The endogenous soluble VEGF receptor-2 isoform suppresses lymph node metastasis in a mouse immunocompetent mammary cancer model

<p>Abstract</p> <p>Background</p> <p>Cancer metastasis contributes significantly to cancer mortality and is facilitated by lymphangiogenesis and angiogenesis. A new splicing variant, endogenous soluble vascular endothelial growth factor receptor-2 (esVEGFR-2) that we recently identified is an endogenous selective inhibitor of lymphangiogenesis. To evaluate the antimetastatic potential of esVEGFR-2, gene therapy with vector expressing esVEGFR-2 (pesVEGFR-2) or endostatin (pEndo) as a positive control was conducted on murine metastatic mammary cancer.</p> <p>Methods</p> <p>Syngeneic inoculated metastatic mammary cancers received direct intratumoral injection of pesVEGFR-2, pEndo or pVec as control, once a week for six weeks. <it>In vivo </it>gene electrotransfer was performed on the tumors after each injection.</p> <p>Results</p> <p>Deaths from metastasis were much lower in the pesVEGFR-2 and pEndo groups than in those of the pVec. Tumor volume was significantly lower in the pesVEGFR-2 and the pEndo groups throughout the study. Multiplicity of lymph node and lung metastatic nodules was significantly suppressed in the pesVEGFR-2 and pEndo groups. Moreover, the total number of overall metastasis including the other organs was also decreased in these groups. However, pesVEGFR-2 was not able to decrease the number of lungs, ovaries, kidneys and adrenals with metastasis as counted by unilateral or bilateral metastasis. The number of CD34⁺/Lyve-1^-blood microvessels was significantly decreased in the pEndo group, while the number of CD34^-/Lyve-1⁺lymphatic vessels was significantly decreased in the pesVEGFR-2 and pEndo groups. In addition, a significant reduction in the number of dilated lymphatic vessels containing intraluminal cancer cells was observed in the pesVEGFR-2 and pEndo groups. Levels of apoptosis were significantly increased in the pEndo group, whereas the rates of cell proliferation were significantly decreased in the pesVEGFR-2 and pEndo groups.</p> <p>Conclusions</p> <p>Our data demonstrate that esVEGFR-2 can inhibit mainly lymph node metastasis. The antimetastatic activity of esVEGFR-2 may be of high clinical significance in the treatment of metastatic breast cancer because lymph node involvement is a most important prognostic factor in cancer patients.</p

Modifiable risk factors for overweight and obesity in children and adolescents from São Paulo, Brazil

<p>Abstract</p> <p>Background</p> <p>Brazil is currently experiencing a nutrition transition: the displacement of traditional diets with foods high in saturated fat, sodium, and cholesterol and an increase in sedentary lifestyles. Despite these trends, our understanding of child obesity in Brazil is limited. Thus, the aims of this study were (1) to investigate the current prevalence of overweight and obesity in a large sample of children and adolescents living in São Paulo, Brazil, and (2) to identify the lifestyle behaviors associated with an increased risk of obesity in young Brazilians.</p> <p>Methods</p> <p>A total of 3,397 children and adolescents (1,596 male) aged 7-18 years were randomly selected from 22 schools in São Paulo, Brazil. Participants were classified as normal weight, overweight, or obese based on international age- and sex-specific body mass index thresholds. Selected sociodemographic, physical activity, and nutrition behaviors were assessed via questionnaire.</p> <p>Results</p> <p>Overall, 19.4% of boys and 16.1% of girls were overweight while 8.9% and 4.3% were obese. Two-way analysis of variance revealed that the prevalence of overweight and obesity was significantly higher in boys and in younger children when compared to girls and older children, respectively (P < 0.05 for both). Logistic regression analysis revealed that overweight was associated with more computer usage, parental encouragement to be active, and light soft drink consumption after controlling for differences in sex, age, and parental education (P < 0.05 for all). Conversely, overweight was associated with less active transport to school, eating before sleep, and consumption of breakfast, full-sugar soft drinks, fried food and confectionery (P < 0.05 for all).</p> <p>Conclusions</p> <p>Our results show that obesity in São Paulo children and adolescents has reached a level equivalent to that seen in many developed countries. We have also identified three key modifiable factors related to obesity that may be appropriate targets for future intervention in Brazilian youth: transport mode to school, computer usage, and breakfast consumption.</p