Biomarkers evaluation

Leonzio C, Monaci F. 1996. Multiresponse biomarker evaluation of interactions between mettiylmercury and Aroclor 1260 in quad. Ecotoxicology 5 365-376. 

So far we have considered biomarkers whose validity has been either somewhat established or discredited by their use in clinical practice or in clinical trials. However, the utility of biomarkers in aiding both drug development and the diagnosis and management of patients has resulted in the introduction of many new biomarkers, many of which are less well characterized. Innovative but incompletely evaluated biomarkers are particularly likely to play an important role in exploratory studies of a new drug candidate. Unfortunately, the degree of innovation represented by a biomarker is likely to vary inversely with the extent of its validation (53). This is a consequence of the fact that prior use in clinical trials is an important component of biomarker evaluation. 

A variety of biomarkers have been shown to be valuable individually for one or several toxicant or disease situations. Few of these biomarkers have been systematically evaluated for the plethora of situations that might provoke false positive responses. Acceleration of the current pace of biomarker evaluation and qualification demands (a) the availability of panels of biomarker-assays that can be comparatively evaluated on well-defined common sample sets, (b) fit-for-purpose performance evaluation in controlled animal studies with carefully benchmarked histological endpoints and samples from well-defined focused clinical trial cohorts, and (c) ready availability of banked blood and urine sample archives from clinical trial populations with carefully documented morbidities such as the Framingham Heart Study,45 or the Drug-Induced Liver Injury Network (DILIN) prospective study,46 to name a few. Availability of such panels of validated biomarker assays and well-documented preclinical and clinical samples, as well as increased cooperation between animal model researchers and clinical researchers will enable individual biomarkers to be qualified for sensitivity of specifically defined adverse events, qualified for appropriate specificity using samples of defined benign events, and collected into panels that yield complementary information about the health and safety of animals and patients. 

Lawrence, J.A., Adamson, P.C., Caruso, R., Chow, C., Kleiner, D., Murphy, R.F., Venzon, D.J., Shovlin, M., Noone, M., Merino, M., Cowan, K.H., Kaiser, M., O Shaughnessy, J. and Zujewski, J. (2001) Phase I clinical trial of alitretinoin and tamoxifen in breast cancer patients toxicity, pharmacokinetic, and biomarker evaluations. Journal of Clinical Oncology, 19, 2754-2763. 

Walker, C.H. (1998d). Biomarker strategies to evaluate the environmental effects of chemicals. Environmental Health Perspectives 106 (Supplement 2), 613-620. 

WILD 0 p ANDERSSON 0, o brien n m, WILSON L and WOODS J A (2001) A critical evaluation of the application of biomarkers in epidemiological studies on diet and health. Br JNutr 86 (Suppl 1) S37-S53. 

Intervention trials confirmed this protective role of lycopene on prostate cancer risk. Three primary intervention studies evaluated the effect of lycopene supplementation on prostate cancer risk or on certain risk markers such as prostate-specific antigen (PSA) plasma concentration or oxidative alterations of leucocyte DNA. - All showed increases of plasma and prostate lycopene levels after diet supplementation with lycopene and inverse correlations between tumor incidence and risk biomarkers. 

Experimental evidence in humans is based upon intervention studies with diets enriched in carotenoids or carotenoid-contaiifing foods. Oxidative stress biomarkers are measured in plasma or urine. The inhibition of low density lipoprotein (LDL) oxidation has been posmlated as one mechanism by which antioxidants may prevent the development of atherosclerosis. Since carotenoids are transported mainly via LDL in blood, testing the susceptibility of carotenoid-loaded LDL to oxidation is a common method of evaluating the antioxidant activities of carotenoids in vivo. This type of smdy is more precisely of the ex vivo type because LDLs are extracted from plasma in order to be tested in vitro for oxidative sensitivity after the subjects are given a special diet. 

Nielsen JB, Andersen O, Grandjean P. 1994. Evaluation of mercury in hair, blood and muscle as biomarkers for methylmercury exposure in male and female mice. Arch Toxicol 68 317-321. 

Because hexachlorobenzene can interfere with porphyrin metabolism and produce chemical porphyria, the evaluation of the urinary porphyrin pattern has been proposed as an early biomarker of effect (San Martin et al., 1977 Schmid, I960, 1966 Wray et al., 1962). However, apart from an outbreak of chemical porphyria which occurred in Turkey in the 1950s following ingestion of hexachlorobenzene-contaminated food, cases of chemical porphyria among... 

There is a growing need to better characterize the health risk related to occupational and environmental exposure to pesticides. Risk characterization is a basic step in the assessment and management of the health risks related to chemicals (Tordoir and Maroni, 1994). Evaluation of exposure, which may be performed through environmental and biological monitoring, is a fundamental component of risk assessment. Biomarkers are useful tools that may be used in risk assessment to confirm exposure or to quantify it by estimating the internal dose. Besides their use in risk assessment, biomarkers also represent a fundamental tool to improve the effectiveness of medical and epidemiological surveillance. 

Laughlin NK University of Wisconsin, Madison, Wl Evaluate blood and soft tissue in adult and geriatric monkeys previously exposed to lead to compare these biomarkers with behavioral endpoints National Center For Research Resources... 

Simmonds PL, Luckhurst CL, Woods JS. 1995. Quantitative evaluation of heme biosynthetic pathway parameters as biomarkers of low-level lead exposure in rats. J Toxicol Environ Health 44 351-367. 

Many diseases are characterized by the expression of specific proteins1 in some cases, malignant cells yield unique protein profiles when total cellular protein extracts are analyzed by proteomic methods such as two-dimensional gel electrophoresis or matrix-assisted laser desorption ionization-mass spectrometry (MALDI-MS).2 High-throughput proteomic studies may be useful to differentiate normal cells from cancer cells, to identify and define the use of biomarkers for specific cancers, and to characterize the clinical course of disease. Proteomics can also be used to isolate and characterize potential drug targets and to evaluate the efficacy of treatments. 

Effects produced by exposure to acrylonitrile, particularly after acute exposures, are characteristic of cyanide toxicity. These effects can be detected in people exposed by evaluating signs and symptoms such as limb weakness, labored and irregular breathing, dizziness and impaired judgement, cyanosis and convulsions. While tests are not specific for acrylonitrile-induced toxicity, they do identify potential health impairment. Studies to develop more specific biomarkers of acrylonitrile-induced effects would be useful in assessing the potential health risk of acrylonitrile near hazardous waste sites. 

C.M. Leys, S. Nomura, E. Montogomery, and J.R. Goldenring, Tissue microarray evaluation of prothymosin as a biomarker for human gastric metaplasia and neoplasia. J. Surg. Res. 121, 327-328 (2004). 

Apart from of investigating the concentration of priority pollutants to assess the temporal and geographic trends as it has been done in the Ebro river basin until nowadays, the SCARCE project pretends to evaluate the consequences of the climate change in the water quality as well as predicting new environmental risks derived from water scarcity. This will be done by determining the presence of new priority (i.e. perfluorinated compounds) and emerging toxicants in Mediterranean river ecosystems in the Iberian Peninsula. In a subsequent step, the effects of chemical and environmental stressors on the biota will be assessed by combining field and experimental studies. The effects of multiple stressors will be addressed from a multi-biomarker perspective [27]. 

Faria M, Huertas D, SotoDX, Grimalt JO, Catalan J, Riva MC, Barata C (2010) Contaminant accumulation and multi-biomarker responses in field collected zebra mussels (Dreissena polymorpha) and crayfish (Procambarus clarkii), to evaluate toxicological effects of industrial hazardous dumps in the Ebro river (NE Spain). Chemosphere 78(3) 232-240... 

Lecoeur S, Videmann B, Bemy P (2004) Evaluation of metallothionein as a biomarker of single and combined Cd/Cu exposure in Dreissena polymorpha. Environ Res 94(2) 184—191... 

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