Disease-specific biomarkers

Ulrich H, Wrenger C (2009) Disease-specific biomarker discovery by aptamers. Cytometry A... 

Microarrays have become robust, reliable research tools that enable researchers to screen for a multitude of parameters using minimal amounts of sample material. The acceptance of protein microarrays is growing constantly they have already been demonstrated to be useful tools in disease-related biomarker discovery. In addition, protein microarrays have been introduced into clinical trials in order to investigate the potential adverse effects of drug candidates. Depending on the number of validated disease-specific biomarkers, as well as on their therapeutic relevance, such assays are performed either on a protein microarray or a bead-based platform. 

There is no clinical disease state that is pathognomonic for lead exposure. The neurotoxic effects and hematopoietic effects of lead are well recognized. The primary biomarkers of effect for lead are EP, ALAD, basophilic stippling and premature erythrocyte hemolysis, and presence of intranuclear lead inclusion bodies in the kidneys. Of these, activity of ALAD is a sensitive indicator of lead exposure (Hemberg et al. 1970 Morris et al. 1988 Somashekaraiah et al. 1990 Tola et al. 1973), but the assay can not distinguish between moderate and severe exposure (Graziano 1994). Sensitive, reliable, well-established methods exist to monitor for these biomarkers however, they are not specific for lead exposure. Therefore, there is a need to develop more specific biomarkers of effect for lead. Recent data... 

We all realize that we need better disease-specific endpoints in very many diseases. There are tremendous opportunities to use imaging and certain biomarkers, if only they could be relied upon. Patient-centered outcome measures are also extremely important in most chronic and symptomatic diseases yet, they are not used as extensively as they need to be. Agreement on acceptable composite endpoints is needed in many diseases. 

The protein profiling approach also provides the use of pattern recognition for discrimination of disease states. Biomarkers for prostate cancer were profiled and a panel assembled that could differentiate cancer patients from noncancer populations (see Fung et al., 2001, Reference 11). Poon et al. (2003) utilized the ProteinChip to obtain tumor-specific proteomic signatures to detect hepatocellular carcinoma (HCC) in patients having chronic liver disease (CLD). 

Biomarkers of Disease. No biomarkers are known that are specific for BCME-induced lung injury. Standard chemical examination of nose and throat can provide an index of local irritation, and examination of sputum for abnormal cell types can provide information on the state of the respiratory epithelium. However, these tests cannot distinguish BCME-induced effects from effects caused by smoking or exposure to other chemicals, and can only discover changes after damage to the tissue has already occurred. Continued efforts to devise more sensitive and more specific early biomarkers of disease (especially lung cancer) would be valuable. 

Molecular risk biomarkers could detect systemic or local changes indicating that the carrier of this specific biomarker is at higher risk for disease development in the future. Examples include the presence of human papillomavirus in the cervix, which is associated with a higher risk for the development of cervical cancer, the association between Hdicohacterpylori and gastric cancer as well as EBV and nasopharyngeal carcinoma. The drawback of these markers is that they are not helpful for the detection of early disease. 

The focus of proteomics has turned to identifying potential biomarkers of disease. A biomarker, by definition, is (a) a molecular indicator for a specific biological property or (b) a feature or facet that can be used to measure the progress of disease or the effects of treatment. As an example, a biomarker... 

In this schema, biomarkers are considered to fall in the three general designations. These include biomarkers of exposures, biomarkers of effect, and biomarkers of susceptibility. Each of these types of biomarkers has specific and relevant applicahons to the understanding of renal injury and disease. Specific and sensitive bi-... 

Data collection is a crucial step to ensure the success of any trial. Phase 1 is not disease specific. Major endpoints must be precisely defined. They are mainly maximum tolerated dose of the treatment and/or mechanism-based biomarkers in the case of targeted therapy. Data collection is focused on measurement and categorization of toxicities. Usually, the data collected includes, but is not limited to ... 

Fig. 8.8 The Host Response Protein Amplification Cascade (HR-PAC). According to this new theory, disease-specific enzymes act as generators of specifically modified marker proteins which can serve as valuable biomarkers by signaling a disease in a...

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