Drug – bio-affecting and body treating compositions – Extract – body fluid – or cellular material of undetermined... – Tissue – other than lymphoid tissue
Patent
1989-06-02
1993-06-15
Robinson, Douglas W.
Drug, bio-affecting and body treating compositions
Extract, body fluid, or cellular material of undetermined...
Tissue, other than lymphoid tissue
530300, A61K 3512
Patent
active
052195791
DESCRIPTION:
BRIEF SUMMARY
The present invention relates to the field of biochemistry and medicine, especially in connection with biologically active material characterised by catabolic activity, particularly lipolytic activity, generally associated with cachexia-inducing tumours.
BACKGROUND
For convenience, publications relating to the following description of the background of the invention are numerically referenced and listed in the appended bibliography.
Evidence (see references 1 to 7) has previously been reported indicating that at least some malignant tumours in mammals, especially cachexia-inducing tumours, give rise to the production of one or more catabolic factors which may be found in the circulatory system, e.g. in blood plasma.
It is well known that cachexia, characterised by progressive weakness, dramatic weight loss and wasting, is a common condition arising in many human cancer patients, especially in patients with gastrointestinal or lung cancer, and this often appears to be the most frequent cause of eventual death in such patients. Since, however, cachexia at least in human patients generally arises, often at an early stage, when the tumour mass is only a very small proportion of body weight it cannot be generally explained by a simple competitive effect between the tumour and body tissues for available nutrients; also, although in some cases cancer cachexia is accompanied by anorexia manifested by a severely reduced food and water intake, anorexia does not occur in all cases or appears only after severe loss of weight and body tissues (fat and muscle) has already become established; anorexia cannot therefore be recognised as a primary cause of all or many cancer cachectic conditions, and it seems possible that catabolic factors arising from the tumour and acting more directly on the host tissues may be primarily responsible.
Additionally, there is also some evidence indicating that growing tumours may derive at least part of the fatty acids they require, e.g. for membrane formation, from tissues of their host, and that in at least some cases these fatty acids may be derived from the fats in adipose tissue of the host through the action of a lipolytic catabolic factor that may be found in the host's circulatory system in the presence of the tumour. However, although this may be deemed suggestive of a possible link or causal relationship between such lipolytic factor, other catabolic factors possibly present, the growing tumour, and symptoms of cachexia independent of anorexia, various previous attempts (references 3, 4, 5, 6 and 7) to isolate, identify and characterise a lipolytic factor of this kind have produced somewhat confusing, uncertain, and inconsistent results and there has also been substantial doubt as to the extent of dependence of any such lipolytic factor on tumour specificity.
Thus, in 1980 it was reported by Kitada et al (reference 3) that the serum of AKR mice bearing thymic lymphoma contained a potent lipid mobilizing factor having lipolytic activity as evidenced by comparative in vivo assaying of the breakdown of adipose tissue labelled with radioactive carbon implanted into test animals of which some were injected with samples of the serum, measurements being taken of the radioactive carbon appearing in the respiratory CO.sub.2. The same effects of breakdown of the implanted adipose tissue were also observed upon injecting samples of extracts of the tumours and also upon injecting samples of culture medium from an AKR mouse lymphoma cell culture. These results were also reported again in 1981 (reference 4) by the same investigators, together with the additional result of a similar adipose tissue breakdown effect being observed upon in vivo assaying in the same way a serum sample from a human cancer patient with adenocarcinoma. In addition, the results then reported (somewhat superfically) also included the results of a preliminary attempt to isolate and characterise the active substance by a gel filtration technique involving chromatographing a dilute acetic acid extract of the thymic lymp
REFERENCES:
Kitada et al. CA 96:178891 (1982).
Kitada et al. CA 99:20427 (1983).
UK Search Report re 8906371.
International Search Report re PCT/GB 89/00296.
European Search Report EP 89 30 2740.
Beck, Susana.; Tisdale, Michael J., "Production of lipolytic and factors by a murine tumor-producing cachexia in the host" CHEMLABS Journal 08(05)035641, Pharm. Sci. Inst. Aston Univ. Birmingham UK GB B4 7ET Cancer Res.: (87) P 5919-23; vol. 47; No. 22.
Tisdale, J. J.; Beck, S. A., "Cachetic Factors Produced by Human and Animal Tumors" Proceedings of AACR vol. 29, Mar. 1988 p. 60, 79th Annual Meeting of the American Association for Cancer Research, New Orleans, May 25-28.
14 Mammalian Pathol. Biochem. vol. 106, 1987 #4 Jul. 27, 1987.
Kekwick and Pawan, "Fat Mobilizing Substance (FMS)", Medical Unit and Institute of Clinical Research, the Medical School, London, England, Nov. 21, 1966 in Metabolism, 16, 787-796 (1967).
Kitada et al Lipolysis Induction in Adipocytes by a Protein from Tumor Cells, J. Cell. Biochem., 2(4), 1982, pp. 409-416.
Kitada et al, Characterization of a Lipid Mobilizing Factor from Tumors, Prog. Lipid Res., 20(1-4), 1981, pp. 823-826.
Beck Susan A.
Tisdale Michael J.
Cancer Research Campaign - Technology Limited
Robinson Douglas W.
Witz Jean C.
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