RESUMO
ABSTRACT: The platelet-albumin-bilirubin (PALBI) grade plays critical role in evaluating liver function. However, the change of PALBI grade from the preoperative to postoperative period in predicting patient outcomes after hepatectomy remains unclear.A total of 489 HCC patients who underwent hepatectomy in West China Hospital between January, 2010 and June, 2016 were analyzed retrospectively.ΔPALBI grade was calculated by PALBI grade at the first postoperative month - preoperative PALBI grade.ΔPALBI >0 was considered as stable; otherwise, worse PALBI grade was considered. Kaplan- Meier method and Cox proportional hazard regression analyses were performed for survival analysis. Prognostic model was constructed by nomogram method.Three hundred forty two patients and 147 patients were classified into training group and validation group, respectively. In the training group, results from Cox model suggested that worse PALBI grade (HR 1.328, 95% CI 1.010-1.746, Pâ=â.042), tumor size (HR 1.460, 95% CI 1.058-2.015, Pâ=â.021), microvascular invasion (MVI, HR 1.802, 95% CI 1.205-2.695, Pâ<â.001), and high alpha-fetoprotein level (AFP, HR 1.364, 95% CI 1.044-1.781, Pâ=â.023) negatively influenced postoperative recurrence. Similarly, worse PALBI grade (HR 1.403, 95% CI 1.020-1.930, Pâ=â.038), tumor size (HR 1.708, 95% CI 1.157-2.520, Pâ=â.007), MVI (HR 1.914, 95% CI 1.375-2.663, Pâ<â.001), and presence of cirrhosis (HR 1.773, 95% CI 1.226-2.564, Pâ=â.002) had negatively impacts on overall survival. Patients with worse PALBI grade had worse recurrence free (RFS) and overall survival (OS). The prognostic model incorporating the change of PALBI grade constructed in training group and tested in the validation group could perform well in predicting the outcomes.Postoperative change of PALBI grade was independently risk factor related with prognosis. Prognostic model incorporating the change of PALBI grade might be a useful index to predict the prognosis of HCC patients following hepatectomy.
Assuntos
Bilirrubina/sangue , Carcinoma Hepatocelular/sangue , Hepatectomia/mortalidade , Testes de Função Hepática/métodos , Neoplasias Hepáticas/sangue , Contagem de Plaquetas , Albumina Sérica/análise , Adulto , Idoso , Biomarcadores Tumorais , Plaquetas , Carcinoma Hepatocelular/mortalidade , Carcinoma Hepatocelular/cirurgia , Feminino , Humanos , Estimativa de Kaplan-Meier , Cirrose Hepática/sangue , Cirrose Hepática/etiologia , Cirrose Hepática/mortalidade , Neoplasias Hepáticas/mortalidade , Neoplasias Hepáticas/cirurgia , Masculino , Pessoa de Meia-Idade , Nomogramas , Período Pós-Operatório , Valor Preditivo dos Testes , Período Pré-Operatório , Prognóstico , Modelos de Riscos Proporcionais , Estudos Retrospectivos , Índice de Gravidade de Doença , Análise de SobrevidaRESUMO
Mammalian target of rapamycin complex 1 (mTORC1) is evolutionally conserved and frequently activated in various tumors, including colorectal cancer (CRC). It has been reported that the ribosome assembly factor Urb1 acts downstream of mTORC1/raptor signaling and contributes to digestive organ development in zebrafish. Previously, we highlighted that URB1 was overexpressed in CRC. Here, we assessed the mTORC1/regulatory associated protein with mTOR (RAPTOR)-URB1 axis in CRC tumorigenesis. We found that RAPTOR was overexpressed in CRC tissues and cell lines, was a favorable predictor in patients with CRC, and positively correlated with URB1. Silencing of RAPTOR suppressed CRC cell proliferation and migration and induced cell cycle arrest and apoptosis in vitro and inhibited xenograft growth in vivo. Moreover, ectopic overexpression of RAPTOR exerted an inverse biological phenotype. Knockdown of RAPTOR quenched mTORC1 activity and reduced the expression of URB1 and cyclinA2 (CCNA2). In contrast, overexpression of RAPTOR activated mTORC1 and upregulated URB1 and CCNA2. Furthermore, URB1 and CCNA2 expression were also impeded by rapamycin, which is a specific inhibitor of mTORC1. Thus, RAPTOR promoted CRC proliferation, migration, and cell cycle progression by inducing mTORC1 signaling and transcriptional activation of both URB1 and CCNA2. Taken together, we concluded that RAPTOR has the potential to serve as a novel biomarker and therapeutic target for CRC.
Assuntos
Biomarcadores Tumorais/metabolismo , Neoplasias Colorretais/genética , Alvo Mecanístico do Complexo 1 de Rapamicina/metabolismo , Proteínas Nucleares/genética , Proteína Regulatória Associada a mTOR/metabolismo , Animais , Apoptose/efeitos dos fármacos , Apoptose/genética , Biomarcadores Tumorais/genética , Carcinogênese/efeitos dos fármacos , Carcinogênese/genética , Linhagem Celular Tumoral , Proliferação de Células/efeitos dos fármacos , Proliferação de Células/genética , Colo/patologia , Colo/cirurgia , Neoplasias Colorretais/diagnóstico , Neoplasias Colorretais/mortalidade , Neoplasias Colorretais/cirurgia , Ciclina A2/genética , Feminino , Regulação Neoplásica da Expressão Gênica/efeitos dos fármacos , Técnicas de Silenciamento de Genes , Humanos , Estimativa de Kaplan-Meier , Masculino , Alvo Mecanístico do Complexo 1 de Rapamicina/antagonistas & inibidores , Camundongos , Pessoa de Meia-Idade , Reto/patologia , Reto/cirurgia , Transdução de Sinais/efeitos dos fármacos , Transdução de Sinais/genética , Sirolimo/farmacologia , Regulação para Cima/efeitos dos fármacos , Ensaios Antitumorais Modelo de XenoenxertoRESUMO
BACKGROUND: Malignant pleural effusion (MPE) is a complicated condition of patients with advanced tumors. Further dissecting the microenvironment of infiltrated immune cells and malignant cells are warranted to understand the immune-evasion mechanisms of tumor development and progression. METHODS: The possible involvement of microRNAs (miRNAs) in malignant pleural fluid was investigated using small RNA sequencing. Regulatory T cell (Treg) markers (CD4, CD25, forkhead box P3), and Helios (also known as IKAROS Family Zinc Finger 2 [IKZF2]) were detected using flow cytometry. The expression levels of IKZF2 and miR-4772-3p were measured using quantitative real-time reverse transcription polymerase chain reaction. The interaction between miR-4772-3p and Helios was determined using dual-luciferase reporter assays. The effects of miR-4772-3p on Helios expression were evaluated using an in vitro system. Correlation assays between miR-4772-3p and functional molecules of Tregs were performed. RESULTS: Compared with non-malignant controls, patients with non-small cell lung cancer had an increased Tregs frequency with Helios expression in the MPE and peripheral blood mononuclear cells. The verified downregulation of miR-4772-3p was inversely related to the Helios Tregs frequency and Helios expression in the MPE. Overexpression of miR-4772-3p could inhibit Helios expression in in vitro experiments. However, ectopic expression of Helios in induced Tregs reversed the effects induced by miR-4772-3p overexpression. Additionally, miR-4772-3p could regulate Helios expression by directly targeting IKZF2 mRNA. CONCLUSION: Downregulation of miR-4772-3p, by targeting Helios, contributes to enhanced Tregs activities in the MPE microenvironment.
Assuntos
Carcinoma Pulmonar de Células não Pequenas/metabolismo , Fator de Transcrição Ikaros/metabolismo , MicroRNAs/metabolismo , Derrame Pleural Maligno/metabolismo , Linfócitos T Reguladores/metabolismo , Adulto , Idoso , Carcinoma Pulmonar de Células não Pequenas/genética , Feminino , Citometria de Fluxo , Humanos , Fator de Transcrição Ikaros/genética , Subunidade alfa de Receptor de Interleucina-2/genética , Subunidade alfa de Receptor de Interleucina-2/metabolismo , Leucócitos Mononucleares/metabolismo , Neoplasias Pulmonares/genética , Neoplasias Pulmonares/metabolismo , Masculino , MicroRNAs/genética , Pessoa de Meia-Idade , Derrame Pleural Maligno/genética , Reação em Cadeia da Polimerase Via Transcriptase ReversaRESUMO
OBJECTIVE: To evaluate the characteristics of the preputial development in Chinese boys and indications as well as occasion of circumcision. METHODS: The shape and retractability of prepuce were evaluated in 1,015 Chinese boys from 0 to 18 years old without heteroplasia of prepuce and penis. RESULTS: Ratio of children with phimosis decreases progressively with increasing age, from 64.09% in the first group (0 approximately 3 years old) to 7.66% in the fourth group (11 approximately 18 years old). CONCLUSION: Phimosis and incomplete separation of the prepuce is normal in the neonate and infant. Prepuce will separate from the glans progressively till adolescence, so it's unnecessary to perform circumcision for them when without any complications.
