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Varani K.,University of Ferrara | Caramori G.,University of Ferrara | Vincenzi F.,University of Ferrara | Tosi A.,University of Ferrara | And 12 more authors.
FASEB Journal | Year: 2010

The primary aim of this study was to investigate adenosine receptors (ARs) in bronchoalveolar lavage (BAL) macrophages from patients with chronic obstructive pulmonary disease (COPD) and age-matched healthy smokers. A 2BARs were significantly decreased in BAL macrophages from patients with COPD when compared with healthy smokers. The effect of proinflammatory cytokines and oxidative/nitrosative stress on AR expression and function in U937 cells before and after PMA treatment was evaluated. IL-1β and TNF-α treatment up-regulated A2A- and A3ARs but not A 1- or A2BARs, whereas IL-6 did not modify AR expression. In contrast, oxidative/nitrosative stress selectively decreased A2BAR expression, which was associated with a reduction in the potency of the adenosine agonist 5′-N-ethylcarboxamideadenosine (NECA) to induce cAMP. Further, the ability of NECA to enhance cell proliferation was increased after oxidative/nitrosative stress. The specific involvement of A2BARs was investigated by using potent and selective A2BAR antagonist and by A2BAR knockdown using siRNA and demonstrated responses similar to those obtained with oxidative/nitrosative stress. N-acetylcysteine (NAC), an antioxidant agent, counteracted the decrease in A2BAR expression, as well as the altered NECA effects on cAMP and cell proliferation. These findings highlight the central role of A2BARs in alveolar macrophages, suggesting that their modulation could represent an innovative pharmacological strategy to manage COPD. © FASEB. Source


Jonczyk-Potoczna K.,Zaklad Radiologii Pediatrycznej | Sosnowski P.,Zaklad Radiologii Klinicznej | Malgorzata W.,Zaklad Radiologii Pediatrycznej | Stezowska-Kubiak S.,Klinika Gastroenterologii Dzieciecej i Chorob Metabolicznych | And 7 more authors.
Family Medicine and Primary Care Review | Year: 2011

Background. In the past, the presence of small, fibrotic pancreas in cystic fibrosis (CF) patients was documented. However, based upon further clinical observations, the organ size does not seem to be so univocal. Objectives. We aimed to assess pancreatic size in CF subjects in relation to pancreatic exocrine function. Material and methods. The study comprised 20 CF patients with steatorrhea (PI group) and 20 CF subjects without steatorrhea (PS group). Twenty healthy subjects (HS) served as controls. In all subjects, pancreatic diameters using magnetic resonance were assessed. Results. All of them pancreatic diameters were significantly smaller in CF PI patients than in HS. However, no differences between PS and PI groups as well as PS subjects and HS were stated. In conclusion, pancreatic diameters are differentiated. Conclusions. The assessment of organ size would not allow for differentiation, not only between PI and PS subjects, but also between CF patients and HS. © Copyright by Wydawnictwo Continuo. Source


Jonczyk-Potoczna K.,Zaklad Radiologii Pediatrycznej | Sosnowski P.,Zaklad Radiologii Klinicznej | Warzywoda M.,Zaklad Radiologii Pediatrycznej | Stezowska-Kubiak S.,Klinika Gastroenterologii Dzieciecej i Chorob Metabolicznych | And 8 more authors.
Family Medicine and Primary Care Review | Year: 2011

Background. The correlation between genotype and exocrine pancreatic function is well known. However, there is no data in regard to pancreatic morphology. Objectives. Therefore, we made an attempt to correlate pancreatic changes to genotype. Material and methods. The study comprised 17 patients with two severe CFTR mutations (SS group) and 18 patients with one mild mutation (SM group). Control group comprised 20 healthy subjects (HS). Results. Fatty replacement of pancreatic tissue and pancreatic atrophy was noted in 10 and 8 CC patients, respectively. Both findings were more common in CC group than in the others (pancreatic steatosis: p < 0.0004 vs HS and p < 0.0011 vs SM; organ atrophy: p < 0.0031 vs HS and p < 0.0064 vs SM). In conclusion, pancreatic morphology strongly correlates with genotype. Conclusions. Pancreatic steatosis and/or atrophy occur almost exclusively in patients with two severe CFTR mutations. © Copyright by Wydawnictwo Continuo. Source


Mutations in epidermal growth factor receptor (EGFR) gene are detected in approximately 10% of non-small cell lung cancer (NSCLC) patients of Caucasian origin and in 30-40% patients of eastern Asian origin. The most commonly found EGFR mutations in NSCLC include deletions in exon 19 (45-50% of all identifi ed mutations) and L858R substitution in exon 21 (40-45% of all mutations). Rare mutations constitute approx. 10-15% of all known EGFR mutations, and include insertion in exon 20, G719X and E709X substitutions in exon 18, L861Q point mutation in exon 21 as well as T790M and S768I substitutions in exon 20. These mutations lead to changes of one or several aminoacids in EGFR tyrosine kinase (TK) protein domain. The types of mutations aff ects the level of tyrosine kinase activity and its conformation and also the effi cacy of EGFR TK inhibitors (EGFR TKIs). Administration of EGFR TKIs in patients with tumours carrying common EGFR mutations (deletions in exon 19 and L858R substitution) is indicated as first-line treatment or, if that was not possible, as a second line therapy. The eff ect of EGFR TKIs therapy in tumours carrying L858R mutation is slightly worse than in cases with deletions in exon 19 of EGFR gene, which however should not exclude this line of therapy in patients with the former mutation. EGFR TKIs seem to be a good therapeutic option in tumours where G719X or L861Q substitution was identifi ed as well as in patients with coexisting rare mutations (included T790M) and common ones. In other cases, available clinical data on the role of rare mutations in development of primary resistance to EGFR TKIs are too scarce. Patients carrying some insertion variants in exon 20 or S768I point mutation seem to have a lesser chance to respond to EGFR TKIs therapy. Therefore, management of patients with private mutations of EGFR gene should be subject to utmost individualisation. © Polskie Towarzystwo Onkologiczne. Source


Krawczyk P.,Katedra I Klinika Pneumonologii | Skorska E.,Katedra I Klinika Pneumonologii | Kowalski D.M.,Klinika Nowotworow Klatki Piersiowej Centrum Onkologii | Milanowski J.,Katedra I Klinika Pneumonologii
Onkologia Polska | Year: 2012

BRCA1 and BRCA2 genes are the tumor suppressor genes. They are responsible for DNA double-strand breaks repair (homologous recombination). BRCA protein also regulates cell division and cell cycle. BRCA1 and BRCA2 gene mutations lead to an increased risk of hereditary breast and ovarian cancer. Moreover, cancer cells with BRCA gene mutations and/or low expression of BRCA proteins are more sensitive to ionizing radiation and cytostatic agents, which cause DNA damage (e.g. platinum compounds). However, high expression of BRCA proteins overlaps with high effectiveness of taxanes which act as antitubulin agents. Examination of BRCA genes molecular status could be useful as a predictive factor in planning of radiotherapy and chemotherapy scheme in different types of malignant neoplasms. Abnormalities in BRCA-dependent DNA repair pathways are the potential aim of molecularly targeted therapies by means of poly (ADP-ribose) polymerase inhibitors or histone deacetlase inhibitors in triple-negative breast cancer and ovarian cancer patients. Copyright © 2012 Cornetis. Source

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