Our results demonstrate that pinoresinol-rich EVOO extracts have potent chemopreventive properties and specifically upregulate the ATM-p53 cascade. This result was achieved at substantially lower concentrations in EVOO than with purified pinoresinol, indicating a possible synergic effect between the various polyphenols in olive oil.
The CpG island methylator phenotype is characterized by DNA hypermethylation in the promoters of tumor suppressor genes with silencing of transcription. Hypermethylation of the promoter of hMLH1 and subsequent microsatellite instability occurs in approximately 12% of sporadic colorectal cancers (CRC). Annurca apple, a variety of southern Italy, is rich in polyphenols that are associated with anticancer properties. Populations in southern Italy have lower incidences of CRC than elsewhere in the western world. We evaluated the mechanisms of putative anticancer effects of Annurca polyphenol extract (APE) in in vitro models of CRC. We extracted polyphenols from Annurca apples and treated RKO, SW48, and SW480 cells with APE and assessed the cell viability, apoptosis, and cell cycle. DNA methylation of selected tumor suppressor genes was evaluated after treatment with APE and was compared with the synthetic demethylating agent 5-aza-2'deoxycytidine (5-aza-2dC). DNA methyltransferase (DNMT)-1 and -3b levels were evaluated. Decreased cell viability and induction of apoptosis was evident after treatment. We found no significant changes in cell cycle dynamics. We observed significant increases of p53 protein expression in RKO after treatment. APE treatment strongly reduced DNA methylation in the promoters of hMLH1, p14(ARF), and p16(INK4a) with consequent restoration of normal expression. These effects were qualitatively comparable with those obtained with 5-aza-2dC. We observed a significant reduction in expression of DNMT proteins after treatment without changes in messenger RNA. In conclusion, APE have potent demethylating activity through the inhibition of DNMT proteins. The lack of toxicity in Annurca extracts makes them excellent candidates for the chemoprevention of CRC.
The levels of sedation required for patients to comfortably undergo colonoscopy with propofol were examined. One hundred patients undergoing colonoscopy with propofol were enrolled. In addition to standard-of-care monitoring, sedation level was monitored with the Patient State Index (PSI) obtained from a brain function monitor, transcutaneous carbon dioxide (tcpCO2) was monitored with the TCM TOSCA monitor, and end-tidal carbon dioxide was monitored via nasal cannula. The Ramsay Sedation Score (RSS) was also assessed and recorded. After baseline data were obtained from the first 40 consecutive patients enrolled in the study, the remaining 60 patients were randomized into two groups. In one group the PSI value was blinded from the anesthesiologist and in the second group the PSI was visible and the impact of this information on the management of the sedation was analyzed. Overall 96% of patients reached levels of deep sedation and 89% reached levels of general anesthesia. When comparing the blinded to PSI versus unblinded groups, the blinded group had a significantly lower PSI and higher RSS and tcpCO2, indicating the blinded group was maintained at a deeper sedation level with more respiratory compromise than the unblinded group. Patients undergoing colonoscopy under propofol sedation delivered by a bolus technique are frequently taken to levels of general anesthesia and are at risk for respiratory depression, airway obstruction, and hemodynamic compromise.
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