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1.
Zhonghua Gan Zang Bing Za Zhi ; 27(8): 634-637, 2019 Aug 20.
Artigo em Chinês | MEDLINE | ID: mdl-31594082

RESUMO

Objective: To explore the diagnostic value of single or combined detection of serum tumor markers alpha-fetoprotein (AFP), α-fetoprotein (AFP)-L3 and abnormal clotting (PIVKA-II) in the primary hepatic carcinoma. Methods: Serum AFP, AFP-L3 and PIVKA-II of 56 cases with primary hepatic carcinoma, 46 cases with cirrhosis, 45 cases with other liver disease and 41 healthy persons (control group) were examined by chemiluminescence method, and the differences in the levels of AFP, AFP-L3 and PIVKA-II in each group were compared. Results: Serum level of AFP, AFP-L3 and PIVKA-II in patients with primary liver cancer was significantly higher than that of the cirrhosis, other liver disease and control groups, and the difference was statistically significant (P < 0.05). The receiver operating characteristic curve analysis showed that the areas under the curve for the diagnosis of primary hepatic carcinoma by AFP, AFP-L3 and PIVKA-II were 0.887, 0.846 and 0.885, respectively. The combined use of the three tumor markers for the diagnosis of primary hepatic carcinoma increased the area under the curve to 0.899. Among the single detection, AFP had the highest sensitivity of 91.07% and PIVKA-II had the highest specificity at 88.63%. In the combined detection, AFP/PIVKA-II combination had the highest sensitivity of 94.64 %, while the AFP + AFP-L3 + PIVKA-II combination had the highest specificity at 98.48%. Conclusion: Combined detection of AFP, AFP-L3 and PIVKA-II could improve the diagnostic specificity and the sensitivity of primary hepatic carcinoma; thereby make up the deficiency of single detection and improve the early diagnosis rate.


Assuntos
Carcinoma Hepatocelular/diagnóstico , Neoplasias Hepáticas/diagnóstico , Protrombina/análise , alfa-Fetoproteínas/análise , Biomarcadores Tumorais/sangue , Carcinoma Hepatocelular/sangue , Estudos de Casos e Controles , Humanos , Cirrose Hepática , Neoplasias Hepáticas/sangue
2.
Nihon Shokakibyo Gakkai Zasshi ; 116(9): 764-772, 2019.
Artigo em Japonês | MEDLINE | ID: mdl-31511463

RESUMO

A 77-year-old man with chronic hepatitis C underwent transcatheter arterial chemoembolization (TACE) and radiofrequency ablation (RFA) for early-stage hepatocellular carcinoma (HCC) in segment 8 of the liver. Necrosis was confirmed radiologically. After 19 months, recurrent HCC in segment 6 was treated with TACE and RFA. There was no recurrence. Direct-acting antiviral (DAA) therapy 24 months after the initial procedure led to a sustained virologic response. AFP-L3 markedly increased 11 months after DAA therapy, and MRI 6 months after that showed a solitary lymph node near the common bile duct. Because no intrahepatic recurrence or other lymph nodes were seen, the solitary node was excised. Histopathology showed metastatic HCC. There has been no subsequent recurrence over 13 months of follow-up.


Assuntos
Carcinoma Hepatocelular/diagnóstico , Ablação por Cateter , Quimioembolização Terapêutica , Hepatite C Crônica , Neoplasias Hepáticas/diagnóstico , Idoso , Antivirais , Terapia Combinada , Humanos , Japão , Linfonodos , Masculino , Recidiva Local de Neoplasia , Ablação por Radiofrequência , Resultado do Tratamento
3.
Anticancer Res ; 39(9): 5149-5156, 2019 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-31519627

RESUMO

BACKGROUND: Factors associated with response to lenvatinib have not been clarified in patients with hepatocellular carcinoma (HCC). PATIENTS AND METHODS: This study retrospectively analyzed 50 patients treated with lenvatinib as first-line therapy between March 2018 and March 2019. Patients were divided into two groups by the Modified Response Evaluation Criteria in Solid Tumours (mRECIST) (responders and non-responders, whose best overall responses were complete (CR)/partial response (PR) and stable (SD)/progressive disease (PD), respectively). Factors associated with response were assessed, including the relative dose intensity 8 weeks after lenvatinib induction (8W-RDI). RESULTS: The best overall responses were 0/22/14/14 of CR/PR/SD/PD. Multivariate analysis revealed that only 8W-RDI was significantly associated with response. The receiver operating characteristic curve for 8W-RDI in differentiating responders from non-responders revealed a cut-off value of 75%. Patients with 8W-RDI ≥75% experienced a higher response rate and longer progression-free survival than patients with 8W-RDI <75%. CONCLUSION: Our results suggest that maintaining an RDI ≥75% during the initial 8 weeks of lenvatinib treatment has a favorable impact on response.


Assuntos
Antineoplásicos/uso terapêutico , Carcinoma Hepatocelular/tratamento farmacológico , Neoplasias Hepáticas/tratamento farmacológico , Compostos de Fenilureia/uso terapêutico , Inibidores de Proteínas Quinases/uso terapêutico , Quinolinas/uso terapêutico , Idoso , Idoso de 80 Anos ou mais , Antineoplásicos/administração & dosagem , Antineoplásicos/efeitos adversos , Carcinoma Hepatocelular/diagnóstico , Carcinoma Hepatocelular/etiologia , Carcinoma Hepatocelular/mortalidade , Feminino , Humanos , Neoplasias Hepáticas/diagnóstico , Neoplasias Hepáticas/etiologia , Neoplasias Hepáticas/mortalidade , Masculino , Pessoa de Meia-Idade , Estadiamento de Neoplasias , Compostos de Fenilureia/administração & dosagem , Compostos de Fenilureia/efeitos adversos , Inibidores de Proteínas Quinases/administração & dosagem , Inibidores de Proteínas Quinases/efeitos adversos , Quinolinas/administração & dosagem , Quinolinas/efeitos adversos , Curva ROC , Estudos Retrospectivos , Resultado do Tratamento
4.
Medicine (Baltimore) ; 98(32): e16725, 2019 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-31393380

RESUMO

BACKGROUND: To verify the accuracy of serum dickkopf-1 protein (DKK-1) in the diagnosis of hepatocellular carcinoma (HCC) by an updated meta-analysis. METHODS: We searched potential eligible studies in PubMed and Embase before July 8, 2018. Sensitivity (SN), specificity (SP), positive likelihood ratio (PLR), negative likelihood ratio (NLR), summary receiver operating characteristics curve (sROC), and diagnostic odds ratio (DOR) were pooled with their 95% confidence intervals CIs) using a bivariate random-effects model. RESULTS: A total of 8 articles contained 10 studies on diagnosis of HCC with DKK-1 alone,7 articles contained 9 studies on diagnosis of HCC with a-fetoprotein (AFP) alone and 5 articles contained 7 studies on diagnosis of HCC with DKK-1 + AFP were identified. The pooled SN, SP, PLR, NLR, and DOR of DKK-1 alone, AFP alone and DKK-1 + AFP were 0.72 (95% CI: 0.70-0.75), 0.62 (95% CI:0.59-0.64) and 0.80 (95% CI:0.78-0.83), 0.86 (95% CI: 0.84-0.87), 0.82 (95% CI:0.80-0.84) and 0.87 (95% CI: 0.85-0.88), 4.91 (95% CI: 2.73-8.83), 3.60 (95% CI:2.01-6.44) and 6.18 (95% CI: 4.68-8.16), 0.32 (95% CI: 0.22-0.47), 0.49 (95% CI:0.40-0.60) and 0.20 (95% CI: 0.15-0.26), and 17.21 (95% CI: 9.10-32.57), 7.45 (95% CI:3.69-15.01) and 31.39 (95% CI: 23.59-43.20), respectively. The area under the sROC was 0.88, 0.70, and 0.92 for the 3 diagnostic methods. CONCLUSIONS: Serum DKK-1 + AFP showed a high accuracy for diagnosis of HCC, and serum DKK-1 alone had moderate accuracy as compared to a previous meta-analysis, while AFP alone owned an unsatisfied diagnostic behavior for HCC. Due to the limitations of the current analysis, further well-designed studies are needed to confirm the diagnostic value of DKK-1 and DKK-1 + AFP in HCC diagnosis.


Assuntos
Carcinoma Hepatocelular/sangue , Peptídeos e Proteínas de Sinalização Intercelular/sangue , Neoplasias Hepáticas/sangue , Carcinoma Hepatocelular/diagnóstico , Humanos , Neoplasias Hepáticas/diagnóstico , Valor Preditivo dos Testes , alfa-Fetoproteínas/análise
5.
Anticancer Res ; 39(8): 4315-4324, 2019 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-31366523

RESUMO

BACKGROUND/AIM: This study aimed to obtain accurate differential diagnosis (DDx) of multicentric carcinogenesis (MC) and intrahepatic metastasis (IM) in recurrent lesions of hepatocellular carcinoma. MATERIALS AND METHODS: A total of 79 patients who underwent re-hepatectomy (2000-2013) were examined. PCR was used to analyze 13 chromosomal microsatellite loci by PCR. On the basis of this genetic analysis, the recurrent lesions were diagnosed as IM, MC or not determined (ND). Subsequently, DDx was compared with types of resection and outcome. RESULTS: The recurrent lesions were diagnosed as IM in 33 patients, MC in 44, and ND in 2. The anatomical resection group included 14 IM lesions (28%) and 36 MC lesions (72%), while the non-anatomical resection group included 19 IM lesions (70%) and 8 MC lesions (30%) (p<0.001). CONCLUSION: Anatomical resection at initial hepatectomy may reduce the likelihood of IM recurrence, leading to a better outcome for patients with HCC.


Assuntos
Carcinoma Hepatocelular/diagnóstico , Neoplasias Hepáticas/diagnóstico , Metástase Neoplásica/diagnóstico , Recidiva Local de Neoplasia/diagnóstico , Adulto , Idoso , Carcinogênese/genética , Carcinoma Hepatocelular/genética , Carcinoma Hepatocelular/patologia , Carcinoma Hepatocelular/cirurgia , Diagnóstico Diferencial , Feminino , Hepatectomia/métodos , Humanos , Neoplasias Hepáticas/genética , Neoplasias Hepáticas/patologia , Neoplasias Hepáticas/secundário , Masculino , Repetições de Microssatélites/genética , Pessoa de Meia-Idade , Metástase Neoplásica/genética , Metástase Neoplásica/patologia , Recidiva Local de Neoplasia/genética , Recidiva Local de Neoplasia/patologia , Recidiva Local de Neoplasia/cirurgia
6.
Anticancer Res ; 39(8): 4423-4430, 2019 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-31366540

RESUMO

BACKGROUND/AIM: To evaluate the impact of DEPDC1 expression on patient prognosis after hepatic resection for hepatocellular carcinoma (HCC). PATIENTS AND METHODS: We reviewed data from 75 patients who underwent hepatic resection for HCC between 2004 and 2013. Recurrence at 2 years following resection, which mainly included metastatic recurrence, was defined as late recurrence. RESULTS: DEPDC1 was up-regulated in HCC tissue and in non-tumor tissue of patients with HCC compared to normal liver (p<0.01 and p<0.01, respectively). High expression of DEPDC1 was associated with poor overall, disease-specific, and disease-free survival (p=0.02, p<0.01, and p<0.01, respectively). High DEPDC1 expression was an independent predictor of death and recurrence (p=0.03 and p<0.01, respectively). High expression of DEPDC1 in non-tumor liver was an independent risk factor for late recurrence (p=0.04). CONCLUSION: High expression of DEPDC1 in tumor tissue appears to be associated with tumor progression and poor prognosis.


Assuntos
Carcinoma Hepatocelular/genética , Proteínas Ativadoras de GTPase/genética , Neoplasias Hepáticas/genética , Proteínas de Neoplasias/genética , Prognóstico , Idoso , Carcinoma Hepatocelular/diagnóstico , Carcinoma Hepatocelular/mortalidade , Carcinoma Hepatocelular/patologia , Intervalo Livre de Doença , Feminino , Regulação Neoplásica da Expressão Gênica , Humanos , Neoplasias Hepáticas/diagnóstico , Neoplasias Hepáticas/mortalidade , Neoplasias Hepáticas/patologia , Masculino , Pessoa de Meia-Idade
7.
Medicine (Baltimore) ; 98(30): e16369, 2019 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-31348238

RESUMO

Previous studies have demonstrated a positive relationship between liver cancer and diabetes mellitus. However, elevated fasting blood glucose (FBG) itself may be a risk factor for the development of hepatocellular carcinoma (HCC) rather than diabetes, and during the follow-up period, death is an event that may occur before the occurrence of HCC, which should be dealt with competing risk models. Our study aims to investigate the relationship between FBG and new-onset HCC by using competing risk regression models.We prospectively studied the relationship between FBG concentrations and risk of HCC in a cohort of 93,447 participants who were free of prior HCC, and whose demographic characteristics and biochemical parameters were recorded. Cox proportional hazards regression models and competing risk regression models were used to evaluate the association between FBG concentrations and risk of incident HCC.A total of 302 participants were diagnosed with HCC among 93,447 subjects during 810,499 person-years of follow-up. The multivariable hazard ratios (HRs) [95% confidence interval (95% CI)] for the association of FBG and log(FBG) with HCC were 1.07 (1.01∼1.12), 1.84 (1.23∼2.74) in an analysis adjusted for other potential variables. In the multivariable adjusted analysis, participants who were in 4.82 mmol/L≤FBG≤5.49 mmol/L group and FBG >5.49 mmol/L group would have increased the risk of HCC by 47% and 69%, respectively. In a cause-specific hazard model (CS model), the multivariable HRs (95% CI) for the association of FBG with HCC were 1.46 (1.09∼1.98), 1.69 (1.27∼2.27) in the multivariable adjusted analysis. Similar results were also observed in sub-distribution hazard function model (SD model) with corresponding multivariate HRs (95% CI) of 1.46 (1.09∼2.00), 1.69 (1.25∼2.27) in 4.82 mmol/L≤FBG≤5.49 mmol/L group and FBG >5.49 mmol/L group, respectively.Higher FBG concentrations itself were positively associated with new-onset HCC in the Cox proportional hazards regression models and competing risk models. FBG concentrations can be used as a scientific and important way to identify individuals with a higher risk of HCC and control of FBG concentrations might serve as a possible way to decrease the risk of HCC among Chinese population.Trial registration: ChiCTR-TNRC-11001489. Registered August 24, 2011 (retrospectively registered).


Assuntos
Glicemia/análise , Carcinoma Hepatocelular/sangue , Carcinoma Hepatocelular/epidemiologia , Neoplasias Hepáticas/sangue , Neoplasias Hepáticas/epidemiologia , Fatores Etários , Idoso , Índice de Massa Corporal , Carcinoma Hepatocelular/diagnóstico , Comorbidade , Jejum/sangue , Feminino , Comportamentos Relacionados com a Saúde , Humanos , Testes de Função Hepática , Neoplasias Hepáticas/diagnóstico , Masculino , Pessoa de Meia-Idade , Modelos de Riscos Proporcionais , Estudos Prospectivos , Fatores de Risco , Fatores Sexuais
8.
J Surg Oncol ; 120(5): 847-850, 2019 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-31309559

RESUMO

Cancers of the hepatobiliary tract are highly fatal, prompting the need for early detection to provide treatment and decrease the mortality rate. Screening patients for hepatobiliary cancers can provide early detection, but it is not feasible or efficient to screen all patients. Therefore, it is important to consider the known risk factors for each hepatobiliary cancer which creates a smaller population that is amenable to screening.


Assuntos
Neoplasias do Sistema Biliar/diagnóstico , Carcinoma Hepatocelular/diagnóstico , Detecção Precoce de Câncer/métodos , Predisposição Genética para Doença , Neoplasias Hepáticas/diagnóstico , Neoplasias do Sistema Biliar/epidemiologia , Neoplasias do Sistema Biliar/genética , Carcinoma Hepatocelular/epidemiologia , Carcinoma Hepatocelular/genética , Humanos , Neoplasias Hepáticas/epidemiologia , Neoplasias Hepáticas/genética , Prevalência , Fatores de Risco
9.
Life Sci ; 231: 116660, 2019 Aug 15.
Artigo em Inglês | MEDLINE | ID: mdl-31319086

RESUMO

Hepatocellular carcinoma (HCC), a leading cause of cancer-related death with high invasive and metastatic potential, has a low survival rate. To improve the survival and quality of life in HCC patients, it is urgently needed to explore novel biomarkers for early diagnosis and prognosis of HCC, as well as therapeutic strategies. Circular RNAs (circRNAs) are a class of highly conserved, stable and abundant non-coding RNAs (ncRNAs) that can regulate gene expression at transcriptional or post-transcriptional levels. Recently, some circRNAs are identified to be potential biomarkers for HCC diagnosis and prognosis. Furthermore, some circRNAs are found to play oncogenic or suppressive roles in HCC progression by regulating various biological processes, including cell proliferation, migration, invasion and metastasis, epithelial-mesenchymal transition (EMT), as well as apoptosis. In this review, we summarize recent findings of deregulated circRNAs, their functions and molecular mechanisms in HCC, and discuss their potential roles as diagnostic biomarkers, prognostic biomarkers, as well as therapeutic targets for HCC.


Assuntos
Carcinoma Hepatocelular/genética , Neoplasias Hepáticas/genética , RNA/metabolismo , Biomarcadores Tumorais/genética , Biomarcadores Tumorais/metabolismo , Carcinoma Hepatocelular/diagnóstico , Carcinoma Hepatocelular/patologia , Linhagem Celular Tumoral , Progressão da Doença , Humanos , Neoplasias Hepáticas/diagnóstico , Neoplasias Hepáticas/patologia , MicroRNAs/genética , Invasividade Neoplásica , Prognóstico , RNA/genética
10.
Zhonghua Gan Zang Bing Za Zhi ; 27(7): 505-510, 2019 Jul 20.
Artigo em Chinês | MEDLINE | ID: mdl-31357775

RESUMO

Objective: To investigate the diagnostic value of serum α-enolase (ENO1) in the primary hepatocellular carcinoma. Methods: From May 2012 to March 2017, 163 cases with liver diseases who met the inclusion and exclusion criteria were admitted to the Infectious Diseases Department of the General Hospital of Ningxia Medical University. Among them, 28 cases were of chronic hepatitis B (CHB), 31 cases with liver cirrhosis (LC), 104 cases with hepatocellular carcinoma (HCC), and 18 healthy volunteers (NC). Patient data and serum samples were collected and liver disease related indicators were measured to detect ENO1 levels with enzyme-linked immunosorbent assay (ELISA). The measured indicators were expressed in median. Mann-Whitney U nonparametric test was used to analyze the differences between the data. A Spearman's correlation analysis was used for bivariate correlation analysis. The sensitivity and specificity of ENO1 and alpha-fetoprotein in the diagnosis of liver cancer were analyzed by ROC curve. Results: Serum level of ENO1 in CHB group, LC group and HCC group was significantly higher than normal group. Serum level of ENO1 in HCC group was higher than CHB group (P = 0.001) and LC group (P < 0.01). Area under the curve (AUC) for serum ENO1 and alpha-fetoprotein were 0.782 (cut-off value 75.96, P = 0.000 1) and 0.800 (cut-off value 27.02, P = 0.000 1), respectively. There was a positive correlation between ENO1 and AFP (P = 0.001). The combined detection had significantly improved the detection efficiency (AUC = 0.835). Serum ENO1 was statistically significant (P < 0.05) in HCC tumor size (AUC = 0.663), tumor metastasis (AUC = 0.681), TNM stage (AUC = 0.710, stage I vs. II), and Edmondson grade (AUC = 0.685) (P < 0.05) and the elevated levels of ENO1 had significantly reduced (P < 0.05) the survival time. Conclusion: ENO1 can be a new candidate marker for the diagnosis of early stage HCC and its progression.


Assuntos
Biomarcadores Tumorais/sangue , Carcinoma Hepatocelular/diagnóstico , Proteínas de Ligação a DNA/sangue , Neoplasias Hepáticas/diagnóstico , Fosfopiruvato Hidratase/sangue , Proteínas Supressoras de Tumor/sangue , Carcinoma Hepatocelular/sangue , Estudos de Casos e Controles , Humanos , Cirrose Hepática , Neoplasias Hepáticas/sangue , Gradação de Tumores , Estadiamento de Neoplasias , Curva ROC , Taxa de Sobrevida , alfa-Fetoproteínas/análise
11.
Zhonghua Gan Zang Bing Za Zhi ; 27(7): 511-515, 2019 Jul 20.
Artigo em Chinês | MEDLINE | ID: mdl-31357776

RESUMO

Objective: To comparatively study intrahepatic cholangiocarcinoma (ICC) and hepatocellular carcinoma (HCC) with reference to clinical features and prognosis in Chinese Han population. Methods: 699 cases of HCC and 170 cases of ICC confirmed by surgical pathological files from 2009 to 2010 were included and followed-up. The differences in demographic characteristics, hepatitis B virus infection, clinical characteristics, biochemical indexes, tumor markers and prognosis of HCC and ICC were analyzed retrospectively by means of paired t-test, analysis of variance, chi-square test and Pearson's correlation coefficient. Results: Among 869 cases of primary liver cancer, HCC and ICC accounted for 80.43% and 19.57%. The old aged (P < 0.001) male incidence of HCC was higher than that of ICC (P < 0.001). The infection rates of hepatitis B virus were 89.84% and 35.88% in HCC and ICC, respectively, and the infection rates of hepatitis B, serum HBsAg postive rate and DNA account in HCC were higher than ICC (P < 0.001). The incidence of liver cirrhosis and hepatic schistosomiasis in HCC was also significantly different from that in ICC (both P < 0.01). Pearson's correlation analysis showed that there was a significant negative correlation between HCC or ICC tumor type and hepatic schistosomiasis (r = -0.018, P < 0.001), and there was a significant positive correlation between HCC and hepatic cirrhosis (r = 0.179, P < 0.001, and r = 0.528, P < 0.001, respectively). However, the proportion of cirrhosis and schistosomiasis in hepatitis B positive ICC cases was not significantly different from that in HCC cases (P > 0.05). Among the biochemical indicators, there were significant differences between HCC and ICC in the abnormal rate of ALT(P < 0.01), AST(P < 0.05), ALP (P < 0.01), GGT (P < 0.01) and TBIL (P < 0.01) while there was no significant difference between ALB and pre-ALB (P > 0.05) in HCC and ICC groups. The content and abnormal rate of alpha-fetoprotein were higher in HCC (P < 0.01), while the content and abnormal rate of carcinoembryonic antigen and carbohydrate antigen 19-9 were higher in ICC (P < 0.01). The 10-year survival rate and median survival time (46.92% and 80.3 months) of HCC were higher than those of ICC (12.57% and 12.4 months) (P < 0.01). Conclusion: In the study population, compared with ICC cases, the old aged male HCC cases are more common and has higher infection rate of hepatitis B virus and cirrhosis, but liver schistosomiasis is less common. The inflammatory damage, secretion and metabolic function of HCC were different from that of ICC cases, while the synthetic reserve function was similar to that of ICC and the prognosis of HCC cases was significantly better. The incidence of cirrhosis and schistosomiasis in ICC cases with positive hepatitis B virus infection was not significantly different from that of HCC cases.


Assuntos
Carcinoma Hepatocelular/diagnóstico , Carcinoma Hepatocelular/patologia , Colangiocarcinoma/diagnóstico , Colangiocarcinoma/patologia , Neoplasias Hepáticas/diagnóstico , Neoplasias Hepáticas/patologia , Idoso , Neoplasias dos Ductos Biliares/diagnóstico , Neoplasias dos Ductos Biliares/patologia , Humanos , Masculino , Prognóstico , Estudos Retrospectivos
12.
Analyst ; 144(16): 4858-4864, 2019 Aug 21.
Artigo em Inglês | MEDLINE | ID: mdl-31294738

RESUMO

An enzyme-free electrochemical aptasensing platform based on a graphene oxide nanosheet-modified gold-disk electrode was developed for the voltammetric detection of alpha-fetoprotein (AFP) in hepatocellular carcinoma by using a Prussian blue nanoparticle (PBNP)-labeled aptamer. The electroactive PBNP, a typical signal-generation tag, was utilized for the labeling of the aminated AFP aptamer by using covalent conjugation. The electrochemical sensing platform was prepared in a simple manner on the basis of a π-π stacking reaction between the immobilized graphene oxide and the PBNP-labeled AFP aptamer. Upon target AFP introduction, the analyte reacted with the aptamer, thus resulting in the dissociation of the PBNP from the nanosheets. In the presence of DNase I, the newly formed AFP/aptamer-PBNP complex was cleaved to release target AFP, which could react again with the aptamer on the nanosheets, thereby causing target recycling. During this process, the cleaved PBNP-aptamer was far away from the electrode to decrease the voltammetric signal. Under optimum conditions, the voltammetric peak current of the modified electrode decreased with the increment of the target AFP concentration within the linear range of 0.01-300 ng mL-1 at a low detection limit of 6.3 pg mL-1. The precision and reproducibility of the aptasensing protocol were acceptable (CV: <15% for intra-assay and inter-assay). Other possible nontarget biomarkers did not interfere significantly with the voltammetric signal of this system. Human serum samples containing target AFP were assayed with electrochemical aptasensing and a commercial human AFP ELISA kit, and gave well-matched results from these two methods. Importantly, our strategy provides a new horizon for the determination of disease-related proteins.


Assuntos
Carcinoma Hepatocelular/diagnóstico , Ferrocianetos/química , Grafite/química , Neoplasias Hepáticas/diagnóstico , Nanopartículas/química , alfa-Fetoproteínas/análise , Técnicas Biossensoriais , Carcinoma Hepatocelular/química , Técnicas Eletroquímicas , Eletrodos , Ouro/química , Humanos , Limite de Detecção , Neoplasias Hepáticas/química , Sensibilidade e Especificidade
13.
Toxicol Lett ; 314: 75-81, 2019 Oct 10.
Artigo em Inglês | MEDLINE | ID: mdl-31284020

RESUMO

Aflatoxin is a fungal secondary metabolite with high toxicity that is capable of contaminating various types of food crops. It has been identified as a Group 1 human carcinogen by the International Agency for Research on Cancer. Chronic aflatoxin exposure has caused worldwide concern as a matter of public food safety. Peanuts and peanut products are the major sources of aflatoxin exposure. Therefore, some reduction interventions have been developed to minimize contamination throughout the peanut production chain. The purpose of this study is to estimate the efficacy of interventions in reducing the health impact of hepatocellular carcinoma caused by aflatoxin contamination in peanuts. The estimated total Disability-Adjusted Life Years (DALYs) were calculated using FDA-iRISK software. Six aflatoxin reduction strategies were evaluated, including good agricultural practice (GAP), biocontrol, Purdue Improved Crop Storage packaging, basic processing, ozonolysis, and ultraviolet irradiation. The results indicated that basic processing could prevent huge public health loss of 4,079.7-21,833 total DALYs per year. In addition, GAP and biocontrol were both found to be effective strategies in the farm field. Meanwhile, the other three interventions had limited effectiveness in reducing total DALYs. In conclusion, this study could help farmers, processing plants, and government policy makers to alleviate aflatoxin contamination issues in the peanut production chain.


Assuntos
Aflatoxinas/efeitos adversos , Arachis/microbiologia , Carcinoma Hepatocelular/prevenção & controle , Produtos Agrícolas/microbiologia , Exposição Dietética/efeitos adversos , Exposição Dietética/prevenção & controle , Microbiologia de Alimentos/métodos , Doenças Transmitidas por Alimentos/prevenção & controle , Neoplasias Hepáticas/prevenção & controle , Anos de Vida Ajustados por Qualidade de Vida , Agentes de Controle Biológico , Carcinoma Hepatocelular/diagnóstico , Carcinoma Hepatocelular/epidemiologia , Efeitos Psicossociais da Doença , Avaliação da Deficiência , Manipulação de Alimentos/métodos , Armazenamento de Alimentos , Doenças Transmitidas por Alimentos/diagnóstico , Doenças Transmitidas por Alimentos/epidemiologia , Humanos , Neoplasias Hepáticas/diagnóstico , Neoplasias Hepáticas/epidemiologia , Ozônio/química , Fatores de Proteção , Medição de Risco , Fatores de Risco , Fatores de Tempo , Raios Ultravioleta
15.
Cancer Immunol Immunother ; 68(8): 1223-1233, 2019 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-31201473

RESUMO

Plasmacytoid dendritic cells (pDCs) are present in various primary and metastatic human neoplasms; however, their clinical significance in hepatocellular carcinoma (HCC) is unclear. In this study, we investigated the distribution, prognostic value, and potential function of pDCs in HCC patients undergoing curative resection. We performed immunohistochemical analyses of whole tumor sections from 224 patients to assess the expression of BDCA2, CD3, CD4, CD8, Foxp3, granzyme B, IL-17, and CD34. The findings were validated using tissue microarrays from another two independent cohorts totaling 841 HCC patients undergoing curative resection. Our results demonstrated that high numbers of BDCA2+ pDCs within tumors correlated with high alpha-fetoprotein levels, greater vascular invasion, advanced tumor-node-metastasis stage, shorter overall survival, and a higher recurrence rate. However, patient outcomes were not associated with pDCs in peritumoral stromal or nontumor tissues. Furthermore, an increase in intratumoral pDCs was associated with increased intratumoral infiltration of Foxp3+ regulatory T cells and IL-17-producing cells and correlated with tumor vascular density. Univariate and multivariate analyses revealed that the presence of intratumoral pDCs alone or in combination with regulatory T and/or IL-17-producing cells was an independent predictor of time to recurrence and overall survival. In conclusion, our study demonstrated that intratumoral infiltration by pDCs is a novel indicator for poor prognosis in patients with HCC, possibly through the induction of an immune tolerogenic and inflammatory tumor microenvironment comprising regulatory T and IL-17-producing cells. An assessment of the combination of these cells represents a superior predictor of patient outcome.


Assuntos
Carcinoma Hepatocelular/diagnóstico , Células Dendríticas/imunologia , Interleucina-17/metabolismo , Neoplasias Hepáticas/diagnóstico , Linfócitos T Reguladores/imunologia , Adulto , Idoso , Carcinoma Hepatocelular/imunologia , Carcinoma Hepatocelular/mortalidade , Progressão da Doença , Feminino , Seguimentos , Fatores de Transcrição Forkhead/metabolismo , Hepatectomia , Humanos , Lectinas Tipo C/metabolismo , Neoplasias Hepáticas/imunologia , Neoplasias Hepáticas/mortalidade , Masculino , Glicoproteínas de Membrana/metabolismo , Pessoa de Meia-Idade , Metástase Neoplásica , Prognóstico , Receptores Imunológicos/metabolismo , Análise de Sobrevida , alfa-Fetoproteínas/metabolismo
16.
Artigo em Chinês | MEDLINE | ID: mdl-31245960

RESUMO

OBJECTIVE: To screen genes associated with poor prognosis of hepatocellular carcinoma (HCC) and to explore the clinical significance of these genes. METHODS: The proper expression profile data of HCC was obtained from the Gene Expression Omnibus (GEO) database, and the differentially expressed genes (DEGs) were identified by differential expression analysis. The DAVID and String database were used for function enrichment analysis and to construct the protein-protein interaction (PPI) network respectively. The Cancer Genome Atlas (TCGA) database and the Cox Proportional Hazard Model were used for prognosis analysis of the DEGs. RESULTS: A eligible human HCC data set (GSE84402) met the requirements. A total of 1141 differentially expressed genes were identified, including 720 up-regulated and 421 down-regulated genes. The results of function enrichment analysis and PPI network performed that CDK1、CDC6、CCNA2、CHEK1、CENPE 、PIK3R1、RACGAP1、BIRC5、KIF11 and CYP2B6 were prognosis key genes. And the prognosis analysis showed that the expressions of CDC6、PIK3R1、KIF11 and RACGAP1 were increased, and the expression of CENPE was decreased, which was closely related to prognosis of HCC. CONCLUSION: CDC6、CENPE、PIK3R1、KIF11 and RACGAP1 may be closely related to poor prognosis of HCC, and can be used as molecular biomarkers for future research of HCC prognosis.


Assuntos
Carcinoma Hepatocelular , Biologia Computacional , Genes Neoplásicos , Neoplasias Hepáticas , Carcinoma Hepatocelular/diagnóstico , Carcinoma Hepatocelular/genética , Quinase 1 do Ponto de Checagem , Regulação para Baixo , Perfilação da Expressão Gênica , Humanos , Neoplasias Hepáticas/diagnóstico , Neoplasias Hepáticas/genética , Prognóstico , Regulação para Cima
17.
J Biochem ; 166(3): 271-279, 2019 Sep 01.
Artigo em Inglês | MEDLINE | ID: mdl-31157375

RESUMO

Hepatocellular carcinoma (HCC) is one of the leading causes of cancer-related death worldwide. miR-484 is previously reported to be a crucial modulator during the process from precancerous lesion to cancer. Tumour suppressor candidate 5 (TUSC5) is a potential tumour suppressor, but its expression and function in HCC are obscure. In this study, we aimed to explore the roles of miR-484 and TUSC5 in HCC, and clarify the relationship between them. We demonstrated that miR-484 was significantly up-regulated in HCC, while TUSC5 was down-regulated. TUSC5 was validated as the target gene of miR-484 and both of them were associated with the prognosis of HCC patients. miR-484 mimics markedly promoted the malignant phenotypes while TUSC5 plasmid had the opposite effect. In conclusion, miR-484/TUSC5 is potential diagnostic biomarkers and therapy targets for HCC.


Assuntos
Biomarcadores Tumorais/metabolismo , Carcinoma Hepatocelular/metabolismo , Neoplasias Hepáticas/metabolismo , Proteínas de Membrana/metabolismo , MicroRNAs/metabolismo , Proteínas Supressoras de Tumor/metabolismo , Biomarcadores Tumorais/análise , Biomarcadores Tumorais/genética , Carcinoma Hepatocelular/diagnóstico , Linhagem Celular Tumoral , Feminino , Humanos , Neoplasias Hepáticas/diagnóstico , Masculino , Proteínas de Membrana/análise , Proteínas de Membrana/genética , MicroRNAs/análise , MicroRNAs/genética , Pessoa de Meia-Idade , Proteínas Supressoras de Tumor/análise , Proteínas Supressoras de Tumor/genética
18.
Artif Cells Nanomed Biotechnol ; 47(1): 1908-1916, 2019 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-31072138

RESUMO

INTRODUCTION: Hepatocellular carcinoma (HCC) ranks fourth in global cancer mortality, accounting for 8.2% of all cancer deaths. Early detection of HCC has a significant impact on clinical outcomes. The aim of this study was to identify blood-based biomarkers which are HCC-specific. METHODS: Comprehensive gene expression raw data of purified RNA of peripheral blood mononuclear cells (PBMC) was downloaded from GEO and was then analyzed. Differentially expressed genes (DEGs) in HCC were screened and the method of weighted gene co-expression network analysis was applied to identify candidate blood-based biomarkers associated with HCC. RESULTS: Three modules closely related to HCC were screened using WGCNA. Nuclear localization signal (NLS)-bearing protein import into nucleus biological process was the most significant enriched physiological process identified by MCODE, and 3 genes (DICER1, GMPS and NCOR1) were selected as biomarkers. CONCLUSION: In our study, three novel blood-based HCC-specific diagnostic biomarkers for human hepatocellular carcinoma were identified. These findings may contribute to the non-invasive detection of early HCC patients.


Assuntos
Biomarcadores Tumorais/sangue , Carcinoma Hepatocelular/sangue , Carcinoma Hepatocelular/diagnóstico , Biologia Computacional , Neoplasias Hepáticas/sangue , Neoplasias Hepáticas/diagnóstico , Carcinoma Hepatocelular/genética , Carcinoma Hepatocelular/metabolismo , Análise por Conglomerados , Perfilação da Expressão Gênica , Humanos , Estimativa de Kaplan-Meier , Neoplasias Hepáticas/genética , Neoplasias Hepáticas/metabolismo , Mapeamento de Interação de Proteínas
19.
World J Gastroenterol ; 25(15): 1890-1898, 2019 Apr 21.
Artigo em Inglês | MEDLINE | ID: mdl-31057302

RESUMO

BACKGROUND: Exosomes contain proteins, lipids, and biological molecules such as DNA and RNA. Nucleic acids in exosomes are a group of molecules that can act as biomarkers. Currently, there are many reports on exosomal microRNAs, which are ideal biomarkers for the early diagnosis of cancer. However, there are few reports on the role of exosomal microRNAs in the diagnosis and prognosis of hepatocellular carcinoma (HCC). AIM: To understand the mechanism of exosomal microRNA-224 (miR-224) in the development of HCC and evaluate its diagnostic and prognostic value. METHODS: Cell culture and transfection of exosomal miRNA-224, real-time quantitative PCR, luciferase reporter assay, and other methods were used to find new biomarkers related to the development of HCC that can be used to diagnose HCC and predict HCC prognosis. RESULTS: By targeting glycine N-methyltransferase, incubating exosomes with miR-224 mimic resulted in a significant increase in cell proliferation compared to that of the control group, while incubation with the miR-224 inhibitor significantly reduced cell proliferation. The same results were obtained for the cell invasion assay. Serum exosomal miR-224 did have some ability to differentiate patients with HCC from healthy controls, with an area under the curve of 0.910, and HCC patients with higher serum exosomal miR-224 expression had lower overall survival. CONCLUSION: Exosomal miR-224 is a tumor promotor and can be a marker of diagnosis and prognosis of HCC patients, however, its ability to distinguish liver diseases needs further verification.


Assuntos
Biomarcadores Tumorais/metabolismo , Carcinoma Hepatocelular/genética , Regulação Neoplásica da Expressão Gênica , Glicina N-Metiltransferase/genética , MicroRNAs/metabolismo , Regiões 3' não Traduzidas/genética , Adulto , Idoso , Idoso de 80 Anos ou mais , Biomarcadores Tumorais/sangue , Biomarcadores Tumorais/genética , Carcinogênese/genética , Carcinoma Hepatocelular/sangue , Carcinoma Hepatocelular/diagnóstico , Carcinoma Hepatocelular/mortalidade , Linhagem Celular Tumoral , Proliferação de Células/genética , Exossomos/metabolismo , Feminino , Glicina N-Metiltransferase/metabolismo , Humanos , Estimativa de Kaplan-Meier , Neoplasias Hepáticas/sangue , Neoplasias Hepáticas/diagnóstico , Neoplasias Hepáticas/genética , Neoplasias Hepáticas/mortalidade , Masculino , MicroRNAs/sangue , MicroRNAs/genética , Pessoa de Meia-Idade , Prognóstico
20.
Life Sci ; 228: 128-134, 2019 Jul 01.
Artigo em Inglês | MEDLINE | ID: mdl-31054270

RESUMO

AIMS: Forkhead box (FOX) proteins constitute a huge family of transcriptional regulators, which are involved in a wide range of cancers. FOXK1 is a little studied member of FOXK subfamily. This study aimed to investigate the potential prognostic value of FOXK1 in human hepatocellular carcinoma (HCC) and explore potential underlying mechanisms. MAIN METHODS: We performed bioinformatic analyses to evaluate the prognostic value of FOXK1 expression in human HCC and to reveal the underlying mechanism by which FOXK1 regulates HCC. RT-PCR, FACS analysis and sphere formation assay were carried out to investigate the role of FOXK1 in regulating liver cancer stem cells. KEY FINDINGS: Our results demonstrated that FOXK1 was overexpressed in human HCC and positively correlated with cancer progression. DNA hypomethylation and gene copy number variation contributed to the overexpression of FOXK1. Importantly, high FOXK1 expression was associated with both low overall survival probability (OS) and low relapse free survival probability (RFS) of HCC patients. Intriguingly, we found that high FOXK1 expression was correlated with activation of stem cell-regulating pathways in human HCC. Knockdown of FOXK1 resulted in downregulation of the cancer stem cell marker EpCAM and ALDH1 and decreased sphere-forming ability of hepatocellular carcinoma cells. SIGNIFICANCE: Overall, our study identified FOXK1 as a new biomarker for prognosis of HCC patients and revealed its role in regulating stemness of hepatocellular carcinoma cells.


Assuntos
Carcinoma Hepatocelular/genética , Fatores de Transcrição Forkhead/genética , Neoplasias Hepáticas/genética , Regulação para Cima , Adulto , Idoso , Carcinoma Hepatocelular/diagnóstico , Carcinoma Hepatocelular/patologia , Metilação de DNA , Feminino , Dosagem de Genes , Regulação Neoplásica da Expressão Gênica , Células Hep G2 , Humanos , Neoplasias Hepáticas/diagnóstico , Neoplasias Hepáticas/patologia , Masculino , Pessoa de Meia-Idade , Prognóstico , Análise de Sobrevida
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