title: Thymidylate synthase level and DNA-ploidy pattern as possible prognostic factors in human colorectal cancer: a preliminary study.
abstract: 5-Fluorouracil is the drug chosen for the treatment of patients with advanced colorectal carcinoma; its major site of action is thymidylate synthase (TS), resulting in pronounced and prolonged inhibition of DNA synthesis. The aim of this study was to evaluate the possibility of considering TS level in human colorectal carcinomas of previously untreated patients (pts) as a prognostic factor. Our data demonstrate that there is no association with age, sex, tumor site and tumor size; however, there is a relationship between TS levels and staging: in fact, the TS values are higher (P < 0.05) in Dukes-A tumors than in the others. A significant association was also found between the TS levels and survival parameters: in fact, pts with longer disease-free and overall survivals had a significantly increased TS level compared to pts with a poorer outcome (P < 0.05). Moreover, pts with DNA-aneuploid tumors had lower TS level (median = 0.044 pmol/mg protein) than diploid pts who had higher TS level (median = 0.093 pmol/mg protein); however the difference is not significant. Our result are based on preliminary data; however, they seem to support the hypothesis that a high TS level is a favourable prognostic factor in human colorectal carcinoma.
authors.affiliation: Instituto di Farmacologia, Policlinico, Palermo, Italy.
authors.forename: R
authors.initials: R
authors.lastname: Sanguedolce
authors.forename: I
authors.initials: I
authors.lastname: Brumarescu
authors.forename: G
authors.initials: G
authors.lastname: Dardanoni
authors.forename: A
authors.initials: A
authors.lastname: Grassadonia
authors.forename: G
authors.initials: G
authors.lastname: Vultaggio
authors.forename: L
authors.initials: L
authors.lastname: Rausa
mesh_terms: D000230:Adenocarcinoma / Q000378:metabolism / Q000401:mortality / Q000473:pathology* / Q000601:surgery; D000367:Age Factors; D000368:Aged; D000782:Aneuploidy; D015179:Colorectal Neoplasms / Q000378:metabolism / Q000401:mortality / Q000473:pathology* / Q000601:surgery; D004273:DNA, Neoplasm / Q000032:analysis* / Q000235:genetics; D004171:Diploidy; D018572:Disease-Free Survival; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D009367:Neoplasm Staging; D011003:Ploidies; D011237:Predictive Value of Tests; D011379:Prognosis; D012727:Sex Characteristics; D015996:Survival Rate; D013940:Thymidylate Synthase / Q000032:analysis* / Q000378:metabolism
chemical_list: D004273:DNA, Neoplasm; D013940:Thymidylate Synthase