Aglianico Grape Seed Semi-Polar Extract Exerts Anticancer Effects by Modulating MDM2 Expression and Metabolic Pathways.

Grapevine (Vitis vinifera L.) seeds are rich in polyphenols including proanthocyanidins, molecules with a variety of biological effects including anticancer action. We have previously reported that the grape seed semi-polar extract of Aglianico cultivar (AGS) was able to induce apoptosis and decrease cancer properties in different mesothelioma cell lines. Concomitantly, this extract resulted in enriched oligomeric proanthocyanidins which might be involved in determining the anticancer activity. Through transcriptomic and metabolomic analyses, we investigated in detail the anticancer pathway induced by AGS. Transcriptomics analysis and functional annotation allowed the identification of the relevant causative genes involved in the apoptotic induction following AGS treatment. Subsequent biological validation strengthened the hypothesis that MDM2 could be the molecular target of AGS and that it could act in both a p53-dependent and independent manner. Finally, AGS significantly inhibited tumor progression in a xenograft mouse model of mesothelioma, confirming also in vivo that MDM2 could act as molecular player responsible for the AGS antitumor effect. Our findings indicated that AGS, exerting a pro-apoptotic effect by hindering MDM2 pathway, could represent a novel source of anticancer molecules.

Age does not hamper the response to pulmonary rehabilitation of COPD patients.

BACKGROUND: pulmonary rehabilitation (PR) improves health status and exercise tolerance, but not respiratory function in patients with chronic obstructive pulmonary disease (COPD). Our objective was to identify predictors of improvement in the 6-min walked distance (6'WD) in elderly COPD patients after PR. METHODS: this was a prospective observational study performed in an ambulatory rehabilitation setting. We enrolled 74 patients aged 65-83 years (mean: 74.2, SD: 4.4) with stable COPD in GOLD stage 3-4. About half (45.6%) of them had a basal O(2) saturation of 90% or less. After a baseline multi-dimensional assessment, patients underwent a 20-session rehabilitation cycle including training of the upper and lower extremities, and respiratory exercises, along with education sessions. The difference between final and basal 6'WD was expressed as a per cent of the basal value (6'WD gain). Patients were divided into two groups according to whether the 6'WD gain was above or under the 75th percentile, corresponding to 33% gain. RESULTS: patients whose 6'WD improved more had lower baseline forced expiratory volume in the first second (FEV1)/forced vital capacity (FVC) (46.0 versus 52.2%, P = 0.03) and baseline 6'WD, both as an absolute value (329.5 versus 408.9 m, P = 0.01) and as a per cent of the predicted (71.1 versus 93.5%, P = 0.002). After correction for potential confounders, baseline 6'WD was the only variable associated with the outcome (OR for 5% increments: 0.79; 95% CI 0.65-0.95). CONCLUSIONS: among elderly patients with COPD, a comprehensive rehabilitation programme can significantly improve the 6'WD even in the presence of chronic hypoxemia. The most physically impaired patients achieve the greatest benefit from rehabilitation, but we could not develop a model accurately predicting the response to rehabilitation.