TY - JOUR
T1 - Habitual myofibrillar protein synthesis is normal in patients with upper GI cancer cachexia
AU - MacDonald, Alisdair J.
AU - Johns, Neil
AU - Stephens, Nathan A.
AU - Greig, Carolyn A.
AU - Ross, James A.
AU - Small, Alexandra C.
AU - Husi, Holger
AU - Fearon, Kenneth C.H.
AU - Preston, Tom
PY - 2015/4/1
Y1 - 2015/4/1
N2 - 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 5.6100d. 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.
AB - 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 5.6100d. 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.
U2 - 10.1158/1078-0432.CCR-14-2004
DO - 10.1158/1078-0432.CCR-14-2004
M3 - Article
SN - 1557-3265
VL - 21
SP - 1734
EP - 1740
JO - Clinical Cancer Research
JF - Clinical Cancer Research
IS - 7
ER -