Showing papers in "Disease Markers in 2013"

Serum circulating microRNA profiling for identification of potential breast cancer biomarkers.

Abstract: MicroRNAs (miRNAs) are a class of small, non-coding RNA molecules that can regulate gene expression, thereby affecting crucial processes in cancer development. miRNAs offer great potential as biomarkers for cancer detection because of their remarkable stability in blood and their characteristic expression in different diseases. We investigated whether quantitative RT-PCR miRNA profiling on serum could discriminate between breast cancer patients and healthy controls. We performed miRNA profiling on serum from breast cancer patients, followed by construction of ROC (Receiver Operating Characteristic) curves to determine the sensitivity and specificity of the assay. We found that seven miRNAs (miR-10b, miR-21, miR-125b, miR-145, miR-155 miR-191 and miR-382) had different expression patterns in serum of breast cancer patients compared to healthy controls. ROC curve analyses revealed that three serum miRNAs could be valuable biomarkers for distinguishing BC from normal controls. Additionally, a combination of ROC curve analyses of miR-145, miR-155 and miR-382 showed better sensitivity and specificity of our assay. miRNA profiling in serum has potential as a novel method for breast cancer detection in the Mexican population.

Rheumatoid factors: Clinical applications

Abstract: Rheumatoid factors are antibodies directed against the Fc region of immunoglobulin G. First detected in patients with rheumatoid arthritis 70 years ago, they can also be found in patients with other autoimmune and nonautoimmune conditions, as well as in healthy subjects. Rheumatoid factors form part of the workup for the differential diagnosis of arthropathies. In clinical practice, it is recommended to measure anti-cyclic citrullinated peptide antibodies and rheumatoid factors together because anti-cyclic citrullinated peptide antibodies alone are only moderately sensitive, and the combination of the two markers improves diagnostic accuracy, especially in the case of early rheumatoid arthritis. Furthermore, different rheumatoid factor isotypes alone or in combination can be helpful when managing rheumatoid arthritis patients, from the time of diagnosis until deciding on the choice of therapeutic strategy.

Oxidative Stress-Related Biomarkers in Essential Hypertension and Ischemia-Reperfusion Myocardial Damage

Abstract: Cardiovascular diseases are a leading cause of mortality and morbidity worldwide, with hypertension being a major risk factor. Numerous studies support the contribution of reactive oxygen and nitrogen species in the pathogenesis of hypertension, as well as other pathologies associated with ischemia/reperfusion. However, the validation of oxidative stress-related biomarkers in these settings is still lacking and novel association of these biomarkers and other biomarkers such as endothelial progenitor cells, endothelial microparticles, and ischemia modified albumin, is just emerging. Oxidative stress has been suggested as a pathogenic factor and therapeutic target in early stages of essential hypertension. Systolic and diastolic blood pressure correlated positively with plasma F2-isoprostane levels and negatively with total antioxidant capacity of plasma in hypertensive and normotensive patients. Cardiac surgery with extracorporeal circulation causes an ischemia/reperfusion event associated with increased lipid peroxidation and protein carbonylation, two biomarkers associated with oxidative damage of cardiac tissue. An enhancement of the antioxidant defense system should contribute to ameliorating functional and structural abnormalities derived from this metabolic impairment. However, data have to be validated with the analysis of the appropriate oxidative stress and/or nitrosative stress biomarkers.

Biomarkers in Schizophrenia: A Brief Conceptual Consideration

Abstract: Biomarkers have been sought after in the field of schizophrenia research for decades. In this paper, we discuss some of the concepts around developing biomarkers in an effort to understand why the use of biomarkers for schizophrenia has not been realized. In particular, we address the following 4 questions. Why would we need a diagnostic biomarker for schizophrenia? How is a biomarker typically defined and how does that influence the discovery of biomarkers in schizophrenia? What is the best use of biomarkers in schizophrenia? Do any biomarkers for schizophrenia currently exist? Thus, while we suggest that no biomarker currently exists for schizophrenia, the heterogeneity associated with schizophrenia will most likely need to be taken into account which will result in multiple biomarkers that identify the multiple underlying pathophysiological processes involved in schizophrenia. Therefore, much additional work will be required prior to obtaining any well-established biomarkers for schizophrenia.

Regulation of breast cancer and bone metastasis by microRNAs.

Abstract: Breast cancer progression including bone metastasis is a complex process involving numerous changes in gene expression and function. MicroRNAs (miRNAs) are small endogenous noncoding RNAs that regulate gene expression by targeting protein-coding mRNAs posttranscriptionally, often affecting a number of gene targets simultaneously. Alteration in expression of miRNAs is common in human breast cancer, possessing with either oncogenic or tumor suppressive activity. The expression and the functional role of several miRNAs (miR-206, miR-31, miR-27a/b, miR-21, miR-92a, miR-205, miR-125a/b, miR-10b, miR-155, miR-146a/b, miR-335, miR-204, miR-211, miR-7, miR-22, miR-126, and miR-17) in breast cancer has been identified. In this review we summarize the experimentally validated targets of up- and downregulated miRNAs and their regulation in breast cancer and bone metastasis for diagnostic and therapeutic purposes.

Serum Levels of Selected Th17 and Th22 Cytokines in Psoriatic Patients

Abstract: Introduction. Psoriasis is a T cell-mediated inflammatory disease in which pathogenesis T helper (Th) lymphocytes (Th1, Th17, and Th22) play an important role. The aim of the study was to assess the serum levels of some cytokines involved in the Th17 and Th22 responses in psoriatic patients. Material and Methods. The study comprised 60 psoriatic patients and 30 healthy controls. In the serum collected from psoriatic patients and healthy controls, the concentrations of IL-6, IL-12, IL-17, IL-20, IL-22, and IL-23 were examined with ELISA kits. Severity of psoriatic skin lesions was assessed by means of PASI, BSA, and PGA scores. Results. IL-6, IL-20, and IL-22 concentrations were significantly higher in psoriatic patients in comparison with the control group. The positive correlations between the concentrations of IL-22 and IL-20 and severity of psoriasis assessed with PASI and BSA scores as well as IL-17 and PASI score were found. There was also a positive correlation between IL-23 and IL-17 concentrations. Conclusions. Results of the conducted studies suggest that Th22 response may contribute to the skin and systemic inflammatory disease in psoriasis. It seems that early identification of soluble biomarkers and initiation of well-matched treatment may prevent exacerbation and progression of psoriasis.

Biomarkers in Posttraumatic Stress Disorder: Overview and Implications for Future Research

Abstract: PTSD can develop in the aftermath of traumatic incidents like combat, sexual abuse, or life threatening accidents. Unfortunately, there are still no biomarkers for this debilitating anxiety disorder in clinical use. Anyhow, there are numerous studies describing potential PTSD biomarkers, some of which might progress to the point of practical use in the future. Here, we outline and comment on some of the most prominent findings on potential imaging, psychological, endocrine, and molecular PTSD biomarkers and classify them into risk, disease, and therapy markers. Since for most of these potential PTSD markers a causal role in PTSD has been demonstrated or at least postulated, this review also gives an overview on the current state of research on PTSD pathobiology.

Serum markers of intrahepatic cholangiocarcinoma.

Abstract: Cholangiocarcinoma (CCA) is a relatively rare type of primary liver cancer that originates in the bile duct epithelium. It is an aggressive malignancy typified by unresponsiveness to chemotherapy and radiotherapy. Despite advances in radiologic techniques and laboratory diagnostic test, the diagnosis of CCA remains highly challenging. Development in molecular techniques has led to go into the possible use of serum markers in diagnosing of cholangiocarcinoma. This review summarizes the principal characteristics of serum markers of cholangiocarcinoma. The tumour markers used frequently such as Carbohydrate antigen 19-9 (CA 19-9), Carcinogenic Embryonic antigen (CEA), and Cancer Antigen 125 have shown sufficient sensitivity and specificity to detect and monitor CCA. In particular, the combination of these tumour markers seems to increase their efficiency in diagnosing of cholangiocarcinoma. New markers such as Soluble fragment of cytokeratin 19 (CYFRA 21-1) Mucins, Tumour Markers2- pyruvate-Kinase (TuM2- PK) and metalloproteinase-7 (MMP-7) have been recently shown to help in the diagnosis of CCA, with in some cases a prognostic value.

Biomarkers Predicting Antidepressant Treatment Response: How Can We Advance the Field?

Abstract: Major depression, affecting an estimated 350 million people worldwide, poses a serious social and economic threat to modern societies. There are currently two major problems calling for innovative research approaches, namely, the absence of biomarkers predicting antidepressant response and the lack of conceptually novel antidepressant compounds. Both, biomarker predicting a priori whether an individual patient will respond to the treatment of choice as well as an early distinction of responders and nonresponders during antidepressant therapy can have a significant impact on improving this situation. Biosignatures predicting antidepressant response a priori or early in treatment would enable an evidence-based decision making on available treatment options. However, research to date does not identify any biologic or genetic predictors of sufficient clinical utility to inform the selection of specific antidepressant compound for an individual patient. In this review, we propose an optimized translational research strategy to overcome some of the major limitations in biomarker discovery. We are confident that early transfer and integration of data between both species, ideally leading to mutual supportive evidence from both preclinical and clinical studies, are most suitable to address some of the obstacles of current depression research.

Circulating microRNAs: A Potential Role in Diagnosis and Prognosis of Acute Myocardial Infarction

Abstract: Rapid and correct diagnosis of acute myocardial infarction (AMI) plays a crucial role in saving patients' life. Although some biomarkers (such as cardiac troponin and creatine kinase) are available for AMI diagnosis so far, there is still a clinical need for novel biomarkers, which can reliably rule in or rule out AMI immediately on admission. Circulating microRNAs (miRNAs) are a potential choice for novel biomarkers in AMI diagnosis and prognosis with high sensitivity and specificity. Circulating microRNAs are endogenous miRNAs that are detectable in whole blood, serum, or plasma in a highly stable form. Until now, around 20 circulating miRNAs were reported to be closely associated with AMI. In this minireview, we summarized recent available data on the correlation between circulating miRNAs and AMI. Some miRNAs, such as miR-208, miR-499, miR-133, and miR-1, were given special attention, since they may have a potential prospect in diagnosis and prognosis of AMI.

Clinical, MRI, and CSF Markers of Disability Progression in Multiple Sclerosis

Abstract: Multiple sclerosis (MS) is a chronic disorder of the central nervous system (CNS) in which the complex interplay between inflammation and neurodegeneration determines varying degrees of neurological disability. For this reason, it is very difficult to express an accurate prognosis based on purely clinical information in the individual patient at an early disease stage. Magnetic resonance imaging (MRI) and cerebrospinal fluid (CSF) biomarkers are promising sources of prognostic information with a good potential of quantitative measure, sensitivity, and reliability. However, a comprehensive MS outcome prediction model combining multiple parameters is still lacking. Current relevant literature addressing the topic of clinical, MRI, and CSF markers as predictors of MS disability progression is reviewed here.

The Use of Plasma and Urine Neutrophil Gelatinase Associated Lipocalin (NGAL) and Cystatin C in Early Diagnosis of Septic Acute Kidney Injury in Critically Ill Patients

Abstract: AIM: To assess and compare the roles of plasma and urine concentrations of neutrophil gelatinase associated lipocalin (NGAL) and Cystatin C for early diagnosis of septic acute kidney injury (AKI) in adult critically ill patients. METHODS: Patients were divided into three groups as sepsis-non AKI, sepsis-AKI and non sepsis-non AKI. Plasma samples for NGAL and Cystatin C were determined on admission and on alternate days and urinary samples were collected for every day until ICU discharge. RESULTS: One hundred fifty one patients were studied; 66 in sepsis-non AKI, 63 in sepsis-AKI, 22 in non-sepsis-non-AKI groups. Although plasma NGAL performed less well (AUC 0.44), urinary NGAL showed significant discrimination for AKI diagnosis (AUC 0.80) with a threshold value of 29.5 ng/ml (88% sensitivity, 73% specificity). Both plasma and urine Cystatin C worked well for the diagnosis of AKI (AUC 0.82 and 0.86, thresholds 1.5 and 0.106 mg/L respectively). CONCLUSION: Plasma and urinary Cystatin C and urinary NGAL are useful markers in predicting AKI in septic critically ill patients. Plasma NGAL raises in patients with sepsis in the absence of AKI and should be used with caution as a marker of AKI in septic ICU patients.

Soluble Lectin-Like Oxidized Low Density Lipoprotein Receptor-1 as a Biochemical Marker for Atherosclerosis-Related Diseases

Abstract: Lectin-like oxidized low density lipoprotein receptor-1 (LOX-1), the main oxidized low-density lipoprotein (OxLDL) in endothelial cells, is upregulated in atherosclerotic lesions and is involved in several cellular processes that regulate the pathogenesis of atherosclerosis. The LOX-1 expressed on the cell surface can be proteolytically cleaved and released in a soluble form (sLOX-1) in the circulation under pathological conditions. Serum levels of sLOX-1, in fact, are elevated at the early stages of acute coronary syndrome and are associated with coronary plaque vulnerability and with the presence of multiple complex coronary lesions. Moreover, in subjects with stable CAD, levels of serum sLOX-1 are associated with the presence of lesions in the proximal and mid-segments of the left anterior descending artery that are the most prone to rupture; in subjects undergoing percutaneous coronary intervention, baseline preprocedural serum sLOX-1 levels are associated with the incidence of periprocedural myocardial infarction. Altogether, these findings suggest that circulating levels of sLOX-1 might be a diagnostic and prognostic marker for atherosclerotic-related events.

Salivary markers of oxidative stress and antioxidant status: influence of external factors.

Abstract: BACKGROUND: Salivary markers of oxidative stress and antioxidant status represent promising tool for the research of oral diseases. One of the criteria is the validation of these biomarkers from the perspective of the confounding and modifying factors.

New markers of early cardiovascular risk in multiple sclerosis patients: oxidized-LDL correlates with clinical staging.

Abstract: OBJECTIVES: This study aimed to characterize a population of multiple sclerosis (MS) patients in terms of traditional and new cardiovascular risk factors and assess their putative correlation with clinical disease activity (evaluated by the Expanded Disability Status Scale [EDSS]).

Increased glutamate and homocysteine and decreased glutamine levels in autism: a review and strategies for future studies of amino acids in autism.

Abstract: There are many reports about the significant roles of some amino acids in neurobiology and treatment of autism. This is a critical review of amino acids levels in autism. No published review article about the level of amino acids in autism was found. The levels of glutamate and homocystein are increased in autism while the levels of glutamine and tryptophan are decreased. Findings regarding the plasma levels of taurine and lysine are controversial. The urinary levels of homocysteine and essential amino acids in both the untreated and treated autistic children are significantly less than those in the controls. The current literature suffers from many methodological shortcomings which needed to be considered in future studies. Some of them are age, gender, developmental level, autism symptoms severity, type of autism spectrum disorders, medical comorbidities, intelligent quotient, diet, concomitant medications, body mass index, and technical method of assessment of amino acids.

Expression of matrix metalloproteinases in human breast cancer tissues.

Abstract: BACKGROUND: Breast cancer is the most common cancer affecting women in the world today. Matrix metalloproteinases (MMPs) are a family of endopeptidases that can degrade extracellular matrix proteins and promote cell invasion and metastasis. MMPs are differentially expressed and their expressions are often associated with a poor prognosis for patients. OBJECTIVE: The aim of this study is to investigate and compare the expression of MMPs in different grades of human breast cancer tissues with normal breast tissues. PATIENTS AND METHODS: We collected 39 breast cancer samples (24 grade II and 15 grade III) along with 16 normal breast tissues from outside the tumor margin during cancer removal surgery. The samples were analysed for the expression of all known MMPs using real-time quantitative PCR. RESULTS: The results indicate that mRNA expressions of MMP-1, -9,-11,-15,-24 and -25 were upregulated in breast cancer tissues when compared to normal breast tissues. But, the mRNA expressions of MMP-10 and MMP-19 were downregulated in cancer tissue. In membrane associated MMPs like MMP-15 and MMP-24 we found a grade dependent increase of their mRNA expression.

Inflammatory Cytokines and the Risk of Cardiovascular Complications in Type 2 Diabetes

Abstract: This study evaluates peripheral blood T lymphocyte expression of inflammatory and proinflammatory cytokines as well as T regulatory (Treg) (FOXP3

Lipoprotein-associated phospholipase A2 (Lp-PLA 2 ): A novel and promising biomarker for cardiovascular risks assessment

Abstract: Atherosclerosis and its manifestations namely cardiovascular diseases (CVD) are still the leading cause of morbidity and mortality worldwide. Although intensified interventions have been applied, the residual cardiovascular (CV) risks are still very high. Lipoprotein-associated phospholipase A2 (Lp-PLA2) is a novel and unique biomarker highly specific for vascular inflammation and atherosclerosis. Both pro-atherogenic property of Lp-PLA2 and positive correlation with CV events have already been demonstrated by a large number of scientific and clinical studies. Currently, in the Adult Treatment Panel III (ATP III) guideline, Lp-PLA2 has been recommended as an adjunct to traditional risk factors in assessing future CV risks. Encouragingly, darapladib, an orally Lp-PLA2 specific inhibitor, has been tested in basic research and preclinical trials and the outcomes are quite striking. Additionally, there are two phase III ongoing clinical trials in evaluating the efficacy and safety of darapladib on cardiovascular outcomes. With regard to the potential values of Lp-PLA2 in risk stratification, therapeutic regimen establishment and prognosis evaluation in patients with moderate or high risk, our present review is going to summarize the relevant data about the bio-chemical characteristics of Lp-PLA2, the actions of Lp-PLA2 on atherosclerosis and the results of Lp-PLA2 in scientific research and clinical studies.

Serum Interleukin-15 Levels Are Associated with Severity of Pain in Patients with Knee Osteoarthritis

Abstract: Background. Inflammation plays a crucial role in the development and progression of osteoarthritis (OA). Interleukin-15 (IL-15) is a well-known proinflammatory cytokine. Objective. We aimed at evaluating the relationship between serum IL-15 levels and the severity of pain as well as radiographic progression in patients with knee OA. Methods. Two hundred and twenty-six OA patients and 106 controls were enrolled in this study. The symptomatic/radiological severity of OA was assessed by the Western Ontario McMaster University Osteoarthritis Index- (WOMAC-)pain scores/Kellgren-Lawrence (KL) grading system. Serum IL-15 levels were measured by enzyme-linked immunosorbent assay (ELISA). Results. Serum IL-15 levels were significantly higher in OA patients compared with controls. Serum IL-15 levels were independently and positively correlated with WOMAC-pain scores but not KL grades in OA patients. Conclusions. We demonstrated that increased serum IL-15 levels were independently correlated with self-reported greater pain in knee OA patients. These results suggest that IL-15 might play a crucial role in the pathogenesis of OA related pain and therapeutic interventions by blocking IL-15 signaling pathways to delay the degenerative process of OA related pain which warrants further investigations.

Study of TNF-α, IL-1β and LPS Levels in the Gingival Crevicular Fluid of a Rat Model of Diabetes Mellitus and Periodontitis

Abstract: OBJECTIVE: In this study, we sought to investigate the dynamic changes in the levels of TNF-α, IL-1β and LPS in the gingival crevicular fluid (GCF) in a rat model of diabetes mellitus (DM) and periodontitis (PD). Additionally, we evaluated alveolar bone loss and the histopathological response associated with experimental diabetes mellitus and experimental periodontitis.

Biomarkers for Psychiatric Disorders: Where Are We Standing?

Abstract: The answer for the question posed in the title is: considering a clinical applicability, we are standing in the very beginning. To date, there are no biomarkers of any kind available to any of the psychiatric disorders, and perhaps establishing those will be one of the most difficult tasks that medical scientists will ever face, This is due to several reasons: (1) the multifactorial characteristic of psychiatric disorders, (2) these are multigenic disorders in which each gene has a small effect; (3) the environment exerts a heavy influence in the establishment of the disease. These reasons lead us to conclude that “the biomarker” for a psychiatric condition will never exist. At best, we will be able to identify panels or sets of biomarkers. Each psychiatric condition is a heterogeneous entity: for example, bipolar disorder is one disease composed by very opposite phases and symptoms, if we consider maniac and depressive episodes. Moreover, there is a significant overlap of symptoms among all psychiatric disorders. It has been shown that up to 31% of the bipolar disorder patients may be initially diagnosed with schizophrenia [1]. Still in this line, there have been concerns about false-positive clinical diagnosis due to the subjective criteria differently adopted among clinicians [2], supporting the necessity of establishing molecular biomarkers that could at least guide a clearer diagnostic decision. Nevertheless, at the current stage, diagnostic biomarkers do not seem to be the most needed ones. First, experienced clinicians have a good notion about the diagnosis, even with all concerns about subjectivity. Also, patients suffer considerably with the uneven kind of treatments available, making medication biomarkers more important at this particular point of psychiatric research. Furthermore, establishing diagnostic biomarkers at the disease onset is not a trivial task. Recently, the first and only diagnostic test proposed for schizophrenia [3], the VeriPsych, was discontinued supporting this notion (http://www.veripsych.com/). The most needed type of biomarkers to be applicable in a short-term future are those which could predict or indicate the likelihood of a successful treatment. The “one treatment fits all” notion it is not applicable in the management of psychiatric symptoms, since these vary significantly among the patients according to their phenotype. For example, one can design longitudinal studies using biological samples collected from living patients prior to and after a certain period of medication. Results may provide the possibility of discovering a set of biomarker candidates to be evaluated prior to the initiation of the treatment that could indicate whether a given treatment is likely to be successful or not for each particular patient. Obviously, such panel of biomarkers must be validated in large cohorts, established from samples collected in a noninvasive manner and employing reliable analytical platforms. Biomarkers to the stratification of patients are also needed [4]. Schizophrenia, for instance, encompasses an umbrella of disorders which may be the result of the dysfunction of distinct molecular mechanisms triggered by environmental factors that will result, at the end of the day, in the same condition. For example, some patients might develop schizophrenia due to metabolic disturbances, while others might develop it due to inflammatory dysfunctions. In these cases, a genetic predisposition seems to play a pivotal role, considering the estimated heritability of schizophrenia in 80 to 85% [5], but acting through different molecular pathways. There are still those patients which suffered a very heavy pressure of the environment, which may have a more definitive part in the establishment of the disease than genetics [6]. In any case, each patient will have his/her particular molecular type of schizophrenia due to their distinct phenotypes. Thus patients must be categorized—or stratified—in a way that distinct treatments are administered in a tailor-made fashion. Such characterization could be done by determining molecular biomarkers to each type of patient. This solution would enhance the treatment, since each patient would be treated according to the type of molecular dysfunction he/she has or according to their phenotype. It has been observed a long time ago that the strategy of treating all patients with one kind of treatment does not seem to be the way to recover patients and place them back to society. Although schizophrenia was used as an example here, this strategy would be applicable for other psychotic and affective disorders. Last but not least, it is important to be aware of how the concept of biomarker has been used. A biomarker is a measurable characteristic (i.e., molecule, physical structure or observation) assessed by a validated analytical platform which can indicate unequivocally a particular disease or physiological state of an organism or even the positive/negative response of such organism to a given treatment. The great majority of the data which has been published in the field of biomarkers do not fulfill this definition. Therefore, most of what we know so far are biomarker candidates or potential biomarkers only [7]. It is necessary to consider the different types of biomarkers proposed by the USA Food and Drug Administration (FDA) such as exploratory biomarkers, probably valid biomarkers, and known valid biomarkers when performing biomarker studies [8]. This special issue of Disease Markers approaches which is the current situation regarding the discovery of biomarkers to psychiatric disorders such as schizophrenia (Weickert et al. 2013), depression (Labermaier et al. 2013, Carboni 2013), posttraumatic stress disorder (Schmidt et al. 2013), and autism spectrum disorders (Voineagu and Yoo, 2013). I hope that the information presented in this edition may be useful to generate validation studies, develop trustworthy analytical platforms, launch new lines of research towards personalized medicine studies in order to approximate scientific studies to solutions clinically applicable, or yet to approximate the bench to the bedside. Daniel Martins-de-Souza

Levels of circulating microparticles in lung cancer patients and possible prognostic value.

Abstract: Background. Endothelial-derived microparticles (EDMPs) and platelet-derived microparticles (PDMPs) have been reported to be increasing in various diseases including malignant diseases. Here, we investigated whether these MPs may be useful biomarkers for predicting lung cancer (LC) disease status, cell type, or metastasis. Methods and Results. One hundred and thirty LC patients were prospectively enrolled into the study between April 2011 and February 2012. Flow cytometric analysis demonstrated that the circulating levels of platelet-derived activated MPs (PDAc-MPs), platelet-derived apoptotic MPs (PDAp-MPs), endothelial-derived activated MPs (EDAc-MPs), and endothelial-derived apoptotic MPs (EDAp-MPs) were significantly higher in LC patients than in 30 age- and gender-matched normal control subjects (all ). Additionally, circulating level of PDAc-MPs was significantly lower (), whereas the circulating levels of the other three biomarkers did not differ (all ) in early stage versus late stage LC patients. Furthermore, the circulating levels of the four types of MPs did not differ among patients with different disease statuses (i.e., disease controlled, disease progression, and disease without treatment, i.e., fresh case) (all ) or between patients with or without LC metastasis (all ). Moreover, only the circulating level of EDAp-MPs was significantly associated with the different cell types (i.e., squamous cell carcinoma, adenocarcinoma, and small cell carcinoma) of LC (). Conclusion. Circulating MP levels are significantly increased in LC patients as compared with normal subjects. Among the MPs, only an increased level of EDAp-MPs was significantly associated with different LC cell types.

Risk Factors for Mortality in Hemodialysis Patients: Two-Year Follow-Up Study

Abstract: Background. End-stage renal disease (ESRD) patients under hemodialysis (HD) have high mortality rate. Inflammation, dyslipidemia, disturbances in erythropoiesis, iron metabolism, endothelial function, and nutritional status have been reported in these patients. Our aim was to identify any significant association of death with these disturbances, by performing a two-year follow-up study. Methods and Results. A large set of data was obtained from 189 HD patients (55.0% male; 66.4 ± 13.9 years old), including hematological data, lipid profile, iron metabolism, nutritional, inflammatory, and endothelial (dys)function markers, and dialysis adequacy. Results. 35 patients (18.5%) died along the follow-up period. Our data showed that the type of vascular access, C-reactive protein (CRP), and triglycerides (TG) are significant predictors of death. The risk of death was higher in patients using central venous catheter (CVC) (Hazard ratio [HR] =3.03, 95% CI = 1.49–6.13), with higher CRP levels (fourth quartile), compared with those with lower levels (first quartile) (HR = 17.3, 95% CI = 2.40–124.9). Patients with higher TG levels (fourth quartile) presented a lower risk of death, compared with those with the lower TG levels (first quartile) (HR = 0.18, 95% CI = 0.05–0.58). Conclusions. The use of CVC, high CRP, and low TG values seem to be independent risk factors for mortality in HD patients.

Increased LEF1 expression and decreased Notch2 expression are strong predictors of poor outcomes in colorectal cancer patients.

Abstract: Background/Objective. We aimed to examine the expression of lymphoid enhancer factor 1 (LEF1) and Notch2 in colorectal cancer (CRC) and their association with clinicopathologic variables and CRC patients' prognosis. Methods. Immunohistochemistry, quantitative real-time polymerase chain reaction (qRT-PCR), and Western blot analysis were performed to assess the expression of LEF1 and Notch2 in 184 patients with CRC. Results. We observed a strong negative correlation between LEF1 expression and Notch2 expression (P < 0.001). Both LEF1 mRNA and protein expression increased while the Notch2 mRNA and protein expression decreased in tumor specimens compared with the matched paratumorous normal tissue (P < 0.001). An increase in LEF1 protein expression was significantly associated with lymph node metastases, distant metastasis, advanced TNM (tumor-node-metastasis) stage, and shorter overall survival. A decrease in Notch2 protein expression was associated with poorly differentiated tumors, lymph node metastases, distant metastasis, advanced TNM stage, and shorter overall survival of patients. In the multivariate Cox regression analysis, the LEF1 protein expression (P < 0.001), Notch2 protein expression (P < 0.001), TNM stage (P < 0.001), and the combination of increased LEF1 protein coexpression and decreased Notch2 protein coexpression (P < 0.001) were found to be independent prognostic indicators in CRC. Conclusion. Our results suggest that increased LEF1 coexpression and decreased Notch2 coexpression represent a risk factor for poor overall survival of CRC patients.

Reduced Paraoxonase 1 Activity as a Marker for Severe Coronary Artery Disease

Abstract: Paraoxonase-1 (PON1), a high-density-lipoprotein- (HDL-) associated enzyme, has the potential to protect against atherogenesis. We examine the relationships between plasma PON1 activity and the progression of atherosclerosis as well as coronary artery disease (CAD). Fasting blood samples were collected from female apolipoprotein E-deficient (apoE(-/-)) mice and 149 patients undergoing coronary angiography for the biochemical parameters measurement. The severity of CAD was defined using angiographic Gensini score (GSS). Compared to 3-month-old apoE(-/-) mice, aged mice had significantly lower PON1 activity, which is negatively correlated with the size of atherosclerotic lesion and plasma interleukin-6 (IL-6) and tumor necrosis factor α (TNF- α ) levels. In study patients, PON1 activity was correlated with age, sex, and HDL-cholesterol, apolipoprotein AI, and high-sensitivity C-reactive protein (hs-CRP) levels and was significantly lower in CAD group than that in non-CAD control group. Interestingly, PON1 activity in severe CAD group (GSS > 40) was further significantly reduced compared to those in mild and moderate subgroups (GSS ≤ 40) (P < 0.01). There is a significant correlation between PON1 activity and the severity of CAD as assessed by GSS (r = -0.393, P < 0.001). PON1 activity may be a potential biomarker for the severity of CAD.

TMEM25 Is a Candidate Biomarker Methylated and Down-Regulated in Colorectal Cancer

Abstract: The identification of novel genes involved in colorectal cancerogenesis is of high clinical relevance for early diagnosis, applying new therapeutic strategies and monitoring disease recurrence, in order to reduce disease incidence and mortality. Gene silencing through CpG island hypermethylation is a major epigenetic mechanism involved in cancer development. In our study, we aimed to identify and validate novel genes with a tumour specific DNA methylation profile in colorectal cancer. We performed a whole-genome methylation scan and identified several possible candidate genes that are hypermethylated in tumour in comparison to healthy colon mucosa. Using methylation-specific high-resolution melting analysis in a set consisting of 133 colorectal cancer samples, we were able to confirm an altered CpG site in TMEM25 in 69.2% (92/133) tumours analysed. Furthermore, the expression of TMEM25 was found to be significantly lower in tumour tissue. An inverse correlation between hypermethylation of TMEM25 and TMEM25 down-regulated expression was observed. Our results suggest that epigenetic down-regulation of TMEM25 is cancer-related; we thus suggest that TMEM25 hypermethylation might play a significant role in altering expression of this gene in colorectal cancer.

Positive ALDH1A3 and negative GPX3 expressions are biomarkers for poor prognosis of gallbladder cancer.

Abstract: Background. Gallbladder cancers (GBCs) are highly aggressive cancers with high mortality. However, biological markers for the progression and prognosis of GBC are currently unavailable in the clinic. Objective. To identify biomarkers for predicting GBC metastasis and prognosis. Methods. We examined ALDH1A3 and GPX3 expressions in 46 squamous cell/adenosquamous carcinomas (SC/ASC) and 80 adenocarcinomas (AC) by using immunohistochemistry. Results. Positive ALDH1A3 and negative GPX3 expressions were significantly associated with lymph node metastasis and invasion of SC/ASCs and ACs. Univariate Kaplan-Meier analysis showed that either positive ALDH1A3 or negative GPX3 expression significantly correlated with decreased overall survival in both SC/ASC and AC patients. Multivariate Cox regression analysis showed that positive ALDH1A3 expression or negative GPX3 expression was an independent poor-prognostic predictor in both SC/ASC and AC patients. Conclusions. Our study suggested that positive ALDH1A3 and negative GPX3 expressions are closely associated with clinical pathological behaviors and poor prognosis of gallbladder cancer.

Salivary Markers of Oxidative Stress and Their Relation to Periodontal and Dental Status in Children

Abstract: Background: Previous studies have shown that salivary thiobarbituric acid reactive substances are related to the periodontal status in adults. Such an analysis has not been done on children yet. The aim of our study was to analyze salivary markers of oxidative stress in relation to periodontal and dental status in children. Methods: The periodontal and dental status of 82 consecutive pediatric dental patients was assessed. The oral hygiene index (OHI), the papillary bleeding index (PBI) and the caries index (CI) were assessed as clinical parameters. Markers of oxidative stress and antioxidant status were measured in whole saliva samples. Results: Multivariate analysis of covariance showed that the variability of PBI explains 10.9% of the variance of salivary thiobarbituric acid reacting substances (TBARS). Advanced oxidation protein products (AOPP) were related to CI (eta 8.6%). Measures of antioxidant status (total antioxidant capacity and ferric reducing ability of saliva) were partially determined by OHI (13.6% and 7.2%) and PBI (16.9% and 7.9%). Conclusions: Antioxidant status in saliva is related to oral hygiene and periodontal status. Salivary TBARS are a potential sensitive marker of periodontitis in children, similarly to adults, at least on a population level. Salivary AOPP are related to caries. Potential diagnostic value of the analyzed markers should be analyzed in further interventional studies.

Association between -308 G/A TNF-α polymorphism and appendicular skeletal muscle mass index as a marker of sarcopenia in normal weight obese syndrome.

Abstract: Background and Aim. Normal weight obese (NWO) syndrome is characterized by normal body mass index (BMI), but high amount of fat mass and reduced lean mass. We evaluated allelic frequency of the G/A −308 TNF-α polymorphism and prevalence of sarcopenia in NWO. Methods. We enrolled 120 Italian healthy women, distinguished into 3 groups: normal weight (NW); NWO, and preobese-obese (PreOB/OB) and evaluated anthropometric parameters, body composition by dual X-ray absorptiometry, blood tests, and genotyping of G/A −308 TNF-α polymorphism. Results. We found a positive association between sarcopenic obesity and −308 TNF-α polymorphism. All obese women were sarcopenic and were no carrier of mutation (G/G). Among all G/G, NWO showed significant differences in lean mass and total body lean mass (TBLean) with respect to NW and PreOB/OB (P < 0.001). Regarding appendicular skeletal muscle mass index values, 4.21% of NW were sarcopenic (50% G/G and 50% G/A); the same percentage was observed in NWO subjects (100% G/G). Moreover, 2.10% of PreOB/OB were sarcopenic and all were G/G. Conclusion. Our study suggests that TNF-α polymorphism contributes to sarcopenic obesity susceptibility, in association with body composition. This is the first study that shows the importance of TNF-α polymorphism to determine TBLean variation in NWO syndrome.