The Experts below are selected from a list of 72 Experts worldwide ranked by ideXlab platform
E G E De Vries - One of the best experts on this subject based on the ideXlab platform.
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Genetic factors influencing Pyrimidine-Antagonist chemotherapy
The Pharmacogenomics Journal, 2005Co-Authors: J G Maring, H J M Groen, F M Wachters, D R A Uges, E G E De VriesAbstract:Pyrimidine Antagonists, for example, 5-fluorouracil (5-FU), cytarabine (ara-C) and gemcitabine (dFdC), are widely used in chemotherapy regimes for colorectal, breast, head and neck, non-small-cell lung cancer, pancreatic cancer and leukaemias. Extensive metabolism is a prerequisite for conversion of these Pyrimidine prodrugs into active compounds. Interindividual variation in the activity of metabolising enzymes can affect the extent of prodrug activation and, as a result, act on the efficacy of chemotherapy treatment. Genetic factors at least partly explain interindividual variation in antitumour efficacy and toxicity of Pyrimidine Antagonists. In this review, proteins relevant for the efficacy and toxicity of Pyrimidine Antagonists will be summarised. In addition, the role of germline polymorphisms, tumour-specific somatic mutations and protein expression levels in the metabolic pathways and clinical pharmacology of these drugs are described. Germline polymorphisms of uridine monophosphate kinase (UMPK), orotate phosphoribosyl transferase (OPRT), thymidylate synthase (TS), dihydroPyrimidine dehydrogenase (DPD) and methylene tetrahydrofolate reductase (MTHFR) and gene expression levels of OPRT, UMPK, TS, DPD, uridine phosphorylase, uridine kinase, thymidine phosphorylase, thymidine kinase, deoxyuridine triphosphate nucleotide hydrolase are discussed in relation to 5-FU efficacy. Cytidine deaminase (CDD) and 5′-nucleotidase (5NT) gene polymorphisms and CDD, 5NT, deoxycytidine kinase and MRP5 gene expression levels and their potential relation to dFdC and ara-C cytotoxicity are reviewed.
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Genetic factors influencing Pyrimidine-Antagonist chemotherapy
The Pharmacogenomics Journal, 2005Co-Authors: J G Maring, H J M Groen, F M Wachters, D R A Uges, E G E De VriesAbstract:Pyrimidine Antagonists, for example, 5-fluorouracil (5-FU), cytarabine (ara-C) and gemcitabine (dFdC), are widely used in chemotherapy regimes for colorectal, breast, head and neck, non-small-cell lung cancer, pancreatic cancer and leukaemias. Extensive metabolism is a prerequisite for conversion of these Pyrimidine prodrugs into active compounds. Interindividual variation in the activity of metabolising enzymes can affect the extent of prodrug activation and, as a result, act on the efficacy of chemotherapy treatment. Genetic factors at least partly explain interindividual variation in antitumour efficacy and toxicity of Pyrimidine Antagonists. In this review, proteins relevant for the efficacy and toxicity of Pyrimidine Antagonists will be summarised. In addition, the role of germline polymorphisms, tumour-specific somatic mutations and protein expression levels in the metabolic pathways and clinical pharmacology of these drugs are described. Germline polymorphisms of uridine monophosphate kinase (UMPK), orotate phosphoribosyl transferase (OPRT), thymidylate synthase (TS), dihydroPyrimidine dehydrogenase (DPD) and methylene tetrahydrofolate reductase (MTHFR) and gene expression levels of OPRT, UMPK, TS, DPD, uridine phosphorylase, uridine kinase, thymidine phosphorylase, thymidine kinase, deoxyuridine triphosphate nucleotide hydrolase are discussed in relation to 5-FU efficacy. Cytidine deaminase (CDD) and 5′-nucleotidase (5NT) gene polymorphisms and CDD, 5NT, deoxycytidine kinase and MRP5 gene expression levels and their potential relation to dFdC and ara-C cytotoxicity are reviewed.
Murat Cihan - One of the best experts on this subject based on the ideXlab platform.
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Determination of 5-fluorouracil and dihydrofluorouracil levels by using a liquid chromatography–tandem mass spectrometry method for evaluation of dihydroPyrimidine dehydrogenase enzyme activity
Cancer Chemotherapy and Pharmacology, 2011Co-Authors: Muhittin A. Serdar, Erdim Sertoglu, Metin Uyanik, Serkan Tapan, Okhan Akin, Murat CihanAbstract:Purpose 5-Fluorouracil (5-FU), acting as a Pyrimidine Antagonist, is a major chemotherapy drug used for the treatment of tumors such as gastrointestinal, breast, ovary, and head and neck cancers. The key and rate-limiting enzyme in 5-FU catabolism is dihydroPyrimidine dehydrogenase (DHPDH), whose partial or complete deficiency exposes to a severe 5-FU toxicity in patients. The determination of DHPDH activity in patients before the treatment and setting up a personalized therapy for each patient receiving the drug can help us to prevent the possible risk of toxicity. Methods To isolate peripheral blood mononuclear cells (PBMCs), EDTA-anticoagulated blood samples were collected from randomly selected 47 patients and examined for 5-FU and its metabolite dihydrofluorouracil (FUH2) by using a liquid chromatography–tandem mass spectrometry (LC–MS/MS) to observe DHPDH activity at different intervals (0 and 4th hour) indirectly. Results Intra-assay and interassay CV % values of samples from the measurements of the modified methods are found 1.3–11.9, 2.3–9.4 for 5-FU and 3.1–14.4, 3.3–12.6 for FUH2, respectively. The reference values derived from 45 patients treated with 5-FU are 1.84 ± 0.34 ug/gr protein for 5-FU, 40.15 ± 11.43 ng/gr protein for FUH2, respectively. FUH2/5-FU ratio is 21.9 ± 3.72. In addition, the results determined from two patients, in which the lack of DHPDH is considered, were 3.24 and 4.16 ug/gr protein for 5-FU, 4.1 and 6.7 ng/gr protein for FUH2. FUH2/5-FU ratio is 1.26 and 1.61. Conclusion The measurements of 5-FU, FUH2, and especially their ratio (FUH2/5-FU) by the modified LC–MS/MS method could be used to determine DHPDH enzyme activity.
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Determination of 5-fluorouracil and dihydrofluorouracil levels by using a liquid chromatography-tandem mass spectrometry method for evaluation of dihydroPyrimidine dehydrogenase enzyme activity.
Cancer chemotherapy and pharmacology, 2010Co-Authors: Muhittin Serdar, Erdim Sertoglu, Metin Uyanik, Serkan Tapan, Okhan Akin, Murat CihanAbstract:Purpose 5-Fluorouracil (5-FU), acting as a Pyrimidine Antagonist, is a major chemotherapy drug used for the treatment of tumors such as gastrointestinal, breast, ovary, and head and neck cancers. The key and rate-limiting enzyme in 5-FU catabolism is dihydroPyrimidine dehydrogenase (DHPDH), whose partial or complete deficiency exposes to a severe 5-FU toxicity in patients. The determination of DHPDH activity in patients before the treatment and setting up a personalized therapy for each patient receiving the drug can help us to prevent the possible risk of toxicity.
J G Maring - One of the best experts on this subject based on the ideXlab platform.
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Genetic factors influencing Pyrimidine-Antagonist chemotherapy
The Pharmacogenomics Journal, 2005Co-Authors: J G Maring, H J M Groen, F M Wachters, D R A Uges, E G E De VriesAbstract:Pyrimidine Antagonists, for example, 5-fluorouracil (5-FU), cytarabine (ara-C) and gemcitabine (dFdC), are widely used in chemotherapy regimes for colorectal, breast, head and neck, non-small-cell lung cancer, pancreatic cancer and leukaemias. Extensive metabolism is a prerequisite for conversion of these Pyrimidine prodrugs into active compounds. Interindividual variation in the activity of metabolising enzymes can affect the extent of prodrug activation and, as a result, act on the efficacy of chemotherapy treatment. Genetic factors at least partly explain interindividual variation in antitumour efficacy and toxicity of Pyrimidine Antagonists. In this review, proteins relevant for the efficacy and toxicity of Pyrimidine Antagonists will be summarised. In addition, the role of germline polymorphisms, tumour-specific somatic mutations and protein expression levels in the metabolic pathways and clinical pharmacology of these drugs are described. Germline polymorphisms of uridine monophosphate kinase (UMPK), orotate phosphoribosyl transferase (OPRT), thymidylate synthase (TS), dihydroPyrimidine dehydrogenase (DPD) and methylene tetrahydrofolate reductase (MTHFR) and gene expression levels of OPRT, UMPK, TS, DPD, uridine phosphorylase, uridine kinase, thymidine phosphorylase, thymidine kinase, deoxyuridine triphosphate nucleotide hydrolase are discussed in relation to 5-FU efficacy. Cytidine deaminase (CDD) and 5′-nucleotidase (5NT) gene polymorphisms and CDD, 5NT, deoxycytidine kinase and MRP5 gene expression levels and their potential relation to dFdC and ara-C cytotoxicity are reviewed.
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Genetic factors influencing Pyrimidine-Antagonist chemotherapy
The Pharmacogenomics Journal, 2005Co-Authors: J G Maring, H J M Groen, F M Wachters, D R A Uges, E G E De VriesAbstract:Pyrimidine Antagonists, for example, 5-fluorouracil (5-FU), cytarabine (ara-C) and gemcitabine (dFdC), are widely used in chemotherapy regimes for colorectal, breast, head and neck, non-small-cell lung cancer, pancreatic cancer and leukaemias. Extensive metabolism is a prerequisite for conversion of these Pyrimidine prodrugs into active compounds. Interindividual variation in the activity of metabolising enzymes can affect the extent of prodrug activation and, as a result, act on the efficacy of chemotherapy treatment. Genetic factors at least partly explain interindividual variation in antitumour efficacy and toxicity of Pyrimidine Antagonists. In this review, proteins relevant for the efficacy and toxicity of Pyrimidine Antagonists will be summarised. In addition, the role of germline polymorphisms, tumour-specific somatic mutations and protein expression levels in the metabolic pathways and clinical pharmacology of these drugs are described. Germline polymorphisms of uridine monophosphate kinase (UMPK), orotate phosphoribosyl transferase (OPRT), thymidylate synthase (TS), dihydroPyrimidine dehydrogenase (DPD) and methylene tetrahydrofolate reductase (MTHFR) and gene expression levels of OPRT, UMPK, TS, DPD, uridine phosphorylase, uridine kinase, thymidine phosphorylase, thymidine kinase, deoxyuridine triphosphate nucleotide hydrolase are discussed in relation to 5-FU efficacy. Cytidine deaminase (CDD) and 5′-nucleotidase (5NT) gene polymorphisms and CDD, 5NT, deoxycytidine kinase and MRP5 gene expression levels and their potential relation to dFdC and ara-C cytotoxicity are reviewed.
H J M Groen - One of the best experts on this subject based on the ideXlab platform.
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Genetic factors influencing Pyrimidine-Antagonist chemotherapy
The Pharmacogenomics Journal, 2005Co-Authors: J G Maring, H J M Groen, F M Wachters, D R A Uges, E G E De VriesAbstract:Pyrimidine Antagonists, for example, 5-fluorouracil (5-FU), cytarabine (ara-C) and gemcitabine (dFdC), are widely used in chemotherapy regimes for colorectal, breast, head and neck, non-small-cell lung cancer, pancreatic cancer and leukaemias. Extensive metabolism is a prerequisite for conversion of these Pyrimidine prodrugs into active compounds. Interindividual variation in the activity of metabolising enzymes can affect the extent of prodrug activation and, as a result, act on the efficacy of chemotherapy treatment. Genetic factors at least partly explain interindividual variation in antitumour efficacy and toxicity of Pyrimidine Antagonists. In this review, proteins relevant for the efficacy and toxicity of Pyrimidine Antagonists will be summarised. In addition, the role of germline polymorphisms, tumour-specific somatic mutations and protein expression levels in the metabolic pathways and clinical pharmacology of these drugs are described. Germline polymorphisms of uridine monophosphate kinase (UMPK), orotate phosphoribosyl transferase (OPRT), thymidylate synthase (TS), dihydroPyrimidine dehydrogenase (DPD) and methylene tetrahydrofolate reductase (MTHFR) and gene expression levels of OPRT, UMPK, TS, DPD, uridine phosphorylase, uridine kinase, thymidine phosphorylase, thymidine kinase, deoxyuridine triphosphate nucleotide hydrolase are discussed in relation to 5-FU efficacy. Cytidine deaminase (CDD) and 5′-nucleotidase (5NT) gene polymorphisms and CDD, 5NT, deoxycytidine kinase and MRP5 gene expression levels and their potential relation to dFdC and ara-C cytotoxicity are reviewed.
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Genetic factors influencing Pyrimidine-Antagonist chemotherapy
The Pharmacogenomics Journal, 2005Co-Authors: J G Maring, H J M Groen, F M Wachters, D R A Uges, E G E De VriesAbstract:Pyrimidine Antagonists, for example, 5-fluorouracil (5-FU), cytarabine (ara-C) and gemcitabine (dFdC), are widely used in chemotherapy regimes for colorectal, breast, head and neck, non-small-cell lung cancer, pancreatic cancer and leukaemias. Extensive metabolism is a prerequisite for conversion of these Pyrimidine prodrugs into active compounds. Interindividual variation in the activity of metabolising enzymes can affect the extent of prodrug activation and, as a result, act on the efficacy of chemotherapy treatment. Genetic factors at least partly explain interindividual variation in antitumour efficacy and toxicity of Pyrimidine Antagonists. In this review, proteins relevant for the efficacy and toxicity of Pyrimidine Antagonists will be summarised. In addition, the role of germline polymorphisms, tumour-specific somatic mutations and protein expression levels in the metabolic pathways and clinical pharmacology of these drugs are described. Germline polymorphisms of uridine monophosphate kinase (UMPK), orotate phosphoribosyl transferase (OPRT), thymidylate synthase (TS), dihydroPyrimidine dehydrogenase (DPD) and methylene tetrahydrofolate reductase (MTHFR) and gene expression levels of OPRT, UMPK, TS, DPD, uridine phosphorylase, uridine kinase, thymidine phosphorylase, thymidine kinase, deoxyuridine triphosphate nucleotide hydrolase are discussed in relation to 5-FU efficacy. Cytidine deaminase (CDD) and 5′-nucleotidase (5NT) gene polymorphisms and CDD, 5NT, deoxycytidine kinase and MRP5 gene expression levels and their potential relation to dFdC and ara-C cytotoxicity are reviewed.
F M Wachters - One of the best experts on this subject based on the ideXlab platform.
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Genetic factors influencing Pyrimidine-Antagonist chemotherapy
The Pharmacogenomics Journal, 2005Co-Authors: J G Maring, H J M Groen, F M Wachters, D R A Uges, E G E De VriesAbstract:Pyrimidine Antagonists, for example, 5-fluorouracil (5-FU), cytarabine (ara-C) and gemcitabine (dFdC), are widely used in chemotherapy regimes for colorectal, breast, head and neck, non-small-cell lung cancer, pancreatic cancer and leukaemias. Extensive metabolism is a prerequisite for conversion of these Pyrimidine prodrugs into active compounds. Interindividual variation in the activity of metabolising enzymes can affect the extent of prodrug activation and, as a result, act on the efficacy of chemotherapy treatment. Genetic factors at least partly explain interindividual variation in antitumour efficacy and toxicity of Pyrimidine Antagonists. In this review, proteins relevant for the efficacy and toxicity of Pyrimidine Antagonists will be summarised. In addition, the role of germline polymorphisms, tumour-specific somatic mutations and protein expression levels in the metabolic pathways and clinical pharmacology of these drugs are described. Germline polymorphisms of uridine monophosphate kinase (UMPK), orotate phosphoribosyl transferase (OPRT), thymidylate synthase (TS), dihydroPyrimidine dehydrogenase (DPD) and methylene tetrahydrofolate reductase (MTHFR) and gene expression levels of OPRT, UMPK, TS, DPD, uridine phosphorylase, uridine kinase, thymidine phosphorylase, thymidine kinase, deoxyuridine triphosphate nucleotide hydrolase are discussed in relation to 5-FU efficacy. Cytidine deaminase (CDD) and 5′-nucleotidase (5NT) gene polymorphisms and CDD, 5NT, deoxycytidine kinase and MRP5 gene expression levels and their potential relation to dFdC and ara-C cytotoxicity are reviewed.
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Genetic factors influencing Pyrimidine-Antagonist chemotherapy
The Pharmacogenomics Journal, 2005Co-Authors: J G Maring, H J M Groen, F M Wachters, D R A Uges, E G E De VriesAbstract:Pyrimidine Antagonists, for example, 5-fluorouracil (5-FU), cytarabine (ara-C) and gemcitabine (dFdC), are widely used in chemotherapy regimes for colorectal, breast, head and neck, non-small-cell lung cancer, pancreatic cancer and leukaemias. Extensive metabolism is a prerequisite for conversion of these Pyrimidine prodrugs into active compounds. Interindividual variation in the activity of metabolising enzymes can affect the extent of prodrug activation and, as a result, act on the efficacy of chemotherapy treatment. Genetic factors at least partly explain interindividual variation in antitumour efficacy and toxicity of Pyrimidine Antagonists. In this review, proteins relevant for the efficacy and toxicity of Pyrimidine Antagonists will be summarised. In addition, the role of germline polymorphisms, tumour-specific somatic mutations and protein expression levels in the metabolic pathways and clinical pharmacology of these drugs are described. Germline polymorphisms of uridine monophosphate kinase (UMPK), orotate phosphoribosyl transferase (OPRT), thymidylate synthase (TS), dihydroPyrimidine dehydrogenase (DPD) and methylene tetrahydrofolate reductase (MTHFR) and gene expression levels of OPRT, UMPK, TS, DPD, uridine phosphorylase, uridine kinase, thymidine phosphorylase, thymidine kinase, deoxyuridine triphosphate nucleotide hydrolase are discussed in relation to 5-FU efficacy. Cytidine deaminase (CDD) and 5′-nucleotidase (5NT) gene polymorphisms and CDD, 5NT, deoxycytidine kinase and MRP5 gene expression levels and their potential relation to dFdC and ara-C cytotoxicity are reviewed.
