Effects of gallium nitrate in nude mice bearing a canine adenocarcinoma (CAC-8) model of humoral hypercalcemia of malignancy.
Effects of gallium nitrate in nude mice bearing a canine adenocarcinoma (CAC-8) model of humoral hypercalcemia of malignancy.
复制标题
硝酸镓对犬腺癌（CAC-8）恶性肿瘤体液高钙血症裸鼠模型的影响。
DOI：
10.1002/jbmr.5650090518
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发表时间：
1994
期刊：
影响因子：
--
通讯作者：
Rosol,TJ
中科院分区：
文献类型：
--
作者：
Merryman,JI;Capen,CC;Rosol,TJ
携带恶性体液性高钙血症（HHM）的犬腺癌（CAC-8）模型的高钙血症裸鼠每天用硝酸镓（在第0天皮下（SC）60 mg/kg元素镓，随后20 mg/kg/天）治疗5天。在治疗的第2天和第5天，硝酸镓显著降低了荷瘤动物的血清钙（p< 0.01）（第0天的平均值为13.7 ± 0.7 mg/dl，第2天为11.6 ± 0.3 mg/dl，第5天为12.4 ± 0.5 mg/dl）。与高钙血症荷瘤小鼠（0.30 ± 0.06）相比，镓治疗的荷瘤动物（0.11 ± 0.01 mg钙/mg肌酐）的尿钙排泄减少（p< 0.05）。用硝酸镓治疗的非肿瘤对照和荷瘤小鼠在治疗期间体重减轻（p< 0.01）。硝酸镓对肿瘤生长没有影响。抗酒石酸酸性磷酸酶染色的腰椎组织形态学评价显示，与荷瘤对照组相比，镓处理的荷瘤小鼠中破骨细胞/mm骨小梁数量和由活性成骨细胞排列的骨小梁周长显著降低（p < 0.05）（p< 0.01）。与非肿瘤和荷瘤对照小鼠相比，非肿瘤和荷瘤镓治疗动物的破骨细胞长度（mm）显著增加（p< 0.05）。荷瘤动物的血清肿瘤坏死因子α（TNF-α）水平升高，但硝酸镓对循环水平无影响（在非肿瘤对照小鼠中未检出，而荷瘤小鼠为82 ± 21 pg/ml，镓治疗荷瘤小鼠为107 ± 12 pg/ml）。在未处理的对照小鼠中，骨中的镓浓度检测不到（<0.00005 μg/g骨），但在镓处理的小鼠中，骨中的镓浓度显著升高（非荷瘤小鼠为235 ± 6 μg/g骨，荷瘤小鼠为155 ± 18 μg/g骨）。这些结果表明，硝酸镓在HHM的裸鼠模型中降低了骨细胞骨吸收和血清钙水平。
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 α (TNF‐α) 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). Concentrations of gallium in bone were undetectable in untreated control mice (<0.00005 μg/g bone), but markedly elevated concentrations were present in gallium‐treated mice (235 ± 6 μg/g bone in nontumor‐bearing and 155 ± 18 in tumor‐bearing). These results indicate that gallium nitrate decreased osteoclastic bone resorption and serum calcium levels in a nude mouse model of HHM.