Rich66
01-03-2009, 02:48 PM
<dl class="AbstractPlusReport"><dt class="head">Breast Cancer Res Treat. (javascript:AL_get(this,%20'jour',%20'Breast%20Can cer%20Res%20Treat.');) 2008 Nov 7. [Epub ahead of print]http://www.ncbi.nlm.nih.gov/corehtml/query/egifs/http:--production.springer.de-OnlineResources-Logos-springerlink.gif (http://www.ncbi.nlm.nih.gov/entrez/utils/fref.fcgi?PrId=3055&itool=AbstractPlus-def&uid=18989771&db=pubmed&url=http://dx.doi.org/10.1007/s10549-008-0236-6) <script language="JavaScript1.2"><!-- var Menu18989771 = [ ["UseLocalConfig", "jsmenu3Config", "", ""], ["LinkOut", "window.top.location='/sites/entrez?Cmd=ShowLinkOut&Db=pubmed&TermToSearch=18989771&ordinalpos=1&itool=EntrezSystem2.PEntrez.Pubmed.Pubmed_ResultsP anel.Pubmed_DiscoveryPanel.Pubmed_RVAbstractPlus' ", "", ""] ] --></script>Links (javascript:PopUpMenu2_Set(Menu18989771);)
</dt><dd class="abstract"> Synergistic effect of bisphosphonate and docetaxel on the growth of bone metastasis in an animal model of established metastatic bone disease.
<!--AuthorList-->van Beek ER (http://www.ncbi.nlm.nih.gov/sites/entrez?Db=pubmed&Cmd=Search&Term=%22van%20Beek%20ER%22%5BAuthor%5D&itool=EntrezSystem2.PEntrez.Pubmed.Pubmed_ResultsP anel.Pubmed_DiscoveryPanel.Pubmed_RVAbstractPlus), Lowik CW (http://www.ncbi.nlm.nih.gov/sites/entrez?Db=pubmed&Cmd=Search&Term=%22Lowik%20CW%22%5BAuthor%5D&itool=EntrezSystem2.PEntrez.Pubmed.Pubmed_ResultsP anel.Pubmed_DiscoveryPanel.Pubmed_RVAbstractPlus), van Wijngaarden J (http://www.ncbi.nlm.nih.gov/sites/entrez?Db=pubmed&Cmd=Search&Term=%22van%20Wijngaarden%20J%22%5BAuthor%5D&itool=EntrezSystem2.PEntrez.Pubmed.Pubmed_ResultsP anel.Pubmed_DiscoveryPanel.Pubmed_RVAbstractPlus), Ebetino FH (http://www.ncbi.nlm.nih.gov/sites/entrez?Db=pubmed&Cmd=Search&Term=%22Ebetino%20FH%22%5BAuthor%5D&itool=EntrezSystem2.PEntrez.Pubmed.Pubmed_ResultsP anel.Pubmed_DiscoveryPanel.Pubmed_RVAbstractPlus), Papapoulos SE (http://www.ncbi.nlm.nih.gov/sites/entrez?Db=pubmed&Cmd=Search&Term=%22Papapoulos%20SE%22%5BAuthor%5D&itool=EntrezSystem2.PEntrez.Pubmed.Pubmed_ResultsP anel.Pubmed_DiscoveryPanel.Pubmed_RVAbstractPlus).
Department of Endocrinology & Metabolic Diseases, C4-R Leiden University Medical Center, Albinusdreef 2, 2300 RC, Leiden, The Netherlands.
Bisphosphonates decrease bone resorption and reduce significantly the rate of skeletal complications in patients with metastatic bone disease. Bisphosphonates have also been shown to exhibit antitumor activity in vitro but in vivo results have been equivocal. In the present study, we investigated the effects of bisphosphonate treatment alone or in combination with the cytostatic docetaxel on the growth of breast cancer cells in bone. Tumor gowth was studied in an athymic nude mice model inoculated with MDA-231-B/luc+ breast cancer cells. Two days after the inoculation, mice were treated with risedronate, zolendronate or docetaxel alone or with a combination of risedronate and docetaxel. Bone destruction and tumor growth were evaluated radiographically, histologically and by whole-body bioiluminescent reporter imaging (BLI). Five week treatment with high doses risedronate or zoledronate (37.5-150 mug/kg, 5 times/week), fully protected the bones from osteolysis, but did not affect tumour growth. Docetaxel (2, 4, and 8 mg/kg, 2 times/week) inhibited tumour growth dose-dependently and after 5 weeks treatment with the highest dose, there was no detectable tumour in bone. The combination of a dose of docetaxel (4 mg/kg) that demonstrated only a minimal effect on tumour growth, with risedronate (150 mug/kg), protected bone integrity and nearly completely inhibited the growth of the cancer cells. Risedronate and docetaxel act synergistically to protect bone and decrease tumour burden in an animal model of established bone metastases from breast cancer cells.
</dd></dl>
</dt><dd class="abstract"> Synergistic effect of bisphosphonate and docetaxel on the growth of bone metastasis in an animal model of established metastatic bone disease.
<!--AuthorList-->van Beek ER (http://www.ncbi.nlm.nih.gov/sites/entrez?Db=pubmed&Cmd=Search&Term=%22van%20Beek%20ER%22%5BAuthor%5D&itool=EntrezSystem2.PEntrez.Pubmed.Pubmed_ResultsP anel.Pubmed_DiscoveryPanel.Pubmed_RVAbstractPlus), Lowik CW (http://www.ncbi.nlm.nih.gov/sites/entrez?Db=pubmed&Cmd=Search&Term=%22Lowik%20CW%22%5BAuthor%5D&itool=EntrezSystem2.PEntrez.Pubmed.Pubmed_ResultsP anel.Pubmed_DiscoveryPanel.Pubmed_RVAbstractPlus), van Wijngaarden J (http://www.ncbi.nlm.nih.gov/sites/entrez?Db=pubmed&Cmd=Search&Term=%22van%20Wijngaarden%20J%22%5BAuthor%5D&itool=EntrezSystem2.PEntrez.Pubmed.Pubmed_ResultsP anel.Pubmed_DiscoveryPanel.Pubmed_RVAbstractPlus), Ebetino FH (http://www.ncbi.nlm.nih.gov/sites/entrez?Db=pubmed&Cmd=Search&Term=%22Ebetino%20FH%22%5BAuthor%5D&itool=EntrezSystem2.PEntrez.Pubmed.Pubmed_ResultsP anel.Pubmed_DiscoveryPanel.Pubmed_RVAbstractPlus), Papapoulos SE (http://www.ncbi.nlm.nih.gov/sites/entrez?Db=pubmed&Cmd=Search&Term=%22Papapoulos%20SE%22%5BAuthor%5D&itool=EntrezSystem2.PEntrez.Pubmed.Pubmed_ResultsP anel.Pubmed_DiscoveryPanel.Pubmed_RVAbstractPlus).
Department of Endocrinology & Metabolic Diseases, C4-R Leiden University Medical Center, Albinusdreef 2, 2300 RC, Leiden, The Netherlands.
Bisphosphonates decrease bone resorption and reduce significantly the rate of skeletal complications in patients with metastatic bone disease. Bisphosphonates have also been shown to exhibit antitumor activity in vitro but in vivo results have been equivocal. In the present study, we investigated the effects of bisphosphonate treatment alone or in combination with the cytostatic docetaxel on the growth of breast cancer cells in bone. Tumor gowth was studied in an athymic nude mice model inoculated with MDA-231-B/luc+ breast cancer cells. Two days after the inoculation, mice were treated with risedronate, zolendronate or docetaxel alone or with a combination of risedronate and docetaxel. Bone destruction and tumor growth were evaluated radiographically, histologically and by whole-body bioiluminescent reporter imaging (BLI). Five week treatment with high doses risedronate or zoledronate (37.5-150 mug/kg, 5 times/week), fully protected the bones from osteolysis, but did not affect tumour growth. Docetaxel (2, 4, and 8 mg/kg, 2 times/week) inhibited tumour growth dose-dependently and after 5 weeks treatment with the highest dose, there was no detectable tumour in bone. The combination of a dose of docetaxel (4 mg/kg) that demonstrated only a minimal effect on tumour growth, with risedronate (150 mug/kg), protected bone integrity and nearly completely inhibited the growth of the cancer cells. Risedronate and docetaxel act synergistically to protect bone and decrease tumour burden in an animal model of established bone metastases from breast cancer cells.
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