Relationship between cyclooxygenase 8473T>C polymorphism and the risk of lung cancer: a case-control study

BACKGROUND: Cyclooxygenase-2 (COX-2) plays an important role in the development of lung cancer. DNA sequence variations in the COX-2 gene may lead to altered COX-2 production and/or activity, and so they cause inter-individual differences in the susceptibility to lung cancer. To test this hypothesis, we investigated the association between the 8473T>C polymorphism in the 3'-untranslated region of the COX-2 gene and the risk of lung cancer in a Korean population. METHODS: The COX-2 genotypes were determined using PCR-based primer-introduced restriction analysis in 582 lung cancer patients and in 582 healthy controls that were frequency-matched for age and gender. RESULTS: The distribution of the COX-2 8473T>C genotypes was not significantly different between the overall lung cancer cases and the controls. However, when the cases were categorized by the tumor histology, the combined 8473 TC + CC genotype was associated with a significantly decreased risk of adenocarcinoma as compared with the 8473 TT genotype (adjusted OR = 0.64; 95% CI = 0.46–0.90, P = 0.01). On the stratification analysis, the protective effect of the combined 8473 TC + CC genotype against adenocarcinoma was statistically significant in the males, older individuals and ever-smokers (adjusted OR = 0.59; 95% CI = 0.39–0.91, P = 0.02; adjusted OR = 0.55; 95% CI = 0.33–0.93, P = 0.03; and adjusted OR = 0.57; 95% CI = 0.37–0.87, P = 0.01, respectively). CONCLUSION: These findings suggest that the COX-2 8473T>C polymorphism could be used as a marker for the genetic susceptibility to adenocarcinoma of the lung

Small molecule sensitization to TRAIL is mediated via nuclear localization, phosphorylation and inhibition of chaperone activity of Hsp27

10.1038/cddis.2013.413Cell Death and Disease410

RNA Binding Protein CUGBP2/CELF2 Mediates Curcumin-Induced Mitotic Catastrophe of Pancreatic Cancer Cells

Curcumin inhibits the growth of pancreatic cancer tumor xenografts in nude mice; however, the mechanism of action is not well understood. It is becoming increasingly clear that RNA binding proteins regulate posttranscriptional gene expression and play a critical role in RNA stability and translation. Here, we have determined that curcumin modulates the expression of RNA binding protein CUGBP2 to inhibit pancreatic cancer growth.In this study, we show that curcumin treated tumor xenografts have a significant reduction in tumor volume and angiogenesis. Curcumin inhibited the proliferation, while inducing G2-M arrest and apoptosis resulting in mitotic catastrophe of various pancreatic cancer cells. This was further confirmed by increased phosphorylation of checkpoint kinase 2 (Chk2) protein coupled with higher levels of nuclear cyclin B1 and Cdc-2. Curcumin increased the expression of cyclooxygenase-2 (COX-2) and vascular endothelial growth factor (VEGF) mRNA, but protein levels were lower. Furthermore, curcumin increased the expression of RNA binding proteins CUGBP2/CELF2 and TIA-1. CUGBP2 binding to COX-2 and VEGF mRNA was also enhanced, thereby increasing mRNA stability, the half-life changing from 30 min to 8 h. On the other hand, silencer-mediated knockdown of CUGBP2 partially restored the expression of COX-2 and VEGF even with curcumin treatment. COX-2 and VEGF mRNA levels were reduced to control levels, while proteins levels were higher.Curcumin inhibits pancreatic tumor growth through mitotic catastrophe by increasing the expression of RNA binding protein CUGBP2, thereby inhibiting the translation of COX-2 and VEGF mRNA. These data suggest that translation inhibition is a novel mechanism of action for curcumin during the therapeutic intervention of pancreatic cancers

Genetic polymorphisms in the cyclooxygenase-2 gene, use of nonsteroidal anti-inflammatory drugs, and breast cancer risk

INTRODUCTION: The association between use of nonsteroidal anti-inflammatory drugs (NSAIDs) and breast cancer risk remains unclear. Inconsistencies in previously reported findings may be partly due to differences in expression of cyclooxygenase (COX)-2. We hypothesized that genetic polymorphisms (COX-2 .926, COX-2 .5209, and COX-2 .8473) may reduce overall breast cancer risk or risk for subtypes of breast cancer by modulating the inflammatory response and may interact with aspirin or any NSAID use. METHODS: We conducted a population-based, case-control study in which we genotyped 1,067 breast cancer cases and 1,110 control individuals included in the Long Island Breast Cancer Study Project. RESULTS: No major effects of the three COX-2 variant alleles on breast cancer risk were found. A total of eight distinct haplotypes and 18 diplotypes were observed in the population. Overall, no significant associations between COX-2 haplotypes/diplotypes and breast cancer risk were observed. Among women who used aspirin or any NSAID there was little evidence for an interaction with the at-risk COX-2 genotypes, with one exception. Among women with hormone receptor positive breast cancer, the reduced risk for any NSAID use was only evident among those who had at least one variant C allele of COX-2 .8473 (odds ratio = 0.7, 95% confidence interval = 0.5 to 1.0; P for the interaction = 0.02). There was no corresponding interaction for aspirin use, possibly because of limited power. CONCLUSION: These data provide modest evidence that the C allele of COX-2 .8473 may interact with NSAIDs to reduce risk for hormone receptor positive breast cancer

Percepção da imagem corporal e nível socioeconômico em adolescentes: revisão sistemática Adolescent body image perceptions and socioeconomic status: a systematic review

OBJETIVO: Discutir as relações entre percepção da imagem corporal e fatores socioeconômicos como renda, grau de escolaridade e etnia em adolescentes. FONTES DE DADOS: Artigos selecionados nas bases PubMed e SciELO, sem limite de data de publicação, com amostras de adolescentes, nos idiomas inglês, espanhol, português ou francês, utilizando os descritores: "percepção da imagem corporal", "nível socioeconômico" e "adolescentes". SÍNTESE DOS DADOS: A influência do contexto socioeconômico na percepção da imagem corporal e satisfação/insatisfação com o corpo é tema relevante no entendimento da saúde dos adolescentes. Identificou-se que as relações entre imagem corporal e nível socioeconômico são complexas e os resultados dos estudos publicados não são conclusivos. As principais tendências observadas foram: jovens norte-americanos de classe baixa apresentaram maior chance de serem obesos ao contrário dos brasileiros; moças e rapazes apresentaram comportamentos diferenciados na percepção da imagem corporal, independentemente da etnia e do nível socioeconômico; moças brancas apresentaram maior insatisfação com a imagem corporal e maior busca por dietas do que moças negras, as quais parecem sofrer menos influência dos padrões de beleza em voga; jovens de menor nível socioeconômico apresentaram uma tendência a desejarem corpos maiores. CONCLUSÕES: Considerando-se amostras estrangeiras, houve uma tendência de maiores índices de insatisfação com o corpo em adolescentes de classe socioeconômica mais privilegiada. Em amostras brasileiras, análises sobre o assunto são escassas e pesquisas são necessárias, especialmente pelo fato de a população estar passando por modificações tanto econômicas como nutricionais.<br>OBJECTIVE: To discuss the relationships between body image perceptions and socioeconomic factors such as income, level of education, and ethnicity among adolescents. DATA SOURCE: Articles were selected from PubMed and SciELO databases, involving adolescents, without limits of publication dates, in English, Spanish, Portuguese, or French, with the following keywords: "body image perception", "socioeconomic status", and "adolescents". DATA SYNTHESIS: The influence of the socioeconomic context upon body image perceptions and satisfaction/dissatisfaction with the body is a relevant subject in understanding adolescent's health. This study identified that relationships between body image and socioeconomic levels are complex and the results of published studies are not conclusive. The main findings are: North-American lower class youths present greater chances for obesity, but this is not true in Brazil; girls and boys have different behaviors concerning body image perceptions, despite ethnicity or socioeconomic status; Caucasian girls show more dissatisfaction with their body images and greater search for diets than African American girls, who seem to suffer less influence of the current beauty patterns; youth of lower socioeconomic status presents a tendency to desire larger bodies. CONCLUSIONS: Considering foreign samples, there was a tendency for greater levels of dissatisfaction with the body among adolescents of higher socioeconomic classes. In Brazilian samples, studies about this subject are scarce and further research is needed, especially because Brazilian population is experiencing economical and nutritional modifications

The RNA-binding protein RBM3 is required for cell proliferation and protects against serum deprivation-induced cell death

Hypoxia and other adverse conditions are commonly encountered by rapidly growing cells. The RNA-binding protein RBM3 (RNA-binding motif protein 3), which is transcriptionally induced by low temperature and hypoxia, has recently been implicated in survival of colon cancer cells by mechanisms involving cyclooxygenase-2 (COX-2) signaling. Immunohistochemically, we found strong RBM3 expression in a variety of malignant and proliferating tissues but low expression in resting and terminally differentiated cells. RBM3 expression in fibroblasts and human embryonal kidney (HEK293) cells subjected to serum deprivation or contact inhibition closely paralleled proliferation rates, assessed by real-time RT-PCR and immunoblotting. siRNA-mediated RBM3 knockdown reduced cell viability and finally led to cell death, which did not involve caspase-3-mediated apoptosis, cell cycle arrest, or COX-2 regulation. In contrast, RBM3 over-expression rescued cells from death under serum starvation. This was associated with increased translation rates, as measured by C serine and H phenylalanine incorporation. Together, RBM3 is a critical factor providing cellular survival advantages in an adverse microenvironment presumably by restoring translation efficacy