PMID- 15671562
OWN - NLM
STAT- MEDLINE
DCOM- 20050628
LR  - 20231213
IS  - 1078-0432 (Print)
IS  - 1078-0432 (Linking)
VI  - 11
IP  - 1
DP  - 2005 Jan 1
TI  - Growth suppression of ovarian cancer xenografts in nude mice by vitamin D 
      analogue EB1089.
PG  - 323-8
AB  - PURPOSE: The poor response of advanced epithelial ovarian cancer to current 
      treatments necessitates the development of alternative therapeutic strategies. 
      Inhibition of cancer growth by 1,25-dihydroxyvitamin D3 [1,25(OH)2D3] compounds 
      represents an innovative approach for cancer therapy. The current study evaluated 
      the therapeutic potential of a synthetic 1,25(OH)2D3 analogue EB1089 in the 
      treatment of ovarian cancer. EXPERIMENTAL DESIGN: The response of human ovarian 
      cancer cells to 1,25(OH)2D3 and EB1089 were first compared in cell growth, gene 
      transcription, and apoptotic assays. Then, nude mice bearing OVCAR3 tumor 
      xenografts were treated with EB1089 at different dosages, and tumor volumes were 
      monitored. The effect of EB1089 and 1,25(OH)2D3 on the level of serum calcium was 
      also examined. After the treatment, tumors were excised and processed for 
      histologic examination, Ki-67 staining, and tissue terminal deoxynucleotide 
      transferase-mediated dUTP nick end labeling (TUNEL) assays to evaluate the 
      morphologic, proliferative, and apoptotic changes induced by EB1089, 
      respectively. RESULTS: The study shows that EB1089 suppresses the in vitro growth 
      of ovarian cancer cells and transcriptionally activates the GADD45 reporter gene 
      more effectively than 1,25(OH)2D3. Clinically more importantly, EB1089 suppresses 
      the growth of OVCAR3 tumor xenografts in nude mice without inducing 
      hypercalcemia. Ki-67 staining and tissue TUNEL assays showed that both inhibition 
      of cell proliferation and induction of apoptosis contribute to the EB1089-induced 
      tumor suppression in vivo. CONCLUSIONS: This study is the first demonstration 
      that ovarian cancer responds positively in vivo to treatment with a 1,25(OH)2D3 
      compound and thus supports continued development of 1,25(OH)2D3 analogues for 
      possible use as an alternative or complementary therapy for human ovarian cancer.
FAU - Zhang, Xiaohui
AU  - Zhang X
AD  - Department of Pathology and Interdisciplinary Oncology, University of South 
      Florida College of Medicine, Programs of Molecular Oncology and Drug Discovery, 
      H. Lee Moffitt Cancer Center, Tampa, Florida, USA.
FAU - Jiang, Feng
AU  - Jiang F
FAU - Li, Pengfei
AU  - Li P
FAU - Li, Chunrong
AU  - Li C
FAU - Ma, Qiuping
AU  - Ma Q
FAU - Nicosia, Santo V
AU  - Nicosia SV
FAU - Bai, Wenlong
AU  - Bai W
LA  - eng
PT  - Journal Article
PT  - Research Support, U.S. Gov't, Non-P.H.S.
PL  - United States
TA  - Clin Cancer Res
JT  - Clinical cancer research : an official journal of the American Association for 
      Cancer Research
JID - 9502500
RN  - 0 (Antineoplastic Agents)
RN  - 0 (Intracellular Signaling Peptides and Proteins)
RN  - 0 (Ki-67 Antigen)
RN  - FXC9231JVH (Calcitriol)
RN  - Q0OZ0D9223 (seocalcitol)
RN  - SY7Q814VUP (Calcium)
SB  - IM
MH  - Animals
MH  - Antineoplastic Agents/*pharmacology
MH  - Apoptosis
MH  - Calcitriol/*analogs & derivatives/*pharmacology
MH  - Calcium/metabolism
MH  - Cell Line, Tumor
MH  - Cell Proliferation
MH  - Female
MH  - Genes, Reporter
MH  - Humans
MH  - Immunohistochemistry
MH  - In Situ Nick-End Labeling
MH  - Intracellular Signaling Peptides and Proteins/metabolism
MH  - Ki-67 Antigen/biosynthesis
MH  - Mice
MH  - Mice, Nude
MH  - Neoplasm Transplantation
MH  - Ovarian Neoplasms/*drug therapy
MH  - Time Factors
MH  - Transcriptional Activation
MH  - GADD45 Proteins
EDAT- 2005/01/27 09:00
MHDA- 2005/06/29 09:00
CRDT- 2005/01/27 09:00
PHST- 2005/01/27 09:00 [pubmed]
PHST- 2005/06/29 09:00 [medline]
PHST- 2005/01/27 09:00 [entrez]
AID - 11/1/323 [pii]
PST - ppublish
SO  - Clin Cancer Res. 2005 Jan 1;11(1):323-8.