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Article ; Online: Cancer cachexia and fat-muscle physiology.

Fearon, Kenneth C H

2011 Volume 365, Issue 6, Page(s) 565–567

MeSH term(s)	Adipose Tissue/enzymology ; Adipose Tissue/physiopathology ; Animals ; Cachexia/enzymology ; Cachexia/etiology ; Cachexia/metabolism ; Disease Models, Animal ; Humans ; Lipase/metabolism ; Lipolysis ; Mice ; Muscle, Skeletal/physiopathology ; Neoplasms/complications ; Neoplasms/enzymology ; Neoplasms/physiopathology ; Sarcopenia/etiology
Chemical Substances	Lipase (EC 3.1.1.3)
Language	English
Publishing date	2011-08-11
Publishing country	United States
Document type	Journal Article
ZDB-ID	207154-x
ISSN	1533-4406 ; 0028-4793
ISSN (online)	1533-4406
ISSN	0028-4793
DOI	10.1056/NEJMcibr1106880
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Ua VI Zs.34: Show issues

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Article ; Online: The oncology wall: Could Ali Baba have got to the nutrition treasure without using the correct words?

Laviano, Alessandro / Fearon, Kenneth C H

Clinical nutrition (Edinburgh, Scotland)

2013 Volume 32, Issue 1, Page(s) 6–7

MeSH term(s)	Cachexia/diet therapy ; Cachexia/etiology ; Cachexia/prevention & control ; Combined Modality Therapy ; Communication Barriers ; Culture ; Dietetics/manpower ; Humans ; Interdisciplinary Communication ; Malnutrition/diet therapy ; Malnutrition/etiology ; Malnutrition/prevention & control ; Medical Oncology/manpower ; Neoplasms/physiopathology ; Neoplasms/therapy
Language	English
Publishing date	2013-02
Publishing country	England
Document type	Editorial
ZDB-ID	604812-2
ISSN	1532-1983 ; 0261-5614
ISSN (online)	1532-1983
ISSN	0261-5614
DOI	10.1016/j.clnu.2012.12.003
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Zs.A 1774: Show issues

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Article ; Online: Cancer-associated cachexia.

Baracos, Vickie E / Martin, Lisa / Korc, Murray / Guttridge, Denis C / Fearon, Kenneth C H

Nature reviews. Disease primers

2018 Volume 4, Page(s) 17105

Abstract: Cancer-associated cachexia is a disorder characterized by loss of body weight with specific losses of skeletal muscle and adipose tissue. Cachexia is driven by a variable combination of reduced food intake and metabolic changes, including elevated energy ...

Abstract	Cancer-associated cachexia is a disorder characterized by loss of body weight with specific losses of skeletal muscle and adipose tissue. Cachexia is driven by a variable combination of reduced food intake and metabolic changes, including elevated energy expenditure, excess catabolism and inflammation. Cachexia is highly associated with cancers of the pancreas, oesophagus, stomach, lung, liver and bowel; this group of malignancies is responsible for half of all cancer deaths worldwide. Cachexia involves diverse mediators derived from the cancer cells and cells within the tumour microenvironment, including inflammatory and immune cells. In addition, endocrine, metabolic and central nervous system perturbations combine with these mediators to elicit catabolic changes in skeletal and cardiac muscle and adipose tissue. At the tissue level, mechanisms include activation of inflammation, proteolysis, autophagy and lipolysis. Cachexia associates with a multitude of morbidities encompassing functional, metabolic and immune disorders as well as aggravated toxicity and complications of cancer therapy. Patients experience impaired quality of life, reduced physical, emotional and social well-being and increased use of healthcare resources. To date, no effective medical intervention completely reverses cachexia and there are no approved drug therapies. Adequate nutritional support remains a mainstay of cachexia therapy, whereas drugs that target overactivation of catabolic processes, cell injury and inflammation are currently under investigation.
MeSH term(s)	Body Mass Index ; Cachexia/diagnosis ; Cachexia/enzymology ; Cachexia/etiology ; Humans ; Mass Screening/methods ; Neoplasms/complications ; Neoplasms/enzymology ; Obesity/complications ; Obesity/physiopathology ; Quality of Life/psychology ; Translational Medical Research
Language	English
Publishing date	2018-01-18
Publishing country	England
Document type	Journal Article ; Review
ISSN	2056-676X
ISSN (online)	2056-676X
DOI	10.1038/nrdp.2017.105
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Article: Identification of diagnostic upper gastrointestinal cancer tissue type-specific urinary biomarkers.

Husi, Holger / Fernandes, Marco / Skipworth, Richard J / Miller, Janice / Cronshaw, Andrew D / Fearon, Kenneth C H / Ross, James A

Biomedical reports

2019 Volume 10, Issue 3, Page(s) 165–174

Abstract: Several potential urinary biomarkers exhibiting an association with upper gastrointestinal tumour growth have been previously identified, of which S100A6, S100A9, rabenosyn-5 and programmed cell death 6-interacting protein (PDCD6IP) were further ... ...

Abstract	Several potential urinary biomarkers exhibiting an association with upper gastrointestinal tumour growth have been previously identified, of which S100A6, S100A9, rabenosyn-5 and programmed cell death 6-interacting protein (PDCD6IP) were further validated and found to be upregulated in malignant tumours. The cancer cohort from our previous study was subclassified to assess whether distinct molecular markers can be identified for each individual cancer type using a similar approach. Urine samples from patients with cancers of the stomach, oesophagus, oesophagogastric junction or pancreas were analysed by surface-enhanced laser desorption/ionization-time-of-flight mass spectrometry using both CM10 and IMAC30 (Cu
Language	English
Publishing date	2019-02-05
Publishing country	England
Document type	Journal Article
ZDB-ID	2763624-0
ISSN	2049-9442 ; 2049-9434
ISSN (online)	2049-9442
ISSN	2049-9434
DOI	10.3892/br.2019.1190
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Article ; Online: Cancer cachexia: mediators, signaling, and metabolic pathways.

Fearon, Kenneth C H / Glass, David J / Guttridge, Denis C

Cell metabolism

2012 Volume 16, Issue 2, Page(s) 153–166

Abstract: Cancer cachexia is characterized by a significant reduction in body weight resulting predominantly from loss of adipose tissue and skeletal muscle. Cachexia causes reduced cancer treatment tolerance and reduced quality and length of life, and remains an ... ...

Abstract	Cancer cachexia is characterized by a significant reduction in body weight resulting predominantly from loss of adipose tissue and skeletal muscle. Cachexia causes reduced cancer treatment tolerance and reduced quality and length of life, and remains an unmet medical need. Therapeutic progress has been impeded, in part, by the marked heterogeneity of mediators, signaling, and metabolic pathways both within and between model systems and the clinical syndrome. Recent progress in understanding conserved, molecular mechanisms of skeletal muscle atrophy/hypertrophy has provided a downstream platform for circumventing the variations and redundancy in upstream mediators and may ultimately translate into new targeted therapies.
MeSH term(s)	Activins/metabolism ; Cachexia/etiology ; Cachexia/metabolism ; Cachexia/physiopathology ; Cachexia/therapy ; Humans ; Interleukin-6/metabolism ; Lipolysis/physiology ; Metabolic Networks and Pathways/physiology ; Models, Biological ; Muscular Atrophy/metabolism ; Muscular Atrophy/physiopathology ; Myostatin/metabolism ; Neoplasms/complications ; Signal Transduction/physiology ; Tumor Necrosis Factor-alpha/metabolism
Chemical Substances	Interleukin-6 ; Myostatin ; Tumor Necrosis Factor-alpha ; Activins (104625-48-1)
Language	English
Publishing date	2012-08-08
Publishing country	United States
Document type	Journal Article ; Research Support, Non-U.S. Gov't ; Review
ZDB-ID	2176834-1
ISSN	1932-7420 ; 1550-4131
ISSN (online)	1932-7420
ISSN	1550-4131
DOI	10.1016/j.cmet.2012.06.011
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Zs.A 6169: Show issues

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Article: Is tissue cross-talk important in cancer cachexia?

Johns, Neil / Greig, C / Fearon, Kenneth C H

Critical reviews in oncogenesis

2012 Volume 17, Issue 3, Page(s) 263–276

Abstract: Recent work suggests molecular cross-talk between adipose tissue and muscle that occurs through adipokines and myokines. These molecules act in an endocrine fashion to play an intricate role in regulating body composition in both health and disease. ... ...

Abstract	Recent work suggests molecular cross-talk between adipose tissue and muscle that occurs through adipokines and myokines. These molecules act in an endocrine fashion to play an intricate role in regulating body composition in both health and disease. Studies in exercise physiology have focused on the molecular cross-talk between adipose tissue and muscle that occurs through adipokines and myokines and on the role these molecules may play in chronic diseases. Similarly, integrative physiology in obesity and diabetes has long emphasised the importance of chronic inflammation, increased adipocyte lipolysis, and increased levels of circulating free fatty acids in the adipose-muscle cross-talk that contributes to lipotoxicity and insulin resistance in muscle. Cachexia affects the majority of patients with advanced cancer and is associated with a reduction in treatment tolerance, response to therapy, quality of life, and duration of survival. Although cachexia in patients with cancer is characterized by systemic inflammation, increased lipolysis, insulin resistance, and reduced physical activity, there has been little effort to manipulate the integrative physiology of adipose tissue and muscle tissue for therapeutic gain.
MeSH term(s)	Adipose Tissue/physiology ; Cachexia/etiology ; Cachexia/metabolism ; Cytokines/physiology ; Diabetes Mellitus/metabolism ; Energy Metabolism ; Exercise ; Humans ; Muscle Proteins/biosynthesis ; Neoplasms/complications ; Obesity/metabolism
Chemical Substances	Cytokines ; Muscle Proteins
Language	English
Publishing date	2012-06-11
Publishing country	United States
Document type	Journal Article ; Review
ZDB-ID	1036388-9
ISSN	0893-9675
ISSN	0893-9675
DOI	10.1615/critrevoncog.v17.i3.40
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Zs.A 2587: Show issues

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Article: Urinary diagnostic proteomic markers for dynapenia in cancer patients.

Husi, Holger / MacDonald, Alisdair / Skipworth, Richard J E / Miller, Janice / Cronshaw, Andrew / Greig, Carolyn / Fearon, Kenneth C H / Ross, James A

Biomedical reports

2018 Volume 8, Issue 6, Page(s) 547–556

Abstract: Dynapenia is defined as the age-related loss of muscle strength, and plays a significant role in the loss of physical function and increased risk of disability among older individuals. The need for an early diagnosis supports the search for a biomarker ... ...

Abstract	Dynapenia is defined as the age-related loss of muscle strength, and plays a significant role in the loss of physical function and increased risk of disability among older individuals. The need for an early diagnosis supports the search for a biomarker that reflects muscle 'weakening'. This has previously proven difficult due to patient heterogeneity at presentation and lack of understanding of the underlying molecular mechanisms. The aim of the present study was to identify potential urinary biomarkers of dynapenia in patients undergoing potentially curative surgery for upper gastrointestinal cancer. Maximum isometric knee extensor strength (strain gauge) and maximum leg extensor power (Nottingham power rig) measurements were taken. Cut-off values for dynapenia were based on the Allied Dunbar national fitness survey. Values below the 5th percentile for the population matched for age and sex on the Allied Dunbar national fitness survey were used to stratify the cohort into dynapenic or normal. Urine samples taken at induction of anaesthesia were analysed by SELDI-TOF mass spectrometry using CM10 and IMAC30 chip-types to establish statistically significant m/z peak fingerprint patterns, followed by in-gel LC-MS/MS to identify molecular constituents. Statistical analysis of decision-tree calculations using Biomarker Pattern software resulted in models with sensitivities of 86 and 96%, specificities of 81 and 89%, and overall correctness of 84 and 93%, when applied to the entire cohort for power and strength measurement-based stratifications using the IMAC30 chip-type and the CM10 chip-type, respectively. The molecular identities of 10 peaks of interest were further investigated. After subtraction of potentially unrelated proteins, they were identified as fragments of Annexin A1, collagen α-1 (XV), perlecan and myotrophin. These results demonstrate that urinary screening can be used to define cancer-associated muscle weakness, and the identification of potential biomarkers could be invaluable in establishing a rapid test to measure and assess dynapenia in the clinical setting.
Language	English
Publishing date	2018-04-25
Publishing country	England
Document type	Journal Article
ZDB-ID	2763624-0
ISSN	2049-9442 ; 2049-9434
ISSN (online)	2049-9442
ISSN	2049-9434
DOI	10.3892/br.2018.1092
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Article: Proteomic identification of potential markers of myosteatosis in human urine.

Husi, Holger / MacDonald, Alisdair / Skipworth, Richard J E / Miller, Janice / Cronshaw, Andrew / Fearon, Kenneth C H / Ross, James A

Biomedical reports

2018 Volume 8, Issue 6, Page(s) 557–564

Abstract: ... resulted in the identification of significant fragments of cathepsin C, argin, arylsulfatase A and ...

Abstract	Myosteatosis, the infiltration of fat in skeletal muscle, is associated with lower skeletal muscle density (SMD) as detected by computed tomography (CT). It increases with aging and obesity and is thought to play a role in the aetiology of insulin resistance and type II diabetes. The clinical significance of myosteatosis in cancer cachexia, however, remains to be determined. Along with demonstrable subcutaneous and visceral lipolysis, myosteatosis may also be a key component of the syndrome. We aimed to investigate the use of human urine as a non-invasive way to screen for molecular biomarkers of myosteatosis/reduced SMD using SELDI-TOF mass spectrometry. Pre-operative CT scans of patients undergoing surgery for upper gastrointestinal or hepatopancreaticobiliary cancer were analysed at the level of the third lumbar vertebrae. Myosteatosis was inferred as the presence of reduced SMD, which was defined as Hounsfield units for skeletal muscle <39.5 (two standard deviations below a normal healthy cohort). Urine was analysed by mass spectrometry using CM10 and IMAC30 SELDI-chips. Peaks observed in the CM10 and IMAC30 chip types, showed marked expressional differences between control and myosteatosis, were further investigated by mascot SELDI matrix matching. A total of 55 patients was recruited; 31 patients were found to be myosteatotic on CT scan. Application of the IMAC30-derived model to the entire cohort showed a sensitivity of 97%, specificity of 71% and an overall correctness of 85%. Application of the CM10 chipset-based model to the entire cohort, showed a 77% sensitivity, 67% specificity and 73% overall correctness. Analysis of the peaks of interest resulted in the identification of significant fragments of cathepsin C, argin, arylsulfatase A and glial fibrillary acidic protein. We identified several potential urinary molecular biomarkers associated with reduced SMD in cancer. Such markers are potentially useful in deriving a clinical screening test for myosteatosis.
Language	English
Publishing date	2018-04-25
Publishing country	England
Document type	Journal Article
ZDB-ID	2763624-0
ISSN	2049-9442 ; 2049-9434
ISSN (online)	2049-9442
ISSN	2049-9434
DOI	10.3892/br.2018.1091
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Article ; Online: Proteomic identification of potential cancer markers in human urine using subtractive analysis.

Husi, Holger / Skipworth, Richard J E / Cronshaw, Andrew / Fearon, Kenneth C H / Ross, James A

International journal of oncology

2016 Volume 48, Issue 5, Page(s) 1921–1932

Abstract: Urine is an ideal medium in which to focus diagnostic cancer research due to the non-invasive nature and ease of sampling. Many large-scale proteomic studies have shown that urine is unexpectedly complex. We hypothesised that novel diagnostic cancer ... ...

Abstract	Urine is an ideal medium in which to focus diagnostic cancer research due to the non-invasive nature and ease of sampling. Many large-scale proteomic studies have shown that urine is unexpectedly complex. We hypothesised that novel diagnostic cancer biomarkers could be discovered using a comparative proteomic analysis of pre-existing data. We assembled a database of 100 published datasets of 5,620 urinary proteins, as well as 46 datasets of 8,620 non-redundant proteins derived from kidney and blood proteome analyses. The data were then used to either subtract or compare molecules from a novel urinary proteome profiling dataset that we generated. We identified 1,161 unique proteins in samples from either cancer-bearing or healthy subjects. Subtractive analysis yielded a subset of 44 proteins that were found uniquely in urine from cancer patients, 30 of which were linked previously to cancer. In conclusion, this approach is useful in discovering novel biomarkers in tissues where unrelated profiling data is available. Only a limited disease-specific novel dataset is required to define new targets or substantiate previous findings. We have shared this discovery platform in the form of our Large Scale Screening Resource database, accessible through the Proteomic Analysis DataBase portal (www.PADB.org).
MeSH term(s)	Adult ; Aged ; Biomarkers, Tumor/blood ; Biomarkers, Tumor/urine ; Chromatography, Liquid ; Databases, Protein ; Female ; Humans ; Kidney/metabolism ; Male ; Neoplasms/blood ; Neoplasms/diagnosis ; Neoplasms/urine ; Organ Specificity ; Proteomics/methods ; Tandem Mass Spectrometry
Chemical Substances	Biomarkers, Tumor
Language	English
Publishing date	2016-05
Publishing country	Greece
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	1154403-x
ISSN	1791-2423 ; 1019-6439
ISSN (online)	1791-2423
ISSN	1019-6439
DOI	10.3892/ijo.2016.3424
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Zs.A 3690: Show issues

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Article ; Online: The energy balance in cancer cachexia revisited.

de Vos-Geelen, Judith / Fearon, Kenneth C H / Schols, Annemie M W

Current opinion in clinical nutrition and metabolic care

2014 Volume 17, Issue 6, Page(s) 509–514

Abstract: Purpose of review: To review new putative mechanisms involved in the pathophysiology of a disturbed energy balance in cancer cachexia, which can lead to novel targets for clinical cachexia management. In the context of rapid developments in tumour ... ...

Abstract	Purpose of review: To review new putative mechanisms involved in the pathophysiology of a disturbed energy balance in cancer cachexia, which can lead to novel targets for clinical cachexia management. In the context of rapid developments in tumour treatment with potential systemic consequences, this article reviews recent data on energy requirements. Furthermore, we focus on new insights in brown adipose tissue (BAT) activity and reward processing in the brain in relation to the cachexia process. Recent findings: Nearly no new data have been published on energy requirements of cancer patients in the light of comprehensive new therapies in oncology. New developments, such as the introduction of staging with 18F-fluorodeoxyglucose PET-computed tomography scanning, led to the observation that BAT activation may contribute to impaired energy balance in cancer cachexia. Animal and human data to date provide an indication that BAT activation indeed occurs, but its quantitative impact on the degree of cachexia is controversial. The peripheral and central nervous system is known to influence satiation, with a possible role for impaired food reward processing in the brain. To date, there are limited confirmatory data, but this is an interesting new area to explore for better understanding and treating cancer-induced anorexia. Summary: The multimodal approach to counteract cancer cachexia should expand its targets to BAT and food reward processing in the brain.
MeSH term(s)	Adipose Tissue, Brown/physiology ; Animals ; Brain/physiology ; Cachexia/physiopathology ; Disease Models, Animal ; Energy Metabolism ; Humans ; Neoplasms/complications ; Neoplasms/physiopathology ; Nutritional Requirements ; Positron-Emission Tomography
Language	English
Publishing date	2014-11
Publishing country	England
Document type	Journal Article ; Review
ZDB-ID	1460178-3
ISSN	1473-6519 ; 1363-1950
ISSN (online)	1473-6519
ISSN	1363-1950
DOI	10.1097/MCO.0000000000000106
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Zs.A 5586: Show issues

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