Warning: file_get_contents(https://eutils.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&id=26919975
&cmd=llinks): Failed to open stream: HTTP request failed! HTTP/1.1 429 Too Many Requests
in C:\Inetpub\vhosts\kidney.de\httpdocs\pget.php on line 215
Warning: imagejpeg(C:\Inetpub\vhosts\kidney.de\httpdocs\phplern\26919975
.jpg): Failed to open stream: No such file or directory in C:\Inetpub\vhosts\kidney.de\httpdocs\pget.php on line 117 Reprod+Sci
2016 ; 23
(9
): 1139-47
Nephropedia Template TP
gab.com Text
Twit Text FOAVip
Twit Text #
English Wikipedia
Fenretinide: A Potential Treatment for Endometriosis
#MMPMID26919975
Pavone ME
; Malpani SS
; Dyson M
; Kim JJ
; Bulun SE
Reprod Sci
2016[Sep]; 23
(9
): 1139-47
PMID26919975
show ga
OBJECTIVE: Fenretinide is a synthetic retinoid analogue that promotes apoptosis
but has decreased toxicity when compared to other retinoids. We have previously
shown that retinoic acid (RA) production in endometriotic tissue is decreased,
resulting in reduced estrogen metabolism and apoptotic resistance. We hypothesize
fenretinide may induce apoptosis in endometriotic cells and tissues, thereby
reducing disease burden. MATERIALS AND METHODS: Primary endometriotic stromal
cells were collected, isolated, cultured, and treated with fenretinide in doses
from 0 to 20 µmol/L. Cell count, viability, and immunoblots were performed to
examine apoptosis. Quantitative reverse transcription-polymerase chain reaction
from endometriotic cells treated with fenretinide was used to examine expression
of genes involved in RA signaling including stimulated by RA 6 (STRA6), cellular
RA binding protein 2 (CRABP2), and fatty acid binding protein 5 (FABP5).
Endometriotic tissue was xenografted subcutaneously into the flanks of mice which
were treated with fenretinide for 2 weeks, after which the mice were killed and
lesion volumes calculated. Statistical analysis was performed using t test and
analysis of variance. RESULTS: Treatment with fenretinide significantly decreased
total cell count (doses 5-20 µL) and viability (doses 10-20 µmol/L). Fenretinide
increased protein levels of the apoptotic marker poly (ADP ribose) polymerase
(starting at 10 µmol/L) and decreased proliferation marker proliferating cell
nuclear antigen (10 µmol/L, starting at 8-day treatment). Examination of genes
involved in retinoid uptake and action showed that treatment induced STRA6
expression while expression of CRABP2 and FABP5 remained unchanged. Fenretinide
also significantly decreased the endometriotic lesion xenograft volume.
CONCLUSIONS: Fenretinide increases STRA6 expression thereby potentially reversing
the pathological loss of retinoid availability. Treatment with this compound
induces apoptosis. In vivo treatments decrease lesion volume. Targeting the RA
signaling pathway may be a promising novel treatment for women with
endometriosis.
free
free
free
