PMID- 27461772
OWN - NLM
STAT- MEDLINE
DCOM- 20170926
LR  - 20180514
IS  - 1938-0690 (Electronic)
IS  - 1525-7304 (Linking)
VI  - 18
IP  - 1
DP  - 2017 Jan
TI  - Consequences of Late-Stage Non-Small-Cell Lung Cancer Cachexia on Muscle 
      Metabolic Processes.
PG  - e1-e11
LID - S1525-7304(16)30143-7 [pii]
LID - 10.1016/j.cllc.2016.06.003 [doi]
AB  - INTRODUCTION: The loss of muscle is common in patients with advanced 
      non-small-cell lung cancer (NSCLC) and contributes to the high morbidity and 
      mortality of this group. The exact mechanisms behind the muscle loss are unclear. 
      PATIENTS AND METHODS: To investigate this, 4 patients with stage IV NSCLC who met 
      the clinical definitions for sarcopenia and cachexia were recruited, along with 4 
      age-matched healthy volunteers. After an overnight fast, biopsy specimens were 
      obtained from the vastus lateralis, and the key components associated with 
      inflammation and the control of muscle protein, carbohydrate, and fat metabolism 
      were assessed. RESULTS: Compared with the healthy volunteers, significant 
      increases in mRNA levels for interleukin-6 and NF-kappaB signaling and lower 
      intramyocellular lipid content in slow-twitch fibers were observed in NSCLC 
      patients. Although a significant decrease in phosphorylation of the mechanistic 
      target of rapamycin (mTOR) signaling protein 4E-BP1 (Ser(65)) was observed, along 
      with a trend toward reduced p70 S6K (Thr(389)) phosphorylation (P = .06), no 
      difference was found between groups for the mRNA levels of MAFbx (muscle atrophy 
      F box) and MuRF1 (muscle ring finger protein 1), chymotrypsin-like activity of 
      the proteasome, or protein levels of multiple proteasome subunits. Moreover, 
      despite decreases in intramyocellular lipid content, no robust changes in mRNA 
      levels for key proteins involved in insulin signaling, glycolysis, oxidative 
      metabolism, or fat metabolism were observed. CONCLUSION: These findings suggest 
      that examining the contribution of suppressed mTOR signaling in the loss of 
      muscle mass in late-stage NSCLC patients is warranted and reinforces our need to 
      understand the potential contribution of impaired fat metabolism and muscle 
      protein synthesis in the etiology of cancer cachexia.
CI  - Copyright (c) 2016 Elsevier Inc. All rights reserved.
FAU - Murton, Andrew J
AU  - Murton AJ
AD  - Division of Nutritional Sciences, School of Biosciences, The University of 
      Nottingham, Loughborough, United Kingdom; MRC Arthritis Research UK Centre for 
      Musculoskeletal Ageing Research, School of Life Sciences, The University of 
      Nottingham Medical School, Queen's Medical Centre, Nottingham, United Kingdom. 
      Electronic address: andrew.murton@nottingham.ac.uk.
FAU - Maddocks, Matthew
AU  - Maddocks M
AD  - Department of Palliative Medicine, The University of Nottingham, Nottingham 
      University Hospitals NHS Trust, Nottingham, United Kingdom; King's College 
      London, Cicely Saunders Institute, London, United Kingdom.
FAU - Stephens, Francis B
AU  - Stephens FB
AD  - MRC Arthritis Research UK Centre for Musculoskeletal Ageing Research, School of 
      Life Sciences, The University of Nottingham Medical School, Queen's Medical 
      Centre, Nottingham, United Kingdom.
FAU - Marimuthu, Kanagaraj
AU  - Marimuthu K
AD  - MRC Arthritis Research UK Centre for Musculoskeletal Ageing Research, School of 
      Life Sciences, The University of Nottingham Medical School, Queen's Medical 
      Centre, Nottingham, United Kingdom.
FAU - England, Ruth
AU  - England R
AD  - Department of Palliative Medicine, The University of Nottingham, Nottingham 
      University Hospitals NHS Trust, Nottingham, United Kingdom.
FAU - Wilcock, Andrew
AU  - Wilcock A
AD  - Department of Palliative Medicine, The University of Nottingham, Nottingham 
      University Hospitals NHS Trust, Nottingham, United Kingdom.
LA  - eng
PT  - Comparative Study
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20160625
PL  - United States
TA  - Clin Lung Cancer
JT  - Clinical lung cancer
JID - 100893225
RN  - 0 (Lipids)
RN  - 0 (Muscle Proteins)
RN  - EC 3.4.25.1 (Proteasome Endopeptidase Complex)
SB  - IM
MH  - Adenocarcinoma/*complications/metabolism/pathology
MH  - Aged
MH  - Cachexia/etiology/*metabolism/pathology
MH  - Carcinoma, Non-Small-Cell Lung/*complications/metabolism/pathology
MH  - Carcinoma, Squamous Cell/*complications/metabolism/pathology
MH  - Case-Control Studies
MH  - Female
MH  - Follow-Up Studies
MH  - Humans
MH  - Inflammation/etiology/*metabolism/pathology
MH  - Lipids/analysis
MH  - Lung Neoplasms/*complications/metabolism/pathology
MH  - Male
MH  - Muscle Proteins/*metabolism
MH  - Neoplasm Staging
MH  - Prognosis
MH  - Proteasome Endopeptidase Complex/metabolism
OTO - NOTNLM
OT  - Lipid metabolism
OT  - Muscle protein synthesis
OT  - Proteolysis
OT  - Ubiquitin proteasome system
OT  - mTOR signaling
EDAT- 2016/07/28 06:00
MHDA- 2017/09/28 06:00
CRDT- 2016/07/28 06:00
PHST- 2016/01/12 00:00 [received]
PHST- 2016/06/07 00:00 [revised]
PHST- 2016/06/13 00:00 [accepted]
PHST- 2016/07/28 06:00 [pubmed]
PHST- 2017/09/28 06:00 [medline]
PHST- 2016/07/28 06:00 [entrez]
AID - S1525-7304(16)30143-7 [pii]
AID - 10.1016/j.cllc.2016.06.003 [doi]
PST - ppublish
SO  - Clin Lung Cancer. 2017 Jan;18(1):e1-e11. doi: 10.1016/j.cllc.2016.06.003. Epub 
      2016 Jun 25.