A series of studies to identify the aetiology of aberrant body composition status in cancer and possible methods of body composition manipulation
File(s)
Author(s)
Pring, Edward Tobias
Type
Thesis
Abstract
Host body composition (BC) is associated with outcomes in colorectal cancer (CRC). Muscle and fat appear to be crucial in both disease causation and response. The aim of this thesis is to identify and understand the aetiology of deleterious changes in BC; explore the underlying immune dysfunction of the disease and ascertain whether we can arrest the process of muscle dysfunction in CRC.
In Chapters 2-5, using our population data, we identify relationships between tumour, environment and host. Visceral obesity (VO) is independently associated with prognostically favourable tumour characteristics whilst myosteatosis is independently associated with an aggressive tumour phenotype and is a strong a predictor of future distant recurrence. The environment and genetic background are implicated; deprivation appears a determinant of sarcopenia and BMI whilst ethnicity determines BC status and inflammatory state.
In Chapters 7-9 we identified that dendritic cell (DC) lipid status is dependent on anatomical location and is associated with BC status. Increased intracellular lipid within circulating DC is significantly associated with myosteatosis. Whilst, in response to microbial stimulation, oxidised fat content is significantly increased in DC in healthy controls compared to the CRC population. Fat scavenger receptor CD36 expression is significantly increased in the CRC DC population suggesting DC in CRC fail to respond appropriately to commensal antigens.
Finally, to ascertain if we could modulate this response through intervention, we undertook a review of the literature which informed the construction of a randomised trial to identify whether using neuromuscular muscular electrical stimulation (NMES) pre- and post-operatively in rectal cancer patients could alter BC, reduce inflammation and improve outcome.
Host BC and the immune response to CRC is influenced by both the tumour and host’s environment. Cellular targets exist which may moderate the immune response. Manipulating host BC by interventions such as NMES may prompt an anti-inflammatory response.
In Chapters 2-5, using our population data, we identify relationships between tumour, environment and host. Visceral obesity (VO) is independently associated with prognostically favourable tumour characteristics whilst myosteatosis is independently associated with an aggressive tumour phenotype and is a strong a predictor of future distant recurrence. The environment and genetic background are implicated; deprivation appears a determinant of sarcopenia and BMI whilst ethnicity determines BC status and inflammatory state.
In Chapters 7-9 we identified that dendritic cell (DC) lipid status is dependent on anatomical location and is associated with BC status. Increased intracellular lipid within circulating DC is significantly associated with myosteatosis. Whilst, in response to microbial stimulation, oxidised fat content is significantly increased in DC in healthy controls compared to the CRC population. Fat scavenger receptor CD36 expression is significantly increased in the CRC DC population suggesting DC in CRC fail to respond appropriately to commensal antigens.
Finally, to ascertain if we could modulate this response through intervention, we undertook a review of the literature which informed the construction of a randomised trial to identify whether using neuromuscular muscular electrical stimulation (NMES) pre- and post-operatively in rectal cancer patients could alter BC, reduce inflammation and improve outcome.
Host BC and the immune response to CRC is influenced by both the tumour and host’s environment. Cellular targets exist which may moderate the immune response. Manipulating host BC by interventions such as NMES may prompt an anti-inflammatory response.
Version
Open Access
Date Issued
2022-09
Date Awarded
2023-11
Copyright Statement
Creative Commons Attribution NonCommercial Licence
License URL
Advisor
Athanasiou, Thanos
Jenkins, John Taylor
Knight, Stella
Sponsor
London North West University Healthcare NHS Trust
St Mark's Hospital Foundation
Publisher Department
Department of Surgery & Cancer
Publisher Institution
Imperial College London
Qualification Level
Doctoral
Qualification Name
Doctor of Philosophy (PhD)