Pathogenesis of humoral hypercalcemia of malignancy. 1988

T J Rosol, and C C Capen
Department of Veterinary Pathobiology, Ohio State University, Columbus 43210.

The three biologic activities most commonly associated with tumors that produce Humoral Hypercalcemia of Malignancy (HHM) include; 1) adenylate cyclase stimulating activity (PTH-like activity), 2) in vitro bone resorbing activity, and 3) transforming growth factor activity. The canine adenocarcinoma (CAC-8) model of HHM contains all three activities and the first two are inhibited by a PTH receptor antagonist. These data in light of the recent purification of PTH-related peptides from human tumors suggest that CAC-8 produces a PTH-related protein that is important in the pathogenesis of hypercalcemia. The CAC-8 tumor is a well characterized example of HHM and offers several advantages for further investigations on the pathogenesis of HHM: 1) transplantable tumor line from a spontaneous neoplasm in the dog, 2) tumor extracts contain the three biologic activities associated with HHM, 3) slow progressive growth rate in nude mice permits investigations on treatment of HHM, 4) increased bone resorption and formation in nude mice mimics the effects of PTH on bone, and 5) the only model of HHM that has been demonstrated to contain bone resorbing activity that can be inhibited by a PTH receptor antagonist.

UI MeSH Term Description Entries
D008819 Mice, Nude Mutant mice homozygous for the recessive gene "nude" which fail to develop a thymus. They are useful in tumor studies and studies on immune responses. Athymic Mice,Mice, Athymic,Nude Mice,Mouse, Athymic,Mouse, Nude,Athymic Mouse,Nude Mouse
D004283 Dog Diseases Diseases of the domestic dog (Canis familiaris). This term does not include diseases of wild dogs, WOLVES; FOXES; and other Canidae for which the heading CARNIVORA is used. Canine Diseases,Canine Disease,Disease, Canine,Disease, Dog,Diseases, Canine,Diseases, Dog,Dog Disease
D004285 Dogs The domestic dog, Canis familiaris, comprising about 400 breeds, of the carnivore family CANIDAE. They are worldwide in distribution and live in association with people. (Walker's Mammals of the World, 5th ed, p1065) Canis familiaris,Dog
D006934 Hypercalcemia Abnormally high level of calcium in the blood. Milk-Alkali Syndrome,Hypercalcemias,Milk Alkali Syndrome,Syndrome, Milk-Alkali
D000230 Adenocarcinoma A malignant epithelial tumor with a glandular organization. Adenocarcinoma, Basal Cell,Adenocarcinoma, Granular Cell,Adenocarcinoma, Oxyphilic,Adenocarcinoma, Tubular,Adenoma, Malignant,Carcinoma, Cribriform,Carcinoma, Granular Cell,Carcinoma, Tubular,Adenocarcinomas,Adenocarcinomas, Basal Cell,Adenocarcinomas, Granular Cell,Adenocarcinomas, Oxyphilic,Adenocarcinomas, Tubular,Adenomas, Malignant,Basal Cell Adenocarcinoma,Basal Cell Adenocarcinomas,Carcinomas, Cribriform,Carcinomas, Granular Cell,Carcinomas, Tubular,Cribriform Carcinoma,Cribriform Carcinomas,Granular Cell Adenocarcinoma,Granular Cell Adenocarcinomas,Granular Cell Carcinoma,Granular Cell Carcinomas,Malignant Adenoma,Malignant Adenomas,Oxyphilic Adenocarcinoma,Oxyphilic Adenocarcinomas,Tubular Adenocarcinoma,Tubular Adenocarcinomas,Tubular Carcinoma,Tubular Carcinomas
D000818 Animals Unicellular or multicellular, heterotrophic organisms, that have sensation and the power of voluntary movement. Under the older five kingdom paradigm, Animalia was one of the kingdoms. Under the modern three domain model, Animalia represents one of the many groups in the domain EUKARYOTA. Animal,Metazoa,Animalia
D051379 Mice The common name for the genus Mus. Mice, House,Mus,Mus musculus,Mice, Laboratory,Mouse,Mouse, House,Mouse, Laboratory,Mouse, Swiss,Mus domesticus,Mus musculus domesticus,Swiss Mice,House Mice,House Mouse,Laboratory Mice,Laboratory Mouse,Mice, Swiss,Swiss Mouse,domesticus, Mus musculus

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