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Loss of oxidative defense and potential blockade of satellite cell maturation in the skeletal muscle of patients with cancer but not healthy elderly

Brzeszczyńska, Joanna and Johns, Neil and Schilb, Alain and Degen, Simone and Degen, Martin and Langen, Ramon and Schols, Annemie and Glass, David and Roubenoff, Ronenn and Greig, Carolyn A. and Jacobi, Carsten and Fearon, Kenneth C.H. and Ross, James A. (2016) Loss of oxidative defense and potential blockade of satellite cell maturation in the skeletal muscle of patients with cancer but not healthy elderly. Clinical Cancer Research, 8 (7). pp. 1-12. ISSN 1945-4589

Abstract

Purpose: Muscle wasting in old age or cancer may result from failure of myofibre regeneration and /or accelerated apoptosis both of which may be up-regulated by oxidative stress or inflammation. The aim of this study was to determine from the transcriptome in human skeletal muscle whether there is evidence for oxidative stress and its relationship with satellite cell differentiation or apoptosis in the muscle of patients with cancer (weight-stable: CWS or weight-losing: CWL) or healthy elderly (HE) when compared with healthy middle aged controls (HMAC) .

Design: 28 patients with resectable upper GI/pancreatic cancer (CWS: 14 and CWL14), 17 HE and 22 HMAC underwent biopsy of the quadriceps muscle. Markers of muscle regeneration, inflammation, oxidative stress and apoptosis were measured by qPCR.

Results: The expression of transcription factors responsible for muscle regeneration (Pax3, Pax7 and MyoD) were increased in the skeletal muscle of CWS and HE when compared with HMAC (P<0.001). In contrast, the expression of myogenic differentiation markers (MyoG and Myh2) was reduced in CWS and CWL but increased in HE when compared with HMAC (P<0.0001). The expression of the pro-apoptotic gene Bax was significantly increased in CWS, CWL and HE compared with HMAC (P<0.0001). Pro-inflammatory cytokine expression was variable with increased expression of TNF in CWS and HE, increased Il-6 in CWS and increased Il-1 in CWL when compared with HMAC. Expression of the oxidative defense genes SOD2, GCLM, and NRF2 was decreased in CWS and CWL but increased in HE when compared with HMA (P<0.0001).

Conclusion: There is evidence for blockade of satellite cell maturation, upregulation of apoptosis and reduced oxidative defense in the skeletal muscle of cancer patients. In contrast, in muscle from healthy elderly the potential for myotube differentiation and oxidative defense is maintained.

Item Type: Article
Keywords: Cancer ,cachexia, elderly, satellite cells, oxidative stress,
Date Deposited: 09 Aug 2016 00:45
Last Modified: 09 Aug 2016 00:45
URI: https://oak.novartis.com/id/eprint/24331

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