Proteomic analysis for early detection of ovarian cancer: a realistic approach?

Ovarian cancer is a multifaceted disease wherein most women are diagnosed with advanced stage disease. One of the most imperative issues in ovarian cancer is early detection. Biomarkers that allow cancer detection at stage I, a time when the disease is amenable to surgical and chemotherapeutic cure in over 90% of patients, can dramatically alter the horizon for women with this disease. Recent developments in mass spectroscopy and protein chip technology coupled with bioinformatics have been applied to biomarker discovery. The complexity of the proteome is a rich resource from which the patterns can be gleaned; the pattern rather than its component parts is the diagnostic. Serum is a key source of putative protein biomarkers, and, by its nature, can reflect organ-confined events. Pioneering use of mass spectroscopy coupled with bioinformatics has been demonstrated as being capable of distinguishing serum protein pattern signatures of ovarian cancer in patients with early- and late-stage disease. This is a sensitive, precise, and promising tool for which further validation is needed to confirm that ovarian cancer serum protein signature patterns can be a robust biomarker approach for ovarian cancer diagnosis, yielding improved patient outcome and reducing the death and suffering from ovarian cancer.

Stimulation of rat liver glycerol-3-phosphate acyltransferase activity by acid- and heat-stable low-molecular-weight substances from skeletal muscle of rats treated with insulin.

Experiments were conducted to examine a possible mechanism of activation of rat liver microsomal glycerol-3-phosphate acyltransferase (GPAT) by insulin. Fractions of Mr 1100 were prepared from hind-limb muscles of rats, which had been given intravenous injections of insulin or saline, by a procedure which involved acidification (pH 3.8) and heating (100 degrees C), followed by chromatography on Sephadex G-25 in 50 mM formic acid. These fractions were shown to modify the activity of microsomal GPAT from the livers of fed rats which had not been treated with insulin. The difference in GPAT activity between microsomes supplemented with the Mr 1100 material and those treated with an equal volume of 50 mM formic acid from before the void volume of the column was determined. Relative to the formic acid control, the Mr 1100 material from saline-treated rats decreased GPAT activity, whereas Mr 1100 material from insulin-treated rats increased GPAT activity and the difference of 0.64 nmol/min/mg microsomal protein was significant (P less than 0.01). Fractions of approximately 3000 Da were found to behave in a similar manner and caused a significant (P less than 0.01) increase in GPAT activity of 0.46 nmol/min/mg microsomal protein. These substances, which stimulate GPAT activity, may be related to the putative insulin mediator substance.

Insulin-dependent production of low-molecular-weight compounds that modify key enzymes in metabolism.

The mechanism by which the metabolic effects of insulin are transmitted is yet to be resolved. Second messengers mediating the action of insulin have been proposed and recently an insulin-dependent, peptide-like, heat- and acid-stable substance (Mr approx. 1000-3000) released from plasma membranes has been described which regulates the activity of key enzymes such as pyruvate dehydrogenase by altering its state of phosphorylation. It has been suggested that this material is the elusive second messenger of insulin and its discovery, generation, properties, isolation and mode of action are reviewed.