Cachexia in Patients with Gastrointestinal Cancers: Contributing Factors, Prevention, and Current Management Approaches

Cancer cachexia is highly prevalent among patients with the advanced stage of cancers and leads to a higher risk of mortality. Delayed management of cachexia results in suboptimal treatment outcomes and irreversible progression to refractory cachexia. The purpose of this review is to provide the pathophysiology of cancer cachexia, emerging diagnostic criteria with potential biomarkers, prevention strategies, and novel treatment approaches. Cachexia is characterised by the presence of an inflammatory process in conjunction with muscle mass and unintentional body weight loss. Various biomarkers such as leptin, ghrelin, TNFα, essential amino acids, total amino acids, and C-reactive protein are indicative of cachexia. Increased circulating levels of β-dystroglycan, myosin heavy-chain, and dystrophin are indicators of shortened survival time as skeletal muscle tissues break down. Despite muscle wasting being a hallmark of cachexia, recommended cachexia management is limited to nutritional counselling and administration of an appetite stimulant and corticosteroids for a short period, which often fail to reverse cancer cachexia. It is critical to monitor weight loss using the cachexia grading system for early detection, to halt progression to refractory cachexia and improve the survival of patients with cancer cachexia.

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Body Weight Loss and Tissue Wasting in Late Middle-Aged Mice on Slightly Imbalanced Essential/Non-essential Amino Acids Diet

Frontiers in Medicine ◽

10.3389/fmed.2018.00136 ◽

2018 ◽

Vol 5 ◽

Cited By ~ 7

Author(s):

Giovanni Corsetti ◽

Evasio Pasini ◽

Claudia Romano ◽

Riccardo Calvani ◽

Anna Picca ◽

...

Keyword(s):

Amino Acids ◽

Weight Loss ◽

Body Weight ◽

Body Weight Loss ◽

Essential Amino Acids ◽

Middle Aged ◽

Aged Mice

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Whey Protein and Essential Amino Acids Promote the Reduction of Adipose Tissue and Increased Muscle Protein Synthesis During Caloric Restriction-Induced Weight Loss in Elderly, Obese Individuals

Clinical Nutrition and Aging ◽

10.1201/9781315364971-6 ◽

2017 ◽

pp. 69-86

Author(s):

Robert H. Coker ◽

Sharon Miller ◽

Scott Schutzler ◽

Nicolaas Deutz ◽

Robert R. Wolfe

Keyword(s):

Amino Acids ◽

Weight Loss ◽

Protein Synthesis ◽

Adipose Tissue ◽

Whey Protein ◽

Caloric Restriction ◽

Muscle Protein ◽

Muscle Protein Synthesis ◽

Essential Amino Acids

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The Wuhan Pneumonia Outbreak: High Isoleucine and High Valine Plus Glycine Contents Are Features of the Proteins of 2019-nCoV Virus

10.20944/preprints202002.0289.v1 ◽

2020 ◽

Author(s):

Sirui Yan ◽

Yulin Wan ◽

Ying Zhang ◽

Shanshan An ◽

Kaiqiao Yang ◽

...

Keyword(s):

Amino Acids ◽

Animal Studies ◽

Viral Infections ◽

Underlying Mechanism ◽

Essential Amino Acids ◽

Global Scale ◽

Open Reading Frame ◽

Cell Swelling ◽

Reading Frame ◽

Short Period

The current pneumonia epidemic in China could evolve into a pandemic on a global scale if not effectively contained. The 2019-nCoV possesses a 61-amino acid open reading frame resembling SARS-CoV virulence factor - ORF6 peptide. The isoleucine content is 15.9% in ORF6 of SARS-CoV versus 16.4% of that in 2019-nCoV. Given the proton affinity in the carbonyl oxygen in isoleucine, augmented proton traffic can enhance proton-ion antiport and prompt cell swelling. As the content of essential amino acids in the open reading frame of 2019-nCoV reaches 57.4%, a starch/vitamin diet served for short period of time does not give rise to essential amino acids and halts virion production, which could be adopted as prophylactic approach of many viral infections. Plant-based diet or fasting/boiled rice water can also minimize the intake of essential amino acids or all amino acids respectively. Calorie restriction has been confirmed in animal studies to extend lifespan, and its underlying mechanism is not fully known. Furthermore, several proteins of 2019-nCoV possess high valine plus glycine content, which is implicated in heart disease.

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Whey protein and essential amino acids promote the reduction of adipose tissue and increased muscle protein synthesis during caloric restriction-induced weight loss in elderly, obese individuals

Nutrition Journal ◽

10.1186/1475-2891-11-105 ◽

2012 ◽

Vol 11 (1) ◽

Cited By ~ 43

Author(s):

Robert H Coker ◽

Sharon Miller ◽

Scott Schutzler ◽

Nicolaas Deutz ◽

Robert R Wolfe

Keyword(s):

Amino Acids ◽

Weight Loss ◽

Protein Synthesis ◽

Adipose Tissue ◽

Whey Protein ◽

Caloric Restriction ◽

Muscle Protein ◽

Muscle Protein Synthesis ◽

Essential Amino Acids

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The Extract of Arctium lappa L. Fruit (Arctii Fructus) Improves Cancer-Induced Cachexia by Inhibiting Weight Loss of Skeletal Muscle and Adipose Tissue

Nutrients ◽

10.3390/nu12103195 ◽

2020 ◽

Vol 12 (10) ◽

pp. 3195

Author(s):

Yo-Han Han ◽

Jeong-Geon Mun ◽

Hee Dong Jeon ◽

Dae Hwan Yoon ◽

Byung-Min Choi ◽

...

Keyword(s):

Skeletal Muscle ◽

Weight Loss ◽

Adipose Tissue ◽

Cancer Cachexia ◽

Uncoupling Protein ◽

Body Weight Loss ◽

In Vivo Experiments ◽

Wasting Syndrome

Background: Cachexia induced by cancer is a systemic wasting syndrome and it accompanies continuous body weight loss with the exhaustion of skeletal muscle and adipose tissue. Cancer cachexia is not only a problem in itself, but it also reduces the effectiveness of treatments and deteriorates quality of life. However, effective treatments have not been found yet. Although Arctii Fructus (AF) has been studied about several pharmacological effects, there were no reports on its use in cancer cachexia. Methods: To induce cancer cachexia in mice, we inoculated CT-26 cells to BALB/c mice through subcutaneous injection and intraperitoneal injection. To mimic cancer cachexia in vitro, we used conditioned media (CM), which was CT-26 colon cancer cells cultured medium. Results: In in vivo experiments, AF suppressed expression of interleukin (IL)-6 and atrophy of skeletal muscle and adipose tissue. As a result, the administration of AF decreased mortality by preventing weight loss. In adipose tissue, AF decreased expression of uncoupling protein 1 (UCP1) by restoring AMP-activated protein kinase (AMPK) activation. In in vitro model, CM increased muscle degradation factors and decreased adipocytes differentiation factors. However, these tendencies were ameliorated by AF treatment in C2C12 myoblasts and 3T3-L1 cells. Conclusion: Taken together, our study demonstrated that AF could be a therapeutic supplement for patients suffering from cancer cachexia.

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Response of adult rats to deficiencies of different essential amino acids

British Journal Of Nutrition ◽

10.1079/bjn19740007 ◽

1974 ◽

Vol 31 (1) ◽

pp. 47-57 ◽

Cited By ~ 18

Author(s):

A. K. Said ◽

D. M. Hegsted ◽

K. C. Hayes

Keyword(s):

Amino Acids ◽

Amino Acid ◽

Nutritive Value ◽

Plasma Concentrations ◽

Essential Amino Acids ◽

The Body ◽

Adult Rats ◽

Short Period ◽

Body Weights ◽

Fatty Livers

1. Adult rats were fed on diets free of either lysine, methionine, threonine or protein. The threonine- and protein-deficient animals lost weight at approximately the same rate, about 100 g in 14 weeks, at which time several were moribund. In contrast, lysine-deficient animals lost only about 30 g in 14 weeks and had lost only 46 g after 22 weeks, when they were killed. Methionine-deficient animals showed an intermediate response. Losses in weight of several tissues – kidney, heart and two muscles – were related to, but not necessarily proportional to, the loss of body-weight. Liver weights relative to body-weights were large in lysine- and threonine-deficient animals and smallest in methionine-deficient animals.2. Adult rats were fed on diets containing zero, a moderate amount (about twice the estimated minimal requirement) or an excess (about four times the estimated requirement) of lysine or threonine in all combinations (3 × 3 design). Analysis of variance of the body-weights, tissue weights and tissue nitrogen contents indicated, in general, a significant effect of each amino acid, as expected, but also, in most instances, a significant interaction. Plasma concentrations of lysine and threonine were affected by the intakes of the respective amino acids, but plasma lysine concentrations were also affected by the threonine intake.3. Liver histology also suggested significant interactions between the two amino acids. Animals given no lysine but moderate amounts of threonine developed severely fatty livers; next most severely affected were animals receiving excess of both amino acids. Threonine deficiency, in the presence or absence of lysine, produced moderately fatty livers similar to those seen in protein-deficient animals.4. Since animals have varying ability to conserve body nitrogen when they are fed on diets limiting in different essential amino acids, measurements of biological value (BV) and net protein utilization by conventional methods, over a short period of time, over-estimate nutritive value relative to amino acid score and probably over-estimate the true nutritive value of poor-quality proteins, particularly those limiting in lysine. If so, this is a serious error, since it leads to underestimates of the protein requirements if BV is used. The fact that certain tissues, particularly the liver, do not necessarily lose nitrogen in proportion to total body nitrogen and may show specific pathological effects depending on the limiting amino acid or the proportions of amino acids in the diet also indicates that general measures of nitrogen economy may not be sufficiently discriminating tests of the nutritive value of proteins.

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Skeletal Muscle Fibrosis in Pancreatic Cancer Patients with Respect to Survival

JNCI Cancer Spectrum ◽

10.1093/jncics/pky043 ◽

2018 ◽

Vol 2 (3) ◽

Cited By ~ 12

Author(s):

Sarah M Judge ◽

Rachel L Nosacka ◽

Daniel Delitto ◽

Michael H Gerber ◽

Miles E Cameron ◽

...

Keyword(s):

Skeletal Muscle ◽

Weight Loss ◽

Body Weight ◽

Cellular Response ◽

Cancer Cachexia ◽

Cancer Control ◽

Body Weight Loss ◽

Collagen Content ◽

Calcium Deposition ◽

Control Subjects

Abstract Background Cancer cachexia is a catabolic condition characterized by skeletal muscle wasting, consequent to tumor burden, which negatively impacts tolerance to cancer therapies and contributes to increased mortality. Partly because of the limited knowledge of the underlying mechanisms of cancer cachexia derived from human studies, however, the ability to therapeutically intervene remains elusive. The purpose of the current study was therefore to better define the phenotype of skeletal muscle obtained from patients with pancreatic ductal adenocarcinoma (PDAC), which has one of the highest rates of cachexia. Methods Morphological analyses were performed on rectus abdominis muscle biopsies obtained from resectable PDAC patients undergoing tumor resection surgery (N = 20) and from weight-stable non-cancer control subjects undergoing benign abdominal surgery (N = 16). PDAC patients with a body weight loss of greater than 5% during the previous 6 months were considered cachectic (N = 15). Statistical tests were two sided. Results Skeletal muscle from cachectic PDAC patients had increased collagen content compared with non-cancer control subjects (1.43% vs 9.66%, P = .0004, Dunn test). Across all PDAC patients, collagen content positively correlated with body weight loss (P = .0016, r = 0.672), was increased in patients with lymph node metastasis (P = .007, Mann-Whitney U test), and was associated with survival on univariate (HR = 1.08, 95% confidence interval [CI] = 1.02 to 1.04, P = .008) and multivariable analyses (HR = 1.08, 95% CI = 1.00 to 1.17, P = .038). Cachectic PDAC patients also displayed increased lipid deposition (2.63% vs 5.72%, P = .042), infiltration of CD68+ macrophages (63.6 cells/mm2 vs 233.8 cells/mm2, P = .0238), calcium deposition (0.21% vs 2.51%, P = .030), and evidence of deficient cellular quality control mechanisms (Mann-Whitney U test). Transcriptional profiling of all patients supported these findings by identifying gene clusters related to wounding, inflammation, and cellular response to TGF-β upregulated in cachectic PDAC patients compared with non-cancer control subjects. Conclusions To our knowledge, this work is the first to demonstrate increased collagen content in cachectic PDAC patients that is associated with poor survival.

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