Effects of gallium nitrate in nude mice bearing a canine adenocarcinoma (CAC-8) model of humoral hypercalcemia of malignancy.
Hypercalcemic nude mice bearing a canine adenocarcinoma (CAC-8) model of humoral hypercalcemia of malignancy (HHM) were treated daily with gallium nitrate (60 mg/kg of elemental gallium subcutaneously (SC) on day 0, followed by 20 mg/kg/day) for 5 days. Gallium nitrate significantly decreased (p < 0.01) serum calcium in tumor-bearing animals on days 2 and 5 of treatment (mean 13.7 +/- 0.7 mg/dl on day 0 versus 11.6 +/- 0.3 on day 2 and 12.4 +/- 0.5 on day 5). Urinary calcium excretion was decreased (p < 0.05) in the gallium-treated, tumor-bearing animals (0.11 +/- 0.01 mg calcium/mg creatinine) compared with hypercalcemic tumor-bearing mice (0.30 +/- 0.06). Both nontumor control and tumor-bearing mice treated with gallium nitrate lost body weight during the treatment period (p < 0.01). Gallium nitrate had no effect on tumor growth. Histomorphometric evaluation of lumbar vertebrae stained for tartrate-resistant acid phosphatase revealed a significant decrease (p < 0.05) in the number of osteoclasts/mm trabecular bone and perimeter of trabecular bone lined by active osteoblasts (p < 0.01) in the gallium-treated tumor-bearing mice compared with tumor-bearing controls. Osteoclast length (mm) was significantly increased in both the nontumor and tumor-bearing gallium-treated animals (p < 0.05) compared with nontumor and tumor-bearing control mice. Serum tumor necrosis factor alpha (TNF-alpha) levels were increased in tumor-bearing animals, but gallium nitrate had no effect on circulating levels (not detectable in nontumor control mice versus 82 +/- 21 pg/ml in tumor-bearing mice and 107 +/- 12 pg/ml in gallium-treated tumor-bearing mice).(ABSTRACT TRUNCATED AT 250 WORDS)
Merryman
J I
JI
Department of Veterinary Pathobiology, Ohio State University, Columbus.
Capen
C C
CC
Rosol
T J
TJ
D000230:Adenocarcinoma / Q000188:drug therapy*; D000818:Animals; D000970:Antineoplastic Agents / Q000008:administration & dosage / Q000494:pharmacology / Q000627:therapeutic use*; D001862:Bone Resorption / Q000188:drug therapy; D002118:Calcium / Q000097:blood / Q000652:urine; D003404:Creatinine / Q000097:blood / Q000652:urine; D004195:Disease Models, Animal; D004285:Dogs; D005708:Gallium / Q000008:administration & dosage / Q000494:pharmacology / Q000627:therapeutic use*; D006934:Hypercalcemia / Q000188:drug therapy*; D008159:Lumbar Vertebrae / Q000187:drug effects / Q000473:pathology; D051379:Mice; D008819:Mice, Nude; D010010:Osteoclasts / Q000187:drug effects*; D010257:Paraneoplastic Syndromes / Q000188:drug therapy*; D044162:Parathyroid Hormone-Related Protein; D011506:Proteins / Q000378:metabolism; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism
D000970:Antineoplastic Agents; D044162:Parathyroid Hormone-Related Protein; D011506:Proteins; D014409:Tumor Necrosis Factor-alpha; D003404:Creatinine; D005708:Gallium; D002118:Calcium; C027235:gallium nitrate