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Aggressive forms of breast cancer, such as Her2+ and triple negative breast cancer (TNBC), are enriched in breast cancer stem cells (BCSC) and have limited therapeutic options. BCSC represent a key cellular reservoir for relapse, metastatic progression and therapeutic resistance. Their ability to resist common cytotoxic therapies relies on different mechanisms, including improved detoxification. The cystine-glutamate antiporter protein xCT (SLC7A11) regulates cystine intake, conversion to cysteine and subsequent glutathione synthesis, protecting cells against oxidative and chemical insults. Our previous work showed that xCT is highly expressed in tumorspheres derived from breast cancer cell lines and downregulation of xCT altered BCSC function in vitro and inhibited pulmonary metastases in vivo. We further strengthened these observations by developing a virus-like-particle (VLP; AX09-0M6) immunotherapy targeting the xCT protein. AX09-0M6 elicited a strong antibody response against xCT including high levels of IgG2a antibody. IgG isolated from AX09-0M6 treated mice bound to tumorspheres, inhibited xCT function as assessed by reactive oxygen species generation and decreased BCSC growth and self-renewal. To assess if AX09-0M6 impacts BCSC in vivo seeding, Her2+ TUBO-derived tumorspheres were injected into the tail vein of AX09-0M6 or control treated female BALB/c mice. AX09-0M6 significantly inhibited formation of pulmonary nodules. To evaluate its ability to impact metastases, AX09-0M6 was administered to mice with established subcutaneous 4T1 tumors. AX09- 0M6 administration significantly hampered tumor growth and development of pulmonary metastases. These data show that a VLP-based immunization approach inhibits xCT activity, impacts BCSC biology and significantly reduces metastatic progression in preclinical models. [ABSTRACT FROM AUTHOR]

To assess the safety profile of iso-osmolar contrast medium (CM) versus low osmolar CM in cancer patients with an estimated glomerular filtration rate (eGFR) >60 ml/min. In this multicenter, blind trial of patients seeking a chest-abdomen-pelvis contrast enhanced computed tomography (CT) with iodated CM, participants were centrally randomized to iodixanol or iopromide. Contrast induced nephropathy (CIN) at 24 and/or 72 hr were our primary outcomes. We further considered irreversible CIN, average eGFR percentage variation (%Δ), and adverse events (AEs). Overall, 607 patients were enrolled. Among them, 497 eligible patients were randomized to iodixanol ( N: 247) or iopromide ( N: 250). No differences emerged by descriptive characteristics. Seven and 3 CIN at 24 hr ( p = 0.34) and 8 and 2 CIN at 72 hr ( p = 0.11) occurred in the iopromide and iodixanol group, respectively. Within the subgroup of individual patients who developed CIN ( N: 17), the event rate was higher in the iopromide arm ( p = 0.045). No cases of permanent CIN or significant differences in terms of AEs or GFR %Δ were observed. Our results suggest a more favorable safety profile of iodixanol versus iopromide. Adequately sized trials with similar design are warranted to confirm our findings and clarify the underlying biological mechanisms. [ABSTRACT FROM AUTHOR]

Little research has been done monitoring fitness of show jumping horses in field conditions. Therefore, there is a need to define fitness indices, including cardiac evaluation, for horses used in such a technical competition under tropical conditions. The objective of this study was to evaluate the influence of a field exercise test on blood and electrocardiographic parameters of show jumping horses. Twelve horses, 11.3 ± 4.1 years old and 490.4 ± 33.9 kg, were enrolled in the study. Blood sampling and heart rate (HR), respiratory rate, and body temperature measurement were performed before (T0) and immediately after exercise (T1) and at 30 minutes (T2) and 120 minutes (T3) of recovery. Packed cell volume, red blood cell count, hemoglobin concentration, mean corpuscular volume and mean corpuscular hemoglobin concentration, serum aspartate aminotransferase (AST), creatine kinase (CK), and plasma lactate were evaluated. Electrocardiographic variables were analyzed at T0 and T1. All variables were analyzed for normality through Kolmogorov–Smirnov test, and comparisons were made using the Tukey test for hematological variables and t -test for electrocardiographic parameters, considering P ≤ .05. Exercise test significantly altered all physiological and blood parameters, except for AST, with higher values recorded at T1. Rhythm analysis revealed a sinus rhythm in 50.0% of horses, with mean HR of 31.5 ± 5.8 beats/min at rest, and sinus tachycardia in 75.0% of horses, with mean HR of 76.9 ± 15.2 beats/min after exercise. Other findings included significant reductions in P wave and QRS durations and PR and QT intervals, and significant increases in P wave amplitude and HR. The field jump test led to significant alterations in the studied variables. These results can be used to evaluate athletic conditioning of show jumping horses trained under tropical conditions. [ABSTRACT FROM AUTHOR]

Objectives This study assessed behavioral and physiologic stress parameters in cats placed in two environments: home and the veterinary hospital. With a widely used scale, several parameters were assessed, including respiratory rate (RR), heart rate (HR), systolic blood pressure (SBP), vagosympathetic responses using calculated intervals (heart rate variability [HRV]10, HRV20 and vasovagal tonus index [VVTI]) and ‘stress attitude’, such as struggling, vocalization and agitation during handling. In addition, we evaluated whether a feline facial pheromone analogue (FFPA) had an effect on any of these measures in either environment. Methods Using a placebo and a pheromone substance, we evaluated 30 adult and healthy cats at home and in veterinary hospitals. Statistical analyses were performed using the Shapiro–Wilk, Kruskal–Wallis, and Dunn or ANOVA and Tukey tests, as well as Spearman’s correlation (P <0.05). Results We found that exposure to FFPA did not reduce the effects of stress. Some parameters presented differences with regard to environment: the RR was 45 and 70 breaths/min and stress attitude score was 1.3 and 0.0 for cats evaluated at home and at the hospital, respectively. The HR and two vagosympathetic responses were also different between the two environments, with a HR of 160 and 187 beats/min, HRV10 of 14.24 and 14.00, and HRV20 of 14.89 and 14.65 in cats at home and the hospital, respectively. There was no variation in SBP and VVTI parameters between the environments. Conclusions and relevance Exposure to FFPA does not reduce the physiologic and behavioral changes measured in this study. Furthermore, environmental change, physical restraint and manipulation during the physical examination alter RR, HR, HRV and behavior but not SBP and VVTI. This study is relevant because physiologic and behavioral stress can affect the quality and interpretation of physical examination results. This study presents detailed data that show the effects of environment and manipulation on such parameters. Furthermore, this study shows a lack of effect of FFPA on any of these parameters. [ABSTRACT FROM AUTHOR]

Evaluation of performance of equine athletes depends on the correct interpretation of clinical and laboratory tests performed on animals in a workout session. The objectives of the study were to evaluate the influence of barrel racing exercise on the complete blood count, serum biochemistry, and electrocardiographic parameters of Quarter horses. Twenty-eight Quarter horses, 4.5 ± 2.6 years old and 438.5 ± 34.6 kg, were evaluated before (T0) and immediately after exercise (T1) (barrel racing activity) and after 30 minutes (T2) and 120 minutes (T3) of recovery. At these time points, heart rate (HR), respiratory rate (RR) and body temperature (BT) were measured. Blood samples were taken to determine packed cell volume (PCV), red blood cell (RBC) count, hemoglobin concentration, mean corpuscular volume and mean corpuscular hemoglobin concentration, serum aspartate aminotransferase, creatine kinase, and plasma lactate. Electrocardiographic variables were analyzed at T0 and T1. All variables were analyzed for normality through Kolmogorov–Smirnov test, and comparisons were made using the Tukey test for hematological variables and t -test for electrocardiographic parameters, considering P ≤ .05. The actual exercise challenge significantly altered HR, RR, BT, PCV, RBC, hemoglobin concentration, and plasma lactate, with higher values recorded at T1. Rhythm analysis revealed a sinus rhythm in 89.3% of horses and a sinus arrhythmia in 10.7% of horses, with mean HR of 39.5 ± 8.2 beats/min at rest and sinus tachycardia in 100% of horses, with mean HR of 107.6 ± 9.2 beats/min after exercise. Other findings included significant reductions in P wave duration, PR interval, QT interval and QTc, and significant increases in P wave amplitude and HR. The physical activity during barrel racing led to important alterations in the studied variables. These results can be used to evaluate the athletic conditioning of horses trained under tropical conditions. [ABSTRACT FROM AUTHOR]