Prostate Cancer Reshapes the Secreted and Extracellular Vesicle Urinary Proteomes.

Urine is a complex biofluid that reflects both overall physiologic state and the state of the genitourinary tissues through which it passes. It contains both secreted proteins and proteins encapsulated in tissue-derived extracellular vesicles (EVs). To understand the population variability and clinical utility of urine, we quantified the secreted and EV proteomes from 190 men, including a subset with prostate cancer.

Atypical Nelson Syndrome Following Right Partial and Left Total Nephrectomy With Incidental Bilateral Total Adrenalectomy of Renal Cell Carcinoma: A Chat Generative Pre-Trained Transformer (ChatGPT)-Assisted Case Report and Literature Review.

Nelson syndrome (NS) is a dangerous condition that can sometimes manifest after bilateral adrenalectomy (BA), typically in treating Cushing's disease. It is defined by the collection of systemic signs and symptoms that can arise in a state where there are chronically and massively elevated levels of adrenocorticotropic hormone (ACTH). Traditionally it may manifest from six months to 24 years following the loss of both adrenal glands, with the meantime of development being 15 years following BA.

Site-Specific Intact N-Linked Glycopeptide Characterization of Prostate-Specific Membrane Antigen from Metastatic Prostate Cancer Cells.

The composition of N-linked glycans that are conjugated to the prostate-specific membrane antigen (PSMA) and their functional significance in prostate cancer progression have not been fully characterized. PSMA was isolated from two metastatic prostate cancer cell lines, LNCaP and MDAPCa2b, which have different tissue tropism and localization. Isolated PSMA was trypsin-digested, and intact glycopeptides were subjected to LC-HCD-EThcD-MS/MS analysis on a Tribrid Orbitrap Fusion Lumos mass spectrometer.

Urinary NID2 and TWIST1 methylation to augment conventional urine cytology for the detection of bladder cancer.

Background: Abnormal methylation of urinary TWIST1 and NID2 conferred high sensitivity and specificity for the detection of urothelial carcinoma.

Objective: We examine the performance of the urine-based TWIST1/NID2 methylation assay with the addition of urine cytology for the detection of urothelial carcinoma.

Materials And Methods: A prospective multi-institutional study was conducted to assess the performance of a methylation assay for patients with hematuria or under surveillance for non-muscle invasive bladder cancer (NMIBC).

Timing of Adverse Prostate Cancer Reclassification on First Surveillance Biopsy: Results from the Canary Prostate Cancer Active Surveillance Study.

Purpose: During active surveillance for localized prostate cancer, the timing of the first surveillance biopsy varies. We analyzed the Canary PASS (Prostate Cancer Active Surveillance Study) to determine biopsy timing influence on rates of prostate cancer adverse reclassification at the first active surveillance biopsy.

Materials And Methods: Of 1,085 participants in PASS, 421 had fewer than 34% of cores involved with cancer and Gleason sum 6 or less, and thereafter underwent on-study active surveillance biopsy.

Histologic Grading of Prostatic Adenocarcinoma Can Be Further Optimized: Analysis of the Relative Prognostic Strength of Individual Architectural Patterns in 1275 Patients From the Canary Retrospective Cohort.

Histologic grading remains the gold standard for prognosis in prostate cancer, and assessment of Gleason score plays a critical role in active surveillance management. We sought to optimize the prognostic stratification of grading and developed a method of recording and studying individual architectural patterns by light microscopic evaluation that is independent of standard Gleason grade. Some of the evaluated patterns are not assessed by current Gleason grading (eg, reactive stromal response).

Outcomes of Active Surveillance for Clinically Localized Prostate Cancer in the Prospective, Multi-Institutional Canary PASS Cohort.

Purpose: Active surveillance represents a strategy to address the overtreatment of prostate cancer, yet uncertainty regarding individual patient outcomes remains a concern. We evaluated outcomes in a prospective multicenter study of active surveillance.

Materials And Methods: We studied 905 men in the prospective Canary PASS enrolled between 2008 and 2013.

Multi-institutional external validation of urinary TWIST1 and NID2 methylation as a diagnostic test for bladder cancer.

Objectives: We previously reported a clinical trial in which we were unable to replicate the excellent diagnostic metrics produced in the developmental study of the TWIST1 and NID2 gene methylation assay. In this expanded trial with subjects enrolled from another institution, we reexamine the diagnostic capabilities of the test to externally validate our previous study.

Materials And Methods: TWIST1 and NID2 gene methylation was assessed in DNA isolated from the urine of subjects at risk of bladder cancer undergoing cystoscopy for hematuria or bladder cancer surveillance.

Robotic-Assisted Ureteral Re-implantation: A Case Series.

Introduction: Minimally invasive surgical techniques are currently used for numerous urologic disorders and generally offer decreased morbidity and equivalent outcomes compared with open surgery. There is a relative paucity of data on robot-assisted ureteral re-implantation (RAUR) in adult patients for benign stricture disease.

Patients And Methods: We retrospectively reviewed our recent experience with mid-/distal ureteral reconstruction at a single tertiary-care center.

A Randomized Phase II Trial of Sipuleucel-T with Concurrent versus Sequential Abiraterone Acetate plus Prednisone in Metastatic Castration-Resistant Prostate Cancer.

Purpose: This phase II open-label study evaluated the effect of concurrent or sequential administration of abiraterone acetate plus prednisone (AA + P) on sipuleucel-T manufacture and immune responses in metastatic castration-resistant prostate cancer (mCRPC) patients.

Experimental Design: mCRPC patients received sipuleucel-T followed by AA + P 1 day (concurrent) or 10 weeks (sequential) after the first sipuleucel-T infusion. AA + P treatment continued for 26 weeks.

Survival with AGS-003, an autologous dendritic cell-based immunotherapy, in combination with sunitinib in unfavorable risk patients with advanced renal cell carcinoma (RCC): Phase 2 study results.

Background: AGS-003 is an autologous immunotherapy prepared from fully matured and optimized monocyte-derived dendritic cells, which are co-electroporated with amplified tumor RNA plus synthetic CD40L RNA. AGS-003 was evaluated in combination with sunitinib in an open label phase 2 study in intermediate and poor risk, treatment naïve patients with metastatic clear cell renal cell carcinoma (mRCC).

Methods: Twenty-one intermediate and poor risk patients were treated continuously with sunitinib (4 weeks on, 2 weeks off per 6 week cycle).

Precision Medicine in Active Surveillance for Prostate Cancer: Development of the Canary-Early Detection Research Network Active Surveillance Biopsy Risk Calculator.

Background: Men on active surveillance (AS) face repeated biopsies. Most biopsy specimens will not show disease progression or change management. Such biopsies do not contribute to patient management and are potentially morbid and costly.

Clinical validation of an epigenetic assay to predict negative histopathological results in repeat prostate biopsies.

Purpose: The DOCUMENT multicenter trial in the United States validated the performance of an epigenetic test as an independent predictor of prostate cancer risk to guide decision making for repeat biopsy. Confirming an increased negative predictive value could help avoid unnecessary repeat biopsies.

Materials And Methods: We evaluated the archived, cancer negative prostate biopsy core tissue samples of 350 subjects from a total of 5 urological centers in the United States.

Increased bisecting N-acetylglucosamine and decreased branched chain glycans of N-linked glycoproteins in expressed prostatic secretions associated with prostate cancer progression.

Purpose: Using prostatic fluids rich in glycoproteins like prostate-specific antigen and prostatic acid phosphatase (PAP), the goal of this study was to identify the structural types and relative abundance of glycans associated with prostate cancer status for subsequent use in emerging MS-based glycopeptide analysis platforms.

Experimental Design: A series of pooled samples of expressed prostatic secretions (EPS) and exosomes reflecting different stages of prostate cancer disease were used for N-linked glycan profiling by three complementary methods, MALDI-TOF profiling, normal-phase HPLC separation, and triple quadropole MS analysis of PAP glycopeptides.

Results: Glycan profiling of N-linked glycans from different EPS fluids indicated a global decrease in larger branched tri- and tetra-antennary glycans.

In-depth proteomic analyses of exosomes isolated from expressed prostatic secretions in urine.

Expressed prostatic secretions (EPS) are proximal fluids of the prostate that are increasingly being utilized as a clinical source for diagnostic and prognostic assays for prostate cancer (PCa). These fluids contain an abundant amount of microvesicles reflecting the secretory function of the prostate gland, and their protein composition remains poorly defined in relation to PCa. Using expressed prostatic secretions in urine (EPS-urine), exosome preparations were characterized by a shotgun proteomics procedure.

Urinary TMPRSS2:ERG and PCA3 in an active surveillance cohort: results from a baseline analysis in the Canary Prostate Active Surveillance Study.

Purpose: Active surveillance is used to manage low-risk prostate cancer. Both PCA3 and TMPRSS2:ERG are promising biomarkers that may be associated with aggressive disease. This study examines the correlation of these biomarkers with higher cancer volume and grade determined at the time of biopsy in an active surveillance cohort.

Using preoperative albumin levels as a surrogate marker for outcomes after radical cystectomy for bladder cancer.

Objective: To evaluate preoperative albumin levels as a marker for comparing survival outcomes after cystectomy in patients with bladder cancer.

Materials And Methods: We performed a retrospective record review using our bladder cancer database of 238 patients from 2004 to 2011. Of these, we included 187 patients with sufficient data for analysis, aged 35 years or older, who survived to undergo cystectomy.

NADiA ProsVue prostate-specific antigen slope is an independent prognostic marker for identifying men at reduced risk of clinical recurrence of prostate cancer after radical prostatectomy.

Objective: To validate the hypothesis that men displaying serum prostate-specific antigen (PSA) slopes ≤ 2.0 pg/mL/mo after prostatectomy, measured using a new immuno-polymerase chain reaction diagnostic test (NADiA ProsVue), have a reduced risk of clinical recurrence as determined by positive biopsy, imaging findings, or death from prostate cancer.

Materials And Methods: From 4 clinical sites, we selected a cohort of 304 men who had been followed up for 17.

Identification of differentially expressed proteins in direct expressed prostatic secretions of men with organ-confined versus extracapsular prostate cancer.

Current protocols for the screening of prostate cancer cannot accurately discriminate clinically indolent tumors from more aggressive ones. One reliable indicator of outcome has been the determination of organ-confined versus nonorgan-confined disease but even this determination is often only made following prostatectomy. This underscores the need to explore alternate avenues to enhance outcome prediction of prostate cancer patients.

Identification of prostate-enriched proteins by in-depth proteomic analyses of expressed prostatic secretions in urine.

Urinary expressed prostatic secretion or "EPS-urine" is proximal tissue fluid that is collected after a digital rectal exam (DRE). EPS-urine is a rich source of prostate-derived proteins that can be used for biomarker discovery for prostate cancer (PCa) and other prostatic diseases. We previously conducted a comprehensive proteome analysis of direct expressed prostatic secretions (EPS).

Molecular preservation by extraction and fixation, mPREF: a method for small molecule biomarker analysis and histology on exactly the same tissue.

Background: Histopathology is the standard method for cancer diagnosis and grading to assess aggressiveness in clinical biopsies. Molecular biomarkers have also been described that are associated with cancer aggressiveness, however, the portion of tissue analyzed is often processed in a manner that is destructive to the tissue. We present here a new method for performing analysis of small molecule biomarkers and histology in exactly the same biopsy tissue.

Multiple recognition assay reveals prostasomes as promising plasma biomarkers for prostate cancer.

Prostate cancer is the most prevalent cancer in men over the age of 50 years. Prostate-specific antigen is limited as both an early detection and prognostic biomarker. Prostasomes are unique microvesicles of endocytic origin with a unique lamellar membrane composed of cholesterol and phospholipids known to be capable of fusing with other cells and thus acting as messengers between cells.

In-depth proteomic analyses of direct expressed prostatic secretions.

It is expected that clinically obtainable fluids that are proximal to organs contain a repertoire of secreted proteins and shed cells reflective of the physiological state of that tissue and thus represent potential sources for biomarker discovery, investigation of tissue-specific biology, and assay development. The prostate gland secretes many proteins into a prostatic fluid that combines with seminal vesicle fluids to promote sperm activation and function. Proximal fluids of the prostate that can be collected clinically are seminal plasma and expressed prostatic secretion (EPS) fluids.