ΔNp63, also known as p40, regulates stemness of normal mammary gland epithelium and provides stem cell characteristics in basal and HER2-driven murine breast cancer models. Whilst ΔNp63/p40 is a characteristic feature of normal basal cells and basal-type triple-negative breast cancer, some receptor-positive breast cancers express ΔNp63/p40 and its overexpression imparts cancer stem cell-like properties in ER+ cell lines. However, the incidence of ER+ and HER2+ tumours that express ΔNp63/p40 is unclear and the phenotype of ΔNp63/p40+ cells in these tumours remains uncertain. Using immunohistochemistry with p63 isoform-specific antibodies, we identified a ΔNp63/p40+ tumour cell subpopulation in 100 of 173 (58%) non-triple negative breast cancers and the presence of this population associated with improved survival in patients with ER- /HER2+ tumours (p = 0.006). Furthermore, 41% of ER+ /PR+ and/or HER2+ locally metastatic breast cancers expressed ΔNp63/p40, and these cells commonly accounted for <1% of the metastatic tumour cell population that localised to the tumour/stroma interface, exhibited an undifferentiated phenotype and were CD44+ /ALDH- . In vitro studies revealed that MCF7 and T47D (ER+ ) and BT-474 (HER2+ ) breast cancer cell lines similarly contained a small subpopulation of ΔNp63/p40+ cells that increased in mammospheres. In vivo, MCF7 xenografts contained ΔNp63/p40+ cells with a similar phenotype to primary ER+ cancers. Consistent with tumour samples, these cells also showed a distinct location at the tumour/stroma interface, suggesting a role for paracrine factors in the induction or maintenance of ΔNp63/p40. Thus, ΔNp63/p40 is commonly present in a small population of tumour cells with a distinct phenotype and location in ER+ and/or HER2+ human breast cancers.

• MeSH
• fenotyp MeSH
• heterografty MeSH
• lidé MeSH
• myši MeSH
• nádorové biomarkery analýza   metabolismus   MeSH
• nádorové kmenové buňky metabolismus   patologie   MeSH
• nádorové supresorové proteiny metabolismus   MeSH
• nádory prsu genetika   metabolismus   patologie   MeSH
• receptor erbB-2 genetika   metabolismus   MeSH
• receptory pro estrogeny genetika   metabolismus   MeSH
• transkripční faktory metabolismus   MeSH
• zvířata MeSH
• Check Tag
• lidé MeSH
• myši MeSH
• ženské pohlaví MeSH
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH

OBJECTIVE: We performed a retrospective study to determine the different types of seizure onset patterns (SOP) in invasive EEG (IEEG) in patients with temporal lobe epilepsy (TLE). METHODS: We analyzed a group of 51 patients (158 seizures) with TLE who underwent IEEG. We analyzed the dominant frequency during the first 3s after the onset of ictal activity. The cut-off value for distinguishing between fast and slow frequencies was 8 Hz. We defined three types of SOPs: (1) fast ictal activity (FIA) - frequency ≥8 Hz; (2) slow ictal activity (SIA) - frequency <8 Hz; and (3) attenuation of background activity (AT) - no clear-cut rhythmic activity during the first 3s associated with changes of IEEG signal (increase of frequency, decrease of amplitude). We tried to find the relationship between different SOP types and surgery outcome, histopathological findings, and SOZ localization. RESULTS: The most frequent SOP was FIA, which was present in 67% of patients. More patients with FIA were classified postoperatively as Engel I than those with SIA and AT (85% vs. 31% vs. 0) (P < 0.001). There were no statistically significant differences in the type of SOP, in the histopathological findings, or in the SOZ localization. CONCLUSION: In patients with refractory TLE, seizure onset frequencies ≥8 Hz during the first 3s of ictal activity are associated with a better surgical outcome than frequencies <8 Hz. SIGNIFICANCE: Our study suggests that very early seizure onset frequencies in IEEG in patients with TLE could be the independent predictive factor for their outcome, regardless of the localization and etiology.

• MeSH
• dospělí MeSH
• elektroencefalografie * MeSH
• epilepsie temporálního laloku patofyziologie   chirurgie   MeSH
• fixace tkání MeSH
• funkční lateralita fyziologie   MeSH
• implantované elektrody MeSH
• interpretace statistických dat MeSH
• jednofotonová emisní výpočetní tomografie MeSH
• lidé středního věku MeSH
• lidé MeSH
• magnetická rezonanční tomografie MeSH
• mladiství MeSH
• mladý dospělý MeSH
• neurochirurgické výkony MeSH
• počítačové zpracování obrazu MeSH
• pozitronová emisní tomografie MeSH
• výsledek terapie MeSH
• záchvaty patofyziologie   MeSH
• Check Tag
• dospělí MeSH
• lidé středního věku MeSH
• lidé MeSH
• mladiství MeSH
• mladý dospělý MeSH
• mužské pohlaví MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH

Projekt je zaměřen na studium epidemiologických, genetických a klinicko-patologických aspektů ?triple-negativního? (ER-?, PR, c-ErbB2 negativního) karcinomu prsu v populaci českých žen. Chceme stanovit prevalenci ?triple-negativního? karcinomu a jeho bližší molekulární charakteristiku, s cílem identifikovat hereditární a sporadickou formu tohoto onemocnění. Získané poznatky chceme využít zejména ke zvýšení efektivity záchytu přenašečů mutace BRCA1 genu v české populaci, případně i k identifikaci novýchprediktivních a prognostických ukazatelů vůči klasické i cílené protinádorové terapii.; The Project is focused on the study of epidemiological, genetic and clinical-pathological aspects of triple-negative (ER-alpha, PR, C-ErbB2) breast carcinoma in Czech female patients. The prevalence of triple-negative carcinoma and its detailed molecularcharacteristics will be assessed in order to identify hereditary and sporadic forms of this disease. The data obtained will be used particularly to increase the effectiveness of the detection of the BRCA1 gene carriers in Czech population and/or to identify new predictive and prognostic indicators for conventional and targeted anticancer therapy.

• MeSH
• diagnostické techniky molekulární metody   využití   MeSH
• geny BRCA1 MeSH
• mutace MeSH
• mutageneze MeSH
• nádory prsu epidemiologie   genetika   patologie   MeSH
• plošný screening MeSH
• prevalence MeSH
• receptory pro estrogeny MeSH
• receptory progesteronu MeSH
• ženy MeSH

• Konspekt
• Biochemie. Molekulární biologie. Biofyzika
• NLK Obory
• gynekologie a porodnictví
• onkologie
• biologie
• NLK Publikační typ
• závěrečné zprávy o řešení grantu IGA MZ ČR

This study was conducted to determine the incidence of grey-white matter abnormalities (GWMAs) on magnetic resonance images (MRIs) in patients with hippocampal sclerosis (HS), to assess the inter-observer reliability of this finding, and to establish a possible relationship between GWMA and histopathological findings in the anterior part of the temporal lobe, as well as its other relation to clinical variables. We established a group of 55 patients with histologically proven HS. Three observers independently reviewed the MRIs to assess whether GWMA was present. Substantial independent inter-observer agreement was reached for 44 of the 55 patients (80%) (Fleiss' kappa 0.732; p<0.0001). GWMAs were present in 38% of patients (HS+GWMA). Focal cortical dysplasia (FCD) of type IIIa (ILAE classification) was present in 31% of patients. FCD type IIIa was present in 52.4% with HS+GWMA, and in 17.6% without GWMA (HS-GWMA) (p=0.007). We did not find any statistically significant differences in the postoperative outcomes between HS+GWMA and HS-GWMA. We did not find any statistically significant differences in the presence or absence of GWMA and FCD of the temporal pole in relation to the onset of epilepsy, the duration of epilepsy, or the presence of potential epileptogenic insults. GWMA in the anterior part of temporal lobe in patients with HS is a reliable assessment sign for observers who are experienced in evaluating the MRIs of epilepsy patients. The presence of GWMA is significantly associated with the presence of FCD type IIIa in these patients. The presence or absence of GWMA and FCD type IIIa does not influence the postoperative outcome of HS patients.

• MeSH
• anatomická značka patologie   MeSH
• dítě MeSH
• dospělí MeSH
• epilepsie temporálního laloku patologie   chirurgie   MeSH
• hipokampus patologie   MeSH
• laboratorní medicína metody   normy   statistika a číselné údaje   MeSH
• lidé středního věku MeSH
• lidé MeSH
• magnetická rezonanční tomografie metody   normy   statistika a číselné údaje   MeSH
• malformace mozkové kůry patologie   chirurgie   MeSH
• mladiství MeSH
• mladý dospělý MeSH
• odchylka pozorovatele MeSH
• retrospektivní studie MeSH
• skleróza patologie   MeSH
• spánkový lalok patologie   MeSH
• Check Tag
• dítě MeSH
• dospělí MeSH
• lidé středního věku MeSH
• lidé MeSH
• mladiství MeSH
• mladý dospělý MeSH
• mužské pohlaví MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH
• validační studie MeSH

Several models have previously been proposed to predict the probability of non-sentinel lymph node (NSLN) metastases after a positive sentinel lymph node (SLN) biopsy in breast cancer. The aim of this study was to assess the accuracy of two previously published nomograms (MSKCC, Stanford) and to develop an alternative model with the best predictive accuracy in a Czech population. In the basic population of 330 SLN-positive patients from the Czech Republic, the accuracy of the MSKCC and the Stanford nomograms was tested by the area under the receiver operating characteristics curve (AUC). A new model (MOU nomogram) was proposed according to the results of multivariate analysis of relevant clinicopathologic variables. The new model was validated in an independent test population from Hungary (383 patients). In the basic population, six of 27 patients with isolated tumor cells (ITC) in the SLN harbored additional NSLN metastases. The AUCs of the MSKCC and Stanford nomograms were 0.68 and 0.66, respectively; for the MOU nomogram it reached 0.76. In the test population, the AUC of the MOU nomogram was similar to that of the basic population (0.74). The presence of only ITC in SLN does not preclude further nodal involvement. Additional variables are beneficial when considering the probability of NSLN metastases. In the basic population, the previously published nomograms (MSKCC and Stanford) showed only limited accuracy. The developed MOU nomogram proved more suitable for the basic population, such as for another independent population from a mid-European country.

• MeSH
• algoritmy MeSH
• biopsie sentinelové lymfatické uzliny MeSH
• dospělí MeSH
• lidé středního věku MeSH
• lidé MeSH
• lymfatické metastázy diagnóza   patologie   MeSH
• nádory prsu etnologie   patologie   MeSH
• nomogramy MeSH
• prediktivní hodnota testů MeSH
• ROC křivka MeSH
• senioři nad 80 let MeSH
• senioři MeSH
• Check Tag
• dospělí MeSH
• lidé středního věku MeSH
• lidé MeSH
• senioři nad 80 let MeSH
• senioři MeSH
• ženské pohlaví MeSH
• Publikační typ
• srovnávací studie MeSH
• Geografické názvy
• Česká republika MeSH