title: Habitual Myofibrillar Protein Synthesis Is Normal in Patients with Upper GI Cancer Cachexia.
abstract: OBJECTIVE
  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 patients with cancer compared with healthy controls.
  
  
  METHODS
  An oral heavy water (87.5 g 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
  Seven healthy volunteers, 6 weight-stable, and 7 weight-losing (≥5% weight loss) patients undergoing surgery for upper gastrointestinal cancer were recruited. Serial CT scans were available in 10 patients, who lost skeletal muscle mass preoperatively at a rate of 5.6%/100 days. Myofibrillar protein fractional synthetic rate was 0.058%, 0.061%, and 0.073%/hour in controls, weight-stable, and weight-losing patients, respectively. Weight-losing patients had higher synthetic rates than controls (P = 0.03).
  
  
  CONCLUSIONS
  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.
authors.affiliation: Department of Clinical Surgery, University of Edinburgh, Edinburgh Royal Infirmary, Edinburgh, United Kingdom.
authors.forename: Alisdair J
authors.initials: AJ
authors.lastname: MacDonald
authors.affiliation: Department of Clinical Surgery, University of Edinburgh, Edinburgh Royal Infirmary, Edinburgh, United Kingdom.
authors.forename: Neil
authors.initials: N
authors.lastname: Johns
authors.affiliation: Department of Clinical Surgery, University of Edinburgh, Edinburgh Royal Infirmary, Edinburgh, United Kingdom.
authors.forename: Nathan
authors.initials: N
authors.lastname: Stephens
authors.affiliation: School of Sport, Exercise and Rehabilitation Sciences, University of Birmingham, Edgbaston, Birmingham, United Kingdom.
authors.forename: Carolyn
authors.initials: C
authors.lastname: Greig
authors.affiliation: Department of Clinical Surgery, University of Edinburgh, Edinburgh Royal Infirmary, Edinburgh, United Kingdom.
authors.forename: James A
authors.initials: JA
authors.lastname: Ross
authors.affiliation: Stable Isotope Biochemistry Laboratory, Scottish Universities Research Centre, East Kilbride, United Kingdom.
authors.forename: Alexandra C
authors.initials: AC
authors.lastname: Small
authors.affiliation: Institute of Cardiovascular and Medical Sciences, College of Medicine, Veterinary Medicine and Life Science, University of Glasgow, Glasgow, United Kingdom.
authors.forename: Holger
authors.initials: H
authors.lastname: Husi
authors.affiliation: Department of Clinical Surgery, University of Edinburgh, Edinburgh Royal Infirmary, Edinburgh, United Kingdom.
authors.forename: Kenneth C H
authors.initials: KC
authors.lastname: Fearon
authors.affiliation: Stable Isotope Biochemistry Laboratory, Scottish Universities Research Centre, East Kilbride, United Kingdom. Tom.Preston@glasgow.ac.uk.
authors.forename: Tom
authors.initials: T
authors.lastname: Preston
mesh_terms: D000368:Aged; D002100:Cachexia / Q000209:etiology*; D004938:Esophageal Neoplasms / Q000150:complications*; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D009124:Muscle Proteins / Q000378:metabolism*; D018482:Muscle, Skeletal / Q000378:metabolism*; D014176:Protein Biosynthesis; D013274:Stomach Neoplasms / Q000150:complications*
chemical_list: D009124:Muscle Proteins