Subject(s)
Gastrointestinal Neoplasms/drug therapy , Pentoxifylline/therapeutic use , Quality of Life , Colorectal Neoplasms/complications , Colorectal Neoplasms/drug therapy , Colorectal Neoplasms/psychology , Fatigue/etiology , Gastrointestinal Neoplasms/complications , Gastrointestinal Neoplasms/psychology , Humans , Tumor Necrosis Factor-alpha/antagonists & inhibitorsABSTRACT
The expression of genes coding for regulatory enzymes involved in the uptake, synthesis and mobilisation of lipid was measured in adipose tissue of cancer patients. Total RNA was isolated from subcutaneous adipose tissue of control and cancer patients and the various mRNAs measured by Northern blot analysis. The total lipoprotein lipase enzymic activity and the relative levels of the mRNAs for lipoprotein lipase and for fatty acid synthase were not significantly different between cancer patients and control patients. However, there was a significant two-fold increase in the relative level of mRNA for hormone-sensitive lipase (HSL) in adipose tissue of cancer patients compared with control patients. The cancer patients also exhibited a two-fold elevation in serum triacylglycerol levels and serum free fatty acid levels. There was a significant correlation between the serum free fatty acid level and expression of HSL mRNA in the adipose tissue. The serum levels of insulin and tumour necrosis factor-alpha were not different between cancer and control patients. The results suggest that at least one of the mechanisms for depletion of lipid from adipose tissue in cancer patients operates at the level of increased expression of mRNA of the lipolytic regulatory enzyme, hormone-sensitive lipase.
Subject(s)
Adipose Tissue/enzymology , Neoplasms/enzymology , Sterol Esterase/genetics , Adult , Aged , Aged, 80 and over , Blotting, Northern , Fatty Acid Synthases/genetics , Fatty Acid Synthases/metabolism , Female , Humans , Lipoprotein Lipase/genetics , Lipoprotein Lipase/metabolism , Male , Middle Aged , Neoplasms/blood , RNA, Messenger/biosynthesis , RNA, Neoplasm/biosynthesis , Sterol Esterase/metabolismABSTRACT
Cancer cachexia may be mediated by endogenous peptides such as tumour necrosis factor alpha (TNF-alpha). Insulin resistance occurs in these patients, and is also seen experimentally with TNF-alpha administration. In this study, insulin sensitivity and energy metabolism were measured in 11 patients with gastrointestinal cancer and ten controls, using the euglycaemic glucose clamp and indirect calorimetry. Patients with cancer were significantly more insulin resistant than controls (P < 0.01) and in such patients insulin resistance correlated with serum TNF-alpha level (rs = 0.74, P < 0.01). Fasting insulin levels also correlated inversely with insulin sensitivity (rs = -0.62, P = 0.003). These results suggest a possible association between endogenous TNF-alpha production and insulin resistance in patients with gastrointestinal cancer.
Subject(s)
Gastrointestinal Neoplasms/blood , Insulin Resistance/physiology , Tumor Necrosis Factor-alpha/analysis , Aged , Blood Glucose/metabolism , Energy Metabolism/physiology , Female , Glucose Clamp Technique , Humans , Insulin/blood , Male , Middle AgedABSTRACT
Methylxanthines have been used in clinical practice for over 100 years, and although understanding of their mechanisms of action is growing their effects are not fully understood. Nevertheless the knowledge to date has brought about a general upsurge of interest in methylxanthines and the development of novel derivatives. Methylxanthines are poised to escape the confines of their traditional role as these agents are applied in novel ways to surgical illnesses such as septic shock, the adult respiratory distress syndrome, cancer cachexia and functional neutrophil disorders. Methylxanthines, alone or in combination with other compounds, may well become part of the surgeon's future stock-in-trade.
