Although VEGFR-3 deficiency disrupts blood vascular development during early embryogenesis, the underlying mechanism was not clear. To characterize its function in angiogenesis and lymphangiogenesis, we employed two genetically modified mouse models in this study, targeting the coding region for the ligand-binding domain (Vegfr3 ∆LBD ) or the tyrosine kinase domain with an inactivation point mutation (Vegfr3 TKmut ). We show that lymphatic growth was disrupted in Vegfr3 ∆LBD/∆LBD and Vegfr3 TKmut/TKmut mice, but blood vessels developed normally in both embryo and yolk sac. Interestingly, in Vegfr3 ∆LBD/∆LBD but not Vegfr3 TKmut/TKmut mice, lymph sac was present but there was lack of lymphangiogenic sprouting. We further demonstrate that both the wild-type and mutant forms of VEGFR-3 could form heterodimers with VEGFR-2, and decreased the level of phospho-VEGFR-2 and the downstream phospho-Erk1/2 in endothelial cells when they were treated with VEGF-A. These findings indicate that signaling mediated via VEGFR-3 activation by its cognate ligands (VEGF-C/-D) is not required for angiogenesis, and that VEGFR-3 may play a role in this process by modulating VEGFR-2-mediated signals.

Anthracyclines are potent antineoplastic agents associated with cardiotoxicity, which may lead to congestive heart failure, causing impairment of autonomic cardiovascular function as assessed by heart rate variability (HRV). This decreases survival rates. This study aimed to determine whether music therapy intervention improves autonomic function in anthracycline-treated breast cancer patients, and if so, whether such improvements persist after cessation of the intervention. Participants were 12 women with breast cancer who had undergone mastectomy or breast-conserving treatment and adjuvant chemotherapy; they attended 8 weekly music therapy sessions, each lasting 2 hours. Electrocardiogram traces (5 minutes) for HRV analysis were recorded 4 times: prior to the first music session, T1; after the fourth music session, T2; after the eighth music session, T3; and 4 weeks after the completion of music therapy, T4. HRV parameters were subjected to a nonparametric Friedman test on the differences between T1 and T2, T3, and T4. The standard deviation of normal intervals and the total power of HRV parameters, related to global autonomic function, were significantly higher at T3 than at T1. The root-mean-square differences of successive normal R-R intervals and high-frequency (HF) HRV parameters, related to parasympathetic activity, were significantly increased, but no change was seen in the LF/HF ratio of HRV parameters (which is related to sympathetic activity) during the music therapy. Global autonomic function and parasympathetic activity had not changed significantly at T4 relative to T1. The authors provide preliminary evidence of the benefits of music therapy for anthracycline-treated breast cancer survivors.

No abstract

No abstract