Correlation of breast cancer risk factors with HER-2/neu protein overexpression according to menopausal and estrogen receptor status

BACKGROUND: Several researchers have claimed that classification of tumours on the basis of HER-2/neu overexpression or amplification may define a subset of breast cancer in which the net effect of a risk factor could be rather more obvious and its impact on breast cancer development more clear. We decided to investigate, in a group of patients from a geographical area with a low incidence of breast cancer, whether HER-2/neu positive tumours are correlated with established or suspected risk factors for breast cancer and thus to identify distinct subgroups of high risk women. METHODS: This study analysed data from patients who attended the Breast Unit at the University Hospital of Heraklion, Crete, Greece between 1996 and 2002. 384 women with primary invasive breast cancer were compared with 566 screened women who were referred to the Unit and had not developed breast neoplasm by the time the data were analysed. Risk factor data were obtained from each subject by personal interviews using a structured questionnaire. The detection and scoring of the HER-2/neu protein, estrogen and progesterone receptor expression were performed using immunochemistry. Odds ratios and 95% confidence intervals were determined by chi-square test and logistic regression analysis. Case-case odds ratios were calculated in order to measure the risk heterogeneity between HER-2/neu+ and HER-2/neu-tumours. Separate analyses were performed for premenopausal and postmenopausal women and according to estrogen receptor status. RESULTS: In multivariate analysis without HER-2/neu stratification, an increased breast cancer risk was associated with only four of the factors examined: use of oral contraceptives (OR = 4.40, 95%C.I: 1.46–13.28), use of HRT (OR = 7.34, 95%C.I: 2.03–26.53), an age at first full pregnancy more than 23 years (OR = 1.91, 95%C.I: 1.29–2.83) and body mass index more than 29 kg/m(2 )(OR = 3.13, 95%C.I: 2.02–4.84). Additionally, a history of abortion or miscarriage (OR = 0.56, 95%C.I: 0.38–0.82) was correlated with a decreased risk of breast cancer. In the case to case comparison only BMI >29 kg/m(2 )revealed a relative connection that was stronger with positive than with negative HER-2/neu tumours (ratio of OR's = 2.23, 95%C.I: 1.20–4.15, p = 0.011). This may indicate evidence of heterogeneity of a rather significant degree for this factor. In the ER negative group an age at first full pregnancy >23 years and a BMI >29 kg/m(2 )were associated with an increased risk in both HER-2/neu groups, but the association was significantly stronger for the latter factor in the positive HER-2/neu tumours (ratio of OR's = 2.46, 95%CI: 0.97–6.21). CONCLUSIONS: Our study did not confirm that the established or putative hormonal breast cancer risk factors differ regarding their relations with HER-2/neu+ versus HER-2/neu-breast tumours, with the exception of increased BMI. Further innovative studies with larger sample sizes are needed to examine how the status of these potentially modifiable breast cancer risk factors interacts with biological markers such as HER-2/neu oncoprotein

Mutations with pathogenic potential in proteins located in or at the composite junctions of the intercalated disk connecting mammalian cardiomyocytes: a reference thesaurus for arrhythmogenic cardiomyopathies and for Naxos and Carvajal diseases

In the past decade, an avalanche of findings and reports has correlated arrhythmogenic ventricular cardiomyopathies (ARVC) and Naxos and Carvajal diseases with certain mutations in protein constituents of the special junctions connecting the polar regions (intercalated disks) of mature mammalian cardiomyocytes. These molecules, apparently together with some specific cytoskeletal proteins, are components of (or interact with) composite junctions. Composite junctions contain the amalgamated fusion products of the molecules that, in other cell types and tissues, occur in distinct separate junctions, i.e. desmosomes and adherens junctions. As the pertinent literature is still in an expanding phase and is obviously becoming important for various groups of researchers in basic cell and molecular biology, developmental biology, histology, physiology, cardiology, pathology and genetics, the relevant references so far recognized have been collected and are presented here in the following order: desmocollin-2 (Dsc2, DSC2), desmoglein-2 (Dsg2, DSG2), desmoplakin (DP, DSP), plakoglobin (PG, JUP), plakophilin-2 (Pkp2, PKP2) and some non-desmosomal proteins such as transmembrane protein 43 (TMEM43), ryanodine receptor 2 (RYR2), desmin, lamins A and C, striatin, titin and transforming growth factor-β3 (TGFβ3), followed by a collection of animal models and of reviews, commentaries, collections and comparative studies

Capacidade reprodutiva e preferência da traça-das-crucíferas para diferentes brassicáceas Reproductive capacity and preference of the diamondback moth feeding on different brassicacea

O objetivo desta pesquisa foi comparar diferentes cultivares de brassicáceas em relação à capacidade reprodutiva e preferência para alimentação e oviposição da traça-das-crucíferas. Os experimentos foram realizados utilizando-se as cultivares de repolho Midori, Chato-de-Quintal, híbridos da Top Seed® - Agristar (TPC 308, TPC 681 e TPC 668), couve-flor Bola de Neve, couve brócolis Ramoso Piracicaba Precoce e couve Manteiga da Geórgia, sendo esta última utilizada como padrão de suscetibilidade. Por meio dos dados biológicos de P. xylostella foram estimados os parâmetros necessários para a construção de tabela de vida de fertilidade, para comparação das cultivares testadas em relação à capacidade reprodutiva da praga. Em gaiolas de criação da traça-das-crucíferas foram colocados quatro quartos de folha, dois a dois, que justapostos formavam um círculo de 8 cm de diâmetro, confrontando-se os materiais dois a dois. As partes foram dispostas equidistantemente, para realização do teste de dupla chance de escolha (preferência para alimentação e oviposição) e de múltipla chance de escolha, confrontando todos os substratos (preferência para alimentação). As cultivares que proporcionaram melhor desenvolvimento e reprodução para a traça-das-crucíferas foram couve Manteiga da Geórgia e couve brócolis. Para preferência alimentar constatou-se alta suscetibilidade em couve Manteiga e TPC 681 e para preferência de oviposição alta preferência para couve-flor Bola de Neve. Com isso, sugere-se a divisão das cultivares estudadas em quatro classes distintas: repolho Midori como moderadamente resistente (MR); couve-flor Bola de Neve e repolho Chato-de-Quintal como suscetíveis (S); couve brócolis, TPC308, TPC681 e TPC668 como moderadamente suscetíveis (MS); e couve Manteiga como altamente suscetível (AS).<br>We compared different cultivars of crucifer in relation to reproductive capacity and preference for feeding and oviposition of the diamondback moth. The experiments were carried out with the following cultivars: Midori and Chato-de-Quintal cabbage, hybrids of cabbage Top Seed® - Agristar (TPC 308, TPC 681 and TPC 668), cauliflower Bola de Neve, broccolis Ramoso Piracicaba Precoce and collard green Manteiga da Geórgia, being this last one used as the susceptible control. Through the biological parameters of P. xylostella we elaborated a fertility life table, Comparing the cultivars in relation to the pest reproductive capacity. Four leaf parts were placed in diamondback moth rearing chambers, being two leaves of the treatment and two of the control which, put together formed a circle with 8 cm in diameter. The parts were disposed in an equidistantly form, to perform the dual-choice test (feeding and oviposition preference) and multiple-choice test, confronting all substrates (feeding preference). The cultivars that provided better development and reproduction for the diamondback moth were collard green Manteiga da Georgia and broccolis Ramoso Piracicaba Precoce. For feeding preference high susceptibility was verified in collard green Manteiga da Geórgia and TPC 681 and for oviposition preference high preference was observed for cauliflower Bola de Neve. Four different groups of cultivars could be formed: cabbage Midori as moderately resistant (MR); cauliflower Bola de Neve and cabbage Chato-de-Quintal as susceptible (S); broccolis, TPC 308, TPC 681 and TPC 668 as moderately susceptible (MS); and collard green as highly susceptible (HS)