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ABSTRACT: The three main treatment options for primary prostate cancer are surgery, radiation, and active surveillance. Surgical and radiation intervention for prostate cancer can be associated with significant morbidity. Therefore, accurate stratification predictive of outcome for prostate cancer patients is essential for appropriate treatment decisions. Nomograms that use clinical and pathologic variables are often used for risk prediction. Favorable outcomes exist even among men classified by nomograms as being at high risk of recurrence.
Previously, we identified a set of DNA-based biomarkers termed Genomic Evaluators of Metastatic Prostate Cancer (GEMCaP) and have shown that they can predict risk of recurrence with 80% accuracy. Here, we examined the risk prediction ability of GEMCaP in a high-risk cohort and compared it to a Kattan nomogram.
We determined that the GEMCaP genotype alone is comparable with the nomogram, and that for a subset of cases with negative lymph nodes improves upon it.
Thus, GEMCaP shows promise for predicting unfavorable outcomes for negative lymph node high-risk cases, where the nomogram falls short, and suggests that addition of GEMCaP to nomograms may be warranted.
Clinical Cancer Research 12/2009; 16(1):195-202. · 7.74 Impact Factor
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ABSTRACT: Prolonged bicalutamide treatment induced pathology regression although relapses with a more aggressive form of prostate cancer have been observed. This failure could be due to androgen receptor mutation. In the present work we hypothesized an alternative mechanism responsible for bicalutamide failure involving activity of ATP-binding cassette (ABC) pumps such as P-glycoprotein, Breast Cancer Receptor Protein (BCRP), and Multi Resistant Proteins (MRPs) that extrude the androgen antagonist from the cell membrane. As experimental models androgen-dependent (LnCap) and androgen-independent (PC-3) prostate cancer cell lines have been employed. Bicalutamide has been tested in the cell lines mentioned above in the absence and in the presence of MC18, our potent P-glycoprotein/BCRP/MRP1 inhibitor. The results displayed that bicalutamide antiproliferative effect at 72 h was ameliorated in LnCap cells (EC(50) from 51.9+/-6.1 microM to 17.8+/-2.6 microM in the absence and in the presence of MC18, respectively) and restored in PC-3 cells (EC(50) from 150+/-2.4 microM to 60+/-3.5 microM in the absence and in the presence of MC18, respectively). Moreover, we established the contribution of each transporter employing stable transfected cells (MDCK) overexpressing P-glycoprotein or BCRP or MRP1 pump. The results displayed that P-glycoprotein and BCRP were involved in bicalutamide efflux while MRP1 was unable to bind the antiandrogen drug.
European journal of pharmacology 11/2008; 601(1-3):38-42. · 2.59 Impact Factor
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ABSTRACT: In the present study epididymal and prostatic portions of human vas deferens were separately isolated and stimulated with exogenous noradrenaline to study their contractile properties. The results displayed that the epididymal tract produced a phasic-tonic response, while the prostatic strip produced only a phasic response suggesting a different functional role of each vas deferens segment. Moreover, it has been verified if alpha(1)-adrenoceptor antagonists doxazosin, alphuzosin and terazosin could differently block the noradrenaline response in each segment. Doxazosin, the most potent antagonist, displayed similar potency in epididymal and prostatic tract (pA(2)=8.51 and 8.42, respectively). Analogously, alphuzosin, although less potent than doxazosin, displayed in the same tracts a superimposed potency (pA(2)=7.25 and 7.30, respectively). In contrast with doxazosin and alphuzosin, terazosin displayed higher potency in blocking the contractile response in prostatic tract (pA(2)=7.67) than in epididymal segment (pA(2)=6.43). These results showed that alpha(1)-adrenoceptor antagonists doxazosin and alphuzosin, although with a different potency, did not discriminate between epididymal and prostatic segment while terazosin showed high potency in prostatic tract and only a moderate activity in epididymal section. Moreover, the biological model employed in our experiments could be a valid screening method to test the potential interferences of drugs indicated for bladder outlet obstruction with the peristaltic activity or the global tone of the human vas deferens.
European Journal of Pharmacology 01/2008; 577(1-3):150-5. · 2.52 Impact Factor
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Pamela L Paris,
Matthias D Hofer, Giancarlo Albo,
Rainer Kuefer,
Juergen E Gschwend,
Richard E Hautmann,
Jane Fridyland,
Jeffrey Simko,
Peter R Carroll,
Mark A Rubin,
Colin Collins
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ABSTRACT: The progression of organ-confined prostate cancer to metastatic cancer is inevitably fatal. Consequently, identification of structural changes in the genome and associated transcriptional responses that drive this progression is critical to understanding the disease process and the development of biomarkers and therapeutic targets. In this study, whole genome copy number changes in genomes of hormone-naïve lymph node metastases were profiled using array comparative genomic hybridization, and matched primaries were included for a subset. Matched primaries and lymph node metastases showed very similar copy number profiles that are distinct from primary tumors that fail to metastasize.
Neoplasia (New York, N.Y.) 01/2007; 8(12):1083-9. · 5.48 Impact Factor
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ABSTRACT: Prostate biopsy is a fundamental step in the diagnostic flow chart of prostate cancer. We have evaluated the influence of the number of cores taken on the tolerability and morbidity of the transperineal ultrasound-guided prostate biopsy. We have compared a group of 240 pts undergone 16 core prostate biopsy to an historical cohort of 100 pts undergone 10 core prostate biopsy. All the patients in both groups have been investigated about tolerability and morbidity of the procedure. No significant differences emerge between the two groups, and then we conclude that the number of cores taken does not influence the safety and compliance to the transperineal biopsy. This is a significant advantage compared to transrectal biopsy, as the number of cores influences the detection rate of prostate carcinoma.
Archivio italiano di urologia, andrologia: organo ufficiale [di] Società italiana di ecografia urologica e nefrologica / Associazione ricerche in urologia 01/2003; 74(4):279-81.
