RESUMO
A 37-year-old male with tarry stool presented to our hospital. Esophagogastroduodenoscopy revealed advanced gastric cancer, fundic gland polyposis (FGPsis), and negativity for Helicobacter pylori (HP) infection. Computed tomography exhibited multiple liver tumors. Total colonoscopy (TCS) demonstrated 139 tubular adenomas. He was diagnosed as having unresectable gastric cancer and received systemic chemotherapy. His sister and mother had colorectal adenomatous polyposis as revealed by TCS. His sister had FGPsis and was negative for HP infection, whereas his mother had early gastric cancer with HP infection but not FGPsis. Genetic analysis revealed a novel mutation in exon 15 of the APC gene (NM_000038.5: c.7647_7648_delTG) for the patient, his mother, and his sister, whereas no mutation was found for his father who had no gastrointestinal polyps. Therefore, the pedigree was diagnosed as an FAP family with a novel APC germline mutation which had different gastric phenotypes depending on the status of HP infection.
Assuntos
Polipose Adenomatosa do Colo/diagnóstico , Infecções por Helicobacter/diagnóstico , Pólipos/diagnóstico , Neoplasias Gástricas/diagnóstico , Polipose Adenomatosa do Colo/genética , Polipose Adenomatosa do Colo/patologia , Proteína da Polipose Adenomatosa do Colo/genética , Adulto , Colonoscopia , Endoscopia do Sistema Digestório , Mutação em Linhagem Germinativa , Helicobacter pylori/isolamento & purificação , Humanos , Masculino , Fenótipo , Pólipos/genética , Pólipos/patologia , Neoplasias Gástricas/genética , Neoplasias Gástricas/patologia , Tomografia Computadorizada por Raios XRESUMO
In patients with end-stage renal disease, not only renal clearance but also hepatic clearance is known to be impaired. For instance, the concentration of erythromycin, a substrate of cytochrome P450 3A4 (CYP3A4), has been reported to be elevated in patients with end-stage renal disease. The purpose of this study is to elucidate the reason for the decrease in hepatic clearance in patients with end-stage renal disease. Deproteinized pooled sera were used to assess the effects of low-molecular-weight uremic toxins on CYP3A4 activity in human liver microsomes and human LS180 cells. Four uremic toxins (3-carboxy-4-methyl-5-propyl-2-furanpropanoic acid, hippuric acid, indole-3-acetic acid, and 3-indoxyl sulfate) present at high concentrations in uremic serum were also studied. Simultaneous treatment of uremic serum (less than 10%) or uremic toxins did not affect testosterone 6ß-hydroxylation in human liver microsomes. On the other hand, pretreatment of each serum activates CYP3A4 in LS180 cells, and the increased CYP3A4 activity in uremic serum-treated cells was smaller than normal serum-treated cells. In addition, CYP3A4 and CYP24A1 mRNA levels also increased in LS180 cells exposed to normal serum, and this effect was reduced in uremic serum-treated cells and in cells exposed to uremic serum added to normal serum. Furthermore, addition of 1,25-dihydroxyvitamin D to uremic serum partially restored the serum effect on CYP3A4 expression. The present study suggests that the decrease of 1,25-dihydroxyvitamin D and the accumulation of uremic toxins contributed to the decreased hepatic clearance of CYP3A4 substrates in patients with end-stage renal disease.