Sequential volumetric measurements of three cancers of the human bladder transplanted to the hamster cheek pouch were made and recorded by computer methods. Comparative growth curves in treated and control animals have provided a useful quantitative method of testing anticancer agents. Statistical computer analyses have indicated that two primary tumors of the bladder have shown responsiveness to 5‐fluorouraciI, to irradiation and to mitomycin C. The greatest effectiveness was to mitomycin C in dosage acceptable for treatment of human subjects. Irradiation and 5‐fluorouracil combination has demonstrated a synergistic or potentiating action; an enhancement effect of the two agents also has been observed clinically. A third tumor, which probably had its origin in the renal pelvis and later seeded to the bladder, showed relative resistance to chemotherapy, but responsiveness to irradiation. Testing of additional tumors will provide additional information which may have practical clinical significance and application.
PREvrous reports of experiments in our laboratory have described our success in the transplantation of human bladder cancers to the cheek pouch of the cortisone-treated golden hamster (Burt el al., 1965(Burt el al., , 1966. Serial transfer of these tumours has been carried out to produce a continuum of growing cancer for experimental manipulation. We have successfully transferred eight bladder tumours from human to hamster. The purpose of this report is to describe the method used and the results obtained, and to demonstrate the feasibility of obtaining information on the responses of growing tumour to cytostatic drugs.Since the hamster cheek pouch was first used as a transplantation site for homologous and heterologous tumours (Lutz et a/., 1950), a number of investigators have employed it for study of human cancers in vivo (Chute et a/., 1952;Handler, 1956;Patterson et a/., 1957;Friedell et al., 1961). Toolan (1958) developed this method to fruition in her studies at the Sloan-Kettering Institute. It is now generally acknowledged that a wide variety of human tumours of high growth potential can be transplanted to the hamster cheek pouch and that these tumours can be maintained through repeated generations by serial transfer. The general impression from many reports, however, is that about 50 per cent. primary " takes " are possible but that only 5 to 10 per cent. of tumours are transplantable over five or more generations, even when (only) aggressive tumours are used. The wide difference in success rates among various institutions is probably attributable to experience, technique, and types of tumonrs used.As a method of studying tumour responsiveness to oncolytic agents, heterologous transplantation studies have certain advantages over tissue culture methods and tumours induced in laboratory animals. Tumours growing in tissue culture lack tumour-host interactions, isolated cells differ from cells organjsed in the stromal matrix of tumours, and drug testing on tumour cells growing in tissue culture is technically difficult (Walker and Wright, 1962). Bladder tumours have been induced in mice, rats, hamsters and dogs by a number of carcinogenic substances, administered either orally or into the bladder in the form of pellets. At least 20 per cent. of the animal's life span is necessary for tumour development (McDonald, 1960), i.e. 25 to 40 weeks in mice (Bryan and Price, 1963), one year in rats (Dunning eta/., 1947), and 12 to 18 months in dogs (Conzelman et al. 1963). Induced tumours differ from naturally occurring growths in that they do not metastasise, are indolent and transfer poorly to the hamster cheek pouch. It is doubtful whether these tumours respond to anticancer drugs in a fashion similar to human bladder cancers.It has not been entirely explained why the hamster cheek pouch allows growth of heterologous tumours better than do other sites. It is supposed that the unique layer of mucilaginous connective tissue under the skin of the pouch protects the graft from immunological reaction. If the layer, o...
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