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Antineoplastic effect of 1,25-dihydroxy-16-ene-23-yne-vitamin D3 analogue in transgenic mice with retinoblastoma.

AbstractOBJECTIVE:
To evaluate the in vivo efficacy and clinical toxic effects of the 1,25-dihydroxy-16-ene-23-yne-vitamin D3 analogue in beta-luteinizing hormone-Tag (LH beta-Tag) transgenic mice with heritable retinoblastoma.
METHODS:
Forty-two mice (8-10 weeks old), randomly assigned to experimental (n = 21) or control (n = 21) groups, received intraperitoneal injections of 0.05 microgram of 1,25-dihydroxy-16-ene-23-yne-D3 in 0.5-mL mineral oil vehicle (experimental group) or 0.5 mL of mineral oil vehicle (control group) for 5 weeks. One experimental and 3 control animals died of injection-related trauma. Eyes were enucleated 1 week after treatment and were examined histologically in a masked fashion.
RESULTS:
All experimental and control animals showed evidence of tumor. The tumors in the experimental mice showed a significantly smaller cross-sectional area (0.88 +/- 0.08 mm2) compared with that in the control mice (1.12 +/- 0.12 mm2) (P = .02). All mice completed the treatment and showed no clinical evidence of toxic effects.
CONCLUSIONS:
Tumors in transgenic mice with retinoblastoma treated with 1,25(OH)2-16-ene-23-yne-D3 showed a 21% smaller cross-sectional area compared with that in the control mice, without producing clinically apparent toxic effects. This compound may be useful as adjunctive therapy in the treatment of retinoblastoma.
AuthorsI S Shternfeld, J G Lasudry, R J Chappell, S R Darjatmoko, D M Albert
JournalArchives of ophthalmology (Chicago, Ill. : 1960) (Arch Ophthalmol) Vol. 114 Issue 11 Pg. 1396-401 (Nov 1996) ISSN: 0003-9950 [Print] United States
PMID8906031 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't, Research Support, U.S. Gov't, P.H.S.)
Chemical References
  • Antineoplastic Agents
  • Luteinizing Hormone
  • Calcitriol
  • Ro 23-7553
Topics
  • Animals
  • Antineoplastic Agents (pharmacology, toxicity)
  • Calcitriol (analogs & derivatives, pharmacology, toxicity)
  • Disease Models, Animal
  • Eye Neoplasms (drug therapy, genetics, pathology)
  • Female
  • Injections, Intraperitoneal
  • Luteinizing Hormone (genetics)
  • Male
  • Mice
  • Mice, Inbred ICR
  • Mice, Transgenic (genetics)
  • Retinoblastoma (drug therapy, genetics, pathology)
  • Transcriptional Activation

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