Habitual myofibrillar protein synthesis is normal in patients with upper GI cancer cachexia

MacDonald, A. J., Johns, N., Stephens, N. A., Greig, C. A., Ross, J. A., Small, A. C., Husi, H., Fearon, K. C.H. and Preston, T. (2015) Habitual myofibrillar protein synthesis is normal in patients with upper GI cancer cachexia. Clinical Cancer Research, 21(7), pp. 1734-1740. (doi: 10.1158/1078-0432.CCR-14-2004) (PMID:25370466)

Abstract

Purpose: Skeletal muscle wasting and weight loss are characteristic features of cancer cachexia and contribute to impaired function, increased morbidity and poor tolerance of chemotherapy. This study used a novel technique to measure habitual myofibrillar protein synthesis in cancer patients compared with healthy controls. Experimental design: An oral heavy water (87.5g deuterium oxide) tracer was administered as a single dose. Serum samples were taken over the subsequent week followed by a quadriceps muscle biopsy. Deuterium enrichment was measured in body water, serum alanine and alanine in the myofibrillar component of muscle using Gas Chromatography-Pyrolysis-Isotope Ratio Mass Spectrometry and the protein synthesis rate calculated from the rate of tracer incorporation. Net change in muscle mass over the preceding 3 months was calculated from serial CT scans and allowed estimation of protein breakdown. Results: 7 healthy volunteers, 6 weight-stable and 7 weight-losing (≥5% weight loss) patients undergoing surgery for upper GI cancer were recruited. Serial CT scans were available in 10 patients, who lost skeletal muscle mass preoperatively at a rate of 5.6%/100d. Myofibrillar protein fractional synthetic rate was 0.058, 0.061 and 0.073 %/h in controls, weight-stable and weight-losing patients respectively. Weight-losing patients had higher synthetic rates than controls (p=0.03). Conclusion: Contrary to previous studies, there was no evidence of suppression of myofibrillar protein synthesis in patients with cancer cachexia. Our finding implies a small increase in muscle breakdown may account for muscle wasting.

• Item Type: Articles
• Status: Published
• Refereed: Yes
• Glasgow Author(s) Enlighten ID: Preston, Professor Tom and Small, Mrs Sandra and Husi, Dr Holger
• Authors: MacDonald, A. J., Johns, N., Stephens, N. A., Greig, C. A., Ross, J. A., Small, A. C., Husi, H., Fearon, K. C.H., and Preston, T.
• College/School: College of Medical Veterinary and Life Sciences > School of Cardiovascular & Metabolic Health; College of Science and Engineering > Scottish Universities Environmental Research Centre
• Journal Name: Clinical Cancer Research
• Publisher: American Association for Cancer Research
• ISSN: 1078-0432
• ISSN (Online): 1557-3265