Ewing Sarcoma: influence of TP53 Arg72Pro and MDM2 T309G SNPs.

The Ewing Sarcoma is an important tumor of bone and soft tissue. The SNPs Arg72Pro of TP53 and T309G of MDM2 have been associated with many cancer types and have been differently distributed among populations worldwide. Based on a case-control design, this study aimed to assess the role of these SNPs in 24 Ewing Sarcoma patients, compared to 91 control individuals. DNA samples were extracted from blood and genotyped for both SNPs by PCR-RFLP and confirmed by DNA sequencing. The results showed an association between the G allele of the T309G and Ewing Sarcoma (P=0.02). Comparing to the TT carriers, the risk of G allele carriers was 3.35 (95% CI=1.22-9.21) with P=0.02. At the genotypic level, an association of the TT genotype with the control group (P=0.03) was found. Comparing to the TT genotype, the risk of TG and GG was 2.97 (95% CI=1.03-8.58) with P=0.04 and 5.00 (95% CI=1.23-20.34) with P=0.02, respectively. No associations regarding the Arg72Pro SNP were found. Considering that the T309G has been associated with several types of cancer, including sarcomas, our results indicate that this SNP may also be important to Ewing Sarcoma predisposition.

Methotrexate diethyl ester-loaded lipid-core nanocapsules in aqueous solution increased antineoplastic effects in resistant breast cancer cell line.

Breast cancer is the most frequent cancer affecting women. Methotrexate (MTX) is an antimetabolic drug that remains important in the treatment of breast cancer. Its efficacy is compromised by resistance in cancer cells that occurs through a variety of mechanisms. This study evaluated apoptotic cell death and cell cycle arrest induced by an MTX derivative (MTX diethyl ester [MTX(OEt)2]) and MTX(OEt)2-loaded lipid-core nanocapsules in two MTX-resistant breast adenocarcinoma cell lines, MCF-7 and MDA-MB-231. The formulations prepared presented adequate granulometric profile. The treatment responses were evaluated through flow cytometry. Relying on the mechanism of resistance, we observed different responses between cell lines. For MCF-7 cells, MTX(OEt)2 solution and MTX(OEt)2-loaded lipid-core nanocapsules presented significantly higher apoptotic rates than untreated cells and cells incubated with unloaded lipid-core nanocapsules. For MDA-MB-231 cells, MTX(OEt)2-loaded lipid-core nanocapsules were significantly more efficient in inducing apoptosis than the solution of the free drug. S-phase cell cycle arrest was induced only by MTX(OEt)2 solution. The drug nanoencapsulation improved apoptosis induction for the cell line that presents MTX resistance by lack of transport receptors.

TP53 gene polymorphism: importance to cancer, ethnicity and birth weight in a Brazilian cohort.

Arg72Pro SNP of p53 has been associated with many types of cancer as well as with survival and longevity. We evaluated the Arg72Pro SNP frequencies of a Brazilian birth cohort and their association with current, demographic and birth epidemiological parameters available. In 1982, all hospital births of Pelotas, southern Brazil, were identified and studied prospectively. In 2004-5, blood samples were collected and DNA extracted. PCR-RFLP was used to genotype the Arg72Pro SNP in 3794 individual samples of the Brazil birth cohort and DNA sequencing was performed to confirm the genotypes. The genotype distribution, which was in Hardy-Weinberg equilibrium, showed a predominance of the arginine amino acid with a frequency of 46.9% Arg/Arg, 42.2% Arg/Pro and 10.9% Pro/Pro. The allele frequency was 0.68 of Arginine and 0.32 of Proline. The Arg72Pro SNP genotype and allelic frequency were related to skin colour where proline amino acid was observed more among black subjects, while arginine amino acid was observed more among white subjects. The individuals without family history of cancer and those with low birth weight were associated with arginine amino acid. The Arg72Pro SNP was strongly associated with important epidemiological variables confirming that genetic profiles on cohort studies can improve our understanding of the susceptibility of diseases and its risk factors.

Associação entre atividade física, aptidão cardiorrespiratória e biomarcadores inflamatórios em adultos jovens aparentemente saudáveis / Association between physical activity, cardiorespiratory fitness and inflammatory biomarkers in apparently healthy young adults

A inflamação sistêmica crônica de baixa intensidade está relacionada com maior risco de doenças cardiovasculares. Estudos sugerem que a proteína C-reativa, um dos principais biomarcadores inflamatórios, pode estar inversamente relacionada com a prática de atividade física e com a aptidão física. O objetivo deste estudo transversal foi determinar as associações entre os níveis de atividade física e a aptidão cardiorrespiratória, com biomarcadores inflamatórios em homens adultos jovens (18-30 anos) aparentemente saudáveis (N=85). As amostras foram analisadas pelo método ELISA (Enzyme-Linked Immuno Sorbent Assay), usando kits de alta sensibilidade para proteína C-reativa, interleucina 6, interleucina 1? e TNF-?. A prática de atividade física foi mensurada por questionário e acelerometria. O consumo máximo de oxigênio (VO2max) foi estimado por teste incremental em cicloergômetro. Na análise bruta, a média das concentrações de proteína C-reativa da amostra foi de 1,59±1,16 mg/L, e esteve significativamente correlacionada com o VO2max (r=-0,32; p=0,03), mas não com atividade física medida por acelerometria ou questionário. O índice de massa corporal (IMC) e a circunferência abdominal apresentaram correlação significativa com a proteína C-reativa (r=0,37; p<0,001 e r=0,41; p<0,001, respectivamente). Quando incluímos no modelo o IMC e a circunferência da cintura, a aptidão física perdeu a significância. Não houve relação entre atividade física ou aptidão física com os demais marcadores inflamatórios. Conclui-se que nesse grupo de adultos jovens houve relação entre a proteína C-reativa e o VO2max, e que esta associação é explicada pelas modificações no perfil antropométrico decorrentes de altos níveis de aptidão cardiorrespiratória.

Low-intensity chronic systemic inflammation is related to an increased risk of cardiovascular disease. Studies suggest that C-reactive protein, one of the main inflammatory biomarkers, may be inversely related to physical activity levels and physical fitness. The aim of this cross-sectional study was to evaluate the associations between physical activity, fitness and inflammatory biomarkers in apparently healthy men (N=85) aged 18 to 30 years. C-reactive protein, interleukin 6, interleukin 1? and TNF-? were measured using the ELISA method. Physical activity practice was assessed by questionnaire and accelerometry. Maximum oxygen uptake (VO2max) was estimated based on a cycle ergometer incremental test. In the unadjusted analysis, the mean concentration of C-reactive protein in the sample was 1.59±1.16 mg/L, and was inversely correlated with VO2max (r=-0.32, p=0.03), but not with physical activity estimated by accelerometry or questionnaire. Body mass index (BMI) and waist circumference also significantly correlate with C-reactive protein (r=0.37, p<0.001 and r=0.41, p<0.001, respectively). After adjustment for anthropometric characteristics (BMI and waist circumference), the association with fitness was no longer significant. No association was observed between physical activity or fitness levels and the other inflammatory markers. We conclude that in this group of young adults, there was an inverse association between fitness and C-reactive protein, but this association is explained by the influence of fitness on anthropometry.