Background: Extracellular adenosine 5'-triphosphate (ATP) is involved in the regulation of a variety of biologic processes, including neurotransmission, muscle contraction, and liver glucose metabolism, via purine...
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Background: Extracellular adenosine 5'-triphosphate (ATP) is involved in the regulation of a variety of biologic processes, including neurotransmission, muscle contraction, and liver glucose metabolism, via purinergic receptors, In nonrandomized studies involving patients with different tumor types including non-small-cell lung cancer (NSCLC), ATP infusion appeared to inhibit loss of weight and deterioration of quality of life (QOL) and performance status. We conducted a randomized clinical trial to evaluate the effects of ATP in patients with advanced NSCLC (stage IIIB or IV). Methods: Fifty-eight patients were randomly assigned to receive either 10 intravenous 30-hour ATP infusions, with the infusions given at 2- to 4-week intervals, or no ATP, Outcome parameters were assessed every 4 weeks until 28 weeks. Between-group differences were tested for statistical significance by use of repeated-measures analysis, and reported P values are two-sided. Results: Twenty-eight patients were allocated to receive ATP treatment and 30 received no ATP, Mean weight changes per 4-week period were -1.0 kg (95% confidence interval [CI] = -1.5 to -0.5) in the control group and 0.2 kg (95% CI = -0.2 to +0.6) in the ATP group (P = .002). Serum albumin concentration declined by -1.2 g/L (95% CI = -2.0 to -0.4) per 4 weeks in the control group but remained stable (0.0 g/L;95% CI = -0.3 to +0.3) in the ATP group (P = .006). Elbow flexor muscle strength declined by -5.5% (95% CI = -9.6% to -1.4%) per 4 weeks in the control group but remained stable (0.0%;95% CI = -1.4% to +1.4%) in the ATP group (P = .01). A similar pattern was observed far knee extensor muscles (P = .02). The effects of ATP on body weight, muscle strength, and albumin concentration were especially marked in cachectic patients (P = .0002, P = .0001, and P = .0001, respectively, for ATP versus no ATP). QOL score changes per 4-week period in the ATP group showed overall less deterioration than in the control group-physical
Cancer-induced cachexia is a common manifestation observed in patients with malignancies. Elevated levels of circulating,glucocorticoids and interleukin-6 (IL-6) hare been observed in cancer patients with cachexia and...
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Cancer-induced cachexia is a common manifestation observed in patients with malignancies. Elevated levels of circulating,glucocorticoids and interleukin-6 (IL-6) hare been observed in cancer patients with cachexia and are implicated as major mediators in this process. The purpose of this study was to investigate the role of circulating glucocorticoid levels as primary mediators in cancer-induced cachexia. We evaluated whether inhibition of glucocorticoids with the receptor antagonist RU-486 could abrogate the detrimental wasting of muscle and adipose tissues seen in a well-characterized murine tumor-induced cachexia model. Mice (12/group) were randomized to control, tumor-bearing, control + vehicle, or tumor-bearing + glucocorticoid receptor antagonist groups. Circulating serum glucocorticoid and IL-6 levels were measured in addition to multiple body composition parameters, such as total body weight lean body mass, and adipose content. The results of this study indicate a significant physiological alteration in the tumor-bearing host that causes severe and detrimental changes in body composition parameters. Regression analysis demonstrated a significant correlation between increased circulating glucocorticoid levels and alterations in body composition parameters. These observed defects were not abrogated with the administration of a glucocorticoid receptor antagonist. We therefore conclude that the untoward effects of tumor-induced cachexia are not mediated primarily by the peripheral effects of high circulating glucocorticoid levels but may involve a complex interaction with IL-6.
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