The CD8F1 murine breeding and spontaneous tumor holding colonies located at the St. Anthony's Cancer Research Center will serve as a Core Component for this Research Program. Spontaneous, autochthonous tumor-bearing mice, and mice bearing first passage tumor transplants will be provided for Research Project 1 (Experimental Therapy), and Research Project 2 (Biochemical Studies). In addition, samples of plasma, normal tissue and tumor tissue from animals undergoing experimental chemotherapy will be supplied for comparative biochemical and pharmacokinetic studies with human samples in Research Project 3 (Clinical Studies). The Colony consists of two inbred strains (BALB/c and DBA/8, a first generation hybrid (CD8F1), and facilities for holding hybrid females for tumor development (average tumor incidence of approximately 75% at 10 months of age). Approximately 650 CD8F1 mice will be weaned each week. Of these, 500 will be set aside to age for an additional 1-1/2 to 2 months to be used as primary CD8F1 breast tumor transplant recipients. To produce the required 100 spontaneous, autochthonous tumor-bearing CD8F1 females per week, 140 CD8F1 female weanlings (+22 CD8F1 males) are placed in the tumor holding colony each week, where they are observed for tumor development. Caretaking functions for all mice (breeding colonies, spontaneous tumor holding colony, mice being aged for experimentation, and tumor-bearing mice undergoing experimentation) will be the responsibility of the Animal Colony Core Component. CD8F1 tumors arise spontaneously in mid-to-late middle age in a high percentage of CD8F1 female mice. They are morphologically similar to human breast tumors, and metastasize spontaneously. Like human tumors, they have a relatively slow cell cycle time of 3-5 days which is considerably longer than the 24 hour cell cycle time of some of the transplantable murine tumors. Like human tumors, they show a vast degree of heterogeneity of many characteristics including growth rate and chemotherapeutic sensitivity. Like human tumors, and presumably because of their heterogeneity, they are not curable with any currently available single or multiple agent chemotherapy. They show a remarkable 100% correlation in chemotherapeutic sensitivity to drugs which are considered to be active against human breast cancer (22, 23). Because of these and many other parallels with the human disease, the CD8F1 spontaneous mammary tumor system provides an appropriate animal model for the preclinical development of combination chemotherapy for human cancer.
Showing the most recent 10 out of 48 publications
