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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.
Zhonghua Gan Zang Bing Za Zhi ; 29(6): 571-574, 2021 Jun 20.
Artigo em Chinês | MEDLINE | ID: mdl-34225433

RESUMO

Objective: To investigate the expression of miR-495 and its effect on MHCC-97H hepatocellular carcinoma cells. Methods: Fifty-six hepatocellular carcinoma tissue specimens (HCC group) and 40 normal liver tissue specimens (control group) preserved in our hospital from January 2017 to January 2018 were selected. Reverse transcription real-time fluorescent quantitative PCR (qRT-PCR) was used for miR-495 expression detection. MHCC-97H HCC cells were randomly selected and then divide into control group, blank plasmid group and transfection group. The blank plasmid group was transfected with blank plasmid, and the transfection group was transfected with miR-495 inhibitor. The expression of miR-495 in each group of cells were detected using qRT-PCR. CCK method was used to detect each group proliferation activity. Transwell cell migration assay was used to detect each group migration ability. Analysis of variance was used for comparison between multiple groups. Furthermore, LDS-t test was used for pairwise comparison, and t -test was used for comparison between the two groups. Results: The relative expression levels of miR-495 in the HCC group was (2.043 ± 0.382), which was higher than the control group, and the difference between the two groups was statistically significant (P < 0.05). The relative expressions levels of miR-495 in patients with stage III to IV and lymph node metastasis were 2.265 ± 0.284 and 2.290 ± 0.355, which were significantly higher than those of stage I to II and no lymph node metastasis (P < 0.05). The relative expression levels of miR-495 in transfection group was 0.653 ± 0.102, which were significantly lower than control group and blank plasmid group (P < 0.05). The A values of MHCC-97H cells cultured for 24 h and 48 h in transfection group were 0.404 ± 0.106 and 0.604 ± 0.136, which were significantly lower than control group and blank plasmid group (P < 0.05). MHCC-97H cells migration number in the transfection group was (6.10 0 ± 20), which was significantly lower than that of control group and blank plasmid group (P < 0.05). Conclusion: miR-495 high expression has certain relationship with clinicopathological characteristics of HCC tissues. In addition, miR-495 has a certain effect on the proliferation and migration ability of MHCC-97H HCC cells.


Assuntos
Carcinoma Hepatocelular , Neoplasias Hepáticas , MicroRNAs , Carcinoma Hepatocelular/genética , Linhagem Celular Tumoral , Movimento Celular , Proliferação de Células , Regulação Neoplásica da Expressão Gênica , Humanos , Neoplasias Hepáticas/genética , MicroRNAs/genética
3.
Zhonghua Gan Zang Bing Za Zhi ; 29(6): 575-579, 2021 Jun 20.
Artigo em Chinês | MEDLINE | ID: mdl-34225434

RESUMO

Objective: To analyze the factors influencing radiation-induced liver injury after receiving Cyberknife stereotactic radiotherapy in patients with primary hepatocellular carcinoma. Methods: 278 cases with primary hepatocellular carcinoma from July 2016 to April 2019 were prospectively enrolled. Stereotactic radiosurgery with a prescription dose of 48-55gy/5-8 times were given. Liver function, coagulation function, Child-Pugh score, and liver imaging changes were dynamically observed before and after treatment to evaluate the occurrence of radiation-induced liver injury. Logistic regression model was used to analyze the factors influencing radiation-induced liver injury. Results: Among 278 cases, 3 cases of tumor progression were excluded, and a total of 275 cases were included for analysis. The overall survival rate after 8 months of treatment was 100%. Among them, 22 cases were diagnosed as radiation-induced liver injury, with an incidence rate of 8%, and all cases were recovered after symptomatic treatment. Multivariate analysis result suggested that the peripheral white blood cell count was factors influencing the occurrence of radiation-induced liver injury. Conclusion: Cyberknife stereotactic radiotherapy has a low incidence of radiation-induced liver injury in patients with liver cancer, and it is a relatively safe treatment method. Patients with low peripheral white blood cell counts before treatment should be closely monitored for early detection and treatment.


Assuntos
Carcinoma Hepatocelular , Doença Hepática Crônica Induzida por Substâncias e Drogas , Neoplasias Hepáticas , Radiocirurgia , Carcinoma Hepatocelular/cirurgia , Humanos , Neoplasias Hepáticas/cirurgia , Radiocirurgia/efeitos adversos , Estudos Retrospectivos , Resultado do Tratamento
4.
Zhonghua Gan Zang Bing Za Zhi ; 29(6): 600-603, 2021 Jun 20.
Artigo em Chinês | MEDLINE | ID: mdl-34225439

RESUMO

The application of immune checkpoint inhibitors has significantly improved the immunotherapy effect of a variety of solid tumors. With the US Food and Drug Administration's approval of nivolumab and pembrolizumab as second-line treatments for hepatocellular carcinoma, the application of immune checkpoint inhibitors, especially in combination with other treatment methods, has become more and more widely used in hepatocellular carcinoma. Notably, these drugs play a therapeutic role in tumor immunosuppression; however, they can also stimulate related side effects caused by autoimmunity, so their side effects are very different from traditional chemotherapy and targeted drugs. Therefore, effective monitoring, detection and intervention of immune-related side effects are obligatory assurances for patients to attain clinical benefits.


Assuntos
Carcinoma Hepatocelular , Neoplasias Hepáticas , Anticorpos Monoclonais/efeitos adversos , Carcinoma Hepatocelular/tratamento farmacológico , Humanos , Inibidores de Checkpoint Imunológico , Neoplasias Hepáticas/tratamento farmacológico , Nivolumabe/efeitos adversos
5.
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
6.
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
7.
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
8.
Nat Commun ; 12(1): 4091, 2021 07 02.
Artigo em Inglês | MEDLINE | ID: mdl-34215748

RESUMO

Little is known about the transcriptomic plasticity and adaptive mechanisms of circulating tumor cells (CTCs) during hematogeneous dissemination. Here we interrogate the transcriptome of 113 single CTCs from 4 different vascular sites, including hepatic vein (HV), peripheral artery (PA), peripheral vein (PV) and portal vein (PoV) using single-cell full-length RNA sequencing in hepatocellular carcinoma (HCC) patients. We reveal that the transcriptional dynamics of CTCs were associated with stress response, cell cycle and immune-evasion signaling during hematogeneous transportation. Besides, we identify chemokine CCL5 as an important mediator for CTC immune evasion. Mechanistically, overexpression of CCL5 in CTCs is transcriptionally regulated by p38-MAX signaling, which recruites regulatory T cells (Tregs) to facilitate immune escape and metastatic seeding of CTCs. Collectively, our results reveal a previously unappreciated spatial heterogeneity and an immune-escape mechanism of CTC, which may aid in designing new anti-metastasis therapeutic strategies in HCC.


Assuntos
Carcinoma Hepatocelular/genética , Carcinoma Hepatocelular/imunologia , Heterogeneidade Genética , Evasão da Resposta Imune , Neoplasias Hepáticas/genética , Neoplasias Hepáticas/imunologia , Células Neoplásicas Circulantes/imunologia , Idoso , Animais , Biomarcadores Tumorais/metabolismo , Ciclo Celular , Linhagem Celular Tumoral , Quimiocina CCL5/metabolismo , Regulação Neoplásica da Expressão Gênica , Humanos , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Pessoa de Meia-Idade , Metástase Neoplásica , Células Neoplásicas Circulantes/metabolismo , Prognóstico , RNA-Seq , Transcriptoma , Microambiente Tumoral
10.
Z Gastroenterol ; 59(5): 496-497, 2021 05.
Artigo em Alemão | MEDLINE | ID: mdl-34224132
11.
Nutrients ; 13(6)2021 Jun 11.
Artigo em Inglês | MEDLINE | ID: mdl-34208122

RESUMO

The objective of this study was to assess the association between dietary patterns and risk of hepatocellular carcinoma (HCC) among US adults in a hospital-based case-control study. We analyzed data from 641 cases and 1002 controls recruited at The University of Texas MD Anderson Cancer Center during 2001-2018. Cases were patients with a pathologically or radiologically confirmed new diagnosis of HCC; controls were cancer-free spouses of patients with cancers other than gastrointestinal, lung, liver, or head and neck cancer. Cases and controls were frequency-matched by age and sex. Dietary patterns were identified by principal component analysis. Odds ratios (ORs) and corresponding confidence intervals (CIs) were computed using unconditional logistic regression with adjustment for major HCC risk factors, including hepatitis B virus and hepatitis C virus infection. A vegetable-based dietary pattern was inversely associated with HCC risk (highest compared with lowest tertile: OR 0.66, 95% CI 0.46-0.94). A Western diet pattern was directly associated with HCC risk (highest compared with lowest tertile: OR 1.79, 95% CI 1.19-2.69). These findings emphasize the potential role of dietary intake in HCC prevention and clinical management.


Assuntos
Carcinoma Hepatocelular/epidemiologia , Dieta Ocidental , Dieta , Neoplasias Hepáticas/epidemiologia , Verduras , Idoso , Estudos de Casos e Controles , Feminino , Humanos , Estilo de Vida , Modelos Logísticos , Masculino , Pessoa de Meia-Idade , Razão de Chances , Fatores de Risco
12.
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
13.
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
14.
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
15.
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
16.
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
17.
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
18.
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
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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