Adrenokortikální karcinom (ACC) je vzácný, avšak vysoce agresivní maligní nádor kůry nadledvin, který tvoří méně než 0,2 % všech solidních tumorů. Navzdory nízké incidenci je spojen s vysokou morbiditou a mortalitou a vyžaduje mezioborový diagnostický a terapeutický přístup. Tento přehledový článek shrnuje současné poznatky o epidemiologii, etiologii, diagnostice, stagingu, léčebných strategiích a sledování pacientů s ACC se zvláštním důrazem na specifika české urologické praxe. Pozornost je věnována integraci hormonálních vyšetření, zobrazovacích metod (vč. moderních modalit jako PET/MR a nových radiofarmak) i genetických faktorů podílejících se na patogenezi ACC. Základem kurativní léčby zůstává radikální chirurgická resekce doplněná o adjuvantní léčbu mitotanem, případně o systémovou chemoterapii u pokročilých forem onemocnění. Diskutovány jsou i nové terapeutické možnosti vč. imunoterapie a cílené léčby. Vzhledem k raritě a komplexitě tohoto onemocnění je zásadní centralizace péče, dodržování mezinárodních doporučení a mezioborová spolupráce s cílem zlepšení prognózy pacientů v podmínkách České republiky.
Adrenocortical carcinoma (ACC) is a rare but highly aggressive malignancy of the adrenal cortex, accounting for less than 0.2% of all solid tumors. Despite its low incidence, ACC is associated with significant morbidity and mortality and requires a multidisciplinary diagnostic and therapeutic approach. This review summarizes current knowledge of the epidemiology, etiology, diagnostics, staging, treatment strategies, and follow-up of ACC, with an emphasis on the specifics of Czech clinical urological practice. Special attention is paid to the integration of hormonal diagnostics, imaging modalities (including advanced PET/MR and novel tracers), and genetic aspects relevant to ACC pathogenesis. Surgical resection remains the cornerstone of curative treatment, complemented by adjuvant therapy with mitotane and, in advanced cases, cytotoxic chemotherapy. Emerging therapeutic options, including immunotherapy and targeted agents, are also discussed. Given the rarity and complexity of ACC, centralization of care, adherence to international guidelines, and interprofessional collaboration are essential to improving patient outcomes in the Czech Republic.
- MeSH
- adrenalektomie MeSH
- adrenokortikální karcinom * diagnóza patologie terapie MeSH
- adrenokortikální nádory diagnóza patologie terapie MeSH
- cílená molekulární terapie MeSH
- lidé MeSH
- mitotan aplikace a dávkování škodlivé účinky terapeutické užití MeSH
- protokoly protinádorové kombinované chemoterapie aplikace a dávkování terapeutické užití MeSH
- směrnice pro lékařskou praxi jako téma MeSH
- Check Tag
- lidé MeSH
Male infertility is a multifactorial condition contributing to approximately 50% of all cases of couple infertility. In recent years, significant advances have been made in both diagnostics and treatment. This review summarizes key developments from 2019 to 2024 with direct relevance to routine clinical practice in Czech urology and andrology. Particular attention is paid to the updated semen analysis standards (World Health Organisation 6th edition, 2021), sperm DNA fragmentation testing, genetic evaluation (karyotyping, Y chromosome microdeletions, and exome sequencing), surgical management of varicocele, and sperm retrieval techniques for azoospermia, including microdissection testicular sperm extraction (micro-TESE). The article also discusses pharmacological options (gonadotropins, selective estrogen receptor modulators, antioxidants), the impact of lifestyle factors, and the importance of interdisciplinary collaboration with assisted reproduction centers. Future perspectives, including the role of preventive strategies in male reproductive health, are also addressed. The aim is to provide a comprehensive and clinically applicable overview of current recommendations and therapeutic approaches in andrology, with a focus on their implementation in the Czech urological setting.
- MeSH
- analýza spermatu metody MeSH
- antioxidancia farmakologie terapeutické užití MeSH
- asistovaná reprodukce MeSH
- genetické testování metody MeSH
- gonadotropiny terapeutické užití MeSH
- lidé MeSH
- mužská infertilita * diagnóza etiologie terapie MeSH
- odběr spermií MeSH
- selektivní modulátory estrogenních receptorů farmakologie terapeutické užití MeSH
- varikokéla chirurgie MeSH
- životní styl MeSH
- Check Tag
- lidé MeSH
- Publikační typ
- systematický přehled MeSH
Mužská neplodnost je komplexní stav s mnoha etiologickými faktory, včetně hormonálních, anatomických, genetických a vlivů životního stylu. Přestože se mužský faktor podílí až na 40 % případů neplodnosti, přesná příčina zůstává často neznámá (tzv. idiopatická neplodnost). Současné diagnostické metody zahrnují detailní klinické vyšetření, analýzu ejakulátu, hormonální profil, genetické testování a zobrazovací techniky. Výrazný pokrok byl zaznamenán v oblasti testování fragmentace DNA spermií a měření oxidačního stresu, jež poskytují širší pohled na kvalitu spermií. Terapeutické postupy se liší podle příčiny neplodnosti – od farmakologické léčby a chirurgických intervencí až po asistovanou reprodukci. Rychle se rozvíjející výzkum v oblasti regenerativní a genové terapie slibuje nové možnosti léčby. Nedílnou součástí prevence i léčby je rovněž zdravý životní styl a management rizikových faktorů.
Male infertility is a multifactorial condition influenced by hormonal, anatomical, genetic, and lifestyle factors. Although the male factor contributes to up to 40% of infertility cases, the exact etiology often remains unknown (so-called idiopathic infertility). Current diagnostic approaches include detailed clinical evaluation, semen analysis, hormonal assessment, genetic testing, and imaging techniques. Significant progress has been achieved in sperm DNA fragmentation testing and oxidative stress evaluation, offering a broader insight into sperm quality. Treatment strategies vary depending on the underlying cause, ranging from pharmacological therapy and surgical interventions to assisted reproductive technologies. Rapid advances in regenerative medicine and gene therapy show promise for novel therapeutic options. A healthy lifestyle and risk factor management are integral to both prevention and treatment.
Drug resistance is a growing problem for many pathogens, including mycobacteria. Small heterocyclic molecules are among the leading scaffolds for developing potential antimycobacterial agents. Therefore, based on the molecular hybridization approach, we have prepared an extensive series of N-substituted 5-(3,5-dinitrophenyl)-1,3,4-oxadiazol-2-amine derivatives. We also investigated their isosteres and acyclic synthetic precursors. The compounds were evaluated for their in vitro activity against Mycobacterium tuberculosis (Mtb) H37Rv, a panel of multidrug- and extensively drug-resistant Mtb isolates and two nontuberculous mycobacterial strains (NTM; M. avium and M. kansasii). The ability to inhibit mycobacterial growth was quantified using minimum inhibitory concentration (MIC) values. Many compounds achieved MIC values ≤ 0.03 μM for NTM and Mtb, regardless of their resistance profile. The highest activity was associated with oxadiazole and thiadiazole scaffolds with benzylamino or C5-C9 alkylamino substitution. The experimentally confirmed mechanism of action of these compounds consists of disruption of mycobacterial cell wall biosynthesis via inhibition of decaprenylphosphoryl-β-D-ribose 2'-epimerase (DprE1). In vitro toxicity evaluation was performed in a hepatocyte model (HepG2), while in vivo toxicity was evaluated using Danio rerio embryos. These findings identify a promising new chemotype with potent, broad-spectrum and selective antimycobacterial activity, including efficacy against resistant strains, and support its further development as a potential therapeutic candidate.
- MeSH
- antituberkulotika * farmakologie chemická syntéza chemie toxicita MeSH
- dánio pruhované MeSH
- lidé MeSH
- mikrobiální testy citlivosti MeSH
- Mycobacterium tuberculosis účinky léků MeSH
- oxadiazoly * farmakologie chemická syntéza chemie MeSH
- zvířata MeSH
- Check Tag
- lidé MeSH
- zvířata MeSH
- Publikační typ
- časopisecké články MeSH
Extracellular vesicles (EVs) are emerging as critical mediators of intercellular communication in the tumor microenvironment (TME), profoundly influencing cancer progression. These nano-sized vesicles, released by both tumor and stromal cells, carry a diverse cargo of proteins, nucleic acids, and lipids, reflecting the dynamic cellular landscape and mediating intricate interactions between cells. This review provides a comprehensive overview of the biogenesis, composition, and functional roles of EVs in cancer, highlighting their significance in both basic research and clinical applications. We discuss how cancer cells manipulate EV biogenesis pathways to produce vesicles enriched with pro-tumorigenic molecules, explore the specific contributions of EVs to key hallmarks of cancer, such as angiogenesis, metastasis, and immune evasion, emphasizing their role in shaping TME and driving therapeutic resistance. Concurrently, we submit recent knowledge on how the cargo of EVs can serve as a valuable source of biomarkers for minimally invasive liquid biopsies, and its therapeutic potential, particularly as targeted drug delivery vehicles and immunomodulatory agents, showcasing their promise for enhancing the efficacy and safety of cancer treatments. By deciphering the intricate messages carried by EVs, we can gain a deeper understanding of cancer biology and develop more effective strategies for early detection, targeted therapy, and immunotherapy, paving the way for a new era of personalized and precise cancer medicine with the potential to significantly improve patient outcomes.
- MeSH
- extracelulární vezikuly * metabolismus MeSH
- lidé MeSH
- mezibuněčná komunikace * MeSH
- nádorové biomarkery metabolismus MeSH
- nádorové mikroprostředí * MeSH
- nádory * metabolismus patologie terapie MeSH
- zvířata MeSH
- Check Tag
- lidé MeSH
- zvířata MeSH
- Publikační typ
- časopisecké články MeSH
- přehledy MeSH
The consideration of human and environmental exposure to dendrimers, including cytotoxicity, acute toxicity, and cell and tissue accumulation, is essential due to their significant potential for various biomedical applications. This study aimed to evaluate the biodistribution and toxicity of a novel methoxyphenyl phosphonium carbosilane dendrimer, a potential mitochondria-targeting vector for cancer therapeutics, in 2D and 3D cancer cell cultures and zebrafish embryos. We assessed its cytotoxicity (via MTT, ATP, and Spheroid growth inhibition assays) and cellular biodistribution. The dendrimer cytotoxicity was higher in cancer cells, likely due to its specific targeting to the mitochondrial compartment. In vivo studies using zebrafish demonstrated dendrimer distribution within the vascular and gastrointestinal systems, indicating a biodistribution profile that may be beneficial for systemic therapeutic delivery strategies. The methoxyphenyl phosphonium carbosilane dendrimer shows promise for applications in cancer cell delivery, but additional studies are required to confirm these findings using alternative labelling methods and more physiologically relevant models. Our results contribute to the growing body of evidence supporting the potential of carbosilane dendrimers as vectors for cancer therapeutics.
- MeSH
- dánio pruhované MeSH
- dendrimery * toxicita MeSH
- lidé MeSH
- nádory * farmakoterapie MeSH
- techniky 3D buněčné kultury MeSH
- tkáňová distribuce MeSH
- zvířata MeSH
- Check Tag
- lidé MeSH
- zvířata MeSH
- Publikační typ
- časopisecké články MeSH
- práce podpořená grantem MeSH
Extracellular vesicles (EVs) are lipid-enclosed structures that facilitate intercellular communication by transferring cargo between cells. Although predominantly studied in mammals, extracellular vesicles are ubiquitous across metazoans, and thus research in non-mammalian models is critical for fully elucidating extracellular vesicles biology. Recent advances demonstrate that extracellular vesicles mediate diverse physiological processes in non-mammalian vertebrates, including fish, amphibians, and reptiles. Piscine extracellular vesicles promote fin regeneration in zebrafish and carry heat shock proteins regulated by stress. Frog extracellular vesicles containing microRNAs modulate angiogenesis, while turtle extracellular vesicles coordinate reproductive functions. Venom from snakes contains extracellular vesicles that mirror the whole venom composition and interact with mammalian cells. Invertebrates also possess extracellular vesicles involved in immunity, development, and pathogenesis. Molluscan extracellular vesicles participate in shell formation and host interactions. Arthropod models, including Drosophila, genetically dissect conserved pathways controlling extracellular vesicles biogenesis and signalling. Nematode extracellular vesicles regulate larval development, animal communication, and ageing via conserved extracellular vesicles proteins. Ancient metazoan lineages utilise extracellular vesicles as well, with cnidarian extracellular vesicles regulating immunity and regeneration. Ultimately, expanding extracellular vesicles research beyond typical biomedical models to encompass phylogenetic diversity provides an unparalleled perspective on the conserved versus specialised aspects of metazoan extracellular vesicles roles over ∼500 million years. With a primary focus on the literature from the past 5 years, this review aims to reveal fundamental insights into EV-mediated intercellular communication mechanisms shaping animal physiology.
- Publikační typ
- časopisecké články MeSH
- přehledy MeSH
Non-viral gene delivery vectors studied in the gene therapy applications are often designed with the cationic nitrogen containing groups necessary for binding and cell release of nucleic acids. Disadvantage is a relatively high toxicity which restricts the in vivo use of such nanoparticles. Here we show, that the 3rd generation carbosilane dendrimers possessing (trimethyl)phosphonium (PMe3) groups on their periphery were able to effectively deliver the functional siRNA into the cells (B14, Cricetulus griseus), release it into the cytosol and finally to achieve up to 40% gene silencing of targeted gene (glyceraldehyde-3-phosphate dehydrogenase (GAPDH)) with the comparable or, in some cases, even better effectivity as their ammonium counterparts. Moreover, such cationic dendrimers show relatively low in vivo toxicity as compared to their ammonium analogues when analyzed by standard fish embryo test (FET) on Danio rerio in vivo model, with LD50 = 6.26 μM after 48 h of incubation. This is more than 10-fold improvement as compared to published values for various other types of cationic dendrimers. We discuss the potential of further increase of the transfection efficiency, endosomal escape and decrease of toxicity of such non-viral vectors, based on the systematic screening of different types of substituents on central phosphonium atom.
- MeSH
- buněčné linie MeSH
- Cricetulus MeSH
- dánio pruhované MeSH
- dendrimery aplikace a dávkování toxicita MeSH
- embryo nesavčí MeSH
- LD50 MeSH
- malá interferující RNA aplikace a dávkování MeSH
- organofosforové sloučeniny aplikace a dávkování toxicita MeSH
- silany aplikace a dávkování toxicita MeSH
- transfekce metody MeSH
- umlčování genů MeSH
- zvířata MeSH
- Check Tag
- zvířata MeSH
- Publikační typ
- časopisecké články MeSH
Glycodendrimers (Glyco-DDMs) represent a rapidly growing class of nanoparticles with promising properties for biomedical applications but concerns regarding the impact on human health and environment are still justified. Here we report, for the first time, the comparative study of in vivo developmental toxicity of carbosilane Glyco-DDMs and their cytotoxicity in vitro. Carbosilane Glyco-DDMs (generation 1-3) containing 4, 8, and 16 β-d-glucopyranosyl units at the periphery (DDM1Glu, DDM2Glu, and DDM3Glu) were synthesized and characterized by 1H, 13C and 29Si NMR, mass spectrometry, dynamic light scattering, atomic force microscopy (AFM), and computer modeling. In vitro cytotoxicity assay (MTT) of DDM1-3Glu was performed on three different rodent cell lines (Cricetulus griseus) - B14 (ATCC, CCL-14.1), BRL 3A (ATCC, CRL-1442), and NRK 52E (ATCC, CRL-1571). Overall, very low cytotoxicity was observed with calculated IC50 in mM range with slight difference between each cell line and DDM generation investigated. Modified fish embryo test (FET) was further used for DDM3Glu developmental toxicity testing on zebrafish (Danio rerio) embryos. While seemingly harmless to intact embryos, adverse effects of DDMs on the embryonic development become evident after chorion removal (LD50=2.78 μM at 96 hpe). We summarized that the modified FET test showed a two to three orders of magnitude difference between the in vitro cytotoxicity and in vivo developmental toxicity of DDM3Glu. While, in general, the Glyco-DDMs show great promises as efficient vectors in targeted drug delivery or as therapeutic molecules itself, we suggest that their developmental toxicity should be thoroughly investigated to exclude safety risks associated with their potential biomedical use.
- MeSH
- buněčné linie MeSH
- Cricetulus MeSH
- dánio pruhované * embryologie MeSH
- dendrimery chemie toxicita MeSH
- embryo nesavčí účinky léků MeSH
- embryonální vývoj účinky léků MeSH
- glukosa chemie MeSH
- LD50 MeSH
- lidé MeSH
- molekulární modely MeSH
- povrchové vlastnosti MeSH
- silany chemie toxicita MeSH
- teratogeny chemie toxicita MeSH
- testy toxicity MeSH
- viabilita buněk účinky léků MeSH
- zvířata MeSH
- Check Tag
- lidé MeSH
- zvířata MeSH
- Publikační typ
- časopisecké články MeSH
- práce podpořená grantem MeSH
