Whole genome expression analysis for biologic rational pathway modeling: application in cancer prognosis and therapy prediction.

Using semi-quantitative microarray technology, almost every one of the approximately 30 000 human genes can be analyzed simultaneously with a low rate of false-positives, a high specificity, and a high quantification accuracy. This is supported by data from comparative studies of microarrays and reverse-transcription PCR for established cancer genes including those for epidermal growth factor receptor (EGFR), human epidermal growth factor receptor-2 (HER2/ERBB2), estrogen receptor (ESR1), progesterone receptor (PGR), urokinase-type plasminogen activator (PLAU), and plasminogen activator inhibitor-1 (SERPINE1). As such, semi-quantitative expression data provide an almost completely comprehensive background of biological knowledge that can be applied to cancer diagnostics. In clinical terms, expression profiling may be able to provide significant information regarding (i) the identification of high-risk patients requiring aggressive chemotherapy; (ii) the pathway control of therapy predictive parameters (e.g. ESR1 and HER2); (iii) the discovery of targets for biologically rational therapeutics (e.g. capecitabine and trastuzumab); (iv) additional support for decisions about switching therapy; (v) target discovery; and (vi) the prediction of the course of new therapies in clinical trials. In conclusion, whole genome expression analysis might be able to determine important genes related to cancer progression and adjuvant chemotherapy resistance, especially in the context of new approaches involving primary systemic chemotherapy. In this review, we will survey the current progress in whole genome expression analyses for cancer prognosis and prediction. Special emphasis is given to the approach of combining biostatistical analysis of expression data with knowledge of biochemical and genetic pathways.

Volumetric and histochemical studies of the adrenal medulla of mouse after reserpine administration.

The effect of single and consecutive doses of reserpine on the morphology and cellular and nuclear sizes of adrenaline and noradrenaline cells in the adrenals of mice were compared with the normal controls receiving saline injections as a placebo. Adopting micrometric measurements for apparent cellular and nuclear diameters, the pooled mean volumes of adrenaline- and noradrenaline-secreting cells and nuclei were calculated. Normal controls, subjected to consecutive daily saline injections for a period of 2 weeks, presented an increase in the intensity of the chromaffin reaction and higher values of cellular and nuclear sized of both cell types than those receiving single saline injection. These findings are believed to be a result of increased cell activity due to the stress of repeated, regular daily handling and injections. The increased measurements of cellular and nuclear sized of both types of adrenomedullary cells are believed to be due to hypermetabolic activity of the cells, thus exceeding action of reserpine shown by the decreased intensity of chromaffin reaction. Mice receiving daily consecutive reserpine injections showed a decrease in the intensity of chromaffin reaction as well as cellular and nuclear sizes compared with their controls. This is attributed to a decrease in the catecholamine content of the adrenal medulla.

Volumetric studies on the red nucleus of the rat at different ages.

The postnatal development of the red nucleus in albino rat was quantitatively studied. Planimetric studies on stained paraffin sections of the midbrain showed that the red nucleus has a rounded contour with tapering ends and a broad centre. The volume of the red nucleus revealed an increase from birth, to reach its maximum at the age of 3 months, then declines until the age of 2 years. However, the size does not regain its newly born value. On the other hand, the number of cells remains constant during the entire life span of the animal.