Relationship between thymidylate synthase and p53 and response to FEC versus taxane adjuvant chemotherapy for breast carcinoma.

Many drugs can be used for adjuvant therapy of breast cancer, including anthracyclines, cyclophosphamide, 5-fluorouracil (5-fU) and, recently, taxanes (TXT) have shown promising results. 5-FU blocks thymidylate synthase (TS) which cross-links p53 mRNA, inhibiting its synthesis. TS overexpression is one of the main mechanisms involved in 5-FU drug resistance.

Analysis of the thymidylate synthase gene structure in colorectal cancer patients and its possible relation with the 5-Fluorouracil drug response.

Thymidylate synthase (TS) catalyzes methylation of dUMP to dTMP and it is the target for the 5-Fluorouracil (5-FU) activity. Barbour et al. showed that variant structural forms of TS in tumour cell lines confer resistance to fluoropyrimidines.

Differing expression of metalloprotease and of adhesion molecules in signet-ring cell and intestinal colorectal carcinoma.

Background: Pure signet-ring cell colorectal carcinoma (SRCC) is an infrequent and highly malignant histological variant of colorectal cancer (CRC), while it is present as a histological component in colorectal carcinomas more frequently.

Materials And Methods: The aim of this work was to widen the knowledge of the biological factors involved in the pathogenesis and aggressiveness of SRCC by the identification and evaluation of possible molecular abnormalities. By means of immunohistochemistry the expression of the proteolytic degradation enzyme matrix metalloprotease (MMP)-1, that is a collagenase specifically degrading collagens I, II, III and of the adhesion proteins E-cadherin, beta-catenin and fibronectin which are usually involved in the carcinogenesis of conventional colorectal tumours was investigated.

The effect of CYP3A5 and ABCB1 single nucleotide polymorphisms on tacrolimus dose requirements in Caucasian liver transplant patients.

Background: Tacrolimus is a substrate of cytochrome P-450 (CYP) 3A enzyme and of the drug transporter ABCB1. We have investigated the effects of possible relevant CYP3A5 and ABCB1 single nucleotide polymorphisms (SNPs) present in both donors and recipients on tacrolimus blood levels achieved in a population of 32 Caucasian liver transplant patients.

Material/methods: At 1, 3 and 6 months after transplantation, tacrolimus doses (mg/kg/day) and trough blood levels (C(0)) were determined.

Different expression of thymidylate synthase in primary tumour and metastatic nodes in breast cancer patients.

Background: To date an accurate evaluation of predictive markers in breast cancer is mainly conducted at the primary site, although the main goal of the adjuvant therapy is the control of micrometastases. Adjuvant therapy drugs need a high proliferative cell rate to be effective. The proliferating activity can be evaluated by the Ki-67 marker and even by thymidylate synthase (TS), a cell cycle enzyme present in proliferating cells.