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CZE Protein Isoform Diagnostics
Presented at 18th International Symposium on MicroScale Bioseparations (MSB) (formerly HPCE)--CaSSS Meeting, February 12-17, 2005, New Orleans, LA
Abstract
Wiliam W.P. Chang, David C. Bomberger, Luke V. Schneider
Protein isoforms are frequently very similar in primary sequence, but contain subtle folding differences (such as albumins), or have post-translational modifications (e.g., glycosylation or phosphorylation). Changes in the expression level of specific isoforms can have significant clinical impact, such as:
Clinical Diagnostics:
- A single prostate specific antigen isoform improves prostate cancer diagnosis over the traditional free/total PSA ratio. Loss of transferrin glycoforms is diagnostic for chronic alcoholism.
- The relative abundance of alpha1-antitrypsin isoforms is diagnostic for carbohydrate-deficient glycoprotein syndrome.
Disease Staging:
- CD44 isoform 3 is 100% diagnostic for breast cancer metastasis but not total CD44 levels.
Drug Resistance & Efficacy:
- P-Glycoprotein isoforms are associated with multi-drug resistance in bladder cancer cells.
- Efficacy of antimitotic chemotherapy agents is associated with tubulin isoforms.
Drug Toxicity:
- Isoforms of cytochrome P-450 are associated with patient-specific drug toxicity.
Yet, isoforms can be impossible to separate in traditional clinical immunoassays. By coupling isoform separation on a CE platform with offline immunoaffinity capture and elution methods, we show that an affinity-CZE isoform analysis platform, suitable for clinical work, is feasible and may be cost-competitive with traditional immunoassays.
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