Expresión de ARNm de hTERT en orina como herramienta diagnóstica útil en cáncer de vejiga. Comparación con citología y NMP22 BladderCheck Test(R) / hTERT mRNA expression in urine as a useful diagnostic tool in bladder cancer. Comparison with cytology and NMP22 BladderCheck Test(R)

Introducción: El objetivo fue estudiar la relación entre la determinación cuantitativa de ARNm (hTERT) en pacientes con tumor vesical, antecedentes de tumor vesical y en sujetos sin antecedentes de esta neoplasia. Material y métodos: Se trata de un estudio prospectivo, aleatorizado y controlado con 91 sujetos incluidos. El valor de ARNm-hTERTN se determinó en 63 pacientes con antecedentes o sospecha de tumor vesical y en 28 controles. Se enviaron muestras de orina para evaluar el nivel de ARNm (hTERT), el estudio citológico y el resultado de NMP22. Resultados: Se observaron diferencias en los niveles medios de hTERTN en cada uno de los grupos: presencia de tumor 21,33 + /- 40,66, antecedente del tumor 2,16 +/ - 2,67, controles 0,9+/- 1, 75 (p < 0,001). En pacientes con tumor, no hubo diferencias en los niveles medios de hTERTN entre los diferentes grados y estadios, aunque hubo una tendencia: tumor de bajo grado 9,04 +/- 16,95, grado alto 28,95+/- 48,36 (p = 0,069), estadio Ta 10,33 +/- 19,39, T1 17,88 +/- 27,14, T2 54,8 +/- 74,05 (p = 0,056). Además, la sensibilidad de hTERTN fue superior a la de otras pruebas (76%), aunque la especificidad y los valores predictivos positivos y negativos fueron mejores para la citología (94%, 88,4% y 72,3% respectivamente) y NMP22 (88%, 80,6% y 73,3% respectivamente). Conclusiones: Los niveles de mRNA de hTERTN en la orina fueron más altos en pacientes con tumores vesicales en comparación con pacientes con antecedentes de tumor de vejiga y con cistoscopia negativa, así como en el grupo de control. Esta determinación mostró un mayor rendimiento diagnóstico en comparación con la detección de NMP22 y citología urinaria

Introduction: To study the relationship between quantitative mRNA determination (hTERT) in patients with bladder tumor, history of bladder tumor, and in subjects without a history of this neoplasia. Material and methods: A prospective randomized controlled study with 91 subjects included. The value of mRNA-hTERTN was determined in 63 patients with a history or suspicion of bladder tumor and in 28 controls. Urine samples were sent for evaluation of the mRNA level (hTERT), the cytological study and the NMP22 result. Results: Differences were observed in mean hTERTN levels in each of the groups: tumor presence 21.33+/- 40.66, tumor history 2.16 +/- 2.67, controls 0.9 +/- 1, 75 (p < 0.001). In patients with tumor, there was no difference in mean hTERTN levels between the different grades and stages, although there was a tendency: low grade tumor 9.04 +/- 16.95, high grade 28.95 +/- 48.36 (p = .069), stage Ta 10.33+/- 19.39, T1 17.88 +/- 27.14, T2 54.8 +/- 74.05 (p = .056). In addition, the sensitivity of hTERTN was superior to that of other test (76%), although specificity and positive and negative predictive values were better for cytology (94%, 88.4% and 72.3% respectively) and NMP22 (88%, 80.6% and 73.3% respectively). Conclusions: hTERTN mRNA levels in urine were higher in patients with bladder tumors compared to patients with a history of bladder tumor and with negative cystoscopy, as well as in the control group. This determination showed a higher diagnostic yield compared with the detection of NMP22 and urinary cytology

hTERT mRNA expression in urine as a useful diagnostic tool in bladder cancer. Comparison with cytology and NMP22 BladderCheck Test®. / Expresión de ARNm de hTERT en orina como herramienta diagnóstica útil en cáncer de vejiga. Comparación con citología y NMP22 BladderCheck Test®.

INTRODUCTION: To study the relationship between quantitative mRNA determination (hTERT) in patients with bladder tumor, history of bladder tumor, and in subjects without a history of this neoplasia. MATERIAL AND METHODS: A prospective randomized controlled study with 91 subjects included. The value of mRNA-hTERTN was determined in 63 patients with a history or suspicion of bladder tumor and in 28 controls. Urine samples were sent for evaluation of the mRNA level (hTERT), the cytological study and the NMP22 result. RESULTS: Differences were observed in mean hTERTN levels in each of the groups: tumor presence 21.33+/- 40.66, tumor history 2.16+/- 2.67, controls 0.9+/- 1, 75 (p<0.001). In patients with tumor, there was no difference in mean hTERTN levels between the different grades and stages, although there was a tendency: low grade tumor 9.04+/- 16.95, high grade 28.95+/- 48.36 (p=.069), stage Ta 10.33+/- 19.39, T1 17.88+/- 27.14, T2 54.8+/- 74.05 (p=.056). In addition, the sensitivity of hTERTN was superior to that of other test (76%), although specificity and positive and negative predictive values were better for cytology (94%, 88.4% and 72.3% respectively) and NMP22 (88%, 80.6% and 73.3% respectively). CONCLUSIONS: hTERTN mRNA levels in urine were higher in patients with bladder tumors compared to patients with a history of bladder tumor and with negative cystoscopy, as well as in the control group. This determination showed a higher diagnostic yield compared with the detection of NMP22 and urinary cytology.

Pharmacogenetic study of ABCB1 and CYP3A5 genes during the first year following heart transplantation regarding tacrolimus or cyclosporine levels.

Pharmacogenetics explains part of the interindividual variability in drug responses. Many published works about the effects of single nucleotide polymorphisms (SNPs) on immunosuppressive drug blood levels present contradictory results. We evaluated the SNPs in ABCB1 (glycoprotein P) and CYP3A5 (metabolic enzyme) genes, seeking correlate them with tacrolimus or cyclosporine levels during the first year after heart transplantation. One blood sample was obtained from each of 41 patients: 26 treated with cyclosporine and 15 with tacrolimus. We characterize the SNPs rs1045642, 1128503, 2032582, 2235013, 2235033, 2229109, 3213619, 9282564 in ABCB1 and rs10264272, 776746 in CYP3A5 genes using the Sequenom platform. The genotype was correlated with the trough drug blood levels corrected by dose and body weight (C(0)/(dose/weight)). The CYP3A5 SNPs showed the expected behavior, where patients carrying the low expression variants displayed higher drug blood levels of more than 100% of the normal expression variant level even at 1 year posttransplantation. To correlate ABCB1 SNPs, the variants described to cause higher blood levels in rs1045642, 1128503, 2032582 (in linkage disequilibrium) showed this effect only until 4 months posttransplantation among patients treated with cyclosporine (more than 100% higher than the other variant). After 1 year, concentrations reached a stable phase with normal levels. The observation was not so evident among those treated with tacrolimus. Remarkably, at this point, patients treated with cyclosporine, showed a significant (P < .01) difference between the two variants of rs9282564 and even if it was not significant there was also a tendency among the intronic rs2235013 and 2235033. The results indicated that SNPs in ABCB1 gene seem to not be relevant for long-term dose adjustment in patients, but to show an effect during the first 4 months.