Fig. 1 The metabolic pathway of DPD action. (View this art in color at www.dekker.com.)

which are associated with reduced enzyme activity and increased risk of toxicity, were identified.1-5'6-1 For instance, a mutation for DPYD*9A was identified in patients suffering from toxic 5-FU side effects. However, DPYD mutations do not always result in reduced enzyme activity (biochemical phenotype). There are patients who have inherited DPD deficiency and are at high risk for 5-FU toxicity, but many others inherit variant alleles without clear association between genotype and 5-FU toxicity. However, van Kuilenburg and coworkers1-6-1 described the correlation of the rather frequent (1.8% heterozygotes in the normal population) mutation (IVS14+ 1G<A) of the DPYD, which might also be associated with 5-FU toxicity. They even described the lethal outcome of 5-FU treatment in a patient who was homozygous for this mutation. So far, various DPYD allelic variants are known. In some cases, these genetic variants correlate with altered DPD activity; in other cases, this connection remains to be further elucidated. However, some of the DPD gene mutations such as DPYD*2A and DPYD*9A are considered to be of clinical relevance. This renders DPYD as a potential candidate for pharmacogenetic profiling prior to chemotherapy with 5-FU, and thus adverse drug effects might be avoided. To be considered beneficial for all patients, a closer correlation between genotype and phenotype needs to be established, and then all relevant genetic alterations, i.e., single nucleotide polymorphisms (SNPs) have to be tested prior to therapy. This could lead to the de-

velopment of personalized therapy for every patient with maximum effect and minimum toxicity.

Getting Started With Dumbbells

Getting Started With Dumbbells

The use of dumbbells gives you a much more comprehensive strengthening effect because the workout engages your stabilizer muscles, in addition to the muscle you may be pin-pointing. Without all of the belts and artificial stabilizers of a machine, you also engage your core muscles, which are your body's natural stabilizers.

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