institute of Tuberculosis and Lung Diseases
Advances in Experimental Medicine and Biology | Year: 2013

The purpose of this study was to evaluate the influence on survival of delays in the diagnosis and treatment in an unselected population of small cell lung (SCLC) patients. Demographic and disease data of 3,479 SCLC patients were registered in the National Tuberculosis and Lung Diseases Research Institute in Warsaw, Poland during 1995-1998. In 50 % of patients, treatment started within 78 days from the appearance of first symptom(s). The median delay was 30 days (mean 47 days) and the median referral delay to a specialist was 19 days (mean 36 days). Half of SCLC patients were diagnosed during 34 days (mean 55 days). The mean time elapse from the diagnosis to the onset of therapy was 30 days (median 6 days). The multivariate analysis revealed that male gender-HR (hazard ratio = 1.2), ECOG Performance Status of 2 (HR = 1.5) and 3 + 4 (HR = 2.4), and clinical stage III (HR = 1.3) and IV (HR = 1.9) of the disease were independent negative predictors of survival. The patients treated with surgery and combined modality treatment had a better prognosis than those treated with chemoradiotherapy (HR = 1.6), chemotherapy (HR = 2.5), symptomatically (HR = 4.0), or those who refused therapy (HR = 3.9). The delay in the diagnosis and treatment had no effect on survival. Interestingly, patients who were diagnosed faster (below 42 days) actually had a worse prognosis than those diagnosed later. We conclude that a prolonged workup of SCLC patients and an extended time for treatment onset have a positive influence on survival, which may likely have to do with the determination of disease stage and more targeted treatment. © 2013 Springer Science+Business Media Dordrecht.

Szturmowicz M.,National Institute of Tuberculosis and Lung Diseases | Kacprzak A.,National Institute of Tuberculosis and Lung Diseases | Blasinska-Przerwa K.,National Institute of Tuberculosis and Lung Diseases | Kus J.,National Institute of Tuberculosis and Lung Diseases
Pneumonologia i Alergologia Polska | Year: 2015

Lung diseases are one of the most frequent causes of pulmonary hypertension (PH). The development of PH influences the course of lung disease, worsening the clinical symptoms and prognosis. According to the most recent publications, PH in the course of lung diseases develops as a result of both “parenchymal” and vascular pathology, in the patients with genetic predisposition. Prolonged infection (especially viral one) may be an additional promoting factor. Right heart catheterization (RHC), which is an invasive procedure, is the only objective method of diagnosing PH. According to the latest recommendations, the management algorithm of PH and coexisting interstitial lung disease is based on RHC and the results of pulmonary function tests. Majority of the patients develop mild PH in the course of advanced lung disease. Best treatment of underlying lung pathology combined with long term oxygen treatment is recommended in this group. In case of severe PH (mean resting pulmonary artery pressure (mPAP) ≥ 35 mm Hg) the alternate cause of PH has to be sought. PAH-specific drugs use should be limited to patients with severe PH participating in clinical trials. In this review, the value of various non-invasive methods (echocardiography, radiological examination, exercise capacity and brain natriuretic peptides assessment) in the process of screening for PH is presented, and the results of recent randomized clinical trials with PAH-specific drugs in patients with diffuse parenchymal lung diseases are discussed. © 2015 PTChP.

Chorostowska-Wynimko J.,National Institute of Tuberculosis and Lung Diseases
European Respiratory Review | Year: 2015

α1-antitrypsin deficiency (AATD) is a significantly under-recognised autosomal genetic disorder with <10% of affected individuals being clinically diagnosed. Moreover, rigorous genetic epidemiological data regarding AATD are lacking. The majority of findings come from the USA and Western Europe, and no information is available for many countries. To address this concern, an α1- antitrypsin (AAT) laboratory was set up in 2009 at the National Institute of Tuberculosis and Lung Diseases (Warsaw, Poland). In 2010, an AATD screening programme targeting patients with respiratory disorders was initiated in Poland. This targeted survey has provided valuable information regarding AATdeficient genotypes, clinical disease and levels of expertise at the physician level. After 4 years, almost 2500 patients with chronic obstructive pulmonary disorders have been screened and, in this cohort, ∼13% had AATD alleles. In these patients, the detection frequency for S and Z alleles was four times greater, and the frequency of homozygous PI*ZZ was 16 times greater than that of the general population. These results highlight the need to build awareness in the medical community, and the project is currently being extended to cover central Eastern Europe, with the creation of the Central Eastern European Alpha-1 Antitrypsin Network. ©ERS 2015.

Rowinska-Zakrzewska E.,National Institute of Tuberculosis and Lung Diseases | Korzeniewska-Kosela M.,National Institute of Tuberculosis and Lung Diseases | Roszkowski-Sliz K.,National Institute of Tuberculosis and Lung Diseases
Pneumonologia i Alergologia Polska | Year: 2014

Introduction: In 2012 the incidence rate of tuberculosis in Poland was 19.6/100,000 but these was great variability between regions concerning notification rates (from 10.9/100,000 to 30.2/100,000). The aim of the study was to assess whether there are elements that might confirm that these differences are true. To answer this question, we compared the population of TB patients from regions with higher notification rates to the population of patients from regions with lower notifications rates. The data collected during three consecutive years were analysed. We selected for comparison the regions with the lowest and highest notification rates and those in which the notification rates for 3 years (2010-2012) were relatively stable. Material and methods: Eight regions were chosen: three regions (Group I) with high notification rates (from 23.7 to 32.3/100,000 - mean rates in the analysed period of time) and five (Group II) with low notification rates (mean rates from 12.2 to 18.6/100,000). Results: It was found that the proportion of sputum culture-positive patients was significantly higher in Group II. Thus, the difference in the notification rate of cases with culture-confirmed tuberculosis was smaller than the difference in the whole notification rate. Nevertheless, it was still significant. Tubercle bacilli in patients from Group I were significantly more often resistant to one drug. The incidence of chronic fibro-cavernous disease and of tuberculous pneumonia was significantly higher in Group I. The proportion of patients with symptoms was higher in Group I than in Group II. In addition, patients in Group I had the so-called primary tuberculosis (tuberculous pleuritis and tuberculous lymphadenopathy in the chest) significantly more often. It was also found that among patients from Group I there were significantly more children, more (though not significantly) youngsters and significantly fewer elderly patients. Conclusions: Based on these observations, it was concluded that there is a real difference in the epidemiological situation of tuberculosis in the selected regions of Poland with high and low rates of notification. Possible causes of this situation will be presented in a following publication. © 2014 PTChP.

Skronski M.,National Diagnostics | Chorostowska-Wynimko J.,National Diagnostics | Szczepulska E.,National Institute of Tuberculosis and Lung Diseases | Szpechcinski A.,National Diagnostics | And 3 more authors.
Advances in Experimental Medicine and Biology | Year: 2013

PNA-LNA PCR clamp real-time PCR method represents allele-specific approach to mutation analysis of EGFR gene in NSCLC. Due to its unique design, it is characterized by exceptionally high specificity and sensitivity but also allows detection of rare or not specifically-targeted EGFR mutations within examined exons, otherwise undetectable by other mutation-specific fluorescent probes. We herein present two cases of rare mutations revealed by PNA-LNA PCR clamping of NSCLC samples referred for routine EGFR gene molecular diagnostics. In one, the EGFR gene L858 codon mutation was detected by standard PNA-LNA PCR clamping, subsequently reconfirmed and characterized by direct sequencing of allele specific amplification products as the missense mutation c.2572C>A (p.L858M) paired with L861Q mutation on the same allele (in cis). In the second sample, low quality FFPE material from pleural biopsy, c.2573C>T missense mutation (p.L858P) was revealed. Still, repeated DNA analysis by PNA-LNA PCR clamp and direct sequencing demonstrated low level of mutant allele existing in a total allele pool suggesting rather artifactual c.2572C>T transition, a phenomenon quite frequent in low-volume FFPE samples upon fixation procedures. In conclusion, superior sensitivity and unique design of PNA-LNA PCR clamping are crucial for its excellent diagnostic effectiveness. As we demonstrated, the method allows detecting rare EGFR mutations, although it increases the risk of detection of a very low signal, e.g., generated by a small pool of mutated allele. Therefore, applicability of PNA-LNA PCR clamp product for the direct sequencing reevaluation is of key importance enabling reliable validation of results. © 2013 Springer Science+Business Media Dordrecht.

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