A partir de la evidencia clinica y molecular se ha propuesto a la enzima DPYD junto con la enzima TS, como las principales determinantes de la farmacocinetica, la toxicidad clinica y la resistencia frente al 5-FU, por lo que gran parte de la investigacion farmacogenomica del 5-FU se han enfocado al estudio de las variantes polimorficas en los genes de estas dos enzimas (19, 20).
La enzima DPYD presenta una considerable variacion entre la poblacion (Tabla II).
The Pearson's correlation coefficients of marbling and two gene's expression levels are highly correlated and also statistically significant by regression analysis (TMEM60: r = 0.72, P-value = 0.013, DPYD: r = 0.85, and P-value = 0.001).
The mRNA expression levels of PPAR[gamma] and CEBP[alpha] were more highly expressed in the high-marbled group (P [less than or equal to] 0.01), In the present study, we identified two genes, TMEM60 and DPYD, which were approximately 2.1 and 3.2 times higher in the high-marbled group and also upregulated with intramuscular fat content increases (P < 0.05) (Table 3 and Figure 3(b)).
For this purpose, blood samples were obtained from 28 cancer patients suffering from severe 5FU-associated toxicity and 1 pediatric patient with a verified mutation in DPYD
. In the radiochemical assay, the activity of DPD was determined in a reaction mixture containing 35 mmol/L potassium phosphate (pH 7.4), 2.5 mmol/L Mg[Cl.sub.2], 1 mmol/L dithiothreitol, 250 [micro]mol/L NADPH, and 25 [micro]mol/L [14C]thymine (7).
, dihydropyrimidine dehydrogenase; KRAS, v-Ki-ras2 Kirsten rat sarcoma viral oncogene homolog.
To better predict toxicity in patients receiving 5-FU, the first step is to find a reliable detection method to identify SNPs in the DPYD gene.
This study describes the use of pyrosequencing to assay four previously described SNPs in the DPYD gene: DPYD*2A, DPYD*5, DPYD*6, and DPYD*9A.
Increased attention is required for detection of the exon 14-skipping mutation of the DPYD
gene in routine diagnostics because of at least one existing nearby polymorphism.
Using the Hardy-Weinberg equilibrium, the frequency of heterozygotes allows the estimation of up to 1 in 1000 homozygotes for DPYD
In the present study involving patients with bone metastases arising from various malignancies, we measured serum bone-specific alkaline phosphatase [with either electrophoretic (BALP) or immunoradiometric (IBALP) assays (23,24)], serum carboxy-terminal telopeptide of type I collagen (ICTP) (25), and urinary deoxypyridinoline (DPYD) (26) as markers of osteoblastic and collagen breakdown activities, respectively.
Urinary DPYD was measured in hydrolyzed urine samples with HPLC, using commercial kits (Metra Biosystem) and expressed as the molar ratio to creatinine.