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Development of AR-V7 as a putative treatment selection marker for metastatic castration-resistant prostate cancer

Asian Journal of Andrology 2016年第4期18卷 580-585页

作者： Jun Luo Department of urology James Buchanan Brady Urological Institute Johns Hopkins University Baltimore MD USA.

Prostate cancer cells demonstrate a remarkable ＂addiction＂ to androgen receptor （AR） signaling in all stages of disease progression. As such, suppression of AR signaling remains the therapeutic goal in systemic treatment of prostate cancer. A number of molecular alterations arise in patients treated with AR-directed therapies. These molecular alterations may indicate the emergence of treatment resistance and may be targeted for the development of novel agents for prostate cancer. The presence of functional androgen receptor splice variants may represent a potential explanation for resistance to abiraterone and enzalutamide, newer AR-directed agents developed to treat metastatic castration-resistant prostate cancer （mCRPC）. In the last 8 years, many androgen receptor splice variants have been identified and characterized. Among these, androgen receptor splice variant-7 （AR-V7） has been investigated extensively. In AR-V7, the entire COOH-terminal ligand-binding domain of the canonical AR is truncated and replaced with a variant-specific peptide of 16 amino acids. Functionally, AR-V7 is capable of mediating constitutive nuclear localization and androgen receptor signaling in the absence of androgens, or in the presence of enzalutamide. In this review, we will focus on clinical translational studies involving detection/measurement of AR-V7. Methods have been developed to detect AR-V7 in clinical mCRPC specimens. AR-V7 can be reliably measured in both tissue and circulating tumor cells derived from mCRPC patients, making it possible to conduct both cross-sectional and longitudinal clinical correlative studies. Current evidence derived from studies focusing on detection of AR-V7 in mCRPC support its potential clinical utility as a treatment selection marker.

关键词： androgen receptor androgen receptor splice variant-7 (AR-V7) castration-resistance prostate cancer circulating tumorcells treatment selection

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NADPH oxidase： recent evidence for its role in erectile dysfunction

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Asian Journal of Andrology 2008年第1期10卷 6-13页

作者： Liming Jin Arthur L.Burnett Department of urology The James Buchanan Brady Urological Institute Johns Hopkins Medical Institutions Baltimore MD 21287 USA

Important roles for reactive oxygen species （ROS） in physiology and pathophysiology have been increasingly recognized. Under normal conditions, ROS serve as signaling molecules in the regulation of cellular functions. However, enhanced ROS production as a result of the activation of nicotinamide adenine dinucleotide phosphate （NADPH） oxidase contributes significantly to the pathogeneses of vascular diseases. Although it has become evident that increased ROS is associated with erectile dysfunction （ED）, the sources of ROS in the penis remain largely unknown. In recent years, emergent evidence suggests the possible role of NADPH oxidase in inducing ED. In this review, we examine the relationship between ROS and ED in different disease models and discuss the current evidence basis for NADPH oxidase-derive＇d ROS in ED.

关键词： reactive oxygen species erectile function superoxide penis nitric oxide

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MicroRNA expression and function in prostate cancer： a review of current knowledge and opportunities for discovery

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Asian Journal of Andrology 2016年第4期18卷 559-567页

作者： Binod Kumar Shawn E Lupold The james buchanan brady Urological Institute Department of Urology Johns Hopkins School of Medicine Baltimore MD USA.

MicroRNAs （miRNAs） are well-conserved noncoding RNAs that broadly regulate gene expression through posttranscriptional silencing of coding genes. Dysregulated miRNA expression in prostate and other cancers implicates their role in cancer biology. Moreover, functional studies provide support for the contribution of miRNAs to several key pathways in cancer initiation and progression. Comparative analyses of miRNA gene expression between malignant and nonmalignant prostate tissues, healthy controls and prostate cancer （PCa） patients, as well as less aggressive versus more aggressive disease indicate that miRNAs may be future diagnostic or prognostic biomarkers in tumor tissue, blood, or urine. Further, miRNAs may be future therapeutics or therapeutic targets. In this review, we examine the miRNAs most commonly observed to be de-regulated in PCa gene expression analyses and review the potential contribution of these miRNAs to important pathways in PCa initiation and progression.

关键词： miRNA prostate cancer noncoding RNA

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Resident involvement in the prostatic urethral lift:implementing innovative technology in an academic setting

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Asian Journal of Andrology 2021年第6期23卷 616-620页

作者： Ridwan Alam Matthew J Rabinowitz Taylor P Kohn Vanessa N Peña james L Liu Yasin Bhanji Amin S Herati Department of urology The James Buchanan Brady Urological InstituteJohns Hopkins University School of MedicineBaltimoreMD 21287USA

Adoption of the prostatic urethral lift(PUL)as a treatment for benign prostatic hyperplasia highlights the importance of training residents with novel technology without compromising patient *** study examines the effect of resident involvement during PUL on patient and procedural *** chart review was conducted on all consecutive PUL cases performed by a single academic urologist between October 2017 and November *** in post-graduate year(PGY)1–3 are considered junior residents,while those in PGY 4–6 are senior *** International Prostate Symptom Score(IPSS)and quality of life(QOL)scores were used to measure *** and mixed-effects linear regression models were used to compare *** were 110 patients with a median age of 66.4 *** were involved in 73 cases(66.4%),and senior residents were involved in 31 of those *** involvement was not associated with adverse perioperative outcomes with respect to the number of implants fired,the percentage of implants successfully placed,or the postoperative catheterization *** adjustment for confounding factors,junior residents were associated with significantly longer case length compared to the attending alone(+12.6 min,P=0.003)but senior residents were not(+2.4 min,P=0.59).IPSS and QOL scores were not significantly affected by resident involvement(P=0.12 and P=0.21,respectively).The presence of surgeons-in-training,particularly those in the early stages,prolongs PUL case length but does not appear to have an adverse impact on patient outcomes.

关键词： internship and residency operative time prostatic hyperplasia prostheses and implants quality of life

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Novel approaches for the molecular classification of prostate cancer

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Asian Journal of Andrology 2010年第5期12卷 620-622页

作者： Robert H. Getzenberg Department of urology James Buchanan Brady Urological Institute The Johns Hopkins University School of MedicineBaltimore 21287 MD USA

Among the urologic cancers, prostate cancer is by far the most common, and it appears to have the potential to affect almost all men throughout the world as they age. A number of studies have shown that many men with prostate cancer will not die from their disease, but rather with the disease but from other causes. These men have a form of prostate cancer that is described as ＂very low risk＂ and has often been called indolent.

关键词： Prostate Cancer (genus) Neoplasms Men Beers Aluminium Classification

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Cancer/testis antigens： novel tools for discerning aggressive and non-aggressive prostate cancer

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Asian Journal of Andrology 2012年第3期14卷 400-404,I0006页

作者： Takumi Shiraishi Robert H Getzenberg Prakash Kulkarni Department of urology James Buchanan Brady Urological Institute Baltimore M D 21287 USA Department of urology Graduate School of Medical Science Kyoto Prefectural University of Medicine Kyoto Japan Department of Oncology James Buchanan Brady Urological Institute Baltimore MD 21287 USA pharmacology and Molecular Sciences The Johns Hopkins University School of Medicine Baltimore MD 21287 USA

The introduction of serum prostate-specific antigen （PSA） in the 1980s has dramatically altered and benefited the initial diagnosis of prostate cancer. However, the widespread use of PSA testing has resulted in overdetection and overtreatment of potentially indolent disease. Thus, a clinical dilemma today in the management of prostate cancer is to discern men with aggressive disease who need definitive treatment from men whose disease are not lethal. Although several serum and tissue biomarkers have been evaluated during the past decade, improved markers are still needed to enhance the accuracy, with which patients at risk can be discerned and treated more aggressively. The cancer/testis antigens （CTAs） are a group of proteins that are restricted to the testis in the normal adult, but are aberrantly expressed in several types of cancers. Because of their restricted expression pattern, the CTAs represent attractive biomarker candidates for cancer diagnosis/prognosis. Furthermore, several studies to date have reported the differential expression of CTAs in prostate cancer. Here, we review recent developments that demonstrate the potential of the CTAs as biomarkers to discern the a^ressive Dhenotvoe of orostate cancer.

关键词： cancer/testis antigens DNA microarrays prostate cancer prostate carcinoma tumor antigen

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Non-invasive actionable biomarkers for metastatic prostate cancer

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Asian Journal of urology 2016年第4期3卷 170-176页

作者： Jun Luo Department of urology and james buchanan brady Urological Institute Johns Hopkins UniversityBaltimoreMDUSA

In the current clinical setting,many disease management options are available for men diagnosed with prostate *** metastatic prostate cancer,first-line therapies almost always involve agents designed to inhibit androgen receptor(AR)***-resistant prostate cancers(CRPCs)that arise following first-line androgen deprivation therapies(ADT)may continue to respond to additional lines of AR-targeting therapies(abiraterone and enzalutamide),chemotherapies(docetaxel and cabazitaxel),bonetargeting Radium-223 therapy,and immunotherapy *** rapidly expanding therapies for CRPC is expected to transform this lethal disease into one that can be managed for prolonged period of *** the past 3 years,a number of promising biomarkers that may help to guide treatment decisions have been proposed and evaluated,including androgen receptor splice variant-7(AR-V7),a truncated AR lacking the ligand-binding domain(LBD)and mediate constitutively-active AR *** treatment selection markers such as ARV7 may further improve survival benefit of existing therapies and help to accelerate development of new agents for metastatic prostate *** the metastatic setting,it is important to consider compatibility between the putative biomarker with non-invasive *** this review,biomarkers relevant to the setting of metastatic prostate cancer are discussed with respect to a number of key attributes critical for clinical development of non-invasive,actionable *** is envisioned that biomarkers for metastatic prostate cancer will continue to be discovered,developed,and refined to meet the unmet needs in both standard-of-care and clinical trial settings.

关键词： Prostate cancer Androgen receptor AR-V7 Biomarker CRPC

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Helping to address the over treatment of prostate cancer： tools to differentiate lethal and non-lethal phenotype in prostate cancer

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Asian Journal of Andrology 2012年第3期14卷 347-348页

作者： Professor Robert H Getzenberg Professor H Ballentine Carter Department of urology The Brady Urological Institute Johns Hopkins Hospital Baltimore MD 21287 USA Department of urology The Johns Hopkins University School of Medicine and The James Buchanan Brady Urological Institute The Johns Hopkins Hospital Baltimore MD 21287 USA

2011 was a noteworthy year for those interested in the care of patients with prostate cancer. First, the US Preventive Services Task Force （USPSTF） released an update on prostate cancer screening, and recommended against the use of the prostate-specific antigen （PSA） test for all men, regardless of family history or race. While this surprised many in the field, the conclusion that there is more harm than benefit is inescapable on a population level--the focus of the USPSTF. Most men with newly diagnosed prostate cancer have favorable risk disease and are at an age when treatment is unlikely to extend life---a conclusion that is supported by randomized trials. Second, the National Institutes of Health convened a ＇State of the Science＇ conference on active surveillance for prostate cancer, and concluded that the rates of overtreatment of prostate cancer are high and surveillance is greatly underutilized. Both the USPSTF and the National Institutes of Health conference were prompted in large part by the recognition that widespread PSA testing leads to prostate biopsies that often uncover indolent disease. In the majority of cases,

关键词： Helping prostate cancer

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Regulation of androgen receptor variants in prostate cancer

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Asian Journal of urology 2020年第3期7卷 251-257页

作者： Yezi Zhu Jun Luo Department of urology James Buchanan Brady Urological InstituteJohns Hopkins UniversityBaltimoreMDUSA LIVESTRONG Cancer Institutes The University of TexasAustinTXUSA

Aberrant activation of androgen receptor(AR)signaling occurs in patients treated with AR-targeted therapies,contributing to the development of castration-resistant prostate cancer(CRPC)and therapeutic *** the past decade,many AR variants(AR-Vs)have been identified in prostate cancer cell lines and clinical CRPC *** AR-Vs lack the COOH-terminal ligand-binding domain(LBD),and may mediate constitutively active AR signaling acquired following AR-targeting *** splice variant-7(AR-V7),one of the most well characterized AR-Vs,can be reliably measured in tissue and liquid biopsy specimens,and blood-based detection of AR-V7 is a reliable indicator of poor outcome to relatively novel hormonal therapies(NHT)such as abiraterone and enzalutamide in men with metastatic CRPC(mCRPC).Given the important clinical implication of AR-Vs,this short review will focus on studies addressing how AR-Vs are regulated in prostate *** regard to the molecular origin of AR-Vs,it is established that expression of AR-Vs is highly correlated with androgen deprivation and suppression of AR *** targeting of the AR axis may result in active transcription of the AR gene,elevated activities of certain components of the mRNA splicing machinery,as well as AR genomic alterations,all of which may explain the molecular origin of *** a unified hypothesis is currently lacking,existing data suggest that elevated expression of AR-Vs,which in general occurs quite specifically in a cellular environment where the canonical AR signaling is suppressed,is driven by both genomic and epigenomic features acquired in the development of CRPC.

关键词： Androgen receptor Androgen receptor splice variant-7 Castration-resistant prostate cancer

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Comparison of 80 W versus 120 W 532 nm Laser Prostatectomy for BPH

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Open Journal of urology 2013年第1期3卷 1-4页

作者： Richard K. Lee Bilal Chughtai Dean S. Elterman Lauren Kurlander Marika Yip-Bannicq Laura McCormick Steven A. Kaplan Alexis E. Te Department of Surgery Weill Cornell Medical College New York USA james buchanan brady foundation dept. of urology Weill Cornell Medical College New York USA

Purpose: Improvements to photoselective vaporization of the prostate (PVP) have been made over time, particularly with the introduction of higher power systems. Few studies however have compared the performance of these systems to their predecessors. The purpose of this study was to compare the clinical and perioperative outcomes of 80 W vs. 120 W PVP. Materials and Methods: A series of 267 and 209 consecutive patients underwent 80 W and 120 W PVP, respectively, from September 2001 to May 2009 at Weill Cornell Medical College (GreenLightTM laser system, American Medical Systems, Inc., Minnetonka, MN). Data were collected on patient demographics, International Prostate Symptom Score (IPSS), prostate-specific antigen (PSA), and perioperative parameters. Maximum flow rate (Qmax), postvoid residual (PVR), and transrectal ultrasound prostate volume were recorded. Statistical analyses were carried out utilizing the Shapiro-Wilk, Mann-Whitney, Wilcoxon and unpaired t tests (SPSS 15.0, SPSS Inc., Chicago, IL, USA). Results: Baseline parameters were similar between the two groups except for greater median age (72.8 vs. 69.2 years, p = 0.01) and lower median PSA (2.0 vs. 3.3, p = 0.01) in the 80 W group. Median laser time was longer in the 80W group (85 vs. 51 minutes, p 0.001) with a higher median energy utilized (253 vs. 210 kJ, p = 0.001). Final IPSS, Qmax, PVR, and PSA were equivalent between the two groups. Conclusions: In our series, PVP was safe and effective. Durable and similar improvements in symptoms and objective parameters were achieved in patients with both 80 W and 120 W laser systems. PVP with the 120 W system, however, provided faster and more efficient vaporization compared to the 80 W system.

关键词： Transurethral Resection of Prostate Prostatic Hyperplasia Surgical Procedures Minimally Invasive Lasers

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