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Shen R.,Iowa State University | Ying K.,Center for Prostate Disease Research | Wang Z.,Iowa State University | Schnable P.S.,Iowa State University
ICASSP, IEEE International Conference on Acoustics, Speech and Signal Processing - Proceedings | Year: 2016

Next-generation sequencing (NGS) has revolutionized the detection of structural variation in genome. Among NGS strategies, read depth is widely used and paramorphism information contained inside is generally ignored. We develop an algorithm that can fully exploit both read depth and paramorphism information. We embed mutation procedure in our system model for estimating prior likelihood of single nucleotide base. Hidden Markov model (HMM) is used to connect single base into segments and belief propagation algorithm is performed for the optimal solution of the HMM model. Simulations show promising results in detecting important types of structural variation. We have applied the algorithm on the maize B73 and MO17 genome data and compared the results with those obtained from arrayCGH method based micro-array data. Inconsistency between the two sets of data is discussed. © 2016 IEEE.

Vallone D.M.,American Legacy Foundation | Niederdeppe J.,Cornell University | Richardson A.K.,American Legacy Foundation | Patwardhan P.,Schroeder Institute for Tobacco Research and Policy Studies | And 2 more authors.
American Journal of Health Promotion | Year: 2011

Purpose. To assess the effectiveness of a large-scale, national smoking cessation media campaign, the EX campaign, across racial/ethnic and educational subgroups. Design. A longitudinal random-digit-dial panel study conducted prior to and 6 months following the national launch of the campaign. Setting. The sample was drawn from eight designated media markets in the United States. Subjects. The baseline survey was conducted on 5616 current smokers, aged 18 to 49 years, and 4067 (73% follow-up response rate) were resurveyed at the 6-month follow-up. Measures. The primary independent variable is confirmed awareness of the campaign advertising, and the outcome variables are follow-up cessation-related cognitions index score and quit attempts. Analysis. Multivariable logistic and linear regression analyses were conducted within racial/ ethnic and educational strata to assess the strength of association between confirmed awareness of campaign advertising and cessation-related outcomes. Results. Confirmed awareness of campaign advertising increased favorable cessation-related cognitions among Hispanics and quit attempts among non-Hispanic blacks, and increased favorable cessation-related cognitions and quit attempts among smokers with less than a high school education. Conclusions. These results suggest that the EX campaign may be effective in promoting cessationrelated cognitions and behaviors among minority and disadvantaged smokers who experience a disproportionate burden of tobacco-related illness and mortality. Copyright © 2011 by American Journal of Health Promotion, Inc.

Farrell J.,U.S. National Institutes of Health | Salter C.,U.S. National Institutes of Health | Cullen J.,Center for Prostate Disease Research | Mordkin R.,Virginia Hospital Center Physician Group Urology | Joel A.,Virginia Hospital Center Physician Group Urology
Urology Practice | Year: 2015

Introduction: The rate of post-prostate biopsy infection is increasing. We noted this trend in ourpractice and began using prebiopsy rectal swab cultures to direct antibiotic prophylaxis. Clinical investigation has shown that culture directed antibiotic prophylaxis is effective. We report our methods and results as validation that culture directed antibiotic prophylaxis works in the community. Methods: We retrospectively reviewed the charts of 686 consecutive patients who underwent transrectal prostate biopsy from March 2010 to April 2013. The electronic medical record was queried for the antibiotic prophylaxis used, rectal swab culture, post-biopsy infection, culture data and post-biopsy hospitalization if applicable. Prebiopsy rectal swab was incorporated into our practice in May 2012. Each patient received 3 days of fluoroquinolone prophylaxis or culture directed antibiotic prophylaxis. If antibiotic resistance to standard fluoroquinolone prophylaxis was identified, antibiotic prophylaxis was adjusted appropriately. Results: Of 543 patients who received standard fluoroquinolone prophylaxis 17 (3.1%) had infectious complications. Eight patients were hospitalized for post-biopsy sepsis and 4 received outpatient treatment for urinary tract infection. A total of 143 patients underwent prebiopsy rectal swabs and received culture directed antibiotic prophylaxis. Compared to standard antibiotic prophylaxis no patient treated with culture directed antibiotic prophylaxis after a rectal swab had infectious complications (p = 0.03). However, 19.5% of the patients in this group had resistant bacteria requiring alternative antibiotic prophylaxis. Conclusions: A prebiopsy rectal swab to direct antibiotic prophylaxis decreased post-biopsy infectious complications in the community setting. The strategy is simple and it improves patient safety. © 2015 American Urological Association Education and Research, Inc.

Rhim J.S.,Center for Prostate Disease Research
Methods in Molecular Biology | Year: 2013

Prostate cancer is the most common male cancer in the United States. Research on the mechanisms of prostate cancer progression has been limited by the lack of suitable in vitro systems. A hurdle in understanding the molecular genetic changes in prostate cancer has been the difficulty in establishing premalignant lesions and primary prostate tumors as in vitro cell cultures. Primary prostate epithelial cells grow for a finite life span and then senesce. Immortalization is defined by continuous growth of otherwise senescing cells and is believed to represent an early stage in tumor progression. To examine these early stages, we and others have developed in vitro models of prostate epithelial cell immortalization. Methods are described for the processing of primary human prostate biopsy samples and the generation of human prostate epithelial (HPE) cells in serum-free conditions. Retrovirus containing human telomerase reverse transcriptase (hTERT) is used for the immortalization of primary HPE cells, and the methods for the characterization of HPE cell lines are discussed. These in vitro prostate cell culture models are useful for the study of prostate normal and cancer stem cells, are critical for defining the mechanisms of prostate cancer progression and for testing preventive and therapeutic regimens. © 2013 Springer Science+Business Media, LLC.

Parker P.M.,U.S. Army | Rice K.R.,U.S. Army | Sterbis J.R.,U.S. Army | Chen Y.,Center for Prostate Disease Research | And 5 more authors.
Urology | Year: 2011

Objective: To compare clinicopathologic features and survival outcomes for men 50 years of age in relation to other age groups stratified by race to further define prostate cancer (CaP) in young men. Controversy exists regarding the appropriate age to undergo CaP screening, outcomes for early intervention, and whether there is unique age-associated tumor biology. We compared clinicopathologic features and survival outcomes for men <50 years of age in relation to other age groups stratified by race to further define CaP in young men. Methods: A multi-institutional review of 12,081 records of patients diagnosed with CaP from 1989-2009 was conducted. Patients were stratified by age group, race, and decade of treatment. Demographic and clinicopathologic characteristics were compared across age groups using chi-square tests and analysis of variance. The primary study endpoints, time to biochemical recurrence and all-cause mortality, were compared across age groups using Kaplan-Meier estimation and univariable and multivariable Cox proportional hazards analysis. Results: Only 4.5% of the study sample was <50 years of age. A higher percentage of African Americans diagnosed were <50 compared with Caucasians (8.3% vs 3.3%, P <.0001). Positive family history was more prevalent in the <50 cohort (36.1% vs 22.0%, P <.0001). Despite these findings, both racial subgroups for men <50 years of age demonstrated improved clinicpathologic features than other age quartiles. Furthermore, both Kaplan-Meier and Cox proportional hazard analysis demonstrated that the <50 cohort had a lower incidence of biochemical recurrence and greater overall survival. Conclusions: Race and family history appear to play a significant role in the incidence of CaP in younger men. Younger age at diagnosis is associated with more favorable outcomes and indicates that population-based screening at younger ages could potentially lead to improved survival for high-risk groups. © 2011 Elsevier Inc.

Brassell S.A.,U.S. National Institutes of Health | Brassell S.A.,Center for Prostate Disease Research | Elsamanoudi S.I.,Center for Prostate Disease Research | Cullen J.,Center for Prostate Disease Research | And 3 more authors.
Urologic Oncology: Seminars and Original Investigations | Year: 2013

Objective: To determine the health-related quality of life (HRQoL) impact of prostate cancer interventions at 2 years post-treatment, and between the 12- and 24-month interval, to better characterize this measure. Materials and methods: Patients treated at the Center for Prostate Disease Research between June 2003 and February 2010 were offered enrollment into a HRQoL study that entailed a baseline evaluation before prostate biopsy and at 3, 6, 9, 12, 18, 24, and 30 months thereafter. The instruments used were the Expanded Prostate Cancer Index Composite (EPIC), EPIC Demographic, and Medical Outcomes Study Short-Form 36 (SF-36). A Student's t-test and ANOVA were used to examine the association between HRQoL scores, patient demographic, and disease features. Multivariable regression models were used to analyze change over time. Estimates of risk, corresponding confidence intervals, and P values are presented for these longitudinal findings. Results: The study group was comprised of 595 patients. African Americans (AA) had slightly lower baseline raw scores in all EPIC and SF-36 HRQoL domains, but on bivariate analysis, there was no statistical difference in change of scores over time. Radical prostatectomy (RP) led to the greatest decline in urinary function. Bowel function significantly worsened with the addition of hormone therapy (HT) to external beam radiation therapy (EBRT). Sexual bother and function had a marked decline in all active treatment options. Despite these changes, there were no differences in overall satisfaction. SF-36 domains were not affected by RP, whereas EBRT and EBRT + HT had universal impact. For the 12- to 24-month interval, specifically, patients who underwent EBRT fared worse over this time period, showing continued worsening of urinary bother, hormonal function, physical role, physical component summary, and overall satisfaction. Patients who underwent RP did not show any further decline in the 12- to 24-month interval, but instead showed improvement. Conclusions: Because of the protracted nature of recovery after surgery, delayed onset of effects from radiation, potential interval decline secondary to age-related symptoms, and longevity of patients with prostate cancer, determination of long-term HRQoL outcomes is integral. Counseling with regard to these outcomes should be balanced with oncologic expectations from treatment. © 2013.

Torosyan Y.,Bethesda University | Dobi A.,Center for Prostate Disease Research | Glasman M.,Bethesda University | Mezhevaya K.,Bethesda University | And 6 more authors.
Oncogene | Year: 2010

Annexin-A7 (ANXA7) tumor suppressor role has been shown in various tumors, and ANXA7 expression has been particularly lost in androgen-resistant prostate cancers. In this study, we studied ANXA7 regulation in normal prostate versus androgen-sensitive and-resistant prostate cancer cells. Deletion mapping analysis showed lowest ANXA7-promoter activities in androgen-sensitive LNCaP prostate cancer cells. Genomatix analysis of ANXA7 promoter identified a cluster of steroid nuclear hormone receptor elements, including VGREF (VGRE.02/ARE.02). Gelshift analysis clearly indicated distinct nuclear protein occupancy at this ANXA7-promoter site (1086/890) in prostate cancer (LNCaP, DU145, and PC3) versus normal prostate (PrEC) cells. In matrix-assisted laser desorption time-of-flight mass spectrometry-based search for ANXA7 nuclear regulators, we identified several heterogeneous nuclear ribonucleoproteins (hnRNPs) (A1, A2/B1 and K) attached to the steroid-associated ANXA7-promoter site in the androgen-resistant PC3 prostate cancer cells with high ANXA7 gene copy number, but not in PrEC. The hnPNP role in ANXA7 regulation (that was validated by hnRNPA2/B1 antibody interference) resulted in multiple ANXA7 cDNA and protein products in PC3, but not in PrEC. Ingenuity pathways analysis showed plausible molecular paths between ANXA7 and the hnRNP-associated network in prostate cancer progression. Thus, a multi-hnRNP complex can be responsible for aberrant ANXA7 transcription and splicing, thereby affecting ANXA7 expression pattern and tumor suppressor function in prostate cancer. © 2010 Macmillan Publishers Limited All rights reserved.

Serkin F.B.,U.S. Army | Soderdahl D.W.,U.S. Army | Cullen J.,Center for Prostate Disease Research | Chen Y.,Center for Prostate Disease Research | Hernandez J.,U.S. Army
Urologic Oncology: Seminars and Original Investigations | Year: 2010

Purpose: To define the impact of discordant Gleason sum (GS) between prostate biopsy (Pbx) tissue and radical prostatectomy (RP) specimen among men initially diagnosed with Gleason 6 or 7 prostate adenocarcinoma. Materials and methods: We evaluated patients diagnosed with GS 6 or 7 and treated primarily with RP. We defined the frequency of GS discordance between Pbx and RP pathology reports. We analyzed pretreatment parameters associated with GS discordance and compared immediate postprostatectomy outcome variables across patient groups defined by their GS and concordance. We then conducted survival analysis for biochemical recurrence across patient groups defined by their GS and concordance status. Results: Among patients with GS 6 on Pbx, 681/1,847 (36.86%) patients were upgraded to GS 7 or higher after RP. Surgical margin, capsular involvement, seminal vesicle, and nodal involvement status were more favorable in patients with concordant Pbx and RP specimen with GS 6 (P < 0.0001). Patients with smaller transrectal ultrasound (TRUS) prostate volume were found to have higher PSA densities and were more likely to be upgraded at RP. Multivariate survival analysis also predicted fewer biochemical recurrence events over time in men with concordant Pbx tissue and RP specimen of GS 6 vs. 6/7 or 7/7 (P = 0.0025) controlling for other relevant covariates. Conclusions: GS discordance between Pbx tissue and RP specimens among prostate cancer patients initially diagnosed with either GS 6 or 7 adenocarcinoma of the prostate is substantial. This discordance has potential clinical significance in predicting oncologic outcomes.

Aims The reported incidence of urinary incontinence (UI) after radical prostatectomy (RP) ranges from 2.5 to 87%. We reviewed data from the Center for Prostate Disease Research (CPDR) to determine the incidence of patient reported UI after RP (postRPUI) and establish risk factors for postRPUI. Methods We obtained IRB approval to query the CPDR database on all patients undergoing RP between 1990 and 2007. We assessed patient age, nerve sparing status, blood loss, margin status, stage, and patient self-reported incontinence status as entered into the database. Patients were counted as having UI only if the database showed patient reported UI in every follow-up encounter. Patients were counted as permanently dry if at any time in the follow-up they answered that they had no UI. Results Four thousand three hundred seventy four patients underwent RP without radiation therapy or hormonal ablation between 1990 and 2007. Complete data were available for 1,616 (37%) and 1,459 (90.3%) reported UI more than 1 year after RP with a median follow-up of 50.7 months. Older age is an independent risk factor for UI (OR=1.021, P ≤ 0.0003). Nerve sparing, blood loss, stage of cancer, and margin status were not predictive for UI. Conclusions Our data indicate that patient reported post-RPUI is higher than expected but is not related to the nerve sparing technique, stage of cancer nor blood loss at the time of surgery. © 2011 Wiley Periodicals, Inc.

PubMed | Institute of Translational Health science, Foundation Medicine, Center for Prostate Disease Research, Uniformed Services University of the Health Sciences and 3 more.
Type: Journal Article | Journal: The Journal of urology | Year: 2016

Active surveillance is an important alternative to definitive therapy for men with low risk prostate cancer. However, the impact of active surveillance on health related quality of life compared to that in men without cancer remains unknown. In this study we evaluated health related quality of life outcomes in men on active surveillance compared to men followed after negative prostate needle biopsy.A prospective study was conducted on men who were enrolled into the Center for Prostate Disease Research Multicenter National Database and underwent prostate needle biopsy for suspicion of prostate cancer between 2007 and 2014. Health related quality of life was assessed at biopsy (baseline) and annually for up to 3years using SF-36 and EPIC questionnaires. Health related quality of life scores were modeled using generalized estimating equations, adjusting for baseline health related quality of life, and demographic and clinical characteristics.Of the 1,204 men who met the initial eligibility criteria 420 had a negative prostate needle biopsy (noncancer comparison group). Among the 411 men diagnosed with low risk prostate cancer 89 were on active surveillance. Longitudinal analysis revealed that for most health related quality of life subscales there were no significant differences between the groups in adjusted health related quality of life score trends over time.In this study most health related quality of life outcomes in patients with low risk prostate cancer on active surveillance did not differ significantly from those of men without prostate cancer. A comparison group of men with a similar risk of prostate cancer detection is critical to clarify the psychological and physical impact of active surveillance.

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