Markers clinical applications

Miller, P.D., et al., "Practical Clinical Application of Biochemical Markers of Bone Turnover," /. Clin. Densitometry 2, 323-342 (1999). 

It is the goal of array-based prognostics to utilize a panel of markers that are more accurately able to stratify patients into prognostic groupings. There are several examples in the literature of biomarker panels identified by microarray analysis that may have some relation to prognostic outcome (4, 77, 78, 79,80). However, the issue remains that many of these biomarker panels do not afford sufficient specificity or sensitivity to warrant clinical application. Microarrays offer the potential to profile tumors at a finer level of detail than what can be obtained by the pathologist however, it is the reliance on classification from traditional pathology that has confounded many studies. 

The body of published clinical EMP reports remains relatively small and varies widely in scope, mainly because the clinical application of the assay of EMPs is still in its early stages. In all disorders studied, the presence of EC perturbation or dysfunction has been implicated by the presence of soluble markers of EC injury. The reports reviewed herein strongly indicate that EMPs are good indicators of EC status in vivo. To simplify the presentation of results, reports have been organized into broader categories based on the clinical presentation of the disease studied. Clinical reports as they pertain to EMPs published to this date have been summarized in Table 2. 

However, for clinical applications, nucleic acids are only a fraction of a broad and very inhomogeneous range of possible analytes, starting with large proteins like antibodies and also including small molecule hormones and markers for various diseases. 

Starting with the first IPCR study, gel electrophoresis retains its potential as a fast and easy method for end-point determination of DNA amplificate for IPCR assays [10, 24, 25, 29, 31, 35, 36, 38, 39, 64], Readout is performed by intercalation fluorescence markers (e.g., ethidium bromide) and photometric/densitometric quantification of band signal intensities. The direct addition of a double-strand specific intercalation marker to the PCR amplificate and subsequent measurement of fluorescence in microwells proved to be of insufficient sensitivity for the quantification of IPCR amplificate [37]. Alternative approaches, such as radioactive labeling during PCR and subsequent imaging [33], were carried out but are not well suited for routine clinical application because of additional methodological requirements. An advantage of gel electrophoresis is the possibility of simultaneous amplificate detection for multiplex IPCR [41] and the ability to detect nonspecific amplification products. 

Wl. Wachter, H., Fuchs, D., Hausen, A., Reibegger, G., and Werner, E., Neopterin as marker for activation of cellular immunity Immunologic basis and clinical application. Adv. Clin. Chem. 27, 81-141 (1989). 

Bates SE, Clinical application of serum tumor markers, Ann. Intern. Med., 115 623-638, 1991. 

The assays most widely employed are the measurement of thiobarbituric acid-reactive species (TBARS) and the formation of conjugated dienes, markers of lipid peroxidation [31-33] the determination of advanced oxidation protein products (AOPP), a marker of protein oxidation, and of advanced glycation end-products (AGE) [34-37] the measurement of erythrocyte antioxidant potential [38]. Of particular importance is the isoprostanes determination, since these compounds are formed by the free radical catalysed peroxidation of arachidonic acid, which is independent of the cyclooxygenase enzyme, giving rise to stable compounds, measurable in urine [39]. As recently assessed in a Workshop on markers of oxidative damage and antioxidant protection [40], currently available methods for the determination of antioxidant and redox status are not yet generally suitable for routine clinical applications, essentially for the lack of standardized tests. 

Modified from Diamandis EP. Tumor markers Past, present, and future. In Diamandis EP, Fritsche HA, Lilja H, Chan DW, Schwartz MK. Tumor markers Physiology, pathobiology, technology, and clinical application. Washington DC AACC Press, 2002 5. 

Calvo MS, Eyre DR, Gundberg CM. Molecular basis and clinical application of biological markers of bone turnover. Endocr. Rev, 1996 17 333-68. 

Miller PD, Baran DT, Bilezhdan JP, Greenspan SL, Lindsay R, Riggs BL, et al Practical clinical application of biochemical markers of bone turnover consensus of an expert panel. J Clin Densitom 1999 2 323-42. 

The use of human-derived stable differentiated cultures of target organs will be extremely useful for the discovery and development of new translational biomarkers. Omic technologies such as transcriptomics, proteomics, and metabolomics have proven to be excellent tools for understanding drug-induced perturbations, especially when used in combination with appropriate cell culture models [13, 122], The further understanding of how cells differentiate and maintain tissue-specific functions will also be crucial for the discovery of new biomarkers [123]. Importantly, the development of new mechanistically informative biomarkers is not just useful for clinical applications, but these markers will also be useful to drive the development of better, more predictive, human-based in vitro test systems to improve on the predictive power of whole-animal experiments in preclinical testing scenarios. 

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