Neoadjuvant therapy and sentinel lymph node biopsy in HER2-positive breast cancer patients: results from the PEONY trial.

OBJECTIVE: The aim of the study is to evaluate the optimal timing of sentinel lymph node biopsy (SLNB) in patients with clinical negative axillary lymph nodes (ALNs) before neoadjuvant therapy (NAT) and the feasibility of SLNB substituting for ALN dissection in patients with positive ALNs who convert to node negative, for HER2-positive disease. METHODS: Patients receiving SLNB with dual tracer mapping in the PEONY trial were analyzed. RESULTS: For 80 patients with clinical negative ALNs, the node negative rate by pathology after NAT was 83.8%. SLNB was performed after NAT in 71 patients. The identification rate of sentinel lymph nodes (SLNs) was 100%. For patients with positive ALNs before NAT, the axillary pathologic complete response rate in the dual HER2 blockade arm was significantly higher than that in the single blockade arm (p = 0.002). SLNB was performed in 71 patients. The identification rate was 100% and the false-negative rate was 17.2%. The false-negative rates were 33.3%, 14.3%, and 0 when 1, 2, and more than 2 SLNs were detected. There was no false-negative case when more than 1 SLN and the clipped nodes were removed simultaneously. CONCLUSIONS: For clinical ALN negative patients, HER2-positive subtype is found to have high node negative rate by pathology and it is recommended to undergo SLNB after NAT. For patients with positive ALNs who convert to negative, the false-negative rate is high. Dual tracer mapping, more than 2 SLNs detected, more than 1 SLN identified plus the clips placed are the guarantees for lower false-negative rate.

Resveratrol reverses chronic restraint stress-induced depression-like behaviour: Involvement of BDNF level, ERK phosphorylation and expression of Bcl-2 and Bax in rats.

Chronic stress occurs in everyday life and induces depression-like behaviors, associated with proteins alterations and apoptosis in brain. Resveratrol is a natural polyphenol enriched in polygonum cuspidatum and has diverse biological activities, including potent antidepressant-like effects. The aim of this study was to determine whether resveratrol administration influences chronic restraint stress (CRS) - induced depression-like behaviors and explores underlying mechanisms. Male Wistar rats were subjected to CRS protocol for a period of 3 weeks to induce depressive-like behavior. The results showed that resveratrol (80mg/kg/i.p) administrated for 3 weeks significantly reversed the CRS-induced behavioral abnormalities (reduced sucrose preference and increased immobility time) in stressed rats. CRS exposure significantly decreased BDNF levels and phosphorylation of extracellular signal-regulated kinase (pERK) in hippocampus and prefrontal cortex (PFC), accompanied by decreased Bcl-2 mRNA expression and increased Bax mRNA expression, while resveratrol treatment normalized these levels. All of these effects of resveratrol were essentially identical to that observed with fluoxetine. In conclusion, our studies showed that resveratrol exerted antidepressant-like effects in CRS rats, mediated in part by the apoptotic machinery and up-regulating BDNF and pERK levels in the brain region.

Resveratrol exerts antidepressant properties in the chronic unpredictable mild stress model through the regulation of oxidative stress and mTOR pathway in the rat hippocampus and prefrontal cortex.

Depression is one of the most common neuropsychiatric disorders and has been associated with oxidative stress and brain protein alterations. Resveratrol is a natural polyphenol enriched in Polygonum cuspidatum and has diverse biological activities including potent antidepressant-like effects. The present study attempts to explore the mechanisms underlying the antidepressant-like action of resveratrol by measuring oxidative stress parameters and phosphorylation of AKT/mTOR pathway in the rat hippocampus and prefrontal cortex (PFC) exposed to the chronic unpredictable mild stress (CUMS). Male Wistar rats were subjected to CUMS protocol for a period of 4 weeks to induce depressive-like behavior. The results showed that resveratrol treatment (80 mg/kg/i.p. 4 weeks) significantly reversed the CUMS-induced behavioral abnormalities (reduced sucrose preference, increased immobility time and decreased locomotor activity) and biochemical changes (increased lipid peroxidation and decreased superoxide dismutase). Additionally, CUMS exposure significantly decreased phosphorylation of Akt and mTOR in the hippocampus and PFC, while resveratrol treatment normalized these parameters. In conclusion, our study showed that resveratrol exerted antidepressant-like effects in CUMS rats, which was mediated in part by its antioxidant action, up-regulation of phosphor-Akt and mTOR levels in the hippocampus and PFC.

Resveratrol reverses the effects of chronic unpredictable mild stress on behavior, serum corticosterone levels and BDNF expression in rats.

Depression is one of the most common neuropsychiatric disorders and has been associated with the neuroendocrine system and alterations in specific brain proteins. Resveratrol is a natural polyphenol enriched in polygonum cuspidatum and has diverse biological activities, including potent antidepressant-like effects. The present study attempts to explore the mechanisms underlying the antidepressant-like action of resveratrol by measuring serum corticosterone levels and the content of brain derived neurotrophic factor (BDNF) in the hippocampus and amygdala of rats exposed to the chronic unpredictable mild stress (CUMS). Male Wistar rats were subjected to the CUMS protocol for a period of 5 weeks to induce depressive-like behavior. Resveratrol treatment (20, 40 and 80mg/kg/i.p. 5 weeks) significantly reversed the CUMS-induced behavioral abnormalities (reduced sucrose preference, increased immobility time and decreased locomotor activity) and the elevated serum corticosterone levels observed in stressed rats. Additionally, 5-weeks of CUMS exposure significantly decreased BDNF levels in the hippocampus and amygdala, and was accompanied by decreased phosphorylation of extracellular signal-regulated kinase (pERK) and cAMP response element-binding protein (pCREB), while resveratrol treatment normalized these levels. All of these effects of resveratrol were essentially identical to that observed with the established antidepressant, desipramine. In conclusion, our study shows that resveratrol exerted antidepressant-like effects in CUMS rats, mediated in part by normalizing serum corticosterone levels while up-regulating pERK, pCREB and BDNF levels in the hippocampus and amygdala.

Antidepressant-like activity of resveratrol treatment in the forced swim test and tail suspension test in mice: the HPA axis, BDNF expression and phosphorylation of ERK.

Resveratrol is a natural polyphenol enriched in Polygonum cuspidatum and has diverse biological activities. There is only limited information about the antidepressant-like effect of resveratrol. The present study assessed whether resveratrol treatment (20, 40 and 80mg/kg, i.p., 21days) has an antidepressant-like effect on the forced swim test (FST) and tail suspension test (TST) in mice and examined what its molecular targets might be. The results showed that resveratrol administration produced antidepressant-like effects in mice, evidenced by the reduced immobility time in the FST and TST, while it had no effect on the locomotor activity in the open field test. Resveratrol treatment significantly reduced serum corticosterone levels, which had been elevated by the FST and TST. Moreover, resveratrol increased brain-derived neurotrophic factor (BDNF) protein and extracellular signal-regulated kinase (ERK) phosphorylation levels in the prefrontal cortex and hippocampus. All of these antidepressant-like effects of resveratrol were essentially similar to those observed with the clinical antidepressant, fluoxetine. These results suggest that the antidepressant-like effects of resveratrol in the FST and TST are mediated, at least in part, by modulating hypothalamic-pituitary-adrenal axis, BDNF and ERK phosphorylation expression in the brain region of mice.