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PubMed2006

ELISA microarray technology as a high-throughput system for cancer biomarker validation.

A large gap currently exists between the ability to discover potential biomarkers and the ability to assess the real value of these proteins for cancer screening. One major challenge in biomarker validation is the inherent variability in biomarker levels. This variability stems from the diversity across the human population and the considerable molecular heterogeneity between individual tumors, even those that originate from a single tissue. An additional challenge with cancer screening is that most cancers are rare in the general population, meaning that assay specificity must be very high. Otherwise, the number of false positives will be much greater than the number of true positives. Due to these challenges associated with biomarker validation, it is necessary to analyze thousands of samples in order to obtain a clear idea of the utility of a screening assay. Enzyme-linked immunosorbent assay (ELISA) microarray technology can simultaneously quantify levels of multiple proteins and, thus, has the potential to accelerate validation of protein biomarkers for clinical use. This review will discuss current ELISA microarray technology and potential advances that could help to achieve the reproducibility and throughput that are required to evaluate cancer biomarkers.

Biomarkers, Tumor↗
PubMed2004

Biomarkers: potential uses and limitations.

Biomarkers provide a dynamic and powerful approach to understanding the spectrum of neurological disease with applications in observational and analytic epidemiology, randomized clinical trials, screening and diagnosis and prognosis. Defined as alterations in the constituents of tissues or body fluids, these markers offer the means for homogeneous classification of a disease and risk factors, and the can extend our base information about the underlying pathogenesis of disease. Biomarkers can also reflect the entire spectrum of disease from the earliest manifestations to the terminal stages. This brief review describes the major uses of biomarkers in clinical investigation. Careful assessment of the validity of biomarkers is required with respect to the stage of disease. Causes of variability in the measurement of biomarkers range from the individual to the laboratory. Issues that affect the analysis of biomarkers are discussed along with recommendations on how to deal with bias and confounding.

Biomarkers↗
PubMed2004

Isoform-specific quantification of metallothionein in the terrestrial gastropod Helix pomatia. II. A differential biomarker approach under laboratory and field conditions.

The two function-specific metallothionein (MT) isoforms characterized from the midgut gland and mantle tissue of Helix pomatia differ substantially in their metal-binding preferences, as well as molecular and biochemical features. These differences make them potential candidates for biomarker studies based on a differential, isoform-specific approach. To prove this hypothesis, induction experiments with two metals (Cd and Cu) that are normally bound by the two isoforms were compared with a range of organic chemicals and physical stressors under laboratory conditions to test the responsiveness of the two isoforms to the stressors applied. In addition, field studies were conducted with Roman snails and substrate samples collected from different metal-contaminated sites in Austria to test the suitability of the two isoforms as biomarkers under field conditions. The results of these combined laboratory and field studies confirmed the validity of the biomarker approach with the two metal- and tissue-specific isoforms. It is demonstrated that the Cd-binding MT specifically and exclusively responds to Cd exposure by increasing concentrations, whereas the Cu-binding MT isoform decreases in its concentration upon exposure to physical stress (X-ray irradiation and cold). This suggests researchers should adopt, under certain preconditions, a dual biomarker approach by combining the simultaneous quantification of Cd-MT concentrations in the midgut gland as a biomarker for Cd pollution and of Cu-MT concentration in the mantle as a biomarker for the impairment of snails by additional physical stressors.

Animals↗
PubMed2006

Sampling and analytical strategies for biomarker discovery using mass spectrometry.

There is an often unspoken truth behind the course of scientific investigation that involves not what is necessarily academically worthy of study, but rather what is scientifically worthy in the eyes of funding agencies. The perception of worthy research is, as cost is driven in the simplest sense in economics, often driven by demand. Presently, the demand for novel diagnostic and therapeutic protein biomarkers that possess high sensitivity and specificity is placing major impact on the field of proteomics. The focal discovery technology that is being relied on is mass spectrometry (MS), whereas the challenge of biomarker discovery often lies not in the application of MS but in the underlying proteome sampling and bioinformatic processing strategies. Although biomarker discovery research has been historically technology-driven, it is clear from the meager success in generating validated biomarkers that increasing attention must be placed at the pre-analytic stage, such as sample retrieval and preparation. As diseases vary, so do the combinations of sampling and sample analyses necessary to discover novel biomarkers. In this review, we highlight different strategies used toward biomarker discovery and discuss them in terms of their reliance on technology and methodology.

Biomarkers↗
PubMed2006

Proteomic-based biomarker discovery with emphasis on cerebrospinal fluid and multiple sclerosis.

Discovery of disease specific biomarkers in human body fluids has become an important challenge in clinical proteomics. Facing the increasing threat of degenerative and disabling diseases like cancer, cardiovascular, neurological and inflammatory diseases in large parts of the world's population, there is an urgent need to improve early diagnostics. In this review we discuss possibilities and limitations connected to using mass spectrometry based proteomics in the search for novel biomarkers, with focus on multiple sclerosis as a typical representative for the large group of non-curable degenerative and disabling disease with the lack of specific tests for early diagnosis. Careful control of the pre-analytical phase including sampling, storage and fractionation of samples, in addition to a thoroughly considered patient selection, is important in order to avoid false biomarkers to appear in the resulting mass spectra. Furthermore, advanced computational tools are needed in order to discover potential biomarkers from the enormous data amounts generated by the mass spectrometers. The development of such computer tools is a research field currently in the start phase and could prove to be a bottle neck in the biomarker discovery the next years. Therefore, a rather detailed review of the most used computational and pre-analytical methods is given in this review. Mass spectrometry based biomarker discovery is undoubtedly still in its early infancy. However, in light of the potential of this technology to provide deep coverage of the body fluid proteomes, it will certainly consolidate its role in developing molecular medicine into clinical practice.

Biomarkers↗
PubMed2004

Evaluation of serum concentrations of biomarkers of skeletal metabolism and results of radiography as indicators of severity of osteochondrosis in foals.

OBJECTIVE: To determine whether serum concentrations of biomarkers of skeletal metabolism can, in conjunction with radiographic evaluation, indicate severity of osteochondrosis in developing horses. ANIMALS: 43 Dutch Warmblood foals with varying severity of osteochondrosis. PROCEDURE: 24 foals were monitored for 5 months and 19 foals were monitored for 11 months. Monthly radiographs of femoropatellar-femorotibial and tibio-tarsal joints were graded for osteochondral abnormalities. Serial blood samples were assayed for 8 cartilage and bone biomarkers. At the end of the monitoring period, foals were examined for macroscopic osteochondrosis lesions. RESULTS: Temporal relationships were evident between certain serum biomarkers and osteochondrosis severity in foals during their first year. Biomarkers of collagen degradation (collagenase-generated neoepitopes of type-II collagen fragments, type-I and -II collagen fragments [COL2-3/4C(short)], and cross-linked telopeptide fragments of type-I collagen) and bone mineralization (osteocalcin) were positive indicators of osteochondrosis severity at 5 months of age. In foals with lesions at 11 months of age, osteochondrosis severity correlated negatively with COL2-3/4C(short) and osteocalcin and positively with C-propeptide of type-II procollagen (CPII), a collagen synthesis marker. Radiographic grading of osteochondrosis lesions significantly correlated with macroscopic osteochondrosis severity score at both ages and was strongest when combined with osteocalcin at 5 months and CPII at 11 months. CONCLUSIONS AND CLINICAL RELEVANCE: The ability of serum biomarkers to indicate osteochondrosis severity appears to depend on stage of disease and is strengthened with radiography. In older foals with more permanent lesions, osteochondrosis severity is significantly related to biomarker concentrations of decreased bone formation and increased cartilage synthesis.

Animals↗
PubMedDate not supplied

Urinary biomarkers: recommendations of the Joint European/United States Workshop for future research.

The session concluded on a positive note with enthusiasm on the part of participates to become involved in one of the proposed joint protocols. Left to be answered was whether or not individual urinary biomarkers can be tailored to be disease specific or will there always be a need for a panel of biomarkers to insure interpretable results? It was agreed that proposals for three studies would be prepared. The first study will take advantage of the fact that field studies are currently being organized by both European and American groups. European scientists are working with the World Health Organization to investigate lead exposure in a region of China. At the same time, scientists in the United States are implementing a surveillance program in a population exposed to lead and other heavy metals in Kellogg, Idaho. These efforts provide an excellent opportunity for the sharing of samples and the study of a biomarkers panel that would contain both standard and candidate biomarkers. It was agreed that the parties interested in participating would alert the workshop organizers. The second study will expand upon a protocol developed by Dr. Debroe that has as its subjects non-transplant patients being treated with cyclosporine. An additional complimentary study of tacrolimus (FK-506) nephrotoxicity will also be developed. This protocol will be designed to follow the loss of renal function with a urinary biomarkers panel. The third study will follow the lead of Dr. Safirstein who urged the consideration of Cisplatin nephrotoxicity as a singular model for analyzing the usefulness of various biomarkers as measures of both acute and chronic nephrotoxicity.

Biomarkers↗
PubMed1997

The use of biomarker expression to characterize neoplastic processes.

Biomarkers have been used by pathologists to aid the diagnosis of tumors for almost three decades. Their use has resulted in the re-evaluation and reclassification of several types of tumors. Currently, biomarkers are required to differentiate certain specific tumors with similar histologic patterns. Additional uses of biomarkers in the characterization of neoplastic processes are discussed including their use is prognosis, detecting early neoplastic processes, identifying tumor recurrence, measuring the effectiveness of various therapies (surrogate end point biomarkers), and identifying targets for novel therapies including immunotherapy and gene therapy. We propose that these newer uses of biomarkers will be just as important to pathology in the future as the uses of biomarkers in diagnosis have been over the past two decades.

Biomarkers, Tumor↗
PubMed2001

Biomarker responses in river otters experimentally exposed to oil contamination.

Investigations in Prince William Sound (Alaska, USA) following the Exxon Valdez oil spill (EVOS) revealed that river otters (Lontra canadensis) on oiled shores had lower body mass and elevated values of biomarkers, than did otters living on nonoiled shores. In addition, otters from oiled areas selected different habitats, had larger home ranges, and less diverse diets than animals living in nonoiled areas. These differences between river otters from oiled shores and those from nonoiled areas strongly suggested that oil contamination had an effect on physiological and behavioral responses of otters. In this study, we explored the effects of crude oil contamination on river otters experimentally. We hypothesized that exposure to oil would result in elevated values of biomarkers, indicating induced physiological stress. Fifteen wild-caught male river otters were exposed to two levels of weathered crude oil (i.e., control, 5 ppm/day/kg body mass, and 50 ppm/day/kg body mass) under controlled conditions in captivity at the Alaska Sealife Center in Seward (Alaska, USA). Responses of captive river otters to oil ingestion provided mixed results in relation to our hypotheses. Although hemoglobin (Hb, and associated red blood cells) and white blood cells, and possibly interleukin-6 immunoreactive responded in the expected manner, other parameters did not. Aspartate aminotransferase, alanine aminotransferase, and haptoglobin (Hp), did not increase in response to oiling or decreased during rehabilitation. Conversely, principle-component analysis identified values of alkaline phosphatase as responding to oil ingestion in river otters. Our results suggested that opposing processes were concurring in the oiled otters. Elevated production of Hp in response to tissue damage by hydrocarbons likely occurred at the same time with increased removal of Hp-Hb complex from the serum, producing an undetermined pattern in the secretion of Hp. Thus, the use of individual biomarkers as indicators of exposure to pollutants may lead to erroneous conclusions because interactions in vivo can be complicated and act in opposite directions. Additionally, the biomarkers used in investigating effects of oiling on live animals usually are related to the heme molecule. Because of the opposing processes that may occur within an animal, data from a suite of heme-related biomarkers may produce results that are difficult to interpret. Therefore, we advocate the exploration and development of other biomarkers that will be independent from the heme cycle and provide additional information to the effect of oiling on live mammals.

Alaska↗
PubMed2004

[Predictive value of human genotoxicological biomarkers in the primary prevention of chronic non-infectious diseases].

The main goal of biomarker research in the frame of primary prevention of chronic diseases is the prevention of appearance of clinical symptoms by an early recognition of the process leading to the symptoms. By the use of well-established biomarkers one can detect such tendencies finally leading to the manifestation of the disease far before the progress turns irreversible. As several parameters play role in such processes, the estimation of biological changes with the help of biomarkers is a precise and relatively simple means of the prevention. Indications of intervention in order to prevent the manifestation of a disease are rather determined by the nature but not the number of alterations. The use of genetic screening and monitoring by adequate biomarkers provide us with a new opportunity to measure such qualitative changes rather than the quantitative ones, ensuring a great improvement to the previous methods. The use of qualitative parameters as a routine method instead of the classic quantitative measures might represent a challenge for current prevention policies in Europe to approach health problems and safety at work. When the biomarkers give positive results that means a high probability to be at risk but not yet the manifestation of a certain illness. This stage may be relevant to the early onset of certain pathological processes, but it does not necessarily turn to a performed disease. In consequence a so-called positive result might cause unnecessary disturbances for the probands leading to ethical issues of risk communication. The monitoring system, however, should find acceptable communication strategies for the high-risk conditions detected by the well-established biomarkers.

Biomarkers↗
PubMed1999

Before the storm: informing and involving stakeholder groups in workplace biomarker monitoring.

The social, legal and ethical implications of advances in biomarker indentification have been discussed by scholars and environmental researchers, but not by the "everyday" professionals and workers who may eventually make and be affected by decisions about their workplace applications. Through the use of a hypothetical scenario, this study introduced members of various professional and occupational groups to the potential uses of biomarkers research on biological monitoring in the workplace. The purpose was to obtain opinions about how events would proceed based on the scenario, leading to a broad discussion of potential uses and abuses of biomarker-based health monitoring. Six professionally homogeneous focus groups, comprised of 1) company health professionals, 2) third-party payers, 3) attorneys, 4) human resource managers, 5) non-unionized workers, and 6) unionized workers, participated in focus groups presented as "think-tank" discussions in Greenville and Charleston, S.C. Participants were given a fictitious "newspaper article" about the use of biomarker-based monitoring at a chemical plant and were asked to comment on what they thought would happen next. The discussion expanded to a general consideration of biological monitoring and its legal, social and ethical ramifications. Data was analyzed through the "immersion/crystallization" method. Few participants reported any knowledge of biological monitoring prior to the focus group session. Some had initial difficulty understanding the concept and how it differs from other means of measuring environmental risk. Although biological monitoring was previously unknown to many participants, occupational groups were relatively consistent in the issues they raised about its use in the workplace. In all groups, questions about potential discrimination against employees were raised. The general consensus was that the use of biomarker-based monitoring would result in conflict and litigation without regulations to protect employees from discrimination. Although most participants saw potential health benefits resulting from the preventive advantages associated with this technology, their concerns about its misuses were paramount. Perceptions varied as a function of occupation. Non-unionized workers expressed the most concern about discriminatory uses of biological monitoring. Unionized workers, who said they believed the union would support their interests, expressed much less concern. Health professionals (company physicians and nurse practitioners) were most alarmed about the "extra work" a monitoring program would create for them. Human resource managers concentrated on the company's "damage control" efforts. Attorneys emphasized that the reliable use of such tests would establish a causal relationship between exposure and personal injury. The results of this project illustrate that people who are most likely to be affected by biomarker-based biological monitoring in the workplace readily understand and are alarmed by its legal and ethical implications. It is unlikely that this technology will be fully accepted as an environmental risk assessment tool or as a prevention strategy without stringent protection of workers' rights. This study demonstrated the value of focus groups in obtaining opinion data about an environmental risk issue that it not yet well known to the general public.

Adult↗
PubMedDate not supplied

LEA.135 expression: its comparison with other prognostic biomarkers for patients with primary breast carcinoma.

The purpose of this retrospective study was to examine the prognostic value of expression of luminal epithelial antigen (LEA.135) for recurrence and overall survival of patients with primary invasive breast carcinoma by both univariate and multivariate analyses. The possible prognostic value of LEA.135 was also compared with some widely utilized prognostic biomarkers such as c-erbB 2, topoisomerase II.alpha (TPII.alpha), MIB 1, estrogen receptor (ER) and progesterone receptor (PR), as well as age of the patients and clinicopathologic parameters. The study was carried out by immunohistochemical methods on formalin-fixed/paraffin-embedded tissue sections in a series of 225 patients with median follow-up of 8.5 years. Prognostic significance of the biomarkers was determined by two-sided p value. In this series of patients, among the age and clinicopathologic parameters, only age, was significantly associated with a decreased overall survival (logrank p = 0.027). Among the prognostic biomarkers, TPII a expression at high (> 50% positive cells) or moderate (6-50% positive cells) level was associated with an increased rate of recurrence (logrank p < 0.001). However, the association of TPII.alpha expression with a decreased overall survival failed to reach a statistically significance. Expression of c-erbB 2 showed a trend of being associated with an increased probability of recurrence, but the association did not reach statistical significance. The remaining biomarkers were not associated with either the probability of recurrence or overall survival. LEA.135 expression was observed in 163 (72.4%) of the 225 patients. The patients with high (> 50% positive cells) or moderate (6-50% positive cells) level of LEA.135-positive cancer cells showed a significantly decreased probability of recurrence (logrank p < 0.001) and an increased overall survival (logrank p < 0.001) compared with those with LEA.135-negative cancer cells. The association remained significant by multivariate analysis for recurrence (likelihood ratio test p < 0.001) and overall survival (likelihood ratio test p < 0.001) when assessed with other prognostic parameters. Furthermore, the combination of LEA.135 with other prognostic biomarkers stratified four subgroups of patients with distinct clinical outcome. The subgroup of patients who were LEA.135+/TPII.alpha- showed the lowest probability of recurrence and the longest overall survival compared with those who were LEA.135-/TPII.alpha+ (logrank p < 0.001). Interestingly, the patients whose cancer cells were LEA.135+/TPII.alpha+, LEA.135+ MIB.1+ or LEA.135+/c-erbB 2+ experienced a decreased probability of recurrence and an increased overall survival compared with those with LEA.135-/TPII.alpha+, LEA.135- MIB.1+ or LEA.135-/c-erbB 2+ (logrank p < 0.001). The results demonstrated that LEA.135 is an independent and favorable prognostic biomarker for patients with primary invasive breast carcinoma, that the loss of LEA.135 expression is associated with aggressive phenotype of cancer cells during the breast cancer progression, and that its continued expression seems to override the adverse effects of expression of an oncogene or cell proliferation-associated molecules.

Age Factors↗
PubMed2000

Influence of personal factors on nasal patency and lavage biomarkers in white-collar workers.

Large biological variability between subjects has been shown for both acoustic rhinometry and nasal lavage biomarker concentrations, but relatively little is known about the influence of personal factors on these techniques. The aim was to evaluate if nasal symptoms, acoustic rhinometric measurements and nasal lavage fluid biomarkers are related to age, gender, smoking, atopy or asthma. A standardized nasal investigation was applied in 411 white-collar workers, belonging to three occupational groups: school personnel (n = 234), office workers (n = 89) and hospital workers (n = 88). Lavage fluid analysis included determination of eosinophil cationic protein (ECP), myeloperoxidase (MPO), lysozyme and albumin. Females had smaller nasal dimensions in the anterior part of the nose (p < 0.001), and lower lavage fluid concentrations of ECP (p = 0.004), MPO (p = 0.002), and albumin (p = 0.01). Rhinometric dimensions or lavage fluid biomarker concentrations were not related to age, smoking, atopy or asthma. Some differences in rhinometric and biomarker measurements were observed between the occupational groups, and adjustment was made for occupation. Rhinometric measures and lavage biomarkers were consistently interrelated, which suggests a combined mucosal swelling and inflammatory reaction. This indicates a potential usefulness of a combined use of acoustic rhinometry and lavage biomarkers to study nasal mucosal reactions.

Albumins↗
PubMed2001

Exposure biomarkers in chemoprevention studies of liver cancer.

Hepatocellular carcinoma (HCC) is the most common type of liver cancer, the major risk factors being hepatitis B and C viruses and aflatoxins; other factors such as alcohol are also of importance in some populations. Aflatoxin exposure biomarkers include urinary aflatoxin metabolites and aflatoxin-albumin adducts in peripheral blood. These biomarkers are well validated and have been applied in studies of many populations worldwide. They are proving to be valuable end-points in intervention studies, including chemoprevention studies. The biomarkers permit assessment of primary prevention measures to reduce aflatoxin intake. In addition, the determination of individual urinary aflatoxin metabolite profiles means that the effectiveness of chemopreventive agents designed to modulate aflatoxin metabolism can also be evaluated. Both aflatoxin-albumin adducts and urinary aflatoxin metabolites have been associated with increased HCC risk in prospective studies, indicating the predictive value of these biomarkers at the group level. However, given the multifactorial and multistep nature of HCC, it is unlikely that these exposure biomarkers will be predictive at the individual level or be of value as surrogate end-points in longer-term intervention trials aimed at reducing disease incidence. Aflatoxin-related mutations at codon 249 of the p53 gene in plasma may be more relevant in this regard but their application requires further understanding of the temporal appearance of this biomarker in relation to the natural history of the disease.

Aflatoxins↗
PubMed2001

Biomarkers of polycyclic aromatic hydrocarbon-DNA damage and cigarette smoke exposures in paired maternal and newborn blood samples as a measure of differential susceptibility.

Human and experimental evidence indicates that the developing fetus may be more susceptible than the adult to the effects of certain carcinogens, including some polycyclic aromatic hydrocarbons (PAHs). Factors that can modulate susceptibility include proliferation rates, detoxification capabilities, and DNA repair capacity. Biomarkers can facilitate quantification of age-related susceptibility among human populations. In this study, we report on three biomarkers measured in paired blood samples collected at birth from 160 Polish mothers and newborns: 70 pairs from Krakow (a city with high air pollution including PAHs) and 90 pairs from Limanowa (an area with lower ambient pollution but greater indoor coal use). Biomarkers were: WBC aromatic-DNA adducts by (32)P-postlabeling and PAH-DNA adducts by ELISA (as indicators of DNA damage from PAHs and other aromatics) and plasma cotinine (as an internal dosimeter of cigarette smoke). Correlations were assessed by Spearman's rank test, and differences in biomarker levels were assessed by the Wilcoxon signed-ranks test. A significant correlation between paired newborn/maternal samples was seen for aromatic-DNA adduct levels (r = 0.3; P < 0.001) and plasma cotinine (r = 0.8; P < 0.001) but not PAH-DNA adduct levels (r = 0.14; P = 0.13). Among the total cohort, levels of the three biomarkers were higher in newborn samples compared with paired maternal samples. The difference was significant for aromatic-DNA adduct levels (16.6 +/- 12.5 versus 14.21 +/- 15.4/10(8) nucleotides; P = 0.002) and plasma cotinine (14.2 +/- 35.5 versus 8.3 +/- 24.5 ng/ml; P < 0.001) but not for PAH-DNA adduct levels (7.9 +/- 9.9 versus 5.9 +/- 8.2/10(8) nucleotides; P = 0.13). When analyses were restricted to the 80 mother/newborn pairs from whom the blood sample was drawn concurrently (within 1 h of each other), levels of all of the three biomarkers were significantly higher in the newborn compared with paired maternal blood samples (P < 0.05). Results suggest reduced detoxification capabilities and increased susceptibility of the fetus to DNA damage, especially in light of experimental evidence that transplacental exposures to PAHs are 10-fold lower than paired maternal exposures. The results have implications for risk assessment, which currently does not adequately account for sensitive subsets of the population.

Adult↗
PubMed2001

The role of biomarkers in alcoholism medication trials.

BACKGROUND: Increasingly, biomarkers are being incorporated into the research design of clinical trials on medications to reduce drinking in alcoholics. To date, however, there has been little analysis of the unique roles that biomarkers can play in such investigations or of the practical and conceptual considerations that surround their best use in this context. METHODS: Clinical trials of alcoholism medications published between 1985 and the present were abstracted to determine how biomarkers were used and how changes in them related to self-report measures of drinking. RESULTS: Six uses of biomarkers were identified: determination of subjects to be included or excluded in the trial; description of baseline sample characteristics; primary and secondary outcome assessment; corroboration of self-reports of drinking status; specification of patients likely to respond to the medication; and evaluation of drug safety. CONCLUSION: Use of biomarkers in such studies appears warranted, particularly as an objective source of information on treatment efficacy that can be considered with patient self-report measures of drinking status. Biomarkers related to liver functioning also can assist in determination of drug safety for medications metabolized by the liver.

Alcoholism↗
PubMed2002

Pan-cadherin as a high level phenotypic biomarker for prostate cancer.

PURPOSE: High level phenotypic biomarkers such as cadherins are needed to identify individuals at risk for biologically active prostate cancer and determine which individuals with elevated prostate specific antigen or a prostate nodule are candidates for re-biopsy. Cadherins are a high level phenotypic biomarker associated with decreased cell adhesion, which is a cardinal event in carcinogenesis. Recently we reported that G-actin and tissue transglutaminase type II are potential biomarkers for prostate cancer. In this study we present cadherins as a potential third component of the biomarker profile. MATERIALS AND METHODS: Prostate tissues from 38 patients with cancer and 33 controls with a 10-year prostate cancer-free followup were labeled for pan-cadherin by immunohistochemical testing. Immunoreactivity was quantified using a Pathology Workstation (Autocyte Inc., Elon College, North Carolina). RESULTS: Visually benign glands from controls generally expressed cadherins, whereas regions of adenocarcinoma were generally negative. On quantitative immunohistochemistry 36 of 38 prostate cancer cases expressed a lower mean percent area positive for cadherin than the 19 benign prostatic hyperplasia and 14 prostatitis cases (odds ratio 978, 95% confidence interval 45 to 21,140, relative risk 18, 95% confidence interval 5 to 67, p <0.0001). Receiver operating characteristics analysis of immunohistochemical testing data showed that an optimal threshold of 7 produced 95% sensitivity and 100% specificity. CONCLUSIONS: Quantitative down-regulation of cadherin expression in prostate cancer tissue sections is a strong biomarker for prostate cancer. Analysis of cadherin and other high level phenotypic biomarker expression in the premalignant field may provide additional diagnostic information to decide which patients need re-biopsy, more intensive monitoring or chemoprevention.

Adenocarcinoma↗
PubMed2002

Integrated biomarker response: a useful tool for ecological risk assessment.

A battery of biomarkers is often used to evaluate the effects of exposure to chemical contaminants and detect responses to environmental stress. Unfortunately, field application of biomarkers is subject to various constraints (e.g., the availability of living material) that can limit data acquisition and prevent the use of multivariate methods during statistical analysis. In these circumstances, a simple method is needed to summarize biomarker responses and simplify their interpretation in biomonitoring programs. The present study used star plots to display results for the panel of biomarkers used for each station and survey. Integrated biomarker response (IBR) was then computed as the star plot area. Star plots using IBR values instead of biomarker data make it possible to visualize between-site and/or between-survey differences for comparison with exposure conditions. This approach was applied to sites in the Baltic Sea and the Seine Estuary, English Channel. In both cases, IBR values were visually compared to polycyclic aromatic hydrocarbons (PAH) or polychlorobiphenyls (PCB) levels measured in mussel or fish tissues. The IBR, as an indicator of environmental stress, appears to be a useful tool for scientists and managers in assessing ecological risk.

Acetylcholinesterase↗