RESUMEN
OBJECTIVES: There are subclinical neurologic deficits in cirrhotic patients without overt hepatic encephalopathy. We aimed to use F-fluorodeoxyglucose PET/computed tomography to explore the impaired brain glucose metabolism of subclinical hepatic encephalopathy in cirrhosis. METHODS: Thirty-seven patients with hepatitis B virus-related cirrhosis without overt hepatic encephalopathy and 49 controls were enrolled in the study. The patients' Model for End-Stage Liver Disease scores were calculated. All participants underwent resting state F-fluorodeoxyglucose PET/computed tomography. Between-group comparisons of brain PET/computed tomography data were conducted with two-sample t-tests and multivariate tests with Statistical Parametric Mapping 8 software. RESULTS: Most of the patients (30/37) had a Model for End-Stage Liver Disease score of less than 20. The patients and controls did not significantly differ in baseline characteristics, such as sex, age, plasma glucose level, smoking history or BMI, but they did significantly differ in blood uric acid level and serum levels of bilirubin, albumin, total protein, alkaline phosphatase, alanine aminotransferase and aspartate aminotransferase (P < 0.0001). Relative to brain glucose metabolism in the controls, that in the patients involved both hyper- and hypometabolic regions (P < 0.001). The relative hypometabolic regions included the parietal, occipital and limbic lobes, and the hypermetabolic regions included the hippocampus, parahippocampal gyri, right basal ganglia and circumventricular organs. CONCLUSION: Patients with cirrhosis have characteristic patterns of brain glycometabolic impairment. F-fluorodeoxyglucose PET/computed tomography may serve as a preclinical biomarker for brain damage in cirrhosis.
Asunto(s)
Encéfalo/metabolismo , Glucosa/metabolismo , Encefalopatía Hepática/metabolismo , Cirrosis Hepática/metabolismo , Femenino , Fluorodesoxiglucosa F18 , Encefalopatía Hepática/complicaciones , Hepatitis B/complicaciones , Hepatitis B/metabolismo , Humanos , Cirrosis Hepática/complicaciones , Cirrosis Hepática/virología , Masculino , Persona de Mediana Edad , Tomografía Computarizada por Tomografía de Emisión de Positrones , Estudios RetrospectivosRESUMEN
Arginine methylation is a ubiquitous posttranslational modification that regulates critical cellular processes including signal transduction and pre-mRNA splicing. Here, we report that the tumor-suppressor PTEN is methylated by protein arginine methyltransferase 6 (PRMT6). Mass-spectrometry analysis reveals that PTEN is dimethylated at arginine 159 (R159). We found that PTEN is mutated at R159 in cancers, and the PTEN mutant R159K loses its capability to inhibit the PI3K-AKT cascade. Furthermore, PRMT6 is physically associated with PTEN, promotes asymmetrical dimethylation of PTEN, and regulates the PI3K-AKT cascade through PTEN R159 methylation. In addition, using transcriptome analyses, we found that PTEN R159 methylation is involved in modulation of pre-mRNA alternative splicing. Our results demonstrate that PTEN is functionally regulated by arginine methylation. We propose that PTEN arginine methylation modulates pre-mRNA alternative splicing and influences diverse physiologic processes.
Asunto(s)
Empalme Alternativo , Proteínas de Neoplasias/metabolismo , Neoplasias/metabolismo , Proteínas Nucleares/metabolismo , Fosfohidrolasa PTEN/metabolismo , Fosfatidilinositol 3-Quinasas/metabolismo , Proteína-Arginina N-Metiltransferasas/metabolismo , Proteínas Proto-Oncogénicas c-akt/metabolismo , Precursores del ARN/metabolismo , ARN Neoplásico/metabolismo , Transducción de Señal , Línea Celular Tumoral , Células HEK293 , Humanos , Metilación , Proteínas de Neoplasias/genética , Neoplasias/genética , Proteínas Nucleares/genética , Fosfohidrolasa PTEN/genética , Fosfatidilinositol 3-Quinasas/genética , Proteína-Arginina N-Metiltransferasas/genética , Proteínas Proto-Oncogénicas c-akt/genética , Precursores del ARN/genética , ARN Neoplásico/genéticaRESUMEN
OBJECTIVE: To investigate the clinical value of 18F-fluorodeoxyglucose positron emission tomography (FDG PET)/CT for the diagnosis and management of lung nodules. METHODS: Twenty patients were evaluated: 15 with suspected cancer and 5 confirmed cancer. PET/CT scans were performed by discovery LS-PET/CT system. RESULTS: (1) The diagnostic accuracy of PET/CT was 100% in these 20 patients. Of 15 patients with suspected cancer, 7 were diagnosed as having benign disease and 8 malignant. All the 5 patients with confirmed cancer were all FDG positive. Of 11 single lesions on CT, 3 were positive by PET/CT images, 6 of 8 with positive CT images were diagnosed as having metastasis to the tissue outside the lung and the other 2 were metastatic. (2) After PET/CT scanning, the therapy scheme of 16 out of 20 patients were changed, and continual observation was practiced in 2, 3 were treated by anti-inflammation regimen, 2 by operation, 4 by local radiotherapy, 3 by chemotherapy only, 4 by radiotherapy plus chemotherapy or operation. (3) The radiotherapists made use of PET/CT fusion imaging for positioning in 8 patients who were indicated for radiotherapy. One of them who had received MM50 one course of intensity medulated conformal radiotherapy was re-examined by PET/CT after one and half months, the former parenchymal nodule disappeared and the glucose metabolism returned to normal. Two of them were finally operated after the surgeons have decided an operative approach on estimation of extent of lesion by the PET/CT fusion images. Pathological results showed no cancer cell involvement in the specimen margin or the local lymph nodes. CONCLUSION: (1) PET/CT is better in discriminating malignant from benign lung nodules than CT only. (2) PET/CT scanning facilitates an accurate assessment of response in clinical staging and neoadjuvant therapy scheme of lung cancer. (3) PET/CT fusion imaging provides an accurate biological target for radiotherapy and confirms the operation plan and extent of surgery.