Tumor markers enzymes

Cocoa powder exerted anticancer properties in in vivo studies. Amin et al. [50] indicated that cocoa liquor extract lowered the activity of tumor marker enzymes (alkaline phosphatase, gamma-glutamyl transpeptidase, glutathione-S-transferase, and glutathione reductase activities) in plasma and/or liver of hepatocarcinogenic male Sprague-Dawley rats, which were induced with diethylnitrosamine and 2-acetylaminofluorene. 

Dictyodendrin alkaloids have been described as the first telomerase inhibitors of marine origin and hence represent potential lead compounds in the quest for small molecule inhibitors of the tumor-marker enzyme. In a 2009 study, Fiirstner et al. [58] reported the synthesis of several members of the series, making use of FI—HMBC data. 

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). 

For non-SI traceable quantities the strategy for introducing traceability has to be different. This concerns a large number of analytes for which no defined molecular structure can be assigned, such as for many enzymes, proteo-homones, tumor markers and cardiac markers. The first and most important step must be the definition of the quantity before it is possible to establish reference systems (reference procedures, materials and reference network laboratories). Whenever possible, a global consensus on the definition of the measurand should be achieved. Consequently, definition of the measurand and establishment of reference systems is the objective of several working groups and committees of the Scientific Division of IFCC. 

In contrast to enzyme activities, the definition of the proteo-hormone measurands as well as of many tumor markers and cardiac markers is very critical and several aspects have to be regarded as it concerns the epitope to be detected, the sub-unit to be measured (/3-chain or complete molecule) and finally the glycosidic structure of the molecule. 

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-... 

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. 

With few exceptions, an increase in the activity or mass of an enzyme or isoenzyme is not specific or sensitive enough to be used for identifying the type of cancer or the specific organ involvement. An exception is PSA. PSA has mild protease activity and amino acid sequence homology with serine protease of the kallikrein family.It is expressed by normal, benign, hyperplastic, and cancerous prostate glands and minimally by other tissue. Until the application of PSA as a marker for prostate cancer, tumor enzymes had lost most of their popularity for use as cancer markers. Enzymes were used historically as tumor markers before the discovery of oncofetal antigens and the advent of monoclonal antibodies. The abnormalities of enzymes as a marker for cancer are either the expression of the fetal form of the enzyme (isozyme) or the ectopic production of enzymes. 

Carbohydrate-related tumor markers either are (1) antigens on the tumor cell surface or (2) secreted by the tumor cells. Monoclonal antibodies have been developed against these antigens. These markers have been found to be clinically useful as tumor markers and tend to be more specific than naturally secreted markers, such as enzymes and hormones. Biochemically, they are high molecular weight mucins (Table 23-10) or blood group antigens (Table 23-11). 

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. 

The present review will focus on the analysis of l-DOPA and L-tyrosine by HPLC in plasma. Both are involved in the first step of melanogenesis controlled by a melanocyte-specific enzyme, tyrosinase. The plasma L-DOPA/L-tyrosine ratio has been evaluated as a tumor marker in melanoma during a 10-year collaboration between the Biochemistry Laboratory, the Dermatology Department of Saint-Louis Hospital (AP-HP) in Paris (France) and the Dermatology Department of the National Center of Oncology in Sofia (Bulgaria). 

Nishizono I, lida S, Suzuki N, Kawada H, Murakami H. eds. Rapid and sensitive chemiluminescent enzyme immunoassay for measuring tumor markers. Clin Chem 1991 37 1639-44. 

Histaminase (diamine oxidase) has been used as a marker for some NE cells and their tumors. This enzyme is present in high concentrations in medullary thyroid carcinomas and has been reported in small cell carcinomas of the lung and other NE neoplasms. High serum levels of histaminase also occur in pregnancy, and immunohistochemical studies have revealed the presence of this enzyme in decidual cells. 

The placental fraction of alkaline phosphatase is a membrane-bound enzyme of 120 kD, normally synthesized by placental syncytiotrophoblasts and released into maternal circulation after the 12th week of pregnancy. However, it is also produced by many neoplasms and is a useful tumor marker. Physiologically, this enzyme is involved in cellular transport, proliferation and cellular differentiation, and regulation of metabolism and gene transcription. 

Whereas the GST were studied originally because of their involvement in mercapturic acid biosynthesis, these enzymes are also currently of interest to researchers working in fields other than toxicology. Some of the research areas in which GST are of importance include tumor markers, inherited cancer susceptibility, drug resistance, biotechnology, and clinical biochemistry. 

The pi-class enzyme is not the only GST that can serve as a tumor marker. A... 

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