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New Biomarkers (new + biomarker)
Selected AbstractsEarly detection of acute kidney injury: Emerging new biomarkers (Review Article)NEPHROLOGY, Issue 2 2008ZOLTAN H ENDRE SUMMARY: Acute kidney injury (AKI) has recently become the preferred term to describe the syndrome of acute renal failure (ARF) with ,failure' or ,ARF' restricted to patients who have AKI and need renal replacement therapy.1 This allows capture of the broader clinical spectrum of modest reductions in creatinine, which are themselves known to be associated with major increases in both short- and long-term mortality risk.2,5 It is hoped that this change in nomenclature will facilitate an expansion of our understanding of the underlying pathophysiology and also facilitate definitions of AKI, which allow comparisons among clinical trials of patients with similar duration and severity of illness. This review will cover the need for early detection of AKI and the role of urinary and plasma biomarkers, including enzymuria. The primary message is that use of existing criteria to diagnose AKI, namely elevation of the serum creatinine with or without oliguria, results in identification that is too late to allow successful intervention. New biomarkers are essential to change the dire prognosis of this common condition. [source] Analysis of Heritability of Hormonal Responses to Alcohol in Twins: Beta-Endorphin as a Potential Biomarker of Genetic Risk for AlcoholismALCOHOLISM, Issue 3 2000J. C. Froehlich Background: Hormonal responses to alcohol have been reported to differ in subjects with and without a family history of alcoholism which suggests that alcohol-induced hormonal changes might be used to identify individuals who are at elevated genetic risk for developing alcoholism. However, before a biological response can be used as a marker of genetic risk for disease, it must first be demonstrated that the response is, in fact, heritable. The present study was designed to determine whether hormonal responses to alcohol are heritable. Methods: The adrenocorticotropic hormone (ACTH), beta-endorphin (,-E), cortisol (CORT), and prolactin (PRL) responses to alcohol were examined in male and female identical (monozygotic or MZ) and fraternal (dizygotic or DZ) twin pairs. Male subjects consumed 0.35g ethanol/kg body weight (BW) and female consumed 0.325 g ethanol/kg BW in each of two alcohol drinking sessions administered 1 hr apar (total dose of 0.7 g/kg BW in males and 0.65 g/kg BW in females). Plasma hormone content was analyzed in samples collected before (resting conditions) and at 15, 60, 75, 120, 180, and 240 min after onset of drinking. Hormonal responses to alcohol were examined with twin analyses using the TWINAN90 program. A separate analysis was performed for each of the four hormones. A subset of subjects from each zygosity was seen on two separate occasions to establish retest reliability. Heritability of hormonal responses to alcohol was estimated using the intraclass correlation approach before and after removing the contribution of covariates that have the potential of influencing the plasma levels of these hormones. Results: Resting plasma levels of all four hormones were within the expected range, and the ,-E, ACTH, and PRL responses to the alcohol challenge evidenced good test-retest reliability. Of the four hormones examined, the only one that showed significant heritability after alcohol drinking was ,-E. Heritability estimates were not altered for any of the four hormones after removal of the variance contributed by covariates, such as gender and age. Conclusions: Taken together with other recent findings, the results suggest that the ,-E response to alcohol may represent a new biomarker that can be used to identify individuals who are at elevated genetic risk for developing alcoholism. [source] Review article: diagnosis and treatment of non-alcoholic fatty liver diseaseALIMENTARY PHARMACOLOGY & THERAPEUTICS, Issue 5 2008M. K. OH Summary Background, Non-alcoholic fatty liver disease (NAFLD) is an increasingly prevalent condition affecting adults and children, leading to significant morbidity. It is often associated with the metabolic syndrome, although multiple pathogenetic mechanisms have been suggested. In the coming decades, it promises to be the leading cause of liver disease in industrial countries. Aim, To provide a comprehensive, updated review of diagnosis and management of NAFLD and to appraise the evolution of new modalities in these areas. Methods, An Ovid MEDLINE search was performed to identify pertinent original research and review articles. Selected references in these articles were also evaluated. Results, The diagnosis of hepatic steatosis and steatohepatitis or non-alcoholic steatohepatitis (NASH) is not yet possible without liver biopsy. This is impractical given the large numbers affected by the condition. Current therapy has focused on improving insulin resistance and mediators of inflammation, factors probably associated with disease progression. Conclusions, There are no proven non-invasive diagnostic modalities to distinguish NAFLD and NASH, but new biomarker panels are approximating the liver biopsy in accuracy. Therapeutic targets of drug development are in early stages, but a multifaceted approach will probably yield several treatment options in the years to come. [source] Quantitative analysis of amoA mRNA expression as a new biomarker of ammonia oxidation activities in a complex microbial communityLETTERS IN APPLIED MICROBIOLOGY, Issue 6 2004Y. Aoi Abstract Aims:, To quantitatively analyse the changes to amoA mRNA (ammonia mono-oxygenase encoding mRNA) profiles in response to a change in ammonia oxidation activity in a complex microbial community. Methods and Results:, The amoA mRNA levels in both a batch-mode incubation and a continuously fed nitrification reactor were determined by real-time reverse transcription-PCR analysis. The amoA mRNA level changed rapidly in response to the change in environmental conditions which affect ammonia oxidation activity. Conclusion:, An increase in amoA mRNA level can be detected within 1,2 h in response to an initiation of cell activity whereas a decrease in amoA mRNA level is detected within 24 h in response to a cessation of activity. Significance and Impact of the Study:,amoA mRNA, which shows sensitive response to ammonia oxidation activity, can be used as a biomarker of ammonia oxidation activity in wastewater treatment processes where many bacterial species exist. [source] CXCR3+CD4+ T cells are enriched in inflamed kidneys and urine and provide a new biomarker for acute nephritis flares in systemic lupus erythematosus patientsARTHRITIS & RHEUMATISM, Issue 1 2009P. Enghard Objective The high frequency of CD4+ T cells in interstitial infiltrates of patients with lupus nephritis suggests a contribution of these cells to local pathogenesis. The aim of this study was to examine the role of CXCR3 and the chemokine CXCL10 in recruiting these cells into the kidney and to determine whether the infiltrating T cells could be monitored in the urine to provide a reliable biomarker for acute lupus nephritis. Methods The frequencies of CD3+ T cells, CXCR3+ cells, and CXCL10+ cells were determined by immunohistochemical and immunofluorescence analyses of kidney sections from 18 patients with lupus nephritis. The frequency of CXCR3+CD4+ T cells was determined by flow cytometry of peripheral blood and urine from 38 patients with systemic lupus erythematosus (SLE), and the values were compared with disease activity as determined by the Systemic Lupus Erythematosus Disease Activity Index. Results In renal biopsy tissues from patients with lupus nephritis, a mean of 63% of the infiltrating cells expressed CXCR3, ,60% of them were T cells, and the CXCR3+ cells colocalized with CXCL10-producing cells. In biopsy tissues from SLE patients with acute nephritis, ,50% of the urinary CD4+ T cells were CXCR3+, as compared with 22% in the peripheral blood, and the frequency of urinary CXCR3+CD4+ T cells correlated with disease activity. Moreover, the number of urinary CD4+ T cells reflected nephritis activity, and elevation above 800 CD4+ T cells per 100 ml of urine sharply delineated active from inactive nephritis. Conclusion CXCR3+ T cells are recruited into the inflamed kidneys, are enriched in the urine, and are a valuable marker of nephritis activity in SLE. They also present a potential target for future therapies. [source] Serum pleiotrophin levels are elevated in multiple myeloma patients and correlate with disease statusBRITISH JOURNAL OF HAEMATOLOGY, Issue 5 2006Howard S. Yeh Summary Pleiotrophin (PTN), a tightly regulated angiogenic and mitogenic heparin-binding protein, is markedly elevated in a variety of aggressive solid tumours. The role of PTN in haematological malignancies, however, has not been previously evaluated. This study demonstrated that PTN serum levels were elevated in multiple myeloma (MM) patients when compared with healthy subjects (P < 0·0001). Serum levels of this protein significantly increased during progression of disease, and decreased during response to anti-MM therapy (P < 0·001). These results suggest that serum PTN may be a new biomarker for monitoring the disease status and therapeutic response of MM patients. [source] Stanniocalcin 2 overexpression in castration-resistant prostate cancer and aggressive prostate cancerCANCER SCIENCE, Issue 5 2009Kenji Tamura Prostate cancer is usually androgen-dependent and responds well to androgen ablation therapy based on castration. However, at a certain stage some prostate cancers eventually acquire a castration-resistant phenotype where they progress aggressively and show very poor response to any anticancer therapies. To characterize the molecular features of these clinical castration-resistant prostate cancers, we previously analyzed gene expression profiles by genome-wide cDNA microarrays combined with microdissection and found dozens of trans -activated genes in clinical castration-resistant prostate cancers. Among them, we report the identification of a new biomarker, stanniocalcin 2, as an overexpressed gene in castration-resistant prostate cancer cells. Real-time polymerase chain reaction and immunohistochemical analysis confirmed overexpression of stanniocalcin 2, a 302-amino-acid glycoprotein hormone, specifically in castration-resistant prostate cancer cells and aggressive castration-naļve prostate cancers with high Gleason scores (8,10). The gene was not expressed in normal prostate, nor in most indolent castration-naļve prostate cancers. Knockdown of stanniocalcin 2 expression by short interfering RNA in a prostate cancer cell line resulted in drastic attenuation of prostate cancer cell growth. Concordantly, stanniocalcin 2 overexpression in a prostate cancer cell line promoted prostate cancer cell growth, indicating its oncogenic property. These findings suggest that stanniocalcin 2 could be involved in aggressive phenotyping of prostate cancers, including castration-resistant prostate cancers, and that it should be a potential molecular target for development of new therapeutics and a diagnostic biomarker for aggressive prostate cancers. (Cancer Sci 2009; 100: 914,919) [source] Protein alterations in ESCC and clinical implications: a reviewDISEASES OF THE ESOPHAGUS, Issue 1 2009D.-C. Lin SUMMARY Esophageal squamous cell carcinoma (ESCC) is the predominant histological subtype of esophageal cancer in Asia, characterized by high incidence and mortality rate. Although significant progress has been made in surgery and adjuvant chemoradiotherapy, the prognosis of the patients with this cancer still remains poor. Investigation into protein alterations that occurred in tumors can provide clues to discover new biomarkers for improving diagnosis and guiding targeted therapy. Hundreds of papers have appeared over the past several decades concerning protein alterations in ESCC. This review summarizes all the dysregulated proteins investigated in the disease from 187 published papers and analyzes their contributions to tumor development and progression. We document protein alterations associated with tumor metastasis and the transition from normal esophageal epithelia to dysplasia in order to reveal the most useful markers for prediction of clinical outcome, early detection, and identification of high-risk patients for targeted therapies. In particluar, we discuss the largest and most rigorous studies on prognostic implications of proteins in ESCC, in which cyclin D1, p53, E-cadherin and VEGF appeared to have the strongest evidence as independent predictors of patient outcome. [source] Detection of elafin as a candidate biomarker for ulcerative colitis by whole-genome microarray screeningINFLAMMATORY BOWEL DISEASES, Issue 9 2006Carl-Fredrik Flach PhD Abstract The cause of ulcerative colitis (UC) is largely unknown. Microarray studies are an efficient way of investigating the various genes involved. Here, we have used whole-genome microarrays to clarify the clinical picture and to identify new biomarkers for improved diagnosis. Rectal biopsies were taken from five UC patients and five matched controls, and RNA transcripts were prepared. After labeling, each sample was individually applied to the microarray chips. All transcripts that were more than 10-fold up-regulated in all five patients were analyzed further in seven additional patients and seven controls using quantitative polymerase chain reaction. Of 47,000 transcripts examined, 4 were highly up-regulated in all patients: those encoding elafin, a secreted protease inhibitor, the ion and amino acid transporter B0,+ (SLC6A14), and the metabolic enzyme aldolase B, as well as a recently identified transcript named similar to numb-interacting homolog. The up-regulation of these transcripts appears to follow the progression of the disease because elevated expression was detected in the proximal part of the colon in patients with total colitis but not in patients with left-sided colitis. Immunohistologic examination showed very distinct differences in the expression of elafin. Extensive expression was detected in enterocytes and goblet cells of the affected mucosa, whereas there was no detectable expression in unaffected mucosa and in healthy controls. The results implicate four transcripts and proteins of special interest as possible targets for pharmacologic interference and as biomarkers in UC. Of these, elafin may be of special interest because it is a secreted protein that may be measured in body fluids. [source] Embryonic transcription factors in human breast cancerIUBMB LIFE, Issue 3 2006Karoline J. Briegel Abstract Growing evidence suggests that breast cancer cells often reactivate latent developmental programs in order to efficiently execute the multi-step process of tumorigenesis. This review focuses on key transcriptional regulators of embryonic development that are deregulated in breast cancer and discusses the molecular mechanisms by which these proteins control carcinogenesis. Reminiscent of their function during development, embryonic transcription factors regulate changes in gene expression that promote tumor cell growth, cell survival and motility, as well as a morphogenetic process called epithelial-mesenchymal transition (EMT), which is implicated in both breast metastasis and tumor recurrence. Because of their pivotal roles in breast tumor progression, these factors represent valuable new biomarkers for breast cancer detection as well as promising new targets for anti-invasive drugs. IUBMB Life, 58: 123-132, 2006 [source] Future Prospects for Biomarkers of Alcohol Consumption and Alcohol-Induced DisordersALCOHOLISM, Issue 6 2010Willard M. Freeman The lack of reliable measures of alcohol intake is a major obstacle to the diagnosis, treatment, and research of alcohol abuse and alcoholism. Successful development of a biomarker that allows for accurate assessment of alcohol intake and drinking patterns would not only be a major advance in clinical care but also a valuable research tool. A number of advances have been made in testing the validity of proposed biomarkers as well as in identifying potential new biomarkers through systems biology approaches. This commentary will examine the definition of a biomarker of heavy drinking, the types of potential biomarkers, the steps in biomarker development, the current state of biomarker development, and critical obstacles for the field. The challenges in developing biomarkers for alcohol treatment and research are similar to those found in other fields. However, the alcohol research field must reach a competitive level of rigor and organization. We recommend that NIAAA consider taking a leadership role in organizing investigators in the field and providing a common set of clinical specimens for biomarker validation studies. [source] Nutrigenomics,new approaches for human nutrition researchJOURNAL OF THE SCIENCE OF FOOD AND AGRICULTURE, Issue 8 2006Helen M Roche Abstract Food intake and nutrient exposure are key environmental factors involved in the pathogenesis and progression of the common polygenic, diet-related diseases. An individual's phenotype represents a complex interaction between the human genome and environmental factors during an individual's lifetime. This review explores the concept that there is a dynamic, two-way interaction between nutrition and the human genome which determines gene expression, the metabolic response and an individual's health status. It addresses the relevance of new high-throughput genomic, transcriptomic, proteomic and metabolomic technologies within human nutrition research. Common, polygenic, diet-related diseases (CVD, obesity, T2DM, etc.) reflect multiple genetic variants interacting with numerous environmental factors, each combination making a relatively small contribution to overall cellular homeostasis, whole body metabolism and health. This review highlights the value of a nutrigenomics-based systems biology approach to understanding human nutrition and identifying new biomarkers of nutrition and health. The challenge will be to develop and apply robust nutritional genomics research initiatives that are sensitive enough to take account of both human genetic heterogeneity and diverse nutrient exposure. If nutrigenomic approaches enhance our understanding of human nutrition at the molecular level, then it may be possible to apply a more targeted and effective personalized nutrition approach to attenuate the effect of risk factors associated with diet-related diseases. Indeed it could be proposed that a personalized nutrition approach may assist in improving the effectiveness of dietary guidelines/recommendations in general. Copyright © 2006 Society of Chemical Industry [source] Toward the discovery of new biomarkers of hepatocellular carcinoma by proteomicsLIVER INTERNATIONAL, Issue 2 2007Enrique Santamarķa Abstract Primary liver cancer is the fifth most frequent neoplasm and the third most common cause of cancer-related death, with more than 500 000 new cases diagnosed yearly. The outcome for hepatocellular carcinoma (HCC) patients still remains dismal, partly because of our limited knowledge of its molecular pathogenesis and the difficulty in detecting the disease at its early stages. Therefore, studies aimed at the definition of the mechanisms associated with HCC progression and the identification of new biomarkers leading to early diagnosis and more effective therapeutic interventions are urgently needed. Proteomics is a rapidly expanding discipline that is expected to change the way in which diseases will be diagnosed, treated, and monitored in the near future. In the last few years, HCC has been extensively investigated using different proteomic approaches on HCC cell lines, animal models, and human tumor tissues. In this review, state-of-the-art technology on proteomics is overviewed, and recent advances in liver cancer proteomics and their clinical projections are discussed. [source] Early detection of acute kidney injury: Emerging new biomarkers (Review Article)NEPHROLOGY, Issue 2 2008ZOLTAN H ENDRE SUMMARY: Acute kidney injury (AKI) has recently become the preferred term to describe the syndrome of acute renal failure (ARF) with ,failure' or ,ARF' restricted to patients who have AKI and need renal replacement therapy.1 This allows capture of the broader clinical spectrum of modest reductions in creatinine, which are themselves known to be associated with major increases in both short- and long-term mortality risk.2,5 It is hoped that this change in nomenclature will facilitate an expansion of our understanding of the underlying pathophysiology and also facilitate definitions of AKI, which allow comparisons among clinical trials of patients with similar duration and severity of illness. This review will cover the need for early detection of AKI and the role of urinary and plasma biomarkers, including enzymuria. The primary message is that use of existing criteria to diagnose AKI, namely elevation of the serum creatinine with or without oliguria, results in identification that is too late to allow successful intervention. New biomarkers are essential to change the dire prognosis of this common condition. [source] Biomarkers of ovulation, endometrial receptivity, fertilisation, implantation and early pregnancy progressionPAEDIATRIC & PERINATAL EPIDEMIOLOGY, Issue 2006Kenneth L. Campbell Summary Increasing interest in early preconception and periconception exposures and human developmental outcomes has led to studies that monitor subjects from before conception to gestation, birth and childhood. Monitoring ovulation, endometrial receptivity, fertilisation, implantation and gestation requires the non-invasive collection of biological information and samples, and the measurement of biochemical and biological markers (biomarkers) that are associated with the aforementioned physiological events. This paper describes some of the key features of biomarkers needed for epidemiological studies, identifies some existing and potential biomarkers and available measurement devices, and suggests some directions for identification and development of new biomarkers that might be employed in longitudinal studies involving the analysis of female reproductive function and of embryonic development. [source] Applications of protein microarrays for biomarker discoveryPROTEOMICS - CLINICAL APPLICATIONS, Issue 10-11 2008Niroshan Ramachandran Abstract The search for new biomarkers for diagnosis, prognosis, and therapeutic monitoring of diseases continues in earnest despite dwindling success at finding novel reliable markers. Some of the current markers in clinical use do not provide optimal sensitivity and specificity, with the prostate cancer antigen (PSA) being one of many such examples. The emergence of proteomic techniques and systems approaches to study disease pathophysiology has rekindled the quest for new biomarkers. In particular the use of protein microarrays has surged as a powerful tool for large-scale testing of biological samples. Approximately half the reports on protein microarrays have been published in the last two years especially in the area of biomarker discovery. In this review, we will discuss the application of protein microarray technologies that offer unique opportunities to find novel biomarkers. [source] An integrated serum proteomic approach capable of monitoring the low molecular weight proteome with sequencing of intermediate to large peptidesRAPID COMMUNICATIONS IN MASS SPECTROMETRY, Issue 17 2009Karen Merrell The low-abundance, low molecular weight serum proteome has high potential for the discovery of new biomarkers using mass spectrometry (MS). Because the serum proteome is large and complex, defining relative quantitative differences for a molecular species between comparison groups requires an approach with robust separation capability, high sensitivity, as well as high mass resolution. Capillary liquid chromatography (cLC)/MS provides both the necessary separation technique and the sensitivity to observe many low-abundance peptides. Subsequent identification of potential serum peptide biomarkers observed in the cLC/MS step can in principle be accomplished by in series cLC/MS/MS without further sample preparation or additional instrumentation. In this report a novel cLC/MS/MS method for peptide sequencing is described that surpasses previously reported size limits for amino acid sequencing accomplished by collisional fragmentation using a tandem time-of-flight MS instrument. As a demonstration of the approach, two low-abundance peptides with masses of ,4000,5000,Da were selected for MS/MS sequencing. The multi-channel analyzer (MCA) was used in a novel way that allowed for summation of 120 fragmentation spectra for each of several customized collision energies, providing more thorough fragmentation coverage of each peptide with improved signal to noise. The peak list from this composite analysis was submitted to Mascot for identification. The two index peptides, 4279,Da and 5061,Da, were successfully identified. The peptides were a 39 amino acid immunoglobulin G heavy chain variable region fragment and a 47 amino acid fibrin alpha isoform C-terminal fragment. The method described here provides the ability both to survey thousands of serum molecules and to couple that with markedly enhanced cLC/MS/MS peptide sequencing capabilities, providing a promising technique for serum biomarker discovery. Copyright © 2009 John Wiley & Sons, Ltd. [source] Population screening and early detection of ovarian cancer in asymptomatic womenAUSTRALIAN AND NEW ZEALAND JOURNAL OF OBSTETRICS AND GYNAECOLOGY, Issue 5 2009Anne E. NELSON The National Breast and Ovarian Cancer Centre position statement: ,Population screening and early detection of ovarian cancer in asymptomatic women', was developed and agreed following a Forum in February 2009 attended by key Australian stakeholders. The final position statement and supporting background information have been endorsed by key Australian colleges and agencies. Position statement on population screening and early detection of ovarian cancer in asymptomatic women 1There is currently no evidence that any test, including pelvic examination, CA125 or other biomarkers, ultrasound (including transvaginal ultrasound), or combination of tests, results in reduced mortality from ovarian cancer. 2There is no evidence to support the use of any test, including pelvic examination, CA125 or other biomarkers, ultrasound (including transvaginal ultrasound), or combination of tests, for routine population-based screening for ovarian cancer. 3Further validation in large clinical trials is required before current or new biomarkers could be recommended for routine use in a population screening setting. [source] Search for new biomarkers of gastric cancer through serial analysis of gene expression and its clinical implicationsCANCER SCIENCE, Issue 5 2004Wataru Yasui Gastric cancer is one of the most common human cancers and is the second most frequent cause of cancer-related death in the world. Serial analysis of gene expression (SAGE) is a powerful technique to allow genome-wide analysis of gene expression in a quantitative manner without prior knowledge of the gene sequences. SAGE on 5 samples of gastric cancer with different histology and clinical stages have created large SAGE libraries of gastric cancer that enable us to identify new cancer biomarkers. Commonly up-regulated genes in gastric cancer in comparison with normal gastric epithelia included CEACAM6, APOC1 and YF13H12. By comparing gene expression profiles of gastric cancers at early and advanced stages, several genes differentially expressed by tumor stage were also identified, including FUS, CDH17, COL1A1 and COL1A2, which should be novel genetic markers for high-grade malignancy. Regenerating gene type IV (REGIV) is one of the most up-regulated genes in a SAGE library of a scirrhous-type gastric cancer. In vitro studies using RegIV-transfected cells revealed that RegIV is secreted by cancer cells and inhibits apoptosis, suggesting that RegIV may serve as a novel biomarker and therapeutic target for gastric cancer. Production of RNA aptamers could be a useful approach to establish a detection system in blood. A custom-made array, named Ex-STO-MACHIP, consisting of 395 genes, including highly differentially expressed genes identified by our SAGE and other known genes related to carcinogenesis and chemosensitivity, is useful to study the molecular pathogenesis of gastric cancer and to obtain information about biological behavior and sensitivity to therapy in the clinical setting. Combined analyses of gene expression profile, genetic polymorphism and genetic instability will aid not only cancer detection, but also characterization of individual cancers and patients, leading to personalized medicine and cancer prevention. [source] | ||||||||||||||||