Responsiveness of human retinoblastoma and neuroblastoma models to a non-calcemic 19-nor Vitamin D analog.
OBJECTIVE
To investigate the effectiveness of 2-methylene-19-nor-(20S)-1alpha-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 hormone-large T antigen (LHbeta-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.


CONCLUSIONS
2MbisP should be considered for use in clinical trials of RB and NB.
Albert
Daniel M
DM
Department of Ophthalmology and Visual Sciences, University of Wisconsin Medical School, F4/344 Clinical Science Center, 600 Highland Avenue, Madison, WI 53792-3284, USA. dalbert@wisc.edu
Plum
Lori A
LA
Yang
William
W
Marcet
Marcus
M
Lindstrom
Mary J
MJ
Clagett-Dame
Margaret
M
DeLuca
Hector F
HF
D000818:Animals; D002117:Calcitriol / Q000009:adverse effects / Q000031:analogs & derivatives* / Q000494:pharmacology / Q000627:therapeutic use*; D002118:Calcium / Q000378:metabolism; D004195:Disease Models, Animal; D006801:Humans; D051379:Mice; D008819:Mice, Nude; D008822:Mice, Transgenic; D015394:Molecular Structure; D009447:Neuroblastoma / Q000188:drug therapy* / Q000473:pathology*; D012175:Retinoblastoma / Q000188:drug therapy* / Q000473:pathology*; D015996:Survival Rate; D023041:Xenograft Model Antitumor Assays
D002117:Calcitriol; D002118:Calcium