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BACKGROUND The prognosis of breast cancer in very young women is generally considered to be unfavourable. Therefore, the outcome of adjuvant therapy was analysed in a population of young (<35 years) premenopausal patients treated in four randomised controlled trials. METHODS Between 1978 and 1993 the International Breast Cancer Study Group (IBCSG) treated(More)
AIMS The importance of polymorphisms in the dihydropyrimidine dehydrogenase gene (DPYD) for the prediction of severe toxicity in 5-fluorouracil (5-FU)-based chemotherapy is still unclear. This study aims to assess the predictive value of DPYD variation with respect to previously described DPYD variants for 5-FU toxicity. It represents the first analysis of(More)
Loss of DNA mismatch repair (MMR) has been observed in a variety of human cancers. In addition to predisposing to oncogenesis, loss of MMR activity is of concern with respect to the use of chemotherapeutic agents to treat established tumors. Loss of MMR results in drug resistance directly by impairing the ability of the cell to detect DNA damage and(More)
Loss of DNA mismatch repair occurs in many types of tumors. The effect of the loss of DNA mismatch repair activity on sensitivity to cisplatin and a panel of analogues was tested using two pairs of cell lines proficient or deficient in this function. HCT116+ch2, a human colon cancer cell line deficient in hMLH1, was 2.1-fold resistant to cisplatin and(More)
In vitro studies have shown that loss of DNA mismatch repair due to lack of either hMSH2 or hMLH1 activity results in low-level resistance to cisplatin but not to oxaliplatin, an analogue that produces a different type of DNA adduct. No information is currently available on whether this low-level resistance is sufficient to result in enrichment of mismatch(More)
In addition to recognizing and repairing mismatched bases in DNA, the mismatch repair (MMR) system also detects cisplatin DNA adducts and loss of MMR results in resistance to cisplatin. A comparison was made of the ability of MMR-proficient and -deficient cells to remove cisplatin adducts from their genome and to reactivate a transiently transfected plasmid(More)
Selection of cells for resistance to cisplatin, a well-recognized mutagen, could result in mutations in genes involved in DNA mismatch repair and thereby to resistance to DNA-alkylating agents. Parental cells of the human ovarian adenocarcinoma cell line 2008 expressed hMLH1 when analyzed with immunoblot. One subline selected for resistance to cisplatin(More)
PURPOSE The value of adjuvant tamoxifen after chemotherapy for premenopausal women with breast cancer has not been adequately assessed. PATIENTS AND METHODS Between 1993 and 1999, International Breast Cancer Study Group Trial 13-93 enrolled 1,246 assessable premenopausal women with axillary node-positive, operable breast cancer. All patients received(More)
PURPOSE To compare patients treated in or outside clinical protocols, using de novo acute myeloid leukemia (AML) as a model disorder. PATIENTS AND METHODS We retrospectively compared the characteristics of all patients with de novo AML diagnosed in the referral area of our university hospital between 1985 and 1994. RESULTS Of a total of 170 AML(More)
We investigated the clinical relevance of dihydropyrimidine dehydrogenase gene (DPYD) variants to predict severe early-onset fluoropyrimidine (FP) toxicity, in particular of a recently discovered haplotype hapB3 and a linked deep intronic splice site mutation c.1129-5923C>G. Selected regions of DPYD were sequenced in prospectively collected germline DNA of(More)