RESUMO
The prognosis of patients with advanced oesophageal cancer (EC) and gastric cancer (GC) is poor. Circulating microRNAs (ci-miRNAs) may have prognostic and predictive value to improve patient selection for palliative treatment. The purpose of this study is to assess the prognostic and predictive value of specific ci-miRNAs in plasma of patients with EC and GC treated with first-line palliative gemcitabine and cisplatin. Droplet digital PCR (ddPCR) was used to quantify miR-200c-3p, miR-375, miR-21-5p, miR-148a-3p, miR-146a-5p, miR-141-3p and miR-218-5p in plasma from 68 patients. ci-miRNA expression was analyzed in relation to overall survival (OS), progression-free survival (PFS), and response to chemotherapy. ci-miRNA levels were detectable in 36 baseline (71%) samples and in 14 (47%) follow-up samples. Increased circulating miR-200c-3p in GC showed a trend (p = 0.06) towards a shorter OS. High circulating miR-375 was associated with a longer OS (p = 0.02) in patients with esophageal adenocarcinoma (EAC). No significant difference was observed in ci-miRNA expression between paired pre- and on-treatment samples. ci-miRNA expression was not associated with response to chemotherapy. ci-miRNAs can be measured in plasma samples of patients treated with first-line palliative chemotherapy using ddPCR despite prolonged storage in heparin. Elevated circulating miR-375 might be a prognostic marker for patients with EAC.
Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Neoplasias Esofágicas/sangue , Neoplasias Esofágicas/tratamento farmacológico , Junção Esofagogástrica , MicroRNAs/sangue , Neoplasias Gástricas/sangue , Neoplasias Gástricas/tratamento farmacológico , Idoso , Cisplatino/administração & dosagem , Ensaios Clínicos Fase II como Assunto , Desoxicitidina/administração & dosagem , Desoxicitidina/análogos & derivados , Feminino , Ácido Fólico/administração & dosagem , Humanos , Masculino , Pessoa de Meia-Idade , Cuidados Paliativos , Prognóstico , Intervalo Livre de Progressão , Ensaios Clínicos Controlados Aleatórios como Assunto , Taxa de Sobrevida , GencitabinaRESUMO
Allopurinol is widely used in the management of multiple disorders including gout, kidney stones and inflammatory bowel disease. Despite of long-term experience, its safety in pregnancy has been debated due to reports on possible teratogenicity. We aimed to review the literature on the safety of allopurinol in pregnancy and offspring. In animals, allopurinol induced species-specific reproductive toxicity. In humans, a total of 53 allopurinol exposed infants were reported in the literature. Major congenital malformations were reported in two cases with a comparable pattern of multiple abnormalities. Five other infants had minor birth defects. In conclusion, the association between allopurinol and teratogenicity appears to be weak and limited to two reports with uncertain causality. However, the available data are insufficient to make a certain judgement, and as allopurinol treatment evolves, report and prospective follow-up of all exposed infants (i.e. deviant and normal cases) should be encouraged.
