RESUMO
Irinotecan (CPT-11) is considered an important drug in the treatment of colorectal cancer, but its continuous administration reduces its sensitivity and influences the curative effect. The metabolism of CPT-11 is mainly controlled by carboxy-lesterase (CES), UDP-glucuronosyltransferase 1A (UGT1A), and ß-glucuronidase (GUSB). Studies to date have shown that methylation acts as an important mechanism for gene expression to suppress the metabolic enzymes of many chemotherapeutics. This study, which selected 99 colorectal cancer patients, 23 of whom had paracancerous tissues and eight of whom had large intestine adenomas, aimed to investigate the correlation between the protein expression of the CPT-11 metabolic enzyme genes CES2, UGT1A1, and GUSB and various clinical pathological parameters of colorectal cancer tissues, as well as the relationship between methylation regulation and the gene expression of CES2, UGT1A1, and GUSB. We used immunohistochemistry staining, methylation-specific PCR, and clinical status to reveal the possible regulatory targets of chemotherapeutic resistance in colorectal cancer and to provide new ideas and countermeasures to reverse anti-cancer drug resistance and chemosensitization. The results showed that the expression of CES2, UGTA1A1, and GUSB varies in colorectal pathology tissues and that the expression of CES2 is somewhat related to tumor staging. This relationship is likely caused by the gene regulation of UGT1A1 and GUSB, and other regulation mechanisms may also be involved. The methylation of the CES2 gene is irrelevant to the morbidity associated with colorectal cancer. The GUSB gene showed no significant differences in methylation, and the hemi-methylation was also positive, the regulating ability of which needs to be verified. The potential role of these genes in the colorectal cancer progression, which may be directly related to the methylation regulation of UGT1A1, requires further research. The promoter of the UGT1A1 gene in colorectal cancer cells is methylated, which is an important mechanism of UGT1A1 gene silencing and can be regarded as the target point of research for CPT-11 drug resistance and control mechanisms for the reversal of drug resistance.
Assuntos
Carboxilesterase/genética , Neoplasias Colorretais/genética , Metilação de DNA , Glucuronidase/genética , Glucuronosiltransferase/genética , Adulto , Idoso , Idoso de 80 Anos ou mais , Carboxilesterase/análise , Neoplasias Colorretais/química , Neoplasias Colorretais/patologia , Feminino , Glucuronidase/análise , Glucuronosiltransferase/análise , Humanos , Imuno-Histoquímica , Masculino , Pessoa de Meia-Idade , Reação em Cadeia da Polimerase , Regiões Promotoras GenéticasRESUMO
There are few reports on CT findings in "fresh" cerebral paragonimiasis. We have experienced four cases of "fresh" cerebral paragonimiasis examined by CT scan. Three patients were children aged 7, 9, and 14 years, and one was an adult aged 25 years. Three patients were examined by CT scan 2 to 6 months after the onset of high grade fever, convulsion and focal deficit signs, and a patient was examined one month after his progressive visual disturbance. The unique CT findings are multilocular cystic lesions in temporo-occipital or in temporo-parietal lobes with extensive brain edema. Two cases were also associated with "soap-bubble" calcifications. The cysts were more dense than CSF and enhanced by contrast media. The histopathological specimen showed that the eggs of paragonimus were in the abscess cavity, of which the wall was composed with highly vascular gliomesenchymal capsule and numerous cell infiltration. Three patients underwent craniotomy for removal of abscess and decompression. Bitionol were administered and all patients recovered well. We also discussed the differential diagnosis of cerebral parasitic granulomas.