• Publikační typ
• abstrakt z konference MeSH

BACKGROUND: Breast cancer (BC), the most frequent malignancy in women worldwide, is currently diagnosed in about 1.4 million female patients annually. Approximately 10-20% of BC is represented by triple negative breast cancer (TNBC) which is aggressive, the prognosis is poor and patients cannot benefit from targeted treatment based on hormonal or HER2 receptors. For this reason, search for markers that can predict the efficacy of chemotherapy in TNBC is a priority. METHODS AND RESULTS: This review focuses on BCL2 protein as a prognostic marker in TNBC and its potential as a predictor of sensitivity to chemotherapy. CONCLUSION: BCL2 protein expression is a positive prognostic factor in BC. Better survival of patients with BCL2 positivity (BCL2+) has been explained by the correlation with estrogen receptor positive (ER+) status. BCL2+ is however not simply a surrogate marker for ER+. Moreover, BCL2 protein expression is also a positive prognostic marker in the TNBC subgroup. We and others show, that low BCL2 expression was associated with good outcome of TNBC patients treated with both adjuvant and neoadjuvant anthracycline-based chemotherapy. On the other hand, recent studies have shown that a subset of TNBC patients may benefit from the classical adjuvant CMF (cyclophosphamide, methotrexate, 5-fluorouracil) regimen. Given the heterogeneity of TNBC there is an urgent need to find and validate the sensitivity predictors to these regimens making them usable in clinical practice. BCL2 enrichment has been described in the mesenchymal stem-like (MSL) TNBC subgroup.

• MeSH
• lidé MeSH
• nádorové biomarkery genetika   metabolismus   MeSH
• protokoly antitumorózní kombinované chemoterapie terapeutické užití   MeSH
• protoonkogenní proteiny c-bcl-2 genetika   metabolismus   MeSH
• triple-negativní karcinom prsu farmakoterapie   genetika   MeSH
• výsledek terapie MeSH
• Check Tag
• lidé MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH
• přehledy MeSH

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.

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.

• 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

• MeSH
• banky biologického materiálu trendy   využití   MeSH
• financování organizované MeSH
• lidé MeSH
• odběr biologického vzorku metody   trendy   využití   MeSH
• Check Tag
• lidé MeSH
• Publikační typ
• abstrakt z konference MeSH

• Publikační typ
• abstrakt z konference MeSH

Malignant gliomas, the deadliest of brain neoplasms, show rampant genetic instability and resistance to genotoxic therapies, implicating potentially aberrant DNA damage response (DDR) in glioma pathogenesis and treatment failure. Here, we report on gross, aberrant constitutive activation of DNA damage signalling in low- and high-grade human gliomas, and analyze the sources of such endogenous genotoxic stress. Based on analyses of human glioblastoma multiforme (GBM) cell lines, normal astrocytes and clinical specimens from grade II astrocytomas (n=41) and grade IV GBM (n=60), we conclude that the DDR machinery is constitutively activated in gliomas, as documented by phosphorylated histone H2AX (gammaH2AX), activation of the ATM-Chk2-p53 pathway, 53BP1 foci and other markers. Oxidative DNA damage (8-oxoguanine) was high in some GBM cell lines and many GBM tumors, while it was low in normal brain and grade II astrocytomas, despite the degree of DDR activation was higher in grade II tumors. Markers indicative of ongoing DNA replication stress (Chk1 activation, Rad17 phosphorylation, replication protein A foci and single-stranded DNA) were present in GBM cells under high- or low-oxygen culture conditions and in clinical specimens of both low- and high-grade tumors. The observed global checkpoint signaling, in contrast to only focal areas of overabundant p53 (indicative of p53 mutation) in grade II astrocytomas, are consistent with DDR activation being an early event in gliomagenesis, initially limiting cell proliferation (low Ki-67 index) and selecting for mutations of p53 and likely other genes that allow escape (higher Ki-67 index) from the checkpoint and facilitate tumor progression. Overall, these results support the potential role of the DDR machinery as a barrier to gliomagenesis and indicate that replication stress, rather than oxidative stress, fuels the DNA damage signalling in early stages of astrocytoma development.

• MeSH
• antigen Ki-67 metabolismus   MeSH
• fyziologický stres * fyziologie   MeSH
• gliom * genetika   metabolismus   patologie   MeSH
• histony metabolismus   MeSH
• lidé MeSH
• nádorové buněčné linie MeSH
• nádorový supresorový protein p53 metabolismus   MeSH
• nádory mozku * genetika   metabolismus   patologie   MeSH
• oxidační stres * fyziologie   MeSH
• poškození DNA * fyziologie   MeSH
• replikace DNA * genetika   fyziologie   MeSH
• signální transdukce genetika   MeSH
• Check Tag
• lidé MeSH

BACKGROUND: Activating point mutation of the BRAF gene, the most common genetic alteration reported in papillary thyroid carcinomas (PTC), has been associated with poor prognostic characteristics. AIM: Our objective was to determine the frequency of BRAFV600E mutation in PTC tumor tissues from the period 1960-2007 and to correlate it with clinicopathological parameters. SUBJECTS AND METHODS: DNAs were extracted from 242 PTCs, 23 sporadic medullary carcinomas, one anaplastic carcinoma and 6 poorly differentiated carcinomas. The presence of BRAFV600E mutation was determined using single strand conformation polymorphism method and verified by direct sequencing. RESULTS: BRAFV600E mutation was detected in 81 of 242 PTCs (33.5%), in one of 6 poorly differentiated carcinomas (16.7%) and in anaplastic carcinoma. BRAFV600E mutation was much less frequent in the follicular variant compared to classical variant and mixed follicular- classical variant of PTCs (p=0.001). BRAFV600E mutation was significantly associated with presence of nodal metastasis (p=0.029), more advanced TNM stage (p=0.014) and recurrence of disease (p=0.008). The mutation correlated with a higher age at diagnosis (p=0.049) and with a greater tumor size (p=0.041). Multivariate analysis confirmed these findings. The prevalence of BRAFV600E mutation before 1986 was significantly lower than after it (p=0.008). CONCLUSIONS: Our data suggest that BRAFV600E mutation is associated with high-risk clinicopathological characteristics of PTC and worse prognosis of patients. The frequency of the mutation significantly varied during the observed period but rather because of the different age distribution of patients in particular periods than as a consequence of Chernobyl accident.

• MeSH
• černobylská havárie MeSH
• DNA nádorová biosyntéza   genetika   MeSH
• dospělí MeSH
• exony genetika   MeSH
• frekvence genu MeSH
• invazivní růst nádoru genetika   MeSH
• kodon genetika   MeSH
• lidé středního věku MeSH
• lidé MeSH
• mutace fyziologie   MeSH
• nádory štítné žlázy epidemiologie   genetika   patologie   MeSH
• papilární karcinom epidemiologie   genetika   patologie   MeSH
• polymerázová řetězová reakce s reverzní transkripcí MeSH
• polymorfismus konformace jednovláknové DNA genetika   MeSH
• protoonkogenní proteiny B-raf genetika   MeSH
• senioři nad 80 let MeSH
• senioři MeSH
• věkové faktory MeSH
• Check Tag
• dospělí MeSH
• lidé středního věku MeSH
• lidé MeSH
• mužské pohlaví MeSH
• senioři nad 80 let MeSH
• senioři MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH
• Geografické názvy
• Česká republika MeSH

Astrocytomas, particularly high grade astrocytoma, are brain tumors with potent angiogenic activity. Our immnunohistochemical study assessed vascular endothelial growth factor (VEGF), VEGF receptors (Flk-1, and Flt-1), the intermediate filamental protein nestin which plays a role in central nervous system development, and MMP-9, which belongs the family of matrix metalloproteinases implicated in tumor invasion and angiogenesis regulation. We investigated the expression of VEGF, its receptors, nestin and MMP-9 in astrocytomas and their correlation with tumor grade. We used paraffin-embedded samples from 66 patients, 29 with low grade (WHO-grade II) and 37 with high grade (WHO-grade III and IV) astrocytomas. Antibodies against VEGF, Flk-1, Flt1, nestin, CD34 and MMP-9 were used, followed by standard indirect immunohistochemical methods. Expression of Flt-1 and Flk-1 showed no significant differences between low and high grade tumor groups. Expression of VEGF and MMP-9 was increased in the high grade group (p equal to or less than 0.026 and 0.024). Nestin expression in tumor astrocytes and endothelial cells increased in high grade group (p same 0.007 and 0.003). Higher expression of VEGF in high grade astrocytomas may subsequently lead to activation of survival, angiogenesis and migration. Expression of nestin and MMP-9 also suggest their likely role in astrocytoma vascular development and proliferation.

• MeSH
• astrocytom etiologie   metabolismus   patofyziologie   MeSH
• dítě MeSH
• dospělí MeSH
• imunoenzymatické techniky MeSH
• lidé středního věku MeSH
• lidé MeSH
• matrixová metaloproteinasa 9 metabolismus   MeSH
• mladiství MeSH
• mladý dospělý MeSH
• nádory mozku etiologie   metabolismus   patofyziologie   MeSH
• prognóza MeSH
• progrese nemoci MeSH
• proteiny intermediálních filament metabolismus   MeSH
• proteiny nervové tkáně metabolismus   MeSH
• receptor 1 pro vaskulární endoteliální růstový faktor metabolismus   MeSH
• receptor 2 pro vaskulární endoteliální růstový faktor metabolismus   MeSH
• senioři nad 80 let MeSH
• senioři MeSH
• vaskulární endoteliální růstový faktor A metabolismus   MeSH
• Check Tag
• dítě MeSH
• dospělí MeSH
• lidé středního věku MeSH
• lidé MeSH
• mladiství MeSH
• mladý dospělý MeSH
• mužské pohlaví MeSH
• senioři nad 80 let MeSH
• senioři MeSH
• ženské pohlaví MeSH
• Publikační typ
• práce podpořená grantem MeSH

Histopatologický atlas je sestaven jako soubor barevných mikrofotografií obsahující základní histopatologické diagnózy a je určen jako učební pomůcka zejména pregraduálním studentům lékařských oborů. Fotografie jsou doplněny stručným, ale výstižným komentářem, charakterizujícím dané onemocnění a popisy podstatných mikroskopických změn. Součástí publikace je i krátká kapitola s technickými poznámkami, která přibližuje mikroskopickou techniku, fixaci a zpracování tkání, ukazuje přehled histochemických metod a základy imunohistochemie.

• Klíčová slova
• Teoretické obory,
• MeSH
• histologie MeSH
• patologické procesy klasifikace   diagnóza   mikrobiologie   MeSH
• patologie MeSH

• NLK Obory
• patologie
• histologie

An intratumoral or peritumoral microbial intracranial abscess is an infrequent diagnosis. The development of this complication may not be preceded by apparent local or general infection in all cases. To identify this diagnosis by radiological (MRI) or laboratory investigations is very intricate. Nevertheless, the recommended life-saving strategy is early surgery with resolution of both the tumor and infection. If subsequent oncological treatment is required, it has to be adjusted for prevention of re-inflammation. The described patient suffered from an intracranial abscess superimposed on a Glioblastoma Multiforme. The confirmed etiological agent was Staphylococcus aureus. The suspected route of microbial migration and colonization in this tumor was bacteremia via agents from thrombophlebitis. The patient is in a good condition following surgery, antimicrobial treatment, and radiotherapy.

• MeSH
• absces chirurgie   komplikace   patologie   MeSH
• financování organizované MeSH
• glioblastom chirurgie   komplikace   patologie   MeSH
• lidé středního věku MeSH
• lidé MeSH
• magnetická rezonanční tomografie metody   MeSH
• nádory mozku chirurgie   komplikace   patologie   MeSH
• Check Tag
• lidé středního věku MeSH
• lidé MeSH
• ženské pohlaví MeSH
• Publikační typ
• kazuistiky MeSH
• přehledy MeSH