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1.
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
2.
J Enzyme Inhib Med Chem ; 34(1): 1287-1297, 2019 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-31288582

RESUMO

Inhibition of NF-κB signalling has been demonstrated as a therapeutic option in treating inflammatory diseases and cancers. Herein, we synthesized novel dissymmetric 3,5-bis(arylidene)-4-piperidones (BAPs, 83-102) and characterized fully. MTT and ELISA assay were performed to screen the anti-hepatoma and anti-inflammation properties. 96 showed the most potential bioactivity. 96 could promote HepG2 apoptosis through up-regulating the expression of C-Caspase-3 and Bax, down-regulating the expression of Bcl-2, while markedly inhibit LPS or TNF-α-induced activation of NF-κB through both inhibiting the phosphorylation of IκBα and p65, and preventing the p65 nuclear translocation to exhibit both anti-hepatoma and anti-inflammatory activities. Molecular docking verified that simulated 96 can effectively bond to the active site of Bcl-2 and NF-κB/p65 proteins. 96 inhibited xenografts growth by reducing the expression of TNF-α and Bcl-2 in the tumour tissue. This study suggested that 96 could be developed as a potential multifunctional agent for treatment of inflammatory diseases and cancers.


Assuntos
Anti-Inflamatórios/farmacologia , Antineoplásicos/farmacologia , Carcinoma Hepatocelular/prevenção & controle , Inflamação/prevenção & controle , Neoplasias Hepáticas/prevenção & controle , NF-kappa B/metabolismo , Apoptose/efeitos dos fármacos , Carcinoma Hepatocelular/patologia , Linhagem Celular , Linhagem Celular Tumoral , Humanos , Neoplasias Hepáticas/patologia , Simulação de Acoplamento Molecular
3.
Toxicol Lett ; 313: 1-10, 2019 Oct 01.
Artigo em Inglês | MEDLINE | ID: mdl-31170421

RESUMO

The constitutive androstane receptor(CAR) activation is connected with mitogenic effects leading to liver hyperplasia and tumorigenesis in rodents. CAR activators, including phenobarbital, are considered rodent non-genotoxic carcinogens. Recently, trans-3,4,5,4´-tetramethoxystilbene(TMS), a potential anticancer drug (DMU-212), have been shown to alleviate N-nitrosodiethylamine/phenobarbital-induced liver carcinogenesis. We studied whether TMS inhibits mouse Car to protect from the PB-induced tumorigenesis. Unexpectedly, we identified TMS as a murine CAR agonist in reporter gene experiments, in mouse hepatocytes, and in C57BL/6 mice in vivo. TMS up-regulated Car target genes Cyp2b10, Cyp2c29 and Cyp2c55 mRNAs, but down-regulated expression of genes involved in gluconeogenesis and lipogenesis. TMS did not change or down-regulate genes involved in liver proliferation or apoptosis such as Mki67, Foxm1, Myc, Mcl1, Pcna, Bcl2, or Mdm2, which were up-regulated by another Car ligand TCPOBOP. TMS did not increase liver weight and had no significant effect on Ki67 and Pcna labeling indices in mouse liver in vivo. In murine hepatic AML12 cells, we confirmed a Car-independent proapoptotic effect of TMS. We conclude that TMS is a Car ligand with limited effects on hepatocyte proliferation, likely due to promoting apoptosis in mouse hepatic cells, while controlling Car target genes involved in xenobiotic and endobiotic metabolism.


Assuntos
Anticarcinógenos/farmacologia , Proliferação de Células/efeitos dos fármacos , Hepatócitos/efeitos dos fármacos , Neoplasias Hepáticas/prevenção & controle , Fígado/efeitos dos fármacos , Receptores Citoplasmáticos e Nucleares/agonistas , Estilbenos/farmacologia , Animais , Anticarcinógenos/metabolismo , Apoptose/efeitos dos fármacos , Hidrocarboneto de Aril Hidroxilases/genética , Hidrocarboneto de Aril Hidroxilases/metabolismo , Sítios de Ligação , Família 2 do Citocromo P450/genética , Família 2 do Citocromo P450/metabolismo , Regulação Enzimológica da Expressão Gênica/efeitos dos fármacos , Gluconeogênese/efeitos dos fármacos , Gluconeogênese/genética , Células Hep G2 , Hepatócitos/metabolismo , Hepatócitos/patologia , Humanos , Lipogênese/efeitos dos fármacos , Lipogênese/genética , Fígado/metabolismo , Neoplasias Hepáticas/enzimologia , Neoplasias Hepáticas/genética , Neoplasias Hepáticas/patologia , Masculino , Camundongos Endogâmicos C57BL , Simulação de Acoplamento Molecular , Ligação Proteica , Piridinas/farmacologia , Receptores Citoplasmáticos e Nucleares/genética , Receptores Citoplasmáticos e Nucleares/metabolismo , Transdução de Sinais/efeitos dos fármacos , Esteroide Hidroxilases/genética , Esteroide Hidroxilases/metabolismo , Estilbenos/metabolismo
4.
Chem Biol Interact ; 308: 377-384, 2019 Aug 01.
Artigo em Inglês | MEDLINE | ID: mdl-31150631

RESUMO

Among the primary neoplasias that affect the liver, hepatocellular carcinoma (HCC) is the most frequent and the third leading cause of death related to cancer. Several risk factors predispose individuals to HCC such as nonalcoholic fatty liver disease (NAFLD), whose incidence has significantly increased worldwide. ß-ionone (ßI) isoprenoid is a known chemopreventive of hepatocarcinogenesis. However, the effects of this compound on NAFLD isolated or in association with hepatocarcinogenesis have not yet been evaluated. A high-fat emulsion administered for 6 weeks resulted in NAFLD in male rats, and oral treatment with ßI during this period significantly attenuated its development. Moreover, the presence of NAFLD potentiated hepatocarcinogenesis induced by the resistant hepatocyte (RH) model in these animals by increasing the number and percentage of the liver section area occupied by placental glutathione S-transferase (GST-P)-positive persistent preneoplastic lesions (pPNLs), that are thought to evolve into HCC. This indicates that this NAFLD/RH protocol is suitable for studies of the influence of NAFLD on the HCC development. Therefore, here we also investigated the chemopreventive effect of ßI under these two associated conditions. In this context, ßI reduced the number and percentage of the liver section area occupied by pPNLs, as well as cell proliferation and the number of oval cells, which are considered potential targets for the development of HCC. Thus, ßI presents not only a promising inhibitory effect on NAFLD isolated but also chemopreventive activity when it is associated with hepatocarcinogenesis.


Assuntos
Carcinoma Hepatocelular/prevenção & controle , Neoplasias Hepáticas/prevenção & controle , Hepatopatia Gordurosa não Alcoólica/prevenção & controle , Norisoprenoides/uso terapêutico , Administração Oral , Animais , Apoptose/efeitos dos fármacos , Carcinoma Hepatocelular/induzido quimicamente , Carcinoma Hepatocelular/patologia , Proliferação de Células/efeitos dos fármacos , Glutationa Transferase/metabolismo , Fígado/efeitos dos fármacos , Fígado/metabolismo , Fígado/patologia , Neoplasias Hepáticas/patologia , Masculino , Hepatopatia Gordurosa não Alcoólica/induzido quimicamente , Hepatopatia Gordurosa não Alcoólica/patologia , Norisoprenoides/farmacologia , Estresse Oxidativo/efeitos dos fármacos , Ratos , Ratos Wistar , Triglicerídeos/análise
5.
BMC Cancer ; 19(1): 511, 2019 May 29.
Artigo em Inglês | MEDLINE | ID: mdl-31142283

RESUMO

BACKGROUND: It has been proved that nucleos(t) ide analogues (NAs) therapy could improve underlying liver disease and reduce the incidence of hepatitis B virus (HBV)-related hepatocellular carcinoma (HCC). However, the difference of effectiveness in reducing HCC occurrence between tenofovir (TDF) and enticavir (ETV), two first-line NAs drugs, is still little known. This meta analysis aims to assess the efficacy in reducing incidence of HCC comparing tenofovir monotherapy with entecavir monotherapy among chronic hepatitis B (CHB) patients by analyzing their long-term clinical outcomes. METHODS: Databases including PubMed, Embase, Cochrane Central Register of Controlled Trial, and ISI Web of Science were fully investigated according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. For the included articles, two of the authors independently extracted and confirmed relevant data. Review Manager software (RevMan 5.3) was using for meta analysis. RESULTS: Seven articles with 3698 patients were finally included in this research, 1574 in tenofovir group and 2124 in entecavir group. For meta analysis, the incidence of HCC was significantly lower among the tenofovir group than entecavir group [rate ratio (95% CI) of 0.66 (0.49, 0.89), P = 0.008], while there was no statistical significance in incidence of death or transplantation [rate ratio (95% CI) of 0.78 (0.55, 1.13), P = 0.19], encephalopathy [risk ratio (95% CI) of 0.72 (0.45, 1.13), P = 0.15] or variceal bleeding [risk ratio (95% CI) of 0.71 (0.34, 1.50), P = 0.37] between the two groups. CONCLUSION: There is a better effect of tenofovir in reducing HCC incidence than entecavir, which indicates tenofovir should be used more widely while treating chronic hepatitis B patients. However before applying, randomized controlled trial and large prospective cohort study should be performed in the future.


Assuntos
Carcinoma Hepatocelular/epidemiologia , Guanina/análogos & derivados , Hepatite B Crônica/tratamento farmacológico , Neoplasias Hepáticas/epidemiologia , Tenofovir/uso terapêutico , Adulto , Carcinoma Hepatocelular/etiologia , Carcinoma Hepatocelular/prevenção & controle , Ensaios Clínicos Controlados como Assunto , Feminino , Guanina/uso terapêutico , Hepatite B Crônica/complicações , Humanos , Incidência , Neoplasias Hepáticas/etiologia , Neoplasias Hepáticas/prevenção & controle , Masculino , Pessoa de Meia-Idade , Estudos Prospectivos , Estudos Retrospectivos
6.
Indian J Med Res ; 149(1): 9-17, 2019 01.
Artigo em Inglês | MEDLINE | ID: mdl-31115369

RESUMO

Hepatocellular carcinoma (HCC) is the sixth most common cancer in world and third largest cause of cancer-related deaths. The last few decades have witnessed the emergence of non-viral causes of HCC, the most important being non-alcoholic fatty liver disease (NAFLD). NAFLD ranges from simple steatosis in the absence of excessive alcohol intake to non-alcoholic steatohepatitis (NASH) with or without cirrhosis. About 3-15 per cent of the obese patients with NASH progress to cirrhosis and about 4-27 per cent of NASH with cirrhosis patients transform to HCC. It is also known that HCC can develop de novo in patients with NASH without the presence of cirrhosis. Yearly cumulative incidence of NASH-related HCC is low (2.6%) compared to four per cent of viral-HCC. NAFLD has been associated with risk factors such as metabolic syndrome, insulin resistance, altered gut flora and persistent inflammation. Due to alarming rise in metabolic diseases, both in the developing as well as the developed world, it is expected that the incidence of NAFLD/NASH-HCC would rise manifold in future. No definite guidelines have been drawn for surveillance and management of NAFLD/NASH-associated HCC. It is thus important to discuss the entity of HCC in NAFLD at length with special focus on its epidemiology, risk factors, pathophysiology, diagnosis, clinical presentation and prevention.


Assuntos
Carcinoma Hepatocelular/epidemiologia , Cirrose Hepática/epidemiologia , Neoplasias Hepáticas/epidemiologia , Hepatopatia Gordurosa não Alcoólica/epidemiologia , Carcinoma Hepatocelular/complicações , Carcinoma Hepatocelular/genética , Carcinoma Hepatocelular/prevenção & controle , Humanos , Resistência à Insulina/genética , Cirrose Hepática/complicações , Cirrose Hepática/genética , Cirrose Hepática/prevenção & controle , Neoplasias Hepáticas/complicações , Neoplasias Hepáticas/genética , Neoplasias Hepáticas/prevenção & controle , Síndrome Metabólica/complicações , Síndrome Metabólica/epidemiologia , Síndrome Metabólica/genética , Síndrome Metabólica/patologia , Hepatopatia Gordurosa não Alcoólica/complicações , Hepatopatia Gordurosa não Alcoólica/genética , Hepatopatia Gordurosa não Alcoólica/prevenção & controle , Fatores de Risco
7.
J BUON ; 24(1): 158-162, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-30941965

RESUMO

PURPOSE: The present study explored the potential of microwaves on membrane fluidity changes in diethylnitrosamine (DEN) induced hepatocellular carcinoma (HCC), in vivo. METHODS: Rats were segregated into four groups: normal control, DEN-treated, microwave-treated, DEN+microwave-treated. Brush border membranes (BBM) were isolated from the rats and, using the membrane extrinsic fluorophore pyrene, we assessed the viscosities as well as fluidity parameters. RESULTS: DEN treatment resulted in a significant rise in lipid peroxidation (LPO). Reduced glutathione levels (GSH) and the activities of glutathione reductase (GR), glutathione transferase (GST), superoxide dismutase (SOD), catalase (CAT) and glutathione peroxidase (GPx) were found to be significantly decreased following DEN treatment. On the other hand, microwave treatment in DEN-treated rats resulted in a significant decrease in the levels of lipid peroxidation but caused a significant rise in the levels of GSH as well in the activities of GR, GST, SOD, CAT and GPx. The results further demonstrated a marked decrease in membrane microviscosity following DEN treatment. On the other hand, a significant increase was observed in the excimer/monomer ratio and fluidity parameter of DEN-treated rats when compared to normal control rats. However, the alterations in membrane microviscosity and the fluidity parameters were significantly restored after microwave treatment. CONCLUSION: The study, therefore, concludes that microwave proved quite useful in the modulation of membrane stability parameters following DEN-induced hepatic cancer.


Assuntos
Membrana Celular/fisiologia , Dietilnitrosamina/toxicidade , Neoplasias Hepáticas/prevenção & controle , Fluidez de Membrana/fisiologia , Micro-Ondas/uso terapêutico , Alquilantes/toxicidade , Animais , Catalase/metabolismo , Membrana Celular/efeitos dos fármacos , Membrana Celular/efeitos da radiação , Glutationa/metabolismo , Glutationa Redutase/metabolismo , Glutationa Transferase/metabolismo , Peroxidação de Lipídeos/efeitos dos fármacos , Neoplasias Hepáticas/induzido quimicamente , Neoplasias Hepáticas/metabolismo , Masculino , Fluidez de Membrana/efeitos dos fármacos , Fluidez de Membrana/efeitos da radiação , Ratos , Ratos Wistar , Superóxido Dismutase/metabolismo
8.
BMC Complement Altern Med ; 19(1): 86, 2019 Apr 23.
Artigo em Inglês | MEDLINE | ID: mdl-31014289

RESUMO

BACKGROUND: The modified Si-Jun-Zi Decoction (SJZ), a Chinese medicine formula, is clinically used against multiple malignancies including colorectal cancer (CRC). This study aims to evaluate the effect of modified SJZ on CRC liver metastasis and identify the therapeutic mechanisms. METHODS: Human CRC cells with GFP fluorescence were transplanted into Balb/c nude mice spleens. Modified SJZ, 5-fluorouracil or the combined treatment was given for 3 weeks. CRC liver metastasis was measured by fluorescence imaging and plasma cytokines were analyzed. Furthermore, the effects of administration time and doses for the modified SJZ were investigated in nude mice. RESULTS: Modified SJZ could increase the survival rate and reduce CRC liver metastasis in the nude mice model. Plasma GM-CSF level was elevated. Three weeks of treatment with the modified SJZ at the full dose (45 g/kg) could significantly increase the number of macrophages but not neutrophils in the spleen. CONCLUSIONS: These results indicate that modified SJZ can inhibit CRC liver metastasis by activating the innate immune system, providing a complementary and alternative therapy for CRC.


Assuntos
Antineoplásicos , Neoplasias do Colo , Medicamentos de Ervas Chinesas , Neoplasias Hepáticas , Macrófagos/efeitos dos fármacos , Animais , Antineoplásicos/farmacologia , Antineoplásicos/uso terapêutico , Linhagem Celular Tumoral , Neoplasias do Colo/tratamento farmacológico , Neoplasias do Colo/patologia , Medicamentos de Ervas Chinesas/farmacologia , Medicamentos de Ervas Chinesas/uso terapêutico , Células HCT116 , Humanos , Neoplasias Hepáticas/tratamento farmacológico , Neoplasias Hepáticas/prevenção & controle , Neoplasias Hepáticas/secundário , Camundongos Endogâmicos BALB C , Camundongos Nus , Ensaios Antitumorais Modelo de Xenoenxerto
9.
J Gastrointestin Liver Dis ; 28(1): 63-71, 2019 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-30851174

RESUMO

BACKGROUND AND AIMS: Direct-acting antiviral agents (DAAs) and the risk of hepatocellular carcinoma (HCC) is controversially reported in the literature. The primary endpoints of this study were to clarify the cumulative incidence and recurrence rate of HCC after DAA treatment. The secondary endpoints were to identify the factors associated with the occurrence or recurrence of HCC after DAAs treatment. METHODS: Of 234 HCV patients, 211 with no history of HCC (no-HCC-history group) and 23 with previous treated HCC history (HCC-history group) were treated with DAAs and followed for more than 24 weeks to determine the incidence of HCC. Platelet count, albumin, α-fetoprotein (AFP) level, L3%, the FIB-4 index and APRI scores were analyzed as possible factors associated with HCC occurrence and recurrence. An intergroup comparison was made of the cumulative incidence of HCC. Cox proportional hazards regression was used to determine associations between blood test values and risk of HCC. RESULTS: The median observation period was 21 months. Cumulative incidence of HCC was higher in the HCC-history group than in the no-HCC-history group (p < 0.0001, 19.0 and 0.52 per 100 patient-years, respectively). Univariate analysis revealed platelet count, albumin, α-fetoprotein (AFP) level, AFP-L3%, and FIB-4 index and APRI scores at the end of DAA treatment as being significantly associated with occurrence/recurrence of HCC. Multivariate analysis revealed that AFP levels before and after the administration of DAAs and AFP-L3% after DAA were independently associated with the occurrence/recurrence of HCC (p = 0.045, 0.043, 0.005, respectively). CONCLUSION: The HCC occurrence rate after DAA treatment was very low, and the recurrence rate lower than that in previous interferon reports. The AFP level and AFP-L3% were identified as important factors in predicting occurrence/recurrence of HCC. Careful observation is needed when increased levels of AFP or AFP-L3% after DAAs treatment are observed.


Assuntos
Antivirais/uso terapêutico , Carcinoma Hepatocelular/prevenção & controle , Hepatite C Crônica/tratamento farmacológico , Neoplasias Hepáticas/prevenção & controle , Adulto , Idoso , Idoso de 80 Anos ou mais , Carcinoma Hepatocelular/diagnóstico por imagem , Carcinoma Hepatocelular/epidemiologia , Carcinoma Hepatocelular/virologia , Feminino , Hepatite C Crônica/diagnóstico , Hepatite C Crônica/epidemiologia , Hepatite C Crônica/virologia , Humanos , Incidência , Neoplasias Hepáticas/diagnóstico por imagem , Neoplasias Hepáticas/epidemiologia , Neoplasias Hepáticas/virologia , Masculino , Pessoa de Meia-Idade , Fatores de Proteção , Recidiva , Estudos Retrospectivos , Medição de Risco , Fatores de Risco , Fatores de Tempo , Tóquio/epidemiologia , Resultado do Tratamento , alfa-Fetoproteínas/metabolismo
10.
World J Gastroenterol ; 25(11): 1307-1326, 2019 Mar 21.
Artigo em Inglês | MEDLINE | ID: mdl-30918425

RESUMO

With the increasing number of individuals with diabetes and obesity, nonalcoholic fatty liver disease (NAFLD) is becoming increasingly prevalent, affecting one-quarter of adults worldwide. The spectrum of NAFLD ranges from simple steatosis or nonalcoholic fatty liver (NAFL) to nonalcoholic steatohepatitis (NASH). NAFLD, especially NASH, may progress to fibrosis, leading to cirrhosis and hepatocellular carcinoma. NAFLD can impose a severe economic burden, and patients with NAFLD-related terminal or deteriorative liver diseases have become one of the main groups receiving liver transplantation. The increasing prevalence of NAFLD and the severe outcomes of NASH make it necessary to use effective methods to identify NAFLD. Although recognized as the gold standard, biopsy is limited by its sampling bias, poor acceptability, and severe complications, such as mortality, bleeding, and pain. Therefore, noninvasive methods are urgently needed to avoid biopsy for diagnosing NAFLD. This review discusses the current noninvasive methods for assessing NAFLD, including steatosis, NASH, and NAFLD-related fibrosis, and explores the advantages and disadvantages of measurement tools. In addition, we analyze potential noninvasive biomarkers for tracking disease processes and monitoring treatment effects, and explore effective algorithms consisting of imaging and nonimaging biomarkers for diagnosing advanced fibrosis and reducing unnecessary biopsies in clinical practice.


Assuntos
Carcinoma Hepatocelular/prevenção & controle , Medicina Baseada em Evidências/métodos , Cirrose Hepática/prevenção & controle , Neoplasias Hepáticas/prevenção & controle , Hepatopatia Gordurosa não Alcoólica/diagnóstico , Algoritmos , Biomarcadores/análise , Biópsia/efeitos adversos , Carcinoma Hepatocelular/patologia , Progressão da Doença , Técnicas de Imagem por Elasticidade/métodos , Estudos de Viabilidade , Humanos , Fígado/diagnóstico por imagem , Fígado/patologia , Cirrose Hepática/patologia , Testes de Função Hepática/métodos , Neoplasias Hepáticas/patologia , Imagem por Ressonância Magnética , Hepatopatia Gordurosa não Alcoólica/epidemiologia , Hepatopatia Gordurosa não Alcoólica/patologia , Hepatopatia Gordurosa não Alcoólica/terapia , Prevalência , Resultado do Tratamento
11.
Drug Des Devel Ther ; 13: 611-621, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-30858692

RESUMO

Hepatocellular carcinoma (HCC), a primary liver malignancy, is one of the deadliest cancers worldwide. Despite orthotopic liver transplantation and hepatic resection representing the principal lines of treatment for this pathology, only a minority of patients can be resected owing to cirrhosis or late diagnosis. Keeping in mind the end goal of conquering these challenges, new alternative approaches have been proposed. Accumulating evidence has demonstrated that epigallocatechin-3-gallate (EGCG), the principal catechin of green tea with multiple biological properties, is able to modulate different molecular mechanisms underlying HCC, mainly through its antioxidant activity. In this article, we revise these findings reported in the literature, in order to highlight the potential roles of EGCG in the treatment of HCC. The CAMARADES criteria were applied for quality assessment of animal studies, and a narrative synthesis performed. New bits of information available for translational perspectives into clinical practice are addressed.


Assuntos
Carcinoma Hepatocelular/tratamento farmacológico , Catequina/análogos & derivados , Neoplasias Hepáticas/tratamento farmacológico , Animais , Carcinoma Hepatocelular/prevenção & controle , Catequina/uso terapêutico , Humanos , Neoplasias Hepáticas/prevenção & controle
12.
Curr Pharm Biotechnol ; 20(3): 197-214, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-30806308

RESUMO

BACKGROUND: Liver ailments are among the leading causes of death; they originate from viral infections, chronic alcoholism, and autoimmune illnesses, which may chronically be precursors of cirrhosis; furthermore, metabolic syndrome may worsen those hepatopathies or cause Non-alcoholic Fatty Liver Disease (NAFLD) that may advance to non-alcoholic steatohepatitis (NASH). Cirrhosis is the late-stage liver disease and can proceed to hepatocellular carcinoma (HCC). Pharmacological treatment options for liver diseases, cirrhosis, and HCC, are limited, expensive, and not wholly effective. The use of medicinal herbs and functional foods is growing around the world as natural resources of bioactive compounds that would set the basis for the development of new drugs. Review and Conclusion: Plant and food-derived sterols and triterpenoids (TTP) possess antioxidant, metabolic-regulating, immunomodulatory, and anti-inflammatory activities, as well as they are recognized as anticancer agents, suggesting their application strongly as an alternative therapy in some chronic diseases. Thus, it is interesting to review current reports about them as hepatoprotective agents, but also because they structurally resemble cholesterol, sexual hormones, corticosteroids and bile acids due to the presence of the steroid nucleus, so they all can share pharmacological properties through activating nuclear and membrane receptors. Therefore, sterols and TTP appear as a feasible option for the prevention and treatment of chronic metabolic-related liver diseases, cirrhosis, and HCC.


Assuntos
Carcinoma Hepatocelular/tratamento farmacológico , Neoplasias Hepáticas/tratamento farmacológico , Fígado/efeitos dos fármacos , Síndrome Metabólica/tratamento farmacológico , Fitosteróis/uso terapêutico , Triterpenos/uso terapêutico , Animais , Antioxidantes/química , Antioxidantes/farmacologia , Antioxidantes/uso terapêutico , Carcinoma Hepatocelular/metabolismo , Carcinoma Hepatocelular/prevenção & controle , Humanos , Fígado/metabolismo , Cirrose Hepática/tratamento farmacológico , Cirrose Hepática/metabolismo , Cirrose Hepática/prevenção & controle , Neoplasias Hepáticas/metabolismo , Neoplasias Hepáticas/prevenção & controle , Síndrome Metabólica/metabolismo , Síndrome Metabólica/prevenção & controle , Hepatopatia Gordurosa não Alcoólica/tratamento farmacológico , Hepatopatia Gordurosa não Alcoólica/metabolismo , Hepatopatia Gordurosa não Alcoólica/prevenção & controle , Fitosteróis/química , Fitosteróis/farmacologia , Triterpenos/química , Triterpenos/farmacologia
13.
World J Gastroenterol ; 25(6): 659-671, 2019 Feb 14.
Artigo em Inglês | MEDLINE | ID: mdl-30783370

RESUMO

Primary sclerosing cholangitis (PSC) is a rare cholestatic liver disease characterized by progressive fibroinflammatory destruction of the intra- and/or extrahepatic biliary ducts. While its features and disease course can be variable, most patients with PSC have concurrent inflammatory bowel disease and will eventually develop liver cirrhosis and end-stage liver disease, with liver transplantation representing the only potentially curative option. Importantly, PSC is associated with a significantly increased risk of malignancy compared to the general population, mainly cholangiocarcinoma, gallbladder carcinoma, hepatocellular carcinoma, and colorectal cancer, with nearly 50% of deaths in patients with PSC being due to cancer. Therefore, robust surveillance strategies are needed, though uncertainty remains regarding how to best do so. In this review, we discuss the epidemiology, prevention, and surveillance of cancers in patients with PSC. Where evidence is limited, we present pragmatic approaches based on currently available data and expert opinion.


Assuntos
Neoplasias do Sistema Biliar/etiologia , Carcinoma/epidemiologia , Colangiocarcinoma/etiologia , Colangite Esclerosante/complicações , Neoplasias do Sistema Biliar/epidemiologia , Neoplasias do Sistema Biliar/prevenção & controle , Carcinoma/etiologia , Carcinoma/prevenção & controle , Carcinoma Hepatocelular/epidemiologia , Carcinoma Hepatocelular/etiologia , Carcinoma Hepatocelular/prevenção & controle , Colangiocarcinoma/epidemiologia , Colangiocarcinoma/prevenção & controle , Neoplasias Colorretais/epidemiologia , Neoplasias Colorretais/etiologia , Neoplasias Colorretais/prevenção & controle , Detecção Precoce de Câncer/métodos , Humanos , Doenças Inflamatórias Intestinais/complicações , Neoplasias Hepáticas/epidemiologia , Neoplasias Hepáticas/etiologia , Neoplasias Hepáticas/prevenção & controle , Vigilância da População , Fatores de Risco
14.
Toxicol Appl Pharmacol ; 365: 51-60, 2019 02 15.
Artigo em Inglês | MEDLINE | ID: mdl-30625338

RESUMO

Hepatocellular carcinoma (HCC) is a lethal malignancy with few effective options for therapeutic treatment in its advanced stages. Metformin, a first-line oral agent used in the treatment of type 2 diabetes, exhibits efficacy in metabolic reprogramming fueling changes in cell growth and proliferation for multiple cancer types, including HCC. However, the molecular mechanism by which metformin delays hepatocarcinogenesis in individuals with hepatic steatosis remains rare. Here, we investigate the preventive efficacy of metformin in a rapid AKT/c-Met-triggered HCC mouse model featuring excessive levels of steatosis. Hematoxylin and eosin staining, Oil Red O staining and immunoblotting were applied for mechanistic investigations. Pharmacological and biochemical strategies were employed to illuminate molecular evidence for HCC cell lines. The results show that metformin obstructs the malignant transformation of hepatocytes in AKT/c-Met mice. Mechanistically, metformin reduces the expression of phospho-ERK (Thr202/Tyr204) and two forms of proto-oncogenes, Cyclin D1 and c-Myc, in AKT/c-Met mice. Moreover, metformin ameliorates FASN-mediated aberrant lipogenesis and HK2/PKM2-driven ATP generation in vivo. Furthermore, metformin represses the expression of FASN and HK-2 by targeting c-Myc in an AMPK-dependent manner in vitro. In addition, metformin is effective at inhibiting PKM2 expression in the presence of an AMPK inhibitor compound C, suggesting that its functioning in PKM2 is AMPK-independent. Our study experimentally validates a novel molecular mechanism by which metformin alleviates enhanced lipogenesis and high energy metabolism during hepatocarcinogenesis, indicating that metformin may serve as an agent for the prevention of HCC in patients with nonalcoholic fatty liver diseases.


Assuntos
Trifosfato de Adenosina/metabolismo , Anticarcinógenos/farmacologia , Carcinoma Hepatocelular/prevenção & controle , Transformação Celular Neoplásica/efeitos dos fármacos , Metabolismo Energético/efeitos dos fármacos , Fígado Gorduroso/tratamento farmacológico , Lipogênese/efeitos dos fármacos , Neoplasias Hepáticas/prevenção & controle , Fígado/efeitos dos fármacos , Metformina/farmacologia , Proteínas Proto-Oncogênicas c-akt/metabolismo , Proteínas Proto-Oncogênicas c-met/metabolismo , Animais , Carcinoma Hepatocelular/enzimologia , Carcinoma Hepatocelular/genética , Carcinoma Hepatocelular/patologia , Linhagem Celular Tumoral , Proliferação de Células/efeitos dos fármacos , Transformação Celular Neoplásica/genética , Transformação Celular Neoplásica/metabolismo , Transformação Celular Neoplásica/patologia , Modelos Animais de Doenças , Ácido Graxo Sintase Tipo I/metabolismo , Fígado Gorduroso/enzimologia , Fígado Gorduroso/genética , Fígado Gorduroso/patologia , Hexoquinase/metabolismo , Humanos , Fígado/enzimologia , Fígado/patologia , Neoplasias Hepáticas/enzimologia , Neoplasias Hepáticas/genética , Neoplasias Hepáticas/patologia , Camundongos , Proteínas Proto-Oncogênicas c-akt/genética , Proteínas Proto-Oncogênicas c-met/genética , Piruvato Quinase/metabolismo , Transdução de Sinais/efeitos dos fármacos
15.
Prev Chronic Dis ; 16: E08, 2019 01 24.
Artigo em Inglês | MEDLINE | ID: mdl-30676936

RESUMO

INTRODUCTION: Mongolia has the highest liver cancer incidence in the world. Hepatocellular carcinoma is the most prevalent primary liver cancer, and the most common risk factors are hepatitis B virus (HBV) or hepatitis C virus (HCV) infection. Although viral hepatitis occurs mostly in the developing world, migration of people from high prevalence countries contributes to the health outcomes of the United States. Data on Mongolian Americans is limited. The objective of this study was to estimate HBV and HCV infection prevalence among Mongolia-born immigrants living in the Washington, District of Columbia, metropolitan area. METHODS: We tested Mongolia-born immigrants for chronic hepatitis at community-based screening events from 2016 to 2017. Descriptive statistics were generated to describe the screening results. Bivariate analysis was conducted to examine the relationship between hepatitis prevalence and sociodemographic characteristics. RESULTS: Of 634 participants, most did not speak English primarily, were uninsured, and did not have a regular primary care provider. Eighty-two participants (12.9%) had chronic HBV or HCV infection after accounting for HBV and HCV co-infection. Thirty-nine (6.2%) were chronically infected with HBV, and 233 (36.8%) were susceptible to HBV. Sixty-three (9.9%) participants were positive for HCV exposure, and 45 (7.1%) had confirmed chronic HCV infection. While no sociodemographic characteristics were associated with HBV infection, age and primary spoken language (Mongolian) were significantly associated with HCV exposure. CONCLUSION: Foreign-born immigrants such as Mongolian Americans have a high prevalence of chronic viral hepatitis infection. Targeted screening, vaccination, and treatment programs can help decrease immigrant risk for developing hepatocellular carcinoma.


Assuntos
Emigrantes e Imigrantes , Hepatite B Crônica/epidemiologia , Hepatite C Crônica/epidemiologia , Adolescente , Adulto , Carcinoma Hepatocelular/etiologia , Carcinoma Hepatocelular/prevenção & controle , District of Columbia/epidemiologia , Feminino , Humanos , Neoplasias Hepáticas/etiologia , Neoplasias Hepáticas/prevenção & controle , Masculino , Pessoa de Meia-Idade , Mongólia/epidemiologia , Prevalência , Vacinação , Vacinas Virais , Adulto Jovem
16.
World J Gastroenterol ; 25(3): 282-286, 2019 Jan 21.
Artigo em Inglês | MEDLINE | ID: mdl-30686897

RESUMO

Long-term nucleos(t)ide analogue therapy in chronic hepatitis B virus (HBV) infection is effective in suppressing viral replication and reducing liver-related complications. However, HBV-related liver events can still occur in different patient sub-groups. There is emerging evidence that, similar to chronic hepatitis C virus infection, metabolic risk factors may play a role in the disease process of chronic HBV. While the mechanistic nature of metabolic-HBV interactions remains uncertain, studies in different HBV-infected populations have demonstrated that hepatic steatosis, increased body-mass index, diabetes, or a combination of different metabolic risk factors are associated with an increased risk of hepatocellular carcinoma and cirrhosis. The impact of metabolic risk factors is especially prominent in patients with quiescent virological activity, including on-treatment patients with effective viral suppression. As the proportion of on-treatment chronic HBV patients increases worldwide, longitudinal studies determining the relative risks of different metabolic parameters with respect to clinical outcomes are needed. Future studies should also determine if metabolic-directed interventions can improve disease outcomes in chronic HBV.


Assuntos
Antivirais/uso terapêutico , Vírus da Hepatite B/patogenicidade , Hepatite B Crônica/metabolismo , Fígado/patologia , Antivirais/farmacologia , Carcinoma Hepatocelular/metabolismo , Carcinoma Hepatocelular/patologia , Carcinoma Hepatocelular/prevenção & controle , Carcinoma Hepatocelular/virologia , Vírus da Hepatite B/efeitos dos fármacos , Hepatite B Crônica/tratamento farmacológico , Hepatite B Crônica/patologia , Hepatite B Crônica/virologia , Humanos , Fígado/metabolismo , Fígado/virologia , Cirrose Hepática/metabolismo , Cirrose Hepática/patologia , Cirrose Hepática/prevenção & controle , Cirrose Hepática/virologia , Neoplasias Hepáticas/metabolismo , Neoplasias Hepáticas/patologia , Neoplasias Hepáticas/prevenção & controle , Neoplasias Hepáticas/virologia , Hepatopatia Gordurosa não Alcoólica/metabolismo , Hepatopatia Gordurosa não Alcoólica/patologia , Hepatopatia Gordurosa não Alcoólica/virologia , Resultado do Tratamento , Replicação Viral/efeitos dos fármacos
17.
Nutr Res ; 61: 82-94, 2019 01.
Artigo em Inglês | MEDLINE | ID: mdl-30683441

RESUMO

Eighty percent of hepatocellular carcinoma (HCC) cases occur after cirrhosis from various etiologies. The association between diet and cancer is well accepted, but the links with cirrhosis progression and HCC risk have been poorly investigated. However, we hypothesized that diet could be a modifiable preventive factor for HCC. Thus, the aim of our study was to explore the relationships between dietary factors and the risk of HCC in a population of cirrhotic patients. A total of 582 cirrhotic patients were studied: 401 without HCC (controls) and 181 with HCC (cases). These patients were recruited between 2008 and 2012 for the "CiRCE" case-control study conducted in six French university hospitals. Information about the consumption of 208 food items and 23 nutrients were collected through a diet history questionnaire. Unconditional multivariate logistic regressions were performed for each residual food group and nutrients in tertiles. HCC patients were more often men, diabetic and older than controls. After adjustment, a significant positive association was found between HCC risk and carbonated beverages (ORTertile3vsTertile1 = 2.44 [1.17-5.09] p-trend = 0.021), total cereals (ORT3vsT1 = 1.87 [1.09-3.22] p-trend = 0.035), processed meat (ORT3vsT1 = 1.97 [1.14-3.41] p-trend = 0.028) and sodium (ORT3vsT1 = 2.00 [1.14-3.53] p-trend = 0.043). Conversely, the consumption of fiber (ORT3vsT1 = 0.49 [0.28-0.86] p-trend = 0.012), vitamin E (ORT3vsT1 = 0.52 [0.30-0.89] p-trend = 0.017), vitamin B9 (folate and folic acid) (ORT3vsT1 = 0.56 [0.33-0.95] p-trend = 0.036), manganese (ORT3vsT1 = 0.56 [0.32-0.97] p-trend = 0.038) and potassium (ORT3vsT1 = 0.44 [0.25-0.76] p-trend = 0.004) were significantly lower in HCC patients compared with cirrhotic controls. Although these findings must be confirmed in prospective studies, using dietary patterns or biological parameters, they suggest that certain dietary components may modulate HCC risk in cirrhotic patients.


Assuntos
Carcinoma Hepatocelular/prevenção & controle , Dieta , Comportamento Alimentar , Cirrose Hepática/dietoterapia , Neoplasias Hepáticas/prevenção & controle , Idoso , Carcinoma Hepatocelular/etiologia , Estudos de Casos e Controles , Diabetes Mellitus , Dieta/efeitos adversos , Ingestão de Energia , Feminino , França , Humanos , Cirrose Hepática/complicações , Neoplasias Hepáticas/etiologia , Modelos Logísticos , Masculino , Pessoa de Meia-Idade , Razão de Chances , Estudos Prospectivos , Fatores de Risco
18.
Zhonghua Gan Zang Bing Za Zhi ; 27(1): 3-5, 2019 Jan 20.
Artigo em Chinês | MEDLINE | ID: mdl-30685915

RESUMO

Since the 40th anniversary of China's reform and opening-up, earth-shattering development has taken place in all walks of life across the country. Research field on the prevention and treatment of chronic hepatitis B has been rewarding after 40 years of trials and tribulations. Additionally, hepatitis B vaccination program and effective antiviral therapy has amazingly reduced the prevalence of hepatitis B virus infection. Coupled with the literary evidence, a consensus has gradually emerged in the field of anti-HBV treatment that "high potency, low incidence of drug resistance and immunomodulation coexists". We believe that in the near future, according to the principle of "prevention first, prevention with treatment", universal vaccination program for infants, vaccination of high-risk groups, active treatment of HBV carriers and chronic hepatitis B patients, and the realization of "early screening, diagnosis and treatment" of hepatocellular carcinoma will eradicate HBV infection.


Assuntos
Carcinoma Hepatocelular/prevenção & controle , Vacinas contra Hepatite B/administração & dosagem , Vírus da Hepatite B/efeitos dos fármacos , Hepatite B Crônica/prevenção & controle , Neoplasias Hepáticas/prevenção & controle , Antivirais/uso terapêutico , Carcinoma Hepatocelular/virologia , China/epidemiologia , Hepatite B/tratamento farmacológico , Hepatite B/epidemiologia , Hepatite B/prevenção & controle , Vacinas contra Hepatite B/imunologia , Hepatite B Crônica/tratamento farmacológico , Hepatite B Crônica/epidemiologia , Humanos , Neoplasias Hepáticas/virologia , Prevalência , Vacinação
19.
Zhonghua Yu Fang Yi Xue Za Zhi ; 53(1): 36-44, 2019 Jan 06.
Artigo em Chinês | MEDLINE | ID: mdl-30605974

RESUMO

Liver cancer is one of the most common cancers in China. The major risk factors are chronic infections of hepatitis B virus (HBV), hepatitis C virus (HCV), high exposure to aflatoxins. In addition, exposure to cyanotoxins and some preventable health behaviors are also recognized to contribute to liver cancer development. To relieve the disease burden, primary prevention of etiological interventions is an important strategy. Based on the liver cancer epidemiology in China and the effective evidences and results from the etiological interventions conduced in Chinese population domestically, the following strategies are recommended in the "Strategies of primary prevention of liver cancer: Expert Consensus (2018)" to promote the effective prevention of liver cancer in general population. Immunization with HBV vaccines, including the immune programs to neonates, infants and children born to mothers with different status of HBV infection. Antiviral therapies to the patients with chronic hepatitis B or hepatitis C. Avoiding or reducing the exposure to aflatoxins as well as the cyanotoxins. Changing harmful life style, including quitting smoking and limiting alcohol consumption etc.


Assuntos
Consenso , Neoplasias Hepáticas/prevenção & controle , Prevenção Primária/métodos , China , Humanos
20.
Biomed Pharmacother ; 109: 2054-2061, 2019 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-30551461

RESUMO

Hepatocellular carcinoma (HCC) is one of the most common cancers and has a high mortality rate in less developed countries, especially in China. Galangin (GA), one of the most important and naturally active flavonoids, extracted primarily from the root of Alpinia officinarum Hance, has been demonstrated to be effective in the treatment of HCC. It is a substance with defensive actions and a broad range of biological properties, including inhibitory effects on bacteria, fungi, viruses, the control of hypertension and diabetes, and chemoprevention of several cancers. Experiments have shown that GA prevents HCC through multiple anti-cancer mechanisms, anti-genotoxic activity against environmental and dietary carcinogens; anti-proliferative effects through reversal of the Warburg effect in HCC; arrest of the cell cycle in the G0/G1 phase; induction of apoptosis via stimulation of reactive oxygen species (ROS), endoplasmic reticulum (ER) stress, and the mitochondrial-dependent apoptosis pathway; induction of autophagy; and inhibition of angiogenesis, metastasis, and multidrug resistance (MDR). In addition, synergistic effects with other chemotherapy drugs have been demonstrated. Therefore, this review is focused on the anti-HCC mechanisms of GA.


Assuntos
Apoptose/efeitos dos fármacos , Carcinoma Hepatocelular/prevenção & controle , Flavonoides/uso terapêutico , Neoplasias Hepáticas/prevenção & controle , Animais , Apoptose/fisiologia , Carcinoma Hepatocelular/metabolismo , Carcinoma Hepatocelular/patologia , Quimioprevenção/métodos , Quimioprevenção/tendências , Flavonoides/farmacologia , Humanos , Neoplasias Hepáticas/metabolismo , Neoplasias Hepáticas/patologia
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