Hospital Bulovka

Prague, Czech Republic

Hospital Bulovka

Prague, Czech Republic
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Moravcikova E.,Charles University | Krepela E.,Charles University | Prochazka J.,Charles University | Benkova K.,Hospital Bulovka | Pauk N.,Charles University
International Journal of Oncology | Year: 2014

The intrinsic apoptosis pathway represents an important mechanism of stress-induced death of cancer cells. To gain insight into the functional status of the apoptosome apparatus in non-small cell lung carcinoma (NSCLC), we studied its sensitivity to activation, the assembly of apopto some complexes and stability of their precursors, and the importance of X-linked inhibitor of apoptosis (XIAP) in the regulation of apoptosome activity, using cell-free cytosols from NSCLC cell lines and NSCLC tumours and lungs from 62 surgically treated patients. Treatment of cytosol samples with cytochrome c (cyt-c) and dATP induced proteolytic processing of procaspase-9 to caspase-9, which was followed by procaspase-3 processing to caspase-3, and by generation of caspase-3-like activity in 5 of 7 studied NSCLC cell lines. Further analysis demonstrated formation of high-Mr Apaf-1 complexes associated with cleaved caspase-9 in the (cyt-c + dATP)-responsive COLO-699 and CALU-1 cells. By contrast, in A549 cells, Apaf-1 and procaspase-9 co-eluted in the high-M r fractions, indicating formation of an apoptosome complex unable of procaspase-9 processing. Thermal pre-treatment of cell-free cytosols in the absence of exogenous cyt-c and dATP lead to formation of Apaf-1 aggregates, unable to recruit and activate procaspase-9 in the presence of cyt-c and dATP, and to generate caspase-3-like activity. Further studies showed that the treatment with cyt-c and dATP induced a substantially higher increase of caspase-3-like activity in cytosol samples from NSCLC tumours compared to matched lungs. Tumour histology, grade and stage had no significant impact on the endogenous and the (cyt-c + dATP)-induced caspase-3-like activity. Upon addition into the cytosol, the XIAP-neutralizing peptides AVPIAQK and ATPFQEG only moderately heightened the (cyt-c + dATP)-induced caspase?3?like activity in some NSCLC tumours. Taken together, the present study provides evidence that the apoptosome apparatus is functional in the majority of NSCLCs and that its sensitivity to the (cyt-c + dATP)-mediated activation is often enhanced in NSCLCs compared to lungs. They also indicate that XIAP does not frequently and effectively suppress the activity of apoptosome apparatus in NSCLCs.


Klezl P.,Charles University | Stanc O.,Hospital Bulovka | Richterova R.,Hospital Bulovka | Gilbert Z.,Hospital Bulovka | Zatura F.,Charles University
Central European Journal of Urology | Year: 2013

Benign tumors of the ureter are rare and most often appear in the form of fbroepithelial polyps [1]. Fibroepithelial polyps represent from 2 to 6% of all benign tumors of the urinary tract [2]. The Authors report on two cases of fbroepithelial polyps of the ureter, which they treated between 1993-2009. One case was presented by acute urinary retention and gross hematuria. In the second case, hematuria and flank pain were observed. The first case was treated with open surgery and partial resection of the ureter, the second was treated endoscopically when the base of the polyp was well identified. © by Polish Urological Association.


Ondrusova L.,Charles University | Vachtenheim J.,Charles University | Reda J.,Charles University | Zakova P.,Charles University | Benkova K.,Hospital Bulovka
PLoS ONE | Year: 2013

Metastasized malignant melanoma has a poor prognosis because of its intrinsic resistance to chemotherapy and radiotherapy. The central role in the melanoma transcriptional network has the transcription factor MITF (microphthalmia-associated transcription factor). It has been shown recently that the expression of MITF and some of its target genes require the SWI/SNF chromatin remodeling complex. Here we demonstrate that survival of melanoma cells requires functional SWI/SNF complex not only by supporting expression of MITF and its targets and but also by activating expression of prosurvival proteins not directly regulated by MITF. Microarray analysis revealed that besides the MITF-driven genes, expression of proteins like osteopontin, IGF1, TGFß2 and survivin, the factors known to be generally associated with progression of tumors and the antiapoptotic properties, were reduced in acute BRG1-depleted 501mel cells. Western blots and RT-PCR confirmed the microarray findings. These proteins have been verified to be expressed independently of MITF, because MITF depletion did not impair their expression. Because these genes are not regulated by MITF, the data suggests that loss of BRG1-based SWI/SNF complexes negatively affects survival pathways beyond the MITF cascade. Immunohistochemistry showed high expression of both BRM and BRG1 in primary melanomas. Exogenous CDK2, osteopontin, or IGF1 each alone partly relieved the block of proliferation imposed by BRG1 depletion, implicating that more factors, besides the MITF target genes, are involved in melanoma cell survival. Together these results demonstrate an essential role of SWI/SNF for the expression of MITF-dependent and MITF-independent prosurvival factors in melanoma cells and suggest that SWI/SNF may be a potential and effective target in melanoma therapy. © 2013 Ondrušová et al.


Novotna B.,University of Hradec Kralove | Koblizek V.,University of Hradec Kralove | Zatloukal J.,Palacky University | Plutinsky M.,Masaryk University | And 6 more authors.
International journal of chronic obstructive pulmonary disease | Year: 2014

PURPOSE: Chronic obstructive pulmonary disease (COPD) has been recognized as a heterogeneous, multiple organ system-affecting disorder. The Global Initiative for Chronic Obstructive Lung Disease (GOLD) places emphasis on symptom and exacerbation management. The aim of this study is examine the course of COPD and its impact on morbidity and all-cause mortality of patients, with respect to individual phenotypes and GOLD categories. This study will also evaluate COPD real-life patient care in the Czech Republic.PATIENTS AND METHODS: The Czech Multicentre Research Database of COPD is projected to last for 5 years, with the aim of enrolling 1,000 patients. This is a multicenter, observational, and prospective study of patients with severe COPD (post-bronchodilator forced expiratory volume in 1 second ≤ 60%). Every consecutive patient, who fulfils the inclusion criteria, is asked to participate in the study. Patient recruitment is done on the basis of signed informed consent. The study was approved by the Multicentre Ethical Committee in Brno, Czech Republic.RESULTS: The objective of this paper was to outline the methodology of this study.CONCLUSION: The establishment of the database is a useful step in improving care for COPD subjects. Additionally, it will serve as a source of data elucidating the natural course of COPD, comorbidities, and overall impact on the patients. Moreover, it will provide information on the diverse course of the COPD syndrome in the Czech Republic.


Hoskovec D.,Charles University | Varga J.,Charles University | Konecna E.,Charles University | Antos F.,Charles University | Antos F.,Hospital Bulovka
Acta Cirurgica Brasileira | Year: 2012

Purpose: Tumor markers are substances found in blood and other biological fluids if tumor is present in the body. They can be produced by tumor itself or can be results of cancer - body relation. They may be used in the follow-up of cancer patients to identify tumor recurrence. Pre-treatment levels have prognostic tool and could signalize persistence of minimal residual disease despite radical surgery. Methods: We operated on 52 patients with upper GI malignancy (32 with gastric cancer and 20 with pancreatic cancer). Blood samples were taken before surgery and peritoneal samples immediately after laparotomy before any manipulation with tumor. All samples were examined by standard biochemical technique and the level was compared with a stage of the disease. Results: Patients suffering from gastric carcinoma of stage I and II had higher level of both markers in sera then in the peritoneal cavity, however most of them were within physiological range. Patients in stage III and IV had average marker levels in the peritoneal cavity higher than in sera. Number of positive findings was increasing according to the stage of the disease. The peritoneal levels of both markers varied extremely in higher stages. In patients suffering from pancreatic carcinoma the CEA levels both in sera and peritoneal cavity were parallel but peritoneal levels were slightly higher in stages III and IV. Ca 19 - 9 was more sensitive for pancreatic cancer. The percentage of positive findings was higher in sera but the level of Ca 19 - 9 was higher in the peritoneal cavity. The number of positive findings again correlated with the stage of the disease. Conclusions: Levels of tumor markers in sera could signalize inoperability of tumor (Ca 19 - 9 in cases of pancreatic carcinoma); peritoneal levels could predict R1 resection especially in gastric cancer patients and risk of early peritoneal recurrence of the disease. Difference between the levels in the peritoneum and sera may signalize the route of dissemination (hematogenous and intraperitoneal).


PubMed | Hospital Bulovka, University of Hradec Kralove, Charles University, Masaryk University and Palacky University
Type: | Journal: International journal of chronic obstructive pulmonary disease | Year: 2014

Chronic obstructive pulmonary disease (COPD) has been recognized as a heterogeneous, multiple organ system-affecting disorder. The Global Initiative for Chronic Obstructive Lung Disease (GOLD) places emphasis on symptom and exacerbation management. The aim of this study is examine the course of COPD and its impact on morbidity and all-cause mortality of patients, with respect to individual phenotypes and GOLD categories. This study will also evaluate COPD real-life patient care in the Czech Republic.The Czech Multicentre Research Database of COPD is projected to last for 5 years, with the aim of enrolling 1,000 patients. This is a multicenter, observational, and prospective study of patients with severe COPD (post-bronchodilator forced expiratory volume in 1 second 60%). Every consecutive patient, who fulfils the inclusion criteria, is asked to participate in the study. Patient recruitment is done on the basis of signed informed consent. The study was approved by the Multicentre Ethical Committee in Brno, Czech Republic.The objective of this paper was to outline the methodology of this study.The establishment of the database is a useful step in improving care for COPD subjects. Additionally, it will serve as a source of data elucidating the natural course of COPD, comorbidities, and overall impact on the patients. Moreover, it will provide information on the diverse course of the COPD syndrome in the Czech Republic.


PubMed | Hospital Bulovka and Charles University
Type: Journal Article | Journal: Central European journal of urology | Year: 2014

Benign tumors of the ureter are rare and most often appear in the form of fibroepithelial polyps [1]. Fibroepithelial polyps represent from 2 to 6% of all benign tumors of the urinary tract [2]. The Authors report on two cases of fibroepithelial polyps of the ureter, which they treated between 1993-2009. One case was presented by acute urinary retention and gross hematuria. In the second case, hematuria and flank pain were observed. The first case was treated with open surgery and partial resection of the ureter, the second was treated endoscopically when the base of the polyp was well identified.


PubMed | Horovice Hospital, Hospital Bulovka, Charles University, Academy of Sciences of the Czech Republic and Institute for Clinical and Experimental Medicine
Type: | Journal: Scandinavian journal of gastroenterology | Year: 2017

Local application of adipose-derived mesenchymal stem cells (ADSC) represents a novel approach for the management of perianal fistula in patients with Crohns disease. A randomised study on an animal model was performed to investigate the efficacy and to detect the distribution of implanted ADSCs by bioluminescence (BLI).A caecostomy was used as a fistula model in 32 Lewis rats. The ADSCs were isolated from transgenic donor expressing firefly luciferase. Animals were randomly assigned to groups given injections of 410The fistula was identified as healed in 6 (38%) animals in group A vs. 1 case (6.3%) in group B (p=.033). The BLI was strongest immediately after administration of ADSCs 31.210Local application of ADSCs resulted in significantly higher fistula closure rate on an animal model. BLI monitoring was proved to be feasible and showed rapid reduction of the ADSC mass after application. More viable cells were detected in animals with healed fistula at the end of the follow-up.


PubMed | Hospital Bulovka
Type: Journal Article | Journal: Scandinavian journal of infectious diseases | Year: 2012

For many years Pneumocystis pneumonia was thought to be caused by the reactivation of a latent infection, but several studies have demonstrated that Pneumocystis jirovecii infection can be acquired de novo. On the basis of our results obtained from a patient with recurrent pneumocystosis, we support the hypothesis that recurrent episodes are caused by reinfection.

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