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Background:: Oral cancer is a significant health problem worldwide. Oral squamous cell carcinoma (OSCC) is a malignant neoplasm of epithelial cells that mostly affects different anatomical sites in the head and neck and derives from the squamous epithelium or displays similar morphological characteristics. Generally, OSCC is often the end stage of several changes in the stratified squamous epithelium, which begin as epithelial dysplasia and progress by breaking the basement membrane and invading adjacent tissues. Several plant-based drugs with potent anti-cancer effects are considered inexpensive treatments with limited side effects for cancer and other diseases. Objective:: The aim of this review is to explore whether some Brazilian plant extracts or constituents exhibit anti-tumorigenic activity or have a cytotoxic effect on human oral carcinoma cells. Methods:: Briefly, OSCC and several metabolites derived from Brazilian plants (i.e., flavonoids, vinblastine, irinotecan, etoposide and paclitaxel) were used as keywords to search the literature on PubMed, GenBank and GeneCards. Results:: The results showed that these five chemical compounds found in Cerrado Biome plants exhibit anti-neoplastic effects. Evaluating the compounds revealed that they play a main role in the regulation of cell proliferation. Conclusion:: Preserving and utilising the biodiversity of our planet, especially in unique ecosystems, such as the Cerrado Biome, may prove essential to preserving and promoting human health in modern contexts.

Background Head and neck squamous cell carcinoma (HNSC) etiopathogenesis remains unclear, and the biological changes with the activation of heat shock proteins (HSPs) and prion protein (PRNP) promoted by hypoxia in HNSC are undetermined. Objective This study investigates hypoxia's effect in lymph node metastasis by PRNP expression changes and its main partners. Methods The study combined a theoretical/cell culture study with a case-control study. First, bioinformatics and cell culture were performed. A case-control study was performed in a second step by comparing HNSC patients with and without lymph node metastasis. Analyses The Cancer Genome Atlas (TCGA) data source validate the theory in the global population study. Results Bioinformatics analysis suggests that hypoxia-inducible factor-1α (HIF1A) is associated with HSPA4, HSP90AA1, and PRNP expression. TCGA data validate the hypothesis that higher HSP90AA1, HSPA4, and PRNP are related to metastases and low survival. Herein, the cell study demonstrated that muted PRNP did not respond to hypoxia. Conclusions Our results collectively provide the first evidence that PRNP promotes HNSC lymph node metastasis progression through the upregulation of HSPA4, HSP90AA1, and HIF1A. Our findings may provide a molecular basis for the promoting Role of PRNP in HNSC progression.

Pigments from microorganisms have triggered great interest in the market, mostly by their "natural" appeal, their favorable production conditions, in addition to the potential new chemical structures or naturally overproducing strains. They have been used in: food, feed, dairy, textile, pharmaceutical, and cosmetic industries. The high rate of pigment production in microorganisms recovered from Antarctica in response to selective pressures such as: high UV radiation, low temperatures, and freezing and thawing cycles makes this a unique biome which means that much of its biological heritage cannot be found elsewhere on the planet. This vast arsenal of pigmented molecules has different functions in bacteria and may exhibit different biotechnological activities, such as: extracellular sunscreens, photoprotective function, antimicrobial activity, biodegradability, etc. However, many challenges for the commercial use of these compounds have yet to be overcome, such as: the low stability of natural pigments in cosmetic formulations, the change in color when subjected to pH variations, the low yield and the high costs in their production. This review surveys the different types of natural pigments found in Antarctic bacteria, classifying them according to their chemical structure. Finally, we give an overview of the main pigments that are used commercially today.

Objectives: This study investigated the relationship between single-nucleotide polymorphisms (SNPs) in cytokine genes and the susceptibility to Squamous Intraepithelial Lesions (SIL), cervical canc...

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.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.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.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.

BACKGROUND: Breast cancer is a common neoplasm in women worldwide. Its varying patterns of incidence and clinical prognosis in Brazil make it an important and complex public health problem that needs to be solved. OBJECTIVES: To analyze the temporal dynamics of hospital admissions and deaths due to female breast cancer in the state of Alagoas, Brazil, from 2009 to 2019. DESIGN AND SETTING: Cross-sectional study including secondary data from hospital admissions and deaths due to female breast cancer in Alagoas. METHODS: A joinpoint regression model was constructed for temporal analysis of hospital admissions and deaths due to female breast cancer in Alagoas, over this period. The hospital information system of the Department of Informatics of the National Health System was used. RESULTS: There were 5,801 hospitalizations and 633 hospital deaths due to neoplasm in Alagoas over the period. The age group from 50 to 59 years old stood out, corresponding to 28.1% of hospitalizations and 31.1% of registered deaths. An increasing trend in the rate of hospital admissions was observed (average annual percentage change, AAPC = 14.0; P-value < 0.001), from 14.9/100,000 inhabitants in 2009 to 53.6 in 2019. There was a growth trend in the in-hospital mortality rate (AAPC = 19.8; P-value < 0.001), from 6.3% in 2009 to 11.0% in 2019. CONCLUSION: The results indicated an increasing trend of hospital admissions and mortality rates in the state of Alagoas, with a higher percentage of hospitalizations and deaths in the 50-59 age group.

RESUMO Introdução: o câncer de mama é a neoplasia maligna mais comum em mulheres no mundo. A cirurgia tem sido o tratamento tradicional e, geralmente consiste em mastectomia com linfadenectomia, podendo causar dor pós-operatória. Por isso, buscamos estudar técnicas anestésicas regionais que possam minimizar esse efeito, como o bloqueio interpeitoral (PEC). Métodos: estudo controlado randomizado com 82 pacientes com câncer de mama submetidos à mastectomia com linfadenectomia de Janeiro de 2020 a Outubro de 2021, em hospital oncológico. Intervenções: dois grupos randomizados (controle - anestesia geral exclusiva e grupo PECS - anestesia geral e bloqueio PEC com levobupivacaína/ropivacaína). Aplicou-se um questionário com Escala Visual Analógica da dor 24h pós-cirurgia. Utilizamos os testes de Shapiro-Wilk, Mann-Whitney e Quiquadrado e analisamos os dados em R versão 4.0.0. Estudo registrado em Ensaios Clínicos Brasileiros (REBec). Resultados: no grupo PEC, 50% não apresentava dor 24 horas após a cirurgia enquanto no grupo controle, 42,86% negava quadro álgico. A maioria que apresentou dor classificou-a como dor leve (EVA de 1 a 3) - (42,50%) grupo PEC e (40,48%) controle (p=0,28). Apenas 17,50% consumiram opioides no grupo PEC, semelhante ao grupo controle com 21,43%. (p=0,65), (17,50%) grupo PEC e (21,43%) grupo controle (p=0,65). Houve baixo índice de complicações como PONV (náuseas, vômitos, cefaleia) em ambos os grupos. Na análise de subgrupo, não houve diferença estatística entre os grupos que usaram Levobupivacaína ou Ropivacaína quanto a dor pós-operatória e o consumo de opioides. Discussão: o grupo estudado apresentou baixa taxa de dor no pós-operatório e isso influenciou na análise estatística. Não houve diferença estatística quanto a dor pós-operatória entre grupos. Conclusão: não foi possível demonstrar melhores resultados com a associação do bloqueio PEC com analgesia intravenosa total. São necessários novos estudos para avaliar a eficácia do bloqueio anestésico no intraoperatório e pós-operatório.

Schwann cells were identified in the tumor surrounding area prior to initiate the invasion process underlying connective tissue. These cells promote cancer invasion through direct contact, while paracrine signaling and matrix remodeling are not sufficient to proceed. Considering the intertwined structure of signaling, regulatory, and metabolic processes within a cell, we employed a genome-scale biomolecular network. Accordingly, a meta-analysis of Schwann cells associated transcriptomic datasets was performed, and the core information on differentially expressed genes (DEGs) was obtained by statistical analyses. Gene set over-representation analyses was performed on core DEGs to identify significantly functional and pathway enrichment analysis between Schwann cells and, lung adenocarcinoma (LUAD) and lung squamous cell carcinoma (LUSC). DEGs were further integrated with genome-scale human biomolecular networks. miRNAs were proposed by the reconstruction of a transcriptional and post-transcriptional regulatory network. Moreover, microarray-based transcriptome profiling was performed, and the prognostic power of selected dedifferentiated Schwann cell biomolecules was predicted. We observed that pathways associated with Schwann cells dedifferentiation was overexpressed in lung cancer samples. However, genes associated with Schwann cells migration inhibition system were downregulated. Besides, miRNA targeting those pathways were also deregulated. In this study, we report valuable data for further experimental and clinical analysis, because the proposed biomolecules have significant potential as systems biomarkers for screening or for therapeutic purposes in perineural invasion of lung cancer.

Polymorphisms in Toll-like receptors (TLRs) genes have been associated with cervical cancer, but some inconsistencies were found in the results. The present study aimed to investigate the role of polymorphisms in the TLRs genes in cervical cancer, through meta-analysis and bioinformatics analysis. Searches were performed in PubMed, Science Direct, Scopus and Web of science online databases until November 2020. For bioinformatics analysis, we used SNP2TFBS, Raptor-X, MUpro, Gene Expression Profiling Interactive Analysis (GEPIA). The results of meta-analysis showed that the +1196T (rs4986791 TLR4), +7764T (rs1927911 TLR4), -1486C (rs187084 TRL9) +2848A (rs352140 TRL9) alleles carriers and -2604G/G (rs10759931 TLR4), -1237C/C (rs5743836 TRL9) genotypes were associated with an increased risk for cervical cancer. The bioinformatics analysis revealed that the -1237TC (rs5743836) and -1486TC (rs187084) polymorphisms can affect the transcription factors binding sites (RELA, NFKB1 and THAP1) in the TLR9 gene, and the +2848GA (rs352140) polymorphism seems to alter the structure and stability of TLR4 protein. Additionally, using GEPIA, was observed a significantly high of IL-1β, IL-18 and TNF-α expression in cervical cancer tissues compared to normal tissues. These finds indicate that polymorphisms in the TLR4 and TLR9 genes can affect intracellular signaling and, consequently, change the patterns of the immune response, leading to an increased risk for cervical cancer.

Glioblastoma multiforme (GBM) is a malignant brain tumor with one of the worst general survivorship cases among the existing neoplasia. This aggressiveness is due to its complex molecular heterogeneity, immunohistochemistry and genetics. The current therapeutic approach brings little contribution to the improvement of the survival of the patients. Due to that, new forms of treatment have been explored, one of them being immunotherapy. In this aspect, the inflammasome pathway, which induces inflammation and immunosuppressive tumor response, contributing to the progression of the tumor, seems to be a new alternative to improve the treatment efficacy and the survival of the patients.

INTRODUCTION: Leprosy is a chronic infectious disease caused by Mycobacterium leprae.This study aimed to analyze the epidemiological, temporal, and spatial dynamics ofleprosy in a municipality in northeastern Brazil. METHODS: This is an ecological study on new leprosy cases in the population of Arapiraca (Alagoas, Northeast Region, Brazil), from 2008 to 2017. Data extracted from a national database were analyzed forepidemiological indicators, factors associated with physical disabilities, and spatialanalysis in the neighborhoods of Arapiraca. RESULTS: A total of 292 new cases of leprosy were recorded, particularly occurring among the following groups: women, the age group of 46-59 years, brown-skinned individuals, people with less than eight years of schooling, and urban residents; the new cases were also predominantly the tuberculoid form and were of the paucibacillary classification of the disease. Almost 1/3 of the people had some degree of physical disability, which was mainly associated with the group 60 years of age and older, black ethnicity, and the multibacillary clinical form of leprosy. The joinpoint regression showed a stationary temporal behavior of indicators. There was a heterogeneous spatial distribution with active transmission areas, especially in the neighborhoods Primavera, Baixão, Ouro Preto, and downtown. CONCLUSIONS: The epidemiological indicators revealed complexity in the process of leprosy development. These spatial and temporal studies are relevant to help in the planning, monitoring, and guidance of interventions in the municipality. The spatial analysis showed heterogeneous distribution in the analyzed neighborhoods.

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.

INTRODUCTION We aimed to analyze trends in Schistosomiasis positivity, mortality, and hospitalization rates in Northeast Brazil. METHODS We conducted an ecological study using data from the Brazilian Schistosomiasis Control Program, and Hospital and Mortality Information Systems. A joinpoint regression model was used for temporal analysis. RESULTS The positivity(−4.7%;p0.05). However, the hospitalization in Alagoas(27.1%;p

Polymorphisms in the cytokine genes have been associated with immunological variations that lead to susceptibility to HPV infection and the development of cervical cancer. This study aims to evaluate the influence of TNF-α -308G>A and IL-10 -819C>T polymorphisms on cervical cancer susceptibility through a case-control study, meta-analysis and Trial Sequential Analysis (TSA). A case–control study including 45 cervical cancer patients and 179 healthy controls was conducted. TNF-α -308G>A and IL-10 -819C>T polymorphisms were analysed using real-time polymerase chain reaction (PCR real-time). For the meta-analysis, published articles were electronically searched through the databases PubMed, Science Direct, Scopus and Web of science. In the case-control study, the IL-10 -819T carriers were associated with an increased risk of cervical cancer. While the TNF-α -308G>A polymorphism was not associated with cervical cancer, but sample power was less than 80% (70%). The meta-analysis and TSA showed that both TNF-α -308A (Overall, Asian, Caucasian and African analysis) and IL-10 -819T (Overall and Asian analysis) carriers were associated with an increased risk of cervical cancer. In conclusion, the IL-10 -819C>T and TNF-α -308G>A polymorphisms may be an important genetic biomarker for identifying the risk of developing cervical cancer.

Clock genes work as an auto-regulated transcription-translational loop of circadian genes that drives the circadian rhythms in each cell and they are essential to physiological requests. Since metabolism is a dynamic process, it involves several physiological variables that circadian cycling. The clock genes alterations can affect multiple systems concomitantly, because they constitute the promoter factors for relevant metabolic pathways. Considering the intertwined structure of signaling, regulatory, and metabolic processes within a cell, we employed a genome-scale biomolecular network. Accordingly, a meta-analysis of diabetic-associated transcriptomic datasets was performed, and the core information on differentially expressed genes (DEGs) was obtained by statistical analyses. In the current study, meta-analysis was performed on type 2 diabetes, circadian rhythm-related genes, and breast, bladder, liver, pancreas, colon and rectum cancer-associated transcriptome data using the integration of gene expression profiles with genome-scale biomolecular networks in diabetes samples. First, we detected downregulated and upregulated DEGs in mouse cortex and hypothalamus samples of mice with sleep deprivation. In summary, upregulated genes active genes associated with oxidative phosphorylation, cancer and diabetes, mainly in hypothalamus specimens. In cortex, we observed mainly downregulation of immune system. DEGs were combined with 214 circadian rhythm related genes to type 2 DM and cancer samples. We observed that several common genes deregulated in both diseases. Klf10, Ntkr3, Igf1, Usp2, Ezh2 were both downregulated in type 2 DM and cancer samples, while Arntl2 and Agrp were upregulated. It seems that the changes in mRNA are contributing to the phenotypic changes in type 2 DM, resulting in phenotypic changes associated with the malignant transformation. Taking those genes to perform a survival analysis, we found only Igf1, Usp2 and Arntl2 genes associated with patient outcomes. While Igf1 and Usp2 downregulation had a negative impact, Arntl2 upregulation was associated with poor survival both in BLCA and BRCA cancer samples. Our data stimulate efforts in news studies to achieve the experimental and clinical validation about these biomolecules.

Aim: Oral health can affect the quality of life (QoL), and the oral health impact profile-14 (OHIP-14) index utility to assess this impact. Objective: To study the impact of oral health on quality of life of patients older than 50 years, verifying, preliminarily, the reliability of the OHIP-14 index. Methods: We studied the internal consistency of the index by applying the alpha-Cronbach coefficient. The OHIP-14 index was obtained by the additive method, and the patients were divided according to gender, age and education level. Results: Considering all the issues that make up the OHIP-14 index, good internal consistency was obtained. The homogeneity of the questions in the index, it was confirmed that condition, since the difference between the value of the total Cronbach's alpha-factor and issues was less than 0.03. The values of the intraclass correlation show the stability of their items. Conclusion: The OHIP-14 index was consistent and proved to be there relatively high impact of oral health on QoL of patients, with a predominance of physical pain in its components "feel bothered to feed" and "feel pain in the mouth" as well as the components of the psychological impairment.

// Talita Antunes Guimaraes 1 , Lucyana Conceicao Farias 1 , Eliane Sobrinho Santos 1, 5 , Carlos Alberto de Carvalho Fraga 6, 7 , Lissur Azevedo Orsini 2 , Leandro de Freitas Teles 1 , John David Feltenberger 3 , Sabrina Ferreira de Jesus 1 , Marcela Goncalves de Souza 1 , Sergio Henrique Sousa Santos 4 , Alfredo Mauricio Batista de Paula 1 , Ricardo Santiago Gomez 2, * Andre Luiz Sena Guimaraes 1, * 1 Department of Dentistry, Universidade Estadual de Montes Claros, Montes Claros, Minas Gerais, Brazil 2 Department of Clinical, Surgery and Oral Pathology, School of Dentistry, Universidade Federal de Minas Gerais, Belo Horizonte, Brazil 3 Texas Tech University Health Science Center, Lubbock, TX, USA 4 Institute of Agricultural Sciences, Food Engineering College, Universidade Federal de Minas Gerais (UFMG), Montes Claros, Minas Gerais, Brazil 5 Instituto Federal de Educacao, Ciencia e Tecnologia do Norte de Minas Gerais (IFNMG), Aracuai, Minas Gerais, Brazil 6 Faculdades Integradas Pitagoras, Montes Claros, Minas Gerais, Brazil 7 Faculdades Unidas do Norte de Minas, Montes Claros, Minas Gerais, Brazil * These authors contributed equally to this work Correspondence to: Andre Luiz Sena Guimaraes, email: andreluizguimaraes@gmail.com Ricardo Santiago Gomez, email: rsgomez.ufmg@gmail.com Keywords: proliferation, oral cancer, metformin, PDH, LDH-A Received: March 21, 2016 Accepted: July 09, 2016 Published: July 26, 2016 ABSTRACT Background: Metformin is a biguanide, belonging to the oral hypoglycemic agents and is a widely used in the treatment of type 2 diabetes. Evidence indicate that Metformin inhibits cell proliferation in several human cancers and inhibits the Warburg phenomenon in tumor cells. Results: Low PDH levels were observed in OSCC, and Metformin promotes an increase in PDH levels in hypoxic conditions. Metformin also reduced HIF-1α mRNA and protein levels. Metformin demonstrated antiproliferative effects, inhibited migration, increased the number of apoptotic cells and increased the transcription of caspase 3. Objective: The present study aims to explore the effects of Metformin in hypoxic conditions. Specifically, we focused on pyruvate dehydrogenase (PDH), (hypoxia-inducible factor 1α) HIF-1α levels and the oral squamous cell carcinoma (OSCC) cell phenotype. Additionally, we also investigated a theoretical consequence of Metformin treatment. Methods: PDH levels in patients with OSCC and oral dysplasia were evaluated. Metformin was administered in vitro to test the effect of Metformin under hypoxic conditions. The results were complemented by Bioinformatics analyses. Conclusions: In conclusion, our current findings show that Metformin reduces HIF-1α gene expression and increases PDH expression. Metformin inhibits cell proliferation and migration in the OSCC cell line model. Additionally, Metformin enhances the number of apoptotic cells and caspase 3 levels. Interestingly enough, Metformin did not increase the mutant p53 levels under hypoxic conditions.

CNPq - Conselho Nacional de Desenvolvimento Científico e Tecnológico FAPEMIG - Fundação de Amparo à Pesquisa do Estado de Minas Gerais CAPES - Coordenação de Aperfeiçoamento de Pessoal de Nível Superior The purpose of the current study was to develop and test a theoretical model that could explain the mechanism of action of gallic acid (GA) in the oral squamous cell carcinoma context for the first time. The theoretical model was developed using bioinformatics and interaction network analysis to evaluate the effect of GA on oral squamous cell carcinoma. In a second step to confirm theoretical results, migration, invasion, proliferation, and gene expression (Col1A1, E-cadherin, HIF-1α, and caspase-3) were performed under normoxic and hypoxic conditions. Our study indicated that treatment with GA resulted in the inhibition of cell proliferation, migration, and invasion in neoplastic cells. Observation of the molecular mechanism showed that GA upregulates E-cadherin expression and downregulates Col1A1 and HIF-1α expression, suggesting that GA might be a potential anticancer compound. In conclusion, the present study demonstrated that GA significantly reduces cell proliferation, invasion, and migration by increasing E-cadherin and repressing Col1A1.

Background Skin cancer represents the most common worldwide malignancy. Angiogenesis is an important factor in tumor growth and metastasis. Given these facts, the purpose of the current study was to compare the levels of angiogenic proteins in the context of the most common malignant and premalignant skin lesions. Methods Immunohistochemistry of CD31, HIF1A, VEGFR1 and VEGFR2 was performed in basal cell carcinoma (BCC), actinic keratosis (AK) and squamous cell carcinoma of the skin (SCCS). Results SCCS presented with increased levels of HIF1A, VEGFR1 and VEGFR2 in comparison to AK. In addition, SCCS also demonstrated increased levels of HIF1A to BCCLR or BCCHR. BCC presented with more vessels than AK. However, no correlation was observed among CD31, HIF1A, VEGFR1 and VEGFR2. Conclusions SCCS presented with higher levels of HIF1A, VEGFR1 and VEGFR2, while BCC demonstrated an increased number of vessels in relation to AK. These data suggest that antiangiogenic therapy might be useful for skin cancer treatment.

INTRODUCTION The Renin-Angiotensin System (RAS) has emerged as being related to vascular disease. Recently the RAS has been associated with obesity, diabetes, and even cancer. OBJECTIVE This review and Bioinformatics analyses focuses on the investigation of Angiotensinconverting enzymes (ACE and ACE2) as therapeutical targets for Malignant Epithelial Neoplasia, specifically for Oral Squamous Cell Carcinoma (OSCC). CONCLUSION The literature review and Bioinformatics analyses showed that ACE and ACE2 are interesting targets for OSCC treatment. Studies involving RAS and OSCC should be encouraged for experimental validation.

CNPq - Conselho Nacional de Desenvolvimento Científico e Tecnológico FAPEMIG - Fundação de Amparo à Pesquisa do Estado de Minas Gerais CAPES - Coordenação de Aperfeiçoamento de Pessoal de Nível Superior 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.

Squamous cell carcinoma (SCC) and basal cell carcinoma (BCC) are 2 skin neoplasms with distinct potentials to invasion and metastasis. Actinic keratosis (AK) is a precursor lesion of SCC. Immunohistochemistry was performed to evaluate the expression of MMP-2 and MT1-MMP in samples of BCC (n = 29), SCC (n = 12), and AK (n = 13). The ratio of positive cells to total cells was used to quantify the staining. Statistical significance was considered under the level P < .05. We found a higher expression of MMP-2 in tumor stroma and parenchyma of SCC as compared to BCC. The expression of this protein was also similar between SCC and its precursor actinic keratosis, and it was higher in the stroma of high-risk BCC when compared to low-risk BCC. MT1-MMP, which is an activator of MMP-2, was similarly expressed in all groups. Our results suggest that MMP-2 expression may contribute to the distinct invasive patterns seen in SCC and BCC.

The presence of cervical metastasis is responsible for high morbidity and mortality rates in individuals with head and neck squamous cell carcinoma (HNSCC). S100A4, a pleiotropic EF-hand calcium-binding protein, is expressed in various normal and cancer cell types. During cancer progression, molecular disturbances in S100A4 can modulate the activity and expression of pre-metastatic and metastatic genes. In this study, we investigated the association between S100A4 methylation status and protein expression as well as the expression of the S100A4 related-proteins annexin A2 (ANXA2), matrix metallopeptidase-9, and endoglin, for metastasis and other clinicopathological parameters in HNSCC. Formalin-fixed, paraffin-embedded blocks of metastatic and non-metastatic HNSCC and matched cervical lymph node (LN) samples (metastatic LN = mLN, non-metastatic = nmLN, and control LN (lymphadenitis) = cLN) were submitted for methylation specific-polymerase chain reaction and immunohistochemistry. Our results showed that S100A4 methylation status failed to demonstrate association with cervical metastasis and other clinicopathological factors related to HNSCC. HNSCC samples from patients that presented with metastatic disease showed high S100A4 and endoglin expression (p

Although studies have provided significant evidence about the role of RAS in mediating cancer risk in type 2 diabetes mellitus (DM), conclusions about the central molecular mechanisms underlying this disease remain to be reached, because this type of information requires an integrative multi-omics approach. In the current study, meta-analysis was performed on type 2 diabetes and breast, bladder, liver, pancreas, colon and rectum cancer-associated transcriptome data, and reporter biomolecules were identified at RNA, protein, and metabolite levels using the integration of gene expression profiles with genome-scale biomolecular networks in diabetes samples. This approach revealed that RAS biomarkers could be associated with cancer initiation and progression, which include metabolites (particularly, aminoacyl-tRNA biosynthesis and ABC transporters) as novel biomarker candidates and potential therapeutic targets. We detected downregulation and upregulation of differentially expressed genes (DEGs) in blood, pancreatic islets, liver and skeletal muscle from normal and diabetic patients. DEGs were combined with 211 renin-angiotensin-system related genes. Upregulated genes were enriched using Pathway analysis of cancer in pancreatic islets, blood and skeletal muscle samples. It seems that the changes in mRNA are contributing to the phenotypic changes in carcinogenesis, or that they are as a result of the phenotypic changes associated with the malignant transformation. Our analyses showed that Ctsg and Ednrb are downregulated in cancer samples. However, by immunohistochemistry experiments we observed that EDNRB protein showed increased expression in tumor samples. It is true that alterations in mRNA expression do not always reflect alterations in protein expression, since post-translational changes can occur in proteins. In this study, we report valuable data for further experimental and clinical analysis, because the proposed biomolecules have significant potential as systems biomarkers for screening or for therapeutic purposes in type 2 diabetes and cancer-associated pathways.

CNPq - Conselho Nacional de Desenvolvimento Científico e Tecnológico FAPEMIG - Fundação de Amparo à Pesquisa do Estado de Minas Gerais CAPES - Coordenação de Aperfeiçoamento de Pessoal de Nível Superior Outra Agência 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.

BACKGROUND: The histopathology and immune responses of the healing process of leishmaniasis are still poorly studied. OBJECTIVES: This study aimed to examine the histopathological and immunological aspects of lesions of patients with cutaneous leishmaniasis before and after different therapeutic methods. METHODS: We studied 23 individuals grouped according to the treatments: Glucantime, Glucantime + Leishvacin and Glucantime + Leishvacin associated with Bacillus Calmette-Guerin. For analysis of the histopathological changes present in the dermis and epidermis, histological sections were stained with hematoxylin and eosin. The samples were immunostained before and after treatment to analyze the expression of interferon (IFN)-γ, interleukin (IL) 12, IL-10 and IL-4. RESULTS: Before treatment the presence of intense infiltrates of mononuclear cells was noticed and after treatment, even with a diagnosis of clinical cure, the subjects still showed a moderate inflammatory process. In the immunohistochemical analyses, we noticed a difference between the cytokines, with increased expression of cytokines IFN-γ and IL-12 compared to IL 10 and IL-4, both before and after treatment and, comparatively, the difference in this expression was more intense before treatment. However, the cytokine expression analyzed by treatment group showed no statistically significant difference. CONCLUSION: We conclude that a clinical cure does not always coincide with the histopathological one, and that before treatment there is a predominance of Th1 cytokines. In terms of treatment type, there was no difference in the progression of healing for all the three types of treatment, indicating their clinical equivalence. FUNDAMENTOS: A histopatologia e as respostas imunológicas do processo de cura da leishmaniose são ainda pouco estudadas. OBJETIVOS: Este estudo teve como objetivo avaliar os aspectos histopatológicos e imunológicos das lesões de pacientes com leishmaniose tegumentar, antes e após diferentes métodos terapêuticos. MÉTODOS: Foram estudados 23 indivíduos agrupados de acordo com os tratamentos: Glucantime, Glucantime + Leishvacin e Glucantime + Leishvacin associado com Bacilo Calmette-Guerin. Para a análise das alterações histopatológicas presentes na derme e epiderme, cortes histológicos foram corados com hematoxilina e eosina. Para avaliar a expressão de interferon (IFN)-γ, interleucina (IL) 12, IL-10 e IL-4 foi utilizada a técnica de imuno-histoquímica antes e após o tratamento. RESULTADOS: Antes do tratamento houve um intenso infiltrado de células mononucleares, após o tratamento, mesmo com um diagnóstico de cura clínica, apresentou-se ainda um moderado processo inflamatório. Na análise imuno-histoquímica, notamos uma diferença entre as citocinas, com expressão aumentada de citocinas IFN-γ e IL-12 em comparação com IL-10 e IL-4 tanto antes quanto depois do tratamento, e comparativamente, a diferença nesta expressão mostrou-se mais intensa antes do tratamento. No entanto, a expressão das citocinas analisadas por grupo de tratamento não mostraram diferenças estatisticamente significativas. CONCLUSÃO: Concluímos que uma cura clínica nem sempre coincide com a cura histopatológica, e que antes do tratamento há uma predominância de citocinas Th1. Para os tratamentos, não houve diferença na progressão da cura para todos os três tipos de tratamento, indicando a equivalência clínica dos tratamentos.

The aim of this study is to assess whether C1772T and G1790A hypoxia-inducible factor-1 (HIF-1)α polymorphisms are associated with risk of oral lichen planus (OLP). Restriction fragment length polymorphism analysis was used to investigate HIF-1α C1779T and G1790A polymorphisms in 32 OLP and 88 individuals without OLP. The frequency of the CC, TT, GA, and AA genotypes was higher in patients with OLP. Notably, individuals carrying the C and A, and T and A haplotypes showed a significant association OLP risk. Our study demonstrated that the C1772T and G1790A polymorphisms of HIF-1α gene increased the risk of OLP. C1772T and G1790A polymorphisms of HIF-1α gene had differing patterns of allelic imbalance in the normal samples and subsequent chronic lesions. Further studies are necessary to elucidate the HIF-1α pathway in OLP, which would facilitate the development of novel therapeutic strategies for the prevention and treatment of OLP. These results, in conjunction with previous studies, suggest that HIF-1α may play important roles in the chronicity of oral mucosa lesions of OLP patients. Taken together, we suggest that HIF-1α polymorphisms enhance its target genes, thereby altering the microenvironment and supporting sequential release of inflammatory mediators or cellular events in OLP. It appears unlikely that inhibition of a single proinflammatory mediator will prove useful in clinical practice, but several ways to reprogram mediators engaged in a wide array of roles simultaneously are encouraging.

This study aimed to evaluate the association between several different aspects of disease in head and neck squamous cell carcinoma (HNSCC): morphological grading, Ki67 proliferation index (PI), invasive front, adjacent non-malignant mucosa (ANMM), recurrence and overall survival of the patients. Sixty-four fully reviewed and followed-up patients with primary HNSCC were matched according to recurrence of the lesion and placed in one of two groups of 32 cases. Chi-square and Fisher's exact tests were used to analyze the clinicopathological parameters between both groups of patients. Association between Ki67 PI and clinicopathological parameters was also analyzed through chi-square and Fisher's exact tests with the binary logistic regression model used as a multivariate analysis. In addition, survival analysis was also performed. Our results showed that high-risk dysplasia in ANMM and high Ki67 PI in ANMM of HNSCC exhibited a higher risk of tumor recurrence. Survival analysis showed that T3/T4 tumor sizes and high Ki67 PI were significantly associated with an increase in the risk of death in multivariate analysis. Our results revealed that high-risk dysplasia and high Ki67 PI of the ANMM are parameters which are indicative of tumor recurrence. Furthermore, T3/T4 tumor sizes and high Ki67 PI in the invasive front appear to be important prognostic tools for HNSCC.

This study investigated the immunodetection of CD57+ inflammatory cells in patients with head and neck squamous cell carcinoma (HNSCC) and its association with clinicopathological parameters and overall survival. Data collected from the morphological analysis and immunohistochemical reaction testing of archived HNSCC specimens (n=70) were statistically analyzed by bivariate and multivariate statistical testing at a significance level of P0.05. The results indicate that CD57+ inflammatory cells predominate within the peritumoral stroma of HNSCC lesions and the existence of two significant relationships: between high CD57+ cell density and the development of a tumor of a large size [odds ratio (OR)=5.610, 95% confidence interval (CI)=1.516-20.763) and between high CD57+ cell density and the development of locoregional metastatic disease (OR=3.401, 95% CI=1.162-9.951). A significant difference in the rate of survival was detected only in HNSCC patients that presented large size tumors (OR=4.747, 95% CI=1.281-17.594). Together, these results suggest that although high CD57+ inflammatory cell density is associated with HNSCC lesions of greater clinical severity, the variable of cell density is not an independent predictor of HNSCC patient survival. Our findings also suggest that the relatively aggressive infiltration of CD57+ inflammatory cells in the peritumoral stroma of head and neck carcinomas may contribute to an ineffective locoregional antitumoral response.

Objective: To investigate the DNMT3B (C46359T) polymorphism and immunoexpression of DNMT3b and DNMT1 in oral lichen planus (OLP) compared to a control group. Methods: We aimed to investigate the DNMT3B (C46359T) polymorphism and immunoexpression of DNMT3b and DNMT1 in OLP (n = 32), comparing it with oral mucosa (control; n = 24). The DNMT3B (C46359T) polymorphism was analyzed using the RFLP-PCR and DNMT1, and DNMT3a proteins were identified using immunohistochemistry. We also compared the DNMT3B expression in OLP and oral inflammatory fibrous hyperplasia (OIFH), another oral inflammatory disease. Differences between the groups were determined by specific statistical analyses. Results: The CT genotype of DNMT3B was associated with OLP development (p = 0.012). Increased expression of DNMT3B and DNMT1 was observed in OLP compared to the control group (p = 0.014 and p = 0.001, respectively). A significant increase in DNMT3B protein levels was observed in the genotype CT in DNMT3B (C46359T) polymorphisms (p = 0.045). No DNMT3B expression differences between OLP and OIFH were observed. Conclusions: Our data show that the DNMT3B (C46359T) polymorphism is associated with OLP development. Furthermore, increased expression of the enzyme DNMT3B, an epigenetic-associated protein, is present in OLP.

This study evaluated 724 primary head and neck squamous cell carcinoma (HNSCC) in young and old patients, with regard to clinical profile and immunohistochemical expression of p53 protein. Associations among age, epidemiological and clinicopathological parameters, and survival analysis were evaluated. HNSCC in young people occurred in 14.5% (median age 40.7years; male-to-female ratio 5.9:1). A statistical association was demonstrated between age and family history of cancer, and between age and anatomical site. Among older patients, a higher presence of disease was noted in posterior sites. Expression of p53 was found in 71.7% of the samples and a higher expression was noted in lesions of young patients. Survival analysis showed that the age parameter is not a reliable prognostic factor for HNSCC. Among young patients, cervical metastasis was associated with worse survival. The presence of a family history of cancer in young patients could indicate genetic susceptibility and molecular disturbances in the p53 pathway in HNSCC of young and older patients seem to be distinct.

Obesity-Related Genes and Oral Cancer: A Bioinformatics Approach and Systematic Review It is important to understand the biological processes linking obesity and cancer to identify new molecular targets for development of better therapeutic strategies. This study aims to synthesize knowledge regarding possible associations between obesity-related genes and oral cancer. We performed literature review about “oral cancer” and “obesity”. Gene databases and bioinformatics algorithms were used to in silico investigation of interactions networks between proteincoding genes, leader genes and molecular pathways that can possibly to link both pathological mechanisms. To this, GeneCards database, softwares STRING, Metaboanalyst and Cytoscape were employed. Genes were found to interact directly or indirectly with both obesity and oral cancer. Analyses of clustering revealed the TP53 gene as leader gene. Leptin was presented in group with the highest scores of relevance. Protein-protein interaction network linking obesity and oral cancer exhibits a power law behavior (correlation: 0.907; R2:0.851). Analysis of linear regression shows that genes related to obesity and oral cancer have higher diseaserelated connectivity than a global connectivity. Onthological analysis demonstrated different mechanisms associated to obesity and oral cancer, such as regulation of apoptosis and positive regulation of cellular process. We hypothesized that leptin is a molecule key in the link between obesity and oral cancer, by interactions with the p53 protein through CREBBP and EP300 proteins and HIF-1α, promoting angiogenesis. This study sought to organize relevant informations to further illuminate the role of genes that may be related to obesity and oral cancer. Angiogenesis genes can to be suggested as important factors to link both pathological processes..

It is estimated that 7.6 million people will die as a consequence of head and neck squamous cell carcinoma (HNSCC). Genetic predisposition has emerged as an important risk factor in the development and prognosis of HNSCC. Considering this, the aim of the current study is to assess whether codon 72 SNP of the TP53 gene (rs1042522) is associated with an increased odds ratio of developing HNSCC or with a worse prognosis in patients with HNSCC. Analysis of the rs1042522 in HNSCC patients and in control individuals. Differences between the case and control groups were determined using chi-squared tests. Multivariate analysis was performed to evaluate the odds ratio of HNSCC. Fussy C Means Clustering was to cluster HNSCC patients for survival analyses. Time of survival was calculated using the Kaplan-Meier estimator and comparing this to the log rank test. Statistical significance was set at p

Introduction Chronic dental periapical lesions result from chronic inflammation of periapical tissues caused by continuous antigenic stimulation from infected root canals. Recent findings have suggested that T helper (Th) 1 and Th2-like cytokines are important in the pathogenesis of chronic periapical inflammatory diseases. However, the mechanisms regulating these immunoinflammatory pathways have not been fully elucidated. Thus, the aim of this study was to evaluate interleukin (IL)-4, IL-12, and interferon γ (IFN-γ) protein levels in human radicular cysts and periapical granulomas. Methods Archived samples of cysts (n = 52) and granulomas (n = 27) were sectioned and submitted to immunohistochemistry to evaluate the tissue expression of IL-4, IL-12, and IFN-γ. The data were analyzed using the Mann-Whitney U test (P Results An increased expression of IFN-γ was observed in radicular cysts. IL-4 expression was stronger in periapical granulomas than in radicular cysts. IL-12 was not detected in any of the samples. Conclusions Our study showed that IFN-γ protein levels are increased in radicular cysts, whereas IL-4 expression is stronger in samples of periapical granulomas. Further studies are necessary to elucidate the signaling pathways mediated by these cytokines and to facilitate the development of more effective periapical disease management strategies.

Introduction Bioinformatics has emerged as an important tool to analyze the large amount of data generated by research in different diseases. In this study, gene expression for radicular cysts (RCs) and periapical granulomas (PGs) was characterized based on a leader gene approach. Methods A validated bioinformatics algorithm was applied to identify leader genes for RCs and PGs. Genes related to RCs and PGs were first identified in PubMed, GenBank, GeneAtlas, and GeneCards databases. The Web-available STRING software (The European Molecular Biology Laboratory [EMBL], Heidelberg, Baden-Wurttemberg, Germany) was used in order to build the interaction map among the identified genes by a significance score named weighted number of links. Based on the weighted number of links, genes were clustered using k-means. The genes in the highest cluster were considered leader genes. Multilayer perceptron neural network analysis was used as a complementary supplement for gene classification. Results For RCs, the suggested leader genes were TP53 and EP300 , whereas PGs were associated with IL2RG , CCL2 , CCL4 , CCL5 , CCR1 , CCR3 , and CCR5 genes. Conclusions Our data revealed different gene expression for RCs and PGs, suggesting that not only the inflammatory nature but also other biological processes might differentiate RCs and PGs.