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Objective: Oral squamous cell carcinoma (OSCC) is one of the most common neoplasms worldwide. The current study aimed to identify potential biomarkers associated with OSCC survival. Materials and Methods: Differentially expressed genes (DEGs) in atypical OSCC cases were identified using two public datasets: The Cancer Genome Atlas and the Gene Expression Omnibus database. Receiver operating characteristic (ROC) analysis was performed to identify the cutoff, and the candidate DEGs related to survival. Kaplan–Meier and Cox regression analysis using the categorized genes were employed to identify genes that impact the overall survival in OSCC. Results: A total of 263 OSCC samples and 105 healthy tissues were used to identify 295 upregulated and 131 downregulated genes expressed only in non‐smokers. ROC analyses identified 25 candidate genes associated with death. Survival analyses demonstrated that the following DEGs, namely CSTA, FGFR2, MMP19, OLR1, PCSK1, RAMP2, and CGB5, are potential OSCC prognostic factors. Conclusion: We found that CSTA, FGFR2, MMP19, OLR1, PCSK1, RAMP2, and CGB5 are associated with a low survival rate in OSCC. However, further studies are needed to validate our findings and facilitate the development of these factors as potential biomarkers for OSCC survival. [ABSTRACT FROM AUTHOR]

Objectives: This study investigated the relationship between single-nucleotide polymorphisms (SNPs) in cytokine genes and the susceptibility to Squamous Intraepithelial Lesions (SIL), cervical cancer and HPV infection through a systematic review with meta-analysis. To verify the effect of SNPs, we also analyzed the transcription factor binding affinity using bioinformatics tools. Methods: Seven electronic databases (MEDLINE, Scielo, BIREME, PubMed, Scopus, Web of Science and Science Direct) were searched for case–control studies. Results: A total of 35 relevant case–control studies were meta-analyzed, including 7 cytokine genes and 15 SNPs. SNPs in IL-17A (rs2275913, rs3748067); IL-17 F (rs763780); IL-12A (rs568408); IL-12B (rs3212227); TNFA (rs1800629, rs361525); IL-1B (rs16944); IL-6 (rs1800795); IL-10 (rs1800896) genes were associated with increased risk for cervical cancer. No association was observed between meta-analyzed polymorphisms and SIL. Additional bioinformatics analysis suggested a possible transcriptional regulation pathway of the TNFA and IL-10 genes through the MZF1 (TNFA −308 G > A and IL-10 − 1082A>G) and ZNF263 (TNFA −238 G > A) transcription factors binding. Conclusion: Overall, 10 SNPs in cytokine genes were associated with increased risk for cervical cancer. Therefore, in our meta-analysis, these SNPs demonstrated to be potential biomarkers for predicting or identifying cases of high risk for SIL and cervical cancer. [ABSTRACT FROM AUTHOR]

The present study is a systematic review of the literature that aimed to characterize the profile in animal models used to study perinatal protein malnutrition correlating with the cardiovascular system and the implications of malnutrition to the heart. Therefore, an extensive search was conducted in the PubMed, BVS, and SciELO databases, using combinations of the descriptors protein malnutrition, pregnancy, heart, lactation, and cardiovascular system. A total of 247 articles were found, but after excluding duplicities and applying the inclusion/exclusion criteria, only 12 papers remained. The analysis of the results shows that the diet used in the studies has a protein content of between 17 and 22% for the control animals, and of between 0 and 9% for the animals submitted to perinatal protein malnutrition. The main morphofunctional changes observed in the cardiovascular system are related to high blood pressure, increased apoptosis of cardiomyocytes, and reduction in the absolute size of the heart, among other ultrastructural and molecular changes. [ABSTRACT FROM AUTHOR]

Leptin, one of the main hormones controlling energy homeostasis, has been associated with different cancer types. In oral cancer, its effect is not well understood. We investigated, through in vitro and in vivo assays, whether leptin can affect the neoplastic behavior of oral squamous cell carcinoma. Expression of genes possibly linked to the leptin pathway was assessed in leptin-treated oral squamous cell carcinoma cells and also in tissue samples of oral squamous cell carcinoma and oral mucosa, including leptin, leptin receptor, hypoxia-inducible factor 1-alpha, E-cadherin, matrix metalloproteinase-2, matrix metalloproteinase-9, Col1A1, Ki67, and mir-210. Leptin treatment favored higher rates of cell proliferation and migration, and reduced apoptosis. Accordingly, leptin-treated oral squamous cell carcinoma cells show decreased messenger RNA caspase-3 expression, and increased levels of E-cadherin, Col1A1, matrix metalloproteinase-2, matrix metalloproteinase-9, and mir-210. In tissue samples, hypoxia-inducible factor 1-alpha messenger RNA and protein expression of leptin and leptin receptor were high in oral squamous cell carcinoma cases. Serum leptin levels were increased in first clinical stages of the disease. In animal model, oral squamous cell carcinoma-induced mice show higher leptin receptor expression, and serum leptin level was increased in dysplasia group. Our findings suggest that leptin seems to exert an effect on oral squamous cell carcinoma cells behavior and also on molecular markers related to cell proliferation, migration, and tumor angiogenesis. [ABSTRACT FROM AUTHOR]

Gallic acid is a polyphenolic compost appointed to interfere with neoplastic cells behavior. Evidence suggests an important role of leptin in carcinogenesis pathways, inducing a proliferative phenotype. We investigated the potential of gallic acid to modulate leptin-induced cell proliferation and migration of oral squamous cell carcinoma cell lines. The gallic acid effect on leptin secretion by oral squamous cell carcinoma cells, as well as the underlying molecular mechanisms, was also assessed. For this, we performed proliferation, migration, immunocytochemical and qPCR assays. The expression levels of cell migration-related genes (MMP2, MMP9, Col1A1, and E-cadherin), angiogenesis (HIF-1α, mir210), leptin signaling (LepR, p44/42 MAPK), apoptosis (casp-3), and secreted leptin levels by oral squamous cell carcinoma cells were also measured. Gallic acid decreased proliferation and migration of leptin-treated oral squamous cell carcinoma cells, and reduced mRNA expression of MMP2, MMP9, Col1A1, mir210, but did not change HIF-1α. Gallic acid decreased levels of leptin secreted by oral squamous cell carcinoma cells, accordingly with downregulation of p44/42 MAPK expression. Thus, gallic acid appears to break down neoplastic phenotype of oral squamous cell carcinoma cells by interfering with leptin pathway., (Copyright © 2017 Elsevier GmbH. All rights reserved.)

Objective: The purpose of the current study is to investigate the association between E-cadherin methylation status, hypoxia and OSCC., Methods: HaCat and SCC9 cell lines were submitted to hypoxic treatment, followed by methylation profile analysis (MS-PCR) and analysis of the expression of mRNA gene E-cadherin (RT-PCR). Study group samples comprise individuals affected by potentially malignant lesions Potential Malignant Oral Lesion (PMOL, n=18) and oral squamous cell carcinoma (OSCC, n=28). The control group oral mucosa (OM, n=15) of patients with an oral mucocele. Cell migration ability was evaluated a scratch wound assay in SCC9 and HaCat cell lines RESULTS: E-cadherin mRNA expression in the cell lines SCC9 and HaCat was significantly reduced under hypoxia, regardless of the methylation profile, when compared to the control group. No differences in methylation profile of the E-cadherin were observed among the groups OM, PMOL and OSCC. HaCat and SCC9 presented increases in cell migration rates under hypoxia., Conclusion: The current study demonstrates that hypoxia reduces E-cadherin expression and increase cell migration, regardless of the methylation profile. Additionally, no differences in E-cadherin methylation patterns were observed among OM, PMOL and OSCC., (Copyright © 2017 Elsevier GmbH. All rights reserved.)

The present study aimed to compare levels of VEGFR2 and MMP-9 among control, epithelial dysplasia (ED) and oral squamous cell carcinoma (OSCC) groups. We analyzed 48 patients with oral leukoplakia (OL), 20 patients with OSCC and 21 patients without OL and OSCC. Immunohistochemistry of VEGFR2 and MMP9 were performed and compared among groups. Analysis of tissue immunolocalization of VEGFR2 and MMP-9 assumed non-parametrical distribution and comparison between groups was performed using the Mann-Whitney and Kruskal-Wallis statistical tests. VEGFR2 and MMP9 immunoexpression appeared to correlate with the degree of dysplasia and was observed to increase in lesions with more severe dysplasia as compared to those with lower degrees of dysplasia. Immunoreactivity of MMP-9 was lower in the OL samples compared to the OSCC samples (p = 0.004). We observed no difference in VEGFR2 protein levels between OL and OSCC samples. A positive correlation was found between VEGFR2 and MMP-9 in OL samples (r = +0.452, p = 0.001), however, no correlation was found in OSCC samples (r = -0.042, p = 0.861). In conclusion, the results of the current study suggest that expression of MMP9 and VEGFR2 is associated with ED grading and MMP9 levels are increased in OSCC., (Copyright © 2014 Elsevier GmbH. All rights reserved.)