Habitual Myofibrillar Protein Synthesis Is Normal in Patients with Upper GI Cancer Cachexia

Alisdair J. MacDonald, Neil Johns, Nathan Stephens, Carolyn Greig, James A. Ross, Alexandra C. Small, Holger Husi, Kenneth C. H. Fearon, Tom Preston*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

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 patients with cancer compared with healthy controls.

Experimental Design: 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).

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. (C) 2014 AACR.

Original languageEnglish
Pages (from-to)1734-1740
Number of pages7
JournalClinical Cancer Research
Volume21
Issue number7
Early online date4 Nov 2014
DOIs
Publication statusPublished - 1 Apr 2015

Keywords

  • SKELETAL-MUSCLE MASS
  • SYNTHESIS RATES
  • IN-VIVO
  • RESISTANCE EXERCISE
  • CACHECTIC PATIENTS
  • PHYSICAL-ACTIVITY
  • BODY-COMPOSITION
  • DISUSE ATROPHY
  • AMINO-ACIDS
  • HUMANS

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