A serially transplantable perianal gland carcinoma (CAC-9) was developed in nude mice from a hypercalcemic dog that has been maintained through passage 20. Tumor doubling rate of CAC-9 was 3.1 ± 0.4 days. Mithramycin (MMC) injected intraperitoneally (8 mg/kg) into nude mice bearing CAC-9 markedly decreased the tumor volume 2 weeks post-injection. MMC returned the elevated serum and urine calcium levels in mice with CAC-9 back to similar values as controls. The few remaining viable tumor cells after MMC were large and had numerous aggregations of intermediate filaments that displaced cytoplasmic organelles. Histomorphometric evaluation of lumbar vertebrae reveled no significant differences in bone resorption of nude mice bearing CAC-9 compared to saline-treated controls. This rapidly growing tumor line in nude mice associated with mild hypercalcemia will be a useful animal model to evaluate combinations of chemotherapy for cancer-associated hypercalcemia.
References
1.
AbramsonECKuklaLJShevrinDHLadTEMcGuireWPKukrejaSC:
A model for malignancy-associated hypercalcemia.Calcif Tissue Int36:
563,
1984
2.
ClarkeJT:
Colorimetric determination and distribution of urinary creatinine and creatine.Clin Chem7:
271,
1961
3.
CorbettTHGriswoldDPJrRobertsBJPeckhamJCSchabelFMJr:
Evaluation of single agents and combinations of chemotherapeutic agents in mouse colon carcinomas.Cancer40:
2660,
1977
4.
FiebigHHSchuchhardtCHenssHFiedlerLLöhrGW:
Comparison of tumor response in nude mice and in the patients.Behring Inst Mitt74:
343,
1984
5.
FiskeCHSubbarowY:
The colorimetric determination of phosphorus.J Biol Chem66:
375,
1925
6.
GiovanellaBCStehlinJSJrWilliamsLJJrLeeSShepardRC:
Heterotransplantation of human cancers into nude mice.Cancer42:
2269,
1978
7.
HirshornJEVrhovsekEPosenS:
Carcinoma of the breast associated with hypercalcemia and the presence of parathyroid hormone-like substances in the tumor.J Clin Endocrinol Metabol48:
217,
1979
8.
KiangDTLokenMKKennedyBJ:
Mechanism of the hypocalcemic effect of mithramycin.J Clin Endocrinol Metabol48:
341,
1979
9.
KubotaTKubouchiKTsuyukiKNakadaMAsanumaFKohJIshibikiKAbeOKawamuraE:
Experimental endocrine therapy of human breast carcinomas transplanted into nude mice.
In: Immune-Deficient Animals, 4th Intl Workshop in Immune-Deficient Animals in Experimental Research, ed. Sordat,
p. 385.
S Karger AG, Basel,
1984
10.
LehtoVPVirtanenI:
Intermediate (10 nm) filaments in human malignant mesothelioma.Virchows Arch B Cell Pathol28:
229,
1978
11.
MundyGRWilkinsonRHeathDA:
Comparative study of available medical therapy for hypercalcemia of malignancy.Am J Med74:
421,
1983
12.
MundyGRIbbotsonKJD'SouzaSMSimpsonELJacobsJWMartinTJ:
The hypercalcemia of cancer. Clinical implications and pathologic mechanisms.N Engl J Med310:
1718,
1984
13.
NordinBECHodgkinsonAPeacockM:
The measurement and meaning of urinary calcium.Clin Orthopaed Rel Res52:
293,
1967
14.
OsborneCAStevensJB:
Pseudohyperparathyroidism in the dog.J Am Vet Med Assoc162:
125,
1973
15.
OvejeraAAHouchensDP:
Human tumor xenografts in athymic nude mice as a preclinical screen for anticancer agents.Seminars Oncol8:
386,
1981
16.
PerliaCPGubischNJWolterJEdelbergDDederickMMTaylorSGIII:
Mithramycin treatment of hypercalcemia.Cancer25:
389,
1970
17.
RiceBFRothLMColeFEMacPheeAADavisKPonthierRLSternbergWH:
Hypercalcemia and neoplasia. Biologic, biochemical and ultrastructural studies of a hypercalcemia-producing Leydig cell tumor of the rat.Lab Invest33:
428,
1975
18.
RobertsonRPBaylinkDJMetzSACummingsKB:
Plasma prostaglandin E in patients with cancer with and without hypercalcemia.J Clin Endocrinol Metabol43:
1330,
1976
19.
RosolTJCapenCCWeisbrodeSEHorstRL:
Humoral hypercalcemia of malignancy: nude mouse model using a canine adenocarcinoma derived from apocrine glands of the anal sac. Biochemical, histomorphometric and ultrastructural evaluation.Lab Invest54:
1986
(in press)
20.
RoyS:
Cytoplasmic filamentous masses in chromophobe adenoma of the human pituitary gland.J Pathol125:
151,
1978
21.
StewartAF:
Therapy of malignancy-associated hypercalcemia: 1983.Am J Med74:
475,
1983
22.
StrewlerGJWilliamsRDNissensonRA:
Human renal carcinoma cells prdouce hypercalcemia in the nude mouse and a novel protein recognized by parathyroid hormone receptors.J Clin Invest71:
769,
1983
23.
TashjianAHJrVoelkelEFLevineLGoldhaberP:
Evidence that the bone resorption-stimulating factor produced by mouse fibrosarcoma cells is prostaglandin E2: a new model for the hypercalcemia of cancer.J Exp Med136:
1329,
1972
24.
TibbettsLMChuMYHagerJCDexterDLCalabresiP:
Chemotherapy of cell-line-derived human colon carcinomas in mice immunosuppressed with antithymocyte serum.Cancer40:
2651,
1977
25.
VoelkelEFTashjianAHJrFranklinRWassermanELevineL:
Hypercalcemia and tumor-prostaglandins: the VX2 carcinoma model in the rabbit.Metabolism24:
973,
1975
26.
WalterRMJrGreenbergBR:
Hypercalcemia in the accelerated phase of chronic myelogenous leukemia.Cancer46:
1174,
1980
