Comparison of weight loss induced by recombinant tumour necrosis factor with that produced by a cachexia-inducing tumour

Mahony, S. M.; Beck, S. A.; Tisdale, M. J.

doi:10.1038/bjc.1988.87

Cited by 53 publications

(18 citation statements)

References 15 publications

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“…The lipid mobilising activity was characterised by the retention by DEAE cellulose, and using this criterion it was observed that similar material was absent from normal serum. This suggests that the lipid mobilising factor is acidic in character, similar to that previously reported (Kitada et al, 1981;Masuno et al, 1981), and is different from the natural lipolytic hormones, which are all basic in character.…”

Section: Mechanism Of Cachexiasupporting

confidence: 53%

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Cancer cachexia

Tisdale¹

1991

Br J Cancer

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Section: Mechanism Of Cachexiasupporting

confidence: 53%

“…A somewhat similar acidic (pI4.7) lipid mobilising factor of molecular weight 65 to 74 kDa (toxohormone L), has been found in the pleural fluid from patients with malignant lymphoma and the ascites fluids of patients with ovarian carcinoma or hepatoma (Masuno et al, 1981).…”

Section: Mechanism Of Cachexiamentioning

confidence: 95%

Cancer cachexia

Tisdale¹

1991

Br J Cancer

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“…This suggests that the two substances are identical. Intravenous injection of this substance in mice causes a state of cachexia similar to that observed after administration of the murine material (Todorov et al, 1996a) in mice bearing the MAC16 tumour in that (a) weight loss occurs without a reduction in food and water intake (Beck and Tisdale, 1987) and thus is not due to toxicity of the material, (b) weight loss can be attenuated by prior administration of the monoclonal antibody, (c) there is marked hypoglycaemia (McDevitt and Tisdale, 1992) and (d) there is a decreased level of plasma triglycerides; in the last respect the effect is unlike that of TNF-a, which causes an increase (Mahony et al, 1988). This observation, together with the finding of decreased plasma levels of 3-hydroxybutyrate, suggests that energy expenditure may be increased.…”

Section: Discussionmentioning

confidence: 99%

Induction of cachexia in mice by a product isolated from the urine of cachectic cancer patients

Cariuk

Lorite²,

Todorov³

et al. 1997

Br J Cancer

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112

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Summary Urine from cancer patients with weight loss showed the presence of an antigen of Mr 24 000 detected with a monoclonal antibody formed by fusion of splenocytes from mice with cancer cachexia. The antigen was not present in the urine of normal subjects, patients with weight loss from conditions other than cancer or from cancer patients who were weight stable or with low weight loss (1 kg month-1). The antigen was present in the urine from subjects with carcinomas of the pancreas, breast, lung and ovary. The antigen was purified from urine using a combination of affinity chromatography with the mouse monoclonal antibody and reversed-phase high-performance liquid chromotography (HPLC). This procedure gave a 200 000-fold purification of the protein over that in the original urine extract and the material isolated was homogeneous, as determined by silver staining of gels. The N-terminal amino acid sequence showed no homology with any of the recognized cytokines. Administration of this material to mice caused a significant (P<0.005) reduction in body weight when compared with a control group receiving material purified in the same way from the urine of a normal subject. Weight loss occurred without a reduction in food and water intake and was prevented by prior administration of the mouse monoclonal antibody. Body composition analysis showed a decrease in both fat and non-fat carcass mass without a change in water content. The effects on body composition were reversed in mice treated with the monoclonal antibody. There was a decrease in protein synthesis and an increase in degradation in skeletal muscle. Protein degradation was associated with an increased prostaglandin E2 (PGE2) release. Both protein degradation and PGE2 release were significantly reduced in mice pretreated with the monoclonal antibody. These results show that the material of Mr 24 000 present in the urine of cachectic cancer patients is capable of producing a syndrome of cachexia in mice.

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“…Although the MAC16 tumour has a large necrotic centre (Bibby et al, 1987) there is no evidence for the involvement of tumour necrosis factor in the production of the cachectic state (Mahony et al, 1988). Tumours from animals fed the MCT diets are possibly less necrotic than those fed a normal diet, but no less necrotic than a tumour of comparable size from animals fed a normal diet.…”

Section: Discussionmentioning

confidence: 98%

A comparison of long-chain triglycerides and medium-chain triglycerides on weight loss and tumour size in a cachexia model

Tisdale

Brennan²

1988

Br J Cancer

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Summary A comparison has been made between the ability of long-chain triglycerides (LCT) and mediumchain triglycerides (MCT) to prevent weight loss induced by the cachexia-inducing colon adenocarcinoma (MAC16) and to reduce tumour size. There was no difference in calorie consumption or nitrogen intake between the various groups. When compared with a normal control high carbohydrate, low fat diet, animals fed MCT showed a reduced weight loss and a marked reduction in tumour size. In contrast neither weight loss nor tumour size differed significantly from the controls in animals fed the LCT diet. An elevated plasma level of 3-hydroxybuturate was found only in the animals fed the MCT diets. Administration of LCT caused an increase in the plasma level of FFA, which was not observed in the MCT group. These results suggest that diets containing MCT would provide the best ketogenic regime to reverse the weight loss in cancer cachexia with a concomitant reduction in tumour size.Weight loss is a common feature of many neoplastic diseases (De Wys, 1986) and appears to be independent of the tumour burden and often precedes clinical diagnosis. The end result of the continuing decline in nutritional status is the clinical syndrome of cancer cachexia. Patients with weight loss have a poorer response to chemotherapy and a shorter survival time than those without weight loss (De Wys et al., 1980).We have utilized the MAC 16 adenocarcinoma of the mouse colon as an experimental model of human cachexia, where weight loss arises from the metabolic effects of the tumour on the host (Bibby et al., 1987). Animals bearing the MAC16 tumour show weight loss at small tumour burdens (less than 1% of the host weight) and without a reduction in either food or water intake. Weight loss is characterized by a progressive loss of both body fat and muscle dry weight, which increases in direct proportion to the tumour burden (Beck & Tisdale, 1987). Although there is extensive mobilization of body fat reserves ketosis does not occur (Bibby et al., 1987). Ketonuria has also been shown not to occur in cancer patients . Since ketone bodies are believed to play an important role in the regulation of lean body mass during starvation we and others (Tisdale, 1982;Magee et al., 1979;Williamson & Matthaei, 1981) have suggested that a high fat/low carbohydrate ketogenic diet should also preserve lean body mass during cancer cachexia, and would not be expected to be utilized by a poorly vascularized tumour, which would depend primarily on glucose as an energy source. In addition 3-hydroxybutyrate has recently been shown to inhibit the lipolytic and proteolytic factors produced by the MAC16 tumour and which may be responsible for the cachexia (Beck & Tisdale, 1987). Such an approach has been vindicated since mice bearing the MAC16 tumour fed a diet in which up to 80% of the energy was supplied as medium-chain triglycerides (MCT) show a reduction in both the extent of weight loss and tumour weight . A ketogenic diet containing 70% MCT and supplemented with D-3-...

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Comparison of weight loss induced by recombinant tumour necrosis factor with that produced by a cachexia-inducing tumour

Cited by 53 publications

References 15 publications

Cancer cachexia

Cancer cachexia

Induction of cachexia in mice by a product isolated from the urine of cachectic cancer patients

A comparison of long-chain triglycerides and medium-chain triglycerides on weight loss and tumour size in a cachexia model

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