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Results for “Biomarker variability”

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PubMed1995

Expression of sialyl-Tn in gastric cancer: correlation with known prognostic factors.

Sialyl-Tn (STn) is a core region carcinoma-associated carbohydrate determinant expressed on cancer-associated mucins. Expression of STn has been associated with poor prognosis in colon and ovarian cancer, independent of other prognostic factors such as tumour grade, stage or histological type. Recent studies have suggested that STn expression may be an independent prognostic variable in gastric cancer. We have examined 158 patients with gastric cancer using the antibody B72.3 (Biomira, Edmonton, Alberta, Canada). Of these, 110 patients (70%) expressed STn. Expression of STn did not correlate with tumour differentiation or the Ming classification, but expression was noted more frequently in the relatively good prognosis intestinal type of tumours (chi 2 = 6.9, P = 0.03). Conversely, early-stage cancers showed a significantly lower frequency of expression than more advanced cases (chi 2 = 13.75, P = 0.003). In this patient group, STn expression did not influence survival, and in multivariate regression analysis only tumour stage and Lauren classification were found to be independent prognostic variables.

Antigens, Tumor-Associated, Carbohydrate↗
PubMed2005

Tumor classification by tissue microarray profiling: random forest clustering applied to renal cell carcinoma.

We describe a novel strategy (random forest clustering) for tumor profiling based on tissue microarray data. Random forest clustering is attractive for tissue microarray and other immunohistochemistry data since it handles highly skewed tumor marker expressions well and weighs the contribution of each marker according to its relatedness with other tumor markers. This is the first tumor class discovery analysis of renal cell carcinoma patients based on protein expression profiles. The tissue array data contained at least three tumor samples from each of 366 renal cell carcinoma patients. The eight tumor markers explore tumor proliferation, cell cycle abnormalities, cell mobility, and the hypoxia pathway. Since the procedure is unsupervised, no clinicopathological data or traditional classifications are used a priori. To explore whether the tissue microarray data can be used to identify fundamental subtypes of renal cell carcinoma patients, we first carried out random forest clustering of all 366 patients. By analyzing the tumor markers simultaneously, the procedure automatically detected classes that correspond to clear- vs non-clear cell tumors (demonstration of proof-of-principle). The resulting molecular grouping provides better prediction of survival (logrank P=0.000090) than this classical pathological grouping (logrank P=0.023). We then sought to extend the class discovery by searching for finer subclasses of clear cell patients. The procedure automatically discovered: (a) two classes corresponding to low- and high-grade patients (demonstration of proof-of-principle); (b) a subgroup of long-surviving clear cell patients with a distinct molecular profile and (c) two novel tumor subclasses in low-grade clear cell patients that could not be explained by any clinicopathological variables (demonstration of discovery).

Biomarkers, Tumor↗
PubMed1996

Comparison of troponin-T with other cardiac markers in a VA hospital.

Measuring protein markers of cardiac damage is important for the diagnosis of myocardial infarction (MI). This study accessed the positive and negative predictive values of cardiac markers for detecting MI and perioperative MI in cardiac surgery by evaluating: creatine kinase (CK); creatine kinase MB isoenzyme mass assay (CK-MB); lactate dehydrogenase (LDH); lactate dehydrogenase isoenzyme-1 (LDH-1); myoglobin; and cardiac troponin T (cTnT) in a Veterans Affairs Medical Center. Inclusion criterion was any patient who had a CK ordered over a 6-month period. Patient history and diagnosis were obtained from discharge summaries. The two groups of patients studied either presented with symptoms of MI (n = 370), or underwent open heart surgery (n = 63). In the patients evaluated for MI, there were 433 suspected cardiac events with 48 MIs diagnosed. Cardiac marker sensitivities and specificities were cTnT (98% and 73%), CK-MB mass (81% and 97%), CK (73% and 78%), LDH (67% and 80%), LDH-1 (33% and 95%), and myoglobin (79% and 66%). For detecting MI, the marker that provided the optimum specificity was CK-MB mass, but cTnT had the highest negative predictive value. There was one perioperative MI in the 63 cardiac surgery patients. Surgical duration and aortic cross clamp time correlated with peak cTnT and CK-MB mass concentrations, but there was a wide degree of variability for any given time period.

Biomarkers↗
PubMed1995

Limited discriminant value of lipoprotein AI, lipoprotein Lp(a) and other lipoprotein particles in patients with and without early onset ischaemic heart disease.

AIMS: To assess whether the ability of lipoprotein related variables to discriminate between individuals with or without premature clinical ischaemic heart disease (IHD) was improved using data on high density lipoprotein-lipoprotein AI (HDL-LpAI) fractions, alone or in combination with data on Lp(a). METHODS: Lipid and apolipoprotein concentrations were measured in 26 middle-aged men (mean age 50.3 years) with early onset IHD and coronary artery bypass grafting prior to sampling, and in 26 matched lipaemic and 26 normolipaemic asymptomatic controls. RESULTS: Triglyceride and Lp(a) concentrations were higher, while HDL cholesterol and apolipoprotein A-I (apoA-I) concentrations were lower in patients than in controls. LpAI concentrations were also lower in IHD patients and were correlated with HDL and apoA-I in both IHD and control groups. Lp(a) was not correlated with any other lipid or apolipoprotein measured in either patients or controls. Univariate discriminant function analysis showed that the proportion correctly classified as patients or controls was marginally greater using LpAI concentrations as the discriminator, which was not increased in combination with Lp(a). Serum triglycerides, HDL cholesterol, apoA-I and Lp(a) alone all had similar, but weaker, discriminant power, which increased in various combinations with LpAI. CONCLUSIONS: LpAI particle measurement may be useful in research to define mechanisms of cardiovascular protection by HDL but the discriminating power for IHD was only marginally superior to measuring total apoA-I or Lp(a) concentrations. Little further advantage arose through combining LpAI data with other variables.

Adult↗
PubMed2003

[Tumor markers in epithelial ovarian cancer].

Many circulating markers are already in clinical practice and in experimental use for the diagnosis, therapeutic monitoring, and in the follow-up of ovarian cancer. The cancer antigen-125 (CA-125) has shown to be useful in epithelial ovarian cancer, but its specificity is too low for the test to be used as a primary screening technique in early stage and particularly in premenopausal women. In the last few years, several studies have focused on using the serial measurement of complementary serum markers to improve the positive predictive value and diagnostic accuracy. The main problem is that the different cellular lines express these markers in a very variable way.

Antigens, Neoplasm↗
PubMed1996

Immunohistochemical markers of prolonged survival in small cell carcinoma of the lung. An immunohistochemical study.

OBJECTIVE: To investigate the association of a variety of cell surface and cytoplasmic antigens in small cell carcinoma of the lung with long-term survival (greater than 2 years). DESIGN: Using immunohistochemical analysis of small cell carcinomas, the tissue expression of corticotropin, bcl-2, p-glycoprotein, cathepsin B, cathepsin D, CD44, carcinoembryonic antigen, collagenase IV, Leu-7, neu oncoprotein, p53, S100, and synaptophysin was assessed. RESULTS: Compared with the control group of short-term survivors, tumors from prolonged survivors were unique in their relative absence of staining for cathepsin B (0/13 vs 3/13 [23%], P = .037), cathepsin D (5/13 [38%] vs 13/15 [87%], P = 0.006), carcinoembryonic antigen (5/13 [38%] vs 11/15 [73%], P = .047), and neu oncoprotein (5/13 [38%] vs 14/15 [93%], P = .0014). A variety of histologic characteristics were also compared, and none were shown to be associated with differences in survival in this study. CONCLUSIONS: Negative immunohistochemical staining for cathepsin B, cathepsin D, carcinoembryonic antigen, and neu oncoprotein is associated with prolonged survival in small cell carcinoma of the lung. Evaluation of these antigens should be considered in future attempts to stratify patients with small cell carcinoma of the lung for prognostic or therapeutic purposes, as this study is limited by the small size of the study group and the large number of clinical and pathologic variables.

Adult↗
PubMed1995

[Prognostic factors in neuroblastoma in children].

The paper presents the review of prognostic factors which were investigated from the first interests of neuroblastoma, as a model for cancer biology in pediatric oncology. The authors on the basis of other authors experiences and on the own observations, as well stress the importance of basic sciences from the field of molecular biology, cytogenetics and biochemistry, leading to better understanding of the nature of neuroblastoma and to introduction of rational treatment. The stratification of neuroblastoma patients according to the known prognostic variables influenced favourably treatment results.

Biomarkers, Tumor↗
PubMed2005

Oxidative stress generated by diesel seawater contamination in the digestive gland of the Antarctic limpet Nacella concinna.

The aim of this work was to investigate the activity of antioxidant enzymes and oxidative damage in the digestive gland of the limpet Nacella concinna, and their suitability as biomarkers for hydrocarbon pollution in Antarctic coasts. Three groups of 30 individuals each were kept in seawater containing 0%, 0.05% or 0.1% diesel. Superoxide dismutase, catalase, glutathione S transferase and glutathione peroxidase activities, as well as lipid peroxidation and protein oxidation were studied in 18 animals of each group after 24, 48 and 168 h of exposure. The activity levels of most enzymes were increased by diesel in a dose-dependent manner. Glutathione peroxidase showed the most clear effect; its activity significantly increased in the 0.1% diesel group respect to the control. Lipid peroxidation and protein oxidation were significantly increased by diesel after 168 h. Both variables were higher in the group exposed to the lowest dose.

Animals↗
PubMed2006

Physiological dysregulation and changes in health in an older population.

We investigate whether a multi-system measure of physiological dysregulation based on 16 biological measures is associated with deterioration in physical and mental health over a 3-year period. The data come from a national survey of persons 54 and older in Taiwan that collected standard clinical markers related to cardiovascular and metabolic function and "non-clinical" measures pertaining to the immune, neuroendocrine and sympathetic nervous systems. The dysregulation score counts the number of biomarkers for which values are in the lowest or highest decile. Statistical models examine whether dysregulation predicts four health outcomes (survival, physical functioning, cognitive functioning and depressive symptoms), in the presence of extensive controls for baseline health. The estimates reveal significant associations between dysregulation and health for each outcome, although there is variability across outcomes. The associations are often attenuated in the presence of health controls, underscoring the importance of longitudinal analysis. This study extends previous research on the health consequences of physiological dysregulation by considering a broader range of outcomes and biomarkers in a non-Western population-based sample. Our analysis suggests that such dysregulation provides early warning signs of a broad range of comorbidities.

Aged↗
PubMed2003

Lead exposure biomarkers and mini-mental status exam scores in older men.

BACKGROUND: Lead is neurotoxic; yet, whether cognitive decline in older persons is associated with lead exposure is unknown. We studied whether lead exposure biomarkers are associated with cognitive test scores, as well as the modifying effects of age on the lead-cognition relationship. METHODS: Lead exposure biomarkers and Mini-Mental Status Exam (MMSE) scores were measured among subjects in the Normative Aging Study. Multiple linear and logistic regression analyses were performed to examine the cross-sectional association of these 2 variables. RESULTS: We found an odds ratio (OR) of 2.1 for MMSE <24 with an increase from the lowest to the highest quartile of patella lead levels (95% confidence interval [CI] = 1.1 to 4.1). From the lowest to the highest quartile of blood lead the OR for low MMSE was 3.4 (CI = 1.6 to 6.2). There was an interaction between lead biomarkers and age. Among subjects in the lowest quartile of patella lead levels, MMSE score decreased by 0.03 points per year (CI = -0.07 to 0.005), whereas in the highest quartile, MMSE score decreased by 0.13 points per year (CI = -0.19 to -0.07). Similar interactions were found between blood lead levels and age. CONCLUSIONS: Increased levels of lead in bone and blood are inversely associated with cognitive performance among older men. Lead exposure might accelerate age-associated cognitive decline.

Aged↗
PubMed2002

Decomposition chemistry of human remains: a new methodology for determining the postmortem interval.

This study was conducted to characterize the chemistry associated with the decomposition of human remains with the objective of identifying time-dependent biomarkers of decomposition. The purpose of this work was to develop an accurate and precise method for measuring the postmortem interval (PMI) of human remains. Eighteen subjects were placed within a decay research facility throughout a four-year time period and allowed to decompose naturally. Field autopsies were performed and tissue samples were regularly collected until the tissues decomposed to the point where they were no longer recognizable (encompassing a cumulative degree hour (CDH) range of approximately 1000 (approximately 3 weeks)). Analysis of the biomarkers (amino acids, neurotransmitters, and decompositional by-products) in various organs (liver, kidney, heart, brain, muscle) revealed distinct patterns useful for determining the PMI when based on CDHs. Proper use of the methods described herein allow for PMIs so accurate that the estimate is limited by the ability to obtain correct temperature data at a crime scene rather than sample variability.

Adult↗
PubMed1995

The relationship between environmental monitoring and biological markers in exposure assessment.

The poor quality of traditional assessments of exposure has encouraged epidemiologists to explore biological monitoring in studies of chronic diseases. Yet, despite theoretical advantages, biomarkers have not been widely used in such applications. This article compares the general utility of a biomarker with that of the measurement of exposure per se. Points are illustrated with a longitudinal study of boat workers in which levels of styrene in the breathing zone and in exhaled air were compared to sister chromatid exchanges (SCEs) in peripheral lymphocytes. First, the linear relationship is explored between personal exposure and the levels of a biomarker in the cohort. A good fit to the straight-line relationship reflected by a correlation coefficient which is close to 1, such as observed with styrene in exhaled air (r2 = 0.83), suggests linear kinetics, that the appropriate route of exposure was measured by personal monitoring, small interindividual differences, adequate sample sizes, and a specific biomarker. However, a small correlation coefficient, as observed between SCEs and styrene exposure (r2 = 0.11), indicates that either kinetics were nonlinear or that more complex issues were involved with one or more of these factors. Second, environmental and biologic measurements are compared for use as independent variables in establishing a straight-line relationship between exposure and the health effect. If the ratio of the within-person to the between-person components of variance of the independent variable is large, then significant attenuation results when estimating the slope of the line.(ABSTRACT TRUNCATED AT 250 WORDS)

Biomarkers↗
PubMed2005

Exposure to CB-153 and p,p'-DDE and bone mineral density and bone metabolism markers in middle-aged and elderly men and women.

The incidence of osteoporotic fractures is rising in western societies, partly due to unknown reasons. Persistent organochlorine compounds (POC) have in animal studies impaired the normal bone metabolism and resulted in increased bone fragility, which might have health implications for POC-exposed human populations. The aim of the present study was to assess whether a high dietary intake of POC through fatty fish from the Baltic may result in decreased bone mineral density (BMD) or disturbances in biochemical markers of bone metabolism. From a study base of fishermen and fishermen's wives from the Swedish east coast who are considerably more POC-exposed than the general Swedish population, 196 men (median age 59 years) and 184 women (median age 62 years) participated in an examination of their forearm BMD, using dual energy x-ray absorptiometry (DXA). Further, POC exposure was assessed by analysis of lipid-adjusted serum levels of 2,2',4,4',5,5'-hexachlorobiphenyl (CB-153) and 1,1-dichloro-2,2-bis(p-chlorophenyl)-ethylene (p,p'-DDE). Cadmium in urine (U-Cd) was also analyzed. Biochemical markers in serum of osteoblastic (osteocalcin) and osteoclastic (CrossLaps) functions were measured. Adjustment for potential confounders was made by employing multiple regression analyses. Univariate analyses showed significant negative associations between CB-153 concentrations and BMD, but after adjustment for age and body mass index, these associations did not remain. None of the POC exposure variables were associated with CrossLaps or osteocalcin. There were no significant associations between U-Cd and BMD or any of the biochemical biomarkers. In conclusion, the results did not provide any support for the hypothesis that the current exposure levels to POC constitute a hazard for impaired bone metabolism in the general Swedish population.

Absorptiometry, Photon↗
PubMed2006

DNA arrays as predictors of efficacy of adjuvant/neoadjuvant chemotherapy in breast cancer patients: current data and issues on study design.

Chemotherapy provides variable benefit to patients with breast cancer, with usually modest but occasionally severe side effects. Hence, there is a need to identify predictive biomarkers for its efficacy. DNA arrays have been used in this setting as potential novel predictive diagnostic tools. Several gene signatures and single gene markers were proposed to predict response to chemotherapy. Although this technology offers interesting perspectives through large-scale analysis of the transcriptome, its ability to identify clinically relevant predictors is highly dependent on study design. In the present manuscript, we will review currently available results of breast cancer pharmacogenomics and focus on aspects of study design that are critical to reliably identify predictive biomarkers using DNA array technology. We will discuss whether studies should be done in the overall, unselected breast cancer population or in specific homogeneous molecular subclasses. Next, we will compare advantages and limitations of cohort-based and case-control studies. The choice of end-point to discriminate between sensitive and resistant patients will also be examined.

Antineoplastic Combined Chemotherapy Protocols↗
PubMed2000

Assessment of environmental tobacco smoke exposure in children with asthmatic symptoms by questionnaire and cotinine concentrations in plasma, saliva, and urine.

To validate a detailed questionnaire for assessment of environmental tobacco smoke (ETS) exposure by the biomarker cotinine in various media, a population-based study in the urban area of Malmö, Sweden was performed in children aged 8-13 years with and without asthmatic symptoms. There were strong correlations between urinary and saliva cotinine concentrations and also, though to a lesser extent, between these media and plasma. Even a detailed questionnaire gave only a rough picture of the ETS exposure, as indicated by the biomarkers. In a multivariate model, the most significant questionnaire-derived predictor of the cotinine levels was the maternal smoking habits; other questionnaire variables gave only a minimal explained variance. Children with a history of asthmatic symptoms had statistically significantly lower median cotinine levels in urine and saliva compared to referent children, most likely because of the antismoking information to their parents. This should be considered in epidemiological studies of ETS risks.

Adolescent↗
PubMed1999

Elevated levels of peritumoral chondroitin sulfate are predictive of poor prognosis in patients treated by radical prostatectomy for early-stage prostate cancer.

The disease course of localized prostate cancer is highly variable, and patients potentially curable by aggressive management are not readily identified by current clinical practice. Chondroitin sulfate (CS) glycosaminoglycan is a candidate biomarker as elevated levels of CS in peritumoral stroma of prostate cancer have been associated with prostate-specific antigen (PSA) failure. Immunoreactive CS was measured using image analysis of archived radical prostatectomy tissues, obtained from 157 men with a median of 47 months (range, 16-111 months) clinical follow-up. CS level, Gleason score, and preoperative serum PSA levels were independent predictors of PSA failure by Cox's multivariate analysis. Patients with low CS levels had significantly fewer PSA failures after radical prostatectomy than patients with high levels of CS (Kaplan-Meier plot; 32% PSA failures at 5 years for CS mean integrated absorbance cut point < 7.0 versus 50% for CS > or = 7.0, P = 0.0001). In the subgroup of patients with preoperative serum PSA levels < 10 ng/ml, CS was particularly useful in discriminating retrospectively those patients most suited for surgery (Kaplan-Meier plot; 14% PSA failures at 5 years for CS mean integrated absorbance cut point < 7.0 versus 47% for CS > or = 7.0, P = 0.0001). We conclude that measurements of CS level can assist in predicting patient outcome after surgery. Additionally, our data suggest that the combination of CS and PSA measurements may improve outcome prediction for patients with intermediate Gleason scores.

Adenocarcinoma↗
PubMedDate not supplied

Early markers of nephrotoxicity: detection of children at risk from environmental pollution.

The current investigation is the largest to date concerned with the assessment of the value of different urinary biomarkers to detect nephrotoxic effects in children exposed to cadmium and lead. A battery of tests which had proved valuable in previous studies on men and women where used, together with a number of more recently developed biomarkers. No significant effect of sex and age were found but the location of the children (site) was important. The results indicated that there might have been variability in either the assay procedures or sample handling between the different sites. A small group of tests were found to be elevated following toxic exposure and should be used in future studies. However, there was considerable variation in the degree of exposure amongst the control groups from different countries and in the test groups. This made pooling of the data difficult but the study does highlight the way forward and demonstrates that children can be at risk from environmental exposure to toxins at a lower level than is acceptable for adults.

Adolescent↗