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Hradec Králové, Czech Republic

Moehler M.,Johannes Gutenberg University Mainz | Mahlberg R.,Mutterhaus der Borromaerinnen | Heinemann V.,Ludwig Maximilians University of Munich | Obermannova R.,Comprehensive Care | And 8 more authors.
Gastric Cancer | Year: 2016

Background: 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). Methods: Patients aged ≥18 years 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 50 mg/m2 followed by oxaliplatin 130 mg/m2 (maximum 8 cycles) and then S-1 [20 mg/m2 (cohort 1) or 25 mg/m2 (cohort 2), twice daily]: first dose, evening of day 1; subsequent administration on days 2–14, twice daily; last dose, morning of day 15 (unlimited number of S-1 cycles). After protocol amendment, enrollment in a third cohort was restricted to patients with chemotherapy-naïve advanced or metastatic esophagogastric cancer. Results: DLT was reported for two of the five patients in cohort 2, defining 20 mg/m2 twice daily as the MTD of S-1 combined with epirubicin and oxaliplatin in heavily pretreated patients. Thirteen patients with chemotherapy-naïve advanced or metastatic esophagogastric cancer were subsequently enrolled and treated at an S-1 dose level of 25 mg/m2 twice daily; no DLTs were reported; median overall survival was 13.1 months. Of the 11 evaluable patients, three (27 %) had partial responses and seven (64 %) had stable disease. The safety profile was in line with expectations. Conclusions: The promising activity of EOS (S-1 dose level, 25 mg/m2 twice daily) and acceptable safety profile support further clinical development of this combination for the first-line treatment of patients with advanced or metastatic esophagogastric cancer. © 2016 The International Gastric Cancer Association and The Japanese Gastric Cancer Association

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.

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.

Kaska M.,Charles University | Hoffmann P.,Faculty Hospital Hradec Kralove | Oberreiter M.,University of Hradec Kralove
Acta Gastro-Enterologica Belgica | Year: 2011

A patient with an advanced carcinoma in the recto-sigmoideum was taken for urgent operation because of abdominal pain, significant distension of colon, clinical symptoms and radiological proofs of ileus. The cause of the complete obstruction of the proximal rectum which was significantly narrowed by a tumour was one tablet of Tralgit SR 100, which had been administered to the patient for 4 weeks after osteosynthesis of the right femur neck following fracture. According to the radiologist between 45 and 50 tablets of the medicament had been found in the digestive tract. The mechanical ileus was solved by operation according to Hartmann. This case has two aspects: 1) surgical - mechanical ileus resulting from a rare set of circumstances, and 2) pharmacological and metabolic - disorder of medicament absorption in the digestive tract. The cause of maldigestion (disorder of absorption) of the Tralgit tablets is further investigated.

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.

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