Serum S100A6 Concentration Predicts Peritoneal Tumor Burden in Mice with Epithelial Ovarian Cancer and Is Associated with Advanced Stage in Patients

BACKGROUND:Ovarian cancer is the 5th leading cause of cancer related deaths in women. Five-year survival rates for early stage disease are greater than 94%, however most women are diagnosed in advanced stage with 5 year survival less than 28%. Improved means for early detection and reliable patient monitoring are needed to increase survival. METHODOLOGY AND PRINCIPAL FINDINGS:Applying mass spectrometry-based proteomics, we sought to elucidate an unanswered biomarker research question regarding ability to determine tumor burden detectable by an ovarian cancer biomarker protein emanating directly from the tumor cells. Since aggressive serous epithelial ovarian cancers account for most mortality, a xenograft model using human SKOV-3 serous ovarian cancer cells was established to model progression to disseminated carcinomatosis. Using a method for low molecular weight protein enrichment, followed by liquid chromatography and mass spectrometry analysis, a human-specific peptide sequence of S100A6 was identified in sera from mice with advanced-stage experimental ovarian carcinoma. S100A6 expression was documented in cancer xenografts as well as from ovarian cancer patient tissues. Longitudinal study revealed that serum S100A6 concentration is directly related to tumor burden predictions from an inverse regression calibration analysis of data obtained from a detergent-supplemented antigen capture immunoassay and whole-animal bioluminescent optical imaging. The result from the animal model was confirmed in human clinical material as S100A6 was found to be significantly elevated in the sera from women with advanced stage ovarian cancer compared to those with early stage disease. CONCLUSIONS:S100A6 is expressed in ovarian and other cancer tissues, but has not been documented previously in ovarian cancer disease sera. S100A6 is found in serum in concentrations that correlate with experimental tumor burden and with clinical disease stage. The data signify that S100A6 may prove useful in detecting and/or monitoring ovarian cancer, when used in concert with other biomarkers

Relationships Between Outdoor Time, Physical Activity, Sedentary Time, and Body Mass Index in Children: A 12-Country Study

Purpose: This study investigated the relationship between outdoor time and physical activity (PA), sedentary time (SED), and body mass index z scores among children from 12 lower-middle-income, upper-middle-income, and high-income countries.Methods: In total, 6478 children (54.4% girls) aged 9-11 years participated. Outdoor time was self-reported, PA and SED were assessed with ActiGraph GT3X+ accelerometers, and height and weight were measured. Data on parental education, neighborhood collective efficacy, and accessibility to neighborhood recreation facilities were collected from parent questionnaires. Country latitude and climate statistics were collected through national weather data sources. Gender-stratified multilevel models with parental education, climate, and neighborhood variables as covariates were used to examine the relationship between outdoor time, accelerometry measures, and body mass index z scores. Results: Each additional hour per day spent outdoors was associated with higher moderate- to vigorous-intensity PA (boys: +2.8 min/d; girls: +1.4 min/d), higher light-intensity PA (boys: +2.0 min/d; girls: +2.3 min/d), and lower SED (boys: -6.3 min/d; girls: -5.1 min/d). Effect sizes were generally weaker in lower-middle-income countries. Outdoor time was not associated with body mass index z scores. Conclusions: Outdoor time was associated with higher PA and lower SED independent of climate, parental education, and neighborhood variables, but effect sizes were small. However, more research is needed in low- and middle-income countries