RESUMO
Post-transcriptional modifications in mitochondrial tRNAs (mt-tRNAs) play critical roles in mitochondrial protein synthesis, which produces respiratory chain complexes. In this study, we took advantage of mass spectrometric analysis to map 5-methylcytidine (m5C) at positions 48-50 in eight mouse and six human mt-tRNAs. We also confirmed the absence of m5C in mt-tRNAs isolated from Nsun2 knockout (KO) mice, as well as from NSUN2 KO human culture cells. In addition, we successfully reconstituted m5C at positions 48-50 of mt-tRNA in vitro with NSUN2 protein in the presence of S-adenosylmethionine. Although NSUN2 is predominantly localized to the nucleus and introduces m5C into cytoplasmic tRNAs and mRNAs, structured illumination microscopy clearly revealed NSUN2 foci inside mitochondria. These observations provide novel insights into the role of NSUN2 in the physiology and pathology of mitochondrial functions.
Assuntos
5-Metilcitosina/metabolismo , Metiltransferases/genética , Mitocôndrias/genética , Processamento Pós-Transcricional do RNA , RNA Mitocondrial/genética , RNA de Transferência/genética , Animais , Sistemas CRISPR-Cas , Fibroblastos/metabolismo , Fibroblastos/patologia , Edição de Genes , Técnicas de Inativação de Genes , Células HEK293 , Células HeLa , Humanos , Metilação , Metiltransferases/deficiência , Camundongos , Camundongos Knockout , Mitocôndrias/metabolismo , Conformação de Ácido Nucleico , Fosforilação Oxidativa , Cultura Primária de Células , Transporte Proteico , RNA Mensageiro/genética , RNA Mensageiro/metabolismo , RNA Mitocondrial/metabolismo , RNA de Transferência/metabolismo , S-Adenosilmetionina/metabolismoRESUMO
An 80-year-old woman presented with acute abdominal pain and distention. A diagnosis of acute chylous peritonitis was made via contrast-enhanced computed tomography and abdominal paracentesis. She underwent ultrasound-guided intranodal lymphangiography with Lipiodol® (IL with Lipiodol), and her persistent abdominal pain was significantly reduced within a day. Moreover, her ascitic fluid showed marked improvement and paracentesis was no longer needed. Based on the findings of the study, IL with Lipiodol could be a promising minimally invasive approach in the treatment of acute chylous peritonitis.
Assuntos
Ascite Quilosa , Peritonite , Idoso de 80 Anos ou mais , Ascite Quilosa/diagnóstico por imagem , Ascite Quilosa/terapia , Óleo Etiodado , Feminino , Humanos , Linfografia , Peritonite/diagnóstico por imagem , Peritonite/etiologia , Peritonite/terapia , Ultrassonografia , Ultrassonografia de IntervençãoRESUMO
BACKGROUND: A family/personal history of breast, ovarian, or pancreatic cancer is a useful predictive marker for response to platinum-based chemotherapy in treating patients with pancreatic cancer. These cancers, and prostate cancer, are known as BRCA-related malignancies. We evaluated the efficacy of gemcitabine plus oxaliplatin (GEMOX) in patients with metastatic pancreatic cancer with a family/personal history of these cancers. METHODS: Chemotherapy-naïve patients with metastatic pancreatic cancer with a family history of pancreatic/breast/ovarian/prostate cancer or a personal history of breast/ovarian/prostate cancer were included. Patients received fixed dose-rate gemcitabine (1000 mg/m2) and oxaliplatin (100 mg/m2) every 2 weeks. The primary endpoint was 1-year survival, and the threshold and expected values were set at 30 and 50%, respectively. The target sample size was determined to be 43, with a one-sided alpha value of 5% and power of 80%. A total of 45 patients were enrolled. RESULTS: Among the first 43 enrolled patients, the 1-year survival rate was 27.9% [90% confidence interval (CI) 17.0-41.3], which did not meet the primary endpoint. Median overall survival, progression-free survival, and response rates were 7.6 months (95% CI 6.0-10.7), 4.0 months (95% CI 2.0-4.6), and 26.7% (95% CI 14.6-41.9), respectively, in all registered patients. The GEMOX regimen was generally tolerated; the most common grade three or higher adverse events were hematological toxicities. CONCLUSION: GEMOX did not show the expected efficacy in patients with metastatic pancreatic cancer with a family or personal history of pancreatic/breast/ovarian/prostate cancer. Selection of GEMOX based on family/personal history is not recommended. TRIAL REGISTRATION NUMBER: UMIN000017894.