Abstract
The effect of the synthetic progesterone, megestrol acetate, on weight loss induced by both tumour necrosis factor alpha (TNF) as a model for the cachexia accompanying the acquired immunodeficiency syndrome and by a cachexia-inducing tumour (MAC16) has been studied in NMRI mice. Megestrol acetate was effective in preventing weight loss in both model systems with treated animals having an increase in intake of both food and water. Megestrol acetate was unable to prevent loss of body weight in animals pair-fed with TNF treated animals, suggesting that the increase in food and water intake was responsible for the increase in body weight. Analysis of body composition showed that the major contribution to the increase in body weight in animals treated with megestrol acetate was an increase in water content, although there was also an increase in carcass fat in animals bearing the MAC16 tumour given the high dose of megestrol acetate. Animals bearing the MAC16 tumour had a significant increase in tumour weight after treatment with megestrol acetate, possibly owing to the increased plasma glucose levels. These results suggest that an increase in appetite and weight gain alone are not sufficient to justify the anticachectic effect of a particular agent and that body composition analysis and tumour growth rate are very important parameters.
Full text
PDF




Selected References
These references are in PubMed. This may not be the complete list of references from this article.
- Aisner J., Tchekmedyian N. S., Tait N., Parnes H., Novak M. Studies of high-dose megestrol acetate: potential applications in cachexia. Semin Oncol. 1988 Apr;15(2 Suppl 1):68–75. [PubMed] [Google Scholar]
- Beck S. A., Tisdale M. J. Effect of insulin on weight loss and tumour growth in a cachexia model. Br J Cancer. 1989 May;59(5):677–681. doi: 10.1038/bjc.1989.140. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Beck S. A., Tisdale M. J. Production of lipolytic and proteolytic factors by a murine tumor-producing cachexia in the host. Cancer Res. 1987 Nov 15;47(22):5919–5923. [PubMed] [Google Scholar]
- Beutler B., Cerami A. Cachectin: more than a tumor necrosis factor. N Engl J Med. 1987 Feb 12;316(7):379–385. doi: 10.1056/NEJM198702123160705. [DOI] [PubMed] [Google Scholar]
- Bibby M. C., Double J. A., Ali S. A., Fearon K. C., Brennan R. A., Tisdale M. J. Characterization of a transplantable adenocarcinoma of the mouse colon producing cachexia in recipient animals. J Natl Cancer Inst. 1987 Mar;78(3):539–546. [PubMed] [Google Scholar]
- Chlebowski R. T. Significance of altered nutritional status in acquired immune deficiency syndrome (AIDS). Nutr Cancer. 1985;7(1-2):85–91. doi: 10.1080/01635588509513843. [DOI] [PubMed] [Google Scholar]
- DeWys W. Management of cancer cachexia. Semin Oncol. 1985 Dec;12(4):452–460. [PubMed] [Google Scholar]
- Feingold K. R., Soued M., Staprans I., Gavin L. A., Donahue M. E., Huang B. J., Moser A. H., Gulli R., Grunfeld C. Effect of tumor necrosis factor (TNF) on lipid metabolism in the diabetic rat. Evidence that inhibition of adipose tissue lipoprotein lipase activity is not required for TNF-induced hyperlipidemia. J Clin Invest. 1989 Apr;83(4):1116–1121. doi: 10.1172/JCI113991. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Grunfeld C., Wilking H., Neese R., Gavin L. A., Moser A. H., Gulli R., Serio M. K., Feingold K. R. Persistence of the hypertriglyceridemic effect of tumor necrosis factor despite development of tachyphylaxis to its anorectic/cachectic effects in rats. Cancer Res. 1989 May 15;49(10):2554–2560. [PubMed] [Google Scholar]
- Heber D., Byerley L. O., Chi J., Grosvenor M., Bergman R. N., Coleman M., Chlebowski R. T. Pathophysiology of malnutrition in the adult cancer patient. Cancer. 1986 Oct 15;58(8 Suppl):1867–1873. doi: 10.1002/1097-0142(19861015)58:8+<1867::aid-cncr2820581413>3.0.co;2-a. [DOI] [PubMed] [Google Scholar]
- Lähdevirta J., Maury C. P., Teppo A. M., Repo H. Elevated levels of circulating cachectin/tumor necrosis factor in patients with acquired immunodeficiency syndrome. Am J Med. 1988 Sep;85(3):289–291. doi: 10.1016/0002-9343(88)90576-1. [DOI] [PubMed] [Google Scholar]
- Mahony S. M., Beck S. A., Tisdale M. J. Comparison of weight loss induced by recombinant tumour necrosis factor with that produced by a cachexia-inducing tumour. Br J Cancer. 1988 Apr;57(4):385–389. doi: 10.1038/bjc.1988.87. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Mahony S. M., Tisdale M. J. Induction of weight loss and metabolic alterations by human recombinant tumour necrosis factor. Br J Cancer. 1988 Sep;58(3):345–349. doi: 10.1038/bjc.1988.216. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Mahony S. M., Tisdale M. J. Reversal of weight loss induced by tumour necrosis factor-alpha. Cancer Lett. 1989 Jun;45(3):167–172. doi: 10.1016/0304-3835(89)90072-4. [DOI] [PubMed] [Google Scholar]
- Oliff A. The role of tumor necrosis factor (cachectin) in cachexia. Cell. 1988 Jul 15;54(2):141–142. doi: 10.1016/0092-8674(88)90543-0. [DOI] [PubMed] [Google Scholar]
- Socher S. H., Martinez D., Craig J. B., Kuhn J. G., Oliff A. Tumor necrosis factor not detectable in patients with clinical cancer cachexia. J Natl Cancer Inst. 1988 Jun 15;80(8):595–598. doi: 10.1093/jnci/80.8.595. [DOI] [PubMed] [Google Scholar]
- von Roenn J. H., Murphy R. L., Weber K. M., Williams L. M., Weitzman S. A. Megestrol acetate for treatment of cachexia associated with human immunodeficiency virus (HIV) infection. Ann Intern Med. 1988 Nov 15;109(10):840–841. doi: 10.7326/0003-4819-109-10-840. [DOI] [PubMed] [Google Scholar]
