ChemInform Abstract: Cancer Cachexia: A Therapeutic Approach

Argilés, Josep Μ.; Meijsing, Sebastiaan H.; Pallarés-Trujillo, J.; López‐Soriano, Francisco J.

doi:10.1002/chin.200120261

Cited by 7 publications

(11 citation statements)

References 1 publication

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“…Advanced CaP is associated with cachexia, which is a serious complication of many cancers [41]. Our results show that growth of C4-2 tumor cells in the bone results in decreased body weight of tumor-bearing animals, and that treatment with RAD001 results in maintenance of body weight and lean body mass.…”

Section: Discussionmentioning

confidence: 59%

RAD001 (Everolimus) inhibits growth of prostate cancer in the bone and the inhibitory effects are increased by combination with docetaxel and zoledronic acid

et al. 2008

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Section: Discussionmentioning

confidence: 59%

RAD001 (Everolimus) inhibits growth of prostate cancer in the bone and the inhibitory effects are increased by combination with docetaxel and zoledronic acid

et al. 2008

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“…There are several reviews that provide extensive citations of animal studies showing that proinflammatory cytokines induce muscle wasting (1,39,43,44). Chronic administration of IL-␤ to rats reduces protein synthesis and muscle mass (2), whereas administration of the IL-1 receptor antagonist to septic mice prevents the decrease in protein synthesis, translational efficiency and muscle mass (2).…”

Section: Discussionmentioning

confidence: 99%

IL-1β Impairs Insulin-Like Growth Factor I-Induced Differentiation and Downstream Activation Signals of the Insulin-Like Growth Factor I Receptor in Myoblasts

Broussard¹,

McCusker²,

Novakofski

et al. 2004

The Journal of Immunology

105

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Proinflammatory cytokines are elevated in disorders characterized by muscle wasting and weakness, such as inflammatory myopathies and AIDS wasting. We recently demonstrated that TNF-α impairs the ability of insulin-like growth factor (IGF)-I to promote protein synthesis in muscle precursor cells. In this study we extend these findings by showing that low concentrations of IL-1β impair IGF-I-dependent differentiation of myoblasts, as assessed by expression of the muscle specific protein, myosin heavy chain. In the absence of exogenous IGF-I, IL-1β (1 ng/ml) did not impair muscle cell development. However, in the presence of IGF-I, 100-fold lower concentrations of IL-1β (0.01 ng/ml) significantly suppressed myoblast differentiation, protein synthesis, and myogenin expression. Increasing IL-1β to 1 ng/ml completely blocked the anabolic actions of IGF-I in murine C2C12 myoblasts. Similarly, IL-1β inhibited IGF-I-stimulated protein synthesis in primary porcine myoblasts. IL-1β impaired the actions of IGF-I at a point distal to the IGF receptor, and this was not due to IL-1β-induced cell death. Instead, IL-1β inhibited the ability of IGF-I to phosphorylate tyrosine residues on both of its downstream docking proteins, insulin receptor substrate 1 and insulin receptor substrate 2. These data establish that physiological concentrations of IL-1β block the ability of IGF-I to promote protein synthesis, leading to reduced expression of the myogenic transcription factor, myogenin, and the subsequent development of more mature differentiated cells that express myosin heavy chain. Collectively, the results are consistent with the notion that very low concentrations of IL-1β significantly impair myogenesis, but they are unable to do so in the absence of the growth factor IGF-I.

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“…1 Cachexia is characterized by weight loss and anorexia that involve the depletion of host adipose tissue and skeletal muscle. 2 Nutritional supplementation has little or no impact on cachexia.…”

mentioning

confidence: 99%

“…3,4 Cachexia is of especially high significance in patients with prostate carcinoma (CaP): 60 -70% of patients with advanced CaP suffer and die from cachexia. 1 However, the etiology of cachexia in patients with CaP, as in patients with other types of malignant disease, is not well understood, and intervention strategies to alleviate the condition are not yet available.…”

mentioning

confidence: 99%

Elevation of cytokine levels in cachectic patients with prostate carcinoma

Pfitzenmaier

Vessella

Higano

et al. 2003

Cancer

144

100

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BACKGROUNDApproximately 60–70% of patients with advanced prostate carcinoma (CaP) suffer from cachexia, one of the most devastating conditions associated with advanced malignant disease. The pathophysiology of cachexia is multifactorial, and several cytokines, such as tumor necrosis factor α (TNFα) and interleukin 1 (IL‐1), IL‐6, and IL‐8, may be involved. The objective of the current study was to determine whether cachexia associated with advanced CaP is accompanied by increased serum levels of TNFα, IL‐1β, IL‐6, and IL‐8.METHODSThe levels of TNFα, IL‐1β, IL‐6, IL‐8, and prostate specific antigen (PSA) were examined in serum samples from normal donors (n = 10 donors), from patients with organ‐confined CaP (n = 19 patients), from patients with advanced CaP without cachexia (n = 17 patients), and from patients with cachectic CaP (n = 26 patients). DPC Immulite and Abbott IMx Total‐PSA assays were used to determine cytokine and PSA levels, respectively.RESULTSLevels of TNFα, IL‐6, and IL‐8 were elevated significantly in the group of patients with advanced, cachectic CaP compared with patients who were without cachexia. In the cachectic patients, levels of TNFα were correlated positively with IL‐8, and there was no correlation between PSA levels and any of the cytokine levels. IL‐1β levels were below the limit of detection in all samples.CONCLUSIONSThe current results show that levels of TNFα, IL‐6, and IL‐8 were increased in CaP patients with cachexia. Increased levels of these cytokines were not correlated with PSA levels, suggesting that they are regulated by a mechanism that is independent of PSA synthesis. Additional fundamental research is needed to determine the mechanisms involved and to identify potential therapeutic targets in patients with cachexia. Cancer 2003;97:1211–6. © 2003 American Cancer Society.DOI 10.1002/cncr.11178

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ChemInform Abstract: Cancer Cachexia: A Therapeutic Approach

Cited by 7 publications

References 1 publication

RAD001 (Everolimus) inhibits growth of prostate cancer in the bone and the inhibitory effects are increased by combination with docetaxel and zoledronic acid

RAD001 (Everolimus) inhibits growth of prostate cancer in the bone and the inhibitory effects are increased by combination with docetaxel and zoledronic acid

IL-1β Impairs Insulin-Like Growth Factor I-Induced Differentiation and Downstream Activation Signals of the Insulin-Like Growth Factor I Receptor in Myoblasts

Elevation of cytokine levels in cachectic patients with prostate carcinoma

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