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Potential Biomarkers (potential + biomarker)
Selected AbstractsAnalysis 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] Regulation of gene expression in inflammatory bowel disease and correlation with IBD drugs.INFLAMMATORY BOWEL DISEASES, Issue 1 2004Screening by DNA microarrays Abstract Potential biomarkers for Crohn's disease (CD) and ulcerative colitis (UC) were identified from two sets of full thickness pathologic samples utilizing DermArray® and PharmArray® DNA microarrays relative to uninvolved (Un) colon or normal colon. Seven of the over-expressed genes were verified using quantitative RT-PCR (i.e., TMPT, FABP1, IFI27, LCN2, COL11A2, HXB, and metallothionein). By correlating gene expression profiles between inflammatory bowel disease (IBD) tissue samples and IBD drug-treated cell cultures it might be possible to identify new candidate molecular target genes for IBD therapy and drug discovery. Potential biomarkers for CaCo2 cell cultures, which are routinely used as a GI tract surrogate model for in vitro pharmacokinetic studies, treated with azathioprine, 5-aminosalicylic acid, metronidazole, and prednisone were also identified from another experiment. Metallothionein mRNA expression was found to be down-regulated in azathioprine-treated CaCo2 cells, and was coincidentally up-regulated in the CD sample, thus resulting in an anti-correlation. These results suggest that this new screening methodology is feasible, that metallothioneins might be biomarkers for azathioprine therapy in vivo in CD, and that azathioprine might mechanistically down-regulate metallothionein gene expression. Correlations were also observed between IBD samples and either metronidazole- or 5-aminosalicylic acid-treated CaCo2 cells. Similar comparisons of disease tissue samples in vivo vs drug-treated cell cultures in vitro might reveal new mechanistic insights concerning established or experimental drug therapies. This affordable in vitro methodology is promising for expanded studies of IBD and other diseases. [source] Immunological factors and their role in the genesis and development of endometriosis ARTICLE HAS BEEN RETRACTEDJOURNAL OF OBSTETRICS AND GYNAECOLOGY RESEARCH (ELECTRONIC), Issue 2 2006Charalambos Siristatidis Abstract The article presents an overview of immunological factors and their role in the genesis and development of endometriosis, with emphasis on inflammatory cytokines and growth and adhesion factors. Although retrograde menstruation is a common phenomenon among women of reproductive age, not all women with retrograde menstruation suffer the disease. Development of endometriosis seems to be a complex process, facilitated by several factors, including quantity and quality of endometrial cells in peritoneal fluid (PF), increased inflammatory activity in PF, increased endometrial,peritoneal adhesion and angiogenesis, reduced immune surveillance and clearance of endometrial cells, and increased production of autoantibodies against endometrial cells. Potential biomarkers like cytokines and autoantibodies, upregulated during development of endometriosis, seem useful in the development of a non-surgical diagnostic tool. In this review work, the immune role in endometriosis is examined through the role of immunological factors in the genesis and development of the disease. Furthermore, it could be concluded that, although endometriosis can be treated using hormonal suppression, there is a need today for non-hormonal drugs, probably to modulate immune function, in order to confront the disease and alleviate pain or infertility without inhibition of ovulation. [source] Liquid chromatography/mass spectrometry for metabonomics investigation of the biochemical effects induced by aristolochic acid in rats: the use of information-dependent acquisition for biomarker identificationRAPID COMMUNICATIONS IN MASS SPECTROMETRY, Issue 6 2008Wan Chan The toxic effects of oral administrations of nephrotoxic and carcinogenic aristolochic acid (AA) to male Sprague-Dawley rats were investigated by using high-performance liquid chromatography coupled with a quadrupole time-of-flight mass spectrometer. Analysis of the urine and plasma samples revealed distinct changes in the biochemical patterns in the AA-dosed rats. After peak finding and alignment, principal component analysis (PCA) and partial least-squares discriminant analysis (PLS-DA) were used for multivariate data analysis. Potential biomarkers were studied by high-resolution mass spectrometry (MS) and tandem mass spectrometry (MS/MS) analyses. The MS/MS spectra of all endogenous metabolites satisfying the pre-defined criteria were acquired in a single information-dependent acquisition (IDA) analysis, demonstrating that IDA was an efficient approach for structural elucidation in metabonomic studies. Citric acid and a glucuronide-containing metabolite were observed as potential biomarkers in rat urine. A significant increase in plasma creatinine concentration was also observed in the AA-dosed rats, which indicated that AA induced an adverse effect on the renal clearance function. Copyright © 2008 John Wiley & Sons, Ltd. [source] Metabolic profiling as a tool for understanding defense response of Taxus Cuspidata cells to shear stressBIOTECHNOLOGY PROGRESS, Issue 5 2009Pei-Pei Han Abstract To obtain a better understanding of responsive mechanism of plant cells in response to hydrodynamic mechanical stress, a metabolic profiling approach was used to profile metabolite changes of Taxus cuspidata cells under laminar shear stress. A total of 65 intracellular metabolites were identified and quantified, using gas chromatography coupled to time-of-flight mass spectrometry. Potential biomarkers were found by the principal component analysis as well as partial least squares combined with variable influence in the projection. Trehalose, sorbitol, ascorbate, sucrose, and gluconic acid were mainly responsible for the discrimination between shear stress induced cells and control cells. Further analysis by mapping measured metabolite concentrations onto the metabolic network revealed that shear stress imposed restrictions on primary metabolic pathways by inhibiting tricarboxylic acid cycle, glycolysis, and N metabolism. To adapt to the shear condition, cells responded by starting defensive programs. These defensive programs included coinduction of glycolysis and sucrose metabolism, accumulation of compatible solutes, and antioxidative strategy. A strategy of defense mechanisms at the level of metabolites for T. cuspidata cells when challenged with the shear stress was proposed. © 2009 American Institute of Chemical Engineers Biotechnol. Prog., 2009 [source] Potential biomarkers involving IKK/RelA signal in early stage non-small cell lung cancerCANCER SCIENCE, Issue 3 2008Xianqing Jin The clinical relevance of nuclear factor ,B (NF-,B) and its regulatory molecules on prognosis of patient with early stages of non-small cell lung cancer (NSCLC), remains unclear. Therefore, we conducted biomarker analyses with survival in patients with stages I and II NSCLC. Tumor samples were collected from 88 patients with early-stage NSCLC (stages I, II). A minimum follow-up period of 5 years was required. RelA, phosphorylated I,B (pI,B,), pIKK,/, were detected by immunostaining. NF-,B DNA binding activity was assessed by electrophoretic mobility shift assay. Association of clinical and pathologic variables (e.g. sex, age, pathologic stage) with relevant molecules was determined by Pearson's ,2 test or Fisher's exact test. Survival analysis based on single expression of RelA, pI,B,, pIKK,/, as well as composite expressions were evaluated using Cox proportional hazards regression models, and log rank test followed Kaplan-Meier estimates. RelA, pI,B,, pIKK,/, were observed as increased expression in NSCLC tissues compared with adjacent normal tissues and normal lung tissues. These molecules were associated with tumor-node-metastasis stages, T stages and histological status, respectively. Among the molecules analyzed, RelA and pI,B,-positive were statistically significant predictors of patient death in the entire patient population adjusted by age, gender and smoking status; furthermore both RelA and pI,B,-positive was the strongest prognostic indicators of poor prognosis by univariate and multivariate analyses. Borderline positive correlations were observed between RelA and pI,B, or pIKK,/, expression. In this cohort of early-stage NSCLC patients, molecular markers, especially composite application of multiple biomarkers (both nuclear RelA and cytoplasmic pI,B-, expression) that independently predict overall survival have been identified. (Cancer Sci 2008; 99: 582,589) [source] Development of a CE-MS method to analyze components of the potential biomarker vascular endothelial growth factor 165ELECTROPHORESIS, Issue 13 2009Angel Puerta Abstract The vascular endothelial growth factor 165 (VEGF165) is the predominant form of the complex VEGF-A family. Its angiogenic effect is involved in many physiological and pathological events. For this reason, its roles as a potential biomarker and as a therapeutic drug have been considered. Nevertheless, very little is known about the existence of different forms of VEGF165 arising from glycosylation and potentially from other PTMs. This aspect is important because different forms may differ in biological activity (therapeutic drug application) and the pattern of the different forms can vary with pathological changes (biomarker application). In this work a CE-MS method to separate up to seven peaks containing, at least, 19 isoforms of intact VEGF165 is described. Comparison between human VEGF165 expressed in a glycosylating system, i.e. insect cells, and in a non-glycosylating system, i.e. E. coli cells, has been carried out. The method developed provides structural information (mass fingerprint) about the different forms of VEGF165 and after the deconvolution and the analysis of the MS spectra, PTMs pattern of VEGF165 including glycosylation and loss of amino acids at the N- and C-terminus was identified. Glycans involved in PTMs promoting different glycoforms observed in the CE-MS fingerprint were confirmed by MALDI-MS after deglycosylation with peptide N-glycosidase F. This approach is a starting point to study the role of VEGF165 as a potential biomarker and to perform quality control of the drug during manufacturing. To our knowledge this is the first time that a CE-MS method for the analysis of VEGF165 has been developed. [source] Association of DRD4 polymorphism with severity of oppositional defiant disorder, separation anxiety disorder and repetitive behaviors in children with autism spectrum disorderEUROPEAN JOURNAL OF NEUROSCIENCE, Issue 6 2010Kenneth D. Gadow Abstract The objective was to examine whether a common polymorphism in the dopamine D4 receptor gene (DRD4) might be a potential biomarker for behavioral variation within the autism spectrum disorder clinical phenotype. Children (N = 66) were evaluated with a validated mother- and teacher-completed DSM-IV-referenced rating scale. Partial eta-squared (,p2) was used to gauge the magnitude of group differences: 0.01,0.06 = small, 0.06,0.14 = moderate and > 0.14 = large. Children who were 7-repeat allele carriers had more severe oppositional defiant disorder behaviors according to mothers' (,p2 = 0.10) and teachers' (,p2 = 0.06) ratings than noncarriers, but the latter was marginally significant (P = 0.07). Children who were 7-repeat allele carriers also obtained more severe maternal ratings of tics (,p2 = 0.07) and obsessions,compulsions (,p2 = 0.08). Findings for maternal ratings of separation anxiety were marginally significant (P = 0.08, ,p2 = 0.05). Analyses of combined DRD4 and dopamine transporter gene (DAT1) genotypes approached significance (P = 0.05) for teachers' ratings of oppositional behavior and mothers' ratings of tics. DRD4 allelic variation may be a prognostic biomarker for challenging behaviors in children with autism spectrum disorder, but these exploratory findings remain tentative pending replication with larger independent samples. [source] Simultaneous assessment of DNA ploidy and biomarker expression in paraffin-embedded tissue sectionsHISTOPATHOLOGY, Issue 1 2010Stijn J H M Fleskens Fleskens S J H M, Takes R P, Otte-Höller I, van Doesburg L, Smeets A, Speel E-J M, Slootweg P J & van der Laak J A W M (2010) Histopathology,57, 14,26 Simultaneous assessment of DNA ploidy and biomarker expression in paraffin-embedded tissue sections Aims:, Aneuploidy is a potential biomarker for predicting progression of premalignancies. Ploidy assessment is mostly performed on nuclei isolated from tissue sections. Ploidy assessment in situ in tissue sections may be a large improvement, enabling selective sampling of nuclei, thus allowing the correlation between ploidy and histology. Existing ploidy analysis methods in sections suffer from limited sensitivity. The aim was to reliably assess ploidy in sections, combined with simultaneous assessment of other markers at the individual cell level. Methods and results:, Ploidy was measured in 22 paraffin-embedded oral premalignancies. The DNA stoichiometric Feulgen procedure was used on isolated nuclei, as well as fluoresence in situ hybridization analysis. In tissue sections, Feulgen was combined with immunohistochemistry for Ki67 proliferation marker, enabling distinction between cycling euploid and aneuploid cells. Aneuploidy was reliably detected in tissue sections (sensitivity 100%, specificity 92%). One section in which aneuploidy was detected was misclassified in isolated nuclei analysis. Sections were also successfully analysed using our model combined with DNA double strand break marker ,-H2AX in fluorescence microscopy, underlining the power of biomarker evaluation on single cells in tissue sections. Conclusions:, The analysis model proposed in this study enables the combined analysis of histology, genotypic and phenotypic information. [source] Auditory orienting and inhibition of return in mild traumatic brain injury: A FMRI studyHUMAN BRAIN MAPPING, Issue 12 2009Andrew R. Mayer Abstract The semiacute phase of mild traumatic brain injury (mTBI) is associated with deficits in the cognitive domains of attention, memory, and executive function, which previous work suggests may be related to a specific deficit in disengaging attentional focus. However, to date, there have only been a few studies that have employed dynamic imaging techniques to investigate the potential neurological basis of these cognitive deficits during the semiacute stage of injury. Therefore, event-related functional magnetic resonance imaging was used to investigate the neurological correlates of attentional dysfunction in a clinically homogeneous sample of 16 patients with mTBI during the semiacute phase of injury (<3 weeks). Behaviorally, patients with mTBI exhibited deficits in disengaging and reorienting auditory attention following invalid cues as well as a failure to inhibit attentional allocation to a cued spatial location compared to a group of matched controls. Accordingly, patients with mTBI also exhibited hypoactivation within thalamus, striatum, midbrain nuclei, and cerebellum across all trials as well as hypoactivation in the right posterior parietal cortex, presupplementary motor area, bilateral frontal eye fields, and right ventrolateral prefrontal cortex during attentional disengagement. Finally, the hemodynamic response within several regions of the attentional network predicted response times better for controls than for patients with mTBI. These objective neurological findings represent a potential biomarker for the behavioral deficits in spatial attention that characterize the initial recovery phase of mTBI. Hum Brain Mapp, 2009. © 2009 Wiley-Liss, Inc. [source] Cyclooxygenase-2 inhibition inhibits PI3K/AKT kinase activity in epithelial ovarian cancerINTERNATIONAL JOURNAL OF CANCER, Issue 2 2010Shahab Uddin Abstract Cyclooxygenase-2 (COX-2) expression contributes to tumor growth and invasion in epithelial ovarian cancer (EOC). COX-2 inhibitors exhibit important anticarcinogenic potential against EOC, but the molecular mechanisms underlying this effect and relation with PI3-kinase/AKT signaling remain the subject of intense investigations. Therefore, the role of COX-2 in EOC and its cross talk with PI3-kinase/AKT pathway were investigated using a large series of EOC tissues in a tissue micro array (TMA) format followed by in vitro and in vivo studies using EOC cell lines and NUDE mice. Clinically, COX-2 was overexpressed in 60.3% of EOC and was significantly associated with activated AKT (p < 0.0001). Cox-1 expression was seen in 59.9% but did not associate with AKT. Our in vitro data using EOC cell line showed that inhibition of COX-2 by aspirin, selective inhibitor NS398 and gene silencing by COX-2 specific siRNA impaired phosphorylation of AKT resulting decreased downstream signaling leading to cell growth inhibition and induction of apoptosis. Finally, treatment of MDAH2774 cell line xenografts with aspirin resulted in growth inhibition of tumors in NUDE mice via down-regulation of COX-2 and AKT activity. These data identify COX-2 as a potential biomarker and therapeutic target in distinct molecular subtypes of ovarian cancer. [source] Raf kinase inhibitor protein correlates with sensitivity of nasopharyngeal carcinoma to radiotherapy,JOURNAL OF CELLULAR BIOCHEMISTRY, Issue 4 2010Lin Ruan Abstract Raf kinase inhibitory protein (RKIP) is a metastasis suppressor whose expression is reduced in nasopharyngeal carcinoma (NPC) tissues and is absent in NPC metastases. To investigate the effect of RKIP on radiosensitivity of NPC, high metastatic 5-8F with low RKIP expression and non-metastatic 6-10B with high RKIP expression were stably transfected with plasmids that expressed sense and antisense RKIP cDNA. Overexpression of RKIP sensitized 5-8F cells to radiation-induced cell death, G2 -M cell cycle arrest and apoptosis. In contrast, downexpression of RKIP in 6-10B cells protected cells from radiation-induced cell death, G2 -M cell cycle arrest and apoptosis. In addition, RKIP expression altered the radiosensitivity of NPC cells through MEK and ERK phosphorylation changes of Raf-1/MEK/ERK signaling pathway. We further investigated the RKIP expression in NPC patients and its association with patients' survival after radiotherapy. Downexpression of RKIP was significantly correlated with advanced clinical stage, lymph node metastasis and radioresistance. Furthermore, survival curves showed that patients with RKIP downexpression had a poor prognosis and induced relapse. Multivariate analysis confirmed that RKIP expression was an independent prognostic indicator. The data suggested that RKIP was a potential biomarker for the radiosensitivity and prognosis of NPC, and its dysregulation might play an important role in the radioresistance of NPC. J. Cell. Biochem. 110: 975,984, 2010. © 2010 Wiley-Liss, Inc. [source] Downregulation of miR-122 in the rodent and human hepatocellular carcinomasJOURNAL OF CELLULAR BIOCHEMISTRY, Issue 3 2006Huban Kutay Abstract MicroRNAs (miRs) are conserved small non-coding RNAs that negatively regulate gene expression. The miR profiles are markedly altered in cancers and some of them have a causal role in tumorigenesis. Here, we report changes in miR expression profile in hepatocellular carcinomas (HCCs) developed in male Fisher rats-fed folic acid, methionine, and choline-deficient (FMD) diet. Comparison of the miR profile by microarray analysis showed altered expression of some miRs in hepatomas compared to the livers from age-matched rats on the normal diet. While let-7a, miR-21, miR-23, miR-130, miR-190, and miR-17-92 family of genes was upregulated, miR-122, an abundant liver-specific miR, was downregulated in the tumors. The decrease in hepatic miR-122 was a tumor-specific event because it did not occur in the rats switched to the folate and methyl-adequate diet after 36 weeks on deficient diet, which did not lead to hepatocarcinogenesis. miR-122 was also silent in a transplanted rat hepatoma. Extrapolation of this study to human primary HCCs revealed that miR-122 expression was significantly (P,=,0.013) reduced in 10 out of 20 tumors compared to the pair-matched control tissues. These findings suggest that the downregulation of miR-122 is associated with hepatocarcinogenesis and could be a potential biomarker for liver cancers. J. Cell. Biochem. 99: 671,678, 2006. © 2006 Wiley-Liss, Inc. [source] Differential expression of proteins in kidney, eye, aorta, and serum of diabetic and non-diabetic ratsJOURNAL OF CELLULAR BIOCHEMISTRY, Issue 1 2006William C. Cho Abstract Diabetes mellitus (DM) is a chronic progressive disease that often results in microvascular and macrovascular complications, yet its pathogenesis is not clear. Automated proteomic technology, coupled with powerful bioinformatics and statistical tools, can provide new insights into the molecular alterations implicated in DM. Following our previous findings of redox changes in the eye and aorta of diabetic rats, as well as the activities of different antioxidant enzymes during the development of DM, this study is further launched to find potential biomarkers by comparing the serum and tissue samples of 26 diabetic rats (8 weeks after streptozotocin [STZ] administration) with 29 normal controls using surface enhanced laser desorption/ionization time-of-flight mass spectrometry (SELDI-TOF MS) technology. Eight potential biomarkers were found in the serum, one potential biomarker was found in the kidney and eye, respectively, whereas three potential biomarkers were discovered in the aorta. One of the serum biomarker candidates was found to match the C-reactive protein (CRP) in the Swiss-Prot knowledgebase. Further validation has been conducted by ELISA kit to confirm the role of CRP during the development of DM. To conclude, the increased level of CRP in diabetic serum demonstrated in this study indicates that the development of DM is associated with inflammation. This is also the first report demonstrating that some potential lysate biomarkers in the kidney, eye, and aorta may be involved in the development of diabetes and its complications. Further identification and evaluation of these potential biomarkers will help unravel the underlying mechanisms of the disease. J. Cell. Biochem. © 2006 Wiley-Liss, Inc. [source] Immunoreactivity of the phosphorylated axonal neurofilament H subunit (pNF-H) in blood of ALS model rodents and ALS patients: evaluation of blood pNF-H as a potential ALS biomarkerJOURNAL OF NEUROCHEMISTRY, Issue 5 2009Kevin Boylan Abstract Levels of neurofilament subunits, potential biomarkers of motor axon breakdown, are increased in amyotrophic lateral sclerosis (ALS) patient's CSF but data on blood are not available. We measured blood levels of the phosphorylated axonal form of neurofilament H (pNF-H) by ELISA in transgenic rodent models of superoxide dismutase 1 (SOD1) ALS, and in 20 ALS patients and 20 similar aged controls monthly for 4 months. All symptomatic rodent ALS models showed robust levels of blood pNF-H, while control rodents or mice transgenic for unmutated SOD1 showed no detectable blood pNF-H. Average pNF-H levels in the G93A SOD1 mouse progressively increased from day 74 through death (day ,130). Median blood pNF-H level in ALS patients was 2.8-fold higher than controls (p < 0.001). Median ALSFRS-R declined a median of 0.8 pt/month (p < 0.001); higher baseline pNF-H level appeared to be associated with faster ALSFRS-R decline over 4 months (p = 0.087). The median rate of decline in ALSFRS-R was 1.9 pt/month in patients with baseline pNF-H levels above the median pNF-H value of 0.53 ng/mL; ALSFRS-R declined at a median of 0.6 pt/month in patients below this level. The pNF-H levels were relatively stable month to month in individual patients, raising questions regarding the molecular pathogenesis of ALS. Baseline control human pNF-H levels were higher in men than women and increased minimally over time. These data suggest that blood pNF-H can be used to monitor axonal degeneration in ALS model rodents and support further study of this protein as a potential biomarker of disease prognosis in ALS patients. [source] Novel Biomarkers for Diagnosis and Therapeutic Assessment of Overactive Bladder: Urinary Nerve Growth Factor and Detrusor Wall ThicknessLUTS, Issue 2009Hann-Chorng KUO Clinical diagnosis of overactive bladder (OAB) varies greatly and is based on subjective symptoms. A better way to diagnose and assess therapeutic outcome in patients who present with OAB needs to be developed. Evidence has shown that urinary proteins, such as nerve growth factor (NGF) and prostaglandin E2 (PGE2) levels increase in patients with OAB, bladder outlet obstruction (BOO) and detrusor overactivity (DO). Urinary NGF level increases physiologically in normal subjects at urge to void, but increases pathologically in OAB patients at small bladder volume and at urgency sensation. Patients with OAB dry and OAB wet have significantly higher urinary NGF levels compared to controls and patients with increased bladder sensation. Urinary NGF levels decrease after antimuscarinic therapy and further decrease after detrusor botulinum toxin injections in refractory OAB. A higher urinary NGF level could be a biomarker for sensory nerve-mediated DO. Urinary NGF levels could be a potential biomarker for diagnosis of OAB and serve for the assessment of the therapeutic effect of antimuscarinic therapy. Another potential biomarker for the diagnosis of OAB is detrusor wall thickness. It has been hypothesized that the bladder wall increases in thickness in patients with OAB. The thickened detrusor wall might decrease in response to antimuscarinic treatment, and measurement of detrusor wall thickness might be a useful biomarker for the evaluation of OAB. However, current investigations do not yet provide a uniform observation among various studies. [source] Effect of pistachio oil on gene expression of IFN-induced protein with tetratricopeptide repeats 2: A biomarker of inflammatory responseMOLECULAR NUTRITION & FOOD RESEARCH (FORMERLY NAHRUNG/FOOD), Issue S1 2010Jun Zhang Abstract When incorporated into the diet, pistachios have a beneficial effect on lipid and lipoprotein profiles. However, little is known about potential anti-inflammatory properties. This study was conducted to determine whether pistachio oil and an organic extract from pistachio oil extract (PE) regulated expression of inflammation-related genes. A mouse macrophage cell line (RAW 264.7 cells) was treated with pistachio oil and gene expression microarray analyses were performed. Pistachio oil significantly affected genes involved in immune response, defense response to bacteria, and gene silencing, of which INF-induced protein with tetratricopeptide repeats 2 (Ifit-2) was the most dramatically reduced. PE reduced the LPS-induced Ifit-2 by 78% and the bioactive molecules contained in PE, linoleic acid, and ,-sitosterol recapitulated this inhibition. Promoter analysis identified two adjacent IFN-stimulated response elements, which lie between ,110 and ,85bp of the 5,-flanking region of the Ifit-2 promoter, as being responsive to LPS activation and inhibition by PE. Our results indicate that pistachio oil and bioactive molecules present therein decrease Ifit-2 expressions, and due to the sensitivity of this effect, this gene is a potential biomarker for monitoring diet-induced changes in inflammation. [source] Proteomic identification of peroxiredoxin 6 for host defence against Opisthorchis viverrini infectionPARASITE IMMUNOLOGY, Issue 5 2010J. KHOONTAWAD Summary Opisthorchis viverrini infection causes opisthorchiasis and is a risk factor for cholangiocarcinoma via chronic inflammation. To investigate the mechanism of O. viverrini -induced liver disease, we applied a proteomic approach to examine alterations in hepatic protein levels in O. viverrini -infected hamsters. Two-dimensional gel electrophoresis (2DE) revealed that O. viverrini infection induced upregulation (1·5- to 4·3-fold) of 25 proteins and downregulation (1·5 to 2·5-fold) of 24 proteins compared with uninfected animals. Expression of proteins related to stress response, DNA replication and repair, and cell structure was significantly increased, whereas that of proteins associated with normal liver function, such as metabolism, blood volume maintenance and fatty acid cycle was decreased. Among the upregulated proteins, a 2·7-fold increase in peroxiredoxin 6 (Prdx6), an antioxidant protein, was confirmed by 2DE and immunoblot analysis, Western blot and quantitative PCR. Immunohistochemical analysis showed that Prdx6 expression was observed mainly in the cytoplasm of inflammatory cells. These results suggest that Prdx6 is important for host defence against O. viverrini infection. This study provides basic information for Prdx6 as a potential biomarker and therapeutic target for opisthorchiasis. [source] Microwave-assisted extraction of total bioactive saponin fraction from Gymnema sylvestre with reference to gymnemagenin: a potential biomarkerPHYTOCHEMICAL ANALYSIS, Issue 6 2009Vivekananda Mandal Abstract Objective , To develop a fast and ecofriendly microwave assisted extraction (MAE) technique for the effective and exhaustive extraction of gymnemagenin as an indicative biomarker for the quality control of Gymnema sylvestre. Methodology , Several extraction parameters such as microwave power, extraction time, solvent composition, pre-leaching time, loading ratio and extraction cycle were studied for the determination of the optimum extraction condition. Scanning electron micrographs were obtained to elucidate the mechanism of extraction Results , The final optimum extraction conditions as obtained from the study were: 40% microwave power, 6,min irradiation time, 85% v/v methanol as the extraction solvent, 15,min pre-leaching time and 25,:,1 (mL/g) as the solvent-to-material loading ratio. The proposed extraction technique produced a maximum yield of 4.3% w/w gymnemagenin in 6,min which was 1.3, 2.5 and 1.95 times more efficient than 6,h of heat reflux, 24,h of maceration and stirring extraction, respectively. A synergistic heat and mass transfer theory was also proposed to support the extraction mechanism Conclusion , Comparison with conventional extraction methods revealed that MAE could save considerable amounts of time and energy, whilst the reduction of volume of organic solvent consumed provides an ecofriendly feature. Copyright © 2009 John Wiley & Sons, Ltd. [source] dUTP Pyrophosphatase, its appearance in extracellular compartment may serve as a potential biomarker for N -methyl- N' -nitro- N -nitrosoguanidine exposure in mammalian cellsPROTEINS: STRUCTURE, FUNCTION AND BIOINFORMATICS, Issue 10 2006Meiping Wu Abstract The monofunctional alkylating agent N -methyl- N' -nitro- N -nitrosoguanidine (MNNG) is a model chemical widely used for studying the molecular events induced by the widespread environmental N -nitroso alkylating carcinogen. Many studies have focused on understanding MNNG-induced mutagenesis and carcinogenesis. However, the search for specific indicators of MNNG exposure is still underway. In this study, we analyzed the proteins in culture medium of human amnion epithelial cells (FL,cells) exposed to MNNG by 2-DE followed by MALDI-TOF,MS, in the hope of finding a specific protein marker suitable for MNNG risk assessment. Image visualization and statistical analysis indicated that 12,spots appeared and 4,spots up-regulated after MNNG exposure. Most of them were identified by MS. These proteins include nuclear isoform of dUTP pyrophosphatase (DUT-N), phosphoglycerate mutase,1, heparan sulfate proteoglycan perlecan, etc., which are involved in multiple cellular functions. Interestingly, 2-DE and MS analyses of cell lysate exposed to MNNG revealed that DUT-N was down-regulated. The appearance of DUT-N in culture medium and its down-regulation in cell lysate was confirmed by Western blot. These data suggest that these proteins, especially DUT-N, could be used as candidate biomarkers for monitoring MNNG exposure. [source] Alpha-1-antitrypsin and complement component C7 are involved in asthma exacerbationPROTEOMICS - CLINICAL APPLICATIONS, Issue 1 2008Tatsuji Nishioka Abstract Asthma is the most common chronic disorder in childhood and asthma exacerbation is an important cause of childhood morbidity and hospitalization. Allergic responses are known to be biased toward T-helper type 2 in asthmatics; however, the pathogenesis of asthma is not simple, and our understanding of the disease mechanism remains incomplete. The aim of the present study was to identify protein expression signatures that reflect acute exacerbation of asthma. Plasma was taken twice from pediatric asthmatic patients, once during asthma exacerbation and once during a stable period. Plasma was also taken from healthy children as a control. The protein profiles of plasma during asthma exacerbation were analyzed by 2-DE and 49 spots were differentially expressed during asthma exacerbation. Thirty-eight of the spots were successfully identified by MALDI-TOF MS. Proteins up- or down-regulated during asthma exacerbation were involved in responses to stress and pathogens, in the complement and coagulation cascades, and in acute-phase responses. Among the differentially expressed proteins, up-regulation of alpha-1-antitrypsin and complement component C7 was confirmed by nephelometry and ELISA. Our present results suggest that protease inhibitors and complement components may be involved in asthma exacerbation, and plasma level of alpha-1-antitrypsin may be a potential biomarker for asthma. [source] Mass spectrometry study of hemoglobin-oxaliplatin complexes in colorectal cancer patients and potential association with chemotherapeutic responsesRAPID COMMUNICATIONS IN MASS SPECTROMETRY, Issue 17 2006Rupasri Mandal Oxaliplatin is the most active platinum (Pt)-containing anticancer drug for the treatment of advanced colorectal cancer. We report here the study of potential association of the levels of oxaliplatin-protein complexes in 19 cancer patients with treatment efficacy using size-exclusion high-performance liquid chromatography with inductively coupled plasma mass spectrometry (HPLC/ICPMS) and nanoelectrospray ionization mass spectrometry (nanoESI-MS) techniques. Blood samples from 19 colorectal cancer patients were collected at 1 and 48,h after the first infusion of oxaliplatin. HPLC/ICPMS quantification of the oxaliplatin-protein complexes showed that the levels of Pt-protein complexes in plasma samples at 48,h were reduced by approximately 50% compared to those at 1,h, whereas those in hemolysates did not change significantly. The concentrations of hemoglobin (Hb)-oxaliplatin complexes determined by HPLC/ICPMS ranged from 3.1 to 8.7,µM. NanoESI-MS analysis of the patient hemolysates showed three distinct mass spectral profiles of the Hb-oxaliplatin complexes: (1) 1:1, (2) 1:1 with 1:2, and (3) multiple complexes of 1:1, 1:2, 1:3, and 1:4, corresponding to the Hb-oxaliplatin complex concentrations determined by HPLC/ICPMS. Potential association of variables including Hb-oxaliplatin complex concentrations with time to progress as the treatment efficacy indicator was analyzed using the Cox model. Multivariate analysis of the potential predictors showed that the statistically significant variables were Hb-oxaliplatin complex concentration (p,=,0.02), performance status (p,=,0.02), baseline neutrophil count (p,=,0.05), and the site of the primary cancer (colon vs. rectal, p,=,0.01). The hazard ratio for the concentration of the Hb-oxaliplatin complexes was 2.4, suggesting that the risk of cancer progression significantly increased with increasing of Hb-oxaliplatin complexes in patients. These results demonstrate that the level of the Hb-oxaliplatin complexes in erythrocytes is a potential biomarker for indicating inter-patient variations in oxaliplatin treatment efficacy. Copyright © 2006 John Wiley & Sons, Ltd. [source] Preclinical evaluation of carcinoembryonic cell adhesion molecule (CEACAM) 6 as potential therapy target for pancreatic adenocarcinoma,THE JOURNAL OF PATHOLOGY, Issue 3 2009Laura A Strickland Abstract Despite the availability of new targeted therapies, ductal pancreatic adenocarcinoma continues to carry a poor prognosis. Carcinoembryonic antigen-related cell adhesion molecule (CEACAM)6 has been reported as a potential biomarker and therapy target for this malignancy. We have evaluated CEACAM6 as a potential therapy target, using an antibody,drug conjugate (ADC). Expression of CEACAM6 in pancreatic adenocarcinomas was determined using immunohistochemistry on tissue microarrays. The expression pattern in granulocytes and granulocytic precursors was measured by flow cytometry. Murine xenograft and non-human primate models served to evaluate efficacy and safety, respectively. Robust expression of CEACAM6 was found in > 90% of invasive pancreatic adenocarcinomas as well as in intraepithelial neoplastic lesions. In the granulocytic lineage, CEACAM6 was expressed at all stages of granulocytic maturation except for the early lineage-committed precursor cell. The anti-CEACAM6 ADC showed efficacy against established CEACAM6-expressing tumours. In non-human primates, antigen-dependent toxicity of the ADC consisted of dose-dependent and reversible depletion of granulocytes and their precursors. This was associated with preferential and rapid localization of the antibody in bone marrow, as determined by sequential in vivo PET imaging of the radiolabelled anti-CEACAM6. Localization of the radiolabelled tracer could be attenuated by predosing with unlabelled antibody confirming specific accumulation in this compartment. Based on the expression pattern in normal and malignant pancreatic tissues, efficacy against established tumours and limited and reversible bone marrow toxicity, we propose that CEACAM6 should be considered for an ADC-based therapy approach against pancreatic adenocarcinomas and possibly other CEACAM6-positive neoplasms. Copyright © 2009 Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd. [source] Identification of RGS1 as a candidate biomarker for undifferentiated spondylarthritis by genome-wide expression profiling and real-time polymerase chain reactionARTHRITIS & RHEUMATISM, Issue 11 2009Jieruo Gu Objective To compare gene expression profiles between ankylosing spondylitis (AS) and undifferentiated spondylarthritis (uSpA) patients with inflammatory low back pain. Methods Peripheral blood mononuclear cells (PBMCs) from patients with AS, patients with uSpA, and healthy subjects were screened using genome-wide microarrays, followed by validation by real-time polymerase chain reaction (PCR). Results Microarray profiling and real-time PCR assays showed only minor differences between AS patients and healthy subjects. In contrast, 20 genes were strikingly more highly expressed in uSpA patients. Regulator of G protein signaling 1 (RGS1) was identified as the most useful biomarker for distinguishing uSpA patients, and to a lesser extent AS patients, from control subjects (P = 2.3 × 10,7 and 6.7 × 10,3, respectively). These findings were verified in an independent cohort that also included patients with rheumatoid arthritis and patients with mechanical low back pain. The receiver operating characteristic area under the curve values in the first and second cohorts of uSpA patients were 0.99 and 0.93, respectively (P = 1 × 10,4). To evaluate the possible derivation of RGS1, we cultured a monocyte-derived cell line with a panel of cytokines and chemokines. RGS1 was significantly induced either by tumor necrosis factor , (TNF,) or by interleukin-17 (IL-17). Conclusion Our findings indicate that uSpA PBMCs carry strikingly more highly expressed genes compared with PBMCs from AS patients or healthy subjects, and that TNF,- and IL-17,inducible RGS1 is a potential biomarker for uSpA, and to a lesser extent for AS, with inflammatory low back pain. [source] Urinary neutrophil gelatinase,associated lipocalin as a biomarker of nephritis in childhood-onset systemic lupus erythematosusARTHRITIS & RHEUMATISM, Issue 8 2006Hermine I. Brunner Objective Renal involvement in systemic lupus erythematosus (SLE) is associated with poor prognosis. Currently available renal biomarkers are relatively insensitive and nonspecific for diagnosing SLE nephritis. Previous research suggests that neutrophil gelatinase,associated lipocalin (NGAL) is a high-quality renal biomarker of acute kidney injury, while its usefulness in SLE is unclear. We undertook this study to determine the relationship between urinary NGAL excretion and SLE disease activity or damage, with a focus on nephritis. Methods A cohort of 35 patients diagnosed as having SLE prior to age 16 years (childhood-onset SLE) was assessed for disease activity (using the Systemic Lupus Erythematosus Disease Activity Index 2000 update) and damage (using the Systemic Lupus International Collaborating Clinics/American College of Rheumatology SLE Damage Index) in a double-blind, cross-sectional study. Information on current markers of renal function and disease was obtained and compared with NGAL levels (ng/mg of urinary creatinine) measured by enzyme-linked immunosorbent assay. Eight children with juvenile idiopathic arthritis (JIA) served as controls. Results NGAL levels did not differ with the age, weight, height, sex, or race of the patients. Patients with childhood-onset SLE had significantly higher NGAL levels than did those with JIA (P < 0.0001). NGAL levels were strongly to moderately correlated with renal disease activity and renal damage (Spearman's r , 0.47, P < 0.0001 for both comparisons), but not with extrarenal disease activity or extrarenal damage. NGAL levels of >0.6 ng/mg urinary creatinine were 90% sensitive and 100% specific for identifying childhood-onset SLE patients with biopsy-proven nephritis. Conclusion Urinary NGAL is a promising potential biomarker of childhood-onset SLE nephritis. The results of the current study require validation in a larger cohort to more accurately delineate urinary NGAL excretion in relation to the diverse SLE phenotypes. [source] Decrease of urinary nerve growth factor levels after antimuscarinic therapy in patients with overactive bladderBJU INTERNATIONAL, Issue 12 2009Hsin-Tzu Liu OBJECTIVE To determine urinary nerve growth factor (NGF) levels in patients with overactive bladder (OAB) and after treatment with antimuscarinics. PATIENTS AND METHODS Urinary NGF levels were measured in 38 ,normal' controls and 70 patients with OAB. Patients were treated with tolterodine 4 mg once daily. Urinary NGF levels were measured by enzyme-linked immunosorbent assay method and normalized by urinary creatinine levels (NGF/Cr). The urinary NGF/Cr levels and urgency severity scale (USS) were compared at baseline, 1, 2 and 3 months after antimuscarinics, and 1 month after discontinuing treatment. RESULTS The urinary NGF/Cr level was very low in normal controls with a mean (sem) of 0.005 (0.003). Patients with OAB had significantly higher baseline urinary NGF/Cr levels than the controls. Urinary NGF/Cr levels were significantly reduced at 3 months in 50 responders (1.10 [0.26] before vs 0.41 [0.09] after, P = 0.008) but not in the 20 non-responders (1.38 [0.54] before vs 1.30 [0.46] after, P = 0.879). However, after discontinuing antimuscarinic treatment for 1 month, the urinary NGF/Cr level was elevated in 23 responders at 0.83 (0.33) and in five non-responders at 2.72 (1.41). The USS scores significantly changed with the change of urinary NGF/Cr levels in responders at different time points. The voided volume increased but maximum urinary flow rate and postvoid residual volume did not increase in responders after 3-months of antimuscarinic treatment. The limitation of this study was the lack of a control arm for comparison. CONCLUSIONS Changes in the urinary NGF levels were associated with the changes of the USS scores after antimuscarinic treatment and discontinued medication. The urinary NGF level could be a potential biomarker for evaluating therapeutic results of antimuscarinics therapy. [source] Urinary nerve growth factor level could be a biomarker in the differential diagnosis of mixed urinary incontinence in womenBJU INTERNATIONAL, Issue 10 2008Hsin-Tzu Liu OBJECTIVES To measure urinary nerve growth factor (NGF) levels in women with stress urinary incontinence (SUI) and overactive bladder symptoms (OAB) and to assess whether urinary NGF levels can be a biomarker of detrusor overactivity (DO) in women with mixed urinary incontinence. PATIENTS, SUBJECTS AND METHODS Urinary NGF levels were measured in 38 women with urodynamic SUI (USI) with OAB, in 26 with urodynamic DO but no SUI, in 21 with persistent USI after anti-incontinence surgery, in 15 with de novo DO, and in 31 normal control subjects. All participants had a video-urodynamic study for the differential diagnosis of the underlying causes of UI. Urinary NGF levels were measured using an enzyme-linked immunosorbent assay and were compared among all subgroups, and corrected using urinary creatinine (Cr) levels. RESULTS The mean (sem) urinary NGF/Cr levels were low both in controls, at 0.06 (0.004) and in women with pure USI, at 0.056 (0.037) (P = 0.108). The NGF/Cr levels were significantly higher in women with mixed USI and DO, at 1.00 (0.244), than in controls (P < 0.001) and those with pure USI (P = 0.006), but were similar to the levels in women with pure DO, at 0.58 (0.17) (P = 0.058). The NGF/Cr levels were undetectable in women with persistent USI but were significantly higher in those with de novo DO, at 2.39 (0.90), after anti-incontinence surgery than in controls and those with USI. A urinary NGF/Cr level of >0.05 was found in 9% of women with USI, 77% with DO, 81% with mixed USI and DO, and 80% with de novo DO. CONCLUSION The urinary NGF level could be a potential biomarker of DO in women with mixed UI. [source] Nanoparticle-Based Electrochemical Immunosensor for the Detection of Phosphorylated Acetylcholinesterase: An Exposure Biomarker of Organophosphate Pesticides and Nerve AgentsCHEMISTRY - A EUROPEAN JOURNAL, Issue 32 2008Guodong Liu Dr. Abstract A nanoparticle-based electrochemical immunosensor has been developed for the detection of phosphorylated acetylcholinesterase (AChE), which is a potential biomarker of exposure to organophosphate (OP) pesticides and chemical warfare nerve agents. Zirconia nanoparticles (ZrO2 NPs) were used as selective sorbents to capture the phosphorylated AChE adduct, and quantum dots (ZnS@CdS, QDs) were used as tags to label monoclonal anti-AChE antibody to quantify the immunorecognition events. The sandwich-like immunoreactions were performed among the ZrO2 NPs, which were pre-coated on a screen printed electrode (SPE) by electrodeposition, phosphorylated AChE and QD-anti-AChE. The captured QD tags were determined on the SPE by electrochemical stripping analysis of its metallic component (cadmium) after an acid-dissolution step. Paraoxon was used as the model OP insecticide to prepare the phosphorylated AChE adducts to demonstrate proof of principle for the sensor. The phosphorylated AChE adduct was characterized by Fourier transform infrared spectroscopy (FTIR) and mass spectroscopy. The binding affinity of anti-AChE to the phosphorylated AChE was validated with an enzyme-linked immunosorbent assay. The parameters (e.g., amount of ZrO2 NP, QD-anti-AChE concentration,) that govern the electrochemical response of immunosensors were optimized. The voltammetric response of the immunosensor is highly linear over the range of 10,pM to 4,nM phosphorylated AChE, and the limit of detection is estimated to be 8.0,pM. The immunosensor also successfully detected phosphorylated AChE in human plasma. This new nanoparticle-based electrochemical immunosensor provides an opportunity to develop field-deployable, sensitive, and quantitative biosensors for monitoring exposure to a variety of OP pesticides and nerve agents. [source] Dynamic Changes in Lymphocyte GRK2 Levels in Cardiac Transplant Patients: A Biomarker for Left Ventricular FunctionCLINICAL AND TRANSLATIONAL SCIENCE, Issue 1 2010Raphael E. Bonita M.D., Sc.M. Abstract G protein-coupled receptor kinase 2 (GRK2), which is upregulated in the failing human myocardium, appears to have a role in heart failure (HF) pathogenesis. In peripheral lymphocytes, GRK2 expression has been shown to reflect myocardial levels. This study represents an attempt to define the role for GRK2 as a potential biomarker of left ventricular function in HF patients. We obtained blood from 24 HF patients before and after heart transplantation and followed them for up to 1 year, also recording hemodynamic data and histological results from endomyocardial biopsies. We determined blood GRK2 protein by Western blotting and enzyme-linked immunosorbent assay. GRK2 levels were obtained before transplant and at first posttransplant biopsy. GRK2 levels significantly declined after transplant and remained low over the course of the study period. After transplantation, we found that blood GRK2 signifi cantly dropped and remained low consistent with improved cardiac function in the transplanted heart. Blood GRK2 has potential as a biomarker for myocardial function in end-stage HF. Clin Trans Sci 2010; Volume #: 1,5 [source] 2-D difference gel electrophoresis of the lung squamous cell carcinoma versus normal sera demonstrates consistent alterations in the levels of ten specific proteinsELECTROPHORESIS, Issue 23 2007Paul Dowling Dr. Abstract Most lung cancers are diagnosed too late for curative treatment to be possible, therefore early detection is crucial. Serum proteins are a rich source of biomarkers and have the potential to be used as diagnostic and prognostic indicators for lung cancer. In order to examine differences in serum levels of specific proteins associated with human lung squamous carcinoma, immunodepletion of albumin and five other high-abundant serum proteins followed by 2-D difference gel electrophoresis (DIGE) analysis and subsequent MS was used to generate a panel of proteins found to be differentially expressed between the cancer and normal samples. Proteins found to have increased abundance levels in squamous cell carcinoma sera compared to normal sera included apolipoprotein A-IV precursor, chain F; human complement component C3c, haptoglobin, serum amyloid A protein precursor and Ras-related protein Rab-7b. Proteins found to have lower abundance levels in squamous cell carcinoma sera compared to normal sera included alpha-2-HS glycoprotein, hemopexin precursor, proapolipoprotein, antithrombin III and SP40; 40. The data presented here demonstrate that high-abundant protein removal combined with 2-D DIGE is a powerful strategy for the discovery of potential biomarkers. The identification of lung cancer-specific biomarkers is crucial to early detection, which in turn could lead to a dramatic increase in survival rates. [source] | |||||||||||||||||||||||||||||||