Showing papers by "Paula Ravasco published in 2007"

Colorectal Cancer: Intrinsic Characteristics Modulate Cancer Energy Expenditure and the Risk of Cachexia

Abstract: Purpose: To conduct a prospective longitudinal study in colorectal cancer (CRC) patients: 1) to evaluate resting energy expenditure (REE), weight/dietary intake changes, and response to treatment, taking into consideration cancer stage and histology; 2) to determine their potential interrelations; and 3) to quantify the relative contributions to REE of cancer/nutrition/treatment. Patients and Methods: 101 CRC patients proposed for neoadjuvant radiotherapy (RT) were evaluated before and after RT: REE (indirect calorimetry measurements), percentage of weight loss, usual diet (diet history), current diet (24 hour recall), and treatment response. Results: REE was higher in Stages III/IV versus I/II, at the RT onset (p < 0.002) and end (p = 0.02), and in moderately/poorly/undifferentiated cancers vs well differentiated (onset, p < 0.001) and (RT end, p = 0.01); weight/intake reductions were also greater in Stages III/IV versus I/II (p < 0.01) and in moderately/poorly/undifferentiated cancers versus well differ...

How relevant are cytokines in colorectal cancer wasting

Abstract: Purpose: The purpose of this article was to investigate the influence of inflammatory cytokines, pro-cachectic (interleukin [IL]-1 receptor agonist [IL-1ra], IL-6, and tumor necrosis factor-a [TNF-a]), immunomodulatory (IL-10 and interferon-γ [IFN-γ]), and pro-angiogenic (vascular endothelial growth factor [VEGF]), on resting energy expenditure (REE), weight, and nutritional intake and to explore potential interactions between their circulating concentrations and colorectal cancer stage/histologic differentiation and response to radiotherapy (RT). Patients and Methods: This was a prospective longitudinal study in 101 patients evaluated before and after neoadjuvant RT, including REE (indirect calorimetry), percent weight loss, usual/current diet (diet history and 24-hour recall), serum concentrations of cytokines (enzyme-linked immunosorbent assay), and RT response. Results: Stages III/IV were often associated with histologic grades 2/3 (P < 0.01), albeit both characteristics independently were associated with higher concentrations of IL-1ra (P ≤ 0.05), IL-6 (P ≤ 0.02), TNF-a (P ≤ 0.05), IFN-γ (P ≤ 0.05), and VEGF (P < 0.03). Before and after RT, higher REE, weight loss ≥5%, and intake reduction ≥25% were associated with advanced stage, histologic grades 2/3, higher IL-1ra, IL-6, TNF-a, IFN-y, and VEGF, and nonresponse to RT (P = 0.003). A general linear model analysis showed that stages III/IV, histologic grades 2/3, and higher IL-1ra, IL-6, TNF-a, IFN-y, and VEGF were major determinants of REE increase, weight loss, and intake reduction. In predictive value analyses, higher baseline pro-cachectic cytokines (IL-1ra + IL-6 + TNF-a) by themselves predicted increased REE (hazard ratio [HR]: 8.25; 95% CI: 2.74-26.47; P < 0.002), greater weight loss (HR: 8.15; 95% CI: 2.22-25.40; P < 0.002), and intake reductions (HR: 7.15; 95% CI: 2.25-16.11; P < 0.004) after RT. Conclusion: This study confirms the fact that wasting in colorectal cancer is correlated with tumor burden and histologic aggressiveness and suggests that both characteristics lead to overproduction of IFN-γ, VEGF, and pro-cachectic cytokines, all of which may cause higher metabolic rates, poor intake, and nonresponse to RT.

NF-kappaB and apoptosis in colorectal tumourigenesis.

Abstract: BACKGROUND Nuclear factor-kappaB (NF-kappaB) may play an important role in colorectal tumourigenesis, controlling cell cycle and apoptosis gene expression. In addition, imbalances between cell proliferation and cell death are thought to underlie neoplastic development. The aims of this study were to investigate apoptosis and expression of several apoptosis-related proteins, and to determine correlations with colorectal tumour progression. MATERIALS AND METHODS Apoptosis was evaluated by the TUNEL assay in 48 patient samples, including adenomas, adenocarcinomas and adjacent normal mucosas. Immunohistochemistry was performed for Bcl-2 and NF-kappaB. Expression levels of p53, Bax and IkappaB proteins were determined by immunoblotting. Cultured human colon cancer cells were used to evaluate NF-kappaB expression and nuclear translocation by immunocytochemistry and immunoblotting. RESULTS Apoptosis and NF-kappaB immunoreactivity were significantly higher in tumour tissue compared with normal mucosa (P < 0.01), increasing in association with histological tumour progression (P < 0.01). Bcl-2 was consistently higher in normal mucosa (P < 0.01) and inversely correlated with the percentage of apoptosis (P < 0.01). Phosphorylated p53 and Bax levels were similar in tumour tissue and normal mucosa; however, the NF-kappaB inhibitor, IkappaB, tended to decrease in tumours. In vitro, nuclear translocation of NF-kappaB was greater in proliferative than in resting phases of colon cancer cells. CONCLUSIONS NF-kappaB expression and apoptosis are increased from adenoma to poorly differentiated adenocarcinoma tissues. Apoptosis is correlated with suppression of Bcl-2 expression, but appears to proceed through a p53- and Bax-independent pathway. Activation of NF-kappaB may play an important role in colorectal tumour progression.

Colorectal cancer nutritional and quality-of-life parameters predict patients outcomes after radiotherapy: Long-term follow-up from a prospective randomized controlled trial

Abstract: 14570 Background: Long term data of our published randomized trial of nutritional therapy in colorectal cancer showed that nutritional counseling optimizes pts prognosis. This study aimed to search...