Search

Perturbations of energy balance induce compensatory processes that may alter expected weight loss. In obese patients, our aim was to investigate the relationships that occurred between fasting plasma concentrations of anorexigenic peptides and metabolic parameters, appetite, physical capacity, and weight loss in the 5 first days of a program associating exercise and caloric reduction. Thirteen obese women were monitored from day 1 to day 5 with 2 exercise sessions in day 2 and day 4. We measured, in a fasted state, changes in body weight, hunger ratings, and plasma concentrations of fatty acids, triglycerides, leptin, insulin, amylin, peptide YY, and insulin- resistance index. Physical performance was assessed by a 6-min walking test. The program resulted in significantly reduced body weight (0.75 ± 0.4 kg; p = 0.001), of plasma concentrations of triglycerides, insulin, amylin, peptide YY, and the insulin-resistance index, and also increased fatty acids (p < 0.05). Hunger ratings were increased (p < 0.05). Program-induced changes in fatty acids, leptin, and insulin concentrations were related to physical performance (r² = 0.45, 0.59, and 0.52; p < 0.05, respectively) and to weight loss (r² = 0.65, 0.57, 0.55; p < 0.05, respectively). Five days of diet and exercise induced weight loss, improved lipid profile, and decreased insulin resistance while hunger ratings increased. Subjects with higher physical capacity lost more weight, presented higher increases in fatty acids and lower changes of leptin and insulin concentrations suggesting a better metabolic flexibility. To reduce the compensatory responses that can occur with energy imbalances, our study supports to account for individual activity level before prescribing weight-loss program associating diet and exercise. [ABSTRACT FROM AUTHOR]

Background:The PI3K/Akt signalling pathway, induced by epidermal growth factor receptor (EGFR) and Her-2, is involved in the constitutive activation of NF-κB in prostate cancer cell lines. In this study, we extended the in vitro observation using an ex vivo model of prostate cancer tissues and assessed the prognostic significance of the PI3K/Ak/NF-κB signalling determinants.Methods:We analysed a prostate cancer tissue microarray of 63 patients for the expression of total and activated EGFR, Her-2 receptors and the signalling molecules PTEN, phospho-PTEN, Akt, phospho-Akt and the NF-κB subunit p65. Data were analysed using Spearman's rho test, Kaplan–Meier curves and multivariate Cox regression analysis. In addition, a non-supervised hierarchical clustering analysis was applied to stratify patients according to prognostic groups in terms of risk of recurrence.Results:The concomitant overexpression of activated EGFR and Her-2 was correlated with the nuclear expression of NF-κB. EGFR, phospho-EGFR, phospho-Her-2, ErbB3 and nuclear NF-κB were associated with the overall biochemical recurrence (BCR) of patients. The non-supervised hierarchical clustering analysis resulted in the separation of patients into five groups according to BCR.Conclusions:These results validate the previous in vitro data on ErbB involvement in NF-κB activation and shows evidence for a significant role of ErbB/PI3K/Akt/NF-κB signalling in the progression of prostate cancer. [ABSTRACT FROM AUTHOR]

Effective treatments for androgen-independent prostate cancer (AIPCa) are lacking. To address this, emerging therapeutics such as proteasome inhibitors are currently undergoing clinical trials. Inositol hexakisphosphate (IP6) is an orally non-toxic phytochemical that exhibits antitumour activity against several types of cancer including PCa. We have previously shown that treatment of PC3 cells with IP6 induces the transcription of a subset of nuclear factor-κB (NF-κB)-responsive and pro-apoptotic BCL-2 family genes. In this study, we report that although NF-κB subunits p50/p65 translocate to the nucleus of PC3 cells in response to IP6, inhibition of NF-κB-mediated transcription using non-degradable inhibitor of κB (IκB)-α does not modulate IP6 sensitivity. Treatment with IP6 also leads to increased protein levels of PUMA, BIK/NBK and NOXA between 4 and 8 h of treatment and decreased levels of MCL-1 and BCL-2 after 24 h. Although blocking transcription using actinomycin D does not modulate PC3 cell sensitivity to IP6, inhibition of protein translation using cycloheximide has a significant protective effect. In contrast, blocking proteasome-mediated protein degradation using MG-132 significantly enhances the ability of IP6 to reduce cellular metabolic activity in both PC3 and DU145 AIPCa cell lines. This effect of combined treatment on mitochondrial depolarisation is particularly striking and is also reproduced by another proteasome inhibitor (ALLN). The enhanced effect of combined MG132/IP6 treatment is almost completely inhibited by cycloheximide and correlates with changes in BCL-2 family protein levels. Altogether these results suggest a role for BCL-2 family proteins in mediating the combined effect of IP6 and proteasome inhibitors and warrant further pre-clinical studies for the treatment of AIPCa.British Journal of Cancer (2008) 99, 1613–1622. doi:10.1038/sj.bjc.6604730 www.bjcancer.com Published online 21 October 2008 [ABSTRACT FROM AUTHOR]

We investigated the correlation between the expression and localisation of Akt-1, Akt-2, Akt-3, phospho-Akt proteins and the clinicopathological parameters in 63 prostate cancer specimens. More than 60% of cancerous tissues overexpressed Akt-1, Akt-2 or Akt-3. Cytoplasmic Akt-1 expression was correlated with a higher risk of postoperative prostate-specific antigen (PSA) recurrence and shorter PSA recurrence interval. Cytoplasmic Akt-2 did not show any significant correlation with clinicopathological parameters predicting outcomes. Cytoplasmic Akt-3 was associated with hormone-refractory disease progression and extracapsular invasion. Nuclear Akt-1 and Akt-2 expression were correlated with favourable outcome parameters such as absence of lymph node and perineural invasion. Kaplan–Meier analysis and Cox regression model also showed that Akt-1 and Akt-2, but not Akt-3 or phospho-Akt was associated with a significantly higher risk of PSA recurrence. In contrast, nuclear Akt-1 was significantly associated with a lower risk of PSA recurrence. Multivariate analysis revealed that clinical stage, Gleason score and the combined cytoplasmic nuclear Akt-1 marker in cancerous tissues were significant independent prognostic factors of PSA recurrence. This is the first report demonstrating in patients with prostate cancer and the particular role of Akt-1 isoform expression as a prognostic marker depending of its localisation.British Journal of Cancer (2006) 94, 1906–1912. doi:10.1038/sj.bjc.6603184 www.bjcancer.com Published online 23 May 2006 [ABSTRACT FROM AUTHOR]

In order to elucidate the biological variance between normal ovarian surface epithelial (NOSE) and epithelial ovarian cancer (EOC) cells, and to build a molecular classifier to discover new markers distinguishing these cells, we analysed gene expression patterns of 65 primary cultures of these tissues by oligonucleotide microarray. Unsupervised clustering highlights three subgroups of tumours: low malignant potential tumours, invasive solid tumours and tumour cells derived from ascites. We selected 18 genes with expression profiles that enable the distinction of NOSE from these three groups of EOC with 92% accuracy. Validation using an independent published data set derived from tissues or primary cultures confirmed a high accuracy (87-96%). The distinctive expression pattern of a subset of genes was validated by quantitative reverse transcription-PCR. An ovarian-specific tissue array representing tissues from NOSE and EOC samples of various subtypes and grades was used to further assess the protein expression patterns of two differentially expressed genes (Msln and BMP-2) by immunohistochemistry. This study highlights the relevance of using primary cultures of epithelial ovarian cells as a model system for gene profiling studies and demonstrates that the statistical analysis of gene expression profiling is a useful approach for selecting novel molecular tumour markers. [ABSTRACT FROM AUTHOR]

In West Africa, new management practices such as conservation agriculture with crop residue mulching can improve crop yields for individual farmers. However, in a context of complex social interactions between farmers, the introduction of such practices can also lead to conflicts between private interests and communal use of resources, for example the free grazing of crop residues. The objective of this paper was to assess ex-ante the impacts of the practice of crop residue mulching on crop productivity in a village of central Burkina Faso using an agent-based model, AMBAWA, that simulates the flows of biomass and nutrients between crop and livestock systems at the village scale. The model considers the interactions between four types of farmers that were identified in the study site: subsistence-oriented crop farmers, market-oriented crop farmers, agro-pastoralists and pastoralists. The model simulated increased cattle migration outside the village due to increased crop residue scarcity during the dry season with increased proportions of cropland under the practice of conservation agriculture, decreasing the manure availability at village scale. Consequently, the assumed direct yield increases due to soil moisture conservation as a result of mulching did not compensate for the yield losses resulting from lesser amounts of manure available. This effect was felt most strongly by farmers who own relatively large numbers of cattle (agro-pastoralists and pastoralists). The total maize production at village level depended more on the proportion of cropping land that was available for grazing by cattle, and thus not mulched, than on a possible direct effect of mulching on yield per se. The AMBAWA model can support discussion among stakeholders (farmers, traditional and administrative authorities) who are involved in the private and communal management of crop residues and other biomass resources, in order to co-design effective arrangements and practices for their sustainable use. • AMBAWA is an agent-based model that simulates biomass and nutrients flows. • Biomass flows (manure, crop residue) were considered between four types of farmers. • AMBAWA was used to assess the effect of crop residue mulching on crop productivity. • Mulching decreased yields at village scale due to livestock migration (manure loss). • Agent based models allows co-designing innovative practices in agro-pastoral areas. [ABSTRACT FROM AUTHOR]