Differential expression of GSPT1 GGCn alleles in cancer

The human eukaryotic release factor 3a (eRF3a), encoded by the G1 to S phase transition 1 gene (GSPT1; alias eRF3a), is upregulated in various human cancers. GSPT1 contains a GGCn polymorphism in exon 1, encoding a polyglycine expansion in the N-terminal of the protein. The longer allele, GGC12, was previously shown to be associated to cancer. The GGC12 allele was present in 2.2% of colorectal cancer patients but was absent in Crohn disease patients and in the control group. Real-time quantitative RT-PCR analysis showed that the GGC12 allele was present at up to 10-fold higher transcription levels than the GGC10 allele (P < 0.001). No GSPT1 amplifications were detected, and there was no correlation between the length of the alleles and methylation levels of the CpG sites inside the GGC expansion. Using flow cytometry, we compared the levels of apoptosis and proliferation rates between cell lines with different genotypes, but detected no significant differences. Finally, we used a cytokinesis-block micronucleus assay to evaluate the frequency of micronuclei in the same cell lines. Cell lines with the longer alleles had higher frequencies of micronuclei in binucleated cells, which is probably a result of defects in mitotic spindle formation. Altogether, these findings indicate that GSPT1 should be considered a potential proto-oncogene.

eRF3a/GSPT1 12-GGC allele increases the susceptibility for breast cancer development

It is now widely recognized that translation factors are involved in cancer development and that components of the translation machinery that are deregulated in cancer cells may become targets for cancer therapy. The eukaryotic Release Factor 3 (eRF3) is a GTPase that associates with eRF1 in a complex that mediates translation termination. eRF3a/GSPT1 first exon contains a (GGC)n expansion coding for proteins with different N-terminal extremities. Herein we show that the longer allele (12-GGC) is present in 5.1% (7/137) of the breast cancer patients analysed and is absent in the control population (0/135), corresponding to an increased risk for cancer development, as revealed by Odds Ratio analysis. mRNA quantification suggests that patients with the 12-GGC allele overexpress eRF3a/GSPT1 in tumor tissues relative to the normal adjacent tissues. However, using an in vivo assay for translation termination in HEK293 cells, we do not detect any difference in the activity of the eRF3a proteins encoded by the various eRF3a/GSPT1 alleles. Although the connection between the presence of eRF3a/GSPT1 12-GGC allele and tumorigenesis is still unknown, our data suggest that the presence of the 12-GGC allele provides a potential novel risk marker for various types of cancer.

The D1822V APC polymorphism interacts with fat, calcium, and fiber intakes in modulating the risk of colorectal cancer in Portuguese persons

Background - Both genetic and environmental factors affect the risk of colorectal cancer (CRC). Objective - We aimed to examine the interaction between the D1822V polymorphism of the APC gene and dietary intake in persons with CRC. Design - Persons with CRC (n = 196) and 200 healthy volunteers, matched for age and sex in a case-control study, were evaluated with respect to nutritional status and lifestyle factors and for the D1822V polymorphism. Results - No significant differences were observed in energy and macronutrient intakes. Cases had significantly (P < 0.05) lower intakes of carotenes, vitamins C and E, folate, and calcium than did controls. Fiber intake was significantly (P = 0.004) lower in cases than in controls, whereas alcohol consumption was associated with a 2-fold risk of CRC. In addition, cases were significantly (P = 0.001) more likely than were controls to be sedentary. The homozygous variant for the APC gene (VV) was found in 4.6% of cases and in 3.5% of controls. Examination of the potential interactions between diet and genotype found that a high cholesterol intake was associated with a greater risk of colorectal cancer only in noncarriers (DD) of the D1822V APC allele (odds ratio: 1.66; 95% CI: 1.00, 2.76). In contrast, high fiber and calcium intakes were more markedly associated with a lower risk of CRC in patients carrying the polymorphic allele (DV/VV) (odds ratio: 0.50; 95% CI: 0.27, 0.94 for fiber; odds ratio: 0.51; 95% CI: 0.28, 0.93 for calcium) than in those without that allele. Conclusion - These results suggest a significant interaction between the D1822V polymorphism and the dietary intakes of cholesterol, calcium, and fiber for CRC risk.

Modulation of translation factor's gene expression by histone deacetylase inhibitors in breast cancer cells

The histone deacetylase inhibitors sodium butyrate (NaBu) and trichostatin A (TSA) exhibit anti-proliferative activity by causing cell cycle arrest and apoptosis. The mechanisms by which NaBu and TSA cause apoptosis and cell cycle arrest are not yet completely clarified, although these agents are known to modulate the expression of several genes including cell-cycle- and apoptosis-related genes. The enzymes involved in the process of translation have important roles in controlling cell growth and apoptosis, and several of these translation factors have been described as having a causal role in the development of cancer. The expression patterns of the translation mechanism, namely of the elongation factors eEF1A1 and eEF1A2, and of the termination factors eRF1 and eRF3, were studied in the breast cancer cell line MCF-7 by real-time quantitative reverse transcription-polymerase chain reaction after a 24-h treatment with NaBu and TSA. NaBu induced inhibition of translation factors' transcription, whereas TSA caused an increase in mRNA levels. Thus, these two agents may modulate the expression of translation factors through different pathways. We propose that the inhibition caused by NaBu may, in part, be responsible for the cell cycle arrest and apoptosis induced by this agent in MCF-7 cells.

Knowledge, attitude and practice of mammography among women users of public health services

OBJECTIVE: To evaluate knowledge, attitude and practice related to mammography among women users of local health services, identifying barriers to its performance. METHODS: A total of 663 women were interviewed at 13 local health centers in a city of Southeastern Brazil, in 2001. Interviewees were randomly selected at each center and they were representative from different socioeconomic conditions. The number of interviewees at each center was proportional to monthly mean appointments. For data analysis, answers were described as knowledge, attitude, practice and their respective adequacies and then they were correlated with control variables through the chi-square test. RESULTS: Only 7.4% of the interviewees had adequate knowledge on mammography, while 97.1% of women had an adequate attitude. The same was seen for the practice of mammography that was adequate in 35.7% of the cases. The main barrier to mammography was lack of referral by physicians working at the health center (81.8%). There was an association between adequacy of attitude and five years or more of education and being married. There was also an association between adequacy of mammography practice and being employed and family income up to four minimum wages. CONCLUSIONS: Women users of local health services had no adequate knowledge and practice related to mammography despite having an adequate attitude about this exam.

Oral health, hygiene practices and oral cancer

OBJECTIVE: To assess the association between oral health and hygiene practices and oral cancer. METHODS: Hospital-based case-control study in the metropolitan area of São Paulo, southeastern Brazil, from 1998 to 2002. A total 309 patients with squamous cell carcinoma of the mouth and the pharynx and 468 controls matched by sex and age were included in the study. Cases were recruited in seven reference hospitals and controls were selected in five out of the seven participating hospitals. Detailed information on smoking, alcohol consumption, schooling, oral health status and hygiene practices were obtained through interviews. Odds ratios (OR) and 95% confidence intervals (95% CI), adjusted by sex, age, schooling, smoking, alcohol consumption as well as the variables oral health status and hygiene practices were estimated using unconditional logistic regression analyses. RESULTS: The use of complete dental prosthesis was not associated with oral cancer but regular gum bleeding showed a strong association (OR 3.1; 95% CI 1.2-7.9). Those who never attended a dental visit were more likely to have oral cancer (OR 2.5; 95% CI 1.3-4.8). Daily mouthwash use showed a stronger association to pharynx (OR 4.7; 95% CI 1.8-12.5) than mouth cancer (OR 3.2; 95% CI 1.6-6.3). CONCLUSIONS: Gum bleeding, no dental care, and daily mouthwash use were factors associated with oral cancer regardless of tobacco and alcohol consumption.

Factors related to inadequate cervical cancer screening in two Brazilian state capitals

OBJECTIVE:To analyze factors associated with cervical cancer screening failure. METHODS:Population-based cross-sectional study with self-weighted two-stage cluster sampling conducted in the cities of Fortaleza (Northeastern Brazil) and Rio de Janeiro (Southeastern Brazil) in 2002. Subjects were women aged 25-59 years in the last three years prior to the study. Data were analyzed through Poisson regression using a hierarchical model. RESULTS: The proportion of women who did not undergo the Pap smear test in Fortaleza and Rio de Janeiro was 19.1% (95% CI: 16.1;22.1) and 16.5% (95% CI: 14.1;18.9), respectively. Higher prevalence ratios of cervical cancer screening failure in both cities were seen among women with low education and low per capita income, old age, unmarried, who never underwent mammography, clinical breast examination, and blood glucose and cholesterol level testing. Smokers also had lower screening rates compared to non-smoker women and this difference was only statistically significant in Rio de Janeiro. CONCLUSIONS:The study findings point to the need of intervention focusing particularly women in worse socioeconomic conditions and access to healthcare, old-aged and unmarried. Education activities must prioritize screening of asymptomatic women and early diagnosis for symptomatic women and access to adequate diagnostic methods and treatment should be provided.

Effectiveness of see-and-treat for approaching pre-invasive lesions of uterine cervix

OBJECTIVE: To compare the effectiveness between the see-and-treat (S&T) approach and the conventional one (with prior biopsy) for squamous intraepithelial lesions of uterine cervix. METHODS: A cross-sectional study was conducted with 900 nonpregnant women with cytology suggestive of high grade squamous intraepithelial lesions in the city of Rio de Janeiro, Southeastern Brazil, between 1998 and 2004. The S&T approach consists of a large loop excision of the transformation zone procedure and is recommended when cytology is suggestive of high grade squamous intraepithelial lesion, satisfactory colposcopy with abnormalities compatible with the suspected cytological results, and the lesion is limited to the ectocervix or extends up to one centimeter of the endocervical canal. A subgroup of 336 patients whose colposcopy was considered satisfactory was analyzed, and they were divided into two groups for comparison: patients treated without prior biopsy (n = 288) and patients treated after a biopsy showing high grade squamous intraepithelial lesions (n = 48). Patients who were not treated or only treated more than a year later after recruitment at the colposcopy unit were considered dropouts. RESULTS: Of patients recruited during the study period, 71 were not treated or were only treated for at least a year. The overall dropout rate was 7.9% (95% CI: 6.1;9.7). Mean time elapsed between patient recruitment and treatment was 17.5 days in the S&T group and 102.5 days in the prior biopsy group. Dropout rates were 1.4% (95% CI: 0.04;2.7) and 5.% (95% CI: 0;12.3), respectively (p=0.07). The proportion of overtreated cases (negative histology) in the S&T group was 2.0% (95% CI: 0.4;3.6). CONCLUSIONS: The difference in the mean time elapsed between patient recruitment and treatment indicates that S&T is a time-saving approach The proportion of negative cases from using the S&T approach can be regarded as low.

Survival of a cohort of women with cervical cancer diagnosed in a Brazilian cancer center

OBJECTIVE: To assess overall survival of women with cervical cancer and describe prognostic factors associated. METHODS: A total of 3,341 cases of invasive cervical cancer diagnosed at the Brazilian Cancer Institute, Rio de Janeiro, southeastern Brazil, between 1999 and 2004 were selected. Clinical and pathological characteristics and follow-up data were collected. There were performed a survival analysis using Kaplan-Meier curves and a multivariate analysis through Cox model. RESULTS: Of all cases analyzed, 68.3% had locally advanced disease at the time of diagnosis. The 5-year overall survival was 48%. After multivariate analysis, tumor staging at diagnosis was the single variable significantly associated with prognosis (p<0.001). There was seen a dose-response relationship between mortality and clinical staging, ranging from 27.8 to 749.6 per 1,000 cases-year in women stage I and IV, respectively. CONCLUSIONS: The study showed that early detection through prevention programs is crucial to increase cervical cancer survival.

Validity of self-reported hearing loss in adults: performance of three single questions

OBJECTIVE: To estimate the validity of three single questions used to assess self-reported hearing loss as compared to pure-tone audiometry in an adult population. METHODS: A validity study was performed with a random sub-sample of 188 subjects aged 30 to 65 years, drawn from the fourth wave of a population-based cohort study carried out in Salvador, Northeastern Brazil. Data were collected in household visits using questionnaires. Three questions were used to separately assess self-reported hearing loss: Q1, "Do you feel you have a hearing loss?"; Q2, "In general, would you say your hearing is 'excellent,' 'very good,' 'good,' 'fair,' 'poor'?"; Q3, "Currently, do you think you can hear 'the same as before', 'less than before only in the right ear', 'less than before only in the left ear', 'less than before in both ears'?". Measures of accuracy were estimated through seven measures including Youden index. Responses to each question were compared to the results of pure-tone audiometry to estimate accuracy measures. RESULTS: The estimated sensitivity and specificity were 79.6%, 77.4% for Q1; 66.9%, 85.1% for Q2; and 81.5%, 76.4% for Q3, respectively. The Youden index ranged from 51.9% (Q2) to 57.0% (Q1) and 57.9% (Q3). CONCLUSIONS: Each of all three questions provides responses accurate enough to support their use to assess self-reported hearing loss in epidemiological studies with adult populations when pure-tone audiometry is not feasible.

Efeitos auditivos em doentes com tumores de cabeça e pescoço e tumores cerebrais sujeitos a Radioterapia e terapia combinada

Introdução: A capacidade auditiva dos doentes com neoplasias de cabeça e pescoço e tumores cerebrais pode ser comprometida com os tratamentos antineoplásicos realizados. A Quimioterapia com cisplatina pode provocar perda auditiva de condução ou neurossensorial, podendo agravar-se quando combinada com Radioterapia (RT). O objectivo deste trabalho foi a análise da relação entre a Terapia Combinada (Cisplatina+RT) e a Radioterapia isolada, e os seus efeitos adversos sobre a audição tendo em consideração a inclusão das estruturas do ouvido no campo de tratamento de RT. Métodos: Foram seguidos 10 doentes submetidos a Terapia Combinada (grupo TC) e 11 a Radioterapia isolada (grupo RT). A avaliação audiológica realizou-se antes do inicio (M1), no fim (M2) e um mês após (M3) o termo dos tratamentos e incluiu anamnese audiológica, otoscopia e audiometria tonal. Resultados: No grupo TC, 94,4% dos doentes apresentaram uma relação directamente proporcional entre a dose de radiação na cóclea e a perda auditiva. Esta relação só se verificou em 31% dos doentes do grupo RT, tendo-se verificado diferenças significativas entre grupos (p <0,001). Conclusões: Verificou-se maior incidência da perda auditiva no grupo TC relativamente ao grupo RT. Sugere-se um melhor planeamento do tratamento de RT, reduz - indo a dose à cóclea com o objectivo de minimizar a perda auditiva neurossensorial irreversível, sobretudo quando são utilizadas as duas modalidades de tratamento.

Self-reported hearing performance in workers exposed to solvents

OBJECTIVE: To compare hearing performance relating to the peripheral and central auditory system between solvent-exposed and non-exposed workers. METHODS: Forty-eight workers exposed to a mixture of solvents and 48 non-exposed control subjects of matched age, gender and educational level were selected to participate in the study. The evaluation procedures included: pure-tone audiometry (500 - 8,000 Hz), to investigate the peripheral auditory system; the Random Gap Detection test, to assess the central auditory system; and the Amsterdam Inventory for Auditory Disability and Handicap, to investigate subjects' self-reported hearing performance in daily-life activities. A Student t test and analyses of covariance (ANCOVA) were computed to determine possible significant differences between solvent-exposed and non-exposed subjects for the hearing level, Random Gap Detection test and Amsterdam Inventory for Auditory Disability and Handicap. Pearson correlations among the three measures were also calculated. RESULTS: Solvent-exposed subjects exhibited significantly poorer hearing thresholds for the right ear than non-exposed subjects. Also, solvent-exposed subjects exhibited poorer results for the Random Gap Detection test and self-reported poorer listening performance than non-exposed subjects. Results of the Amsterdam Inventory for Auditory Disability and Handicap were significantly correlated with the binaural average of subject pure-tone thresholds and Random Gap Detection test performance. CONCLUSIONS: Solvent exposure is associated with poorer hearing performance in daily life activities that relate to the function of the peripheral and central auditory system.

Survey of hearing disorders in an urban population in Rondonia, Northern Brazil

OBJECTIVE: To identify the prevalence of hearing loss for the population in the urban area. METHODS: A cross-sectional household survey based on the World Health Organization Ear and Hearing Disorders Survey Protocol was conducted in 298 households in the urban area of Monte Negro, Rondonia, Northern Brazil, from 2005 to 2007. Ear examinations, behavioral audiometry and pure tone audiometry were conducted on 577 individuals. RESULTS: The results showed that 3.8% (95%CI 2.17;5.45) of population were classified in the disabling hearing impairment category. The prevalence of moderate hearing impairment was 3.4%; severe impairment was 0.4%; and profound hearing impairment was not found. CONCLUSIONS: The impairing hearing loss prevalence found in this study is within of the international prevalence for this level of hearing loss and smaller than observed in a previous study in the South region of Brazil.

Relatório de estágio

I - As minhas expectativas eram elevadas pois este regresso à Escola Superior de Música de Lisboa permitia-me voltar a trabalhar com os professores que me formaram como músico e professor e com eles poder actualizar-me sobre vários temas ligados à pedagogia. Este aspecto é muito importante pois chego à conclusão que o tempo por vezes provoca-nos excesso de confiança que parece “cegar-nos” não nos deixando ver erros pedagógicos muitas vezes evitáveis. Quando ingressei neste estágio sentia-me confiante e seguro quanto às minhas capacidades como professor. O momento de viragem na minha perspectiva do estágio dá-se quando surgem as observações/gravações e respectivas análises e reflexões das aulas. Procurei trabalhar nessas aulas da forma mais natural possível pois o meu objectivo era observar o meu trabalho diário. A primeira observação das aulas permitiu-me anotar algumas coisas menos boas. Contudo, quando essa observação foi feita com o professor de didática os aspectos menos positivos ganharam uma enorme proporção: (1) falhas ao nível da instrução: demasiado longo, (2) feedback de pouca qualidade ou eficácia , (3) pouca percentagem de alunos que atingiam os objectivos., (4) ritmo de aula por vezes baixo devido a períodos longos de instrução ou devido a uma má gestão do espaço. Todos estes problemas eram mais visíveis quando as turmas eram maiores. Ao longo do estágio, e após a detecção destas falhas, fui procurando evitar estas práticas em todas as turmas onde leccionava. Senti que o ritmo de aula aumentou substancialmente não apenas à custa da energia do professor e de boas estratégias mas porque sobretudo se “falava menos e trabalhava-se mais”. Os erros dos alunos passaram a ser corrigos enquanto trabalhavam (feedback corretivo próximo do momento positivo ou negativo), o feedback positivo passou a ser mais destacado, a disposição da sala alterou-se de forma aos alunos estarem mais perto do professor, e este procurou ser menos “criativo” no momento de alterar o plano de aula devido a ideias momentâneas o que provocou mais tempo para cada estratégia e para que mais alunos fossem atingindo os objectivos. Apesar da evolução no sentido de proporcionar aos alunos aulas mais rentáveis e de ainda melhor qualidade, existe a consciência que alguns dos erros cometidos eram hábitos e como tal poderão levar algum tempo a ser corrigidos. Contudo, existe a consciência e a vontade em debelá-los da minha prática docente.

Gender and racial inequalities in trends of oral cancer mortality in Sao Paulo, Brazil

OBJECTIVE:To analyse recent trends in oral cancer mortality, focusing specifically on differences concerning gender and race.METHODS:Official information on deaths and population in the city of Sao Paulo, 2003 to 2009, were used to estimate mortality rates from oral cancer (C00 to C10, International Classification of Diseases, 10th Revision), adjusted for age and stratified by gender (females and males) and race (blacks and whites). The Prais-Winsten auto-regression procedure was used to analyse the time series.RESULTS:During the study period, 8,505 individuals living in the city of Sao Paulo died of oral cancer. Rates increased for females (rate of yearly increase = 4.4%, 95%CI 1.4;7.5), and levelled off for men, which represents an inversion of previous trends among genders in the city. Increases were identified for blacks, with a high rate of yearly increase of 9.1% (95%CI 5.5;12.9), and levelled off for whites. Oral cancer mortality in blacks almost doubled during the study period, and surpassed mortality in whites for almost all categories.CONCLUSIONS:Mortality presented a higher increase among women than in men, and it doubled among backs. The surveillance of trends of oral cancer mortality across gender and racial groups may contribute to implementing socially appropriate health policies, which concurrently reduce the burden of disease and the attenuation of unfair, avoidable and unnecessary inequalities in health.