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BACKGROUND/AIMS To relate severity of intoxication with allyl alcohol and acetaminophen to modulated hepatic gene expression of liver functions and regeneration. METHODS Rats fasted for 12 h received acetaminophen 3.5 or 5.6 g per kg body weight, or allyl alcohol 100 or 125 microl by gastric tube, doses producing no and about 30% mortality, respectively,(More)
PURPOSE Fluourouracil (FU) is a mainstay of chemotherapy, although toxicities are common. Genetic biomarkers have been used to predict these adverse events, but their utility is uncertain. PATIENTS AND METHODS We tested candidate polymorphisms identified from a systematic literature search for associations with capecitabine toxicity in 927 patients with(More)
Cytotoxic effect of 5-fluorouracil 5-FU is mediated through inhibition of thymidylate synthase (TS), and 5-FU is catabolised by dihydropyrimidine dehydrogenase (DPD). Efficacy of 5-FU may therefore depend on the TS and DPD activity of colorectal cancer. Archival tumour specimens from 303 consecutive patients were analysed for the expression of TS and DPD(More)
AIM To elucidate cellular features accountable for colorectal cancers' (CRC) capability to invade normal tissue and to metastasize, we investigated the level of the collagenase matrix metalloproteinase 9 (MMP-9) and its physiological inhibitor tissue inhibitor of metalloproteinases 1 (TIMP-1) in cancer cells and supporting stroma cells of CRC. METHODS(More)
Microsatellite instability (MSI) refers to mutations in short motifs of tandemly repeated nucleotides resulting from replication errors and deficient mismatch repair (MMR). Colorectal cancer with MSI has characteristic biology and chemosensitivity, however the molecular basis remains unclarified. The association of MSI and MMR status with outcome and with(More)
PURPOSE Fluorouracil (FU) is a cornerstone of colorectal cancer treatment; however, it has clinical and subclinical influence on the heart. This study aimed to clarify the pathophysiology, risk factors, and long-term effects of FU cardiotoxicity. PATIENTS AND METHODS The study prospectively accrued colorectal cancer patients (n=106) completely resected(More)
BACKGROUND AND AIMS N-acetylcysteine is used to treat paracetamol overdose but depresses the activity of plasma coagulation factors II, VII, and X, which are often used to assess liver injury. The aim of this study was to investigate the effect of N-acetylcysteine on haemostasis in normal volunteers. METHODS Haemostatic parameters in 10 healthy subjects(More)
BACKGROUND Methylenetetrahydrofolate reductase is a pivotal enzyme in folate metabolism and 5-fluorouracil (5-FU) cytotoxicity. Two common single-nucleotide polymorphisms (SNPs), MTHFR 677C>T (rs1801133) and 1298A>C (rs1801131), reduce enzyme activity. Initially, these SNPs were claimed to predict clinical efficacy, but further studies have yielded(More)
This study aimed to compare efficacy and toxicity of palliative chemotherapy for elderly and younger colorectal cancer patients. Patients aged 24-69 (n = 203) and 70-82 years (n = 57) with advanced colorectal cancer were consequetively treated with first line capecitabine monotherapy or combined with oxaliplatin (XELOX). The response rates were 37% and 33%(More)
BACKGROUND Most human cancer cells have structural aberrations of chromosomal regions leading to loss or gain of gene specific alleles. This study aimed to assess the range of gene copies per nucleus of thymidylate synthase (TYMS), thymidine phosphorylase (TP) and dihydrofolate reductase (DHFR) in colorectal cancer, and to evaluate its prognostic(More)