d-609 and Skin-Neoplasms

A xanthate compound with antiviral and antitumoural activities, tricyclodecan-9-yl-xanthogenate (D609) in combination with the potassium salt of the lauric acid (KC12) and, in a further investigation, the above-mentioned substances together with recombinant human TNF alpha (rh-TNF alpha), were tested on equine sarcoid tumours for therapeutic efficacy. A pilot investigation on 5 healthy horses showed that the compounds were well-tolerated; apart from a local, temporary oedema at the injection site, no other clinical symptoms were observed after subcutaneous administration of volumes from 0.1 to 10 ml per injection. The tested concentrations of D609 and KC12 (5 mg/ml solution) and of rh-TNF alpha (50 micrograms/ml) were used for the treatment experiments. The repeated injections of the compounds to 11 sarcoid affected horses were also well-tolerated, except by one horse. In this case the treatment had to be interrupted after two injections because of severe reaction, i.e. fever and lameness due to oedemas. Five horses (n = 6 sarcoids) were treated by local, subcutaneous injection of D609 and KC12 under the tumour at intervals of 3 weeks. On one periocular sarcoid the compounds were applied as an ointment. After a follow-up period of 18 months, 5 tumours did completely regress and one remained unchanged. The periocular tumour showed a reduction in size. Five horses (n = 9 sarcoids) were then treated with a combination of D609, KC12 and rh-TNF alpha.(ABSTRACT TRUNCATED AT 250 WORDS)

Topics: Animals; Antineoplastic Agents; Bridged-Ring Compounds; Drug Therapy, Combination; Female; Horse Diseases; Horses; Humans; Lauric Acids; Male; Norbornanes; Pilot Projects; Recombinant Proteins; Skin Neoplasms; Thiocarbamates; Thiones; Tumor Necrosis Factor-alpha

The antiviral and antitumoral compound tricyclodecan-9-yl-xanthogenate (D609), which is an inhibitor of protein kinase C activation, has been used for tumor prevention in vivo. When applied chronically together with 12-O-tetradecanoylphorbol-13-acetate (TPA) in the classic initiation-promotion mouse-skin model, D609 prevented tumor induction in a dose-dependent manner. At the concentration that inhibited tumor formation by 97%, no toxic effects were detected and the TPA-induced hyperplasia remained unaffected. As D609 failed to prevent the activity of a chronically applied carcinogen, it is concluded that the observed tumor prevention achieved with D609 is tumor-promotion-specific and is not due to killing of tumor cells.

Topics: 9,10-Dimethyl-1,2-benzanthracene; Administration, Cutaneous; Animals; Antineoplastic Agents; Antiviral Agents; Bridged-Ring Compounds; Carcinoma; Dose-Response Relationship, Drug; Female; Mice; Norbornanes; Papilloma; Skin Neoplasms; Tetradecanoylphorbol Acetate; Thiocarbamates; Thiones