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In mice estradiol tumor suppression incomplete


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Editorial - Estradiol suppresses tissue androgens and prostate cancer growth in castration resistant prostate cancer

Written by Christopher P. Evans, MD

Thursday, 19 August 2010

BERKELEY, CA (UroToday.com) - In BMC Cancer, Dr. Bruce Montgomery and colleagues evaluate the ability for estadiol to inhibit castration-resistant prostate cancer (CRPC) tumors. Despite the association of estrogens with cardiovascular events in men with advanced prostate cancer (CaP), estrogens are known to induce a PSA response in 45% of men with CRPC. In human CaP castrated mouse models, it is known that the effect of estradiol is independent of both testicular and adrenal androgens. It is also known that CRPC tumors can produce their own, intracrine androgens. These researchers hypothesized that 17?-estardiol could inhibit CRPC growth in castrated mice and suppress tumoral androgens by competitively inhibiting steroidogenesis from cholesterol.

The studies were performed in the LuCaP 35V CRPC cell line, which expresses wild-type AR and PSA. LuCaP 35V cells were implanted subcutaneously in castrated mice. When tumors were established, mice were randomized to treatment with placebo (group I), 17?-estardiol (group II), or 17?-estardiol and the estrogen receptor antagonist ICI 182,780 (group III). Control tissue for androgen assays came from non-tumor tissue from the same animals and LuCaP 35 cells growing in eugonadal mice. Tumor volume was monitored and tumors assessed at the conclusion of the in vivo experiment for steroids.

Serum estradiol levels were 79pg/mL in control mice, 636pg/mL in 17?-estardiol alone treated mice and 731pg/mL in mice treated with 17?-estardiol and ICI 182,780. The differences between the treated groups II and III were not significant. Group II animals lived longer compared to group I mice (24 vs. 21 days) and group III did not have an increased improvement on survival. Tumor volume in group I was greater than groups II and III, which did not differ.

These data suggest that the tumor inhibition is independent of the estrogen receptor. Estradiol treated mice had significantly reduced DHT levels compared to controls and addition of ICI 182,780 did not change this further. However, use of estradiol did not decrease tumoral androgen levels to those seen in control tissues. This suggests incomplete tumor suppression with estradiol therapy.

Montgomery B, Nelson PS, Vessella R, Kalhorn T, Hess D, Corey E

BMC Cancer. 2010 May 28;10:244

10.1186/1471-2407-10-244

PubMed Abstract

PMID: 20509933 Forum: Secondary hormone therapy Title: In mice estradiol tumor suppression incomplete

This extract can be found on http://PubMed.com, and is in the public domain.

On PubMed.com there will be a link to the full paper (often $30, sometimes free).

Any highlighting (except the title) is not by the author, but by Jim Marshall.

Jim is not a doctor.

This page was found on the Advanced Prostate Cancer Community for Australian men at http://advancedprost...lia.ipbhost.com.

The link is hard to remember.

An easier way to find it is to go to JimJimJimJim.com and click on Prostate.

That's the word Jim four times, no spaces, followed by .com.

If you need other help - to perhaps find someone to talk to or a local support group:

Click on the Contact Jim button at http://JimJimJimJim.com.

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