Cytoplasmic Skp2 Expression Is Increased in Human Melanoma and Correlated with Patient Survival

BACKGROUND: S-phase kinase protein 2 (Skp2), an F-box protein, targets cell cycle regulators via ubiquitin-mediated degradation. Skp2 is frequently overexpressed in a variety of cancers and associated with patient survival. In melanoma, however, the prognostic significance of subcellular Skp2 expression remains controversial. METHODS: To investigate the role of Skp2 in melanoma development, we constructed tissue microarrays and examined Skp2 expression in melanocytic lesions at different stages, including 30 normal nevi, 61 dysplastic nevi, 290 primary melanomas and 146 metastatic melanomas. The TMA was assessed for cytoplasmic and nuclear Skp2 expression by immunohistochemistry. The Kaplan-Meier method was used to evaluate the patient survival. The univariate and multivariate Cox regression models were performed to estimate the hazard ratios (HR) at five-year follow-up. RESULTS: Cytoplasmic but not nuclear Skp2 expression was gradually increased from normal nevi, dysplastic nevi, primary melanomas to metastatic melanomas. Cytoplasmic Skp2 expression correlated with AJCC stages (I vs II-IV, P<0.001), tumor thickness (≤2.00 vs >2.00 mm, P<0.001) and ulceration (P = 0.005). Increased cytoplasmic Skp2 expression was associated with a poor five-year disease-specific survival of patients with primary melanoma (P = 0.018) but not metastatic melanoma (P>0.05). CONCLUSION: This study demonstrates that cytoplasmic Skp2 plays an important role in melanoma pathogenesis and its expression correlates with patient survival. Our data indicate that cytoplasmic Skp2 may serve as a potential biomarker for melanoma progression and a therapeutic target for this disease

Insights into APC/C: from cellular function to diseases and therapeutics

Anaphase-promoting complex/cyclosome (APC/C) is a multifunctional ubiquitin-protein ligase that targets different substrates for ubiquitylation and therefore regulates a variety of cellular processes such as cell division, differentiation, genome stability, energy metabolism, cell death, autophagy as well as carcinogenesis. Activity of APC/C is principally governed by two WD-40 domain proteins, Cdc20 and Cdh1, in and beyond cell cycle. In the past decade, the results based on numerous biochemical, 3D structural, mouse genetic and small molecule inhibitor studies have largely attracted our attention into the emerging role of APC/C and its regulation in biological function, human diseases and potential therapeutics. This review will aim to summarize some recently reported insights into APC/C in regulating cellular function, connection of its dysfunction with human diseases and its implication of therapeutics

Raça e o uso dos serviços de saúde bucal por idosos Race and the use of dental health services by the elderly

Analisamos se a raça pode ser considerada um fator limitante na utilização dos serviços odontológicos por idosos. O presente estudo é de caráter analítico, com a utilização de dados secundários coletados pela Pesquisa Nacional de Saúde Bucal em 2003. Foram incluídos os examinados que se declararam como brancos, pardos ou pretos, na faixa etária de 65 a 74 anos. O número amostral foi composto por 5.108 idosos sendo 2.575 brancos e 2.533 negros. Dos brancos 3,8% afirmaram nunca terem ido ao dentista enquanto que para os negros esse valor é de 7,8%. Mesmo após o ajuste com interceptação de necessidade de prótese e dor, a chance do idoso negro não ter utilizado o serviço odontológico pelo menos uma vez na vida é 0.62 OR menor que para um idoso branco. Dos que utilizaram os serviços, 21,2% dos idosos brancos visitaram o dentista no último ano, enquanto para os negros o valor foi de 14,2%, no modelo ajustado interceptado pela necessidade de prótese e dor o OR foi de 0.60. Todas as relações foram estatisticamente significantes (p < 0,001). A raça é um fator limitante na utilização dos serviços odontológicos por idosos e, mesmo após ajustes, os idosos negros permanecem com maior dificuldade na utilização dos serviços de saúde bucal.<br>We analyze if race can be considered a limiting factor in the use of dental services by the elderly. This study is of an analytical nature, with the use of secondary data collected by the National Survey of Oral Health in 2003. Those examined who declared themselves as being white, brown or black in the 65 to 74-year-old age bracket were included. The sample was composed of 5,108 elderly people: 2,575 whites and 2,533 blacks. Of the whites, 3.8% stated that they had never been to the dentist, while this figure was 7.8% for the blacks. Even after the adjustment for interception for prosthetics and dental pain, the chance of elderly blacks not having used dental services at least once in their life is 0.62 OR less than for elderly whites. Of those who used the services, 21.2% of the elderly whites visited the dentist in the last year, while for elderly blacks the figure was 14.2%, in the adjusted model for interception for prosthetics and dental pain the OR was 0.60. All the relations were statistically significant (p<0,001). Race is a limiting factor in the use of dental services by the elderly and even after the adjustments the elderly blacks continue to manifest greater resistance to the use of oral health services

Potentially inappropriate medications among older adults in Pelotas, Southern Brazil

OBJETIVO Avaliar o uso de medicamentos potencialmente inadequados entre idosos. MÉTODOS Estudo transversal de base populacional com 1.451 idosos com 60 anos ou mais em Pelotas, RS, em 2014. Investigou-se o uso de medicamentos nos últimos 15 dias. Utilizando os critérios de Beers (2012), verificou-se a potencial inadequação dos medicamentos e sua relação com variáveis socioeconômicas e demográficas, polifarmácia, automedicação e carga de doença. RESULTADOS Dentre os 5.700 medicamentos utilizados, 5.651 puderam ser avaliados quanto à inadequação. Destes, 937 eram potencialmente inadequados para idosos segundo os critérios de Beers de 2012 (16,6%). Cerca de 42,4% dos idosos usaram no mínimo um medicamento considerado potencialmente inapropriado. O grupo de medicamentos para o sistema nervoso correspondeu a 48,9% do total de medicamentos potencialmente inadequados. Na análise ajustada, as variáveis sexo feminino, idade avançada, cor da pele branca, baixa escolaridade, polifarmácia, automedicação e carga de doença mostraram-se associadas ao uso de medicamentos potencialmente inadequados. CONCLUSÕES É importante que sejam bem conhecidas as possíveis consequências do uso de medicamentos entre idosos. Atenção especial deve ser dada aos idosos que fazem uso de polifarmácia. É necessário existir listas específicas com medicamentos mais adequados para uso em idosos na Relação Nacional de Medicamentos Essenciais.OBJECTIVE To assess the use of potentially inappropriate medications among older adults. METHODS This is a population-based cross-sectional study with 1,451 older individuals aged 60 years or more in the city of Pelotas, State of Rio Grande do Sul, Brazil, in 2014. We have investigated the use of medications in the last 15 days. Using the Beers criteria (2012), we have verified the use of potentially inappropriate medications and their relationship with socioeconomic and demographic variables, polypharmacy, self-medication, and burden of disease. RESULTS Among the 5,700 medications used, 5,651 could be assessed as to being inappropriate. Of these, 937 were potentially inappropriate for the older adults according to the 2012 Beers criteria (16.6%). Approximately 42.4% of the older adults studied used at least one medication considered as potentially inappropriate. The group of medications for the nervous system accounted for 48.9% of the total of the potentially inappropriate medications. In the adjusted analysis, the variables female, advanced age, white race, low educational level, polypharmacy, self-medication, and burden of disease were associated with the use of potentially inappropriate medications. CONCLUSIONS It is important to known the possible consequences of the use of medication among older adults. Special attention should be given to the older adults who use polypharmacy. Specific lists should be created with more appropriate medications for the older population in the National Essential Medicine List