Congrats! An enzyme kinetic method as a tumor marker would be a very valuable tool in cancer biology. But I have no Idea about this.

Hai Mohamed, my be you can start with this book and review...(iam senf to you email acc)...but no email acc in you'r profile sir"

An assay for thymidylate synthetase might not only be useful as a tumor marker but also as a differential diagnostic tool and predictor of clinical outcome.

See Foekens et al Cancer Res 2001 ;61: 1421-5.

2 Enzymes that are over-expressed in cancer : Cathepsin B

and MMP-2 + MMP-9

also PSA in prostate

they are all proteases

An assay for thymidilate synthetase (the enzyme that makes thymidine from uracil and is blocked by 5FU) will detect cells that are in cell cycle (unless they have a large pool of thymidine available endogenously or exogenously -- look at old literature on best conditions for labeling cells with tritiated thymidine); it will not be specific for cancer cells.

I agree with Dr Lange but we also know that TYMS is not only a useful indicator of mitotic cell division at least in the case of breast cancer as enzymatic activity in fine needle aspirates ranges from undetectable to 60 fold above background, so what I meant by my earlier post was that in addition to being a useful predictive marker for 5-FU resistance TYMS dysregulation may also be causally related to other histopathological phenotypes..

I agree wth Dr. Barclay that elevated TYMS may be a useful endpoint, but I would caution that it is an indicator that one should examine what is happening. TYMS is an indirect measure of proliferation and it could be due to cancer, inflamation, wound healing, etc. The problem with most biochemical assays is one of specificity. They can tell when something is different, but not always what caused it. Even elevated PSA can be due to non-cancer causes (e.g., prostatic hypertrophy), although if found, prostate cancer should always be checked as as possible cause.

Absolutely agree but I think TYMS is a special case. It has multiple functions, not only manufacturing dTMP but also acting as a metabolic switch and oncoprotein. Aberrant TYMS expression may not only be an indicator of an inflammatory response or initiation of a wound healing cascade but actually cause their initiation. For example low TYMS causes dTTP pool imbalance and elevated rates of uracil incorporation into DNA. In the absence of T DNA-U is not repaired properly leading to genomic instability. Chromosome fragments thus generated could cause local inflammation and a wound healing response. Thus in this view TYMS dysregulation is more a cause than an indicator.

Hi Dr Wibi Riawan, My email is [email protected] Thanxs