Supplementary Figure 1 from Development of a Multiplex Quantitative PCR Signature to Predict Progression in Non–Muscle-Invasive Bladder Cancer

Supplementary Methods, Figures 1-7 from Development of a Multiplex Quantitative PCR Signature to Predict Progression in Non–Muscle-Invasive Bladder Cancer

Supplementary Figure 2 from Development of a Multiplex Quantitative PCR Signature to Predict Progression in Non–Muscle-Invasive Bladder Cancer

This study analyzes whether greater levels of Internet access closed the participation gap between individuals of lower and higher socioeconomic status (SES) in the early stages of the 2012 presidential campaign. Our analysis of data from the Pew Research Center demonstrates that greater levels of access to the Internet are significantly associated with greater political knowledge and engagement for low SES individuals, but not high SES individuals. We explain our results in the context of incidental learning among the disengaged public during high-profile political events, such as a presidential election.

Purpose: Perioperative instillation of intravesical chemotherapy after bladder tumor resection is supported by level I evidence showing a 30% decrease in tumor recurrence. However, studies of administrative data sets show poor use in practice.Materials and Methods: We prospectively evaluated the use of perioperative intravesical chemotherapy in a multipractice quality improvement collaborative. Cases were categorized as ideal for intravesical chemotherapy (1 or 2 papillary tumors, cTa/cT1 and completely resected) and nonideal. The reasons for not administering intravesical chemotherapy in ideal cases were classified as appropriate or modifiable. Before and after comparative feedback and educational interventions we calculated judicious use of intravesical chemotherapy (nonuse in nonideal cases plus use in ideal cases plus appropriate nonuse in ideal cases) and quality improvement potential (use in nonideal cases plus nonuse in ideal cases attributable to modifiable factors).Results: We accrued a total of 2,794 cases at the 5 sites in 22 months. The rate of use in ideal cases was 38% before and 34.8% after intervention (p = 0.36), while use in nonideal cases decreased from 15% to 12% (p = 0.08). Overall, intravesical chemotherapy was used judiciously in 83.0% to 85.7% of cases, while the remaining 14.3% to 17.0% represented quality improvement potential.Conclusions: Judicious use of perioperative intravesical chemotherapy is relatively high in routine practice. Most instances of nonuse represent appropriate clinical judgment. Utilization did not change after quality improvement interventions, suggesting that there may a ceiling effect that makes it difficult to improve care that is high quality at baseline. Moreover, decreasing unnecessary use of an intervention may be easier than encouraging appropriate use of potentially toxic therapy.

Participation in Organized Activities (OA) is associated with positive behavioral and developmental outcomes in children. However, less is known about how particular aspects of participation affect the academic achievement of high school students from different social class positions. Using the Education Longitudinal Study of 2002, this study examines the math achievement gains from organized activity participation for advantaged and disadvantaged youths. Findings indicate that the relationship between OA and achievement does indeed vary by social class. Regardless of the type of OA, less advantaged high school students see substantial academic improvements from time in OA while their more advantaged peers do not. These findings suggest that participation in organized activities is a form of resource compensation that helps to reduce the achievement gap between advantaged and disadvantaged youths, even at the end of the K-12 schooling process.

OBJECTIVES:To review our experience with the newest generation piezoelectric lithotripter, the Piezolith 3000, in adult patients undergoing extracorporeal shock wave lithotripsy for solitary urinary calculi. METHODS:We identified 139 shock wave lithotripsy procedures that had used the Piezolith 3000 from February 2005 to July 2007. All procedures were performed under intravenous sedation. Retrospective chart review was used to obtain the pertinent information. Stone-free status was defined as the absence of any fragments, and success as the absence of stone fragments >4 mm, on follow-up imaging after a single treatment. RESULTS:The stone-free and success rate 1 month after a single shock wave lithotripsy session was 45% and 64%, respectively. Only stone size correlated with the overall success rate (P = .004). The overall complication rate was 15% and included a 5.8% major complication rate requiring intervention or admission. The median time in the procedure room was 33 minutes. The adjunctive procedure rate was 1.4%, and the secondary retreatment rate was 10%. CONCLUSIONS:The Piezolith 3000 provides modest, but acceptable, single-treatment stone-free and success rates, with a reasonable safety profile, and offers rapid and convenient lithotripsy requiring only intravenous sedation.

Replying to: Carver, B. S. et al. , 10.1038/nature07738 (2009) Carver 1 question our recent report that mice expressing ETV1 under the control of the probasin promoter (ARR2Pb) develop mouse prostatic intraepithelial neoplasia (mPIN)2. They report the generation of transgenic ARR2Pb-ERG mice with no phenotypic differences from control mice. They propose that this demonstrates that ETS genetic rearrangements do not initiate prostate tumorigenesis and use data from human prostate cancer studies to propose that ETS rearrangements are associated with progression from PIN to prostate cancer. Although we and others have shown that ARR2Pb-ETV1 and ARR2Pb-ERG mice develop mPIN, we have consistently proposed that in human prostate cancer development, ETS rearrangements mediate the transition from PIN to cancer.

Abstract In bladder cancer, clinical grade and stage fail to capture outcome. We developed a clinically applicable quantitative PCR (QPCR) gene signature to predict progression in non–muscle-invasive bladder cancer. Comparative metaprofiling of 12 DNA microarray data sets (comprising 631 samples and 241,298 probe sets) identified 96 genes, which showed differential expression in seven clinical outcome categories, or were identified as outliers, historic markers, or housekeeping genes. QPCR was done to determine mRNA expression from 96 bladder tumors. Fifty-seven genes differentiated T2 from non-T2 tumors (P < 0.05). Principal components analysis and Cox regression models were used to predict probability of T2 progression for non-T2 patients, placing them into high- and low-risk groups based on their gene expression. At 2 years, high-risk patients exhibited greater T2 progression (45% for high-risk patients versus 12% for low-risk patients; P = 0.003, log-rank test). This difference remained significant within T1 tumors (61% for high-risk patients versus 22% for low-risk patients; P = 0.02) and Ta tumors (29% for high-risk patients versus 0% for low-risk patients; P = 0.03). The best multivariate Cox model included stage and gender, and this signature provided predictive improvement over both (P = 0.002, likelihood ratio test). Immunohistochemistry was done for two genes in the signature not previously described in bladder cancer, ACTN1 and CDC25B, corroborating their up-regulation at the protein level with disease progression. Thus, we identified a 57-gene QPCR panel to help predict progression of non–muscle-invasive bladder cancers and delineate a systematic, generalizable approach to converting microarray data into a multiplex assay for cancer progression. [Cancer Res 2009;69(9):3810–8]

Chromosomal rearrangements play a causal role in haematological and mesenchymal malignancies. Importantly, the resulting gene fusions can serve as specific therapeutic targets, as exemplified by the development of imatinib (Gleevec), which specifically inhibits the BCR‐ABL gene fusion product that defines chronic myeloid leukaemia. Recently, gene fusions involving the prostate‐specific gene transmembrane protease, serine 2 (TMPRSS2) and members of the erythroblastosis virus E26 transforming sequence (ETS) family of transcription factors were identified in most of PSA‐screened prostate cancers. In this review, we summarize the identification, characterization and detection of TMPRSS2:ETS gene fusions and their role in prostate cancer development. We also discuss the discovery of additional 5′ partners that define distinct classes of ETS gene fusions based on the prostate specificity and androgen responsiveness of the 5′ partner. Additionally, we also summarize conflicting reports about associations between gene fusion status and patient outcome. The specificity of ETS gene fusions in prostate cancer suggests that they may have causal roles in prostate cancer and suggest utility in prostate cancer detection, stratification and treatment.

You have accessJournal of Urology1 Apr 2008INTEGRATIVE META-ANALYSIS OF MICROARRAY DATA TO IDENTIFY PROFILES THAT PREDICT BLADDER CANCER OUTCOMES AND PROGRESSION David S Morris, Scott A Tomlins, Daniel R Rhodes, Rou Wang, Robert J Lonigro, Cheryl T Lee, Alon Z Weizer, and Arul M Chinnaiyan David S MorrisDavid S Morris More articles by this author , Scott A TomlinsScott A Tomlins More articles by this author , Daniel R RhodesDaniel R Rhodes More articles by this author , Rou WangRou Wang More articles by this author , Robert J LonigroRobert J Lonigro More articles by this author , Cheryl T LeeCheryl T Lee More articles by this author , Alon Z WeizerAlon Z Weizer More articles by this author , and Arul M ChinnaiyanArul M Chinnaiyan More articles by this author View All Author Informationhttps://doi.org/10.1016/S0022-5347(08)60775-2AboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissionsReprints ShareFacebookLinked InTwitterEmail "INTEGRATIVE META-ANALYSIS OF MICROARRAY DATA TO IDENTIFY PROFILES THAT PREDICT BLADDER CANCER OUTCOMES AND PROGRESSION." The Journal of Urology, 179(4S), p. 267 © 2008 by American Urological AssociationFiguresReferencesRelatedDetails Volume 179Issue 4SApril 2008Page: 267 Advertisement Copyright & Permissions© 2008 by American Urological AssociationMetricsAuthor Information David S Morris More articles by this author Scott A Tomlins More articles by this author Daniel R Rhodes More articles by this author Rou Wang More articles by this author Robert J Lonigro More articles by this author Cheryl T Lee More articles by this author Alon Z Weizer More articles by this author Arul M Chinnaiyan More articles by this author Expand All Advertisement PDF downloadLoading ...

Abstract Although prostate-specific antigen (PSA) serum level is currently the standard of care for prostate cancer screening in the United States, it lacks ideal specificity and additional biomarkers are needed to supplement or potentially replace serum PSA testing. Emerging evidence suggests that monitoring the noncoding RNA transcript PCA3 in urine may be useful in detecting prostate cancer in patients with elevated PSA levels. Here, we show that a multiplex panel of urine transcripts outperforms PCA3 transcript alone for the detection of prostate cancer. We measured the expression of seven putative prostate cancer biomarkers, including PCA3, in sedimented urine using quantitative PCR on a cohort of 234 patients presenting for biopsy or radical prostatectomy. By univariate analysis, we found that increased GOLPH2, SPINK1, and PCA3 transcript expression and TMPRSS2:ERG fusion status were significant predictors of prostate cancer. Multivariate regression analysis showed that a multiplexed model, including these biomarkers, outperformed serum PSA or PCA3 alone in detecting prostate cancer. The area under the receiver-operating characteristic curve was 0.758 for the multiplexed model versus 0.662 for PCA3 alone (P = 0.003). The sensitivity and specificity for the multiplexed model were 65.9% and 76.0%, respectively, and the positive and negative predictive values were 79.8% and 60.8%, respectively. Taken together, these results provide the framework for the development of highly optimized, multiplex urine biomarker tests for more accurate detection of prostate cancer. [Cancer Res 2008;68(3):645–9]

You have accessJournal of Urology1 Apr 2008DEVELOPMENT OF A MULTIPLEX QUANTITATIVE PCR SIGNATURE TO PREDICT POOR OUTCOME IN BLADDER CANCER Rou Wang, Alon Z Weizer, David S Morris, Scott A Tomlins, Robert J Lonigro, Alexander Tsodikov, Cheryl T Lee, and Arul M Chinnaiyan Rou WangRou Wang More articles by this author , Alon Z WeizerAlon Z Weizer More articles by this author , David S MorrisDavid S Morris More articles by this author , Scott A TomlinsScott A Tomlins More articles by this author , Robert J LonigroRobert J Lonigro More articles by this author , Alexander TsodikovAlexander Tsodikov More articles by this author , Cheryl T LeeCheryl T Lee More articles by this author , and Arul M ChinnaiyanArul M Chinnaiyan More articles by this author View All Author Informationhttps://doi.org/10.1016/S0022-5347(08)60918-0AboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissionsReprints ShareFacebookLinked InTwitterEmail "DEVELOPMENT OF A MULTIPLEX QUANTITATIVE PCR SIGNATURE TO PREDICT POOR OUTCOME IN BLADDER CANCER." The Journal of Urology, 179(4S), p. 314 © 2008 by American Urological AssociationFiguresReferencesRelatedDetails Volume 179Issue 4SApril 2008Page: 314 Advertisement Copyright & Permissions© 2008 by American Urological AssociationMetricsAuthor Information Rou Wang More articles by this author Alon Z Weizer More articles by this author David S Morris More articles by this author Scott A Tomlins More articles by this author Robert J Lonigro More articles by this author Alexander Tsodikov More articles by this author Cheryl T Lee More articles by this author Arul M Chinnaiyan More articles by this author Expand All Advertisement PDF downloadLoading ...

ETS gene fusions have been characterized in a majority of prostate cancers; however, the key molecular alterations in ETS-negative cancers are unclear. Here we used an outlier meta-analysis (meta-COPA) to identify SPINK1 outlier expression exclusively in a subset of ETS rearrangement-negative cancers ( approximately 10% of total cases). We validated the mutual exclusivity of SPINK1 expression and ETS fusion status, demonstrated that SPINK1 outlier expression can be detected noninvasively in urine, and observed that SPINK1 outlier expression is an independent predictor of biochemical recurrence after resection. We identified the aggressive 22RV1 cell line as a SPINK1 outlier expression model and demonstrate that SPINK1 knockdown in 22RV1 attenuates invasion, suggesting a functional role in ETS rearrangement-negative prostate cancers.

You have accessJournal of UrologyPodium 46, Tuesday, May 22, 2007, 3:30 - 5:30 pm1 Apr 20071668: Understanding Bladder Cancer Death: Will Pulling the Trigger for Cystectomy Sooner Save Lives? David S. Morris, Alon Z. Weizer, Zaojun Ye, Rodney L. Dunn, James E. Montie, and Brent K. Hollenbeck David S. MorrisDavid S. Morris More articles by this author , Alon Z. WeizerAlon Z. Weizer More articles by this author , Zaojun YeZaojun Ye More articles by this author , Rodney L. DunnRodney L. Dunn More articles by this author , James E. MontieJames E. Montie More articles by this author , and Brent K. HollenbeckBrent K. Hollenbeck More articles by this author View All Author Informationhttps://doi.org/10.1016/S0022-5347(18)31856-1AboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissionsReprints ShareFacebookLinked InTwitterEmail "1668: Understanding Bladder Cancer Death: Will Pulling the Trigger for Cystectomy Sooner Save Lives?." The Journal of Urology, 177(4S), p. 553 © 2016 by American Urological AssociationFiguresReferencesRelatedDetailsCited ByMontie J (2018) Improving Outcomes After Radical CystectomyJournal of Urology, VOL. 180, NO. 1, (12-13), Online publication date: 1-Jul-2008. Volume 177Issue 4SApril 2007Page: 553 Advertisement Copyright & Permissions© 2016 by American Urological AssociationMetricsAuthor Information David S. Morris More articles by this author Alon Z. Weizer More articles by this author Zaojun Ye More articles by this author Rodney L. Dunn More articles by this author James E. Montie More articles by this author Brent K. Hollenbeck More articles by this author Expand All Advertisement PDF DownloadLoading ...