Abstract | PURPOSE: EXPERIMENTAL DESIGN: MDA-MB-231/ BO2 cells were injected via the tail vein into athymic mice. Tumor-induced osteolytic lesions were detected in all animals following X-ray analysis 18 days after tumor cell inoculation (day 18). Mice were administered saline, 100 microg/kg zoledronic acid, 2 mg/kg doxorubicin, doxorubicin and zoledronic acid simultaneously, or doxorubicin followed 24 h later by zoledronic acid. Doxorubicin-treated animals received a second injection on day 25. Tumor growth in the marrow cavity and on the outside surface of the bone was measured as well as tumor cell apoptosis and proliferation. The effects of treatments on bone were evaluated following X-ray and muCT analysis. RESULTS: Sequential treatment with doxorubicin followed by zoledronic acid caused decreased intraosseous tumor burden, which was accompanied by increased levels of tumor cell apoptosis and decreased levels of proliferation, whereas extraosseous parts of the same tumors were unaffected. Administration of zoledronic acid, alone or in combination with doxorubicin, resulted in significantly smaller tumor-induced osteolytic lesions compared with control or doxorubicin-treated animals. CONCLUSIONS:
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Authors | Penelope D Ottewell, Blandine Deux, Hannu Mönkkönen, Simon Cross, Robert E Coleman, Philippe Clezardin, Ingunn Holen |
Journal | Clinical cancer research : an official journal of the American Association for Cancer Research
(Clin Cancer Res)
Vol. 14
Issue 14
Pg. 4658-66
(Jul 15 2008)
ISSN: 1078-0432 [Print] United States |
PMID | 18628481
(Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
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Chemical References |
- Antineoplastic Agents
- Bone Density Conservation Agents
- Diphosphonates
- Imidazoles
- Zoledronic Acid
- Doxorubicin
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Topics |
- Animals
- Antineoplastic Agents
(therapeutic use)
- Apoptosis
(drug effects)
- Bone Density Conservation Agents
(therapeutic use)
- Bone Neoplasms
(drug therapy, secondary)
- Breast Neoplasms
(drug therapy, pathology)
- Diphosphonates
(therapeutic use)
- Doxorubicin
(therapeutic use)
- Female
- Humans
- Imidazoles
(therapeutic use)
- Immunohistochemistry
- Mice
- Mice, Nude
- Zoledronic Acid
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