Malignant neoplasms may be composed of several cell groups, including cancer stem cells (CSC). These cells have been related with the capacity of metastasis, relapse and resistance to multiple drugs during chemotherapy. This study aims to identify CSC biomarkers and their expression pattern in human head and neck carcinomas. This study was conducted following the PRISMA checklist. The search for articles was carried out in five databases (PubMed, Scopus, Web of Science, Lilacs and Scielo). The articles found were selected in two phases: 1) reading the titles and / or abstract and 2) reading the full text. At the end, the selected articles were evaluated by QUADAS-2. Most studies evaluated oral neoplastic tissues and, as a control, samples of normal local mucosa. All studies performed immunohistochemistry as a method of immunolocalization and some also applied immunofluorescence. The most commonly used biomarker was CD44. However, other such as Sox2, Oct4, Nestin, Nanog, BMI1, ALDH1, CD133 and CD166 were also found. Several biomarkers were (ALDH1, Sox2, Oct4, ABCB5, AGR2 and TAZ) correlated with clinical characteristics of the tumor, such as staging, tumor size and lymph node metastasis. These data reinforce the CSC theory and favor the use of these biomarkers as possible determinants of prognosis.
Summary
Over the past years, studies have described that users of antipsychotics are less likely to develop cancer than the population in general due to cytotoxic properties of this class of drugs on cancer cells. For this reason, Pimozide has been widely studied as a potential anticancer treatment, and satisfactory results in melanoma, central nervous system tumours, osteosarcoma, neuroblastoma, myeloproliferative neoplasms, breast, lung, prostate, ovarian, colorectal, pancreatic, and hepatocellular carcinoma have been showed. Moreover, advantages as clinical use approved by the Food and Drug Administration (FDA), high clinical safety, low side effects, and reasonable price have stimulated the treatment with Pimozide instead of other agents. The action mechanism remains unclear, but three vias associated to cancer stem cell (CSC) hypothesis show that Pimozide: (a) blocks CSC features, as epithelial‐to‐mesenchymal transition (EMT), through inhibition of Wnt‐β/catenin signalling; (b) acts as an inhibitor of signal transducer and activator of transcription (STAT‐3 and 5), pathway which is activated and up‐regulated in CSCs; (c) inhibits ubiquitine specific protease (USP1) and WD repeat‐containing protein 48 (WDR48), that are proteins responsible to inhibit the differentiation and to maintain the cell in an undifferentiated state. Based on this perspective, the aim of this manuscript is to review the antineoplastic role of Pimozide during tumorigenesis and its potential to revert the process of undifferentiation and proliferation of CSC through different vias.
AIRmax (maximal inflammation) and AIRmin (minimal inflammation) mice show distinct susceptibilities to pristane-induced arthritis (PIA). The Slc11a1 gene, which regulates macrophage and neutrophil activity, is involved in this infirmity. AIRmaxSS mice homozygous for the non-functional Slc11a1 S (gly169asp) allele obtained by genotype-assisted crosses from AIRmax and AIRmin mice are more susceptible than mice homozygous for the Slc11a1 resistant (R) allele. The present work sought to identify the quantitative trait loci (QTL) regulating PIA and to examine the interactions of these QTL with Slc11a1 alleles in modulating PIA. Mice were given two ip injections of 0.5 mL pristane at 60 day intervals, and the incidence and severity of PIA was scored up to 160 days. Genome-wide linkage studies were performed to search for arthritis QTL in an F2 (AIRmax × AIRmin, n = 290) population. Significant arthritis QTL (LODscore>4) were detected on chromosomes 5 and 8, and suggestive QTL on chromosomes 7, 17 and 19. Global gene expression analyses performed on Affymetrix mouse 1.0 ST bioarrays (27k genes) using RNA from arthritic or control mice paws showed 419 differentially expressed genes between AIRmax and AIRmin mice and demonstrated significantly (P<0.001) over-represented genes related to inflammatory responses and chemotaxis. Up-regulation of the chemokine genes Cxcl1, Cxcl9, Cxcl5, Cxcl13 on chromosome 5 was higher in AIRmaxSS than in the other lines. Macrophage scavenger receptor 1 and hemeoxigenase (decycling) 1 genes on chromosome 8 were also expressed at higher levels in AIRmaxSS mice. Our results show that the gene expression profiles of the two arthritis QTL (on chromosomes 5 and 8) correlate with Slc11a1 alleles, resulting in enhanced AIRmaxSS mice susceptibility to PIA.
In the present study, neurologic diseases, HNC, male sex and underweight were associated to impaired swallowing efficacy. Underweight, independently of the other variables, was not associated with impaired swallowing safety.
This paper studies the mechanical properties including traction, flexion, compression, and hardness characteristics of a composite made from the combination of epoxy resin and granitic stone powder from the fold-and-thrust belt located in the municipality of Nossa Senhora da Glória, in the state of Sergipe, Brazil. Chemical and mineralogical analyses of the stone and analysis by SEM of the particle/matrix interface are performed. Two Granite types, named 53-A and 12-A, were incorporated with different mass percentages of 0%, 30% and 50%, in the polymeric matrix, DGEBA, formed by the Araldite polymer GY 279 and the curing agent Aradur 2963. The test results with 50% show a compression of 79 MPa with a maximum increase of 121% compared with the pure epoxy resin.
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