Publications by authors named "Joel Slaton"

50 Publications

Phase II multi-center trial of optical coherence tomography as an adjunct to white light cystoscopy for intravesical real time imaging and staging of bladder cancer.

Urol Oncol 2021 Apr 29. Epub 2021 Apr 29.

Scott Department of Urology, Dan L. Duncan Cancer Center, Baylor College of Medicine, Houston, TX. Electronic address:

Background: Optical coherence tomography (OCT) is a novel imaging modality that provides microstructural information of different tissue layers using near-infrared light. This prospective, multicenter phase II trial aimed to assess the accuracy of OCT-assisted cystoscopy for bladder tumor staging.

Methods: Patients with primary or recurrent bladder tumors (Ta,T1) identified by outpatient cystoscopy were included. The primary objective was to assess the accuracy and positive predictive value of for determining tumor stage ≥T1 correlated by histopathology. 72 suspicious lesions from 63 patients were eligible to analyze in the study. All suspected lesions were evaluated with conventional cystoscopy, interpreted in real-time using OCT, and then resected. All results were compared to pathology. A total of 363 OCT images of tumor and normal mucosa in 25 patients were obtained to evaluate diagnostic efficacy of the computer-aided texture analysis algorithm.

Results: Sensitivity and specificity for predicting invasive tumors (≥ T1, n = 17) were 58.8% and 92.7% for cystoscopy, 64.7% and 100% for OCT-assisted cystoscopy, respectively. Accuracy of cystoscopy and OCT-assisted cystoscopy for predicting invasive tumor was 84.7% and 91.7% (P = 0.063), respectively. Cystoscopy and OCT-assisted cystoscopy correctly predicted T stage in 52/72 and 59/72 cases, respectively (P = 0.016). Cystoscopy missed 2 more invasive tumors than OCT-assisted cystoscopy. Cystoscopy (14.3%, 1/7) and OCT-assisted cystoscopy (28.6%, 2/7) showed relatively low sensitivity in detecting muscle invasion. Computer aided texture analysis demonstrated 75.1% sensitivity, 64.0% specificity, and 74.4% accuracy for differentiating tumor and normal urothelium.

Conclusion: OCT-assisted cystoscopy is a real time noninvasive and simple procedure that enhanced the accuracy of staging bladder tumors and prediction of any tumor invasion. Though the study did not meet the prespecified primary endpoint, OCT imaging is a promising adjunct to cystoscopy that may supplement intraoperative decision-making during transurethral resection of bladder tumors and additional prospective studies are warranted.
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http://dx.doi.org/10.1016/j.urolonc.2021.03.026DOI Listing
April 2021

Matrix metalloproteinase and heparin-stimulated serine proteinase activities in post-prostate massage urine of men with prostate cancer.

Exp Mol Pathol 2017 12 22;103(3):300-305. Epub 2017 Nov 22.

Minneapolis VA Medical Center, University of Minnesota, Minneapolis, MN 55417, United States; Department of Laboratory Medicine and Pathology, University of Minnesota, Minneapolis, MN 55417, United States; Masonic Cancer Center, University of Minnesota, Minneapolis, MN 55417, United States. Electronic address:

Proteinases secreted by the prostate gland have a reproductive function in cleaving proteins in the ejaculate and in the female reproductive tract, but some may have a fundamental role in disease and pathological processes including cancer. The purpose of this study was to determine if there were differences in proteinase activities in urine samples collected following prostate massage of men positive (CaP) or negative (no evidence of malignancy, NEM) for biopsy determined prostate cancer. Matrix metalloproteinase (MMP) and serine proteinase activities were detected using protein substrate zymography. There were no differences in activities of MMP-2, proMMP-9, and MMP-9/NGAL (neutrophil gelatinase associated lipocalin) complex (gelatin substrate) in men with detected prostate cancer, although the latter two were somewhat diminished. A caseinolytic activity of about 75kDa inhibited by calcium did not differ between the NEM and CaP groups. Heparin stimulated calcium sensitive gelatinolytic activities of approximately 22, 42, and 60kDa, but did not affect activities of MMP-2, MMP-9, or the 75kDa caseinolytic activity. The 22, 42, and 60kDa activities appear to be serine proteinases since they were inhibited by benzamidine. There was a significant decrease in the 22kDa heparin-stimulated serine proteinase activity in urines of men with cancer. Proteinase expression and activities, perhaps in combination with other potential markers, may prove useful in urine for detection and evaluation of prostate cancer.
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http://dx.doi.org/10.1016/j.yexmp.2017.11.015DOI Listing
December 2017

Phosphatidylserine targeted single-walled carbon nanotubes for photothermal ablation of bladder cancer.

Nanotechnology 2018 Jan;29(3):035101

School of Biomedical Engineering, University of Oklahoma, 202 W. Boyd Street, Norman, OK 73019, United States of America.

Bladder cancer has a 60%-70% recurrence rate most likely due to any residual tumour left behind after a transurethral resection (TUR). Failure to completely resect the cancer can lead to recurrence and progression into higher grade tumours with metastatic potential. We present here a novel therapy to treat superficial tumours with the potential to decrease recurrence. The therapy is a heat-based approach in which bladder tumour specific single-walled carbon nanotubes (SWCNTs) are delivered intravesically at a very low dose (0.1 mg SWCNT per kg body weight) followed 24 h later by a short 30 s treatment with a 360° near-infrared light that heats only the bound nanotubes. The energy density of the treatment was 50 J cm, and the power density that this treatment corresponds to is 1.7 W cm, which is relatively low. Nanotubes are specifically targeted to the tumour via the interaction of annexin V (AV) and phosphatidylserine, which is normally internalised on healthy tissue but externalised on tumours and the tumour vasculature. SWCNTs are conjugated to AV, which binds specifically to bladder cancer cells as confirmed in vitro and in vivo. Due to this specific localisation, NIR light can be used to heat the tumour while conserving the healthy bladder wall. In a short-term efficacy study in mice with orthotopic MB49 murine bladder tumours treated with the SWCNT-AV conjugate and NIR light, no tumours were visible on the bladder wall 24 h after NIR light treatment, and there was no damage to the bladder. In a separate survival study in mice with the same type of orthotopic tumours, there was a 50% cure rate at 116 days when the study was ended. At 116 days, no treatment toxicity was observed, and no nanotubes were detected in the clearance organs or bladder.
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http://dx.doi.org/10.1088/1361-6528/aa9c0cDOI Listing
January 2018

Phase IIa, randomized placebo-controlled trial of single high dose cholecalciferol (vitamin D) and daily Genistein (G-2535) versus double placebo in men with early stage prostate cancer undergoing prostatectomy.

Am J Clin Exp Urol 2016 20;4(2):17-27. Epub 2016 Sep 20.

Department of Medicine, University of Wisconsin School of Medicine and Public HealthMadison, WI, USA; University of Wisconsin Carbone Cancer CenterMadison, WI, USA.

Introduction And Objectives: Prostate cancer (PCa) represents an important target for chemoprevention given its prolonged natural history and high prevalence. Epidemiologic and laboratory data suggest that vitamin D and genistein (soy isoflavone) may decrease PCa progression. The effect of vitamin D on prostate epithelial cell proliferation and differentiation is well documented and genistein may augment this affect through inhibition of the CYP24 enzyme, which is responsible for intracellular vitamin D metabolism. In addition, both genistein and vitamin D inhibit the intraprostatic synthesis of prostaglandin E2, an important mediator of inflammation. The objectives of this prospective multicenter trial were to compare prostate tissue calcitriol levels and down-stream related biomarkers in men with localized prostate cancer randomized to receive cholecalciferol and genistein versus placebo cholecalciferol and placebo genistein during the pre-prostatectomy period.

Methods: Men undergoing radical prostatectomy were randomly assigned to one of two treatment groups: (1) cholecalciferol (vitamin D) 200,000 IU as one dose at study entry plus genistein (G-2535), 600 mg daily or (2) placebo cholecalciferol day 1 and placebo genistein PO daily for 21-28 days prior to radical prostatectomy. Serum and tissue analyses were performed and side-effects recorded.

Results: A total of 15 patients were enrolled, 8 in the placebo arm and 7 in the vitamin D + genistein (VD + G) arm. All patients were compliant and completed the study. No significant differences in side effect profiles were noted. Utilization of the VD + G trended toward increased calcitriol serum concentrations when compared to placebo (0.104 ± 0.2 vs. 0.0013 ± 0.08; p=0.08); however, prostate tissue levels did not increase. Calcidiol levels did not change (p=0.5). Immunohistochemistry for marker analyses using VECTRA automated quantitation revealed a increase in AR expression (p=0.04) and a trend toward increased TUNEL staining (p=0.1) in prostate cancer tissues in men randomized to receive VD + G compared to placebo.

Conclusions: In this first study testing the combination of a single, large dose of cholecalciferol and daily genistein, the agents were well tolerated. While an increase in AR expression suggesting differentiation was observed, it is difficult to draw firm conclusions regarding the bioactivity of the combination given the sample size.
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http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5069272PMC
September 2016

Disparities in long-term radiographic follow-up after cystectomy for bladder cancer: Analysis of the SEER-Medicare database.

Urol Ann 2016 Apr-Jun;8(2):178-83

Department of Urology, University of Oklahoma, School of Medicine, Oklahoma City, Oklahoma, USA.

Introduction: It is uncertain whether there are disparities related to receiving long-term radiographic follow-up after cystectomy performed for bladder cancer, and whether intensive follow-up influences survival.

Materials And Methods: We analyzed 2080 patients treated with cystectomy between 1992 and 2004 isolated from the SEER-Medicare database. The number of abdominal computerized tomography scans performed in patients surviving 2 years after surgery was used as an indicator of long-term radiographic follow-up to exclude patients with early failures.

Results: Patients were mainly males (83.18%), had a mean age at diagnosis of 73.4 ± 6.6 (standard deviation) years, and mean survival of 4.6 ± 3.2 years. Multivariate analysis showed age >70 (odds ratio [OR]: 0.796, 95% confidence interval [CI]: 0.651-0.974), African American race (OR: 0.180, 95% CI: 0.081-0.279), and Charlson comorbidity score >2 (OR: 0.694, 95% CI: 0.505-0.954) to be associated with lower odds of long-term radiographic follow-up. Higher disease stage (Stage T4N1) (OR: 1.873, 95% CI: 1.491-2.353), higher quartile for education (OR: 5.203, 95% CI: 1.072-9.350) and higher quartile for income (OR: 6.940, 95% CI: 1.444-12.436) were associated with increased odds of long-term radiographic follow-up. Interestingly, more follow-up with imaging after cystectomy did not improve cancer-specific or overall survival in these patients.

Conclusion: There are significant age, race, and socioeconomic disparities in long-term radiographic follow-up after radical cystectomy. However, more radiographic follow-up may not be associated with better survival.
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http://dx.doi.org/10.4103/0974-7796.164852DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4839235PMC
May 2016

Comprehensive Molecular Characterization of Papillary Renal-Cell Carcinoma.

N Engl J Med 2016 Jan 4;374(2):135-45. Epub 2015 Nov 4.

Background: Papillary renal-cell carcinoma, which accounts for 15 to 20% of renal-cell carcinomas, is a heterogeneous disease that consists of various types of renal cancer, including tumors with indolent, multifocal presentation and solitary tumors with an aggressive, highly lethal phenotype. Little is known about the genetic basis of sporadic papillary renal-cell carcinoma, and no effective forms of therapy for advanced disease exist.

Methods: We performed comprehensive molecular characterization of 161 primary papillary renal-cell carcinomas, using whole-exome sequencing, copy-number analysis, messenger RNA and microRNA sequencing, DNA-methylation analysis, and proteomic analysis.

Results: Type 1 and type 2 papillary renal-cell carcinomas were shown to be different types of renal cancer characterized by specific genetic alterations, with type 2 further classified into three individual subgroups on the basis of molecular differences associated with patient survival. Type 1 tumors were associated with MET alterations, whereas type 2 tumors were characterized by CDKN2A silencing, SETD2 mutations, TFE3 fusions, and increased expression of the NRF2-antioxidant response element (ARE) pathway. A CpG island methylator phenotype (CIMP) was observed in a distinct subgroup of type 2 papillary renal-cell carcinomas that was characterized by poor survival and mutation of the gene encoding fumarate hydratase (FH).

Conclusions: Type 1 and type 2 papillary renal-cell carcinomas were shown to be clinically and biologically distinct. Alterations in the MET pathway were associated with type 1, and activation of the NRF2-ARE pathway was associated with type 2; CDKN2A loss and CIMP in type 2 conveyed a poor prognosis. Furthermore, type 2 papillary renal-cell carcinoma consisted of at least three subtypes based on molecular and phenotypic features. (Funded by the National Institutes of Health.).
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http://dx.doi.org/10.1056/NEJMoa1505917DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4775252PMC
January 2016

Tenfibgen ligand nanoencapsulation delivers bi-functional anti-CK2 RNAi oligomer to key sites for prostate cancer targeting using human xenograft tumors in mice.

PLoS One 2014 15;9(10):e109970. Epub 2014 Oct 15.

Research Service, Minneapolis VA Health Care System, Minneapolis, Minnesota, United States of America; Department of Laboratory Medicine and Pathology, University of Minnesota, Minneapolis, Minnesota, United States of America; Masonic Cancer Center, University of Minnesota, Minneapolis, Minnesota, United States of America; Department of Urology, University of Minnesota, Minneapolis, Minnesota, United States of America.

Protected and specific delivery of nucleic acids to malignant cells remains a highly desirable approach for cancer therapy. Here we present data on the physical and chemical characteristics, mechanism of action, and pilot therapeutic efficacy of a tenfibgen (TBG)-shell nanocapsule technology for tumor-directed delivery of single stranded DNA/RNA chimeric oligomers targeting CK2αα' to xenograft tumors in mice. The sub-50 nm size TBG nanocapsule (s50-TBG) is a slightly negatively charged, uniform particle of 15 - 20 nm size which confers protection to the nucleic acid cargo. The DNA/RNA chimeric oligomer (RNAi-CK2) functions to decrease CK2αα' expression levels via both siRNA and antisense mechanisms. Systemic delivery of s50-TBG-RNAi-CK2 specifically targets malignant cells, including tumor cells in bone, and at low doses reduces size and CK2-related signals in orthotopic primary and metastatic xenograft prostate cancer tumors. In conclusion, the s50-TBG nanoencapsulation technology together with the chimeric oligomer targeting CK2αα' offer significant promise for systemic treatment of prostate malignancy.
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http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0109970PLOS
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4198192PMC
June 2015

Alvimopan accelerates gastrointestinal recovery after radical cystectomy: a multicenter randomized placebo-controlled trial.

Eur Urol 2014 Aug 26;66(2):265-72. Epub 2014 Feb 26.

Indiana University Medical Center, Indianapolis, IN, USA.

Background: Radical cystectomy (RC) for bladder cancer is frequently associated with delayed gastrointestinal (GI) recovery that prolongs hospital length of stay (LOS).

Objective: To assess the efficacy of alvimopan to accelerate GI recovery after RC.

Design, Setting, And Participants: We conducted a randomized double-blind placebo-controlled trial in patients undergoing RC and receiving postoperative intravenous patient-controlled opioid analgesics.

Intervention: Oral alvimopan 12 mg (maximum: 15 inpatient doses) versus placebo.

Outcome Measurements And Statistical Analysis: The two-component primary end point was time to upper (first tolerance of solid food) and lower (first bowel movement) GI recovery (GI-2). Time to discharge order written, postoperative LOS, postoperative ileus (POI)-related morbidity, opioid consumption, and adverse events (AEs) were evaluated. An independent adjudication of cardiovascular AEs was performed.

Results And Limitations: Patients were randomized to alvimopan (n=143) or placebo (n=137); 277 patients were included in the modified intention-to-treat population. The alvimopan cohort experienced quicker GI-2 recovery (5.5 vs 6.8 d; hazard ratio: 1.8; p<0.0001), shorter mean LOS (7.4 vs 10.1 d; p=0.0051), and fewer episodes of POI-related morbidity (8.4% vs 29.1%; p<0.001). The incidence of opioid consumption and AEs or serious AEs (SAEs) was comparable except for POI, which was lower in the alvimopan group (AEs: 7% vs 26%; SAEs: 5% vs 20%, respectively). Cardiovascular AEs occurred in 8.4% (alvimopan) and 15.3% (placebo) of patients (p=0.09). Generalizability may be limited due to the exclusion of epidural analgesia and the inclusion of mostly high-volume centers utilizing open laparotomy.

Conclusions: Alvimopan is a useful addition to a standardized care pathway in patients undergoing RC by accelerating GI recovery and shortening LOS, with a safety profile similar to placebo.

Patient Summary: This study examined the effects of alvimopan on bowel recovery in patients undergoing radical cystectomy for bladder cancer. Patients receiving alvimopan experienced quicker bowel recovery and had a shorter hospital stay compared with those who received placebo, with comparable safety.

Trial Registration: ClinicalTrials.gov identifier NCT00708201.
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http://dx.doi.org/10.1016/j.eururo.2014.02.036DOI Listing
August 2014

Alvimopan, a peripherally acting μ-opioid receptor antagonist, is associated with reduced costs after radical cystectomy: economic analysis of a phase 4 randomized, controlled trial.

J Urol 2014 Jun 14;191(6):1721-7. Epub 2013 Dec 14.

University of Texas M.D. Anderson Cancer Center, Houston, Texas. Electronic address:

Purpose: We evaluated the effect of alvimopan treatment vs placebo on health care utilization and costs related to gastrointestinal recovery in patients treated with radical cystectomy in a randomized, phase 4 clinical trial.

Materials And Methods: Resource utilization data were prospectively collected and evaluated by cost consequence analysis. Hospital costs were estimated from 2012 Medicare reimbursement rates and medication wholesale acquisition costs. Differences in base case mean costs between the study cohorts for total postoperative ileus related costs (hospital days, study drug, nasogastric tubes, postoperative ileus related concomitant medication and postoperative ileus related readmissions) and total combined costs (postoperative ileus related, laboratory, electrocardiograms, nonpostoperative ileus related concomitant medication and nonpostoperative ileus related readmission) were evaluated by probabilistic sensitivity analysis using a bootstrap approach.

Results: Mean hospital stay was 2.63 days shorter for alvimopan than placebo (mean±SD 8.44±3.05 vs 11.07±8.23 days, p=0.005). Use of medications or interventions likely intended to diagnose or manage postoperative ileus was lower for alvimopan than for placebo, eg total parenteral nutrition 10% vs 25% (p=0.001). Postoperative ileus related health care costs were $2,340 lower for alvimopan and mean total combined costs were decreased by $2,640 per patient for alvimopan vs placebo. Analysis using a 10,000-iteration bootstrap approach showed that the mean difference in postoperative ileus related costs (p=0.04) but not total combined costs (p=0.068) was significantly lower for alvimopan than for placebo.

Conclusions: In patients treated with radical cystectomy alvimopan decreased hospitalization cost by reducing the health care services associated with postoperative ileus and decreasing the hospital stay.
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http://dx.doi.org/10.1016/j.juro.2013.12.015DOI Listing
June 2014

Contemporary treatment of low risk stage I non-seminomatous germ cell testicular tumors: a survey of the Society of Urologic Oncology.

Urol Oncol 2012 Nov-Dec;30(6):749-51

Department of Urologic Surgery, University of Minnesota, Minneapolis, MN 55421, USA.

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http://dx.doi.org/10.1016/j.urolonc.2011.05.017DOI Listing
July 2013

Polysaccharide-K augments docetaxel-induced tumor suppression and antitumor immune response in an immunocompetent murine model of human prostate cancer.

Int J Oncol 2012 Apr 12;40(4):905-13. Epub 2011 Dec 12.

Bastyr University Research Institute, 14500 Juanita Dr NE, Kenmore, WA 98028, USA.

Advanced castration-resistant prostate cancer has high mortality rates and limited treatment options. Novel therapies are needed to better contend with this disease. Polysaccharide-K® (PSK), an extract of the mushroom Trametes versicolor, has immunomodulatory and tumor suppressive activities. PSK is used in Asia as a cancer immunotherapy. However, its benefit in combination with taxanes for prostate cancer is unknown. We examined whether PSK would enhance docetaxel-induced apoptosis and augment anti-tumor immune responses in orthotopic tumors using transgenic adenocarcinoma of the mouse prostate (TRAMP)-C2-bearing mice. Combining PSK with docetaxel induced significantly higher tumor suppression than either treatment alone (p<0.05), including a reduction in tumor proliferation and enhanced apoptosis. Combined PSK and docetaxel treatment led to a lower decrease in number of white blood cells than docetaxel alone, an effect accompanied by increased numbers of tumor-infiltrating CD4+ and CD8+ T cells. PSK with or without docetaxel significantly enhanced mRNA expression of IFN-γ compared to control, but did not significantly alter T-regulatory FoxP3 mRNA expression in tumors. PSK also augmented docetaxel-induced splenic natural killer cell cytolytic activity against YAC-1 target cells (p=0.045). This study is the first to show that PSK enhances docetaxel-induced prostate cancer tumor suppression, apoptosis and antitumor responses.
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http://dx.doi.org/10.3892/ijo.2011.1292DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3584555PMC
April 2012

Challenges and potential solutions to meeting accrual goals in a Phase II chemoprevention trial for prostate cancer.

Contemp Clin Trials 2012 Mar 11;33(2):279-85. Epub 2011 Nov 11.

Department of Epidemiology, H. Lee Moffitt Cancer Center & Research Institute at University of South Florida College of Medicine, Tampa, FL 33612, USA.

Objective: The goal of this report is to describe the on going strategies, successes, challenges and solutions for recruitment in this multi-center, phase II chemoprevention trial targeting men at high risk for prostate cancer.

Methods: We developed and implemented a multi-center clinical trial in institutions with supportive infrastructure, lead by a recruitment team of experienced and committed physicians and clinical trial staff, implementing multi-media and community outreach strategies to meet recruitment goals. Screening logs were reviewed to identify trends as well as patient, protocol and infrastructure -related barriers impacting accrual and revisions to protocol implemented.

Results: Between January 2008 and February 2011 a total of 3547 individuals were prescreened with 94% (n=3092) determined to be ineligible based on diagnosis of cancer or benign biopsy results. Of these, 216 were considered eligible for further screening with 52% (n=113) declining to participate due to patient related factors and 14% (n=29) eliminated due to protocol-related criteria for exclusion. Ninety-four (94) subjects consented to participate with 34% of these subjects (n=74) meeting all eligibility criteria to be randomized to receive study agent or placebo. Across all sites, 99% of the recruitment of subjects in this clinical trial is via physician recruitment and referral with less than 1% responding to other recruitment strategies.

Conclusion: A contemporary approach to subject recruitment and frequent evaluation is needed to assure responsiveness to emerging challenges to accrual and the evolving scientific literature. A focus on investing on improving systems for physician recruitment may be key to meeting recruitment target in chemoprevention trials.
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http://dx.doi.org/10.1016/j.cct.2011.11.004DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3268882PMC
March 2012

The risk of bladder cancer in patients diagnosed with other primary neoplasms: analysis of the SEER database.

Urol Oncol 2013 Aug 23;31(6):862-5. Epub 2011 Jul 23.

Department of Urologic Surgery, Biostatistical Consulting Laboratory, University of Minnesota, Minneapolis, MN 55455, USA.

Objective: We evaluated patients with history of previous malignancy to determine risk of an ensuing bladder cancer.

Materials And Methods: The National Cancer Institute's Surveillance, Epidemiology, and End Results 9 registry database from 1973 to 1999 (SEER) was reviewed for patients with initial primary cancers in oral cavity and pharynx, colon and rectum, respiratory system, breast, prostate, testis, or penis. This group of patients was then examined to identify subsequent separate primary malignancies in the bladder. Comparison was made to the incidence of bladder cancer in the general population to determine a standardized incidence ratio (SIR). Additional analysis was performed based on age at diagnosis, stage, gender, race, and use of external beam radiation for treatment of initial cancer.

Results: A total of 7,289 (0.5%) of patients had a bladder cancer following their initial malignancy. Patients with prostate cancer had the largest increase in risk of bladder cancer with a SIR of 8.24, and all initial cancer groups had an elevated risk of bladder cancer relative to the general population. External beam radiation and non-White gender were associated with an increased risk of bladder cancer. Older age at diagnosis of the initial cancer correlated with a lower risk of subsequent bladder cancer.

Conclusions: This study suggests an increased risk of bladder cancer following a separate initial cancer. Lower threshold for working up those patients for bladder cancer may be warranted.
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http://dx.doi.org/10.1016/j.urolonc.2011.06.005DOI Listing
August 2013

Systemic administration of antisense oligonucleotides simultaneously targeting CK2α and α' subunits reduces orthotopic xenograft prostate tumors in mice.

Mol Cell Biochem 2011 Oct 15;356(1-2):21-35. Epub 2011 Jul 15.

Research Service, Minneapolis VA Health Care System, University of Minnesota, Minneapolis, MN 55417, USA.

CK2 is a highly conserved, ubiquitous, signal responsive protein serine/threonine kinase. CK2 promotes cell proliferation and suppresses apoptosis, and increased CK2 expression is observed in all cancers examined. We previously reported that direct injection of antisense (AS) CK2α phosphorothioate oligonucleotides (PTO) into xenograft prostate tumors in mice significantly reduced tumor size. Downregulation of CK2α in tumor cells in vivo appeared to result in overexpression of CK2α' protein. This suggested that in cancer cells downregulation of CK2α might be compensated by CK2α' in vivo, prompting us to design a bispecific (bs) AS PTO (bs-AS-CK2) targeting both catalytic subunits. bs-AS-CK2 reduced CK2α and α' protein expression, decreased cell proliferation, and induced apoptosis in cultured cells. Biodistribution studies of administered bs-AS-CK2 oligonucleotide demonstrated its presence in orthotopic prostate xenograft tumors. High dose injections of bs-AS-CK2 resulted in no damage to normal liver or prostate, but induced extensive cell death in tumor tissue. Intraperitoneal treatment with bs-AS-CK2 PTO decreased orthotopic tumor size and downregulated both CK2 mRNA and protein expression. Tumor reduction was accomplished using remarkably low doses and was improved by dividing the dose using a multi-day schedule. Decreased expression of the key signaling pathway proteins NF-κB p65 and AKT was also observed. We propose that the molecular downregulation of CK2 through bispecific targeting of the two catalytic subunits may be uniquely useful for therapeutic elimination of tumors.
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http://dx.doi.org/10.1007/s11010-011-0943-xDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3893918PMC
October 2011

A three-layer competition-based giant magnetoresistive assay for direct quantification of endoglin from human urine.

Anal Chem 2011 Apr 21;83(8):2996-3002. Epub 2011 Mar 21.

Department of Medicinal Chemistry, College of Pharmacy, University of Minnesota, Minneapolis, Minnesota 55455, USA.

This study presents a three-layer competition-based assay for ultrasensitive detection and quantification of endoglin from unprocessed human urine samples using a giant magnetoresistive (GMR) sensor and high-moment magnetic nanoparticle-based biosensing technology. This biosensing platform detects as few as 1000 copies of endoglin at concentrations as low as 83 fM with high detection specificity and has a three-order dynamic range. The results reveal that endoglin levels in urine have the potential to predict for the presence of prostate cancer and to distinguish between prostate cancers of different grades.
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http://dx.doi.org/10.1021/ac2005229DOI Listing
April 2011

Role for toll-like receptor 4 in TNF-alpha secretion by murine macrophages in response to polysaccharide Krestin, a Trametes versicolor mushroom extract.

Fitoterapia 2010 Oct 13;81(7):914-9. Epub 2010 Jun 13.

Bastyr University, Department of Basic Sciences, School of Natural Health Sciences, Kenmore, WA 98028, USA.

Woody fungi and yeast preparations show promise in cancer treatment by activating anti-tumor immune responses. Macrophages (J774A.1) were treated with PSK, Reishi extract, scleroglucan or vehicle control. Pre-incubation with TLR4 blocking antibody inhibited TNF-alpha secretion by both J774A.1 cells and primary splenocytes but had inconclusive effect on scleroglucan-induced secretion of TNF-alpha. PSK induced TNF-alpha and IL-6 secretion by wild type but not by TLR4-deficient peritoneal macrophages. We conclude that constituents from PSK act as ligands for TLR4 receptors leading to induction of TNF-alpha and IL-6 inflammatory cytokines. Receptor-mediated differences may be due to structural differences in beta glucans or non-glucan constituents.
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http://dx.doi.org/10.1016/j.fitote.2010.06.002DOI Listing
October 2010

Emergence of protein kinase CK2 as a key target in cancer therapy.

Biofactors 2010 May-Jun;36(3):187-95

Cellular and Molecular Biochemistry Research Laboratory, Research Service, Minneapolis V.A. Medical Center, and Department of Laboratory Medicine and Pathology, University of Minnesota, Minneapolis, MN 55417, USA.

Protein kinase CK2, a protein serine/threonine kinase, plays a global role in activities related to cell growth, cell death, and cell survival. CK2 has a large number of potential substrates localized in diverse locations in the cell including, for example, NF-kappaB as an important downstream target of the kinase. In addition to its involvement in cell growth and proliferation it is also a potent suppressor of apoptosis, raising its key importance in cancer cell phenotype. CK2 interacts with diverse pathways which illustrates the breadth of its impact on the cellular machinery of both cell growth and cell death giving it the status of a "master regulator" in the cell. With respect to cancer, CK2 has been found to be dysregulated in all cancers examined demonstrating increased protein expression levels and nuclear localization in cancer cells compared with their normal counterparts. We originally proposed CK2 as a potentially important target for cancer therapy. Given the ubiquitous and essential for cell survival nature of the kinase, an important consideration would be to target it specifically in cancer cells while sparing normal cells. Towards that end, our design of a tenascin based sub-50 nm (i.e., less than 50 nm size) nanocapsule in which an anti-CK2 therapeutic agent can be packaged is highly promising because this formulation can specifically deliver the cargo intracellularly to the cancer cells in vivo. Thus, appropriate strategies to target CK2 especially by molecular approaches may lead to a highly feasible and effective approach to eradication of a given cancer.
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http://dx.doi.org/10.1002/biof.96DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2916697PMC
September 2010

Use of tumor necrosis factor-alpha-coated gold nanoparticles to enhance radiofrequency ablation in a translational model of renal tumors.

Urology 2010 Aug 8;76(2):494-8. Epub 2010 May 8.

Department of Urology, Laboratory Medicine and Pathology, University of Minnesota, Minneapolis, MN, USA.

Objectives: Radiofrequency ablation (RFA) has been most effective when the tumors are small, exophytic, and away from vital structures. We enlarged the size of the ablation kill zone by infusing a 30-nm tumor necrosis factor-alpha and polyethylene glycol-coated gold nanoparticle (CYT-6091, CytImmune Sciences, Inc.) before ablation in a rabbit kidney tumor model.

Materials And Methods: A total of 37 New Zealand White rabbits had VX-2 tumors implanted into their bilateral kidneys; they were then split into 3 treatment groups of 10 rabbits each and a sham group of 7 rabbits as follows: (1) CYT-6091 only, (2) RFA only, (3) CYT-6091 followed 4 hours later by RFA. Gross and microscopic measurements of the ablation size as well as histologic analysis using hematoxylin and eosin staining were performed to determine the effect of CYT-6091 on the ablation.

Results: The RFA + CYT-6091 group had a larger zone of complete cell death than the RFA-only group when measured on microscopic examination (0.30 +/- 0.07 vs 0.23 +/- 0.03 mL, P = .03). The zone of partially ablated tissue was smaller in the RFA + CYT-6091 group than in the RFA-only group (0.08 +/- 0.02 vs 0.13 +/- 0.05 mL, P = .01).

Conclusions: We have demonstrated the efficacy of CYT-6091 in enhancing RFA in a translational kidney tumor model. The potential usage of CYT-6091 to improve RFA of renal cell carcinoma merits further study.
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http://dx.doi.org/10.1016/j.urology.2010.01.085DOI Listing
August 2010

Association between lymph node density and disease specific survival in patients with penile cancer.

J Urol 2009 Dec 17;182(6):2721-7. Epub 2009 Oct 17.

Department of Urologic Oncology, University of Texas M. D. Anderson Cancer Center, Houston, Texas 77030, USA.

Purpose: We assessed the value of lymph node density for predicting disease specific survival after lymphadenectomy for penile cancer.

Materials And Methods: Data were collected retrospectively in 75 and prospectively in 88 consecutive patients with squamous cell carcinoma of the penis treated at M. D. Anderson Cancer Center between 1979 and 2007. We identified 45 patients with penile cancer and nodal metastasis who underwent lymphadenectomy with curative intent. Lymph node density was analyzed as a categorical variable by grouping patients into 2 or 3 categories based on equal percents. We explored the prognostic value of lymph node density for predicting disease specific survival in this cohort.

Results: Median followup was 23.7 months in all patients. By the time of analysis 22 patients had died, including 18 (82%) of penile cancer and 4 (18%) of other causes. Median lymph node density in patients alive or dead of other causes was 3.4% (IQR 2.9-5.9) compared to 43.3% (IQR 15.6-80) in those dead of disease (p <0.001). Median lymph node density in all patients was 6.7%. Estimated 5-year disease specific survival in patients with lymph node density 6.7% or less was significantly better than that in patients with lymph node density greater than 6.7% (91.2%, 95% CI 53.9-98.8 vs 23.3%, 95% CI 7.0-45.1, p <0.001). In models comparing lymph node density to known prognostic features lymph node density remained statistically significant, while the other factors were no longer statistically associated with disease specific survival.

Conclusions: Lymph node density proved to be a significantly better prognosticator of disease specific survival than the current TNM nodal staging system in patients with penile cancer and nodal involvement. Further independent validation is required to determine the clinical usefulness of lymph node density in this patient population.
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http://dx.doi.org/10.1016/j.juro.2009.08.029DOI Listing
December 2009

Adjuvant approaches to enhance cryosurgery.

J Biomech Eng 2009 Jul;131(7):074003

Department of Biomedical Engineering, University of Minnesota, Minneapolis, MN 55455, USA.

Molecular adjuvants can be used to enhance the natural destructive mechanisms of freezing within tissue. This review discusses their use in the growing field of combinatorial or adjuvant enhanced cryosurgery for a variety of disease conditions. Two important motivations for adjuvant use are: (1) increased control of the local disease in the area of freezing (i.e., reduced local recurrence of disease) and (2) reduced complications due to over-freezing into adjacent tissues (i.e., reduced normal functional tissue destruction near the treatment site). This review starts with a brief overview of cryosurgical technology including probes and cryogens and major mechanisms of cellular, vascular injury and possible immunological effects due to freeze-thaw treatment in vivo. The review then focuses on adjuvants to each of these mechanisms that make the tissue more sensitive to freeze-thaw injury. Four broad classes of adjuvants are discussed including: thermophysical agents (eutectic forming salts and amino acids), chemotherapuetics, vascular agents and immunomodulators. The key issues of selection, timing, dose and delivery of these adjuvants are then elaborated. Finally, work with a particularly promising vascular adjuvant, TNF-alpha, that shows the ability to destroy all cancer within a cryosurgical iceball is highlighted.
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http://dx.doi.org/10.1115/1.3156804DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4934372PMC
July 2009

Increased aggressiveness of human prostate PC-3 tumor cells expressing cell surface localized membrane type-1 matrix metalloproteinase (MT1-MMP).

J Androl 2009 May-Jun;30(3):259-74. Epub 2009 Jan 8.

Department of Pharmacology, University of Minnesota, Minneapolis, Minnesota, USA.

Membrane type-1 matrix metalloproteinase (MT1-MMP) is a multidomain transmembrane endopeptidase with a major role in physiological and pathological processes through proteolysis of extracellular matrix and other pericellular proteins. We examined cell surface function of MT1-MMP in PC-3 human prostate tumor cells selected for metastasis in nude mice (PC-3-LN4), or transfected with the full-length wild-type (WT) MT1-MMP or with the mutant form lacking the cytoplasmic tail (Delta C-MT1-MMP). Enhanced cell surface MT1-MMP was determined by fluorescence-activated cell sorting analysis and evidenced mechanistically by increased activation of proMMP-2 and invasion into type-I collagen gels. PC-3 cells overexpressing MT1-MMP grew faster than mock-transfected control cells subcutaneously in nude mice. MT1-MMP localized in caveolae, as judged by immunofluorescence microscopy and sucrose-gradient, detergent-resistant cell fractionation. Delta C-MT1-MMP was strongly associated with caveolae, whereas the WT form was present in both caveolae and noncaveolae fractions. The role of plasma membrane MT1-MMP was supported by localization of MT1-MMP by immunofluorescence microscopy at the cell surface of tumor cells in primary prostate cancers. Increased plasma membrane localization of MT1-MMP, either in caveolae or in other lipid raft structures, is a mechanism to localize this proteinase in contact with extracellular matrix and other pericellular proteins, the cleavage of which can facilitate prostate cancer cell invasion and metastasis.
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http://dx.doi.org/10.2164/jandrol.108.006494DOI Listing
July 2009

WL-276, an antagonist against Bcl-2 proteins, overcomes drug resistance and suppresses prostate tumor growth.

Cancer Res 2008 Jun;68(11):4377-83

Department of Medicinal Chemistry, University of Minnesota, Minneapolis, Minnesota 55455, USA.

Patients with hormone-refractory prostate cancer (HRPC) have an estimated median survival of only 10 months because of acquired drug resistance, urging the need to develop therapies against the drug-resistant HRPC phenotype. Accumulating evidence suggests that overexpressing antiapoptotic Bcl-2 family proteins is at least partially responsible for the development of drug resistance among HRPC patients. Antagonizing the antiapoptotic Bcl-2 family proteins, therefore, is one potential approach to circumventing drug resistance in HRPC. WL-276 was developed as a small-molecule antagonist against antiapoptotic Bcl-2 family proteins, with binding potency comparable to (-)-gossypol. Overexpressing Bcl-2 or Bcl-X(L) failed to confer resistance to WL-276. WL-276 also effectively induced apoptosis in PC-3 cells. In addition, three PC-3 cell lines with acquired drug resistance against standard cancer chemotherapies were more sensitive to WL-276 than the parent PC-3 cell line. The increased cytotoxicity toward drug-resistant PC-3 cells shows the clinical potential of WL-276 against HRPC that is resistant to conventional therapies. The anticancer activity of WL-276 was manifested in its suppression of PC-3-induced prostate tumor growth in vivo. The selective toxicity of WL-276 against drug-resistant PC-3 cells and its in vivo suppression of PC-3 prostate tumor growth suggest that WL-276 is a promising lead candidate for the development of Bcl-2 antagonists against drug-resistant HRPC.
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http://dx.doi.org/10.1158/0008-5472.CAN-07-6590DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2410026PMC
June 2008

Protein kinase CK2--a key suppressor of apoptosis.

Adv Enzyme Regul 2008 30;48:179-87. Epub 2008 Apr 30.

Cellular and Molecular Biochemistry Research Laboratory (151), V.A. Medical Center, Department of Laboratory Medicine and Pathology, University of Minnesota, Minneapolis, MN 55417, USA.

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http://dx.doi.org/10.1016/j.advenzreg.2008.04.002DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2593134PMC
December 2008

Second prize: Comprehensive proteomic analysis of human calcium oxalate monohydrate kidney stone matrix.

J Endourol 2008 Jun;22(6):1161-7

Department of Urologic Surgery, Molecular Biology and Biophysics, University of Minnesota, Minneapolis, Minnesota, USA.

Background And Purpose: Previous efforts to identify the protein content of stone matrix have been limited by the lack of technology necessary to analyze the highly insoluble protein-crystalline complex. Our study objective is to characterize the matrix of calcium oxalate monohydrate (COM) stones using a comprehensive proteomics approach.

Materials And Methods: Seven pure COM stones were powdered, and proteins were extracted using four different buffer solutions. Detergent cleanup spin columns or concentrators were used to remove detergent and to exchange buffers before trypsin digestion. Tryptic peptides were analyzed with reversed-phase, high-performance liquid chromatography (RP-HPLC) and tandem mass spectrometry (MS/MS) using a QSTAR Pulsar i quadrapole time of flight mass spectrometer. Tandem mass spectra were searched against National Center for Biotechnology Information human nonredundant database using ProteinPilot 1.0 software (Applied Biosystems, Inc.) for protein hits; peptide MS/MS spectra were manually inspected.

Results: Of the four buffers, only 2% sodium dodecyl sulfate (SDS) samples had normal HPLC and MS/MS elution patterns. We identified 68 distinct proteins with 95% confidence. More than 50 of the proteins have not been previously identified in stone matrix. Of particular note, a significant number of inflammatory proteins were identified, including immunoglobulins, defensin -3, clusterin, complement C3a, kininogen, and fibrinogen.

Conclusions: SDS reducing buffer was efficient at solubilizing proteins from stone matrix for further MS-based proteomic analysis. A variety of cellular, structural, and plasma proteins comprise COM stone matrix. Several of the stone proteins are involved in cell injury pathways, which suggests that inflammation plays a role in human COM stone formation.
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http://dx.doi.org/10.1089/end.2007.0440DOI Listing
June 2008

Effects of soy protein isolate consumption on prostate cancer biomarkers in men with HGPIN, ASAP, and low-grade prostate cancer.

Nutr Cancer 2008 ;60(1):7-13

Department of Food Science and Nutrition, University of Minnesota, St Paul, MN 55455, USA.

Fifty-eight men at high risk of prostate cancer or with low-grade prostate cancer were randomly assigned to consume 1 of 3 protein isolates containing 40 g protein: 1) soy protein (SPI+, 107 mg isoflavones/d); 2) alcohol-washed soy protein (SPI-, <6 mg isoflavones/d); or 3) milk protein (MPI). Proliferating cell nuclear antigen (PCNA), epidermal growth factor receptor, B-cell non-Hodgkin lymphoma-2 (Bcl-2), and Bcl-2-associated X protein (Bax) were assessed in baseline and ending prostate biopsy cores. Serum collected at 0, 3, and 6 mo was analyzed for total and free prostate specific antigen (PSA). Consumption of SPI+ did not alter any of the prostate cancer tumor markers. Bax expression decreased from baseline in the SPI- group, resulting in lower Bax expression than the MPI group. PCNA expression also decreased from baseline in the SPI- group, but this was not different from the other 2 groups. PSA did not differ among the groups at 3 or 6 mo. Interestingly, a lower rate of prostate cancer developed in the soy groups compared to the milk group (P = 0.01). These data suggest that 6-mo SPI+ consumption does not alter prostate tissue biomarkers, SPI- consumption exerts mixed effects, and less prostate cancer is detected after 6 mo of soy consumption regardless of isoflavone content.
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http://dx.doi.org/10.1080/01635580701586770DOI Listing
May 2008

Soy protein isolate increases urinary estrogens and the ratio of 2:16alpha-hydroxyestrone in men at high risk of prostate cancer.

J Nutr 2007 Oct;137(10):2258-63

Department of Food Science and Nutrition, University of Minnesota, St. Paul, MN 55108, USA.

Specific estrogen metabolites may initiate and promote hormone-related cancers. In epidemiological studies, significantly lower excretion of urinary estradiol (E2) and lower ratio of urinary 2-hydroxy estrogens to 16alpha-hydroxyestrone (2:16 OH-E1) have been reported in prostate cancer cases compared to controls. Although soy supplementation has been shown to increase the ratio 2:16 OH-E1 in women, no studies to our knowledge have investigated the effects of soy supplementation on estrogen metabolism in men. The objective of this randomized controlled trial was to determine the effects of soy protein isolate consumption on estrogen metabolism in men at high risk for developing advanced prostate cancer. Fifty-eight men supplemented their habitual diets with 1 of 3 protein isolates: 1) isoflavone-rich soy protein isolate (SPI+) (107 mg isoflavones/d); 2) alcohol-washed soy protein isolate (SPI-) (<6 mg isoflavones/d); or 3) milk protein isolate (MPI), each providing 40 g protein/d. At 0, 3, and 6 mo of supplementation, the urinary estrogen metabolite profile was measured by GC-MS. Both soy groups had higher E2 excretion than the MPI group at 3 and 6 mo. After 6 mo of supplementation, the SPI+ group had a significantly higher urinary 2:16 OH-E1 ratio than the MPI group. Increased urinary E2 excretion and 2:16 OH-E1 ratio in men consuming soy protein isolate are consistent with studies in postmenopausal women and suggest that soy consumption may be beneficial in men at high risk of progressing to advanced prostate cancer as a result of effects on endogenous estrogen metabolism.
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http://dx.doi.org/10.1093/jn/137.10.2258DOI Listing
October 2007

Isoflavone-rich soy protein isolate suppresses androgen receptor expression without altering estrogen receptor-beta expression or serum hormonal profiles in men at high risk of prostate cancer.

J Nutr 2007 Jul;137(7):1769-75

Department of Food Science and Nutrition, University of Minnesota, Minneapolis, MN 55455, USA.

The purpose of this study was to determine the effects of soy protein isolate consumption on circulating hormone profiles and hormone receptor expression patterns in men at high risk for developing advanced prostate cancer. Fifty-eight men were randomly assigned to consume 1 of 3 protein isolates containing 40 g/d protein: 1) soy protein isolate (SPI+) (107 mg/d isoflavones); 2) alcohol-washed soy protein isolate (SPI-) (<6 mg/d isoflavones); or 3) milk protein isolate (0 mg/d isoflavones). For 6 mo, the men consumed the protein isolates in divided doses twice daily as a partial meal replacement. Serum samples collected at 0, 3, and 6 mo were analyzed for circulating estradiol, estrone, sex hormone-binding globulin, androstenedione, androstanediol glucuronide, dehydroepiandrosterone sulfate, dihydrotestosterone, testosterone, and free testosterone concentrations by RIA. Prostate biopsy samples obtained pre- and postintervention were analyzed for androgen receptor (AR) and estrogen receptor-beta expression by immunohistochemistry. At 6 mo, consumption of SPI+ significantly suppressed AR expression but did not alter estrogen receptor-beta expression or circulating hormones. Consumption of SPI- significantly increased estradiol and androstenedione concentrations, and tended to suppress AR expression (P = 0.09). Although the effects of SPI- consumption on estradiol and androstenedione are difficult to interpret and the clinical relevance is uncertain, these data show that AR expression in the prostate is suppressed by soy protein isolate consumption, which may be beneficial in preventing prostate cancer.
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http://dx.doi.org/10.1093/jn/137.7.1769DOI Listing
July 2007

CK2 signaling in androgen-dependent and -independent prostate cancer.

J Cell Biochem 2006 Oct;99(2):382-91

Cellular and Molecular Biochemistry Research Laboratory (151), Minneapolis Veterans Affairs Medical Center, Minneapolis, Minnesota 55417, USA.

Protein serine/threonine kinase casein kinase 2 (CK2) is a key player in cell growth and proliferation but is also a potent suppressor of apoptosis. CK2 has been found to be dysregulated in all the cancers that have been examined, including prostate cancer. Investigations of CK2 signaling in the prostate were originally initiated in this laboratory, and these studies have identified significant functional activities of CK2 in relation to normal prostate growth and to the pathobiology of androgen-dependent and -independent prostate cancer. We present a brief overview of these developments in the context of prostate biology. An important outcome of these studies is the emerging concept that CK2 can be effectively targeted for cancer therapy.
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http://dx.doi.org/10.1002/jcb.20847DOI Listing
October 2006

Angiomyofibroblastoma-like tumors (cellular angiofibroma).

Int J Urol 2006 Feb;13(2):177-9

Department of Urology, University of Minnesota, and VA Medical Center, Minneapolis, Minnesota 55455-0392, USA.

Angiomyofibroblastoma-like tumor (cellular angiofibroma) is a rare, circumscribed, slow-growing mesenchymal tumor that occurs predominantly in the vulva, perineum, and pelvis of women. We report two cases of this tumor in men arising as paratesticular masses of the scrotum, summarize the history of this tumor, and discuss why efforts should be made to differentiate it from aggressive angiomyxoma. Recommended treatment is complete surgical excision with long-term follow up exams, as local recurrence may occur many years after resection of the lesion.
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http://dx.doi.org/10.1111/j.1442-2042.2006.01255.xDOI Listing
February 2006

Risk factors for upper tract recurrence in patients undergoing long-term surveillance for stage ta bladder cancer.

J Urol 2006 Jan;175(1):74-7

Department of Urologic Surgery, University of Minnesota, Minneapolis, Minnesota, USA.

Purpose: While the evidence is clear that patients with carcinoma in situ or high grade T1 TCC of the bladder are at higher risk for developing UUT tumors, the role of imaging the UUT in patients with Ta tumors remains controversial. We hypothesized that the number and frequency of recurrences in patients with Ta disease would allow us to identify a population who should undergo routine UUT surveillance.

Materials And Methods: We reviewed our database of 375 patients who underwent resection of a stage Ta TCC between 1975 and 1995. Median followup was 6 years. Patients were stratified according to the presence of an UUT occurrence, rate and timing of superficial recurrences, and grade of the initial bladder tumor.

Results: Among the 375 patients 50% had no bladder recurrence, 25% had 1 tumor, 15% had 2 tumors, and 10% had 3 or more tumors. Average time between tumors was 17 months. UUT tumor developed in 13 patients (3.4%) at an average of 22 months after their initial bladder tumor. A high risk group consisting of patients who had 2 or more bladder recurrences recurring within 12 months of each other were at 4.5-fold the risk of UUT tumor.

Conclusions: Stage Ta bladder cancer patients with 2 or more recurrences of bladder tumors with a median of less than 12 months between recurrences are at higher risk for developing an UUT tumor and should be considered for more frequent UUT surveillance.
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http://dx.doi.org/10.1016/S0022-5347(05)00071-6DOI Listing
January 2006