Avaliação das crenças parentais no cuidado domiciliar do recém-nascido prematuro / Evaluation of parental beliefs in the home care of premature newborn / Evaluación de las creencias de los padres en el cuidado domiciliaria del recién nacido prematuro

Objetivo: Avaliar as crenças que norteiam o cuidar do recém-nascido prematuro em domicílio, na perspectiva da mãe cuidadora. Método: Trata-se de um estudo descritivo com abordagem qualitativa. Foram realizadas 30 entrevistadas semiestruturadas com mães que tiveram filhos prematuros. Para a análise dos discursos apreendidos nas entrevistas foi utilizada a Teoria Fundamentada nos Dados. Resultados: As mães de recém-nascidos prematuros apresentaram baixa renda, pouco acesso ao sistema de saúde e eram moradoras de áreas consideradas geográfica e economicamente menos favorecidas. Evidenciou-se que as mães apresentaram medo e insegurança ao cuidar dos seus filhos e não receberam apoio da Estratégia Saúde da Família. Conclusão: As mães do estudo relataram grande interferência na adoção das práticas parentais no domicílio, principalmente da avó e não se sentem preparadas para cuidar do filho prematuro, em casa, por sentirem medo de realizar os cuidados. (AU)

Objective: To evaluate the beliefs that guide the care of the premature newborn at home from the perspective of the caregiving mother. Methods: This is a descriptive study with a qualitative approach. 30 semi-structured interviewees were carried out with mothers who had premature children. The Grounded Theory was used to analyze the speeches seized in the interviews. Results: It was evidenced that the mothers of premature newborns had low income, little access to the health system and lived in areas considered geographically and economically less favored. It was evident that mothers were afraid and insecure when taking care of their children and did not receive support from the Family Health Strategy. Conclusion: The mothers of the study reported great interference in the adoption of parenting practices at home, especially the grandmother and they do not feel prepared to take care of the premature child at home, because they are afraid to perform the care. (AU)

Objetivo: Evaluar las creencias que guían el cuidado del recién nacido prematuro en el hogar desde la perspectiva de la madre que cuida. Métodos: Este es un estudio transversal con un enfoque cualitativo. Se realizaron 30 entrevistados semiestructurados con madres que tuvieron hijos prematuros. The Grounded Theory se utilizó para analizar los discursos incautados en las entrevistas. Resultados: Se evidenció que las madres de recién nacidos prematuros tenían bajos ingresos, poco acceso al sistema de salud y vivían en áreas consideradas geográficamente y económicamente menos favorecidas. Era evidente que las madres tenían miedo e inseguridad al cuidar a sus hijos y no recibían apoyo de la Estrategia Salud Familiar. Conclusión: Las madres del estudio informaron una gran interferencia en la adopción de prácticas parentales en el hogar, especialmente la abuela, y no se sienten preparadas para cuidar al niño prematuro en casa, porque tienen miedo de realizar el cuidado. (AU)

Association between UGT1A1*28 gene polymorphism and severe neutropenia due to colorectal cancer treatment with irinotecan: evidence based on meta-analysis / Associação entre o polimorfismo do gene UGT1A1*28 e a neutropenia severa decorrente do tratamento do câncer colorretal com irinotecano: evidências baseadas em meta-análise

Abstract Objective The present study aimed to evaluate the relationship between UGT1A1*28 gene polymorphism and the prevalence of neutropenia in patients with colorectal cancer treated with irinotecan. Method Thirteen studies were included. These papers were selected from the Virtual Health Library, Scientific Electronic Library Online, International Health Sciences Literature and PubMed, and their data were collected and evaluated using the BioEstat 5.3 software (BioEstat, Belém, PA, Brazil). Results Three genotypes were analyzed, namely 6/6 (wild type), 6/7, and 7/7. In total, 2,146 patients were included in the present study; of these, 55.6% (n=1,193) had 6/6 genotype, 37.3% (n=801) were heterozygous (6/7), and 7.1% (n=152) had the 7/7 genotype. A total of 1,672 (77.9%) patients displayed mild neutropenia, whereas 474 (22.1%) had severe neutropenia. When contrasting the 6/7 and 7/7 genotypes with the 6/6 genotype using statistical tests for meta-analysis, patients with the 7 allele, either Conclusion The analysis of the UGT1A1*28 gene polymorphism can aid the choice of treatment for patients with colorectal cancer in personalized medicine, increasing the chances of therapeutic success.

Resumo Objetivo Avaliar a relação do polimorfismo do gene UGT1A1*28 com a prevalência de neutropenia em pacientes com câncer colorretal submetidos a tratamento com o irinotecano. Método Foram incluídos 13 estudos sobre o tema proposto, selecionados nas bases de dados da Biblioteca Virtual de Saúde, Scientific Electronic Library Online, International Health Sciences Literature e PubMed.Os dados foramcoletados dos artigos científicos selecionados e avaliados com o auxílio do software BioEstat 5.3 (BioEstat, Belém, PA, Brasil). Resultados Osgenótipos analisados foram6/6 (tipo selvagem), 6/7 e 7/7. Foramincluídos 2.146 pacientes. Destes, 55,6% (n=1.193) apresentaram genótipo 6/6, 37,3% (n=801) eramheterozigotos (6/7) e 7,1%(n=152) tinhamo genótipo 7/7.Umtotal de 1.672 (77,9%) pacientes apresentou neutropenia leve e 474 (22,1%) neutropenia severa. Ao contrastar os genótipos 6/7 e 7/7 como 6/6, percebeu-se, coma execução dos testes estatísticos demetaanálise, que os pacientes como alelo 7, emhomozigose ou heterozigose, tinhammaior risco de desenvolver neutropenia severa que pacientes com o genótipo 6/6 (razão de chances =1,559; intervalo de confiança de 95%=1,163-2,090; p=0,003). Conclusão A análise do polimorfismo do gene UGT1A1*28 pode auxiliar na escolha do tratamento do paciente comcâncer colorretal, no contexto da medicina personalizada, ampliando, assim, as chances de sucesso terapêutico.

An In Silico Analysis Identified FZD9 as a Potential Prognostic Biomarker in Triple-Negative Breast Cancer Patients.

OBJECTIVE: Breast cancer (BC) is the main cause of cancer-related deaths in women across the world. It can be classified into different subtypes, including triple-negative (TN), which is characterized by the absence of hormone receptors for estrogen and progesterone and the lack of the human epidermal growth factor receptor 2. These tumors have high heterogeneity, acquire therapeutic resistance, and have no established target-driven treatment yet. The identification of differentially expressed genes in TN breast tumors and the in silico validation of their prognostic role in these tumors. MATERIALS AND METHODS: We employed a microarray dataset and, by using the GEO2R tool, we identified a list of differentially expressed genes. The in silico validation was conducted using several online platforms including the KM Plotter, cBioPortal, bc-GenExMiner, Prognoscan, and Roc Plotter. RESULTS: We observed that FZD9 was among the top differentially expressed genes in a cohort of patients with different TNBC subtypes. The FZD9 expression was significantly different in TN breast tumors than in non-TN (nTN) breast tumors (p<0.0001), and the basal TN subtype showed the highest levels (p<0.0001). In addition, the FZD9 levels were significantly inversely and positively proportional (p<0.0001) to estrogen receptor, progesterone receptor, and human epidermal growth factor receptor-2 clinical parameters. The high levels of FZD9 were associated with worse overall survival (p=0.007), relapse-free survival (p=5.8e-05), and worse survival in patients who received chemotherapy (p=3.2e-05; 0.007). CONCLUSION: Our cumulative results demonstrated that FZD9 plays an important role in TNBC and may be a potential prognostic biomarker. Nevertheless, further in vitro and in vivo assays are necessary to confirm our findings and to strengthen the evidences about the mechanisms by which FZD9 functions in these tumors.

Computed Tomography Colonography as a Sensible Option for Colorectal Cancer Screening: Evidence Based on Metanalysis / Colonografia por tomografia computadorizada como uma opção sensível para o rastreamento do câncer colorretal: Evidências baseadas em metanálise

Abstract Objective This metanalysis aimed to evaluate the sensitivity and specificity of computed tomography colonography in colorectal polyp detection. Methods A literature search was performed in the PubMed and Web of Science databases. Results A total of 1,872 patients (males 57.2%, females 42.8%) aged 49 to 82 years old (mean age 59.7 ± 5.3 years) were included in this metanalysis. The estimated sensitivity of computed tomography colonography was 88.4% (46.3-95.7%, coefficient of variation [CV]=28.5%) and the estimated specificity was 73.6% (47.4-100.0%, CV=37.5%). For lesions up to 9mm, the sensitivity was 82.5% (62.0-99.9%, CV =25.1%) and the specificity was 79.2% (32.0-98.0%, CV=22.9%). For lesions>9mm, the sensitivity was 90.2% (64.0-100.0%, CV=7.4%) and the specificity was 94.7% (80.0-100.0%, CV=6.2%). No statistically significant differences in sensitivity according to the size of the lesion were found (p=0.0958); however, the specificity was higher for lesions>9mm (p<0.0001). Conclusions Most of the studies analyzed in the present work were conducted before 2010, which is about a decade after computed tomography colonography started being indicated as a screening method by European and American guidelines. Therefore, more studies aimed at analyzing the technique after further technological advancements are necessary, which could lead to the development of more modern devices.

Resumo Objetivo Esta meta-análise teve como objetivo avaliar a sensibilidade e especificidade da colonografia por tomografia computadorizada na detecção de pólipos colorretais. Métodos Foi realizada uma pesquisa bibliográfica nas bases de dados da PubMed e da Web of Science. Resultados Um total de 1.872 pacientes, 57,2% homens e 42,8% mulheres, com idades entre 49 a 82 anos de idade (média de 59,7 ± 5,3 anos) foram incluídos nesta meta análise. A sensibilidade da colonografia por tomografia computadorizada foi estimada em 88,4% (46,3-95,7%; coeficiente de variância [CV]=28,5%) e a especificidade em 73,6% (47,4%-100,0%; CV=37,5%). Para lesões de até 9mm, a sensibilidade foi de 82,5% (62,0-99,9%; CV=25,1%) e a especificidade de 79,2% (32,0-98,0%; CV=22,9%). Para lesõesmaiores que 9mm, a sensibilidade foi de 90,2% (64,0-100,0%; CV=7,4%) e a especificidade de 94,7% (80,0-100,0%; CV=6,2%). Não houve diferença estatisticamente significante entre as sensibilidades por tamanho da lesão (p=0,0958), porém a especificidade foi maior em lesões acima de 9mm (p<0,0001). Conclusão A maioria dos estudos analisados no presente trabalho foi realizada antes de 2010, cerca de uma década depois que a colonografia por tomografia computadorizada passou a ser indicada como método de triagem pelas diretrizes europeias e americanas. Portanto, são necessários mais estudos com o objetivo de analisar a técnica apósmaiores avanços tecnológicos, o que poderia levar ao desenvolvimento de dispositivos mais modernos.

Major mutations in the NS3 gene region of hepatitis C virus related to the resistance to direct acting antiviral drugs: a systematic review.

Hepatitis C virus (HCV) remains a global public health problem with high prevalence rates and chronicity of infection. Present work aimed to describe the main mutations in the NS3 region of the HCV genome related to the resistance of patients to the currently available direct-acting antivirals (DAAs). To guide the study description, the preferred items in the PRISMA protocol for systematic review were used. The data collected were HCV genotypes and subtypes and mutations in HCV NS3, general and stratified by continent. The 10 papers selected for this systematic review reported studies in seven countries, on three continents, and generated data of 2937 patients. The most frequent HCV subtype was 1a. Prevalence of genotypes suggested that there were few demographic regions reached by the studies, since there were regional variations in the type of genotypes reported in the available bibliographies. Of the total study population, 35.3% (n = 1037) had mutations in the NS3 gene region of HCV, suggesting a high rate of resistance to DAAs and a low sustained virologic response among those who used some therapeutic option. Ten major mutations were identified: Q80K, V170I, S122G, V36L, T54S, D168Q, A156S, Q80G, S122R, and V55A. The Q80K mutation was the highlight of the study, appearing not only with greater representativity (61.6%) but also as the only one described in the three continents analyzed. This systematic review reinforces the need to carry out more studies of detection of these mutations to fill in all information gaps that might help in optimization of treatment.

Cytotoxic, clastogenic and genotoxic effects of cis-tetraammine(oxalato)ruthenium(III) dithionate on human peripheral blood lymphocytes

There is a concern about stablishing the clinical risk of drugs used for cancer treatment. In this study, the cytotoxic, clastogenic and genotoxic properties of cis-tetraammine(oxalato)ruthenium(III) dithionite - cis-[Ru(C2O4)(NH3)4]2(S2O6), were evaluated in vitro in human lymphocytes. The mitotic index (MI), chromosomal aberrations (CA) and DNA damage by comet assay were also analyzed. The MTT test revealed that the ruthenium compound showed a slight cytotoxic effect at the highest concentration tested. The IC50 value for the compound after 24 hours of exposure was 185.4 µM. The MI values of human peripheral blood lymphocytes treated with 0.015, 0.15, 1.5 and 150 µM of cis-[Ru(C2O4)(NH3)4]2(S2O6) were 6.1, 3.9, 3.2 and 0.2%, respectively. The lowest concentration, 0.015 µM, did not show any cytotoxic activity. The CA values for the 0.015, 0.15 and 1.5 µM concentrations presented low frequency (1.5, 1.6 and 2.3%, respectively), and did not express clastogenic activity when compared to the negative control, although it was observed clastogenic activity in the highest concentration tested (150 µM). The results obtained by the comet assay suggest that this compound does not present genotoxic activity at lower concentrations. The results show that cis-[Ru(C2O4)(NH3)4]2(S2O6) has no cytotoxic, clastogenic or genotoxic in vitro effects at concentrations less than or equal to 0.015 µM. This information proves as promising in the treatment of cancer and is crucial for future trials.

Association between polymorphisms in the genes encoding toll-like receptors and dectin-1 and susceptibility to invasive aspergillosis: a systematic review.

Invasive aspergillosis is a common fungal infection in immunocompromised individuals. Some studies have shown that toll-like receptor and dectin-1 genetic polymorphisms may alter signaling pathways, thus increasing an individual's susceptibility to invasive aspergillosis. We investigated the pertinent literature to determine whether polymorphisms in the genes encoding toll-like receptors and dectin-1 increase the susceptibility to invasive aspergillosis. This study systematically reviewed the literature using the databases PubMed/PMC, Scopus, and Web of Science using the keywords invasive aspergillosis, polymorphism, Toll-like, and Dectin-1. From the initial search, 415 studies were found and according to our inclusion and exclusion criteria, eight studies were selected. Several studies described single-nucleotide polymorphisms (SNPs) that are associated with a greater susceptibility to invasive aspergillosis. These SNPs were found in the genes that encode toll-like receptors 1, 3, 4, and 5 and the gene that encodes dectin-1; upon activation, both cellular receptors initiate a signaling cascade that can result in the production of cytokines and chemokines. Thus, our literature review uncovered a significant association between polymorphisms in the genes that encode toll-like receptors and dectin-1 and invasive aspergillosis. More studies should be performed to better understand the relationship between toll-like receptor and dectin-1 genetic polymorphisms and invasive aspergillosis susceptibility.

Association between polymorphisms in the genes encoding toll-like receptors and dectin-1 and susceptibility to invasive aspergillosis: a systematic review

Abstract Invasive aspergillosis is a common fungal infection in immunocompromised individuals. Some studies have shown that toll-like receptor and dectin-1 genetic polymorphisms may alter signaling pathways, thus increasing an individual's susceptibility to invasive aspergillosis. We investigated the pertinent literature to determine whether polymorphisms in the genes encoding toll-like receptors and dectin-1 increase the susceptibility to invasive aspergillosis. This study systematically reviewed the literature using the databases PubMed/PMC, Scopus, and Web of Science using the keywords invasive aspergillosis, polymorphism, Toll-like, and Dectin-1. From the initial search, 415 studies were found and according to our inclusion and exclusion criteria, eight studies were selected. Several studies described single-nucleotide polymorphisms (SNPs) that are associated with a greater susceptibility to invasive aspergillosis. These SNPs were found in the genes that encode toll-like receptors 1, 3, 4, and 5 and the gene that encodes dectin-1; upon activation, both cellular receptors initiate a signaling cascade that can result in the production of cytokines and chemokines. Thus, our literature review uncovered a significant association between polymorphisms in the genes that encode toll-like receptors and dectin-1 and invasive aspergillosis. More studies should be performed to better understand the relationship between toll-like receptor and dectin-1 genetic polymorphisms and invasive aspergillosis susceptibility.

The FTO rs9939609 polymorphism and obesity risk in teens: Evidence-based meta-analysis.

OBJECTIVE: This meta-analysis aims evaluate the association of the polymorphism rs9939609 of FTO with the risk of obesity among children and adolescents, based on the assessment of four genetic models: codominant, dominant, recessive alleles model. METHODS: Case-control studies, published between the years 2011-2015, were selected from tree available databases (PubMed, Scopus and Web of Science) and were analysed using Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) recommendations. Thirteen studies were included totalling 15,613 participants, divided into 7311 cases and 8302 controls. RESULTS: The FTO rs9939609 polymorphism was significantly associated with increased risk of obesity in children and adolescents for homozygous genotypes AA and heterozygous AT (TT vs. AT+AA: OR=0.723, 95% CI 0.629 to 0.832; p<0.0001). CONCLUSION: This meta-analysis shows that the FTO rs9939609 polymorphism in the gene is a risk factor for obesity in children and adolescents with the presence of the A allele, both homozygous genotype AA situation, as heterozygous AT.

Chronotype in breast cancer and relation to desynchronization of the circadian cycle / O cronotipo no câncer de mama e sua relação com a dessincronização do ciclo circadiano

Introduction: The circadian cycle plays several roles at the organism functions and are important to the maintenance of health, when synchronized. Nowadays, one of the main risk factors for the change of the sleep-wake cycle in the population is the high exposure to light at night, consequently deregulating the circadian cycle, inhibiting the release of melatonin and favoring oncogenesis. Objectives: The aim of this study was to identify the possible associations between circadian rhythm's desynchronization and breast cancer. Methods: This is a descriptive cross-sectional study and two collection instruments were used in it: sociodemographic questionnaire and the Horne and Ostberg matutinal-vespertine questionnaire. They were applied in a group of 74 women in a highly complex oncology service. Results: To evaluate whether the discriminant factors such as night work and chronotype exerted some influence on the discriminated factor that is breast cancer, χ2 test was applied showing that the characteristics among the groups were similar and so it was not possible to confirm that there is a relationship between them. Conclusions: More studies about the subject is needed

Introdução: O ciclo circadiano desempenha vários papéis nas funções do organismo e é importante para a manutenção da saúde, quando sincronizado. Atualmente, um dos principais fatores de risco para a mudança do ciclo vigília-sono na população é a alta exposição à luz noturna, desregulando consequentemente o ciclo circadiano, inibindo a liberação de melatonina e favorecendo a oncogênese. Objetivo: O objetivo deste estudo foi identificar as possíveis associações entre dessincronização do ritmo circadiano e o câncer de mama. Métodos: Trata-se de um estudo descritivo de corte transversal em que foram utilizados dois instrumentos de coleta: um questionário sociodemográfico e o questionário matutino-vespertino de Horne e Ostberg. Os questionários foram aplicados a um grupo de 74 mulheres em um serviço de oncologia. Resultados: Para avaliar se os fatores discriminantes como o trabalho noturno e o cronotipo exerceram alguma influência sobre o fator discriminado, câncer de mama, foi aplicado o teste do χ2, que revelou semelhança entre as características dos grupos estudados. Conclusões: Mais estudos sobre o assunto são necessários de forma a se compreender melhor a possível relação entre o ciclo circadiano e a susceptibilidade ao desenvolvimento de neoplasias, especialmente o câncer de mama

Polimorfismo nulo do gene GSTM1 na suscetibilidade do câncer de mama:evidências baseadas em meta-análise / Null polymorphism of GSTM1 gene in susceptibility of breast cancer: evidence based on meta-analysis

Introdução: O câncer de mama é a segunda neoplasia mais frequente no mundo e a primeira mais comum no sexo feminino. Dados epidemiológicos apontam o efeito de agentes carcinogênicos e fatores ambientais para maior susceptibilidade em desenvolver o câncer de mama. No contexto das avaliações moleculares, o polimorfismo nulo do gene GSTM1 é comumente estudado na tentativa de associá-lo ao desenvolvimento desta neoplasia. Objetivo: Avaliar se os indivíduos que apresentam o polimorfismo nulo para o gene GSTM1 possuem susceptibilidade ao câncer de mama. Métodos: Realizou-se meta-análise com 10 estudos do tipo caso-controle, que apresentavam pacientes com confirmação histológica de câncer de mama e que faziam uso da PCR e/ou sequenciamento de DNA para determinar o polimorfismo nulo do gene GSTM1. A análise foi realizada após a coleta dos dados necessários (autor, ano de publicação, país e resultados). Os cálculos estatísticos e a representação dos dados foram obtidos com o auxílio do software BioEstat® 5.0. Resultados: O total de indivíduos, após o agrupamento dos dados dos estudos, foi de 7.607 (3.759 casos e 3.848 controles). As frequências para o polimorfismo nulo do gene GSTM1 em pacientes com câncer de mama foram, respectivamente, 51,0% no grupo casos e 50,3% no grupo controle. A análise dos dados obtidos revelou OR: 0,967 e IC95% 0,883?1,060. Conclusão: Conforme os dados obtidos na meta-análise, não foi encontrada associação significativa entre o polimorfismo nulo do gene GSTM1 e o desenvolvimento do câncer de mama. Assim, os resultados do presente estudo mostram que o polimorfismo em questão não alterou suscetibilidade ao câncer de mama, portanto, devem-se levar em consideração outros fatores com maior significância, como: tabagismo, outros marcadores genéticos, tais como BRCA1 e BRCA2, paridade, entre outros.

Introduction: Breast cancer is the second most common cancer worldwide and the first more common in females. Epidemiological data show the effect of carcinogens and environmental factors in the increased susceptibility of developing breast cancer. In the context of molecular assessments, the null polymorphism of GSTM1 gene is commonly studied in an attempt to associate with the development of this neoplasm. Objective: To evaluate whether individuals with the GSTM1-null polymorphism possess susceptibility to breast cancer. Methods: It was conducted a meta-analysis of 10 case-control studies, which had patients with histological confirmed breast cancer and used PCR and/or DNA sequencing to determine the null polymorphism of GSTM1 gene. The analysis was performed after gathering the necessary data (author, publication year, country and results). Statistical calculations and the representation of the data were obtained with the help of BioEstat® 5.0 software. Results: The total number of individuals, after grouping the data was 7,607 (3,759 cases and 3,848 controls). The frequencies for the null polymorphism of GSTM1 gene were, respectively, 51.0% in the case group and 50.3% in the control group. The analysis of the obtained data revealed OR: 0.967 and 95%CI 0.883?1.060. Conclusion: According to the data obtained by meta-analysis it was not found significant association between GSTM1-null polymorphism and the development of breast cancer. Thus, the results of this study revealed that the polymorphism in question did not change the susceptibility to breast cancer, so it should be considered other factors with greater significance, such as smoking, other genetic markers like BRCA1 and BRCA2, parity, among others.

MDR1 and cytochrome P450 gene-expression profiles as markers of chemosensitivity in human chronic myelogenous leukemia cells treated with cisplatin and Ru(III) metallocomplexes.

Leukemia is a major type of cancer affecting a significant segment of the population, and especially children. In fact, leukemia is the most frequent childhood cancer, with 26 % of all cases, and 20 % mortality. The multidrug resistance phenotype (MDR) is considered one of the major causes of failure in cancer chemotherapy. The present study aimed to investigate the relationship between the expression of MDR1 and CYP450 genes in human chronic myelogenous leukemia cells (K-562) treated with cisplatin (cisPt) and two ruthenium-based coordinated complexes [cisCRu(III) and cisDRu(III)]. The tested compounds induced apoptosis in K-562 tumor cells as evidenced by caspase 3 activation. Results also revealed that the amplification of P-gp gene is greater in K-562 cells exposed to cisPt and cisCRu(III) than cisDRu(III). Taken together, all these results strongly demonstrate that MDR-1 overexpression in K-562 cells could be associated to a MDR phenotype, and moreover, it is also contributing to the platinum and structurally related compound, resistance in these cells.

Cytotoxic effects of the compound cis-tetraammine(oxalato)ruthenium(III) dithionate on K-562 human chronic myelogenous leukemia cells.

Chemotherapy is a common treatment for leukemia. Ruthenium complexes have shown potential utility in chemotherapy and photodynamic therapy. The identification of new chemotherapeutics agents is critical for further progress in the treatment of leukemia. Ruthenium complexes generally have lower toxicities compared to cisplatin attributed to their specific accumulation in cancer tissues. Based on these evidences, in the present work we studied the cytotoxic activity of the ruthenium(III) compound cis-tetraammine(oxalato)ruthenium(III) dithionate - {cis-[Ru(C2O4)(NH3)4]2(S2O6)} against human chronic myelogenous leukemia cells (K-562) tumor cell line. The tested compound induces cell death in a dose and time dependent manner on K-562 cells. It is found that the effect was improved linearly while prolonging the incubation time. Compared to the cell cycle profiles of untreated cells, flow cytometric analysis indicated the sub-G1 arresting effect of ruthenium compound on K-562 cells. In our study, {cis-[Ru(C2O4)(NH3)4]2(S2O6)} shows a significant increase in tailed cells in any of the concentrations tested compared with negative control. Consequently, the concentration of {cis-[Ru(C2O4)(NH3)4]2(S2O6)} might be associated cytotoxicity with direct effect on K-562 cells DNA. Thus, it can be deducted that ruthenium-based compounds present selectivity to enter both tumor and normal cells. Additional studies are needed to determine the molecular mechanisms of the active components and to evaluate the potential in vivo anticancer activity of the cis-tetraammine(oxalato)ruthenium(III) dithionate.

The ruthenium complexes cis-(dichloro)tetramineruthenium(III) chloride and cis-tetraammine(oxalato)ruthenium(III) dithionate overcome resistance inducing apoptosis on human lung carcinoma cells (A549).

Lung cancer is one of the leading causes of death in the world, and non-small cell lung carcinoma accounts for approximately 75-85 % of all lung cancers. In the present work, we studied the antitumor activity of the compound cis-(dichloro)tetramineruthenium(III) chloride {cis-[RuCl2(NH3)4]Cl} against human lung carcinoma tumor cell line A549. The present study aimed to investigate the relationship between the expression of MDR1 and CYP450 genes in human lung carcinoma cell lines A549 treated with cisCarboPt, cisCRu(III) and cisDRu(III). The ruthenium-based coordinated complexes presented low cytotoxic and antiproliferative activities, with high IC50 values, 196 (±15.49), 472 (±20.29) and 175 (±1.41) for cisCarboPt, cisCRu(III) and cisDRu(III), respectively. The tested compounds induced apoptosis in A549 tumor cells as evidenced by caspase 3 activation, but only at high concentrations. Results also revealed that the amplification of P-gp gene is greater in A549 cells exposed to cisCarboPt and cisCRu(III) than cisDRu(III). Taken together all these results strongly demonstrate that MDR-1 over-expression in A549 cells could be associated to a MDR phenotype of these cells and moreover, it is also contributing to the platinum, and structurally-related compound, resistance in these cells. The identification and characterization of novel mechanisms of drug resistance will enable the development of a new generation of anti-cancer drugs that increase cancer sensitivity and/or represent more effective chemotherapeutic agents.

Association of the TP53 codon 72 polymorphism and breast cancer risk: a meta-analysis.

This study was conducted in order to investigate the implications of the R72P polymorphism in the TP53 gene in breast cancer risk. The enlightenment of this matter might provide a piece of information about the potential implications of this polymorphism in patient risk. A meta-analysis was conducted considering a large sample size from studies with conflicting results on the R72P polymorphism in breast cancer patients. Relevant studies were selected from PubMed and SciELO databases for data extraction and statistical analysis. Database was built according to the continent and considering the genotype frequencies, sample size and genotyping methodology. The dominant models (RR vs RP + PP and RR + RP vs. PP), homozygous (RR vs. PP), heterozygous (RR vs. RP and RP vs. PP) and the allele (R vs. P) were used. Genotype frequencies were summarized and evaluated by χ(2) test of heterogeneity in 2×2 contingency tables with 95% CIs. Odds Ratios (OR) were calculated with a fixed-effect model (Mantel-Haenszel) or a random-effect model (DerSimonian-Laird) if the studies were considered homogeneous (P > 0.05) or heterogeneous (P < 0.05), respectively, using BioEstat® 5.0 software. Supported by a large sample size composed by 25,629 cases and 26,633 controls from 41 studies, we found significant association between the R72P polymorphism in the TP53 gene and the breast cancer risk. The overall data shows an increased risk due to the P allele dominant model, but not in Asia where the risk was associated with the R allele and R dominant model.

Induction of cell cycle arrest and apoptosis by ruthenium complex cis-(dichloro)tetramineruthenium(III) chloride in human lung carcinoma cells A549.

Lung cancer is one of the leading causes of death in the world, and non-small cell lung carcinoma (NSCLC) accounts for approximately 75-85% of all lung cancers. In the present work, we studied the cytotoxic activity, cell cycle arrest and induction apoptosis of the compound cis-(dichloro)tetramineruthenium(III) chloride {cis-[RuCl(2)(NH(3))(4)]Cl} in human lung carcinoma tumor cell line A549. The results of MTT and trypan blue assays showed that cis-[RuCl(2)(NH(3))(4)]Cl causes reduction in the viability of A549 cells when treating with 95 and 383 µM of the compound for 48 and 72 h. Lower concentrations of the compound (19, 3.8 and 0.38 µM), however, only slightly affected cell viability. The IC(50) value for the compound was about 383 µM. Survival analysis of the A549 cells after treatment with ruthenium(III) compound using long term clonogenic assay showed that it reduced colony formation ability at concentrations of 0.38 and 3.8 µM, and at concentrations of 95 and 383 µM no colonies were observed. Cell cycle analysis showed that compound ruthenium led to an accumulation of A549 cells in S phase and increased in the sub-G1 peak. In addition, cis-(dichloro)tetramineruthenium(III) chloride treatment induced apoptosis, as observed by the increased numbers of annexin V-positive cells and increased messenger RNA expression of caspase-3.

The ruthenium complex cis-(dichloro)tetrammineruthenium(III) chloride induces apoptosis and damages DNA in murine sarcoma 180 cells.

Ruthenium (III) complexes are increasingly attracting the interest of researchers due to their promising pharmacological properties. Recently, we reported that the cis-(dichloro)tetrammineruthenium (III) chloride compound has cytotoxic effects on murine sarcoma 180 (S-180) cells. In an effort to understand the mechanism responsible for their cytotoxicity, study we investigated the genotoxicity, cell cycle distribution and induction of apoptosis caused by cis- (dichloro) tetrammineruthenium (III) chloride in S-180 tumour cells. cis-(dichloro) tetrammineruthenium (III) chloride treatment induced significant DNA damage in S-180 cells, as detected by the alkaline comet assay. In the cell cycle analysis, cis-(dichloro) tetrammineruthenium (III) chloride caused an increase in the number of cells in G1 phase, accompanied by a decrease in the S and G2 phases after 24 h of treatment. In contrast, the cell cycle distribution of S-180 cells treated with cis-(dichloro) tetrammineruthenium (III) chloride for 48 h showed a concentration-dependent increase in the sub-G1 phase (indicating apoptosis), with a corresponding decrease in cells in the G1, S and G2 phases. In addition, cis-(dichloro) tetrammineruthenium(III) chloride treatment induced apoptosis in a time-dependent manner,as observed by the increased numbers of annexin V-positive cells. Taken together, these findings strongly demonstrate that DNA damage, cell cycle changes and apoptosis may correlate with the cytotoxic effects of cis-(dichloro) tetrammineruthenium (III) chloride on S-180 cells.

The compound cis-(dichloro)tetrammineruthenium(III) chloride induces caspase-mediated apoptosis in K562 cells.

Ruthenium(III) complexes are increasingly attracting the interest of researchers due to their promising pharmacological properties. In the present study, we investigated the ability of cis-(dichloro)tetrammineruthenium(III) chloride to produce lethal effects in human chronic myelogenous leukemia K562 cells. The MTT tetrazolium reduction test and the trypan blue exclusion assay revealed that the IC(50) for the compound after 48 h of incubation with K562 cells was approximately 10.74 and 73.45 microM, respectively. Interestingly, it was observed that this compound exhibits mild cytotoxicity towards MRC-5 human fibroblast cells (IC(50)>383 microM). Flow cytometric analysis revealed that cis-(dichloro)tetrammineruthenium(III) chloride was capable of change cell cycle distribution since the percentage of cells in the G1, S and G2 phases decreased. In addition, treatment with this compound induced apoptotic cell death in K562 cells, demonstrated by increased DNA content in the sub-G1-peak and a significant increase in caspase-3 activity. Assay using cyclosporin A, an inhibitor of the mitochondrial permeability transition pore (MPT) showed that the preincubation of K562 cells with this inhibitor had not effect on cis-(dichloro)tetrammineruthenium(III) chloride induced caspase-3 activation. In summary, cis-(dichloro)tetrammineruthenium(III) chloride displayed a significant cytotoxic effect through cell cycle arrest and apoptotic induction in K562 cells, which suggests that cis-(dichloro)tetrammineruthenium(III) chloride might have therapeutic potential against leukemia.

The ruthenium complex cis-(dichloro)tetraammineruthenium(III) chloride presents selective cytotoxicity against murine B cell lymphoma (A-20), murine ascitic sarcoma 180 (S-180), human breast adenocarcinoma (SK-BR-3), and human T cell leukemia (Jurkat) tumor cell lines.

The aim of present study was to verify the in vitro antitumor activity of a ruthenium complex, cis-(dichloro)tetraammineruthenium(III) chloride (cis-[RuCl(2)(NH(3))(4)]Cl) toward different tumor cell lines. The antitumor studies showed that ruthenium(III) complex presents a relevant cytotoxic activity against murine B cell lymphoma (A-20), murine ascitic sarcoma 180 (S-180), human breast adenocarcinoma (SK-BR-3), and human T cell leukemia (Jurkat) cell lines and a very low cytotoxicity toward human peripheral blood mononuclear cells. The ruthenium(III) complex decreased the fraction of tumor cells in G0/G1 and/or G2-M phases, indicating that this compound may act on resting/early entering G0/G1 cells and/or precycling G2-M cells. The cytotoxic activity of a high concentration (2 mg mL(-1)) of cis-[RuCl(2)(NH(3))(4)]Cl toward Jurkat cells correlated with an increased number of annexin V-positive cells and also the presence of DNA fragmentation, suggesting that this compound induces apoptosis in tumor cells. The development of new antineoplastic medications demands adequate knowledge in order to avoid inefficient or toxic treatments. Thus, a mechanistic understanding of how metal complexes achieve their activities is crucial to their clinical success and to the rational design of new compounds with improved potency.

The ruthenium complex cis-(Dichloro)Tetraammineruthenium(III) chloride presents immune stimulatory activity on human peripheral blood mononuclear cells.

Ruthenium compounds in general are well suited for medicinal applications. They have been investigated as immunosuppressants, nitric oxide scavengers, antimicrobial agents, and antimalarials. The aim of this study is to evaluate the immunomodulatory activity of cis-(dichloro)tetraammineruthenium(III) chloride (cis-[RuCl(2)(NH(3))(4)]Cl) on human peripheral blood mononuclear cells (PBMC). The cytotoxic studies performed here revealed that the ruthenium(III) complex presents a cytotoxic activity towards normal human PBMC, only at very high concentration. Results also showed that cis-[RuCl(2)(NH(3))(4)]Cl presents a dual role on PBMC stimulating proliferation and interleukin-2 (IL-2) production at low concentration and inducing cytotoxicity, inability to proliferate, and inhibiting IL-2 production at high concentration. The noncytotoxic activity of cis-[RuCl(2)(NH(3))(4)]Cl at low concentration towards PBMC, which correlates with the small number of annexin V positive cells and also the absence of DNA fragmentation, suggest that this compound does not induce apoptosis on PBMC. For the first time, we show that, at low concentration (10-100 microg L(-1)), the cis-[RuCl(2)(NH(3))(4)]Cl compound induces peripheral blood lymphocytes proliferation and also stimulates them to IL-2 production. These results open a new potential applicability of ruthenium(III) complexes as a possible immune regulatory compound acting as immune suppressor at high concentration and as immune stimulator at low concentration.