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At least 199 records · Page 11Linked to original sources
PubMed1995

The mouse/human chimeric monoclonal antibody cA2 neutralizes TNF in vitro and protects transgenic mice from cachexia and TNF lethality in vivo.

The pleiotropic cytokine tumour necrosis factor-alpha (TNF) is thought to play a central role in infectious, inflammatory and autoimmune diseases. Critical to the understanding and management of TNF-associated pathology is the development of highly specific agents capable of modifying TNF activity. We evaluated the ability of a high affinity mouse/human chimeric anti-TNF monoclonal antibody (cA2) to neutralize the in vitro and in vivo biological effects of TNF. cA2 inhibited TNF-induced mitogenesis and IL-6 secretion by human fibroblasts, TNF-priming of human neutrophils, and the stimulation of human umbilical vein endothelial cells by TNF as measured by the expression of E-selectin, ICAM-1 and procoagulant activity. cA2 also specifically blocked TNF-induced adherence of human neutrophils to an endothelial cell monolayer. Receptor binding studies suggested that neutralization resulted from cA2 blocking of TNF binding to both p55 and p75 TNF receptors on the cells. In vivo, repeated administration of cA2 to transgenic mice that constitutively express human TNF reversed the cachectic phenotype and prevented subsequent mortality. These results demonstrated that cA2 effectively neutralized a broad range of TNF biological activities both in vitro and in vivo.

Animals↗
PubMed1976

[Biochemical investigations of cancer cachexia: I. Tumour induced changes of glycogenolysis and gluconeogenesis of Walker carcinoma bearing rats (author's transl)].

Rats (weight 150-200 g) bearing Walker-carcinoma showed tumour size dependent hypoglycemia, diminished mobilization of glycogen following glucagon stimulation and elevated values of the enzyme activity of glucose-6-(P)-ase. A further hormonal stimulation of this enzyme activity towards the values observed in normal rats after betamethasone stimulation was not possible. The values of the enzyme fructose-1,6-di-(P)-ase in liver of tumour bearing rats equalled those found in normal controls and did not show any rise after application of betamethasone. The serum levels of free fatty acids did not show any difference between normal controls and tumour bearing rats, and displayed an equal rise after intensive stimulation of peripheral lipolysis.

Animals↗
PubMed1977

Gastrointestinal absorption studies in cardiac cachexia.

The nutritional status of 11 patients with severe mitral valve disease was investigated pre-operatively and 3 months post-operatively. It was shown that they were malnourished pre-operatively, and that this appeared to be related mainly to anorexia.

Adolescent↗
PubMed1988

Observations on dopamine receptor antagonists and gastric ulceration associated with experimental anorexia cachexia.

Gastric ulceration is frequently reported to occur in tumour-bearing animals and man, even when such tumours are not associated with organs of digestion. That central and peripheral dopamine (DA) containing neurones may be relevant to this phenomenon, is supported by the fact that the DA receptor antagonists domperidone (0.1 and 0.05 mg/kg) and pimozide (0.1 mg/kg) were observed to prevent gastric ulceration commonly reported in rats bearing the Walker 256 carcinosarcoma. Daily administration of these drugs prevented the formation of ulcers similar to those observed in vehicle-treated animals. These results demonstrate that DA neurone function is important in the formation of gastric ulcers in tumour-bearing animals and suggest that such compounds may be useful in cancer management.

Animals↗