Responsiveness of human retinoblastoma and neuroblastoma models to a non-calcemic 19-nor Vitamin D analog

Daniel M. Albert, Lori A. Plum, William Yang, Marcus Marcet, Mary J. Lindstrom, Margaret Clagett-Dame, Hector F. DeLuca

Research output: Contribution to journalArticle

15 Scopus citations

Abstract

Objectives: To investigate the effectiveness of 2-methylene-19-nor-(20S)- 1α-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 β-luteinizing hormone-large T antigen (LHβ-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.

Original languageEnglish (US)
Pages (from-to)165-172
Number of pages8
JournalJournal of Steroid Biochemistry and Molecular Biology
Volume97
Issue number1-2
DOIs
StatePublished - Oct 1 2005

Keywords

  • Hypercalcemia
  • Neuroblastoma
  • Retinoblastoma
  • Tumor inhibition
  • Vitamin D analog

ASJC Scopus subject areas

  • Endocrinology, Diabetes and Metabolism
  • Biochemistry
  • Molecular Medicine
  • Molecular Biology
  • Endocrinology
  • Clinical Biochemistry
  • Cell Biology

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