Adrie van Bokhoven

University of Colorado, Denver, Colorado, United States

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Publications (59)247.06 Total impact

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    ABSTRACT: Factors associated with worsening of benign prostatic hyperplasia (BPH) are not well understood. We measured inflammatory markers from prostate biopsies to study if inflammation is related to BPH clinical progression. We measured inflammatory cell markers CD45, CD4, CD8, and CD68 in transition zone biopsies from 859 men in the Medical Therapy of Prostatic Symptoms (MTOPS) biopsy sub-study. Using novel imaging techniques, we quantified amounts of moderate/severe inflammation. BPH clinical progression was defined as a confirmed ≥4 point increase in the AUA Symptom Score (AUA-SS) from baseline, or occurrence of urinary incontinence, or acute urinary retention (AUR). Baseline clinical parameters including concomitant medication use were determined. Kaplan-Meier curves and multivariate Cox proportional hazard models were used to determine risk for progression. Inflammation as measured by CD45, CD4, and CD68 increased risk for clinical progression of BPH. CD4 showed the highest risk where men in the highest tertile of moderate/severe inflammation were at twice the risk of progression compared to men in the lower two tertiles combined [Hazard ratio (HR)=2.03, p=0.001]. Inflammation was more strongly associated with progression defined by AUR or incontinence [HR ranging from 2.39 (CD8, p=0.03) to 3.08 (CD4, p=0.01] than an AUA-SS increase (CD4: HR=1.86, p=0.01). Men who reported use of NSAIDs or steroids at baseline tended to be at higher risk for progression. Although our data show that inflammation increases the risk of progression, our findings suggest that inflammation plays a greater role in men who have conditions requiring anti-inflammatory medications. Copyright © 2015 American Urological Association Education and Research, Inc. Published by Elsevier Inc. All rights reserved.
    The Journal of urology 03/2015; DOI:10.1016/j.juro.2015.03.103 · 3.75 Impact Factor
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    ABSTRACT: We used next-generation, state-of-the-art, culture-independent methodology to survey urine microbiota of UCPPS males and control participants enrolled in the MAPP Network to investigate a possible microbial etiology. Male UCPPS patients and matched controls were asked to provide VB1, VB2 and VB3 urine specimens. Specimens were analyzed with Ibis T-5000 Universal Biosensor technology to provide comprehensive identification of bacterial and select fungal species. Differences between UCPPS and control study participants for presence of species or species variation within a higher taxonomic grouping (genus) were evaluated using permutational multivariate analysis of variance and logistic regression. VB1 and VB2 urine specimens were obtained from 110 (VB3 in 67) UCPPS participants and 115 (VB3 in 62) controls. A total of 78, 73 and 54 species (42, 39 and 27 genera) were detected in VB1, VB2 and VB3 respectively. Mean (SD) VB1, VB2 and VB3 species count per person was 1.62 (1.28), 1.38 (1.36) and 1.33(1.24) for cases and 1.75(1.32), 1.23(1.15) and 1.56 (0.97) for controls respectively. Overall species and genus composition differed significantly between UCPPS and control participants in VB1 (p=0.002 species level, p=0.004 genus level) with Burkholderia cenocepacia over represented in UCPPS cases. No significant differences were observed at any level in VB2 or VB3 samples. Assessment of baseline culture-independent microbiological data from male subjects enrolled in the MAPP Network has identified over representation of B cenocepacia in UCPPS. Future studies are planned to further evaluate microbiota associations with variable and changing UCPPS symptom patterns. Copyright © 2015 American Urological Association Education and Research, Inc. Published by Elsevier Inc. All rights reserved.
    The Journal of Urology 01/2015; DOI:10.1016/j.juro.2015.01.037 · 3.75 Impact Factor
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    ABSTRACT: Standardization of sample collection, shipping, and storage has been a major focus of biorepositories servicing large, multi-institute studies. The standardization of total protein concentration measurements may also provide an important metric for characterizing biospecimens. The measurement of total protein concentration in urine is challenging because of widely variable sample dilutions obtained in the clinic and the lack of a reference matrix for use with a standard curve and blank subtraction. Urinary proteins are therefore typically precipitated and reconstituted in a reference solution before quantitation. We have tested three different methods for protein precipitation and evaluated them using variability in total protein concentration measurement as a metric. The methods were tested on four urine samples ranging from very concentrated to very dilute. A method using a commercially available kit provided the most reproducible results, with average coefficients of variation <10%. Addition of a freeze/thaw did not lead to significant protein loss or additional variability. Samples were titrated and the measurements obtained appeared to be linearly correlated with sample starting volume. This method was applied to analysis of 77 urine biorepository samples and provided reproducible results when the same sample was assayed on different microwell plates.
    Journal of biomolecular techniques: JBT 10/2014; DOI:10.7171/jbt.14-2504-004
  • Cancer Research 10/2014; 74(19 Supplement):1675-1675. DOI:10.1158/1538-7445.AM2014-1675 · 9.28 Impact Factor
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    ABSTRACT: Objective To investigate the association between the length of the polymorphic trinucleotide CAG microsatellite repeats in exon 1 of the AR gene and the risk of prostate cancer containing TMPRSS2:ETS fusion genes. Methods This nested case-control study came from subjects enrolled in the Prostate Cancer Prevention Trial and included 195 biopsy-proven prostate cancer cases with a known TMPRSS2:ETS status and 1344 matched controls. Results There was no association between the CAG repeat length and the risk of TMPRSS2:ETS–positive (odds ratio, 0.97; 95% confidence interval, 0.91-1.04) or TMPRSS2:ETS–negative prostate cancer (odds ratio, 1.04; 95% confidence interval, 0.97-1.11) and in patients with low- or high-grade disease. Conclusion Our findings suggested that AR CAG repeats are not associated with TMPRSS2:ETS formation in prostate cancer.
    Urology 10/2014; 74(19 Supplement). DOI:10.1158/1538-7445.AM2014-1863 · 2.13 Impact Factor
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    ABSTRACT: The "Multidisciplinary Approach to the Study of Chronic Pelvic Pain" (MAPP) Research Network was established by the NIDDK to better understand the pathophysiology of urologic chronic pelvic pain syndromes (UCPPS), to inform future clinical trials and improve clinical care. The evolution, organization, and scientific scope of the MAPP Research Network, and the unique approach of the network's central study and common data elements are described.
    BMC Urology 08/2014; 14(1):58. DOI:10.1186/1471-2490-14-58 · 1.94 Impact Factor
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    ABSTRACT: Transrectal ultrasound guided prostate biopsies often fail to diagnose prostate cancer with 90% of cores reported as benign. Thus, it is desirable to target prostate cancer lesions while reducing the sampling of benign tissue. The concentrations of natural fluorophores in prostate tissue fluctuate with disease states. Hence, fluorescence spectroscopy could be used to quantify these fluctuations to identify prostate cancer. An optical biopsy needle with a light sensitive optical probe at the tip of the inner needle was developed to take prostate biopsies after measuring tissue fluorescence with a laboratory fluorometer. The optical probe consists of eight 100 μm fibers for tissue excitation and a single 200 μm fiber to capture fluorescence spectra. Random biopsy cores were taken from 20 surgically excised prostates after measuring fluorescence spectra of tissue between 295-550nm for several excitations between 280-350nm. Each biopsy core was histopathologically classified and correlated with corresponding spectra. Prostate biopsies were grouped into benign or malignant based on the histological findings. Out of 187 biopsy cores, 109 were benign and 78 were malignant. Partial least square analysis of tissue spectra was performed to identify diagnostically significant principal components as potential classifiers. A linear support vector machine and leave-one-out cross validation method was employed for tissue classification. Study results show 86% sensitivity, 87% specificity, 90% negative predictive value, and 83% positive predictive value for benign versus malignant prostate tissue classification. This study demonstrates potential clinical applications of fluorescence spectroscopy guided optical biopsy needle for prostate cancer diagnosis with the consequent improvement of patient care.
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    ABSTRACT: To investigate the association between the length of the polymorphic trinucleotide CAG microsatellite repeats in exon 1 of the AR gene and the risk of prostate cancer containing TMPRSS2:ETS fusion genes. This nested case-control study came from subjects enrolled in the Prostate Cancer Prevention Trial and included 195 biopsy-proven prostate cancer cases with a known TMPRSS2:ETS status and 1344 matched controls. There was no association between the CAG repeat length and the risk of TMPRSS2:ETS-positive (odds ratio, 0.97; 95% confidence interval, 0.91-1.04) or TMPRSS2:ETS-negative prostate cancer (odds ratio, 1.04; 95% confidence interval, 0.97-1.11) and in patients with low- or high-grade disease. Our findings suggested that AR CAG repeats are not associated with TMPRSS2:ETS formation in prostate cancer.
    Urology 05/2014; 84(1). DOI:10.1016/j.urology.2014.03.015 · 2.13 Impact Factor
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    ABSTRACT: Introduction and Objective: High grade (HG) prostatic cancer (PCa) (Gleason grades 4 & 5) correlate with poorer clinical outcome. Due to sampling error, transrectal ultrasound guided prostate biopsies often fail to diagnose HG PCa. Consequently, patients are often upgraded following prostatectomy. Diffuse reflectance spectra (DRS) discriminate healthy from malignant tissues depending in part on tissue morphology/architecture; hence DRS may be useful to differentiate cancer grades. We investigated whether DRS can be used to diagnose HG PCa. Methods: An optical biopsy needle with a light sensitive sensor was prototyped to take prostate biopsies after measuring DRS with a laboratory fluorometer. The optical sensor consists of eight 100m fibers for tissue excitation and a single 200m fiber to capture DRS. We obtained correlative biopsy cores from surgically excised prostates after measuring DRS between 500-700nm. Histopathology of tissue within the measurement window was correlated with corresponding spectra. Gleason score 3+3 cancer was classified as low grade (LG), Gleason score ≥7 as HG, and otherwise as benign. Partial least square analysis of tissue spectra was performed to identify partial least square components (PLSCs) as potential classifiers. Using linear support vector machine (SVM) and leave-one-out cross validation methods, a selection of PLSCs were tested for their ability to classify biopsy tissue. Results: A total of 187 biopsies taken from 20 prostates were studied. By histopathology we classified 29 as HG cancer, 49 as LGand 109 as benign within the measurement window. Four different SVMs, each with different sets of PLSCs were used for binary classification of prostate tissue as summarized in the table. Classification Type Sensitivity Specificity Negative Predictive Value Positive Predictive Value High Grade versus Benign 76% 80% 93% 50% High Grade versus Low Grade 76% 73% 84% 63% Low Grade versus Benign 65% 71% 82% 50% Malignant versus Benign 70% 73% 77% 65% Conclusions: Optical biopsy needle guided by DRS can differentiate with sufficient accuracy LG from HG cancer . This method may be applied for more precise targeting of HG PCa lesions, providing more accurate assessment of grade of the disease, with the consequent improvement of patient care. To confirm these findings, DRS data from in vivo studies are required. We anticipate that the presence of blood flow may affect tissue morphology in a positive manner as angiogenesis becomes a major contributing factor to further improve detection results.
    The Journal of Urology 04/2014; 191(4):e593. DOI:10.1016/j.juro.2014.02.1644 · 3.75 Impact Factor
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    ABSTRACT: Prostate biopsies are usually taken from the peripheral rather than anterior region of the prostate. Consequently, tumors originating from the anterior apical region and transition zones may be under-sampled. We examined whether addition of transrectal anterior biopsy (TAB) would improve efficacy of prostate biopsies. Simulations of TAB and sextant biopsy (SB) were performed using computer models of 86 autopsy prostates (AP) and 40 radical prostatectomy (RP) specimens. TAB was obtained bilaterally from apex, mid, and base regions by advancing the biopsy needle 5 mm-35 mm beyond the prostatic capsule. A phase I clinical trial with 114 patients was conducted to determine the performance of an extended biopsy protocol consisting of TAB, SB, and laterally-directed biopsy (LDB). The overall cancer detection rates of SB and TAB were 33% and 55% for AP series (p = 0.00003); 60% and 88% for RP series (p = 0.006). Alternatively, SB + bilateral apical TAB and SB + bilateral mid TAB had cancer detection rates of 45% and 42% for AP series; 80% and 78% for RP series. The extended biopsy protocol detected cancer in 33% (38/114) of patients with 29, 25, and 15 diagnosed by SB, LDB, and bilateral apical TAB, respectively. Patients diagnosed by bilateral apical TAB versus SB (p = 0.01) and LDB (p = 0.02) were statistically significant. Without bilateral apical TAB, the overall cancer detection rate decreased to 30% (34/114). Inclusion of bilateral TAB from apical region for first time and repeat prostate biopsies may increase diagnosis of prostate cancer. The clinical significance of these findings needs further investigations and clinical follow up.
    The Canadian Journal of Urology 10/2013; 20(5):6897-6906. · 0.91 Impact Factor
  • M Scott Lucia, Adrie van Bokhoven
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    ABSTRACT: Thirty years have witnessed dramatic changes in the manner in which we diagnose and manage prostate cancer. With prostate-specific antigen screening, there was a shift towards smaller, clinically localized tumors. Tumors are often multifocal and display phenotypic and molecular heterogeneity. Pathologic evaluation of tissue obtained by needle biopsy remains the gold standard for the diagnosis and risk assessment of prostate cancer. Years of experience with grading, along with changes in the amount of biopsy tissue obtained and diagnostic tools available, have produced shifts in grading practices among genitourinary pathologists. Trends in Gleason grading and advances in pathological risk assessment are reviewed with particular emphasis on recent Gleason grading modifications of the International Society of Urologic Pathology. Efforts to maximize the amount of information from pathological specimens, whether it be morphometric, histochemical, or molecular, may improve predictive accuracy of prostate biopsies. New diagnostic techniques are needed to optimize management decisions.
    JNCI Monographs 12/2012; 2012(45):157-61. DOI:10.1093/jncimonographs/lgs029
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    ABSTRACT: Finasteride, an inhibitor of 5α-reductase (type II), lowers intraprostatic dihydrotestosterone (DHT), which is reflected in serum as reduced 5α-androstane-3α,17β-diol glucuronide (3α-dG). It also modestly increases serum testosterone (T), estrone (E(1)), and estradiol (E(2)). In this altered hormonal milieu, it is unknown whether serum concentrations of these hormones are associated with prostate cancer risk. In this nested case-control study of men in the finasteride arm of the Prostate Cancer Prevention Trial, sex steroid hormones and sex hormone binding globulin were measured at baseline and approximately 3-year posttreatment in 553 prostate cancer cases and 694 controls. Median posttreatment changes in concentrations of 3α-dG, T, E(1), and E(2) were -73.8%, +10.1%, +11.2%, and +7.5% (all P < 0.001), respectively. Neither the pre- nor posttreatment concentrations of 3α-dG, nor its change, were associated with risk. Pretreatment, high concentrations of E(1) and low concentrations of T were associated with increased cancer risk [OR; 95% confidence interval (CI) quartile 4 vs. 1: 1.38 (0.99-1.93) P(trend) = 0.03; 0.64 (0.43-0.93) P(trend) = 0.07, respectively]. Posttreatment, high concentrations of both E(1) and E(2) were associated with increased cancer risk [OR; 95% CI quartile 4 vs. 1: 1.54 (1.09-2.17) P(trend) = 0.03; 1.49 (1.07-2.07) P(trend) = 0.02, respectively]. Among finasteride-treated men, concentrations of 3α-dG were not associated with total or Gleason grades 2 to 6, 7 to 10, or 8 to 10 cancer. High serum estrogens may increase cancer risk when intraprostatic DHT is pharmacologically lowered. Impact: Low posttreatment serum estrogens may identify men more likely to benefit from use of finasteride to prevent prostate cancer. Cancer Epidemiol Biomarkers Prev; 21(10); 1823-32. ©2012 AACR.
    Cancer Epidemiology Biomarkers & Prevention 08/2012; 21(10):1823-32. DOI:10.1158/1055-9965.EPI-12-0695 · 4.32 Impact Factor
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    ABSTRACT: Cadmium, a widespread toxic pollutant of occupational and environmental concern, is a known human carcinogen. The prostate is a potential target for cadmium carcinogenesis, although the underlying mechanisms are still unclear. Furthermore, cadmium may induce cell death by apoptosis in various cell types, and it has been hypothesized that a key factor in cadmium-induced malignant transformation is acquisition of apoptotic resistance. We investigated the in vitro effects produced by cadmium exposure in normal or tumor cells derived from human prostate epithelium, including RWPE-1 and its cadmium-transformed derivative CTPE, the primary adenocarcinoma 22Rv1 and CWR-R1 cells and LNCaP, PC-3 and DU145 metastatic cancer cell lines. Cells were treated for 24 hours with different concentrations of CdCl(2) and apoptosis, cell cycle distribution and expression of tumor suppressor proteins were analyzed. Subsequently, cellular response to cadmium was evaluated after siRNA-mediated p53 silencing in wild type p53-expressing RWPE-1 and LNCaP cells, and after adenoviral p53 overexpression in p53-deficient DU145 and PC-3 cell lines. The cell lines exhibited different sensitivity to cadmium, and 24-hour exposure to different CdCl(2) concentrations induced dose- and cell type-dependent apoptotic response and inhibition of cell proliferation that correlated with accumulation of functional p53 and overexpression of p21 in wild type p53-expressing cell lines. On the other hand, p53 silencing was able to suppress cadmium-induced apoptosis. Our results demonstrate that cadmium can induce p53-dependent apoptosis in human prostate epithelial cells and suggest p53 mutation as a possible contributing factor for the acquisition of apoptotic resistance in cadmium prostatic carcinogenesis.
    PLoS ONE 01/2012; 7(3):e33647. DOI:10.1371/journal.pone.0033647 · 3.53 Impact Factor
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    ABSTRACT: To examine the incidence and prognostic value of circulating tumor cells (CTCs) in urothelial cancer (UC). The detection of CTCs is prognostic in several cancer types. A total of 44 subjects with UC were assessed for CTCs using CellSearch Technology and 7.5 mL of peripheral blood, sorted by magnetic separation (epithelial cell adhesion molecule positive) and immunofluorescent staining (positive for cytokeratin 8, 18, or 19, negative for CD45, positive for 4',6-diamidino-2-phenylindole) to identify the CTCs. Five (17%) of 30 subjects with clinically localized and 7 (50%) of 14 subjects with metastatic UC had ≥1 detectable CTC (range 1-177). Six subjects had ≥5 CTCs. Fluorescence in situ hybridization analysis was performed in 20 samples from 18 unique subjects using the UroVysion probe set. Copy number gains consistent with neoplasm were observed in those with measurable CTCs but not in any of the CTC-negative samples tested. With a median follow-up of 337 days, all 7 patients with metastasis and detectable CTCs had died compared with 3 (43%) of the 7 with metastasis but without detectable CTCs. CTCs are commonly observed in metastatic UC. CTCs were observed in 50% of the patients with metastatic UC tested. Fluorescence in situ hybridization analysis confirmed the aneusomic chromosomal content in the CTCs. These findings suggest that measurable CTCs might be prognostic for shortened survival in patients with metastatic UC, although the optimal threshold for a "positive" finding is unknown. CTCs were also detected in a subset of patients with clinically localized disease, identifying a potential high-risk, preoperative group for future study.
    Urology 08/2011; 78(4):863-7. DOI:10.1016/j.urology.2011.05.045 · 2.13 Impact Factor
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    ABSTRACT: Introduction and Objective: Random transrectal prostate biopsies often fail to diagnose prostate cancer (PCa) and to accurately grade and stage this disease. The concentrations of natural fluorophores (eg: tryptophan) in prostate tissue fluctuate with disease states. Thus, fluorescence spectroscopy could quantify these fluctuations to identify PCa. The objective of this research is to determine the potential clinical utility of an optical biopsy needle to diagnose PCa. Methods: An optical biopsy needle with a light sensitive optical probe at the tip of the inner needle was developed to take prostate biopsies using BARD MAGNUM gun while measuring tissue fluorescence with a fluorometer. Optical probe consists of eight 100m fibers for tissue excitation and a single 200m fiber to capture fluorescence spectra. We took random biopsy cores from 10 prostates ex vivo after measuring emission spectra between 295-550nm from tissue fluorescence for excitation wavelengths between 280-350nm. Each biopsy core was histopathologically classified and correlated with their respective spectra. Prostate biopsies were grouped into benign or malignant based on the histological findings within 1mm length of each core’s distal-end. Partial least square analysis of tissue spectra was performed to identify principal components (PCs) as potential classifiers. Using linear support vector machine and leave-one-out cross validation method, selected PCs were tested for their ability to classify benign vs. malignant prostatic tissue. Results: A total of 104 biopsies, 73 benign and 31 malignant, were studied. P values for PC1-PC5 as potential classifiers are shown in Table I. Based on Pearson correlation coefficients, one set of statistically significant (p<0.05) but least correlative PCs were identified: PC1-PC3 each at 290 and 330nm, and PC1 & PC2 at 350nm (shown in bold). These PCs provided 83.9% sensitivity, 95.9% specificity, 91.2% positive predictive value, and 93.3% negative predictive value for benign vs. malignant prostatic tissue classification. Conclusions: Optical biopsy needle guided by tissue fluorescence can differentiate ex vivo benign vs. malignant prostatic tissues. This method could be applied in vivo for more precise targeting of PCa lesions, providing more accurate assessment of grade and stage of disease, with the consequent improvement of patient care. Table I: Principle Components and corresponding p values Principle Components Excitation Wavelengths 280nm 290nm 300nm 330nm 340nm 350nm PC1 7.82 x 10-6 5.42 x 10-5 4.57 x 10-6 2.08 x 10-4 1.24 x 10-4 1.16 x 10-5 PC2 1.28 x 10-5 1.45 x 10-5 2.92 x 10-6 3.04 x 10-3 2.40 x 10-3 2.91 x 10-3 PC3 6.50 x 10-5 3.48 x 10-7 1.38 x 10-3 0.02 0.09 0.02 PC4 3.11 x 10-3 9.49 x 10-3 5.83 x 10-3 2.59 x 10-4 8.16 x 10-4 3.41 x 10-3 PC5 0.14 0.63 0.04 4.58 x 10-3 0.05 5.96 x 10-3
    The Journal of Urology 04/2011; 185(4). DOI:10.1016/j.juro.2011.02.2334 · 3.75 Impact Factor
  • The Journal of Urology 04/2011; 185(4). DOI:10.1016/j.juro.2011.02.2047 · 3.75 Impact Factor
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    ABSTRACT: Prostate cancer in men has a high mortality and morbidity due to metastatic disease. The pathobiology of prostate cancer metastasis is not well understood and cell lines and animal models that recapitulate the complex nature of the disease are needed. Therefore, the goal of the study was to establish and characterize a new prostate cancer line derived from a dog with spontaneous prostate cancer. A new cell line (Leo) was derived from a dog with spontaneous prostate cancer. Immunohistochemistry and PCR were used to characterize the primary prostate cancer and xenografts in nude mice. Subcutaneous tumor growth and metastases in nude mice were evaluated by bioluminescent imaging, radiography and histopathology. In vitro chemosensitivity of Leo cells to therapeutic agents was measured. Leo cells expressed the secretory epithelial cytokeratins (CK)8, 18, and ductal cell marker, CK7. The cell line grew in vitro (over 75 passages) and was tumorigenic in the subcutis of nude mice. Following intracardiac injection, Leo cells metastasized to the brain, spinal cord, bone, and adrenal gland. The incidence of metastases was greatest to the central nervous system (80%) with a lower incidence to bone (20%) and the adrenal glands (16%). In vitro chemosensitivity assays demonstrated that Leo cells were sensitive to Velcade and an HDAC-42 inhibitor with IC(50) concentrations of 1.9 nm and 0.95 µm, respectively. The new prostate cancer cell line (Leo) will be a valuable model to investigate the mechanisms of the brain and bone metastases.
    The Prostate 01/2011; 71(12):1251-63. DOI:10.1002/pros.21341 · 3.57 Impact Factor
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    ABSTRACT: It is currently estimated that infections and inflammatory responses are linked to 15-20% of all deaths from cancer worldwide. Many studies point to an important role of inflammation in prostate growth, although the contribution of inflammation to benign prostatic hyperplasia and prostate cancer is not completely understood. There is an unmet need for epidemiologic and molecular pathologic approaches to address the issue of inflammation and prostate cancer. Here we review the published evidence with respect to the involvement of inflammation and infection in prostate cancer. We also present an overarching hypothesis that chronic inflammation associated with aging and infection may play an important role in the etiology and progression of prostate cancer. As such, chronic inflammation may represent an important therapeutic target in prostate cancer.
    Drugs of today (Barcelona, Spain: 1998) 12/2010; 46(12):929-43. DOI:10.1358/dot.2010.46.12.1537942 · 1.00 Impact Factor
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    ABSTRACT: Silibinin is a polyphenolic flavonolignan derived from milk thistle (Silybum marianium) with anti-oxidant properties. The purpose of the current trial was to determine the tissue and blood effects of high-dose silybin-phytosome in prostate cancer patients. Subjects with localized prostate cancer planning for a prostatectomy were eligible to enroll. Six patients received 13 g of silybin-phytosome daily with six additional participants serving as control subjects. Patients in the treatment arm received silybin-phytosome for 14-31 days (mean was 20 days) prior to surgery. Silibinin blood levels were measured 1 hr after the first silybin-phytosome dose with a mean value of 19.7 microM. Trough silibinin levels were assessed at the end of the trial with an average concentration of 1.2 microM. In contrast to the high peak levels of silibinin observed in blood, the highest silibinin level observed in the harvested prostate tissue was 496.6 pmol/g. There were no significant differences noted in baseline and post-treatment blood levels of IGF-I and IGFBP-3. One of the treated patients developed a grade 4 post-operative thromboembolic event. The other observed toxicities in the treatment group were mild: four subjects had diarrhea and one had asymptomatic grade 2 hyperbilirubinemia which was transient. High-dose oral silybin-phytosome achieves high blood concentrations transiently, but low levels of silibinin are seen in prostate tissue. Silibinin's lack of tissue penetration may be explained by its short half-life, the brief duration of therapy in this study or an active process removing silibinin from the prostate.
    The Prostate 01/2010; 70(8):848-55. DOI:10.1002/pros.21118 · 3.57 Impact Factor
  • The Journal of Urology 04/2009; 181(4):654-654. DOI:10.1016/S0022-5347(09)61836-X · 3.75 Impact Factor

Publication Stats

2k Citations
247.06 Total Impact Points

Institutions

  • 2011–2015
    • University of Colorado
      • Department of Pathology
      Denver, Colorado, United States
  • 2014
    • University of Michigan
      • Department of Urology
      Ann Arbor, Michigan, United States
    • Chonbuk National University
      Tsiuentcheou, Jeollabuk-do, South Korea
  • 1993–2001
    • Radboud University Medical Centre (Radboudumc)
      • Department of Human Genetics
      Nymegen, Gelderland, Netherlands
    • KU Leuven
      • Department of Human Genetics
      Leuven, VLG, Belgium
  • 1998
    • University of Tsukuba
      • Department of Urology
      Tsukuba, Ibaraki-ken, Japan
  • 1989–1992
    • Radboud University Nijmegen
      • Department of Biochemistry
      Nijmegen, Provincie Gelderland, Netherlands
    • Catholic University of Louvain
      Лувен-ла-Нев, Walloon, Belgium