- Publikační typ
- abstrakt z konference MeSH
- Publikační typ
- abstrakt z konference MeSH
Small noncoding RNAs play an important role in various disease states, including cancer. PIWI proteins, a subfamily of Argonaute proteins, and PIWI-interacting RNAs (piRNAs) were originally described as germline-specific molecules that inhibit the deleterious activity of transposable elements. However, several studies have suggested a role for the piRNA-PIWI axis in somatic cells, including somatic stem cells. Dysregulated expression of piRNAs and PIWI proteins in human tumors implies that, analogously to their roles in undifferentiated cells under physiological conditions, these molecules may be important for cancer stem cells and thus contribute to cancer progression. We provide an overview of piRNA biogenesis and critically review the evidence for the role of piRNA-PIWI axis in cancer stem cells. In addition, we examine the potential of piRNAs and PIWI proteins to become biomarkers in cancer.
- Publikační typ
- časopisecké články MeSH
- přehledy MeSH
- Publikační typ
- abstrakt z konference MeSH
Brain metastases are a very common and serious complication of oncological diseases. Despite the vast progress in multimodality treatment, brain metastases significantly decrease the quality of life and prognosis of patients. Therefore, identifying new targets in the microenvironment of brain metastases is desirable. Fibroblast activation protein (FAP) is a transmembrane serine protease typically expressed in tumour-associated stromal cells. Due to its characteristic presence in the tumour microenvironment, FAP represents an attractive theranostic target in oncology. However, there is little information on FAP expression in brain metastases. In this study, we quantified FAP expression in samples of brain metastases of various primary origin and characterised FAP-expressing cells. We have shown that FAP expression is significantly higher in brain metastases in comparison to non-tumorous brain tissues, both at the protein and enzymatic activity levels. FAP immunopositivity was localised in regions rich in collagen and containing blood vessels. We have further shown that FAP is predominantly confined to stromal cells expressing markers typical of cancer-associated fibroblasts (CAFs). We have also observed FAP immunopositivity on tumour cells in a portion of brain metastases, mainly originating from melanoma, lung, breast, and renal cancer, and sarcoma. There were no significant differences in the quantity of FAP protein, enzymatic activity, and FAP+ stromal cells among brain metastasis samples of various origins, suggesting that there is no association of FAP expression and/or presence of FAP+ stromal cells with the histological type of brain metastases. In summary, we are the first to establish the expression of FAP and characterise FAP-expressing cells in the microenvironment of brain metastases. The frequent upregulation of FAP and its presence on both stromal and tumour cells support the use of FAP as a promising theranostic target in brain metastases.
- MeSH
- fibroblasty patologie MeSH
- individualizovaná medicína MeSH
- karcinom z renálních buněk * patologie MeSH
- kvalita života MeSH
- lidé MeSH
- membránové proteiny metabolismus MeSH
- nádorové mikroprostředí MeSH
- nádory ledvin * patologie MeSH
- nádory mozku * patologie MeSH
- serinové endopeptidasy metabolismus MeSH
- Check Tag
- lidé MeSH
- Publikační typ
- časopisecké články MeSH
- Publikační typ
- abstrakt z konference MeSH
IL-6 signaling is involved in the pathogenesis of a number of serious diseases, including chronic inflammation and cancer. Targeting of IL-6 receptor (IL-6R) by small molecules is therefore an intensively studied strategy in cancer treatment. We describe the design, synthesis, and characteristics of two new bis-pentamethinium salts 5 and 6 (meta and para) bearing indole moieties. Molecular docking studies showed that both compounds have the potential to bind IL-6R (free energy of binding -9.5 and -8.1 kcal/mol). The interaction with IL-6R was confirmed using microscale thermophoresis analyses, which revealed that both compounds had strong affinity for the IL-6R (experimentally determined dissociation constants 26.5 ± 2.5 nM and 304 ± 27.6 nM, respectively). In addition, both compounds were cytotoxic for a broad spectrum of cancer cell lines in micromolar concentrations, most likely due to their accumulation in mitochondria and inhibition of mitochondrial respiration. In summary, the structure motif of bis-pentamethinium salts represents a promising starting point for the design of novel multitargeting compounds with the potential to inhibit IL-6 signaling and simultaneously target mitochondrial metabolism in cancer cells.
- Publikační typ
- časopisecké články MeSH
V průběhu spánku se může objevit celá řada záchvatových motorických projevů s různou etiologií. Při jejich hodnocení je klíčové zejména odlišení epileptických záchvatů od jiných poruch spánku. Epileptické záchvaty ve spánku jsou relativně časté a v přibližně 12 % jsou téměř výhradně vázány na spánek. Nejčastějším typem epileptických záchvatů ve spánku jsou fokální hyperkinetické záchvaty v rámci tzv. na spánek vázané hypermotorické epilepsie (sleep-related hypermotor epilepsy - SHE), dříve známé pod názvem noční frontální epilepsie, přičemž po stránce etiologie a lokalizace epileptického ložiska se jedná o heterogenní skupinu. Odlišení SHE může být obtížné zejména od NREM parasomnií vzhledem k některým společným patofyziologickým mechanismům a časté koincidenci obou poruch. Další typy záchvatových projevů ve spánku představuje porucha chování v REM spánku, poruchy pohybu souvisejících se spánkem, jakými jsou rytmické pohyby vázané na spánek, hypnagogické záškuby, periodické pohyby dolními končetinami a různé formy myoklonu. V neposlední řadě se během noci můžeme setkat s panickými atakami a psychogenními neepileptickými záchvaty.
There is a wide range of different paroxysmal motor events with various aetiology during sleep. The most important issue in their evaluation is to distinguish epileptic seizures from other sleep disorders. Sleep-related epileptic seizures are relatively frequent and they may occur predominantly or exclusively during sleep in approximately 12 %. The most frequent seizure type during sleep is a focal hyperkinetic seizure in the frame of the sleep-related hypermotor epilepsy (SHE), previously known as nocturnal frontal lobe epilepsy, which is a heterogeneous group in terms of aetiology and localization of epileptic focus. The differentiation of SHE from NREM parasomnia may sometimes be difficult, because of relatively frequent cooccurrence of both disorders and because of some shared pathophysiological mechanisms. Other possibilities of paroxysmal motor events during sleep represent REM sleep behaviour disorder, sleep-related movement disorders including sleep-related rhythmic movement disorder, sleep startle, periodic leg movement and various forms of myoclonus. Last but not least the psychogenic non-epileptic seizures or panic attacks may occur during the night.
- Klíčová slova
- záchvatové stavy ve spánku,
- MeSH
- epilepsie diagnóza terapie MeSH
- lidé MeSH
- parasomnie spojené s REM spánkem diagnóza terapie MeSH
- porucha chování v REM spánku * diagnóza terapie MeSH
- poruchy spánku a bdění * diagnóza terapie MeSH
- spánek pomalých vln MeSH
- záchvaty * diagnóza terapie MeSH
- Check Tag
- lidé MeSH
- Publikační typ
- přehledy MeSH
Dipeptidyl peptidase IV (DPP-IV, CD26) is frequently dysregulated in cancer and plays an important role in regulating multiple bioactive peptides with the potential to influence cancer progression and the recruitment of immune cells. Therefore, it represents a potential contributing factor to cancer pathogenesis and an attractive therapeutic target. Specific DPP-IV inhibitors (gliptins) are currently used in patients with type 2 diabetes mellitus to promote insulin secretion by prolonging the activity of the incretins glucagon-like peptide 1 (GLP-1) and glucose-dependent insulinotropic polypeptide (GIP). Nevertheless, the modulation of the bioavailability and function of other DPP-IV substrates, including chemokines, raises the possibility that the use of these orally administered drugs with favorable side-effect profiles might be extended beyond the treatment of hyperglycemia. In this review, we critically examine the possible utilization of DPP-IV inhibition in cancer prevention and various aspects of cancer treatment and discuss the potential perils associated with the inhibition of DPP-IV in cancer. The current literature is summarized regarding the possible chemopreventive and cytotoxic effects of gliptins and their potential utility in modulating the anti-tumor immune response, enhancing hematopoietic stem cell transplantation, preventing acute graft-versus-host disease, and alleviating the side-effects of conventional anti-tumor treatments.
- Publikační typ
- časopisecké články MeSH
- přehledy MeSH
