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.

Human melanoma, G361, which induces cachexia in nude mice, has been shown to produce a proteolysis-inducing factor (PIF) of M r 24 000, which is immunologically identical to that isolated from a cachexia-inducing murine tumour (MAC16). Biosynthetic labelling of G361 cells using a combination of [ 35 S]sulphate and [6- 3 H]glucosamine gave a single component of M r 24 000 after affinity chromatography employing a murine monoclonal antibody. The material contained both radiolabels and, after digestion with peptide N -glycosidase F, two fragments were produced of M r 14 000 and 10 000 also containing both radiolabels. Digestion with O -glycosidase produced three fragments of M r 14 000, 6000 and 4000, the first two of which contained both radiolabels, while the third only contained 3 H. This digestion pattern is the same as that previously observed with PIF from the MAC16 tumour and is commensurate with one N-linked sulphated oligosaccharide chain of M r 10 000, one O-linked sulphated oligosaccharide chain of M r 6000 and a central polypeptide chain of M r 4000 with some residual carbohydrate. When PIF from G361 cells was administered to female NMRI mice (20 g) a pronounced depression of body weight (1.36 ± 0.36 g; P < 0.0001 from control) was observed over a 24 h period without a decrease in either food or water consumption. Body composition analysis showed a significant decrease in the non-fat carcass mass without a change in carcass fat or body water. This result suggests that depletion of lean body mass in mice bearing G361 melanoma arises from the production of PIF. © 1999 Cancer Research Campaign

Factors relating to the transfer of latex microspheres of 0.87 micron mean diameter from the gastrointestinal tract (GIT) to the circulation have been investigated. The rapidity of appearance and the number of particles increased when the volume of water used as a suspending vehicle was increased. This was probably due to barrier cell integrity being compromised so that the movement of particles across the enterocytes would be enhanced. Particles were swept into these channels by the waterflow. The tonicity of the fluid was important as isotonic and hypertonic saline were not as effective as water in transferring particles. Particles were transferred from GIT segments adjacent to the stomach which may in part explain the rapid appearance of particles in the circulation. Particle uptake was blocked by cytochalasin B which suggests an active component may also be involved.

Background: Patients with advanced cancer suffer from cachexia, which is characterised by a marked weight loss, and is invariably associated with the presence of tumoral and humoral factors which are mainly responsible for the depletion of fat stores and muscular tissue.

The distribution of latex microspheres (1.1 microns diam) has been investigated in-vivo, as a potential passive targeted system for the treatment of inflammation. Microspheres administered orally were found in the circulation and in inflamed tissues and exudates of inflammatory air pouches in rats. Oral absorption was also found in a rabbit. Particles administered directly into the circulation also penetrated into the air pouch tissues and fluids. The possibility of using microspheres as a passive targeted system for the treatment of inflammation is discussed.