Comparison of three exercise interventions with and without gemcitabine treatment on pancreatic tumor growth in mice: No impact on tumor infiltrating lymphocytes.

Exercise has been shown to slow pancreatic tumor growth, but whether exercise interventions of differing volume or intensity yield differential effects on tumor outcomes is unknown. In this study, we compared three exercise training interventions implemented with and without chemotherapy on pancreatic tumor growth in mice. Methods: Male C57BL/6 mice (6-8 weeks old) were subcutaneously inoculated with pancreatic ductal adenocarcinoma tumor cells (PDAC 4662). Upon tumor detection, mice received gemcitabine 15 mg/kg intraperitoneally 3 days/week and were assigned to exercise: high volume continuous exercise (HVCE), low volume continuous exercise (LVCE), high intensity interval training (HIIT), or sedentary (SED). HVCE ran at 12 m/min for 45 min and LVCE for 15 min, 5 days/week. HIIT ran 1-min at 20 m/min, followed by 1-min walking at 8 m/min for 20 total intervals, 3 days/week. SED did not run. Additional sets of inoculated mice were assigned to the exercise interventions but did not receive gemcitabine. Tumor volume was measured every other day for 2 weeks; tumor-infiltrating lymphocytes were assessed by flow cytometry 3-week post-inoculation. Results: Tumor growth did not differ between groups that received gemcitabine (F(3, 34) = 1.487; p = 0.235; η2 = 0.116). In contrast, tumor growth differed between groups not provided gemcitabine (F(3,14) = 3.364; p = 0.049, η2 = 0.419), with trends for slower growth in LVCE than SED (p = 0.088) and HIIT (p = 0.084). Groups did not differ in tumor infiltrating lymphocytes. Conclusion: Contrary to our hypotheses, the exercise interventions compared here did not further reduce pancreatic tumor growth beyond that provided by gemcitabine. However, in mice not receiving gemcitabine, there was a trend for reduced tumor growth in LVCE.

Vascular modulation through exercise improves chemotherapy efficacy in Ewing sarcoma.

Recent studies in mouse models of cancer have shown that exercise improves tumor vascular function, thereby improving chemotherapy delivery and efficacy. However, the mechanisms underlying this improvement remain unclear and the effect of exercise on Ewing sarcoma (ES), a pediatric bone and soft tissue cancer, is unknown. The effect of exercise on tumor vascular hyperpermeability, which inversely correlates with drug delivery to the tumor, has also not been evaluated. We hypothesized that exercise improves chemotherapy efficacy by enhancing its delivery through improving tumor vascular permeability. We treated ES-bearing mice with doxorubicin with or without moderate treadmill exercise. Exercise did not significantly alter ES tumor vessel morphology. However, compared to control mice, tumors of exercised mice had significantly reduced hyperpermeability, significantly decreased hypoxia, and higher doxorubicin penetration. Compared to doxorubicin alone, doxorubicin plus exercise inhibited tumor growth more efficiently. We evaluated endothelial cell sphingosine-1-phosphate receptors 1 and 2 (S1PR1 and S1PR2) as potential mediators of the improved vascular permeability and increased function afforded by exercise. Relative to tumors from control mice, vessels in tumors from exercised mice had increased S1PR1 and decreased S1PR2 expression. Our results support a model in which exercise remodels ES vasculature to reduce vessel hyperpermeability, potentially via modulation of S1PR1 and S1PR2, thereby improving doxorubicin delivery and inhibiting tumor growth more than doxorubicin alone does. Our data suggest moderate aerobic exercise should be tested in clinical trials as a potentially useful adjuvant to standard chemotherapy for patients with ES.

Aerobic Exercise During Early Murine Doxorubicin Exposure Mitigates Cardiac Toxicity.

We report the cardioprotective effects of moderate aerobic exercise from parallel pediatric murine models of doxorubicin (Doxo) exposure in non-tumor-bearing immune competent (NTB-IC) mice and tumor-bearing nude mice (TB-NM). In both models, animals at 4 weeks of age underwent Doxo treatment with or without 2 weeks of simultaneous exercise. In sedentary NTB-IC or TB-NM mice, Doxo treatment resulted in a statistically significant decrease in ejection fraction and fractional shortening compared with control animals. Interestingly, moderate aerobic exercise during Doxo treatment significantly mitigated decreases in ejection fraction and fractional shortening. In contrast, these protective effects of exercise were not observed when exercise was started after completion of Doxo treatments. Moreover, in the TB-NM model, Doxo caused a decrease in heart mass: tibia length and in body weight that was prevented by exercise, whereas NTB-IC mice exhibited no change in these measurements. Doxo delivery to the hearts of TB-NM was decreased by consistent moderate aerobic exercise before Doxo injection. These findings demonstrate the important but subtle differences in cardiotoxicity observed in different mouse models. Collectively, these results also strongly suggest that aerobic exercise during early-life Doxo exposure mitigates cardiotoxicity, possibly through altered delivery of Doxo to myocardial tissue.

[HIV/AIDS prevalence in Medellin and presumptive test diagnostic accuracy (2006-2012)]. / Prevalencia de VIH/Sida en Medellín y evaluación del desempeño de la prueba presuntiva, 2006-2012.

OBJECTIVE: Determining HIV/AIDS prevalence in Medellin, Colombia, and its association with demographic factors2006-2012,as well as exploring screening test performance. METHODS: This was a cross-sectional study involving 5,851subjects. Descriptive statistics were used to describe the population (i.e. frequencies and summary measures); infection prevalence was calculated and its association with demographic factors identified by using parametric and non-parametric statistical tests, prevalence ratios and odds ratios. Predictive values were calculated, as were the percentage of false results and percentage of subjects correctly diagnosed. RESULTS: Mean age was 27 years old (0 to 94 year range); 70.5% of the population were female. HIV/AIDS prevalence was found to be 1.8% during the study period (0.32% annually). A statistical association was found with gender and age, a higher prevalence being found in males and adults. The false positive rate was 0.7%, negative predictive value100%, positive predictive value 71% and there was 99% overall efficiency. CONCLUSION: HIV/AIDS prevalence found in this study was significantly higher than that found in other studies in the Antioquia department and for Colombia overall. The male and female infection prevalence ratio revealed increased diagnosis in women. The screening test performed well in areas having less than 1% infection prevalence.

Correlación entre la vacunación y lapresencia de anticuerpos protectorescontra el virus de la hepatitis B en personas de la Facultad de Medicina, Universidad Cooperativa de Colombia, Medellín, 2011 / Correlation among vaccination and the presence of protector antibodies anti-hepatitis B virus in the personnel of Universidad Cooperativa de Colombia Medical School-Medellín, 2011

Introducción: El personal de la salud es uno de los principales grupos en riesgo de infeccióncon el virus de la hepatitis B y aunque existe una vacuna recombinante basada en el antígeno desuperficie del virus, no todos los individuos vacunados logran el título de anticuerpos protectores.Objetivo: determinar la relación entre los títulos de anticuerpos contra el antígeno de superficiedel virus de la hepatitis B y el número de dosis de vacuna contra la hepatitis B, en personal dela Facultad de Medicina de la Universidad Cooperativa de Colombia, sede Medellín, en 2011. Materiales y Métodos: se realizó un estudio descriptivo transversal en una muestra probabilísticade 162 personas. La recolección de la información fue a partir de fuente primaria. El análisisestadístico se realizó con base en proporciones, medidas de resumen, estadística paramétrica y noparamétrica. Resultados: el 80% del grupo de estudio presentó anticuerpos en un nivel protector,el promedio del título de anticuerpos fue 396 mUI/mL, éste presentó asociación estadística conel número de dosis y no se observó asociación estadística con el sexo ni la edad. Conclusión: la protección hallada contra el virus de la hepatitis B fue menor a la reportada internacionalmentepara vacunas recombinantes (aproximadamente del 90% al 95% en adultos jóvenes). Esto sepodría atribuir a la inclusión de personas con esquemas de vacunación incompletos o con pobrerespuesta inmunológica a la vacuna, como los hombres, los individuos con alto índice de masacorporal, la edad adulta, la presencia de tabaquismo o los individuos con HLA DR3-DQ2.

Introduction: Health personnel is one of the main risk groups for infection with Hepatitis B virus, andalthough there is a vaccine based on recombinant surface antigen of the virus, not all vaccinatedindividuals reach protective antibody titers. Objective: to establish the relationship between serumtiters of anti-Hepatitis B Virus and the number of doses of vaccine against hepatitis B, in staff of the Medical School at Universidad Cooperativa de Colombia, Medellin, in 2011. Materials and methods:a cross-sectional study in a probability sample of 162 people was conducted. The data collectionwas from primary source. Statistical analysis was made based on proportions, summary measures, parametric and nonparametric statistics. Results: 80% of the study group had protective antibodies, the average antibody titer was 396 mIU/mL, it was statistically associated with the number of doses,and there was no statistical association with sex or age. Conclusion: the protection found againsthepatitis B virus was lower than that reported internationally for recombinant vaccines (approximately 90-95% in young adults). This could be attributed to the inclusion of people with incompletevaccination schedules or poor immune response to the vaccine, such as men, individuals with highbody mass index, adulthood, smoking status, and individuals with HLA DR3-DQ2.