Angiogenesis Inhibitors in the Treatment of Prostate Cancer

2013 ◽  
pp. 197-215 ◽  
Author(s):  
Bamidele A. Adesunloye ◽  
Fatima H. Karzai ◽  
William L. Dahut
Keyword(s):  
Prostate Cancer ◽  
Angiogenesis Inhibitors

Effect of thalidomide on the TGFβ-1-mediated synthesis of testosterone from DHEA in prostate cancer.

2012 ◽  
Vol 30 (5_suppl) ◽  
pp. 141-141
Author(s):  
Tristan Sissung ◽  
C. Tyler Kirkland ◽  
Kelie M Reece ◽  
Julia T Arnold ◽  
William Douglas Figg
Keyword(s):  
Prostate Cancer ◽  
Stromal Cells ◽  
Angiogenesis Inhibitors ◽  
Castration Resistant Prostate Cancer ◽  
Androgen Synthesis ◽  
Castration Resistant ◽  
The Difference ◽  
Dose Dependent Increase ◽  
Dose Dependent ◽  
Testosterone Synthesis

141 Background: TGFβ-1 induces conversion of DHEA to testosterone in prostate cancer stromal cells. We hypothesized that thalidomide would inhibit TGFβ-1-mediated formation of testosterone from DHEA. Methods: We grew LAPC4 or LNCaP prostate cancer epithelial cells and 6S primary prostate stromal cells in mono-/co-culture with DHEA (100nM) and/or TGFβ-1 (40 or 100pM). Testosterone and PSA concentration in media were ascertained using ELISA and corrected for cell count using CCK8 (%DHEA controls). Results: TGFβ-1 and DHEA induced a dose-dependent increase in the formation of testosterone over controls (∼5-6 fold; P<0.0001). Thalidomide (100μM) inhibited the formation of testosterone in cocultured cells treated with DHEA and TGFβ-1 (40pM) by 35% (P=0.0008). The thalidomide analogues, CPS49 (10μM) and lenalidomide (10μM) also had activity; CPS49 inhibited testosterone synthesis by 54% (P=0.010) while lenalidomide reduced testosterone by 15% (P=0.011). However, only thalidomide and CPS49 decreased median PSA secretion (40% and 93% respectively; P≤0.031). Other angiogenesis inhibitors (i.e., suramin (10μM) and sorafenib (500pM)) had no effect on testosterone synthesis (P>0.05). Therefore, anti-androgen activity was not a class effect of antiangiogenesis agents. Ketoconazole also did not have activity suggesting that TGFβ-1-induced testosterone synthesis from DHEA evades standard therapies designed to inhibit androgen synthesis enzymes (i.e. CYP3A4 and CYP17 inhibitors). We assessed the phosphorylation status of TGFβ-1 pathway constituents (i.e., SMAD2/3, p38, JNK, and ERK) in cocultured cells treated as above. Thalidomide inhibits the phosphorylation of ERK without affecting total ERK levels; however, neither MEK inhibition (via U0126) nor Raf inhibition (via sorafenib) resulted in anti-androgenic effects in these cells suggesting that the canonical RAF/MEK/ERK pathway is not responsible for the difference in testosterone secretion phenotype. Conclusions: These results indicate that thalidomide and its analogues have anti-androgen activity and may explain the success of thalidomide and its analogues in clinical treatment of hormone-dependent and castration-resistant prostate cancer.

scholarly journals Angiogenesis inhibitors in the treatment of prostate cancer

2010 ◽  
Vol 11 (2) ◽  
pp. 233-247 ◽  
Author(s):  
Paul G Kluetz ◽  
William D Figg ◽  
William L Dahut
Keyword(s):  
Prostate Cancer ◽  
Angiogenesis Inhibitors

The Role of Angiogenesis Inhibitors in Prostate Cancer

2008 ◽  
Vol 14 (1) ◽  
pp. 20-25 ◽  
Author(s):  
Jeanny B. Aragon-Ching ◽  
William L. Dahut
Keyword(s):  
Prostate Cancer ◽  
Angiogenesis Inhibitors

Angiogenesis Inhibitors in Prostate Cancer

2006 ◽  
pp. 127-141
Author(s):  
William D. Figg ◽  
Michael C. Cox ◽  
Tania Alachalabi ◽  
William L. Dahut
Keyword(s):  
Prostate Cancer ◽  
Angiogenesis Inhibitors

Sigmoidoscopic findings following radiation for prostate cancer

2001 ◽  
Vol 120 (5) ◽  
pp. A284-A284
Author(s):  
T BOLIN ◽  
A KNEEBONE ◽  
T LARSSON
Keyword(s):  
Prostate Cancer

1625: Neuroligin 4 ISOFORM Y: A Novel Marker for Prostate Cancer

2007 ◽  
Vol 177 (4S) ◽  
pp. 538-539
Author(s):  
Joseph F. Pazona ◽  
C. Shad Thaxton ◽  
Neema Navai ◽  
Brian T. Helfand ◽  
Lee C. Zhao ◽  
...  
Keyword(s):  
Prostate Cancer
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