Slow drug release at the tumor tissue and poor tumor penetration are two big challenges for the successful application of nanosystems in tumor therapy. Here, we report that a high concentration of the natural reducing agent vitamin C (VC) triggers rapid extracellular PTX release from PTX-loaded shell-sheddable PEG-SS-PCL micelles (SSM) in tumors in vivo. An in vivo tolerance study showed that VC at a blood concentration of 40mM had little toxicity to nude mice. Notably, SSM rapidly disassembled and released the payloads (Cy5 or PTX) in response to 40mM VC. In vivo near-infrared imaging of tumor-bearing mice showed that with post-injection of VC to establish a blood concentration of 40mM, Cy5 was quickly released from the micelles and diffused deep into the tumor tissue. Biodistribution studies revealed that 6h after the injection of PTX-loaded micelles the highest tumor accumulation was reached, which was set as the injection time for VC. The antitumor efficacy of a combination therapy of PTX-loaded micelles and VC was evaluated in both MCF-7 and U87MG tumor models. In both tumor models, single injections of VC didn't show any antitumor effect, while sequential administration of PTX-loaded SSM and VC exhibited significantly higher tumor inhibition effects and better survival rates as compared to single treatment with PTX-loaded micelles, demonstrating that exogenous administration of VC effectively triggered the release of PTX from SSM in vivo. The combination of reduction-sensitive nanomedicines with exogenous VC appears a promising approach to achieve potent treatment of malignant tumors.

OBJECTIVES:Previous research has found that yoga can enhance quality of life and ease menopausal symptoms of breast cancer survivors. The study examined whether self-esteem mediated the effects of yoga on quality of life, fatigue and menopausal symptoms, utilizing validated outcome measures.

STUDY DESIGN:This is a secondary analysis of a randomized controlled trial comparing the effects of yoga with those of usual care in 40 breast cancer survivors who suffered from menopausal symptoms. All participants completed all 3 assessments (week 0, week 12, and week 24) and provided full data.

MAIN OUTCOME MEASURES:Outcomes were measured using self-rating instruments. Mediation analyses were performed using SPSS.

RESULTS:Self-esteem mediated the effect of yoga on total menopausal symptoms (B=-2.11, 95% BCI [-5.40 to -0.37]), psychological menopausal symptoms (B=-0.94, 95% BCI [-2.30 to -0.01]), and urogenital menopausal symptoms (B=-0.66, 95% BCI [-1.65 to -0.15]), quality of life (B=8.04, 95% BCI [3.15-17.03]), social well-being (B=1.80, 95% BCI [0.54-4.21]), emotional well-being (B=1.62, 95% BCI [0.70-3.34]), functional well-being (B=1.84, 95% BCI [0.59-4.13]), and fatigue (B=4.34, 95% BCI [1.28-9.55]). Self-esteem had no effect on somatovegetative menopausal symptoms (B=-0.50, 95% BCI n.s.) or on physical well-being (B=0.79, 95% BCI n.s.).

CONCLUSIONS:Findings support the assumption that self-esteem plays a vital role in the beneficial effect of yoga and that yoga can have long-term benefits for women diagnosed with breast cancer and undergoing menopausal transition.