Recombinant human erythropoietin attenuates weight loss in a murine cancer cachexia model

Halteren, H.K. van; Bongaerts, G.P.A.; Verhagen, C.A.H.H.V.M.; Kamm, Y. J. L.; Grutters, G.; Koopman, J. P.; Wagener, D. J. Th.

doi:10.1007/s00432-003-0526-7

Cited by 16 publications

(7 citation statements)

References 21 publications

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“…The definition of the C26 tumor as adenocarcinoma is a major mistake in terminology [10,12,35]. We have confirmed that the C26 cells, originally obtained from a colon carcinoma, when ectopically implanted in mice form an undifferentiated carcinoma, which should thus be referred to as such.…”

Section: Discussionsupporting

confidence: 68%

“…Myostatin negatively regulates skeletal muscle mass, though inhibition of its downstream pathways does not attenuate C26-induced cachexia, thereby suggesting that myostatin does not play a role in this context [39]. Anaerobic glycolysis in a C26 tumor is related to weight loss, while erythropoietin administration has been shown to reduce weight loss [12]. Accordingly, exercise training attenuates C26-induced muscle wasting [40].…”

Section: Introductionmentioning

confidence: 99%

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Molecular, cellular and physiological characterization of the cancer cachexia-inducing C26 colon carcinoma in mouse

et al. 2010

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BackgroundThe majority of cancer patients experience dramatic weight loss, due to cachexia and consisting of skeletal muscle and fat tissue wasting. Cachexia is a negative prognostic factor, interferes with therapy and worsens the patients' quality of life by affecting muscle function. Mice bearing ectopically-implanted C26 colon carcinoma are widely used as an experimental model of cancer cachexia. As part of the search for novel clinical and basic research applications for this experimental model, we characterized novel cellular and molecular features of C26-bearing mice.MethodsA fragment of C26 tumor was subcutaneously grafted in isogenic BALB/c mice. The mass growth and proliferation rate of the tumor were analyzed. Histological and cytofluorometric analyses were used to assess cell death, ploidy and differentiation of the tumor cells. The main features of skeletal muscle atrophy, which were highlighted by immunohistochemical and electron microscopy analyses, correlated with biochemical alterations. Muscle force and resistance to fatigue were measured and analyzed as major functional deficits of the cachectic musculature.ResultsWe found that the C26 tumor, ectopically implanted in mice, is an undifferentiated carcinoma, which should be referred to as such and not as adenocarcinoma, a common misconception. The C26 tumor displays aneuploidy and histological features typical of transformed cells, incorporates BrdU and induces severe weight loss in the host, which is largely caused by muscle wasting. The latter appears to be due to proteasome-mediated protein degradation, which disrupts the sarcomeric structure and muscle fiber-extracellular matrix interactions. A pivotal functional deficit of cachectic muscle consists in increased fatigability, while the reported loss of tetanic force is not statistically significant following normalization for decreased muscle fiber size.ConclusionsWe conclude, on the basis of the definition of cachexia, that ectopically-implanted C26 carcinoma represents a well standardized experimental model for research on cancer cachexia. We wish to point out that scientists using the C26 model to study cancer and those using the same model to study cachexia may be unaware of each other's works because they use different keywords; we present strategies to eliminate this gap and discuss the benefits of such an exchange of knowledge.

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Section: Discussionsupporting

confidence: 68%

Section: Introductionmentioning

confidence: 99%

Molecular, cellular and physiological characterization of the cancer cachexia-inducing C26 colon carcinoma in mouse

et al. 2010

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“…Others explored rHuEpo in combination with fractionated radiation in a murine cancer cachexia model: They concluded that rHuEpo had a beneficial effect by contributing to radiosensitization and/or reducing weight loss 72, 73. In contrast, no radiosensitizing effect was observed in a rat tumor model with darbepoetin alpha (DA) at a high dose, even though there was an increase in tumor oxygenation 74.…”

Section: Esas In Animal Models Of Tumor Growthmentioning

confidence: 99%

Expression and function of erythropoietin receptors in tumors

Sinclair

Todd

Forsythe

et al. 2007

Cancer

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Safety concerns surrounding the use of recombinant human erythropoietin (Epo) to treat anemia in cancer patients were raised after 2 recent clinical studies reported a worse survival outcome in patients who received epoetin a or epoetin b compared with patients who received placebo. Although those findings con- KEYWORDS: tumor, erythropoietin, receptor, proliferation, survival, angiogenesis, animal models, hypoxia.C oncerns that recombinant human erythropoietin (rHuEpo) may adversely affect the survival of cancer patients through promoting tumor growth recently were raised by 2 randomized clinical trials that used rHuEpo to prevent anemia in patients with breast or head and neck cancer. 1,2 In those trials, decreased survival and increased tumor progression were observed in patients who received epoetin a or epoetin b compared with patients who received placebo. These outcomes were in contrast to many clinical trials, which demonstrated that erythropoiesis-stimulating agents (ESAs) are safe and efficacious for the treatment of anemia in cancer patients. 3,4 These trials were criticized for poor study design and execution. 4 However, a number of hypotheses were proposed to explain the potential role of ESAs in promoting tumor proliferation and reduced survival including, stimulation of tumor expression of the erythropoietin (Epo) receptor (EpoR), tumor neovascularization, enhanced tumor oxygenation, and, most recently, the role of coadministered iron, 5 although that topic is not addressed herein.This review reflects conclusions from a comprehensive survey of the literature that investigated the expression and function of EpoR

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“…Other drugs that are investigated to be used for cancer cachexia include Erythropoetin [171][172][173] , ACE inhibitors [174] , and β-blockers [175] .…”

Section: Othersmentioning

confidence: 99%

Cancer cachexia, mechanism and treatment

Aoyagi¹,

Terracina²,

Ali³

et al. 2015

WJGO

370

282

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It is estimated that half of all patients with cancer eventually develop a syndrome of cachexia, with anorexia and a progressive loss of adipose tissue and skeletal muscle mass. Cancer cachexia is characterized by systemic inflammation, negative protein and energy balance, and an involuntary loss of lean body mass. It is an insidious syndrome that not only has a dramatic impact on patient quality of life, but also is associated with poor responses to chemotherapy and decreased survival. Cachexia is still largely an underestimated and untreated condition, despite the fact that multiple mechanisms are reported to be involved in its development, with a number of cytokines postulated to play a role in the etiology of the persistent catabolic state. Existing therapies for cachexia, including orexigenic appetite stimulants, focus on palliation of symptoms and reduction of the distress of patients and families rather than prolongation of life. Recent therapies for the cachectic syndrome involve a multidisciplinary approach. Combination therapy with diet modification and/or exercise has been added to novel pharmaceutical agents, such as Megestrol acetate, medroxyprogesterone, ghrelin, omega-3-fatty acid among others. These agents are reported to have improved survival rates as well as quality of life. In this review, we will discuss the emerging understanding of the mechanisms of cancer cachexia, the current treatment options including multidisciplinary combination therapies, as well an update on new and ongoing clinical trials.

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Recombinant human erythropoietin attenuates weight loss in a murine cancer cachexia model

Abstract: Anaerobic glycolysis in a growing C26-B tumor is related to weight loss. RhEPO administration results in a reduction of the percentage weight loss; this effect is probably mediated by an increased hemoglobin concentration.

Cited by 16 publications

References 21 publications

Molecular, cellular and physiological characterization of the cancer cachexia-inducing C26 colon carcinoma in mouse

Molecular, cellular and physiological characterization of the cancer cachexia-inducing C26 colon carcinoma in mouse

Expression and function of erythropoietin receptors in tumors

Cancer cachexia, mechanism and treatment

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