Neurotrophins are a family of secreted proteins that act by binding to tropomyosin receptor kinase (Trk) or p75NTR receptors to regulate nervous system development and plasticity. Increasing evidence indicates that neurotrophins and their receptors in cancer cells play a role in tumor growth and resistance to treatment. In this review, we summarize evidence indicating that neurotrophin signaling influences medulloblastoma (MB), the most common type of malignant brain cancer afflicting children. We discuss the potential of neurotrophin receptors as new therapeutic targets for the treatment of MB. Overall, activation of TrkA and TrkC types of receptors seem to promote cell death, whereas TrkB might stimulate MB growth, and TrkB inhibition displays antitumor effects. Importantly, we show analyses of the gene expression profile of neurotrophins and their receptors in MB primary tumors, which indicate, among other findings, that higher levels of NTRK1 or NTRK2 are associated with reduced overall survival (OS) of patients with SHH MB tumors.

Medulloblastoma (MB) is the most common malignant pediatric brain tumor. Deregulation of brain-derived neurotrophic factor (BDNF)/tropomyosin-related kinase B (TrkB) signaling has been associated with increased proliferative capabilities, invasiveness, and chemoresistance in several types of cancer. However, the relevance of this pathway in MB remains unknown. Here, we show that the selective TrkB inhibitor N-[2-[[(hexahydro-2-oxo-1H-azepin-3-yl)amino]carbonyl]phenyl]-benzo[b]thiophene-2-carboxamide (ANA-12) markedly reduced the viability and survival of human cell lines representative of different MB molecular subgroups. These findings provide the first evidence supporting further investigation of TrkB inhibition as a potential novel strategy for MB treatment.

The study aimed to evaluate the antifungal potential of an extract of propolis obtained with edible vegetable oil (ODEP) and to identify antifungal compounds in this extract. Propolis sample was extracted with canola oil. After filtration, the oily liquid extract was submitted to solvent partition and dried to obtain ODEP, which was tested in vitro against Candida albicans strains. ODEP was fractioned on Sephadex and by high-performance liquid chromatography (HPLC). Active fractions and/or a pure compound were analyzed by nuclear magnetic resonance, liquid chromatographic mass spectrometry (LC-MS) and liquid chromatographytandem mass spectrometry (LC-MS/MS) to characterize their chemical composition. Bioassay-guided fractionation allowed the isolation of dihydrokaempferide, which was also quantified in ODEP by HPLC together with the total flavonoid content. Kaempferide and isosakuranetin were identified by LC-MS and LC-MS/MS in fractions with a potential activity against C. albicans. In vitro assays showed that some fractions from ODEP produced better inhibition of C. albicans than the propolis extract itself. PRACTICAL APPLICATIONSAqueous or ethanolic extracts of propolis (EEP) are widely used in alternative homemade medicine products mainly because of their antimicrobial and healing properties. Edible vegetal oils are known to extract bioactive compounds from propolis. The resulting extract (ODEP) has several advantages over the common EEP, such as the possibility of new pharmaceutical presentations for topical or internal applications. Because of the absence of ethanol in its formulation, edible ODEP are expected to be more tolerated. In this study, ODEP was active in vitro against Candida albicans strains. This supports the use of ODEP as an alternative to EEP and also its potential for topical application in combination with antifungal drugs. In addition, the ingestion of ODEP (e.g., contained in gelatin capsules), which have a high percentage of flavonoids, could be of nutritional value, helping to reach the recommended daily amounts of flavonoids and phenolic compounds. bs_bs_banner Journal of Food Quality