Chmelarova M.,Faculty Hospital Hradec Kralove |
Krepinska E.,Faculty Hospital Hradec Kralove |
Spacek J.,Faculty Hospital Hradec Kralove |
Laco J.,Charles University |
And 2 more authors.
Folia Biologica (Czech Republic) | Year: 2012
Epigenetic changes are considered to be a frequent event during tumour development. Hypermethylation of promoter CpG islands represents an alternative mechanism for inactivation of tumour suppressor genes, DNA repair genes, cell cycle regulators and transcription factors. The aim of this study was to investigate promoter methylation of specific genes in ovarian cancer by comparison with normal ovarian tissue. To search for epigenetic events we used methylation-specific multiplex ligation-dependent probe amplification (MS-MLPA) to compare the methylation status of 69 tissue samples of ovarian cancer with 40 control samples. Using a 15% cut-off for methylation, we observed significantly higher methylation in genes MGMT, PAX5, CDH13, WT1, THBS1, GATA5 in the ovarian cancer group, while in the ESR1 gene we observed significantly higher methylation in the control group compared with the ovarian cancer group. These findings could potentially be used in screening of ovarian cancer and may have implications for future chemotherapy based on epigenetic changes.
Balik M.,Charles University |
Zakharchenko M.,Charles University |
Otahal M.,Charles University |
Hruby J.,Charles University |
And 5 more authors.
Blood Purification | Year: 2012
Background: There are limited data on systemic delivery of metabolic substrates during citrate anticoagulation. The direct citrate measurements are usually not available. Methods: Patients on 2.2% acid-citrate-dextrose (ACD, n = 41) were compared to a control group on unfractionated heparin (n = 17). All were treated on 1.9-m 2 polysulfone filters. Samples were taken from the central venous catheter, ports pre-and post-filter and from effluent. Results: The gain of citrate in CVVH (n = 18) was not different from CVVHDF (n = 23, p = 0.8). Mean gain of citrate was 25.4 ± 6.4 mmol/h. The systemic loads of lactate (p = 0.12) and glucose (p = 0.23) in CVVH were similar to CVVHDF. Mean inputs of lactate and glucose were 62.9 ± 21.1 and 26.6 ± 10.4 mmol/h, respectively. The mean difference between post-and prefilter unmeasured anions (d-UA) correlated with mean difference of citrate concentrations (p < 0.0001, r 2 = 0.66). The estimated caloric load of the citrate modalities was 5,536 ± 1,385 kJ/24 h. Conclusions: ACD might represent a significant load of metabolic substrates, particularly if used with lactate buffer. Systemic delivery of citrate can be predicted using d-UA in the extracorporeal circuit. © 2011 S. Karger AG, Basel.
PubMed | The Christie Hospital NHS Foundation Trust, Republic Services, Nordic Group, Mutterhaus Der Borromaerinnen and 6 more.
Type: | Journal: Gastric cancer : official journal of the International Gastric Cancer Association and the Japanese Gastric Cancer Association | Year: 2016
This phase I study investigated the safety and the maximum tolerated dose (MTD) of the oral fluoropyrimidine S-1 when combined with epirubicin and oxaliplatin (EOS).Patients aged 18years with advanced or metastatic solid tumors were enrolled in a 3+3 design with S-1 dose escalation (two planned cohorts) performed according to the occurrence of dose-limiting toxicity (DLT). On day 1 of each 21-day cycle, patients received epirubicin 50mg/mDLT was reported for two of the five patients in cohort 2, defining 20mg/mThe promising activity of EOS (S-1 dose level, 25mg/m
PubMed | Faculty Hospital Hradec Kralove and Charles University
Type: Journal Article | Journal: Molecular cytogenetics | Year: 2014
Both high hyperdiploidy (HeH) and the translocation t(9;22)(q34;q11) are recurrent abnormalities in childhood B-cell acute lymphoblastic leukemia (ALL) and both are used in current classification to define different genetic and prognostic subtypes of the disease. The coexistence of these two primary genetic aberrations within the same clone is very rare in children with ALL. Here we report a new case of a 17-year-old girl with newly diagnosed ALL and uncommon cytogenetic and clinical finding combining high hyperdiploidy and a cryptic BCR/ABL1 fusion and an inherited Charcot-Marie-Tooth neuropathy detected during the induction treatment.High hyperdiploid karyotype 51,XX,+X,+4,+14,+17,+21 without apparent structural aberrations was detected by conventional cytogenetic analysis and multicolor FISH. A cryptic BCR/ABL1 fusion, which was caused by the insertion of part of the ABL1 gene into the 22q11 region, was proved in HeH clone by FISH, RT-PCR and CGH-SNP array. In addition, an abnormal FISH pattern previously described as the deletion of the 3BCR region in some BCR/ABL1 positive cases was not proved in our patient.A novel case of extremely rare childhood ALL, characterized by HeH and a cryptic BCR/ABL1 fusion, is presented and to the best of our knowledge described for the first time. The insertion of ABL1 into the BCR region in malignant cells is supposed. Clearly, further studies are needed to determine the genetic consequences and prognostic implications of these unusual cases.
Cervinka P.,Faculty Hospital Hradec Kralove |
Cervinka P.,Krajska zdravotni a.s. |
Spacek R.,Krajska zdravotni a.s. |
Bystron M.,Krajska zdravotni a.s. |
And 4 more authors.
Canadian Journal of Cardiology | Year: 2014
Background: The objective of our study was to assess whether optical coherence tomography (OCT) guidance could guide intervention to avoid balloon angioplasty and stenting during primary percutaneous coronary intervention. Methods: One hundred patients with ST-segment elevation myocardial infarction and thrombus-containing lesion were enrolled in this study. Thrombus aspiration was performed in all cases followed by an OCT study. After thrombectomy, no stent was implanted in residual significant stenosis (> 50%) if examination using OCT suggested that the occlusion was mostly thrombotic, provided that the patient was symptom-free and the Thrombolysis in Myocardial Infarction (TIMI) flow was ≥ 2. All patients managed only using thrombectomy underwent 1-week and 9-month angiography and OCT. Patients with significant lesion or those in whom thrombectomy failed to re-establish flow underwent standard treatment. Results: Based on the OCT information, 20 patients (20%) were treated only with aspiration even in the presence of angiographically detected "high-grade stenosis." Angiogram and OCT performed at 1 week and 9 months showed a "normal vessel" without significant stenosis in all 20 cases. There were no cases of major adverse cardiovascular event (including death, myocardial infarction, and target lesion revascularization) during the in-hospital period or at the 12-month follow-up. Conclusions: The results of our pilot study suggest that ST segment elevation myocardial infarction patients with TIMI 2/3 flow in the angiogram and without significant coronary narrowing using OCT examination (even in the presence of angiographically detected "high-grade stenosis"), in whom thrombus aspiration is performed in addition to optimal medical therapy might benefit only from thrombus aspiration without plain old balloon angioplasty/stenting during primary percutaneous coronary intervention. Validation of these preliminary data in larger randomized studies is warranted. © 2014 Canadian Cardiovascular Society.
Mlcochova J.,Masaryk University |
Faltejskova-Vychytilova P.,Masaryk University |
Ferracin M.,University of Ferrara |
Zagatti B.,University of Ferrara |
And 8 more authors.
Oncotarget | Year: 2015
The aim of our study was to investigate whether microRNAs (miRNAs) could serve as predictive biomarkers to anti-EGFR therapy (cetuximab, panitumumab) in patients with RAS wild-type (wt-RAS) metastatic colorectal cancer (mCRC). Historical cohort of 93 patients with mCRC (2006-2009) was included and further divided into exploratory and validation cohorts. MiRNAs expression profiling was performed on the exploratory cohort of 41 wt-KRAS mCRC patients treated with cetuximab to identify miRNAs associated with time to progression (TTP). The validation was performed on two independent cohorts: 28 patients of wt-RAS mCRC treated with cetuximab and 24 patients of wt-RAS mCRC treated with panitumumab. We identified 9 miRNAs with significantly different expression between responders and non-responders to cetuximab therapy (P ≤ 0.01). These 9 miRNAs were further evaluated in two independent cohorts of patients and miR-31-3p (P < 0.001) and miR-31-5p (P < 0.001) were successfully confirmed as strongly associated with TTP in wt-RAS mCRC patients treated with cetuximab but not panitumumab. When evaluated on the complete cohort of cetuximab patients (N = 69), miR-31-3p (HR, 5.10; 95% CI, 2.52-10.32; P < 0.001) and miR-31-5p (HR, 4.80; 95% CI, 2.50-9.24; P < 0.001) were correlated with TTP on the comparable level of significance. There was no difference in miR-31-5p/3p expression levels in RAS mutated and wild-type tumor samples. MiR-31-5p/3p are promising predictive biomarkers of cetuximab response in wt-RAS mCRC patients.
Bar M.,University of Ostrava |
Mikulik R.,University of Ostrava |
Jonszta T.,University of Ostrava |
Krajina A.,Faculty Hospital Hradec Kralove |
And 3 more authors.
American Journal of Neuroradiology | Year: 2012
BACKGROUND AND PURPOSE: Recanalization is the important outcome measure for acute stroke therapy. Several methods of recanalization assessment are used in clinical practice, but few studies have addressed their reliability. We, therefore, sought to assess interobserver reliability of the diagnosis of intracranial artery recanalization following intervention by using TIMI criteria. MATERIALS AND METHODS: The digital angiography scans of all patients with acute ischemic stroke during 2009 undergoing DSA and endovascular procedures at Ostrava University Hospital were assessed in the study. Images were retrospectively evaluated for intracranial artery recanalization on the TIMI scale by 2 experienced neuroradiologists who were blinded to clinical findings and to each other. RESULTS: The angiography scans of 43 patients (16 females; age, 70.5 ± 14 years; median baseline NIHSS score, 15 [IQR, 11-18]) were retrospectively evaluated in our study. At 3 months, 27% of patients had mRS scores ≤ 2 and mortality was 18%. Two radiologists diagnosed TIMI grades as follows: TIMI 0, 16%, and 16%; TIMI 1, 21%, and 8%; TIMI 2a, 32% and 29%; TIMI 2b, 13% and 16%; TIMI 3, 18, and 31%. Interobserver agreement for recanalization was weighted κ = 0.4 (95% CI, 0.2 - 0.6). CONCLUSIONS: The diagnosis of recanalization after interventional procedures was found to have poor interobserver agreement between 2 experienced neuroradiologists. TIMI criteria, therefore, do not permit reliable comparison of the efficacy of recanalization therapy among different studies.
PubMed | Faculty Hospital Hradec Kralove, University of Ferrara and Masaryk University
Type: Journal Article | Journal: Oncotarget | Year: 2015
The aim of our study was to investigate whether microRNAs (miRNAs) could serve as predictive biomarkers to anti-EGFR therapy (cetuximab, panitumumab) in patients with RAS wild-type (wt-RAS) metastatic colorectal cancer (mCRC). Historical cohort of 93 patients with mCRC (2006-2009) was included and further divided into exploratory and validation cohorts. MiRNAs expression profiling was performed on the exploratory cohort of 41 wt-KRAS mCRC patients treated with cetuximab to identify miRNAs associated with time to progression (TTP). The validation was performed on two independent cohorts: 28 patients of wt-RAS mCRC treated with cetuximab and 24 patients of wt-RAS mCRC treated with panitumumab. We identified 9 miRNAs with significantly different expression between responders and non-responders to cetuximab therapy (P 0.01). These 9 miRNAs were further evaluated in two independent cohorts of patients and miR-31-3p (P < 0.001) and miR-31-5p (P < 0.001) were successfully confirmed as strongly associated with TTP in wt-RAS mCRC patients treated with cetuximab but not panitumumab. When evaluated on the complete cohort of cetuximab patients (N = 69), miR-31-3p (HR, 5.10; 95% CI, 2.52-10.32; P < 0.001) and miR-31-5p (HR, 4.80; 95% CI, 2.50-9.24; P < 0.001) were correlated with TTP on the comparable level of significance. There was no difference in miR-31-5p/3p expression levels in RAS mutated and wild-type tumor samples. MiR-31-5p/3p are promising predictive biomarkers of cetuximab response in wt-RAS mCRC patients.
Tylova L.,Czech Technical University |
Kukal J.,Czech Technical University |
Vysata O.,Faculty Hospital Hradec Kralove
Neural Network World | Year: 2013
The new method is based on non-linear one-step predictor, which is designed as MLP neural network. It is a kind of low-pass non-linear filter. The difference between raw EEG and the ANN output is then a subject of band spectral analysis. The differences in this power spectrum between Alzheimer's diseased and control patient group are statistically significant. © CTU FTS 2013.
PubMed | Faculty Hospital Hradec Kralove and University of Hradec Kralove
Type: Journal Article | Journal: Journal of labelled compounds & radiopharmaceuticals | Year: 2016
Radioimmunoassay belongs to the analytical method enabling highly specific and sensitive quantification of molecules. The verification of the real-time radioimmunoassay technology usefulness for ligand-quality characteristics evaluation such as concentration, influence of radiolabeling on binding affinity and stability was estimated. The anti-epidermal growth factor receptor antibody