Monocyte chemoattractant protein-1 (MCP-1) overproduction from inflamed adipose tissue is a major contributor to obesity-related metabolic syndromes. 3T3-L1 embryonic fibroblasts were cultured and differentiated into adipocytes using an established protocol. Adipocytes were treated with lipopolysaccharide (LPS) to induce inflammation and thus MCP-1 release. Read More
The urokinase plasminogen activator receptor (uPAR) has been proposed as a potential prognostic factor for various malignancies. The aim of this study is to assess the prognostic value of uPAR expression in neoplastic and stromal cells of patients with pancreatic adenocarcinoma. Urokinase plasminogen activator receptor expression was determined by immunohistochemistry in 122 pancreatic ductal adenocarcinomas. Read More
This review discusses the current state of biomarker discovery for the purposes of diagnostics and therapeutic monitoring. We underscore relevant challenges that have defined the gap between biomarker discovery and meaningful clinical use. We highlight recent advancements in and propose a way to think about future biomarker development. Read More
Blood-brain barrier (BBB) breakdown, inflammatory and immune cell activation, and chronic cerebral hypoperfusion are features of multiple sclerosis (MS). The aim is to determine the influence of endothelin-1 (ET1) and asymmetric dimethylarginine (ADMA) on cerebral circulation time (CCT) in patients with MS. In all, 64 patients with MS (39 relapsing-remitting [RR]-MS; 25 secondary progressive [SP]-MS subtype) and 37 controls (C) were studied. Read More
A data-independent acquisition (DIA)/parallel reaction monitoring (PRM) workflow was implemented to identify improved ovarian cancer biomarkers. Data-independent acquisition on ovarian cancer versus control sera and literature searches identified 50 biomarkers and indicated that apolipoprotein A-IV (ApoA-IV) is the most significantly differentially regulated protein. Parallel reaction monitoring with Targeted Ovarian Cancer Proteome Assay validated differential ApoA-IV expression and quantified 9 other biomarkers. Read More
Inflammation has been proposed to play a role in the generation of depressive symptoms. Previously, we demonstrated that patients with major depressive disorder (MDD) have increased plasma levels of the soluble form of the urokinase receptor (suPAR), a marker for low-grade inflammation. The aim of this study was to test the hypothesis that acute exercise would induce inflammatory response characterized by increased suPAR and elucidate whether patients with MDD display altered levels of suPAR in response to acute exercise. Read More
MicroRNAs (miRNAs) regulate the expression of protein-coding genes and represent potential biomarkers for childhood acute lymphoblastic leukemia (ALL). However, information linking miRNAs with their messenger RNA (mRNA) target genes modulating white blood cell (WBC) count is lacking. Here, we analyzed miRNAs and gene expression data from pediatric patients with ALL to identify a signature of miRNAs involved in ALL and their mRNA target genes, molecular networks, and biological pathways modulating WBC. Read More
The hepatocyte growth factor (HGF)/c-met axis plays a crucial role in cancer development by promoting cellular proliferation, motility, and morphogenesis, as well as angiogenesis. Different cellular distributions of both the ligand and the receptor in benign vs malignant lesions indicate this biological system as a candidate for a diagnostic biomarker of malignancy occurring in endocrine glands, such as the thyroid and pituitary. Furthermore, the HGF/c-met expression may help to identify a subset of patients eligible for potential targeted therapies with HGF/c-met inhibitors or antagonists in thyroid tumour, as well as in other malignancies. Read More
In preclinical studies, heregulin (HRG) expression was shown to be the most relevant predictive biomarker for response to patritumab, a fully human anti-epidermal growth factor receptor 3 monoclonal antibody. In support of a phase 2 study of erlotinib ± patritumab in non-small cell lung cancer (NSCLC), a reverse-transcription quantitative polymerase chain reaction (RT-qPCR) assay for relative quantification of HRG expression from formalin-fixed paraffin-embedded (FFPE) NSCLC tissue samples was developed and validated and described herein. Test specimens included matched FFPE normal lung and NSCLC and frozen NSCLC tissue, and HRG-positive and HRG-negative cell lines. Read More
Idiopathic nephrotic syndrome (NS) is the most common glomerular disorder of childhood. Response to initial treatment with corticosteroids is an indicator of prognosis, as resistant patients often present more progressive disease. In this cross-sectional pilot study, we set out to discover a panel of noninvasive biomarkers that could distinguish steroid-resistant nephrotic syndrome (SRNS) from steroid-sensitive nephrotic syndrome (SSNS). Read More
High-throughput genotyping has enabled discovery of genetic variants associated with an increased risk of developing prostate cancer using genome-wide association studies (GWAS). The goal of this study was to associate GWAS information of patients with primary organ-confined and metastatic prostate cancer using gene expression data and to identify molecular networks and biological pathways enriched for genetic susceptibility variants involved in the 2 disease states. The analysis revealed gene signatures for the 2 disease states and a gene signature distinguishing the 2 patient groups. Read More
Leptomeningeal carcinomatosis (LC) is a rare and mainly secondary site of metastasis in solid tumors. In gastric cancer (GC), it is associated with a devastating prognosis, lacking an efficient and standardized treatment approach. We report a case of primary manifestation of LC due to metastatic GC with rapid deterioration and refractory course to conventional and intrathecal chemotherapy. Read More
The molecular basis of the pathophysiological role of oxidative stress in autism is understudied. Herein, we used polymerase chain reaction (PCR) array to analyze transcriptional pattern of 84 oxidative stress genes in peripheral blood mononuclear cell pools isolated from 32 autistic patients (16 mild/moderate and 16 severe) and 16 healthy subjects (each sample is a pool from 4 autistic patients or 4 controls). The PCR array data were further validated by quantitative real-time PCR in 80 autistic children (55 mild/moderate and 25 severe) and 60 healthy subjects. Read More
The Cytochrome P-4501B1 (CYP1B1) Leu432Val polymorphism has been previously shown to be associated with some types of cancer and affects CYP1B1-mediated metabolism of various infertility drugs. To establish the frequency of CYP1B1 Leu432Val polymorphism among women with a history of infertility drug use, we studied the genotypes of 147 patients with breast cancer with a history of infertility and 150 cancer-free, infertile women (control group) in Northern Iran. A polymerase chain reaction-based restriction fragment length polymorphism assay was used to detect GG (Val/Val), CG (Leu/Val), and CC (Leu/Leu) genotype frequencies, which did not vary significantly between the 2 patient groups (P = . Read More
Aims: This study investigated the ability of soluble platelet selectin (sP-selectin) to identify infection and predict 30-day mortality in patients with a systemic inflammatory response syndrome (SIRS) on the intensive care unit.
Methods: Soluble platelet selectin levels were measured daily in the first 48 hours in patients presenting with SIRS. The outcome, proven infection, was established using predefined definitions. Read More
Cow's milk is economically important to the agricultural industry with the nutritive value of milk being routinely measured. This does not give full insight into normal mammary tissue turnover during the course of lactation, which could be important for both an understanding of milk production and animal welfare. We have previously demonstrated that submicron particles, including extracellular vesicles (EVs), can be measured in unprocessed cow's milk by flow cytometry and that they correlate with stage of lactation. Read More
Background: MammaPrint® is a microarray-based gene expression test cleared by the US Food and Drug Administration to assess recurrence risk in early-stage breast cancer, aimed to guide physicians in making neoadjuvant and adjuvant treatment decisions. The increase in the incidence of invasive lobular carcinomas (ILCs) over the past decades and the modest representation of ILC in the MammaPrint development data set calls for a stratified survival analysis dedicated to this specific subgroup.
Study Aim: The current study aimed to validate the prognostic value of the MammaPrint test for breast cancer patients with early-stage ILCs. Read More
It is encouraging to observe that a search for publications on "asymmetric dimethylarginine (ADMA)" in PubMed, as updated on June 2016, yielded >2500 items, 24 years after a splendid paper published by Vallance et al in which the authors proposed that ADMA accumulation could be a cardiovascular risk factor in chronic kidney diseases. ADMA is the endogenous inhibitor of nitric oxide synthase and is related to endothelial dysfunction, which plays an important role in vascular damage elicited by various cardiometabolic risk factors. Although current knowledge suggests that ADMA has critical central roles in renal diseases, there are still unexplained details. Read More
Objectives: To assess the kinetics of procalcitonin (PCT) and C-reactive protein (CRP) in newborns after cardiothoracic surgery (CS), with and without cardiopulmonary bypass, and to assess whether PCT was better than CRP in identifying sepsis in the first 72 hours after CS.
Patients And Methods: This is a prospective study of newborns admitted to the neonatal intensive care unit after CS.
Interventions: PCT and CRP were sequentially drawn 2 hours before surgery and at 0, 12, 24, 48, and 72 hours after surgery. Read More
Cisplatin is a known antitumor drug, but its mechanisms of action are not fully elucidated. In this research, we studied the anticancer potential of cisplatin at doses of 1, 2, or 3 µM using HL-60 cells as a test model. We investigated cisplatin effects at the molecular level using RNA sequencing, cell cycle analysis, and apoptotic assay after 24, 48, 72, and 96 hours of treatment. Read More
Shifting from the historical TNM paradigm to the determination of molecular and genetic subtypes of tumors has been a major improvement to better picture cancerous diseases. The sharper the picture is, the better will be the possibility to develop subsequent strategies, thus achieving higher efficacy and prolonged survival eventually. Recent studies suggest that urokinase-type plasminogen activator (uPA), uPA Receptor (uPAR), and plasmino-gen activator inhibitor-1 (PAI-1) may play a critical role in cancer invasion and metastasis. Read More
Diabetes is a global endemic with rapidly increasing prevalence in both developing and developed countries. The American Diabetes Association has recommended glycated hemoglobin (HbA1c) as a possible substitute to fasting blood glucose for diagnosis of diabetes. HbA1c is an important indicator of long-term glycemic control with the ability to reflect the cumulative glycemic history of the preceding two to three months. Read More
Objective: The aim of our study is to describe the changes in urinary and serum levels of novel biomarkers after gadolinium contrast administration in patients with normal renal function.
Methods: We measured four biomarkers in 28 volunteers: interleukin-18 (IL-18), N-acetyl-glucosaminidase (NAG), neutrophil gelatinase-associated lipocalin, and cystatin C. Urinary and serum samples were collected at 0, 3, and 24 hours following gadolinium administration. Read More
Pulmonary hypertension is a severe and debilitating disease with no definite cure, and the domain of targeted therapies is a promising field for better management of this severe condition. The disease comprises pulmonary arterial remodeling, hypoxia, endothelial dysfunction, and inflammation, with subsequent organ damage including right heart and liver dysfunction. Biomarkers have a valuable role at different levels of the disease, from diagnosis to risk assessment and management, in order to decrease the burden of the disease in terms of both morbidity and mortality. Read More
The aim of this study was to set up an ex vivo model for renal interstitial fibrosis in order to investigate the extracellular matrix (ECM) turnover profile in the fibrotic kidney. We induced kidney fibrosis in fourteen 12-week-old male Sprague Dawley rats by unilateral ureteral obstruction (UUO) surgery of the right ureter. The left kidney (contralateral) was used as internal control. Read More
Background: The guanine nucleotide-binding protein beta polypeptide 3 (GNB3) 825T allele encodes a product that enhances the activation of heterotrimeric G proteins, which is associated with the occurrence of the splice variant Gβ3 s that could play a role in vascular reactivity and hyperproliferation of smooth muscle cells, that makes such proteins attractive candidate gene products for susceptibility to essential hypertension (EH).
Objective: To predict the risk for EH in individuals with C825T genetic polymorphism of G protein β3 gene.
Methods: The study consisted of 222 normotensive individuals and 216 hypertensive patients. Read More
Heme oxygenase (HO) catalyzes the breakdown of heme to carbon monoxide, iron, and biliverdin. While the use of genetically altered animal models in investigation has established distinct associations between HO activity and systemic iron availability, studies have not yet confirmed such participation of HO in iron homeostasis of humans. Carbon monoxide produced through HO activity will bind to hemoglobin in circulating erythrocytes, and therefore, blood carboxyhemoglobin (COHb) can be used as an index of HO activity. Read More
Aim: This study aimed at evaluation of ischemia-modified albumin (IMA), malondialdehyde (MDA), and advanced oxidative protein products (AOPP) as markers of vascular injury in diabetic nephropathy (DN) with derivation of cutoff values for the same.
Materials And Methods: Study population comprised 60 diabetes patients and 30 controls, with diabetes patients further categorized into three groups based on urine albumin/creatinine ratio (UACR) of <30 mg/g (diabetes without microalbuminuria), 30-300 mg/g (early DN), and >300 mg/g of creatinine (overt DN). Serum IMA, MDA, and AOPP were estimated by enzyme-linked immunosorbent assay; HbA1c, serum creatinine, urine albumin, and urine creatinine were estimated using automated analyzers. Read More
Femoral head necrosis (FHN) is a skeletal problem in broiler chickens, where the proximal femoral head cartilage shows susceptibility to separation from its growth plate. The selected birds with FHN showed higher body weights and reduced plasma cholesterol. The proteomic differences in the plasma of healthy and FHN-affected chickens were explored using matrix-assisted laser desorption ionization time of flight mass spectrometry (MALDI-TOF-MS) and liquid chromatography/electrospray ionization-tandem mass spectrometry (LC-MS/MS) to prospect for protein biomarkers. Read More
Urine proteome is a potential source of information in renal diseases, and it is considered a natural area of investigation for biomarkers. Technology developments have markedly increased the power analysis on urinary proteins, and it is time to confront methodologies and results of major studies on the topics. This is a first part of a series of reviews that will focus on the urine proteome as a site for detecting biomarkers of renal diseases; the theme of the first review concerns methodological aspects applied to normal urine. Read More
Diabetic nephropathy (DN) is one of the most serious microvascular complications of diabetes. The study aims to evaluate the diagnostic value of serum neutrophil gelatinase-associated lipocalin (NGAL) and retinol-binding protein 4 (RBP4) as biomarkers for early detection of nephropathy in type 2 diabetic patients. The current study was performed on 150 type 2 diabetic patients. Read More
To streamline in vivo biomarker discovery, we developed a suppression subtractive DNA hybridization technique adapted for phage-displayed combinatorial libraries of 12 amino acid peptides (PhiSSH). Physical DNA subtraction is performed in a one-tube-all-reactions format by sequential addition of reagents, producing the enrichment of specific clones of one repertoire. High-complexity phage repertoires produced by in vivo selections in the multiple sclerosis rat model (experimental autoimmune encephalomyelitis, EAE) and matched healthy control rats were used to evaluate the technique. Read More
Unlabelled: Evaluation of patient's response to chemotherapeutic drugs is often difficult and time consuming. Skin punch biopsies are easily accessible material that can be used for the evaluation of surrogate biomarkers of a patient's response to a drug. In this study, we hypothesized that assessment of phosphorylated histone H3 in human skin punch biopsies could be used as a pharmacodynamics biomarker of patient's response to the kinesin spindle protein inhibitor SCH2047069. Read More
This review discusses biomarkers that are being researched for their usefulness to phenotype chronic inflammatory lung diseases that cause remodeling of the lung's architecture. The review focuses on asthma, chronic obstructive pulmonary disease (COPD), and pulmonary hypertension. Bio-markers of environmental exposure and specific classes of biomarkers (noncoding RNA, metabolism, vitamin, coagulation, and microbiome related) are also discussed. Read More
Chronic myeloid leukemia (CML) is a myeloproliferative disorder associated with a characteristic chromosomal translocation called the Philadelphia chromosome. This oncogene is generated by the fusion of breakpoint cluster region (BCR) and Abelson leukemia virus (ABL) genes and encodes a novel fusion gene translating into a protein with constitutive tyrosine kinase activity. The discovery and introduction of tyrosine kinase inhibitors (TKIs) irreversibly changed the landscape of CML treatment, leading to dramatic improvement in long-term survival rates. Read More
This study describes our efforts to further the field of noninvasive diagnostics, specifically in the area of liquid biopsies in oncology. We employed laser scanning cytometry using highly selective antibodies to interrogate circulating tumor cells (CTCs) that were isolated using ApoStream(®) technology to identify folate receptor alpha (FRα)-positive cells. We demonstrate that FRα(+) CTCs can be isolated from patients with metastatic cancers, including NSCLC adenocarcinoma, breast cancer, and ovarian cancer, whereas squamous cell lung cancer and normal healthy controls were devoid of FRα(+) CTCs. Read More
High-throughput sequencing studies of small RNAs reveal a complex milieu of noncoding RNAs in biological samples. Early data analysis was often limited to microRNAs due to their regulatory nature and potential as biomarkers; however, many more classes of noncoding RNAs are now being recognized. A class of fragments initially excluded from analysis were those derived from transfer RNAs (tRNAs) because they were thought to be degradation products. Read More
Biomarker identification is often associated with the diagnosis and evaluation of various diseases. Recently, the role of microRNA (miRNA) has been implicated in the development of diseases, particularly cancer. With the advent of next-generation sequencing, the amount of data on miRNA has increased tremendously in the last decade, requiring new bioinformatics approaches for processing and storing new information. Read More
MicroRNAs (miRNAs) are short sequences of noncoding single-stranded RNAs that exhibit inhibitory effects on complementary target mRNAs. Recently, it has been discovered that certain viruses express their own miRNAs, while other viruses activate the transcription of cellular miRNAs for their own benefit. This review summarizes the viral and/or cellular miRNAs that are transcribed during infection, with a focus on the biomarker and therapeutic potential of miRNAs (or their antagomirs). Read More
Background: Idiopathic nephrotic syndrome (NS) is one of the most common glomerular disorders of childhood and is associated with increased urinary vitamin D-binding protein (uVDBP) excretion. We tested the hypothesis that uVDBP represents a biomarker to differentiate steroid-resistant nephrotic syndrome (SRNS) from the more benign forms of steroid-sensitive nephrotic syndrome (SSNS).
Methods: This cross-sectional study included children with SRNS (n = 24), SSNS (n = 28), and normal controls (n = 5). Read More
Induced pluripotent stem cells (iPSCs) are somatic cells that have been transcriptionally reprogrammed to an embryonic stem cell (ESC)-like state. iPSCs are a renewable source of diverse somatic cell types and tissues matching the original patient, including nephron-like kidney organoids. iPSCs have been derived representing several kidney disorders, such as ADPKD, ARPKD, Alport syndrome, and lupus nephritis, with the goals of generating replacement tissue and 'disease in a dish' laboratory models. Read More
Bacterial meningitis (BM) is a pyogenic infection present in the subarachnoid space, potentially fatal and frequently associated with neurological sequelae. During BM, cytokines (CTs) are locally produced. We sought to determine the CTs' clinical role as disease severity predictors in adults, which is not completely clear. Read More
Biomark Insights 2015 13;10:113-24. Epub 2015 Dec 13.
Programa de Pós-Graduação em Genética e Biologia Molecular, Universidade Federal do Rio Grande do Sul, Porto Alegre, Rio Grande do Sul, Brazil. ; Laboratório de Medicina Genômica, Centro de Pesquisa Experimental, Hospital de Clínicas de Porto Alegre, Porto Alegre, Rio Grande do Sul, Brazil.
Pancreatic ductal adenocarcinoma (PDAC), a rare but lethal tumor, is difficult to diagnose without performing an invasive procedure. miRNAs are known to be deregulated in PDAC patients, and recent studies have shown that they can be used as diagnostic and prognostic of the disease. The detection of miRNAs in samples acquired through minimally or noninvasive procedures, such as serum, plasma, and saliva, can have a positive impact on the clinical management of these patients. Read More
The introduction of tyrosine kinase inhibitors (TKIs) in the treatment of chronic myeloid leukemia (CML) has significantly increased survival rate and quality of life for patients with CML. Despite the high efficacy of imatinib, not all patients benefit from this treatment. Resistance to imatinib can develop from a number of mechanisms. Read More
The objective of the present study was to validate prognostic gene signature for estrogen receptor alpha-positive (ER03B1+) and lymph node (+) breast cancer for improved selection of patients for adjuvant therapy. In our previous study, we identified a group of seven genes (GATA3, NTN4, SLC7A8, ENPP1, MLPH, LAMB2, and PLAT) that show elevated messenger RNA (mRNA) expression levels in ERα (+) breast cancer patient samples. The prognostic values of these genes were evaluated using gene expression data from three public data sets of breast cancer patients (n = 395). Read More
MicroRNA-155 (miR-155) is a multifunctional molecule involved in both normal and malignant hematopoiesis. It has been found to be involved in the pathogenesis of many different hematological malignancies with either an oncogenic or a tumor-repressor effect, depending on the nature of the cell and the type of malignancy. In particular, it has been strongly implicated in the causation of diffuse large B-cell lymphomas. Read More
Dysregulation of the PI3K/AKT/mammalian target of rapamycin (mTOR) pathway could contribute to the pathogenesis of autism spectrum disorders. In this study, phosphorylated Akt concentration was measured in 37 autistic children and 12, gender and age similar neurotypical, controls using an enzyme-linked immunosorbent assay. Akt levels were compared to biomarkers known to be associated with epidermal growth factor receptor (EGFR) and c-Met (hepatocyte growth factor (HGF) receptor) pathways and severity levels of 19 autism-related symptoms. Read More
The use of tyrosine kinase inhibitors (TKIs) in the treatment of solid tumors is the expected standard of care for many types of tumors. Since the description of signal transduction pathways, followed by the development of small molecules designed to inhibit those pathways, there has been significant improvement not only in progression-free survival and overall survival but also in aiming toward chemotherapy-free treatment of solid tumors to maximize quality of life. This article reviews available TKIs and discusses toxicity, dosing, and resistance. Read More
Recognizing an increasing need for biomarkers that predict clinical outcomes in type 1 diabetes (T1D), JDRF, a major funding organization for T1D research, recently instituted the Core for Assay Validation (CAV) to accelerate the translation of promising assays from discovery to clinical implementation via a process of coordinated evaluation of biomarkers. In this model, the CAV facilitates the validation of candidate assay methods as well as qualification of proposed biomarkers for a specific clinical use in well-characterized patients. We describe here a CAV-driven pilot project aimed at identifying biomarkers that predict the rate of decline in beta cell function after diagnosis. Read More