Clinical Validation of IsoPSA™, a Single Parameter, Structure Based Assay for Improved Detection of High Grade Prostate Cancer.

Purpose: Current prostate specific antigen markers to detect prostate cancer are limited by low specificity for high grade disease. IsoPSA™ is a blood based, structure focused assay which predicts risk by partitioning the isoforms of prostate specific antigen that are linked to cancer in an aqueous 2-phase reagent system. We validated the clinical performance of this assay for identifying high grade disease in a new contemporary biopsy cohort.

The Single-parameter, Structure-based IsoPSA Assay Demonstrates Improved Diagnostic Accuracy for Detection of Any Prostate Cancer and High-grade Prostate Cancer Compared to a Concentration-based Assay of Total Prostate-specific Antigen: A Preliminary Report.

Background: IsoPSA is a serum-based assay that predicts prostate cancer (PCa) risk by partitioning isoforms of prostate-specific antigen (PSA) with an aqueous two-phase reagent.

Objectives: To determine the diagnostic accuracy of IsoPSA in identifying the presence or absence of PCa and the presence of high-grade disease in a contemporary biopsy cohort.

Design, Setting, And Participants: Multicenter prospective study of 261 men scheduled for prostate biopsy at five academic and community centers in the USA enrolled between August 2015 and December 2016.

Analytical applications of partitioning in aqueous two-phase systems: Exploring protein structural changes and protein-partner interactions in vitro and in vivo by solvent interaction analysis method.

This review covers the fundamentals of protein partitioning in aqueous two-phase systems (ATPS). Included is a review of advancements in the analytical application of solute partitioning in ATPS over the last two decades, with multiple examples of experimental data providing evidence that phase-forming polymers do not interact with solutes partitioned in ATPS. The partitioning of solutes is governed by the differences in solute interactions with aqueous media in the two phases.

Solvent interaction analysis as a proteomic approach to structure-based biomarker discovery and clinical diagnostics.

Proteins have several measurable features in biological fluids that may change under pathological conditions. The current disease biomarker discovery is mostly based on protein concentration in the sample as the measurable feature. Changes in protein structures, such as post-translational modifications and in protein-partner interactions are known to accompany pathological processes.

Solvatochromic relationship: prediction of distribution of ionic solutes in aqueous two-phase systems.

Partition ratios of several ionic compounds in 20 different polymer/polymer aqueous two-phase systems (ATPS) containing 0.15 M NaCl in 0.01 M phosphate buffer, pH 7.

High throughput characterization of structural differences between closely related proteins in solution.

Partitioning of a protein in an aqueous two-phase system (ATPS) is governed by interactions of the protein with aqueous media in the two phases. Here we describe how partitioning of proteins in a set of ATPS of different compositions can be used to quantify differences between 3D structures of closely related proteins. We also provide perspective on practical applications of the technology when comparative analysis of the higher-order structure of proteins is desired.

Prostate-specific antigen/solvent interaction analysis: a preliminary evaluation of a new assay concept for detecting prostate cancer using urinary samples.

Objective: To provide preliminary clinical performance evaluation of a novel prostate cancer (CaP) assay, prostate-specific antigen/solvent interaction analysis (PSA/SIA) that focused on changes to the structure of PSA.

Methods: Two-hundred twenty-two men undergoing prostate biopsy for accepted clinical criteria at 3 sites (University Hospitals Case Medical Center in Cleveland, Cleveland Clinic, and Veterans Administration Boston Healthcare System) were enrolled in institutional review board-approved study. Before transrectal ultrasound-guided biopsy, patients received digital rectal examination with systematic prostate massage followed by collection of urine.

Effect of salt additives on partition of nonionic solutes in aqueous PEG-sodium sulfate two-phase system.

Partition of 12 nonionic organic compounds in aqueous PEG-8000-Na(2)SO(4) two-phase system was examined. Effects of four salt additives (NaCl, NaSCN, NaClO(4), and NaH(2)PO(4)) in the concentration range from 0.027 up to ca.

Solvent properties governing protein partitioning in polymer/polymer aqueous two-phase systems.

Distribution coefficients of various proteins were measured in aqueous Dextran-Ficoll, Dextran-PES, and Ficoll-PES two-phase systems, containing 0.15M NaCl in 0.01 M phosphate buffer, pH 7.

Protein crystallization: virtual screening and optimization.

Advances in genomics have yielded entire genetic sequences for a variety of prokaryotic and eukaryotic organisms. This accumulating information has escalated the demands for three-dimensional protein structure determinations. As a result, high-throughput structural genomics has become a major international research focus.

Relative hydrophobicity and lipophilicity of drugs measured by aqueous two-phase partitioning, octanol-buffer partitioning and HPLC. A simple model for predicting blood-brain distribution.

Relative hydrophobicity and lipophilicity of 63 compounds with known permeability through the blood-brain barrier (BBB) was examined by partitioning in aqueous dextran-poly(ethylene glycol) two-phase system and octanol-buffer system, and by gradient RP-HPLC at pH 7.4. Combination of the relative hydrophobicity estimates, N(CH(2)) obtained by aqueous two-phase partitioning and the lipophilicity (logD(exp) or logD(HPLC)) values obtained by the shake-flask technique or HPLC technique allows one to differentiate between compounds capable of crossing the BBB and those that cannot.

Efficient protein crystallization.

High-throughput molecular biology and crystallography advances have placed an increasing demand on crystallization, the one remaining bottleneck in macromolecular crystallography. This paper describes three experimental approaches, an incomplete factorial crystallization screen, a high-throughput nanoliter crystallization system, and the use of a neural net to predict crystallization conditions via a small sample (approximately 0.1%) of screening results.

Relative hydrophobicity and lipophilicity of beta-blockers and related compounds as measured by aqueous two-phase partitioning, octanol-buffer partitioning, and HPLC.

Partitioning of 15 beta-blockers and structurally related compounds was examined in aqueous dextran-PEG two-phase systems and octanol-buffer systems at pH from 2.0 up to 12.5.