Cancer cachexia: the molecular mechanisms

Argilés, Josep Μ.; Moore‐Carrasco, Rodrigo; Fuster, Gemma; Busquets, Sı́lvia; López‐Soriano, Francisco J.

doi:10.1016/s1357-2725(02)00251-0

Cited by 104 publications

(68 citation statements)

References 16 publications

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“…All three pathways may be involved in cachexia, although the ubiquitin-dependent system is considered to be the most important and has been most studied. 67 Recent evidence suggests that PIF and TNF-α, but not other cytokines, can induce expression of the key regulatory components of this pathway. 65,68 TNF-α induces muscle wasting via inhibition of pathways involved in muscle cell differentiation and regeneration.…”

Section: Effects Of Cachexia On Skeletal Musclementioning

confidence: 99%

Cancer cachexia-anorexia syndrome and skeletal muscle wasting

Jurdana

2009

Radiology and Oncology

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Section: Effects Of Cachexia On Skeletal Musclementioning

confidence: 99%

Cancer cachexia-anorexia syndrome and skeletal muscle wasting

Jurdana

2009

Radiology and Oncology

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“…This highly debilitating condition is also associated with weight loss, depletion of fat stores, anemia, insulin resistance, and alterations in carbohydrate, lipid, and protein metabolism [7,30]. Cachexia is seen in as many as 80% of patients with advanced malignancy and, rather than tumor burden, accounts for an estimated 20 to 30% of all cancer related deaths [30,37,65].…”

Section: Introductionmentioning

confidence: 99%

Selective Inhibition of NF-kappa-B with NBD Peptide Reduces Tumor- Induced Wasting in a Murine Model of Cancer Cachexia In vivo

Wysong¹,

Asher

Yin

et al. 2011

JCST

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Cancer cachexia is a severe wasting syndrome characterized by the progressive loss of lean body mass and systemic inflammation, which is seen in as many as 80% of patients with advanced malignancy. It accounts for an estimated 20-30% of all cancer-related deaths. The mechanism by which cancer induces skeletal muscle atrophy in cachexia involves tumor-derived cytokines, including TNFα, IL-1, and IL-6. Upon interaction with their unique receptors on skeletal muscle, these cytokines activate NF-kappaB, a transcription factor crucial for atrophy related sarcomere proteolysis to occur. The significance of NF-κB is highlighted in studies demonstrating that genetic inhibition of NF-κB ameliorates cancer-induced muscle loss in vivo. In the present study, we evaluate a selective NF-kappaB inhibitor (NBD peptide) which targets the IkappaB complex to prevent cancer-induced skeletal muscle atrophy in an established mouse model (C26 adenocarcinoma). We identified for the first time that NBD peptide can directly inhibit tumor-induced NFkappaB activation in skeletal muscle, resulting in a decrease loss of lean muscle. We also identified that NBD peptide reduces the expression of the tumor induced ubiquitin ligases MuRF-1 and MAFbx/Atrogin-1 necessary for atrophy. These findings highlight that NBD peptide may be a potential selective therapeutic agent for the treatment of cancer cachexia.

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“…progressive loss of body weight with depletion of skeletal muscle and adipose tissue (Argiles et al, 2003). Cachexia and its consequences are detrimental and considered to be the direct cause of B20% of cancer deaths (Tisdale, 2002).…”

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confidence: 99%

Adipose atrophy in cancer cachexia: morphologic and molecular analysis of adipose tissue in tumour-bearing mice

et al. 2006

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Extensive loss of adipose tissue is a hallmark of cancer cachexia but the cellular and molecular basis remains unclear. This study has examined morphologic and molecular characteristics of white adipose tissue in mice bearing a cachexia-inducing tumour, MAC16. Adipose tissue from tumour-bearing mice contained shrunken adipocytes that were heterogeneous in size. Increased fibrosis was evident by strong collagen-fibril staining in the tissue matrix. Ultrastructure of 'slimmed' adipocytes revealed severe delipidation and modifications in cell membrane conformation. There were major reductions in mRNA levels of adipogenic transcription factors including CCAAT/enhancer binding protein alpha (C/EBPa), CCAAT/enhancer binding protein beta, peroxisome proliferatoractivated receptor gamma, and sterol regulatory element binding protein-1c (SREBP-1c) in adipose tissue, which was accompanied by reduced protein content of C/EBPa and SREBP-1. mRNA levels of SREBP-1c targets, fatty acid synthase, acetyl CoA carboxylase, stearoyl CoA desaturase 1 and glycerol-3-phosphate acyl transferase, also fell as did glucose transporter-4 and leptin. In contrast, mRNA levels of peroxisome proliferators-activated receptor gamma coactivator-1alpha and uncoupling protein-2 were increased in white fat of tumour-bearing mice. These results suggest that the tumour-induced impairment in the formation and lipid storing capacity of adipose tissue occurs in mice with cancer cachexia.

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Cancer cachexia: the molecular mechanisms

Cited by 104 publications

References 16 publications

Cancer cachexia-anorexia syndrome and skeletal muscle wasting

Cancer cachexia-anorexia syndrome and skeletal muscle wasting

Selective Inhibition of NF-kappa-B with NBD Peptide Reduces Tumor- Induced Wasting in a Murine Model of Cancer Cachexia In vivo

Adipose atrophy in cancer cachexia: morphologic and molecular analysis of adipose tissue in tumour-bearing mice

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