Journal
JOURNAL OF STEROID BIOCHEMISTRY AND MOLECULAR BIOLOGY
Volume 97, Issue 1-2, Pages 165-172Publisher
PERGAMON-ELSEVIER SCIENCE LTD
DOI: 10.1016/j.jsbmb.2005.06.019
Keywords
retinoblastoma; neuroblastoma; Vitamin D analog; hypercalcemia; tumor inhibition
Funding
- PHS HHS [R01 E401917-25] Funding Source: Medline
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Objectives: To investigate the effectiveness of 2-methylene-19-nor-(20S)-1 alpha-hydroxybishomopregnacalciferol (2MbisP) in inhibiting the growth of retinoblastoma (RB) and neuroblastoma (NB). Methods: For the RB study, the xenograft athymic mouse/human retinoblastoma cell (Y-79) model and the transgenic beta-luteinizing honnone-large T antigen (LH beta-Tag) mice were systemically treated with 2MbisP or vehicle for 5 weeks. For the NB study, the xenograft athymic mouse/human neuroblastoma cell (SK-N-AS) model was treated with 2MbisP or vehicle for 5 weeks. Tumor size and toxicity were assessed. Results: In the xenograft models of RB and NB, 2MbisP caused statistically significant inhibition of tumor growth. Tumor growth inhibition was also observed in the transgenic RB mice, but did not achieve statistical significance. In all the groups, no biologically significant toxic effects were observed using the following variables: serum calcium levels, degree of kidney calcification, changes in body weight or survival. Conclusions: In athymic mice, 2MbisP was effective in inhibiting RB and NB growth compared with controls. A lesser effect was seen in the transgenic RB model. 2MbisP did not cause hypercalcemia or a significant increase in mortality. Clinical relevance: 2MbisP should be considered for use in clinical trials of RB and NB. (c) 2005 Elsevier Ltd. All rights reserved.
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