Assessment of Subgingival Biofilm and its Relationship with the Status of Tumors in a Population with Breast Cancer

This study aimed to compare the subgingival microbiota of subjects with and without breast cancer (BC). Patients with BC (Group 1; n= 50) and without BC (Group 2; n=50) with periodontitis (A) and without periodontitis (B). The study was conducted in two phases (P1 and P2). One biofilm sample was collected from each subject and analyzed by DNA-DNA Hybridization (Checkerboard DNA-DNA). The relative abundance of the subgingival microbiota differed between the Case and Control groups. However, some species were higher in patients in the Case than in Control subjects and differed between the groups in both phases. Composition of the subgingival microbial community according to the Socransky complex was related to periodontal disease, followed by clinical attachment of level (CAL ≥4mm), age, and tooth loss, which were found to be abundant in Cases when compared with controls. Patients with Tumor Grade II and III had a higher prevalence of tooth loss and CAL≥4mm. It was concluded that in individuals with BC, the sub-gingival microbiota exhibited atypical changes, but they developed periodontal disease.

El objetivo de este estudio fue comparar la microbiota subgingival de sujetos con y sin cáncer de mama (CM). Pacientes con CM (Grupo 1; n= 50) y sin CM (Grupo 2; n=50) con periodontitis (A) y sin periodontitis (B). El estudio se realizó en das fases (P1 y P2). Se recogió una muestra de biopelícula de cada sujeto y se analizó mediante hibridación ADN-ADN (tablero de ajedrez ADN-ADN). La abundancia relativa de la microbiota subgingival difirió entre los grupos de Caso y Control. Sin embargo, algunas especies fueron más altas en los pacientes del Caso que en los sujetos del Control y difirieron entre los grupos en ambas fases. La composición de la comunidad microbiana subgingival según el complejo de Socransky se relacionó con la enfermedad periodontal, seguida por el nivel de inserción clínica (CAL≥4mm), la edad y la pérdida de dientes, que se mostró abundante en los casos en comparación con los controles. Los pacientes con Tumor Grado II y III tuvieron mayor prevalencia de pérdida dental y CAL≥4mm. Se concluyó que en individuos con CM la microbiota subgingival presentó cambios atípicos, pero sin embargo, desarrollaron enfermedad periodontal.

Psychotropic drug use and suggestive depression symptoms associated with NR3C1 DNA methylation / Uso de drogas psicotrópicas e sintomas sugestivos de depressão associados à metilação do DNA do NR3C1

Introduction: Psychiatric disorders have become a global problem that leads millions of people to use psychotropic medications, especially benzodiazepines. The effects of these substances are widely known regarding tolerance and chemical dependence, however, from epigenetics perspective, there are still little known.Objective: To evaluate the association between psychotropic drug use, NR3C1 gene methylation and its relation with symptoms suggestive of depression in adult individuals assisted in the public health system.Methods: 385 adult volunteers (20-59 years) users of the Brazilian Unified Health System were recruited to evaluate socioeconomic, health, lifestyle conditions in a cross sectional study. BDI-II evaluated symptoms suggestive of depression and pyrosequencing evaluated NR3C1 DNA methylation. Bivariate and multivariate Poisson regression model with robust variance (p < 0.05) evaluated the association between psychotropic drug use and NR3C1 gene methylation.Results: Specific depressive symptoms such as irritability, insomnia and fatigability were associated with psychotropic drug use. Symptoms of past failure, indecision and loss of appetite were associated with hypermethylation patterns in CpGs 40 to 47 of NR3C1 gene. Moreover, psychotropic drug use is associated with 50% reduction in NR3C1 gene methylation, through model adjusted with socioeconomic, health and lifestyle confounding variables.Conclusions: Psychotropic drug use and depressive symptoms was associated with changes in NR3C1 DNA methylation. In this context, epigenetic modification resulting from psychotropic drug use and depressive symptoms could be considered, mainly in population studies with epigenetic evaluation, where these factors may be influencing the findings of future studies.

Introdução: os distúrbios psiquiátricos tornaram-se um problema global que leva milhões de pessoas ao uso de medicamentos psicotrópicos. Os efeitos dessas substâncias são amplamente conhecidos quanto à tolerância e dependência química, porém, do ponto de vista epigenético, ainda são pouco conhecidos.Objetivos: avaliar a associação entre o uso de drogas psicotrópicas, metilação do gene NR3C1 e sua relação com sintomas sugestivos de depressão em indivíduos entre 20 a 59 anos usuários da rede pública de saúde.Método: 385 voluntários de 20-59 anos, usuários do Sistema Único de Saúde brasileiro foram recrutados para avaliação das condições socioeconômicas, de saúde e de estilo de vida em estudo transversal. O BDI-II avaliou sintomas sugestivos de depressão e o pirosequenciamento avaliou a metilação do DNA de NR3C1. Modelo de regressão de Poisson bivariado e multivariado com variância robusta (p < 0,05) avaliou a associação entre o uso de drogas psicotrópicas e metilação do gene NR3C1.Resultados: sintomas depressivos específicos como irritabilidade, insônia e fadiga foram associados ao uso de medicamentos psicotrópicos. Sintomas de fracasso passado, indecisão e perda de apetite foram associados a padrões de hipermetilação nos CpGs 40 a 47 do gene NR3C1. Além disso, o uso de psicofármacos está associado à redução de 50% na metilação do gene NR3C1, por meio de modelo ajustado com variáveis de confusão socioeconômicas, de saúde e estilo de vida.Conclusão: o uso de drogas psicotrópicas e sintomas específicos depressivos foram associados a alterações na metilação do DNA de NR3C1.

Metformin synergistically enhances antiproliferative effects of cisplatin and etoposide in NCI-H460 human lung cancer cells / Metformina sinergicamente potencializa os efeitos antiproliferativos de cisplatina e etoposideo em linhagem de celulas de cancer humano de pulmao NCI-H460

OBJECTIVE: To test the effectiveness of combining conventional antineoplastic drugs (cisplatin and etoposide) with metformin in the treatment of non-small cell lung cancer in the NCI-H460 cell line, in order to develop new therapeutic options with high efficacy and low toxicity. METHODS: We used the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay and calculated the combination index for the drugs studied. RESULTS: We found that the use of metformin as monotherapy reduced the metabolic viability of the cell line studied. Combining metformin with cisplatin or etoposide produced a synergistic effect and was more effective than was the use of cisplatin or etoposide as monotherapy. CONCLUSIONS: Metformin, due to its independent effects on liver kinase B1, had antiproliferative effects on the NCI-H460 cell line. When metformin was combined with cisplatin or etoposide, the cell death rate was even higher. .

OBJETIVO: Testar a eficácia da combinação terapêutica de antineoplásicos convencionais (cisplatina e etoposídeo) com metformina em linhagem celular NCI-H460 de câncer de pulmão não pequenas células, a fim de desenvolver novas possibilidades terapêuticas com eficácia superior e reduzida toxicidade. MÉTODOS: Foi utilizado o ensaio de brometo de 3-(4,5-dimetiltiazol-2-il)-2,5-difeniltetrazólio (MTT) e calculado o índice de combinação dos fármacos estudados. RESULTADOS: Observamos que o uso de metformina em monoterapia reduziu a viabilidade celular metabólica da linhagem de células estudada. O uso de metformina em combinação com cisplatina ou etoposídeo foi sinérgico e superior à monoterapia com cisplatina ou etoposídeo. CONCLUSÕES: A metformina, devido às suas ações independentes em liver kinase B1, apresentou atividade antiproliferativa na linhagem NCI-H460 e, em combinação com cisplatina ou etoposídeo, ampliou a taxa de morte celular. .

Lung cancer and smoking: molecular aspects

Lung cancer (LC) is characterized as one of the most common and lethal types of cancers worldwide, with approximately 230.000 new cases each year in the US and 160.000 deaths are estimated for 2012. In Brazil, the outlook is also bleak, with 27,320 new cases expected in 2012, according to the Brazilian National Cancer Institute (INCA). LC is classified into two major histological types: small cell lung cancer (SCLC) and non-small-cell lung cancer (NSCLC). In addition to sizable mortality and incidence, LC has low 5-year survival rates when compared to other types of common cancers such as breast and prostate, even with recent diagnostic and therapeutic advances. For the survival rate of patients with LC to increase, a greater understanding of the molecular events that lead to the emergence of this malignancy is necessary in order to identify genetic markers involved in tumor progression, and thus enable early detection and to develop new specific therapeutic strategies, allowing for a more individualized treatment in patients with LC. Different situations are classified as risk factors for the development of LC, but unquestionably, the most responsible risk factor for the high incidence of LC in the world population by far is smoking.

Prevalence of estrogen receptor alpha PvuII (c454-397T>C) and XbaI (c454A>G) polymorphisms in a population of Brazilian women

The aim of this work was to study the estrogen receptor alpha (ERS1) PvuII and XbaI gene polymorphisms prevalence in randomly selected women population from Rio de Janeiro and Espírito Santo states in Brazil by polymerase chain reaction restriction fragment lengths polymorphism (PCR_RFLP) methodology. It was shown that Rio de Janeiro women exhibited a significantly different prevalence of XbaI polymorphism comparing to Espirito Santo women. Nonetheless, similar prevalence of PvuII polymorphism was found in both women´s populations. Moreover, a strong linkage disequilibrium was observed between these SNPs reinforcing the hypothesis of differential pattern of inheritance observed on such populations.

O papel paradoxal do sistema imune no câncer de ovário

Introdução: O sistema imune atua nos tumores desde o surgimento destes. Observa-se que o sistema imune exerce papel paradoxal sobre os tumores: é capaz de proteger o hospedeiro contra o surgimentodestes e também de promover o crescimento tumoral. Nos cânceres de ovário clinicamente detectáveis esse padrão é mantido, pois determinadas populações celulares imunológicas exercem efeito protetor, visto quesuas presenças associadas ao tumor ou ascites correlacionam- se com maior sobrevida, maior taxa de citorredução ótima e melhor resultado clínico, ao passo que a presença de outras afeta negativamente a sobrevivência das pacientes e estão associadas à inibição das respostas imunológicas protetoras. Objetivo: O objetivo desse artigo foi realizar umarevisão da literatura acerca do tema ?o papel paradoxal do sistema imune no câncer de ovário?. Métodos: Foram selecionados livros e artigos, sendoa busca destes realizada no Portal de Periódicos CAPES (Coordenação de Aperfeiçoamento de Pessoal de Nível Superior) e na base de dados Pub Med. Conclusão: De acordo com o descrito na literatura, dentre as células do sistema imune cuja presença no tumor correlaciona-se com bom prognóstico da doença, estão as populações de linfócitos T citotóxicos, células natural killer e T natural killer e entre as células imunológicas cuja presença no tumor está relacionada com pior resultado clínico destacam-se as células T reguladoras e macrófagos (fenótipo M2). Assim, acredita- se que o perfil imunológico associado ao câncer deovário pode ter aplicação prognóstica e implicações terapêuticas que permitam melhor controle da doença e melhor qualidade de vida para as pacientes.

Background: The immune system recognizes tumors cells since their very beginning of the malignancy. It is observed that immune system has a paradoxical role on tumors: it is able to protect the host from the malignant cells but also stimulates the tumor growth. In clinically detectable ovarian cancer, this common pattern is maintained. Several immune cellular populations show a protective effect because their presence associated to the tumor or ascites are correlated to higher survival rate, cytoreduction rate, and better clinical outcome. Nevertheless, the presence of other immune cells negatively affects the survival from the patients being associated to inhibited immune response. Objective: The purpose of this article was to review the topic ?the paradoxical role of the immunesystem in ovarian cancer?. Methods: Were selected books and articles thatwas search in the CAPES?s Portal (Coordenação de Aperfeiçoamento de Pessoal de Nível Superior) and in the database Pub Med. Conclusion: According to what has been described in the literature, among immunesystem cells whose presence in the tumor correlates with good prognosis, are the populations of cytotoxic T cells, natural killer and natural killer T cells and between immune cells whose presence in the tumor is associated with worse clinical outcome are includeregulatory T cells and macrophages (M2 phenotype). Them, it is believed that immunological profile associated to ovarian cancer may be used in disease prognosis and, also, be used for therapeutic reasons thatleads to better control of such disease and improved quality of life for patients.

The Cotransporter NaPi-IIb: characteristics, regulation and its role in carcinogenesis

Inorganic phosphate (Pi) presents a crucial role in cellular metabolism, with the kidney and intestine as the principal regulating organs of the homeostasis of this nutrient. Maintaining phosphate balance results from the activity of different subtype of transporters of sodium-dependent phosphate that use the electrochemical gradient of sodium ions to carry out cotransport. Several diseases have been related to dysfunctions of phosphate cotransporters, including in the area of oncology. A study using the SAGE technique pointed to a possible role of the type IIb sodium-phosphate cotransporter (NaPi-IIb), encoded by the SLC34A2 gene, in ovarian carcinogenesis. More recently, such protein was associated with the development of other carcinomas and some of the components that regulate its function were determined. It is believed that in the future, the analysis of SLC34A2 expression in tumor samples will help in the choice of treatment, evaluation of prognosis and be a possible target for new therapeutic strategies.

O papel dos polimorfismos de nucleotídeos único (SNPs) PvuII e XbaI e das pequenas repetições em tandem (STRs)(TA)n e (GT)n do receptor de estrogênio Alfa (ESR1) na suscetibilidade do câncer de mama (BRCA) da mama (BRCA) / The role of single nucleotide polymorphisms (SNPs) PvuII and XbaI and short tandem repeats (STRs) (TA)n and (GT)n of estrogen alpha receptor (ESR1) in breast cancer (BRCA) susceptibility

O estrogênio é um hormônio esteroide sexual que possui efeito sobre o sistema reprodutor feminino e masculino. Esses efeitos são mediados principalmente pelas isoformas Alfa e Beta (ER Alfa e Beta), componente da superfamília de receptores nucleares que controlam a transcrição gênica. De fato, a resposta do gene ao estrogênio depende de muitos fatores, incluindo a avaliação dos subtipos de ER, os correguladores, o tempo de exposição ao estrogênio e a quantidade desse hormônio. Os processamentos (do inglês splicing) alternativos geram diversas variantes de RNAm de ESR1. As isoformas de RNAm com distintas regiões 5 não traduzidas resultam na expressão da proteína ESR1 de diferentes tamanhos. Sabe-se que o gene ESR1 possui muitos sítios de polimorfismos que podem ser responsáveis por diferentes variantes alélicas da proteína, podendo alterar a função e a atividade dessa proteína e, então, resultar nas diferenças do efeito do estrogênio sobre o desenvolvimento de doenças. Existem vários fatores de risco relacionados ao BRCA, porém os polimorfismos do gene ESR1 contribuem de maneira expressiva para carcinogênese mamária. Os SNPs Pvu II e Xba I e os STRs (GT)n e (TA)n despertam curiosidade por se localizarem em regiões não traduzidas do gene ESR1 e poderem estar relacionados a doenças de grande impacto, como o BRCA. Nota-se certa interferência desses polimorfismos nessa neoplasia, porém os resultados são divergentes. Contudo, é importante ampliar o conhecimento da genética do ESR1, pois existem evidências que suas propriedades interferem no desenvolvimento do BRCA.