Nová WHO klasifikace nádorů CNS se do značné míry opírá o molekulární diagnostiku, bez které již nelze některé jednotky prakticky diagnostikovat. Snažíme se ukázat racionální přístup k diagnostice nádorů CNS, který se opírá o konvenční molekulární metody jako je RT-PCR, Sangerovo sekvenování, MLPA, rozšířené o sekvenování nové generace (NGS) a metylační SNP array.
The new WHO classification of CNS tumors is largely based on molecular diagnostic. Without molecular methods some entities can no longer be diagnosed. We are trying to show a rational approach to the CNS tumors diagnostics, which is based on conventional molecular methods such as RT-PCR, Sanger sequencing, MLPA, extended by the next generation sequencing (NGS) and methylation SNP array.
- MeSH
- gliom diagnóza MeSH
- lidé MeSH
- nádory centrálního nervového systému * diagnóza MeSH
- polymerázová řetězová reakce s reverzní transkripcí MeSH
- předškolní dítě MeSH
- sekvenční analýza hybridizací s uspořádaným souborem oligonukleotidů MeSH
- vysoce účinné nukleotidové sekvenování MeSH
- Check Tag
- lidé MeSH
- předškolní dítě MeSH
- ženské pohlaví MeSH
- Publikační typ
- kazuistiky MeSH
Resistance to chemotherapeutics and targeted drugs is one of the main problems in successful cancer therapy. Various mechanisms have been identified to contribute to drug resistance. One of those mechanisms is lysosome-mediated drug resistance. Lysosomes have been shown to trap certain hydrophobic weak base chemotherapeutics, as well as some tyrosine kinase inhibitors, thereby being sequestered away from their intracellular target site. Lysosomal sequestration is in most cases followed by the release of their content from the cell by exocytosis. Lysosomal accumulation of anticancer drugs is caused mainly by ion-trapping, but active transport of certain drugs into lysosomes was also described. Lysosomal low pH, which is necessary for ion-trapping is achieved by the activity of the V-ATPase. This sequestration can be successfully inhibited by lysosomotropic agents and V-ATPase inhibitors in experimental conditions. Clinical trials have been performed only with lysosomotropic drug chloroquine and their results were less successful. The aim of this review is to give an overview of lysosomal sequestration and expression of acidifying enzymes as yet not well known mechanism of cancer cell chemoresistance and about possibilities how to overcome this form of resistance.
- MeSH
- antitumorózní látky farmakologie MeSH
- chemorezistence * účinky léků MeSH
- exocytóza MeSH
- koncentrace vodíkových iontů MeSH
- lidé MeSH
- lyzozomy účinky léků enzymologie MeSH
- nádorové buněčné linie MeSH
- nádory farmakoterapie enzymologie MeSH
- regulace genové exprese u nádorů účinky léků MeSH
- vakuolární protonové ATPasy antagonisté a inhibitory MeSH
- Check Tag
- lidé MeSH
- Publikační typ
- časopisecké články MeSH
- přehledy MeSH
Intracranial ependymoma represents one of the most common pediatric central nervous system malignancies, and exhibits a wide range of clinical behavior from relatively indolent lesions to highly malignant anaplastic ependymomas. Due to the heterogeneous nature of this disease there is lack of prognostic markers, which would reliably predict the outcome of patients. MicroRNAs (miRNAs) have emerged as important molecules in cancer biology during past decade; however, very little is known about their role in ependymomas. The aim of the present study was to evaluate expression of miRNAs in archived formalin-fixed paraffin-embedded (FFPE) samples of pediatric intracranial ependymomas. The expression of miRNAs were examined in 29 samples of ependymoma and we observed that miR-135a-3p, miR-137, miR-17-5p, miR-181d and let-7d-5p were upregulated. In addition, a significantly higher expression of miR-203a was detected in Grade III tumors suggesting its possible use as a prognostic or diagnostic marker. The present study also demonstrated that storage of (FFPE) ependymoma samples for >20 years did not result in a deterioration of miRNAs. The present findings broaden the presently available knowledge regarding miRNA expression in ependymomas and provide further evidence for the employment of miRNA analysis as a supplementary method for the morphological assessment of ependymoma samples.
- Publikační typ
- časopisecké články MeSH
- Publikační typ
- abstrakt z konference MeSH
Cisplatin (CDDP) is a widely used agent in the treatment of neuroblastoma. Unfortunately, the development of acquired chemoresistance limits its clinical use. To gain a detailed understanding of the mechanisms underlying the development of such chemoresistance, we comparatively analyzed established cisplatin-resistant neuroblastoma cell line (UKF-NB-4CDDP) and its sensitive counterpart (UKF-NB-4). First, using viability screenings, we confirmed the decreased sensitivity of tested cells to cisplatin and identified a cross-resistance to carboplatin and oxaliplatin. Then, the proteomic signatures were analyzed using nano liquid chromatography with tandem mass spectrometry. Among the proteins responsible for UKF-NB-4CDDP chemoresistance, ion channels transport family proteins, ATP-binding cassette superfamily proteins (ATP = adenosine triphosphate), solute carrier-mediated trans-membrane transporters, proteasome complex subunits, and V-ATPases were identified. Moreover, we detected markedly higher proteasome activity in UKF-NB-4CDDP cells and a remarkable lysosomal enrichment that can be inhibited by bafilomycin A to sensitize UKF-NB-4CDDP to CDDP. Our results indicate that lysosomal sequestration and proteasome activity may be one of the key mechanisms responsible for intrinsic chemoresistance of neuroblastoma to CDDP.
- MeSH
- apoptóza účinky léků MeSH
- chemorezistence genetika MeSH
- cisplatina škodlivé účinky farmakologie MeSH
- lidé MeSH
- lyzozomy genetika MeSH
- nádorové buněčné linie MeSH
- neuroblastom farmakoterapie genetika patologie MeSH
- proliferace buněk účinky léků MeSH
- proteasomový endopeptidasový komplex genetika MeSH
- proteomika * MeSH
- regulace genové exprese u nádorů genetika MeSH
- transkriptom genetika MeSH
- Check Tag
- lidé MeSH
- Publikační typ
- časopisecké články MeSH
- práce podpořená grantem MeSH
- Publikační typ
- abstrakt z konference MeSH
