Biochemical differences in the mass and activity tests of lipoprotein-associated phospholipase A explain the discordance in results between the two assay methods.

Objectives: There are two platforms for the detection of Lp-PLA in sera or plasmas: by its enzymatic activity (PLAC® activity test) and by its mass concentration (PLAC® mass test). It has been long recognized that these two platforms are not correlated well. The underlying cause for this is therefore investigated by the biochemical characterization of the two PLAC tests.

Metabolomics and its Application to the Development of Clinical Laboratory Tests for Prostate Cancer.

Introduction: There is a critical need to develop clinical laboratory assays that provide risk assessment for men at elevated risk for prostate cancer, and once diagnosed, could further identify those men with clinically significant disease.

Methods: Recent advancements in analytical instrumentation have enabled mass spectrometry-based metabolomics methodologies. Further advancements in chromatographic techniques have facilitated high throughput, quantitative assays for a broad spectrum of biochemicals.

Bladder cancer biomarker discovery using global metabolomic profiling of urine.

Bladder cancer (BCa) is a common malignancy worldwide and has a high probability of recurrence after initial diagnosis and treatment. As a result, recurrent surveillance, primarily involving repeated cystoscopies, is a critical component of post diagnosis patient management. Since cystoscopy is invasive, expensive and a possible deterrent to patient compliance with regular follow-up screening, new non-invasive technologies to aid in the detection of recurrent and/or primary bladder cancer are strongly needed.

Lipoprotein-associated phospholipase A2 is associated with atherosclerotic stroke risk: the Northern Manhattan Study.

Background: Lipoprotein-associated phospholipase A2 (LpPLA2) levels are associated with stroke, though whether this extends to all populations and stroke subtypes is unknown.

Methods: Serum samples from stroke-free community participants in the Northern Manhattan Study were assayed for LpPLA2 mass and activity. Participants were followed annually for stroke.

Lipoprotein-associated phospholipase A2, a novel cardiovascular inflammatory marker, in HIV-infected patients.

Background: Lipoprotein-associated phospholipase A2 (Lp-PLA2) is an emerging biomarker of cardiovascular disease. This study was conducted to describe the distribution of Lp-PLA2 in a cohort of human immunodeficiency virus (HIV)-infected adults and to determine associations between Lp-PLA2, cardiometabolic risk factors, and subclinical atherosclerosis in this population.

Methods: Lp-PLA2 was assessed in 341 (25% women, 52% white, 74% on highly active antiretroviral therapy [HAART]) participants of a cohort with detailed characterization of atherogenic risk factors, including surrogate markers of carotid and coronary atherosclerosis.

The elevation of apoB in hypercholesterolemic patients is primarily attributed to the relative increase of apoB/Lp-PLA₂.

Lipoprotein-associated phospholipase A₂ (Lp-PLA₂) is a risk factor of cardiovascular disease. Plasma Lp-PLA₂ is mainly associated with apolipoprotein (apo)B-containing lipoproteins, primarily with low density lipoproteins (LDLs). Importantly, only a proportion of circulating lipoproteins contain Lp-PLA₂.

Metabolomic signatures of aggressive prostate cancer.

Background: Current diagnostic techniques have increased the detection of prostate cancer; however, these tools inadequately stratify patients to minimize mortality. Recent studies have identified a biochemical signature of prostate cancer metastasis, including increased sarcosine abundance. This study examined the association of tissue metabolites with other clinically significant findings.

Lipoprotein-associated phospholipase A2 activity predicts cardiovascular events in high risk coronary artery disease patients.

Objective: Lipoprotein-associated phospholipase A2 (Lp-PLA2) is deemed to play a role in atherosclerosis and plaque destabilization as demonstrated in animal models and in prospective clinical studies. However, most of the literature is either focused on high-risk, apparently healthy patients, or is based on cross sectional studies. Therefore, we tested the hypothesis that serum Lp-PLA2 mass and activity are useful for predicting cardiovascular (CV) events over the coronary atherosclerotic burden and conventional risk factors in high-risk coronary artery disease patients.

Relationship of lipoprotein-associated phospholipase A₂ mass and activity with incident vascular events among primary prevention patients allocated to placebo or to statin therapy: an analysis from the JUPITER trial.

Background: Although lipoprotein-associated phospholipase A(2) (Lp-PLA(2)) levels are associated with cardiovascular events, Lp-PLA(2) is physically linked to LDL cholesterol (LDL-C). Whether measures of Lp-PLA(2) mass or activity continue to predict risk after LDL-C reduction by statin therapy is uncertain.

Methods: Lp-PLA(2) mass concentration and activity were evaluated at baseline and after treatment in the Justification for the Use of Statins in Prevention: an Intervention Trial Evaluating Rosuvastatin (JUPITER) trial comparing rosuvastatin 20 mg to placebo among 17 802 men and women without cardiovascular disease or diabetes at study entry.

Lipoprotein-associated phospholipase A(2) mass and activity and risk of cardiovascular disease in a population with high prevalences of obesity and diabetes: the Strong Heart Study.

Objective: To investigate the association of lipoprotein-associated phospholipase A(2) (LpPLA(2)) mass and activity with incident cardiovascular disease (CVD) in a population with high prevalences of insulin resistance and diabetes, conditions for which epidemiological data remain sparse.

Research Design And Methods: We conducted a nested, case-control study (n = 1,008) within a population-based cohort of American Indians. Case subjects were defined by incidence of first-ever CVD up to 10 years later.

Lipoprotein associated phospholipase A2 concentration predicts total and cardiovascular mortality independently of established risk factors (The Ludwigshafen Risk and Cardiovascular Health Study).

Background: Lipoprotein-associated phospholipase A2 (LpPLA2) is a lipoprotein-bound enzyme involved in inflammation and atherosclerosis. This cohort study investigates LpPLA2 concentration to predict cardiovascular and total mortality in patients scheduled for coronary angiography.

Methods: LpPLA2 concentration was determined in 2298 patients with and in 661 patients without angiographically confirmed coronary artery disease (CAD).

Lipoprotein associated phospholipase A(2): role in atherosclerosis and utility as a biomarker for cardiovascular risk.

Atherosclerosis and its clinical manifestations are widely prevalent throughout the world. Atherogenesis is highly complex and modulated by numerous genetic and environmental risk factors. A large body of basic scientific and clinical research supports the conclusion that inflammation plays a significant role in atherogenesis along the entire continuum of its progression.

Epitope binning of murine monoclonal antibodies by a multiplexed pairing assay.

We describe an assay and data evaluation technique for sorting a panel of murine monoclonal antibodies according to epitope specificities. The assay analyzes the simultaneous binding (pairing) of antibodies to an antigen and groups together antibodies with similar pairing profiles. Similar profiles indicate that the antibodies bind to the same or closely related epitopes.

Enhancing the secretion of recombinant proteins by engineering N-glycosylation sites.

N-glycosylation is important for the folding and quality control of membrane and secretory proteins. We used mutagenesis to introduce N-glycosylation sequons in recombinant proteins to improve their secretion in HEK293 cells. Seven recombinant proteins, with or without endogenous N-glycosylation sequons, were tested by this method.

A twin study of heritability of plasma lipoprotein-associated phospholipase A2 (Lp-PLA2) mass and activity.

Objective: We investigated heritability of plasma levels (mass) and activity of lipoprotein-associated phospholipase A(2) (Lp-PLA(2)).

Materials And Methods: In 54 healthy twins pairs we estimated genetic variance and heritability of Lp-PLA(2) mass and activity using maximum likelihood and least squares methods. We estimated intra-class correlation (ICC) and proportion of additive genetic variance from a model comprising additive genetic influence (A), environmental effect common to cotwins (C) and individually unique environmental (E) influence (ACE) model.

Lipoprotein-associated phospholipase A2 is an independent predictor of incident coronary heart disease in an apparently healthy older population: the Rancho Bernardo Study.

Objectives: Lipoprotein-associated phospholipase A2 (Lp-PLA2) levels predict incident coronary heart disease (CHD) in adults without known CHD, independent of heart disease risk factors. We examined whether the independent association was apparent in older adults.

Background: Serum levels of Lp-PLA2, an enzyme that hydrolyzes oxidized phospholipids to yield potentially proatherogenic particles, have been associated with CHD and may help predict cardiovascular risk.

A multiparametric panel for ovarian cancer diagnosis, prognosis, and response to chemotherapy.

Purpose: Our goal was to examine a panel of 11 biochemical variables, measured in cytosolic extracts of ovarian tissues (normal, benign, and malignant) by quantitative ELISAs for their ability to diagnose, prognose, and predict response to chemotherapy of ovarian cancer patients.

Experimental Design: Eleven proteins were measured (9 kallikreins, B7-H4, and CA125) in cytosolic extracts of 259 ovarian tumor tissues, 50 tissues from benign conditions, 35 normal tissues, and 44 tissues from nonovarian tumors that metastasized to the ovary. Odds ratios and hazard ratios and their 95% confidence interval were calculated.

Differential effect of hypolipidemic drugs on lipoprotein-associated phospholipase A2.

Objective: Lipoprotein-associated phospholipase A2 (Lp-PLA2) is a predictor for incident atherosclerotic disease. We investigated the effect of 3 hypolipidemic drugs that exert their action through different mechanisms on plasma and lipoprotein-associated Lp-PLA2 activity and mass.

Methods And Results: In 50 patients with Type IIA dyslipidemia were administered rosuvastatin (10 mg daily), whereas in 50 Type IIA dyslipidemic patients exhibiting intolerance to previous statin therapy were administered ezetimibe as monotherapy (10 mg daily).

B7-H4 is over-expressed in early-stage ovarian cancer and is independent of CA125 expression.

Objective: This study characterizes the expression of the novel biomarker B7-H4 in ovarian cancer tissue, normal ovaries, and benign ovarian tumors, and evaluates its relationship to CA125.

Methods: Ovarian tissue lysates from 251 patients with ovarian carcinoma were assessed for the levels of B7-H4 and CA125 by ELISA assays. For comparison, ovarian tissues from patients with benign ovarian tumors (n=43) and patients with normal ovaries (n=32) were tested.

Evaluation of the novel serum markers B7-H4, Spondin 2, and DcR3 for diagnosis and early detection of ovarian cancer.

Objective: Early detection through regular screening could significantly reduce mortality from ovarian cancer. Advances in biomarkers and imaging continue to improve the sensitivity and specificity of cancer detection, but further improvements are still needed. In this study, we identified and evaluated three new serum biomarkers that may be used to improve detection of ovarian cancer.

Lipoprotein-associated phospholipase A2 independently predicts the angiographic diagnosis of coronary artery disease and coronary death.

Background: Whereas C-reactive protein (CRP) is a nonspecific marker of coronary artery disease (CAD) and cardiovascular (CV) events, Lp-PLA2 may be a nonvariable inflammatory biomarker. We evaluated the independent association of lipoprotein-associated phospholipase A2 (Lp-PLA2) to angiographic CAD and CV events adjusting for standard factors, lipids, and CRP.

Methods: Lipoprotein-associated phospholipase A2 (PLAC test, diaDexus, Inc, San Francisco, CA) and CRP were measured from samples donated by consecutive consenting patients (N = 1493) enrolled in the registry of the Intermountain Heart Collaborative Study.

Lipoprotein-associated phospholipase A2: review and recommendation of a clinical cut point for adults.

Recently, several epidemiologic studies have demonstrated an association between plasma lipoprotein-associated phospholipase A2 (Lp-PLA2) concentration and risk of subsequent cardiovascular events. Several major commercial and reference laboratories across the United States are now offering Lp-PLA2 testing for clinical use to evaluate cardiovascular risk and as a guide to intensity of therapy in individuals at intermediate risk for developing coronary heart disease. Each laboratory has established its own cut points, or "decision values," for Lp-PLA2, which vary from the 50th to the 95th percentile values of individual populations tested at each site.

The reduction of inflammatory biomarkers by statin, fibrate, and combination therapy among diabetic patients with mixed dyslipidemia: the DIACOR (Diabetes and Combined Lipid Therapy Regimen) study.

Objectives: The primary objective was to determine the effect of statin-fibrate combination therapy on inflammatory biomarkers in patients with diabetes.

Background: Atherosclerosis is a long-term, chronic inflammatory disease that is exacerbated in patients with diabetes.

Methods: Patients (n = 300) with type II diabetes, mixed dyslipidemia (2 or more of low-density lipoprotein > or =100 mg/dl, triglycerides > or =200 mg/dl, or high-density lipoprotein <40 mg/dl), and no history of coronary heart disease were randomly assigned to receive simvastatin 20 mg, fenofibrate 160 mg, or a combination of simvastatin 20 mg and fenofibrate 160 mg daily.

B7-h4 is a novel membrane-bound protein and a candidate serum and tissue biomarker for ovarian cancer.

Using cDNA database mining strategies and real-time quantitative reverse transcription-PCR, we identified B7-H4 as a novel gene that is overexpressed in ovarian and breast cancer tissues when compared with normal tissues. The gene encodes a protein of 282 amino acids with a signal sequence, an immunoglobulin domain, and a COOH-terminal hydrophobic transmembrane domain. Immunohistochemistry experiments show plasma membrane staining in serous ovarian and breast cancer, confirming the tissue specificity and cell surface localization.