Tumor markers proteins

Bergman AC, Benjamin T, Alaiya A, Waltham M, Sakaguchi K, Franzen B, et al. Identification of gel-separated tumor marker proteins by mass spectrometry. Electrophoresis 2000 21(3) 679-686. 

Other members of the chymotrypsin family include a collection of proteins that take part in blood clotting, to be discussed in Chapter 10, as well as the tumor marker protein prostate specific antigen (PSA). In addition, a wide range of proteases found in bacteria, viruses, and plants belong to this clan. 

To date, 16 GST isozymes have been found in humans [48]. Studies of several cancer tissues have revealed the overexpression of different GST isozymes, with GST Pl-1 (GST Pi, GST ji) being the most predominant. For this reason, GST Pl-1 is regarded as a potential tumor marker [5,49-53]. The high expression levels of GST Pl-1 (up to 2.7% of the total cytosolic protein [52]), combined with its detoxification role against xenobiotics, make GST Pl-1 a major player responsible for drug resistance in patients undergoing anticancer chemotherapy [49]. 

Sometimes it is not possible to measure the direct effect of the drug. Endpoints or surrogate biomarkers are used to monitor the pharmacodynamics and pharmacokinetics of the drug. These markers may be changes in blood pressure, cholesterol level, concentrations of certain enzymes, proteins, blood glucose levels, and similar factors (see Table 6.2 for serum tumor markers and Appendix 7 for general biomarkers). 

Tumor markers are clinically important for detecting certain tumors. These are proteins that are formed with increasing frequency by... 

As yet, a phenomenon has not been observed in CSF. Orosomucoid in CSF can be considered to be a reliable tumor marker. Assessment of CSF orosomucoid levels has become a routine method in CSF laboratories and has become a mandatory parameter of the CSF protein status. 

The ability of a tumor cell to manufacture proteins is a result of intact DNA, RNA and biochemical intracellular mechanisms. Interference with any one of these structures or processes will result in the inability of the cell to produce required proteins. Hence, quantitation of tumor cell protein synthesis over a period of time may constitute a marker allowing determination of the efficacy of a macromolecular drug conjugate. The technique is based on the fact that decreased cell viability in the presence of radiolabeled amino adds correlates to a decrease in radioactivity relative to a control cell population. For example, 3H-leucine [175, 208], a mixture of [14C]-labeled amino acids [205], and 75Se-lenomethionine [54, 209] have been used to evaluate the activity of conjugates. 

DNA Microarrays for Transcription Profiling Tumor Tissue Microarray and Proteomic Profiling Of Protein Kinases Molecular Profiling for Cancer Therapeutics New Guidelines For Reporting Tumor Marker Studies Conclusions References... 

This plasma cell malignancy is one of the models of neoplastic disease in humans because it arises from a single tumor stem cell, and the tumor cells produce a marker protein (myeloma immunoglobulin) that allows the total body burden of tumor cells to be quantified. Multiple myeloma principally involves the bone marrow and the surrounding bone, causing bone pain, lytic lesions, bone fractures, and anemia as well as an increased susceptibility to infection. 

Because 2D-PAGE and MS patterns can be used to differentiate between healthy and cancer patients, the proteins in these spectra contain tumor markers. If they could be isolated and identified, they would be useful for innumerable purposes, most notably for early detection. If a tumor marker can warn of the presence of disease at an early stage, before the cancer can be visualized using imaging studies, this would increase the chances of treating at a curative stage. 

Many tumor markers have been identified in recent years since the improvements in proteomic technologies. For example, one study analyzed human serum with 2D-PAGE and MALDI-TOF-MS to identify a distinct repertoire of autoantibodies associated with hepatocellular carcinoma. These proteins differentiated the cancer patients from those chronically infected with hepatitis B or C, which constitute a high-risk group for developing hepatocellular carcinoma. Thus, proteomic-based technology was used to identify a set of four proteins that may have utility in early diagnosis of hepatocellular carcinoma [87]. 

Tumor Markers and Disease-Associated Proteins Conventional IPCR and... 

Tumor markers and disease associated proteins (see also Chapter 3.1) ... 

Similar to tumor markers discussed above, a number of hazardous proteins are not immediately linked to an accompanying nucleic acid and therefore are prime targets for IPCR. These are interesting examples of how the clinical importance of IPCR is not limited to the diagnosis of diseases. IPCR was reported as a useful tool for the prevention of intoxications or infections because of highly sensitive detection of potentially dangerous compounds, especially in food analysis. 

Up to the present time, various techniques of nonisotopic immunoassay have been developed. Substances to be measured by these techniques include hormones (peptide and nonpeptide), biologically active trace substances, carrier proteins, immunoglobulins, viruses, tumor markers, antibodies against microorganisms (viruses, bacteria, and parasites), autoantibodies, etc. Innumerable papers concerning nonisotopic immunoassay have been published, and enzyme (15, Kl, N5, N6, PI, S2, V4, W9) and fluores-... 

Wiesner, A. Detection of tumor markers with Protein-Chip(R) technology. Curr. Pharm. Biotechnol. 2004, 5 (1), 45-67. 

Fig. 1. Pertussis toxin-mediated ADP ribosylation of membrane G proteins. Isolated cell membranes (50 ng of protein) from N1E 115 cells (mouse neuroblastoma cell line), N2A cells (mouse neuroblastoma cell line), S49-1 eye cells (S49(-) mutated mouse lymphoma cell line deficient in Ga ), 549 wt cells (wild-type mouse lymphoma cell line), RBL (RBL 2H3 rat basophilic leukemia cell line), GH3 cells (GH3 rat hypophyseal tumor cell line), PC-12 (rat pheochromocytoma cell line), HIT-T15 cells (hamster insulinoma cell line), Y-1 cells (mouse adrenal cortex tumor cell line), 108 cc 15 cells (mouse/rat neuroblastoma x glioma hybrid cell line), HL-60 cells (DMSO-differentiated human leukemia cell line), HL-60 (+PT) cells (HL-60 cells pretreated with 25 ng/ml of pertussis toxin for 24 h prior to preparation of membranes), RINm5F cells (rat insulinoma cell line), and C6-2 cells (rat glioma cell line) were subjected to P-ADP-ribosylation as described in section 4.3.3. Samples were precipitated as outlined in section 4.3.5 and subjected to SDS-PAGE with separating gels containing 8% acrylamide (w/v). An autoradiogram of the dried gel is shown. Molecular masses of marker proteins are indicated (kDa). Modified Ga proteins migrate at approximately 40 kDa. Radioactivity running in front of the 30 kDa marker protein comigrates with the dye front...

The first tumor marker reported was the Bence Jones protein. Since its discovery in 1847 by precipitation of a protein in acidified boiled urine, the measurement of Bence Jones protein has been a diagnostic test for multiple myeloma (a tumor of plasma cells). More than 100 years after its discovery, the Nobel Prize-winning studies of Porter... 

Tumor markers are measured by a variety of analytical techniques including enzyme assay (Chapters 8 and 21) immunoassay (Chapter 9) receptor assay and instrumental techniques such as chromatography (Chapter 6) electrophoresis (Chapter 5) mass spectrometry interfaced with either liquid or gas chromatographs (Chapter 7) and microarrays. Details of these techniques are found in the indicated chapters. Here we expand on the use of mass spectrometry and microarrays for the assay of protein and genetic tumor markers. 

Enzymes were one of the first groups of tumor markers identified. Their elevated activities were used to indicate the presence of cancer. Measurement of enzymes was relatively easy using spectrophotometric determination of enzymatic activities. With the introduction of radioimmunoassay (RIA) in the late 1950s, the mass of an enzyme could be measured as a protein antigen instead of its catalytic activity. 

Several proteins having tumor marker potential are listed in Table 23-12. Included in this group of tumor markers are proteins that are not enzymes, hormones, or high in carbohydrate content. Additional research is required to assess the clinical usefulness of most of these markers. 

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