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1.
Cell Signal ; 92: 110246, 2022 04.
Artigo em Inglês | MEDLINE | ID: mdl-35033667

RESUMO

Medulloblastoma (MB) is the most common and aggressive pediatric intracranial tumor. Estrogen receptor ß (ERß) expression correlates with MB development and its phosphorylation modifies its transcriptional activity in a ligand-dependent or independent manner. Using in silico tools, we have identified several residues in ERß protein as potential targets of protein kinases C (PKCs) α and δ. Using Daoy cells, we observed that PKCα and PKCδ associate with ERß and induce its phosphorylation. The activation of ERß promotes MB cells proliferation and invasion, and PKCs downregulation dysregulates these steroid receptor mediated processes. Our data suggest that these kinases may play a crucial role in the regulation of the ERß transcriptional activity. Overexpression of both PKCα and PKCδ in MB biopsies samples supports their relevance in MB progression.


Assuntos
Neoplasias Cerebelares , Receptor beta de Estrogênio , Meduloblastoma , Proteína Quinase C-alfa/metabolismo , Proteína Quinase C-delta/metabolismo , Proteína Quinase C , Linhagem Celular Tumoral , Proliferação de Células , Criança , Receptor alfa de Estrogênio , Receptor beta de Estrogênio/genética , Receptor beta de Estrogênio/metabolismo , Humanos , Meduloblastoma/genética , Meduloblastoma/metabolismo
2.
Int J Mol Sci ; 22(21)2021 Oct 20.
Artigo em Inglês | MEDLINE | ID: mdl-34768763

RESUMO

A connection between compromised asymmetric cell division (ACD) and tumorigenesis was proven some years ago using Drosophila larval brain neural stem cells, called neuroblasts (NBs), as a model system. Since then, we have learned that compromised ACD does not always promote tumorigenesis, as ACD is an extremely well-regulated process in which redundancy substantially overcomes potential ACD failures. Considering this, we have performed a pilot RNAi screen in Drosophila larval brain NB lineages using RasV12 scribble (scrib) mutant clones as a sensitized genetic background, in which ACD is affected but does not cause tumoral growth. First, as a proof of concept, we have tested known ACD regulators in this sensitized background, such as lethal (2) giant larvae and warts. Although the downregulation of these ACD modulators in NB clones does not induce tumorigenesis, their downregulation along with RasV12 scrib does cause tumor-like overgrowth. Based on these results, we have randomly screened 79 RNAi lines detecting 15 potential novel ACD regulators/tumor suppressor genes. We conclude that RasV12 scrib is a good sensitized genetic background in which to identify tumor suppressor genes involved in NB ACD, whose function could otherwise be masked by the high redundancy of the ACD process.


Assuntos
Divisão Celular Assimétrica/genética , Drosophila melanogaster/genética , Drosophila melanogaster/metabolismo , Genes Supressores de Tumor/fisiologia , Células-Tronco Neurais/metabolismo , Animais , Regulação para Baixo , Proteínas de Drosophila/genética , Larva/citologia , Larva/genética , Larva/metabolismo , Proteínas de Membrana/genética , Interferência de RNA , Proteínas ras/genética , Proteínas ras/metabolismo
3.
Mycopathologia ; 181(9-10): 671-9, 2016 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-27193417

RESUMO

Diapers create particular conditions of moisture and friction, and with urine and feces come increased pH and irritating enzymes (lipases and proteases). Fungi can take advantage of all these factors. Candida yeasts, especially C. albicans, are responsible for the most frequent secondary infections and are isolated in more than 80 % of cases. Correct diagnosis is important for ensuring the correct prescription of topical antimycotics. Nystatin, imidazoles and ciclopirox are effective. It is important to realize there are resistant strains. Dermatophytes can infect the diaper area, with the most common agent being Epidermophyton floccosum. The clinical characteristics of dermatophytosis are different from those of candidiasis, and it can be diagnosed and treated simply. Malassezia yeasts can aggravate conditions affecting the diaper area, such as seborrheic dermatitis, atopic dermatitis, and inverse psoriasis. Additional treatment is recommended in this case, because they usually involve complement activation and increased specific IgE levels. Erythrasma is a pseudomycosis that is indistinguishable from candidiasis and may also occur in large skin folds. It is treated with topical antibacterial products and some antimycotics.


Assuntos
Dermatite de Contato/complicações , Dermatomicoses/epidemiologia , Dermatomicoses/microbiologia , Fungos/classificação , Fungos/isolamento & purificação , Antifúngicos/uso terapêutico , Dermatomicoses/tratamento farmacológico , Dermatomicoses/patologia , Humanos
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