Browsing by Subject "Prostatic Neoplasms"

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Open Access
MST1 is a multifunctional caspase-independent inhibitor of androgenic signaling
(2011) Cinar, B.; Collak F.K.; Lopez, D.; Akgul, S.; Mukhopadhyay, N.K.; Kilicarslan, M.; Gioeli, D.G.; Freeman, M.R.
The MST1 serine - threonine kinase, a component of the RASSF1-LATS tumor suppressor network, is involved in cell proliferation and apoptosis and has been implicated in cancer. However, the physiologic role of MST1 in prostate cancer (PCa) is not well understood. Here, we investigated the possibility of a biochemical and functional link between androgen receptor (AR) and MST1 signaling. We showed that MST1 forms a protein complex with AR and antagonizes AR transcriptional activity as shown by coimmunoprecipitation (co-IP), promoter reporter analysis, and molecular genetic methods. In vitro kinase and site-specific mutagenesis approaches indicate that MST1 is a potent AR kinase; however, the kinase activity of MST1 and its proapoptotic functions were shown not to be involved in inhibition of AR. MST1 was also found in AR - chromatin complexes, and enforced expression of MST1 reduced the binding of AR to a well-characterized, androgen-responsive region within the prostate-specific antigen promoter. MST1 suppressed PCa cell growth in vitro and tumor growth in mice. Because MST1 is also involved in regulating the AKT1 pathway, this kinase may be an important new link between androgenic and growth factor signaling and a novel therapeutic target in PCa. ©2011 AACR.
Open Access
System for MR image-guided prostate interventions: Canine study
(Radiological Society of North America, Inc., 2003) Susil, R. C.; Krieger, A.; Derbyshire, J. A.; Tanacs, A.; Whitcomb, L. L.; Fichtinger, G.; Atalar, Ergin
The purpose of this study was to demonstrate the use of a transrectal system that enables precise magnetic resonance (MR) image guidance and monitoring of prostate interventions. The system used a closed-bore 1.5-T MR imaging unit and enables one to take advantage of the higher signal-to-noise ratio achieved with traditional magnet designs, which is crucial for accurate targeting and monitoring of prostate interventions. In the first of the four canine studies, reliable needle placement, with all needles placed within 2 mm of the desired target site, was achieved. In two other studies, MR imaging was used to monitor distribution of injected contrast agent solution (gadopentetate dimeglumine mixed with trypan blue dye) in and around the prostate, thereby confirming that solution had been delivered to the desired tissue and also detecting faulty injections. In the final study, accurate placement and MR imaging of brachytherapy seeds in the prostate were demonstrated. The described system provides a flexible platform for a variety of minimally invasive MR image-guided therapeutic and diagnostic prostate interventions. © RSNA, 2003.