1,720,981 research outputs found
The transcription factor Foxm1 controls pro-stemness microRNAs in cerebellar neural stem cells (NSCs)
Full text linkBackground: Cerebellar neural stem cells (NSCs) maintenance is of great interest since NSCs can be used to treat impaired cells and tissues or improve regenerative power of degenerating cells in neurodegenerative diseases or spinal cord injuries. Under maintenance conditions, NSCs express a number of Hedgehog-Gli (Hh-Gli) linked and stemness genes (e.g. Nanog, Oct4, Sox2) whose mechanisms of regulation have been under investigation. However, the interplay between transcription factors and microRNAs in NSCs is still being charted.
Aim: Identification of new molecular players involved in NSCs’ maintenance with particular interest in the major regulatory pathway Hedgehog-Gli.
Materials and Methods: Cells used for the study were NSCs isolated from postnatal day 4 (P4) wild type (C57BL/6) mice cultured both as neurospheres in selective medium and as differentiated NSCs when cultured in medium with serum. NSCs and their differentiated counterparts were analysed by high-throughput technologies. Bioinformatics analysis was used for the identification of the Foxm1-regulated miRNAs; knock-down experiments and clonogenic assays were used for functional studies. Chromatin immunoprecipitation experiments (ChIP) were used to investigate the binding between Foxm1 and its targets and between Foxm1 and its regulators.
Results: NSCs and their differentiated counterparts were analysed using next-generation mRNA- and miRNA-sequencing. The transcriptional analysis allowed the identification of Foxm1 as one of the highest transcripts in NSCs and the miRNA-sequencing provided a number of highly expressed miRNAs. The use of bioinformatics analysis resulted in the Foxm1-regulated miRNAs, miR-15 ~ 16 cluster, miR-17 ~ 92 cluster, miR- 130b and miR-301a. Functional experiments, such as knock-down experiments and clonogenic assays enabled the identification of Foxm1 as a downstream mediator of the Hh-Gli signalling and with the ability to regulate the above mention miRNAs.
Conclusion: The study presented reveals a new Foxm1-microRNAs network with a major role in the maintenance of NSCs. These results add a previously unidentified important molecular aspect that could be used in future neurodegenerative disease studies, thus enriching the field of translational medicine
Quercetin improves the effects of sorafenib on growth and migration of thyroid cancer cells
No full textQuercetin improves the effects of sorafenib on growth
and migration of thyroid cancer cel
MDB-72. BREFELDIN A (BFA) INDUCES CD133 PROTEOLYTIC PROCESSING IN MEDULLOBLASTOMA STEM CELLS (MBSCS)
No full textModeling Brain Tumors: A Perspective Overview of in vivo and Organoid Models
No full textBrain tumors are a large and heterogeneous group of neoplasms that affect the central nervous system and include some of the deadliest cancers. Almost all the conventional and new treatments fail to hinder tumoral growth of the most malignant brain tumors. This is due to multiple factors, such as intra-tumor heterogeneity, the microenvironmental properties of the human brain, and the lack of reliable models to test new therapies. Therefore, creating faithful models for each tumor and discovering tailored treatments pose great challenges in the fight against brain cancer. Over the years, different types of models have been generated, and, in this review, we investigated the advantages and disadvantages of the models currently used
Going Beyond Counting First Authors in Author Co-citation Analysis
Full text linkThe present study examines one of the fundamental aspects of author co-citation analysis (ACA) - the way co-citation
counts are defined. Co-citation counting provides the data on which all subsequent statistical analyses and mappings
are based, and we compare ACA results based on two different types of co-citation counting - the traditional type that
only counts the first one among a cited work's authors on the one hand and a non-traditional type that takes into
account the first 5 authors of a cited work on the other hand. Results indicate that the picture produced through this non-traditional author co-citation counting contains more coherent author groups and is therefore considerably clearer. However, this picture represents fewer specialties in the research field being studied than that produced through the traditional first-author co-citation counting when the same number of top-ranked authors is selected and analyzed. Reasons for these effects are discussed
BRAF mutant colorectal cancer: ErbB2 expression levels as predictive factor for the response to combined BRAF/ErbB inhibitors
Full text linkBackground: Colorectal cancer (CRC) is a heterogeneous disease with a complex biology and a wide number of altered genes such as BRAF, KRAS and PIK3CA. Advances with new-targeted therapies have been achieved and available treating options have prolonged patient's survival. However, BRAF-mutated CRC patients remain unresponsive to available therapies with RAF inhibitors (RAFi) alone or combined with ErbB inhibitors (ErbBi). These unmet needs require further exploitation of oncogenic signaling in order to set up individualized treatments. Methods: To this end, we tested the efficacy of single agent or combined treatments using the BRAFi, vemurafenib and two different ErbBi: panitumumab and afatinib in CRC cells characterized by different molecular phenotypes. Results: Combination strategies with BRAFi and ErbBi achieved a better response in BRAFV600E mutated cells expressing high levels of ErbB2. Conclusions: Our findings support the importance of ErbB2 evaluation in BRAF-mutated CRC patients and its role as a positive predictor factor of response to BRAFi/ErbBi combination
Variations on the Author
Full text link“Variations on the Author” discusses two of Eduardo Coutinho’s recent films (Um Dia na Vida, from 2010, and Últimas Conversas, posthumously released in 2015) and their contribution to the general question of documentary authorship. The director’s filmography is characterized by a consistent yet self-effacing form of authorial self-inscription: Coutinho often features as an interviewer that rather than express opinions propels discourses; an interviewer that is good at listening. This mode of self-inscription characterizes him as an author who is not expressive but who is nonetheless markedly present on the screen. In Um Dia na Vida, however, Coutinho is completely absent form the image, while Últimas Conversas, on the contrary, includes a confessional prologue that moves the director from the margins to the center of his films. This article examines the ways in which these works stand out in the filmography of a director who offers new insights into the notion of cinematic authorship
Appropriate Similarity Measures for Author Cocitation Analysis
Full text linkWe provide a number of new insights into the methodological discussion about author cocitation analysis. We first argue that the use of the Pearson correlation for measuring the similarity between authors’ cocitation profiles is not very satisfactory. We then discuss what kind of similarity measures may be used as an alternative to the Pearson correlation. We consider three similarity measures in particular. One is the well-known cosine. The other two similarity measures have not been used before in the bibliometric literature. Finally, we show by means of an example that our findings have a high practical relevance.information science;Pearson correlation;cosine;similarity measure;author cocitation analysis
Albumin nanoparticles for glutathione-responsive release of cisplatin: new opportunities for medulloblastoma treatment
Full text linkRedox-responsive nanoparticles were synthesized by desolvation of bovine serum albumin followed
by disulfide-bond crosslinking with N, Nʹ-Bis (acryloyl) cystamine. Dynamic light scattering and
transmission electron microscopy studies revealed spherical nanoparticles (mean diameter: 83 nm,
polydispersity index: 0.3) that were glutathione-responsive. Confocal microscopy revealed rapid,
efficient internalization of the nanoparticles by Daoy medulloblastoma cells and healthy controls
(HaCaT keratinocytes). Cisplatin-loaded nanoparticles with drug:carrier ratios of 5%, 10%, and
20% were tested in both cell lines. The formulation with the highest drug:carrier ratio reduced Daoy
and HaCaT cell viability with IC50 values of 6.19 and 11.17 μg mL-1, respectively. The differential
cytotoxicity reflects the cancer cells’ higher glutathione content, which triggers more extensive
disruption of the disulfide bond-mediated intra-particle cross-links, decreasing particle stability and
increasing their cisplatin release. These findings support continuing efforts to improve the safety
and efficacy of antineoplastic drug therapy for pediatric brain tumors using selective nanoparticlebased
drug delivery systems
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