Ovarian cancer

Ovarian cancer is not a single disease and can be subdivided into at least five different histological subtypes that have different identifiable risk factors, cells of origin, molecular compositions, clinical features and treatments. Ovarian cancer is a global problem, is typically diagnosed at a late stage and has no effective screening strategy. Standard treatments for newly diagnosed cancer consist of cytoreductive surgery and platinum-based chemotherapy. In recurrent cancer, chemotherapy, anti-angiogenic agents and poly(ADP-ribose) polymerase inhibitors are used, and immunological therapies are currently being tested. High-grade serous carcinoma (HGSC) is the most commonly diagnosed form of ovarian cancer and at diagnosis is typically very responsive to platinum-based chemotherapy. However, in addition to the other histologies, HGSCs frequently relapse and become increasingly resistant to chemotherapy. Consequently, understanding the mechanisms underlying platinum resistance and finding ways to overcome them are active areas of study in ovarian cancer. Substantial progress has been made in identifying genes that are associated with a high risk of ovarian cancer (such as BRCA1 and BRCA2), as well as a precursor lesion of HGSC called serous tubal intraepithelial carcinoma, which holds promise for identifying individuals at high risk of developing the disease and for developing prevention strategies

Structural characterization of diastereoisomeric ethano adducts derived from the reaction of 2'-deoxyguanosine with trans,trans-2,4-decadienal

Background levels of exocyclic DNA adducts have been detected in rodent and human tissues. Several studies have focused on bifunctional electrophiles generated from lipid peroxidation as one of the endogenous sources of these lesions. We have previously shown that the reaction of 2'-deoxyguanosine (dGuo) with trans,trans-2,4-decadienal (DDE), a highly cytotoxic aldehyde generated as a product of lipid peroxidation in cell membranes, results in the formation of a number of different base derivatives. Three of these derivatives have been fully characterized as 1,N-2-etheno-2'-deoxyguanosine adducts. In the present work, four additional adducts, designated A3-A6, were isolated from in vitro reactions by reversed-phase HPLC and fully characterized on the basis of spectroscopic measurements. Adducts A3-A6 are four diastereoisomeric 1,N-2-hydroxyethano-2'-deoxyguanosine derivatives possessing a carbon side chain with a double bond and a hydroxyl group. The systematic name of these adducts is 6-hydroxy3-(2'-deoxy-beta-D-erythro-pentafuranosyl)-7-((E)-1-hydroxy-oct-2-enyl)-3,5,6,7-tetrahydro-imidazo- [1,2-a]purin-9-one. The proposed reaction mechanism yielding adducts A3-A6 involves DDE epoxidation at C2, followed by nucleophilic addition of the exocyclic amino group of dGuo to the C1 of the aldehyde and cyclization, via nucleophilic attack, on the C2 epoxy group by N-1. The formation of adducts A1-A6 has been investigated in acidic, neutral, and basic pH in the presence of H2O2 or tent-butyl hydroperoxide. Neutral conditions, in the presence of H2O2, have favored the formation of adducts A1 and A2, with minor amounts of A3-A6, which were prevalent under basic conditions. These data indicate that DDE can modify DNA bases through different oxidative pathways involving its two double bonds. It is important to structurally characterize DNA base derivatives induced by alpha,beta-unsaturated aldehydes so that the genotoxic risks associated with the lipid peroxidation process can be assessed

Structural characterization of an etheno-2 '-deoxyguanosine adduct modified by tetrahydrofuran

The reaction of 2'-deoxyguanosine with the alpha,beta-unsaturated aldehydes trans-2-octenal, trans-2-nonenal, trans-2-decenal, trans,trans-2,4-nonadienal, and trans,trans-2,4-decadienal in THF gives rise to three novel adducts: 3-(2'-deoxy-beta-D-erythro-pentafuranosyl)-7-[3-hydroxy-1-(3(2'-deoxy-beta-D-erythro-pentafuranosyl)-3,5-dihydro-imidazo[1,2-alpha]purin-9-one-7-yl)-propyl] -3,5-dihydro-imidazo[1,2-alpha]purin-9-one (M) and 3-(2'-deoxy-beta-D-erythro-pentafuranosyl)-7-(tetrahydrofuran-2-yl)-3,5-dihydro-imidazo[1,2-alpha]purin-9-one (A8 and A9), which are not observed in the absence of THF. These adducts were isolated from in vitro reactions by reversed-phase HPLC and fully characterized on the basis of spectroscopic measurements. Adduct A7 consists of two 1,N-2-etheno-2'-deoxyguanosine (1,N-2-epsilondGuo) residues linked to a hydroxy-carbon side chain; adducts A8 and A9 are interconvertible 1,N-2-epsilondGuo derivatives bearing a THF moiety. The proposed reaction mechanism involves the electrophilic attack on 1,N-2-epsilondGuo by the carbonyl of 4-hydroxy-butanal, generated via ring opening of alpha-hydroxy-THF (THF-OH), yielding adducts A8 and A9. A further combination of these adducts with another 1,N-2-epsilondGuo produces the double adduct A7. These findings demonstrate that reactions of unsaturated aldehydes in the presence of THF produce novel condensation 1,N-2-epsilondGuo-THF adducts. Further studies would indicate the relevance of these adducts in THF toxicity.Univ Sao Paulo, Inst Quim, Dept Bioquim, BR-05508900 Sao Paulo, BrazilUniv Estadual Paulista, Inst Ciencias Exatas & Tecnol, Programa Posgrad Engn Prod, BR-04026002 Sao Paulo, BrazilUniv Sao Paulo, Dept Anal Clin & Toxicol, Fac Ciencias Farmaceut, BR-05508900 Sao Paulo, BrazilUniv Estadual Paulista, Inst Ciencias Exatas & Tecnol, Programa Posgrad Engn Prod, BR-04026002 Sao Paulo, Brazi

Relação entre o tempo e o tipo de amamentação e as funções do sistema estomatognático

OBJETIVO: investigar a relação do tempo e tipo de aleitamento com as funções de mastigação, deglutição e respiração. MÉTODO: a amostra foi constituída por 52 crianças de ambos os sexos, na faixa etária de 5 a 8 anos. Utilizando-se de questionário, foram coletados dados referentes ao tipo e tempo de amamentação e respiração das crianças. As mesmas foram submetidas à avaliação clínica das funções, a qual baseou-se no Protocolo de Avaliação Miofuncional Orofacial com Escores Expandido (AMIOFE- E). Os dados foram analisados de forma descritiva e estatística. Para testar a normalidade da variável quantitativa, utilizou-se o teste Lilliefors. Todas as relações entre variáveis foram realizadas por meio do teste Qui-quadrado, considerando nível de significância de 5%. RESULTADOS: não houve relação estatisticamente significante entre o tempo e o tipo de aleitamento e as variáveis respiração e deglutição. Encontrou-se significância estatística entre tipo de aleitamento e a mastigação, mas não entre o tempo de aleitamento e esta variável. Além disso, a relação significante não seguiu padrão esperado. CONCLUSÃO: foi possível concluir que, de um modo geral, não houve relação significante entre o tempo e o tipo de aleitamento com as funções estudadas, exceto pela significância entre o tipo de aleitamento e a mastigação. Provavelmente a falta de significância deva-se ao fato do desenvolvimento de todo o sistema estomatognático ter origem multifatorial. A significância estatística encontrada para a função de mastigação, visto que foi com padrão inesperado, pode ter ocorrido em virtude do restrito número de sujeitos em cada subgrupo.PURPOSE: to investigate the relation between time and type of feeding with chewing, swallowing and breathing functions. METHOD: the sample consisted of 52 children of both genders, aged between 5 and 8 year-old. Through a questionnaire, we collected data regarding type and duration of children’s breastfeeding and breathing. The children were submitted to clinical evaluation of functions, based on the Orofacial Myofunctional Assessment Protocol with Expanded Scores (AMIOFE-E). Data were descriptively and statistically analyzed. For testing the normality of the quantitative variable, we used the Lilliefors test. All relations among the variables were checked through Chi-square test, considering a 5% significance level. RESULTS: there was no statistically significant relation between duration and type of feeding and breathing and swallowing variables. There was a statistical significance between feeding type and chewing, but not between feeding duration and this variable. Furthermore, the significant relation failed to follow the expected pattern. CONCLUSION: it was possible to conclude that, generally, there was no significant relation between time and type of feeding and the investigated functions, except for the significance between type of feeding and chewing. Probably, the lack of significance is due to the fact that the development of all the stomatognathic system has multifactorial sources. The statistical significance found as for the chewing function, since it showed an unexpected pattern, may have occurred because of the restricted number of subjects in each subgroup

Aleitamento materno como fator de proteção contra a instalação de hábitos bucais deletérios

Objetivo: avaliar a possível associação entre as variáveis sociodemográficas, desmame precoce e o desenvolvimento e manutenção dos hábitos bucais deletérios em crianças de três a cinco anos de idade das creches públicas de Vitória/ES.Método: trata-se de um estudo longitudinal, retrospectivo, com uma amostra final de 903 escolares, aleatorizada e representativa das 9.829 crianças matriculadas. Para a comparação entre as variáveis predictoras e hábitos foi utilizado o teste exato de Fisher e a força da associação medida pelo Odds Ratio.Resultados: 12,4% das crianças apresentaram hábito de sucção digital e 37,7%, o de chupeta. Não foi verificada associação estatisticamente significante do hábito de sucção digital com desmame precoce. As crianças do sexo feminino (p=0,045) demonstraram 20% mais chance de adquirir e permanecer com o hábito de chupeta, e as que tiveram o desmame precoce apresentaram aproximadamente quatro vezes mais a chance de desenvolver o hábito de chupetas (p= 0.000).Conclusão: associação entre hábito de chupeta e desmame precoce foi verificada. O desmame precoce pode ser considerado fator de risco para a permanência do hábito de chupeta