Serum tests for colorectal cancer screening.

Colorectal cancer (CRC) persists as one of the most significant causes of cancer death worldwide. Recent progress in reducing cancer mortality can largely be attributed to the implementation of screening programs. However, screening programs have not realized their full potential for the reduction of CRC mortality, because of poor adherence rates among patients. Serum biomarker screening tests offer the potential for improved patient adherence to CRC screening programs. In this review, we assess the literature regarding serum biomarkers for use as CRC screening tests for colorectal cancer and adenomas. A systematic review was performed of Medline-indexed articles pertaining to serum biomarkers for CRC screening published within the past 4 years. In addition, we searched non-Medline sources for information pertaining to screening guidelines and practice patterns for CRC. We identified 51 articles from Medline pertaining to serum biomarkers as screening tests for CRC. Non-Medline sources yielded an additional 12 articles, for a total of 63 publications reviewed. We conclude that serum tests that involve simple blood draws during routine check-ups hold significant promise for improving patient acceptance and adherence to CRC screening.

Biological variation of total prostate-specific antigen: a survey of published estimates and consequences for clinical practice.

BACKGROUND: The objectives of this study were to determine whether a single result for total prostate-specific antigen (tPSA) can be used confidently to guide the need for prostate biopsy and by how much serial tPSA measurements must differ to be significant. tPSA measurements include both analytical and biological components of variation. The European Group on Tumor Markers conducted a literature survey to determine both the magnitude and impact of biological variation on single, the mean of replicate, and serial tPSA measurements. METHODS: The survey yielded 27 studies addressing the topic, and estimates for the biological variation of tPSA could be derived from 12 of these studies. RESULTS: The mean biological variation was 20% in the concentration range 0.1-20 microg/L for men over 50 years. The biological variation means that the one-sided 95% confidence interval (CI) of the dispersion for a single tPSA result is approximately 33%. Three replicate samples with one analysis on each narrow the one-sided 95% CI for the mean concentration to approximately 20% and facilitate decisions on prostate biopsy. During monitoring of serial measurements, the change needed for significance is approximately 50% (P <0.05). CONCLUSIONS: The biological variation of tPSA has implications for screening, diagnosis, and monitoring. Single measurements may not be sufficiently precise for screening and diagnosis. Replicate samples and calculation of the mean concentration may improve precision by reducing the dispersion. Monitoring of tPSA requires an estimate of either the change needed for significance or, alternatively, of the significance of the change.

The oxygenase component of the 2-aminobenzenesulfonate dioxygenase system from Alcaligenes sp. strain O-1.

Growth of Alcaligenes sp. strain O-1 with 2-aminobenzenesulfonate (ABS; orthanilate) as sole source of carbon and energy requires expression of the soluble, multicomponent 2-aminobenzenesulfonate 2,3-dioxygenase system (deaminating) (ABSDOS) which is plasmid-encoded. ABSDOS was separated by anion-exchange chromatography to yield a flavin-dependent reductase component and an iron-dependent oxygenase component. The oxygenase component was purified to about 98% homogeneity and an alpha2beta2 subunit structure was deduced from the molecular masses of 134,45 and 16 kDa for the native complex, and the alpha and beta subunits, respectively. Analysis of the amount of acid labile sulfur and total iron, and the UV spectrum of the purified oxygenase component indicated one [2Fe-2S] Rieske centre per alpha subunit. The inhibition of activity by the iron-specific chelator o-phenanthroline indicated the presence of an additional iron-binding site. Recovery of active protein required strictly anoxic conditions during all purification steps. The FAD-containing reductase could not be purified. ABSDOS oxygenated nine sulfonated compounds; no oxygen uptake was detected with carboxylated aromatic compounds or with aliphatic sulfonated compounds. Km values of 29, 18 and 108 microM and Vmax values of 140, 110 and 72 pkat for ABS, benzenesulfonate and 4-toluenesulfonate, respectively, were observed. The N-terminal amino acid sequences of the alpha- and beta-subunits of the oxygenase component allowed PCR primers to be deduced and the DNA sequence of the alpha-subunit was thereafter determined. Both redox centres were detected in the deduced amino acid sequence. Sequence data and biochemical properties of the enzyme system indicate a novel member of the class IB ring-hydroxylating dioxygenases.