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Objective To investigate the inhibitory effect of cocoa polyphenol extract (CPE) on adipogenesis and obesity along with its mechanism of action. Methods and results 3T3-L1 preadipocytes were cultured with isobutylmethylxanthine, dexamethasone and insulin (MDI), and male C57BL/6N mice (N=44) were fed a high-fat diet (HFD) for 5 weeks with or without CPE. CPE at 100 or 200 μg ml(-1) inhibited MDI-induced lipid accumulation without diminishing cell viability. In particular, CPE reduced the protein expression levels of PPARγ and CEBPα, and blocked mitotic clonal expansion (MCE) of preadipocytes by reducing proliferating signaling pathways. This in turn attenuates lipid accumulation during the differentiation of 3T3-L1 preadipocytes. CPE effectively suppressed MDI-induced phosphorylation of extracellular signal-regulated kinase (ERK) and Akt, and their downstream signals. We then examined whether CPE regulates insulin receptor (IR), a common upstream regulator of ERK and Akt. We found that although CPE does not affect the protein expression level of IR, it significantly inhibits the activity of IR kinase via direct binding. Collectively, the results suggested that CPE, a direct inhibitor of IR kinase activity, inhibits cellular differentiation and lipid accumulation in 3T3-L1 preadipocytes. Consistently, CPE attenuated HFD-induced body weight gain and fat accumulation in obese mice fed with a HFD. We also found that HFD-induced increased fasting glucose levels remained unaffected by CPE. Conclusion This study demonstrates that CPE inhibits IR kinase activity and its proliferative downstream signaling markers, such as ERK and Akt, in 3T3-L1 preadipocytes, and also prevents the development of obesity in mice fed with a HFD.

To evaluate the accuracy of integrated positron emission tomography (PET) and computed tomography (CT) for depiction of suspected recurrent ovarian carcinoma after treatment, with use of clinical or histological findings as the reference standard.Seventy-seven women (median age, 51 years) with ovarian carcinoma treated with primary cytoreductive surgery followed by platinum-based combination chemotherapy were included, and [18F]fluorodeoxyglucose (FDG) PET/CT was performed for suspected recurrence. In all patients, imaging findings were compared with results of histological examination after surgical exploration or clinical follow-up to determine the diagnostic accuracy of PET/CT in the evaluation of disease status. Fisher's exact test was used to measure the ability of PET/CT to predict recurrent lesions.Forty-five (58.4%) of the 77 patients had documented recurrence during surgical exploration or clinical follow-up, while 32 (41.6%) had no evidence of recurrent tumour. Of the 45 patients with recurrent disease, 27 (60%) were confirmed to have recurrence by surgical biopsy. A correlation was found between PET/CT and histological or clinical analyses (kappa = 0.894). The overall sensitivity, specificity, accuracy, positive predictive value and negative predictive value of PET/CT were 93.3%, 96.9%, 94.8%, 97.7% and 91.2%, respectively. PET/CT modified the diagnostic or treatment plan in 19 (24.7%) patients, by leading to the use of previously unplanned therapeutic procedures in 11 (57.9%) patients and the avoidance of previously planned diagnostic procedures in eight (42.1%) patients.Integrated FDG PET/CT is a sensitive post-therapy surveillance modality for the detection of recurrent ovarian cancer; it aids decisions on treatment plans and may ultimately have a favourable impact on prognosis.

ERCC1 is a DNA repair gene and has been associated with resistance to DNA damaging agents. In this study we hypothesized that a polymorphism of ERCC1 Asn118Asn (C →T) might affect the platinum-resistance of epithelial ovarian cancer patients to platinum-taxane chemotherapy administered postoperatively. Using the SNapShot assay, we assessed this polymorphism in ERCC1 in 60 ovarian cancer patients. Platinum-resistance was defined as pro - gression on platinum-based chemotherapy or recurrence within 6 months of completing therapy. Although not significant, platinum-resistance was less frequently observed in patients with the C/T + T/T genotype (P = 0.064). Multivariate analysis showed that the C/T + T/T genotypes constituted an independent predictive factor of reduced risk of platinum-resistance in ovarian cancer (odds ratio 0.17, 95% confidence interval 0.04-0.74, P = 0.018, Fisher's exact test). No significant correlation was observed between overall survival and the ERCC1 polymorphism. Our results suggest that genotyping of the ERCC1 polymorphism Asn118Asn may be useful for predicting the platinum-resistance of epithelial ovarian cancer patients. However, these findings require prospective confirmation.