BACKGROUND: Prostate cancer is the second leading cause of male cancer-related deaths in Western countries, which is predominantly attributed to the metastatic castration-resistant stage of the disease (CRPC). There is an urgent need for better prognostic and predictive biomarkers, particularly for androgen receptor targeted agents and taxanes. METHODS: We have searched the PubMed database for original articles and meta-analyses providing information on blood-based markers for castration-resistant prostate cancer monitoring, risk group stratification and prediction of therapy response. RESULTS: The molecular markers are discussed along with the standard clinical parameters, such as prostate specific antigen, lactate dehydrogenase or C-reactive protein. Androgen receptor (AR) alterations are commonly associated with progression to CRPC. These include amplification of AR and its enhancer, point mutations and splice variants. Among DNA methylations, a novel 5-hydroxymethylcytosine activation marker of TOP2A and EZH2 has been identified for the aggressive disease. miR-375 is currently the most promising candidate among non-coding RNAs and sphingolipid analysis has recently emerged as a novel approach. CONCLUSIONS: The promising biomarkers have the potential to improve the care of metastatic prostate cancer patients, however, they need further validation for routine implementation.
- Publikační typ
- časopisecké články MeSH
- přehledy MeSH
INTRODUCTION: Immunotherapy represents a significant and essential component of renal carcinoma therapy (RCC), but the selection of an optimal regimen for an individual patient remains unclear. Despite significant improvements in therapeutic options for RCC, predictive biomarkers for immunotherapeutic agents remain elusive. Neopterin is a biomarker of cell-mediated immune response, with concentrations increased in different disorders, including cancer. High neopterin levels herald, in general, a poor prognosis. AREAS COVERED: This review briefly overviews the contemporary clinical data on biomarkers in metastatic RCC therapy, focusing on neopterin. EXPERT OPINION: Elevated neopterin levels have been observed in tumors of different primary locations. Research indicates that neopterin may serve as a potential biomarker for assessing the inflammatory status associated with certain cancers. However, it is necessary to interpret neopterin levels in the context of a comprehensive clinical evaluation, as elevated neopterin alone is not specific to cancer and can be influenced by other factors, including comorbid conditions. Neopterin has also been identified as a prognostic biomarker. An increasing neopterin level in serum and urine is associated with advanced cancer, but the role as a potential predictor of response to immunotherapy has yet to be established. A reliable biomarker for optimal therapy selection in metastatic RCC is still putative.
- MeSH
- imunoterapie * metody MeSH
- inhibitory kontrolních bodů * aplikace a dávkování farmakologie MeSH
- karcinom z renálních buněk * farmakoterapie patologie MeSH
- lidé MeSH
- metastázy nádorů * MeSH
- nádorové biomarkery * metabolismus MeSH
- nádory ledvin * patologie farmakoterapie MeSH
- neopterin * MeSH
- prognóza MeSH
- Check Tag
- lidé MeSH
- Publikační typ
- časopisecké články MeSH
- přehledy MeSH
Graphene oxide (GO) as the most studied hydrophilic graphene derivative can be deployed in a broad spectrum of environmental technologies opening the issue of its ecotoxicity. Nevertheless, the information about its behavior in complex aquatic environment is still not sufficient. Here, we studied the interaction of three differently oxidized GO systems with planktonic and benthic crustaceans. By standard toxicity tests, we observed the importance of feeding strategy as well as the surface oxidation of GO with respect to GO's ecotoxicity. However, to gain a clearer insight into GO's environmental fate, we introduced a pre-treatment with algae as the most common source of food for crustaceans. Such an adjustment mimicking the conditions in real aquatic ecosystems resulted in complete mitigation of acute toxicity of GOs to all organisms and, more importantly, to the eradication of oxidative stress caused by GOs. We argue, that the pre-exposition of food is a crucial factor in GO's overall environmental fate, even though this fact has been completely neglected in recent studies. These experiments proved that GO is not a hazardous material in complex aquatic environments because its acute toxicity can be successfully mitigated through the interaction with algae even at very high concentrations (25 mg/L).
- MeSH
- chemické látky znečišťující vodu * toxicita MeSH
- ekosystém MeSH
- grafit * toxicita MeSH
- plankton MeSH
- testy toxicity MeSH
- zvířata MeSH
- Check Tag
- zvířata MeSH
- Publikační typ
- časopisecké články MeSH
- práce podpořená grantem MeSH
Targeted delivery combined with controlled drug release has a pivotal role in the future of personalized medicine. This review covers the principles, advantages, and drawbacks of passive and active targeting based on various polymer and magnetic iron oxide nanoparticle carriers with drug attached by both covalent and noncovalent pathways. Attention is devoted to the tailored conjugation of targeting ligands (e.g., enzymes, antibodies, peptides) to drug carrier systems. Similarly, the approaches toward controlled drug release are discussed. Various polymer-drug conjugates based, for example, on polyethylene glycol (PEG), N-(2-hydroxypropyl)methacrylamide (HPMA), polymeric micelles, and nanoparticle carriers are explored with respect to absorption, distribution, metabolism, and excretion (ADME scheme) of administrated drug. Design and structure of superparamagnetic iron oxide nanoparticles (SPION) and condensed magnetic clusters are classified according to the mechanism of noncovalent drug loading involving hydrophobic and electrostatic interactions, coordination chemistry, and encapsulation in porous materials. Principles of covalent conjugation of drugs with SPIONs including thermo- and pH-degradable bonds, amide linkage, redox-cleavable bonds, and enzymatically-cleavable bonds are also thoroughly described. Finally, results of clinical trials obtained with polymeric and magnetic carriers are analyzed highlighting the potential advantages and future directions in targeted anticancer therapy.
- MeSH
- koncentrace vodíkových iontů MeSH
- lékové transportní systémy * MeSH
- ligandy MeSH
- magnetické nanočástice chemie MeSH
- nosiče léků chemie MeSH
- polymery chemie MeSH
- poréznost MeSH
- povrchové vlastnosti MeSH
- uvolňování léčiv * MeSH
- Publikační typ
- časopisecké články MeSH
- práce podpořená grantem MeSH
- přehledy MeSH
In this critical review, we outline various covalent and non-covalent approaches for the functionalization of iron oxide nanoparticles (IONPs). Tuning the surface chemistry and design of magnetic nanoparticles are described in relation to their applicability in advanced medical technologies and biotechnologies including magnetic resonance imaging (MRI) contrast agents, targeted drug delivery, magnetic separations and immobilizations of proteins, enzymes, antibodies, targeting agents and other biosubstances. We review synthetic strategies for the controlled preparation of IONPs modified with frequently used functional groups including amine, carboxyl and hydroxyl groups as well as the preparation of IONPs functionalized with other species, e.g., epoxy, thiol, alkane, azide, and alkyne groups. Three main coupling strategies for linking IONPs with active agents are presented: (i) chemical modification of amine groups on the surface of IONPs, (ii) chemical modification of bioactive substances (e.g. with fluorescent dyes), and (iii) the activation of carboxyl groups mainly for enzyme immobilization. Applications for drug delivery using click chemistry linking or biodegradable bonds are compared to non-covalent methods based on polymer modified condensed magnetic nanoclusters. Among many challenges, we highlight the specific surface engineering allowing both therapeutic and diagnostic applications (theranostics) of IONPs and magnetic/metallic hybrid nanostructures possessing a huge potential in biocatalysis, green chemistry, magnetic bioseparations and bioimaging.
