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1.
Intern Med ; 60(13): 2047-2053, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34193774

RESUMO

A 68-year-old man with hepatocellular carcinoma (HCC) visited his previous hospital due to abdominal pain and was diagnosed with ruptured HCC. Before visiting our hospital, he underwent HCC treatment at his previous hospital, but his tumors did not improve. Although he started treatment with sorafenib, the tumors rapidly grew. Subsequently, regorafenib was given, and the tumors shrank. After 22 months being treated with regorafenib, HCC reoccurred, with a new lung metastasis and a contrast-enhanced nodule on the peritoneal dissemination appearing. He underwent conversion surgery and survived for 4.5 years after his HCC was diagnosed.


Assuntos
Antineoplásicos , Carcinoma Hepatocelular , Neoplasias Hepáticas , Idoso , Antineoplásicos/uso terapêutico , Carcinoma Hepatocelular/tratamento farmacológico , Humanos , Neoplasias Hepáticas/tratamento farmacológico , Masculino , Compostos de Fenilureia/uso terapêutico , Piridinas , Sorafenibe/uso terapêutico
2.
Acta Gastroenterol Belg ; 84(2): 347-359, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34217187

RESUMO

Liver transplantation (LT) remains the only curative option for patients suffering from end-stage liver disease, acute liver failure and selected hepatocellular carcinomas and access to the LT-waiting list is limited to certain strict indications. However, LT has shown survival advantages for patients in certain indications such as acute alcoholic hepatitis, hepatocellular carcinoma outside Milan criteria and colorectal cancer metastases. These newer indications increase the pressure in an already difficult context of organ shortage. Strategies to increase the transplantable organ pool are therefore needed. We will discuss here the use of HCV positive grafts as the use of normothermic isolated liver perfusion. Belgian Liver Intestine Advisory Committee (BeLIAC) from the Belgian Transplant Society (BTS) aims to guarantee the balance between the new indications and the available resources.


Assuntos
Carcinoma Hepatocelular , Neoplasias Hepáticas , Transplante de Fígado , Comitês Consultivos , Bélgica , Humanos , Intestinos
3.
Int J Mol Sci ; 22(13)2021 Jun 27.
Artigo em Inglês | MEDLINE | ID: mdl-34199035

RESUMO

Non-alcoholic fatty liver disease (NAFLD) is a major public health problem worldwide. NAFLD (both simple steatosis and steatohepatitis) is characterized by alterations in hepatic lipid metabolism, which may lead to the development of severe liver complications including cirrhosis and hepatocellular carcinoma. Thus, an exhaustive examination of lipid disorders in the liver of NAFLD patients is much needed. Mass spectrometry-based lipidomics platforms allow for in-depth analysis of lipid alterations in a number of human diseases, including NAFLD. This review summarizes the current research on lipid alterations associated with NAFLD and related complications, with special emphasis on the changes in long-chain and short-chain fatty acids levels in both serum and liver tissue, as well as in the hepatic expression of genes encoding the enzymes catalyzing lipid interconversions.


Assuntos
Suscetibilidade a Doenças , Ácidos Graxos/metabolismo , Hepatopatia Gordurosa não Alcoólica/metabolismo , Hepatopatia Gordurosa não Alcoólica/patologia , Animais , Biomarcadores , Carcinoma Hepatocelular/etiologia , Carcinoma Hepatocelular/metabolismo , Progressão da Doença , Ácidos Graxos/sangue , Ácidos Graxos/química , Microbioma Gastrointestinal , Regulação da Expressão Gênica , Humanos , Metabolismo dos Lipídeos , Lipidômica/métodos , Neoplasias Hepáticas/etiologia , Neoplasias Hepáticas/metabolismo , Estrutura Molecular , Hepatopatia Gordurosa não Alcoólica/complicações , Hepatopatia Gordurosa não Alcoólica/etiologia
4.
Int J Mol Sci ; 22(11)2021 Jun 07.
Artigo em Inglês | MEDLINE | ID: mdl-34200243

RESUMO

Hepatocellular carcinoma (HCC) exerts huge effects on the health burden of the world because of its high mortality and poor prognosis. HCC is often clinically detected late in patients. If HCC could be detected and treated earlier, the survival rate of patients will be greatly improved. Therefore, identifying specific biomarkers is urgent and important for HCC. The liver is also recognized as an immune organ. The occurrence of HCC is related to exacerbation of immune tolerance and/or immunosurveillance escape. The host immune system plays an important role in the recognition and targeting of tumor cells in cancer immunotherapy, as can be seen from the clinical success of immune checkpoint inhibitors and chimeric antigen receptor (CAR) T cells. Thus, there is a pressing medical need to discover immunodiagnostic biomarkers specific to HCC for understanding the pathological mechanisms of HCC, especially for immunotherapy targets. We have reviewed the existing literature to summarize the immunodiagnostic markers of HCC, including autoantibodies against tumor-associated antigens (TAAs) and exosomes, to provide new insights into HCC and early detection of this deadly cancer.


Assuntos
Biomarcadores Tumorais/análise , Carcinoma Hepatocelular/diagnóstico , Carcinoma Hepatocelular/terapia , Imunoterapia/métodos , Neoplasias Hepáticas/diagnóstico , Neoplasias Hepáticas/terapia , Animais , Carcinoma Hepatocelular/imunologia , Humanos , Neoplasias Hepáticas/imunologia , Microambiente Tumoral/imunologia
5.
Molecules ; 26(13)2021 Jun 27.
Artigo em Inglês | MEDLINE | ID: mdl-34199025

RESUMO

Ginsenoside Rk1 and Rg5 are minor ginseng saponins that have received more attention recently because of their high oral bioavailability. Each of them can effectively inhibit the survival and proliferation of human liver cancer cells, but the underlying mechanism remains largely unknown. Network pharmacology and bioinformatics analysis demonstrated that G-Rk1 and G-Rg5 yielded 142 potential targets, and shared 44 putative targets associated with hepatocellular carcinoma. Enrichment analysis of the overlapped genes showed that G-Rk1 and G-Rg5 may induce apoptosis of liver cancer cells through inhibition of mitogen-activated protein kinase (MAPK) and nuclear factor-kappa B (NF-κB) signal pathways. Methyl thiazolyl tetrazolium (MTT) assay was used to confirm the inhibition of cell viability with G-Rk1 or G-Rg5 in highly metastatic human cancer MHCC-97H cells. We evaluated the apoptosis of MHCC-97H cells by using flow cytometry and 4',6-diamidino-2-phenylindole (DAPI) staining. The translocation of Bax/Bak led to the depolarization of mitochondrial membrane potential and release of cytochrome c and Smac. A sequential activation of caspase-9 and caspase-3 and the cleavage of poly(ADP-ribose) polymerase (PARP) were observed after that. The levels of anti-apoptotic proteins were decreased after treatment of G-Rk1 or G-Rg5 in MHCC-97H cells. Taken together, G-Rk1 and G-Rg5 promoted the endogenous apoptotic pathway in MHCC-97H cells by targeting and regulating some critical liver cancer related genes that are involved in the signal pathways associated with cell survival and proliferation.


Assuntos
Antineoplásicos Fitogênicos/farmacologia , Carcinoma Hepatocelular/metabolismo , Ginsenosídeos/farmacologia , Neoplasias Hepáticas/metabolismo , Transdução de Sinais/efeitos dos fármacos , Antineoplásicos Fitogênicos/química , Carcinoma Hepatocelular/tratamento farmacológico , Linhagem Celular Tumoral , Proliferação de Células/efeitos dos fármacos , Sobrevivência Celular/efeitos dos fármacos , Regulação Neoplásica da Expressão Gênica/efeitos dos fármacos , Ginsenosídeos/química , Humanos , Neoplasias Hepáticas/tratamento farmacológico , Proteínas Quinases Ativadas por Mitógeno/metabolismo , NF-kappa B/metabolismo
6.
Sensors (Basel) ; 21(13)2021 Jun 29.
Artigo em Inglês | MEDLINE | ID: mdl-34209996

RESUMO

Unresectable liver tumors are commonly treated with percutaneous radiofrequency ablation (RFA). However, this technique is associated with high recurrence rates due to incomplete tumor ablation. Accurate image guidance of the RFA procedure contributes to successful ablation, but currently used imaging modalities have shortcomings in device guidance and treatment monitoring. We explore the potential of using photoacoustic (PA) imaging combined with conventional ultrasound (US) imaging for real-time RFA guidance. To overcome the low penetration depth of light in tissue, we have developed an annular fiber probe (AFP), which can be inserted into tissue enabling interstitial illumination of tissue. The AFP is a cannula with 72 optical fibers that allows an RFA device to slide through its lumen, thereby enabling PA imaging for RFA device guidance and ablation monitoring. We show that the PA signal from interstitial illumination is not affected by absorber-to-surface depth compared to extracorporeal illumination. We also demonstrate successful imaging of the RFA electrodes, a blood vessel mimic, a tumor-mimicking phantom, and ablated liver tissue boundaries in ex vivo chicken and bovine liver samples. PA-assisted needle guidance revealed clear needle tip visualization, a notable improvement to current US needle guidance. Our probe shows potential for RFA device guidance and ablation detection, which potentially aids in real-time monitoring.


Assuntos
Ablação por Cateter , Neoplasias Hepáticas , Ablação por Radiofrequência , Animais , Bovinos , Iluminação
7.
Medicine (Baltimore) ; 100(27): e26584, 2021 Jul 09.
Artigo em Inglês | MEDLINE | ID: mdl-34232206

RESUMO

ABSTRACT: The aim of this study was to investigate factors affecting tumor necrosis with transcatheter arterial chemoembolization (TACE). Factors associated with early hepatocellular carcinoma recurrence after curative hepatectomy were also evaluated.Data of 51 patients who underwent surgery after a single session of TACE at a single university hospital were retrospectively analyzed. Factors that might affect tumor necrosis were determined by evaluating the TACE approach and by analyzing computed tomography and TACE findings, pathologic reports, and laboratory findings.In univariate analysis, microvascular invasion (MVI), radiological capsule appearance on the computed tomography, chronic hepatitis B, diabetes mellitus and serum albumin, MVI were significantly associated with tumor necrosis by TACE (P < .02). In multivariate analysis, MVI was the only statistically significant factor in TACE-induced tumor necrosis (P = .001). In univariate and multivariate analysis, MVI was the strongest factor for recurrence-free survival rate within 2 years (P = .008, P = .002).MVI could be a crucial factor in determining TACE as an initial treatment for hepatocellular carcinoma. MVI is also a strong indicator of recurrence within 2 years after curative hepatic resection.


Assuntos
Carcinoma Hepatocelular/patologia , Quimioembolização Terapêutica/métodos , Neoplasias Hepáticas/patologia , Microvasos/patologia , Carcinoma Hepatocelular/terapia , Feminino , Hepatectomia/métodos , Humanos , Neoplasias Hepáticas/terapia , Masculino , Pessoa de Meia-Idade , Invasividade Neoplásica , Estudos Retrospectivos
8.
Zhongguo Yi Xue Ke Xue Yuan Xue Bao ; 43(3): 366-370, 2021 Jun 30.
Artigo em Chinês | MEDLINE | ID: mdl-34238412

RESUMO

Objective To observe the effect of cryptotanshinone on the ferroptosis of human liver cancer HepG2 cells. Methods The viability of the HepG2 cells cultured in vitro was determined using the Cell Counting Kit-8(CCK-8),and the half maximal inhibitory concentration(IC50)was calculated.The cell morphology was observed using an inverted microscope.The reactive oxygen species(ROS)level was detected with the 2',7'-dichlorodihydrofluorescein diacetate(DCFH-DA)probe.The glutathione(GSH)assay kit was used to determine the GSH level.Western blot analysis was employed to detect the expression of cystine/glutamate antiporter system light chain(xCT)and glutathione peroxidase 4(GPX4),two marker proteins in ferroptosis.Additionally,the cell viability,ROS level,GSH level,and the expression levels of xCT and GPX4 were detected for the cells treated with the ferroptosis inhibitor ferrostain-1(Fer-1),the iron chelator deferoxamine(DFO),and the ROS scavenger N-acetylcysteine(NAC).Results Cryptotanshinone significantly inhibited the cell viability of HepG2 cells with an IC50 of 93.73 µmol/L,and caused the morphological changes and death of the cells.It could significantly induce ROS accumulation,reduce GSH level,and down-regulate the expression of xCT and GPX4 in HepG2 cells.Fer-1,DFO,and NAC can remedy the cryptotanshinone-caused decrease in the cell viability of HepG2 cells.Fer-1 could inhibit cryptotanshinone-induced ROS accumulation,restore GSH level,and recover the expression of xCT and GPX4. Conclusion Cryptotanshinone may increase the accumulation of ROS by inhibiting the expression of xCT and GPX4 to induce the ferroptosis of HepG2 cells.


Assuntos
Ferroptose , Neoplasias Hepáticas , Fenantrenos , Células Hep G2 , Humanos , Fenantrenos/farmacologia , Espécies Reativas de Oxigênio
9.
Zhongguo Yi Xue Ke Xue Yuan Xue Bao ; 43(3): 371-381, 2021 Jun 30.
Artigo em Chinês | MEDLINE | ID: mdl-34238413

RESUMO

Objective To explore the function and mechanism of related genes in the occurrence and development of liver cancer, and the possibility of key genes as potential biomarkers and prognostic indicators for the treatment of liver cancer.Methods We selected 4 datasets(GSE57957, GSE121248, GSE36376 and GSE14520)from the GEO database.With P<0.05 and |log2FC|>1 as the thresholds, we used GEO2R and Venn Diagram Software to filter out the common significant differentially expressed genes(DEGs).Cytoscape 3.6.1 plug-ins CytoHubba and molecular complex detection(MCODE)were used to screen out the hub genes and modules of DEGs.In addition, survival analysis of DEGs was performed by gene expression profiling(GEPIA), and Human Protein Atlas(HPA)were used to examine the protein expression levels of key genes in normal liver tissue and liver cancer tissue.Results There were 45 obviously up-regulated genes and 132 down-regulated genes, and MCODE identified 13 clusters.The cluster 1 and cluster 2 with higher scores included 16 genes and 13 genes, respectively.Among the 32 significant DEGs, IGFALS, HGFAC, CYP3A4, SLC22A1, TAT and CYP2E1 demonstrated significantly higher expression levels in liver tissue than in other organs.The HPA immunohistochemistry(IHC)data showed that the expression levels of IGFALS, CYP3A4, SLC22A1 and CYP2E1 in liver cancer tissue were significantly down-regulated and related to the low overall survival rate of patients.Conclusion The liver tissue-specific genes IGFALS, CYP3A4, SLC22A1 and CYP2E1 are under-expressed in liver cancer and associated with poor prognosis, which may be potential biomarkers and prognostic indicators for liver cancer.


Assuntos
Citocromo P-450 CYP2E1 , Neoplasias Hepáticas , Biomarcadores Tumorais/genética , Biologia Computacional , Citocromo P-450 CYP3A , Perfilação da Expressão Gênica , Regulação Neoplásica da Expressão Gênica , Redes Reguladoras de Genes , Humanos , Neoplasias Hepáticas/genética , Prognóstico , Mapas de Interação de Proteínas
10.
World J Gastroenterol ; 27(24): 3429-3439, 2021 Jun 28.
Artigo em Inglês | MEDLINE | ID: mdl-34239261

RESUMO

Although hepatocellular carcinoma is considered a highly lethal malignancy, recent therapeutic advances have been achieved during the last 10 years. This scenario resulted in an unprecedented improvement in survival for patients with advanced hepatocellular carcinoma, almost reaching 20-26 mo of overall survival after first-second line sequential treatment. The advent of the combination of atezolizumab with bevacizumab showed, for the first time, superiority over sorafenib with improvement in overall survival. However, first and second-line trials were correctly based on the premise that a strict selection of patients enhances the power to capture the positive effect of treatment by excluding competing risks for mortality such as liver failure, decompensated cirrhosis or other underlying medical conditions. As a result, the inclusion criteria used in clinical trials do not support the use of novel therapies in several real-world scenarios involving underrepresented subgroups, such as patients with unpreserved liver function, other comorbid conditions, a history of solid-organ transplantation, autoimmune disorders and those with a high risk of bleeding. The present text aims at discussing treatment strategies in these subgroups.


Assuntos
Carcinoma Hepatocelular , Neoplasias Hepáticas , Bevacizumab , Carcinoma Hepatocelular/tratamento farmacológico , Humanos , Neoplasias Hepáticas/tratamento farmacológico , Sorafenibe
11.
World J Gastroenterol ; 27(24): 3466-3482, 2021 Jun 28.
Artigo em Inglês | MEDLINE | ID: mdl-34239263

RESUMO

Primary liver cancers carry significant morbidity and mortality. Hepatocellular carcinoma (HCC) develops within the hepatic parenchyma and is the most common malignancy originating from the liver. Although 80% of HCCs develop within background cirrhosis, 20% may arise in a non-cirrhotic milieu and are referred to non-cirrhotic-HCC (NCHCC). NCHCC is often diagnosed late due to lack of surveillance. In addition, the rising prevalence of non-alcoholic fatty liver disease and diabetes mellitus have increased the risk of developing HCC on non-cirrhotic patients. Viral infections such as chronic Hepatitis B and less often chronic hepatitis C with advance fibrosis are associated with NCHCC. NCHCC individuals may have Hepatitis B core antibodies and occult HBV infection, signifying the role of Hepatitis B infection in NCHCC. Given the effectiveness of current antiviral therapies, surgical techniques and locoregional treatment options, nowadays such patients have more options and potential for cure. However, these lesions need early identification with diagnostic models and multiple surveillance strategies to improve overall outcomes. Better understanding of the NCHCC risk factors, tumorigenesis, diagnostic tools and treatment options are critical to improving prognosis and overall outcomes on these patients. In this review, we aim to discuss NCHCC epidemiology, risk factors, and pathogenesis, and elaborate on NCHCC diagnosis and treatment strategies.


Assuntos
Carcinoma Hepatocelular , Hepatite B Crônica , Hepatite B , Neoplasias Hepáticas , Carcinoma Hepatocelular/epidemiologia , Carcinoma Hepatocelular/etiologia , Carcinoma Hepatocelular/terapia , Hepatite B Crônica/complicações , Hepatite B Crônica/tratamento farmacológico , Hepatite B Crônica/epidemiologia , Humanos , Cirrose Hepática/epidemiologia , Cirrose Hepática/terapia , Neoplasias Hepáticas/epidemiologia , Neoplasias Hepáticas/terapia
12.
World J Gastroenterol ; 27(24): 3530-3542, 2021 Jun 28.
Artigo em Inglês | MEDLINE | ID: mdl-34239267

RESUMO

The hepatitis delta virus (HDV) is a small RNA virus that encodes a single protein and which requires the hepatitis B virus (HBV)-encoded hepatitis B surface antigen (HBsAg) for its assembly and transmission. HBV/HDV co-infections exist worldwide and show a higher prevalence among selected groups of HBV-infected populations, specifically intravenous drug users, practitioners of high-risk sexual behaviours, and patients with cirrhosis and hepatocellular carcinoma. The chronic form of HDV-related hepatitis is usually severe and rapidly progressive. Patterns of the viral infection itself, including the status of co-infection or super-infection, virus genotypes (both for HBV and HDV), and persistence of the virus' replication, influence the outcome of the accompanying and manifested liver disease. Unfortunately, disease severity is burdened by the lack of an effective cure for either virus type. For decades, the main treatment option has been interferon, administered as mono-therapy or in combination with nucleos(t)ide analogues. While its efficacy has been reported for different doses, durations and courses, only a minority of patients achieve a sustained response, which is the foundation of eventual improvement in related liver fibrosis. The need for an efficient therapeutic alternative remains. Research efforts towards this end have led to new treatment options that target specific steps in the HDV life cycle; the most promising among these are myrcludex B, which inhibits virus entry into hepatocytes, lonafarnib, which inhibits farnesylation of the viral-encoded L-HDAg large hepatitis D antigen, and REP-2139, which interferes with HBsAg release and assembly.


Assuntos
Hepatite B , Hepatite D , Neoplasias Hepáticas , Hepatite B/diagnóstico , Hepatite B/tratamento farmacológico , Hepatite B/epidemiologia , Antígenos de Superfície da Hepatite B , Vírus da Hepatite B/genética , Hepatite D/diagnóstico , Hepatite D/tratamento farmacológico , Hepatite D/epidemiologia , Vírus Delta da Hepatite/genética , Humanos
13.
World J Gastroenterol ; 27(24): 3556-3567, 2021 Jun 28.
Artigo em Inglês | MEDLINE | ID: mdl-34239269

RESUMO

Chronic infections due to hepatitis B and hepatitis C viruses are responsible for most cases of hepatocellular carcinoma (HCC) worldwide, and this association is likely to remain during the next decade. Moreover, viral hepatitis-related HCC imposes an important burden on public health in terms of disability-adjusted life years. In order to reduce such a burden, some major challenges must be faced. Universal vaccination against hepatitis B virus, especially in the neonatal period, is probably the most relevant primary preventive measure against the development of HCC. Moreover, considering the large adult population already infected with hepatitis B and C viruses, it is also imperative to identify these individuals to ensure their access to treatment. Both hepatitis B and C currently have highly effective therapies, which are able to diminish the risk of development of liver cancer. Finally, it is essential for individuals at high-risk of HCC to be included in surveillance programs, so that tumors are detected at an early stage. Patients with hepatitis B or C and advanced liver fibrosis or cirrhosis benefit from being followed in a surveillance program. As hepatitis B virus is oncogenic and capable of leading to liver cancer even in individuals with early stages of liver fibrosis, other high-risk groups of patients with hepatitis B are also candidates for surveillance. Considerable effort is required concerning these strategies in order to decrease the incidence and the mortality of viral hepatitis-related HCC.


Assuntos
Carcinoma Hepatocelular , Hepatite B Crônica , Hepatite B , Hepatite Viral Humana , Neoplasias Hepáticas , Adulto , Carcinoma Hepatocelular/epidemiologia , Carcinoma Hepatocelular/etiologia , Carcinoma Hepatocelular/prevenção & controle , Hepatite B/complicações , Hepatite B/epidemiologia , Hepatite B/prevenção & controle , Vírus da Hepatite B , Hepatite B Crônica/complicações , Hepatite B Crônica/epidemiologia , Hepatite Viral Humana/complicações , Hepatite Viral Humana/epidemiologia , Humanos , Recém-Nascido , Neoplasias Hepáticas/epidemiologia , Neoplasias Hepáticas/prevenção & controle , Fatores de Risco
14.
World J Gastroenterol ; 27(24): 3630-3642, 2021 Jun 28.
Artigo em Inglês | MEDLINE | ID: mdl-34239274

RESUMO

BACKGROUND: Liver transplantation (LT) presents a curative treatment option in patients with early stage hepatocellular carcinoma (HCC) who are not eligible for resection or ablation therapy. Due to a risk of up 30% for waitlist drop-out upon tumor progression, bridging therapies are used to halt tumor growth. Transarterial chemoembolization (TACE) and less commonly stereotactic body radiation therapy (SBRT) or a combination of TACE and SBRT, are used as bridging therapies in LT. However, it remains unclear if one of those treatment options is superior. The analysis of explant livers after transplantation provides the unique opportunity to investigate treatment response by histopathology. AIM: To analyze histopathological response to a combination of TACE and SBRT in HCC in comparison to TACE or SBRT alone. METHODS: In this multicenter retrospective study, 27 patients who received liver transplantation for HCC were analyzed. Patients received either TACE or SBRT alone, or a combination of TACE and SBRT as bridging therapy to liver transplantation. Liver explants of all patients who received at least one TACE and/or SBRT were analyzed for the presence of residual vital tumor tissue by histopathology to assess differences in treatment response to bridging therapies. Statistical analysis was performed using Fisher-Freeman-Halton exact test, Kruskal-Wallis and Mann-Whitney-U tests. RESULTS: Fourteen patients received TACE only, four patients SBRT only, and nine patients a combination therapy of TACE and SBRT. There were no significant differences between groups regarding age, sex, etiology of underlying liver disease or number and size of tumor lesions. Strikingly, analysis of liver explants revealed that almost all patients in the TACE and SBRT combination group (8/9, 89%) showed no residual vital tumor tissue by histopathology, whereas TACE or SBRT alone resulted in significantly lower rates of complete histopathological response (0/14, 0% and 1/4, 25%, respectively, P value < 0.001). CONCLUSION: Our data suggests that a combination of TACE and SBRT increases the rate of complete histopathological response compared to TACE or SBRT alone in bridging to liver transplantation.


Assuntos
Carcinoma Hepatocelular , Quimioembolização Terapêutica , Neoplasias Hepáticas , Radiocirurgia , Carcinoma Hepatocelular/terapia , Quimioembolização Terapêutica/efeitos adversos , Terapia Combinada , Humanos , Neoplasias Hepáticas/terapia , Radiocirurgia/efeitos adversos , Estudos Retrospectivos , Resultado do Tratamento
15.
Artigo em Inglês | MEDLINE | ID: mdl-34199687

RESUMO

Objectives: China is the country most afflicted by hepatocellular carcinoma in the world. However, little is known about the epidemiology of hepatocellular carcinoma in China. This study aimed to examine the trends of the prevalence, incidence, and mortality of hepatocellular carcinoma in China, and to investigate the effects of age, period, and birth cohort on the epidemiological trend. Methods: The data were obtained from the Urban Employee Basic Medical Insurance claims database (2003-2017) in Tianjin, China, which covers 5.95 million individuals. The average annual percentage change of the prevalence, incidence, and mortality were accessed using joinpoint regression. Age-period-cohort models were produced to quantify the effects of age, period, and cohort. Results: The hepatocellular carcinoma prevalence rate increased by 5.13% annually from 20.12/100,000 in 2008 to 30.49/100,000 in 2017, and the incidence rate was almost unchanged, from 13.91/100,000 in 2008 to 14.09/100,000 in 2017, but mortality decreased by 1.80% annually from 8.18/100,000 in 2008 to 7.34/100,000 in 2017. The age-period-cohort analysis revealed that the prevalence rate was remarkably increased from age 25, peaked in age 60, and decreased at age 70 and over. In the period index, the prevalence rate increased gradually from 2008 to 2016, and decreased a little in 2017. In the cohort index, the prevalence rate decreased approximately linearly from the 1925 cohort to the 1990 cohort. The result for the incidence was similar to the prevalence. The mortality rate increased approximately linearly from age 45 to 85, decreased from the 1925 cohort to the 1990 cohort, but it changed a little with the change of period. Conclusions: The findings of this study could inform the necessity of conducting earlier screening for high-risk individuals and improving the treatment of hepatocellular carcinoma, which may also help to predict future changes in hepatocellular carcinoma epidemiology.


Assuntos
Carcinoma Hepatocelular , Neoplasias Hepáticas , Adulto , Idoso , Idoso de 80 Anos ou mais , Carcinoma Hepatocelular/epidemiologia , China/epidemiologia , Efeito de Coortes , Humanos , Incidência , Neoplasias Hepáticas/epidemiologia , Pessoa de Meia-Idade , Mortalidade , Prevalência
16.
Molecules ; 26(13)2021 Jun 25.
Artigo em Inglês | MEDLINE | ID: mdl-34202121

RESUMO

The effect of ellagic acid (EA), a naturally occurring polyphenolic compound, on the secretion of apolipoproteins from human hepatocytes, HepG2, was investigated. The levels of apoB and apoA-1 secreted in the cell culture medium were determined by sandwich ELISA. EA did not affect cell viability at the tested concentrations (up to 50 µM). EA suppressed the secretion of apoB and enhanced that of apoA-1 from HepG2 cells. However, cellular apoB levels were increased, suggesting that EA inhibited the trafficking of apoB during the process of secretion. In contrast, the increase in the cellular levels of apoA-1 was consistent with its secreted levels. These results indicate that EA inhibits the secretion of apoB from hepatocytes and increases the secretion of apoA-1. Both of these effects are beneficial for lipoprotein metabolism in the prevention of lifestyle-related diseases. The detailed mechanism underlying these effects of EA on lipoprotein metabolism should be elucidated in the future, but this naturally occurring polyphenolic compound might be antihyperlipidemic. Based on these results, EA is suggested as a candidate food-derived compound for the prevention of hyperlipidemia.


Assuntos
Apolipoproteína A-I/metabolismo , Apolipoproteína B-100/metabolismo , Carcinoma Hepatocelular/metabolismo , Ácido Elágico/farmacologia , Neoplasias Hepáticas/metabolismo , Proteínas de Neoplasias/metabolismo , Carcinoma Hepatocelular/patologia , Células Hep G2 , Humanos , Neoplasias Hepáticas/patologia
17.
Molecules ; 26(11)2021 Jun 03.
Artigo em Inglês | MEDLINE | ID: mdl-34204938

RESUMO

The aim of the study was to evaluate the influence of vitamin K2 (VK2) supplementation on the sphingolipid metabolism pathway in palmitate-induced insulin resistant hepatocytes. The study was carried out on human hepatocellular carcinoma cells (HepG2) incubated with VK2 and/or palmitic acid (PA). The concentrations of sphingolipids were measured by high-performance liquid chromatography. The expression of enzymes from the sphingolipid pathway was assessed by Western blotting. The same technique was used in order to determine changes in the expression of the proteins from the insulin signaling pathway in the cells. Simultaneous incubation of HepG2 cells with palmitate and VK2 elevated accumulation of sphinganine and ceramide with increased expression of enzymes from the ceramide de novo synthesis pathway. HepG2 treatment with palmitate and VK2 significantly decreased the insulin-stimulated expression ratio of insulin signaling proteins. Moreover, we observed that the presence of PA w VK2 increased fatty acid transport protein 2 expression. Our study showed that VK2 activated the ceramide de novo synthesis pathway, which was confirmed by the increase in enzymes expression. VK2 also intensified fatty acid uptake, ensuring substrates for sphingolipid synthesis through the de novo pathway. Furthermore, increased concentration of sphingolipids, mainly sphinganine, inhibited insulin pathway proteins phosphorylation, increasing insulin resistance development.


Assuntos
Vias Biossintéticas/efeitos dos fármacos , Carcinoma Hepatocelular/metabolismo , Ceramidas/análise , Resistência à Insulina , Neoplasias Hepáticas/metabolismo , Ácido Palmítico/efeitos adversos , Vitamina K 2/farmacologia , Cromatografia Líquida de Alta Pressão , Regulação Neoplásica da Expressão Gênica/efeitos dos fármacos , Células Hep G2 , Humanos , Insulina/metabolismo , Modelos Biológicos , Fosforilação , Esfingosina/análogos & derivados , Esfingosina/análise , Regulação para Cima
18.
Int J Nanomedicine ; 16: 4495-4513, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34239301

RESUMO

Purpose: Hepatocellular carcinoma (HCC) is a common malignant tumor that seriously threatens human life and health. Currently, the majority of antitumor drugs are administered in an injectable manner, which can cause pain and side effects to patients. Objective of this study is to establish an effective oral drug delivery system for anti hepatoma drugs. Methods: In this study, intestinal targeting cell penetrating peptide (R6LRVG) was obtained by binding cell penetrating peptide (R6) with the polypeptide of LRVG (targeting intestinal epithelial cells). Next, R6LRVG-modified tyroserleutide-poly(lactic-co-glycolic acid) (PLGA) nanoparticles (YSL-PLGA/R6LRVG NPs) were prepared. After that, the nanoparticles were characterized and their stability was evaluated. The cellular uptake, in vitro bioactivity and in vivo antitumor activity of the nanoparticles were investigated. In addition, the mechanism, including the endocytic pathway and respiratory rate detection of mitochondria, was further investigated. Results: YSL-PLGA/R6LRVG NPs were successfully prepared. Characterization revealed YSL-PLGA/R6LRVG NPs to be globular particles with smooth surfaces and an average diameter of 222.6 nm. The entrapment efficiency and drug loading of tyroserleutide were 70.27% and 19.69%, respectively. Furthermore, the YSL-PLGA/R6LRVG NPs group exhibited the largest amount of YSL uptake. We also found that cell uptake of YSL-PLGA/R6LRVG NPs could be related to the endocytosis pathways mediated by reticulin and caveolae/lipid rafts. Additionally, the YSL-PLGA/R6LRVG NPs could interfere with mitochondrial function. In vivo experiments revealed that orally administered YSL-PLGA/R6LRVG NPs exerted excellent anticancer effects in tumor-bearing mice. Hematoxylin-eosin staining did not show any histological changes in the major organs. Conclusion: To summarize, YSL-PLGA/R6LRVG NPs could be a useful oral delivery system of YSL and may provide a new platform for the oral delivery of anticancer drugs.


Assuntos
Antineoplásicos/química , Carcinoma Hepatocelular/tratamento farmacológico , Neoplasias Hepáticas/tratamento farmacológico , Nanopartículas/química , Oligopeptídeos/química , Ácido Poliglicólico/química , Copolímero de Ácido Poliláctico e Ácido Poliglicólico/química , Administração Oral , Animais , Antineoplásicos/administração & dosagem , Antineoplásicos/uso terapêutico , Humanos , Camundongos
19.
Int J Mol Sci ; 22(12)2021 Jun 15.
Artigo em Inglês | MEDLINE | ID: mdl-34203895

RESUMO

Although hepatocellular carcinoma (HCC) is developed with various etiologies, protection of hepatocytes seems basically essential to prevent the incidence of HCC. Keratin 8 and keratin 18 (K8/K18) are cytoskeletal intermediate filament proteins that are expressed in hepatocytes. They maintain the cell shape and protect cells under stress conditions. Their protective roles in liver damage have been described in studies of mouse models, and K8/K18 mutation frequency in liver patients. Interestingly, K8/K18 bind to signaling proteins such as transcription factors and protein kinases involved in HCC development. Since K8/K18 are abundant cytoskeletal proteins, K8/K18 binding with the signaling factors can alter the availability of the factors. Herein, we discuss the potential roles of K8/K18 in HCC development.


Assuntos
Carcinogênese/metabolismo , Carcinoma Hepatocelular/metabolismo , Queratina-18/metabolismo , Queratina-8/metabolismo , Neoplasias Hepáticas/metabolismo , Transdução de Sinais , Carcinogênese/patologia , Ensaios Clínicos como Assunto , Humanos
20.
Int J Mol Sci ; 22(11)2021 Jun 01.
Artigo em Inglês | MEDLINE | ID: mdl-34206143

RESUMO

Primary liver cancer accounts for the third most deadly type of malignant tumor globally, and approximately 80% of the cases are hepatocellular carcinoma (HCC), which highly relies on the activity of hypoxia responsive pathways to bolster its metastatic behaviors. MicroRNA-29a (MIR29A) has been shown to exert a hepatoprotective effect on hepatocellular damage and liver fibrosis induced by cholestasis and diet stress, while its clinical and biological role on the activity hypoxia responsive genes including LOX, LOXL2, and VEGFA remains unclear. TCGA datasets were retrieved to confirm the differential expression and prognostic significance of all genes in the HCC and normal tissue. The Gene Expression Omnibus (GEO) dataset was used to corroborate the differential expression and diagnostic value of MIR29A. The bioinformatic identification were conducted to examine the interaction of MIR29A with LOX, LOXL2, and VEGFA. The suppressive activity of MIR29A on LOX, LOXL2, and VEGF was verified by qPCR, immunoblotting, and luciferase. The effect of overexpression of MIR29A-3p mimics in vitro on apoptosis markers (caspase-9, -3, and poly (ADP-ribose) polymerase (PARP)); cell viability and wound healing performance were examined using immunoblot and a WST-1 assay and a wound healing assay, respectively. The HCC tissue presented low expression of MIR29A, yet high expression of LOX, LOXL2, and VEGFA as compared to normal control. Serum MIR29A of HCC patients showed decreased levels as compared to that of normal control, with an area under curve (AUC) of 0.751 of a receiver operating characteristic (ROC) curve. Low expression of MIR29A and high expression of LOX, LOXL2, and VEGFA indicated poor overall survival (OS). MIR29A-3p was shown to target the 3'UTR of LOX, LOXL2, and VEGFA. Overexpression of MIR29A-3p mimic in HepG2 cells led to downregulated gene and protein expression levels of LOX, LOXL2, and VEGFA, wherein luciferase reporter assay confirmed that MIR29A-3p exerts the inhibitory activity via directly binding to the 3'UTR of LOX and VEGFA. Furthermore, overexpression of MIR29A-3p mimic induced the activity of caspase-9 and -3 and PARP, while it inhibited the cell viability and wound healing performance. Collectively, this study provides novel insight into a clinical-applicable panel consisting of MIR29, LOX, LOXL2, and VEGFA and demonstrates an anti-HCC effect of MIR29A via comprehensively suppressing the expression of LOX, LOXL2, and VEGFA, paving the way to a prospective theragnostic approach for HCC.


Assuntos
Aminoácido Oxirredutases/genética , Carcinoma Hepatocelular/genética , MicroRNAs/genética , Proteína-Lisina 6-Oxidase/genética , Fator A de Crescimento do Endotélio Vascular/genética , Carcinoma Hepatocelular/patologia , Intervalo Livre de Doença , Feminino , Regulação Neoplásica da Expressão Gênica/genética , Células Hep G2 , Humanos , Estimativa de Kaplan-Meier , Neoplasias Hepáticas/genética , Neoplasias Hepáticas/patologia , Masculino , Pessoa de Meia-Idade , Metástase Neoplásica , Prognóstico , Transdução de Sinais/genética
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