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1.
Anticancer Res ; 41(7): 3419-3427, 2021 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-34230137

RESUMO

BACKGROUND/AIM: Liver metastases are among the principal mortality causes in cancer patients. Dendritic cell immunotherapies have shown promising results in some tumors by mediating immunological mechanisms that could be involved in liver metastases during primary tumor growth. The present study aimed to evaluate the impact of prophylactic dendritic cell vaccination on the liver of mice with 4T1 mouse breast carcinoma. MATERIALS AND METHODS: Adult female Balb/c mice were submitted or not to vaccination with dendritic cells before the induction of 4T1 tumor lineage. Liver tissues from mice were analyzed by flow cytometry (markers CD3, CD4, CD8, CD25, IL-10, IL-12, IL-17, TNF-α, IFN-γ, T-bet, GATA3, RORγt, and FoxP3) and hematoxylin-eosin. The dendritic cell vaccine was differentiated and matured ex vivo from the bone marrow. RESULTS: Prophylactic vaccination reduced areas of liver metastases (p=0.0049), induced an increase in the percentage of total T and cytotoxic T lymphocytes (p<0.0001), as well as FoxP3+ (p<0.0001). It also increased the levels of cytokines IL-10 and IL-17 in helper T lymphocytes (p<0.0001). CONCLUSION: The prophylactic dendritic cell vaccine changed the cell phenotype in the immune response of liver, and it was able to reduce metastases. Cytotoxic T cells and regulatory T lymphocytes were more present, likewise, the production of IL-10 and IL-7 simultaneously, demonstrating that the vaccine can induce a state of control of pro-inflammatory responses, which can provide a less favorable environment for metastatic tumor growth.


Assuntos
Neoplasias da Mama/imunologia , Vacinas Anticâncer/imunologia , Células Dendríticas/imunologia , Neoplasias Hepáticas/imunologia , Fígado/imunologia , Animais , Biomarcadores Tumorais/imunologia , Medula Óssea/imunologia , Neoplasias da Mama/patologia , Modelos Animais de Doenças , Feminino , Imunidade/imunologia , Imunoterapia/métodos , Fígado/patologia , Neoplasias Hepáticas/patologia , Camundongos , Camundongos Endogâmicos BALB C , Linfócitos T Citotóxicos/imunologia , Linfócitos T Reguladores/imunologia , Vacinação/métodos
2.
Anticancer Res ; 41(7): 3657-3665, 2021 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-34230164

RESUMO

BACKGROUND/AIM: We attempted to stratify prognosis using the modified Journal of Hepato-Biliary-Pancreatic Sciences (mJHBPS) nomogram upon identification of colorectal liver metastasis (CRLM) and to investigate which strategy is better, surgery first (SF) or chemotherapy first (CF), in each risk group. PATIENTS AND METHODS: A total of 137 patients with CRLM who underwent resection of the primary tumor were included. Patients with brain, bone, or perihilar lymph node metastases were excluded. Patients were scored using the mJHBPS nomogram upon identification of CRLM. Prognosis was investigated using event-free survival (EFS) and overall survival (OS). RESULTS: The nomogram allowed stratification of patients using EFS and OS: low-risk (0-6 score, n=38), medium-risk (7-11 score, n=42), and high-risk (12≥ score, n=57). In the low-risk group, the EFS and OS of the CF group were significantly poorer than those of the SF group (p=0.019 and p=0.014, respectively). CF was an independent prognostic factor for both EFS and OS. CONCLUSION: The mJHBPS nomogram can stratify CRLM patients with sufficient differences in EFS and OS. SF was recommended for patients in the low-risk group.


Assuntos
Neoplasias Colorretais/patologia , Neoplasias Colorretais/terapia , Neoplasias Hepáticas/patologia , Neoplasias Hepáticas/terapia , Fígado/patologia , Idoso , Feminino , Humanos , Metástase Linfática/patologia , Masculino , Nomogramas , Pâncreas/patologia , Prognóstico , Intervalo Livre de Progressão , Estudos Retrospectivos
3.
Zhonghua Gan Zang Bing Za Zhi ; 29(6): 505-509, 2021 Jun 20.
Artigo em Chinês | MEDLINE | ID: mdl-34225424

RESUMO

Nonalcoholic fatty liver disease (NAFLD) has become the most common chronic liver disease in the world. Liver cirrhosis, liver cancer and a variety of extrahepatic chronic diseases are important risk factors for NAFLD. Currently, there is still a lack of effective therapeutic drugs. Liver inflammation is a key driving factor for the progression of NAFLD, so regulating liver inflammation may provide a potential means to delay and reverse the progression of nonalcoholic steatohepatitis (NASH). Studies have found that the gut-liver-immune axis plays an important role in the progression of NASH. Gut microbiota can use its metabolites to induce glycolipid toxicity, oxidative stress and intestinal barrier damage, while bacterial components such as lipopolysaccharides, peptidoglycans, bacterial DNA and extracellular vesicles can translocate into the liver through the damaged intestinal barrier, causing excessive activation of immune cells, thus aggravating liver inflammation and promoting the progress of NASH. This paper focuses on the gut-liver-immune axis to analyze the gut microbiota mediated liver immunity and its mechanism in the occurrence and development of NASH, so as to lay a theoretical foundation for the research and development of new therapeutic strategies for NASH.


Assuntos
Microbioma Gastrointestinal , Neoplasias Hepáticas , Hepatopatia Gordurosa não Alcoólica , Humanos , Fígado/patologia , Cirrose Hepática/patologia , Neoplasias Hepáticas/patologia , Hepatopatia Gordurosa não Alcoólica/etiologia , Hepatopatia Gordurosa não Alcoólica/patologia
4.
Zhonghua Gan Zang Bing Za Zhi ; 29(6): 604-608, 2021 Jun 20.
Artigo em Chinês | MEDLINE | ID: mdl-34225440

RESUMO

Nonalcoholic fatty liver disease (NAFLD) is one of the most common chronic liver diseases worldwide and it includes simple fatty liver disease (NAFL), nonalcoholic steatohepatitis (NASH), liver cirrhosis, and hepatocellular carcinoma-related NASH. The degree of hepatic necrotizing inflammation and fibrosis is closely related to the long-term prognosis of NAFLD patients. Therefore, early monitoring of disease progression and intervention are of great significance. Liver biopsy, as an invasive test, has always been the gold standard for the diagnosis of NAFLD; however, it is not easy to carry out widely in clinical practice. With the development of omics-related research technologies, the potential application value of omics biomarkers such as genomics, transcriptomics, proteomics, glycomics, metabolomics, and so on in the diagnosis of NAFLD has gradually emerged. This review mainly summarizes the research progress of omics biomarkers for NAFLD.


Assuntos
Neoplasias Hepáticas , Hepatopatia Gordurosa não Alcoólica , Biomarcadores , Progressão da Doença , Humanos , Fígado/patologia , Cirrose Hepática/patologia , Neoplasias Hepáticas/patologia , Hepatopatia Gordurosa não Alcoólica/diagnóstico , Hepatopatia Gordurosa não Alcoólica/genética , Hepatopatia Gordurosa não Alcoólica/patologia
5.
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
6.
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
7.
Int J Mol Sci ; 22(11)2021 May 29.
Artigo em Inglês | MEDLINE | ID: mdl-34072570

RESUMO

Sorafenib, a multi-kinase inhibitor, is the first-line treatment for advanced hepatocellular carcinoma (HCC) patients. However, this drug only provides a short improvement of patients' overall survival, and drug resistance is commonly developed. Thus, the identification of resistant factor(s) or biomarker(s) is needed to develop more efficient therapeutic strategies. Long, non-coding RNAs (lncRNAs) have recently been viewed as attractive cancer biomarkers and drive many important cancer phenotypes. A lncRNA, ZFAS1 (ZNFX1 antisense RNA 1) has been found to promote HCC metastasis. This study found that sorafenib induced ZFAS1 expression specifically in sorafenib-resistant HCC cells. Although ZFAS1 knockdown did not restore the sensitivity of HCC cells to sorafenib, its expression may act as a resistant biomarker for sorafenib therapy. Bioinformatics analysis predicted that sorafenib tended to induce pathways related to endoplasmic reticulum (ER) stress and the unfolded protein response (UPR) in sorafenib-resistant HCC cells. In vitro experimental evidence suggested that sorafenib induced protein kinase RNA-like ER kinase (PERK)/activating transcription factor 4 (ATF4)-dependent ZFAS1 expression, and sorafenib resistance could be overcome by PERK/ATF inhibitors. Therefore, PERK/ATF4/ZFAS1 signaling axis might be an attractive therapeutic and prognostic biomarker for sorafenib therapy in HCC.


Assuntos
Fator 4 Ativador da Transcrição/metabolismo , Resistencia a Medicamentos Antineoplásicos/genética , Regulação Neoplásica da Expressão Gênica , Inibidores de Proteínas Quinases/farmacologia , RNA Longo não Codificante/genética , Sorafenibe/farmacologia , eIF-2 Quinase/metabolismo , Carcinoma Hepatocelular/genética , Carcinoma Hepatocelular/metabolismo , Carcinoma Hepatocelular/mortalidade , Carcinoma Hepatocelular/patologia , Linhagem Celular Tumoral , Técnicas de Silenciamento de Genes , Humanos , Estimativa de Kaplan-Meier , Neoplasias Hepáticas/genética , Neoplasias Hepáticas/metabolismo , Neoplasias Hepáticas/mortalidade , Neoplasias Hepáticas/patologia , Prognóstico , Análise de Sequência de RNA
8.
World J Gastroenterol ; 27(21): 2784-2794, 2021 Jun 07.
Artigo em Inglês | MEDLINE | ID: mdl-34135554

RESUMO

According to Barcelona Clinic Liver Cancer recommendations, intermediate stage hepatocellular carcinomas (stage B) are excluded from liver resection and are referred to palliative treatment. Moreover, Child-Pugh B patients are not usually candidates for liver resection. However, many hepatobiliary centers in the world manage patients with intermediate stage hepatocellular carcinoma or Child-Pugh B cirrhosis with liver resection, maintaining that hepatic resection is not contraindicated in selected patients with non-early-stage hepatocellular carcinoma and without normal liver function. Several studies demonstrate that resection provides the best survival benefit for selected patients in very early/early and even in intermediate stages of Barcelona Clinic Liver Cancer classification, and this treatment gives good results in the setting of multinodular, large tumors in patients with portal hypertension and/or Child-Pugh B cirrhosis. In this review we explore this controversial topic, and we show through the literature analysis how liver resection may improve the short- and long-term survival rate of carefully selected Barcelona Clinic Liver Cancer B and Child-Pugh B hepatocellular carcinoma patients. However, other large clinical studies are needed to clarify which patients with intermediate stage hepatocellular carcinoma are most likely to benefit from liver resection.


Assuntos
Carcinoma Hepatocelular , Neoplasias Hepáticas , Carcinoma Hepatocelular/patologia , Carcinoma Hepatocelular/cirurgia , Hepatectomia/efeitos adversos , Humanos , Cirrose Hepática/complicações , Cirrose Hepática/cirurgia , Neoplasias Hepáticas/patologia , Neoplasias Hepáticas/cirurgia , Estadiamento de Neoplasias , Estudos Retrospectivos
9.
Medicine (Baltimore) ; 100(25): e26373, 2021 Jun 25.
Artigo em Inglês | MEDLINE | ID: mdl-34160411

RESUMO

RATIONALE: Hepatocellular carcinoma (HCC) is the most common liver cancer. The efficacy of the present treatment is disappointing, and the prognosis is poor. Donafenib, a novel multikinase inhibitor, is a new deuterated derivative of sorafenib. It can improve overall survival in patients with advanced HCC, with a favorable safety and tolerability profile over sorafenib. PATIENT CONCERNS: Here, we report the case of a 51-year-old male patient who presented with experienced epigastric discomfort for the prior several days. He had a history of untreated chronic hepatitis B virus infection for >29 years and no other underlying diseases. Based on further investigations, he was diagnosed with advanced HCC and refused surgery. DIAGNOSIS: Based on the patient's performance status, tumor status assessed by computed tomography, liver function, and percutaneous liver biopsy, he was diagnosed with advanced HCC Barcelona Clinic Liver Cancer Stage C. INTERVENTIONS: The patient was administered a 200-mg oral dose of donafenib twice-daily. OUTCOMES: The patient was followed-up from the time of diagnosis. He received donafenib for 31 months, and the progression-free survival time was 31 months (from May 2017 to December 2019); the overall survival time was not reached. The patient reported little abdominal distension with no other obvious discomfort while taking the medication. LESSON: Donafenib showed good efficacy for the treatment of advanced HCC, with mild side effects. Deuterium-containing drugs seem to be a promising avenue for medical innovation.


Assuntos
Carcinoma Hepatocelular/terapia , Guanina/análogos & derivados , Hepatite B Crônica/terapia , Neoplasias Hepáticas/terapia , Piridinas/uso terapêutico , Biópsia , Carcinoma Hepatocelular/diagnóstico , Carcinoma Hepatocelular/patologia , Carcinoma Hepatocelular/virologia , Progressão da Doença , Quimioterapia Combinada/métodos , Guanina/uso terapêutico , Hepatectomia , Hepatite B Crônica/patologia , Hepatite B Crônica/virologia , Humanos , Fígado/diagnóstico por imagem , Fígado/patologia , Fígado/cirurgia , Neoplasias Hepáticas/diagnóstico , Neoplasias Hepáticas/patologia , Neoplasias Hepáticas/virologia , Masculino , Pessoa de Meia-Idade , Terapia Neoadjuvante/métodos , Tomografia Computadorizada por Raios X , Resultado do Tratamento
10.
Medicine (Baltimore) ; 100(25): e26390, 2021 Jun 25.
Artigo em Inglês | MEDLINE | ID: mdl-34160420

RESUMO

ABSTRACT: Hepatocellular carcinoma (HCC) involving the inferior vena cava rarely occurs, but its prognosis is extremely poor, with no established treatment to date. This study aimed to analyze the clinical outcome and toxicity of radiotherapy (RT) targeting inferior vena cava tumor thrombus (IVCTT) in HCC patients.From November 2011 to July 2020, medical record of 19 HCC patients who were treated with RT for IVCTT was retrospectively reviewed. RT was delivered using 3-dimensional conformal radiation therapy, intensity-modulated radiation therapy, and stereotactic body radiation therapy. The median radiation dose was 50 Gy (range, 45-55.8 Gy) for intensity-modulated radiation therapy and three-dimensional conformal radiotherapy. Stereotactic body radiation therapy was performed in 5 patients, for a total of 32 Gy in 4 fractions.The median follow-up duration was 8.1 months (range, 3.3-26.5 months). The median overall survival was 9.4 months (range, 3.7-26.5 months), and the 1-year overall survival rate was 37.1%. Eight of 19 patients (42.1%) had extrahepatic metastasis at the start of RT. Six of 11 patients (54.5%) who did not have extrahepatic metastasis at the start of RT showed extrahepatic metastasis after RT. The major cause of death was progression of extrahepatic metastasis (11 patients, 57.9%). The overall response rate of IVCTT for RT was 84.2%, and the local control rate at the time of the last follow-up was 89.4%. After RT, the most common first progression site was the lungs (9 patients, 47.4%). Most toxicities were grade 1 to 2 gastrointestinal (26.3%) and liver enzyme elevation (68.4%). Three patients occurred pulmonary embolism after RT later than 5 months after.RT is a feasible and safe local therapy for IVCTT, with favorable tumor control and acceptable toxicity. Extrahepatic metastasis is the major progression pattern and a leading cause of death in patients treated with RT. The combination of effective systemic therapy with RT may have to be considered.


Assuntos
Carcinoma Hepatocelular/radioterapia , Neoplasias Hepáticas/radioterapia , Veia Cava Inferior/patologia , Trombose Venosa/radioterapia , Adulto , Idoso , Carcinoma Hepatocelular/complicações , Carcinoma Hepatocelular/mortalidade , Carcinoma Hepatocelular/patologia , Progressão da Doença , Estudos de Viabilidade , Feminino , Seguimentos , Humanos , Fígado/irrigação sanguínea , Fígado/diagnóstico por imagem , Fígado/patologia , Neoplasias Hepáticas/complicações , Neoplasias Hepáticas/mortalidade , Neoplasias Hepáticas/patologia , Imageamento por Ressonância Magnética , Masculino , Pessoa de Meia-Idade , Invasividade Neoplásica/patologia , Prognóstico , Intervalo Livre de Progressão , Radiocirurgia/efeitos adversos , Dosagem Radioterapêutica , Radioterapia Conformacional/efeitos adversos , Radioterapia de Intensidade Modulada/efeitos adversos , Critérios de Avaliação de Resposta em Tumores Sólidos , Estudos Retrospectivos , Taxa de Sobrevida , Tomografia Computadorizada por Raios X , Veia Cava Inferior/diagnóstico por imagem , Trombose Venosa/diagnóstico , Trombose Venosa/etiologia , Trombose Venosa/patologia
11.
Nat Commun ; 12(1): 3684, 2021 06 17.
Artigo em Inglês | MEDLINE | ID: mdl-34140495

RESUMO

Interaction between tumor cells and immune cells in the tumor microenvironment is important in cancer development. Immune cells interact with the tumor cells to shape this process. Here, we use single-cell RNA sequencing analysis to delineate the immune landscape and tumor heterogeneity in a cohort of patients with HBV-associated human hepatocellular carcinoma (HCC). We found that tumor-associated macrophages suppress tumor T cell infiltration and TIGIT-NECTIN2 interaction regulates the immunosuppressive environment. The cell state transition of immune cells towards a more immunosuppressive and exhaustive status exemplifies the overall cancer-promoting immunocellular landscape. Furthermore, the heterogeneity of global molecular profiles reveals co-existence of intra-tumoral and inter-tumoral heterogeneity, but is more apparent in the latter. This analysis of the immunosuppressive landscape and intercellular interactions provides mechanistic information for the design of efficacious immune-oncology treatments in hepatocellular carcinoma.


Assuntos
Carcinoma Hepatocelular/imunologia , Regulação da Expressão Gênica/imunologia , Neoplasias Hepáticas/imunologia , Macrófagos/imunologia , Microambiente Tumoral/imunologia , Algoritmos , Animais , Carcinoma Hepatocelular/genética , Carcinoma Hepatocelular/patologia , Carcinoma Hepatocelular/virologia , Proliferação de Células , Regulação da Expressão Gênica/genética , Vírus da Hepatite B/genética , Humanos , Neoplasias Hepáticas/genética , Neoplasias Hepáticas/patologia , Neoplasias Hepáticas/virologia , Macrófagos/citologia , Macrófagos/metabolismo , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Nectinas/genética , Nectinas/metabolismo , Análise de Componente Principal , Prognóstico , RNA-Seq , Receptores Imunológicos/metabolismo , Análise de Célula Única , Linfócitos T/citologia , Linfócitos T/imunologia , Microambiente Tumoral/genética
12.
Medicine (Baltimore) ; 100(26): e26414, 2021 Jul 02.
Artigo em Inglês | MEDLINE | ID: mdl-34190159

RESUMO

ABSTRACT: Transcatheter arterial chemoembolization (TACE) is a standard treatment modality for intermediate stage hepatocellular carcinoma (HCC). The aim of this study was to determine the tumor radiological characteristics associated with prognosis of patients with early-staged HCC receiving TACE.Patients with BCLC stage A HCC were enrolled at Taichung Veterans General Hospital from January 2005 to December 2009. According to mRECIST criteria, patients with or without complete response (CR) were assigned to either the CR group or the non-CR group. Clinical and radiological characteristics were compared between the two groups.In 40 enrolled patients, 24 (60%) were in the CR group, and 16 (40%) in the non-CR group. Clinical parameters were similar between the 2 groups. Radiological characteristics including complete lipidol retention and the absence of residual tumor blush were significantly correlated with achievement of CR in the patients with small-sized HCC. Patients with CR after TACE had a significantly longer overall survival than those without (31.29 vs 22.63 months, P = .021).Complete lipidol retention and the absence of residual tumor blush were correlated with the radiological complete tumor response of these patients with small-sized early-stage HCC receiving TACE.


Assuntos
Carcinoma Hepatocelular/diagnóstico por imagem , Carcinoma Hepatocelular/terapia , Quimioembolização Terapêutica , Neoplasias Hepáticas/diagnóstico por imagem , Neoplasias Hepáticas/terapia , Idoso , Carcinoma Hepatocelular/patologia , Meios de Contraste/administração & dosagem , Feminino , Humanos , Óleo Iodado/administração & dosagem , Neoplasias Hepáticas/patologia , Masculino , Estadiamento de Neoplasias , Radiologia , Resultado do Tratamento
13.
Medicine (Baltimore) ; 100(26): e26441, 2021 Jul 02.
Artigo em Inglês | MEDLINE | ID: mdl-34190168

RESUMO

ABSTRACT: This study retrospectively studied transarterial chemoembolization (TACE) combined with partial splenic embolization (PSE) in the treatment of hepatocellular carcinoma (HCC) with severe hypersplenism.Seventy patients with HCC in Barcelona Clinic Liver Cancer (BCLC) stage B or C with hypersplenism were divided into non-partial splenic embolization group (N-PSE, n = 51) and partial splenic embolization group (PSE, n = 19). The N-PSE group was further divided into N-PSE with mild to moderate hypersplenism (N-PSE-M, 47 cases) and N-PSE with severe hypersplenism (N-PSE-S, 4 cases).In the PSE group, leukocytes, neutrophils, lymphocytes, and platelets were significantly increased (P < .05) and were significantly different from that in the N-PSE group (P < .05). In the N-PSE group, except for a slight increase in neutrophils, other blood cells were decreased, including lymphocytes that were significantly decreased (P < .05). There was no significant difference in the changes of liver function between the 2 groups before and after surgery (P > .05). The analysis showed a significant increase in ascites after 6 months of TACE in the N-PSE group (P < .05). According to the follow-up results, the median overall survival (OS) in the PSE group was 24.47 ±â€Š3.68 (months) and progression-free survival (PFS) was 12.63 ±â€Š4.98 (months). Regardless of OS or PFS, the PSE group was superior to the N-PSE group and its subgroups, with a statistically significant difference in PFS between the N-PSE group and PSE group (P < .05). Moreover, the time of extrahepatic progression was significantly earlier in the N-PSE group than in the PSE group (P < .05). N-PSE-S group had the worst prognosis, and PFS and OS were worse than the other 2 groups, suggesting that PSE in severe hypersplenism may improve PFS and OS.In patients with HCC and severe hypersplenism, TACE should be actively combined with PSE treatment.


Assuntos
Carcinoma Hepatocelular , Quimioembolização Terapêutica/métodos , Hiperesplenismo , Neoplasias Hepáticas , Baço/patologia , Carcinoma Hepatocelular/complicações , Carcinoma Hepatocelular/epidemiologia , Carcinoma Hepatocelular/patologia , Carcinoma Hepatocelular/terapia , Quimioembolização Terapêutica/estatística & dados numéricos , China/epidemiologia , Progressão da Doença , Feminino , Humanos , Hiperesplenismo/sangue , Hiperesplenismo/complicações , Hiperesplenismo/diagnóstico , Hiperesplenismo/terapia , Testes de Função Hepática/métodos , Neoplasias Hepáticas/epidemiologia , Neoplasias Hepáticas/patologia , Neoplasias Hepáticas/terapia , Masculino , Pessoa de Meia-Idade , Estadiamento de Neoplasias , Tamanho do Órgão , Avaliação de Processos e Resultados em Cuidados de Saúde , Prognóstico , Índice de Gravidade de Doença
14.
Medicine (Baltimore) ; 100(26): e26487, 2021 Jul 02.
Artigo em Inglês | MEDLINE | ID: mdl-34190174

RESUMO

ABSTRACT: To evaluate the effect of preoperative serum alpha-fetoprotein(AFP) level to total tumor volume (TTV) ratio as a prognostic marker on predicting the tumor recurrence and overall survival time of patients with hepatocellular carcinoma (HCC) after liver transplantation.One-hundred eight patients with HCC who underwent liver transplantation in Beijing Chaoyang Hospital from April 2013 to October 2017 were studied. Divided into AFP/TTV≤2 group and AFP/TTV>2 group by the best cut-off score calculated by receiver operation characteristic curve, the clinical and pathological data of the patients in two groups were compared to explore the relationship between AFP/TTV and tumor recurrence together with the prognosis of HCC patients after liver transplantation. Risk factors of early tumor recurrence and poor prognosis of HCC in patients after liver transplantation were studied by multivariate regression analysis. Kaplan-Meier survival analysis was used to compare the tumor-free survival and overall survival between the two groups of patients.In 108 patients, 47 patients have AFP/TTV≤2 while 61 patients have AFP/TTV>2. Patients in AFP/TTV≤2 group have longer tumor-free survival time and overall survival time compared with patients in AFP/TTV>2 group. The age, total bilirubin level, serum AFP level, TTV, portal vein tumor thrombus and AFP/TTV (all P < .05) of patient with HCC are closely related to poor prognosis after liver transplantation. Multivariate regression analysis showed that have portal vein tumor thrombus (hazard ratio [HR] = 2.345, P < .05), TTV≥65.5 cm3 (HR = 2.701, P < .05) and AFP/TTV > 2 (HR = 4.624, P < .05) are independent risk factors for poor prognosis of patients with HCC after liver transplantation while TTV≥65.5 cm3 (HR = 2.451, P < .05) and AFP/TTV > 2 (HR = 4.257, P < 0.05) were independent risk factors for tumor recurrence at the same time.The tumor recurrence and the prognosis of patients with HCC after liver transplantation is affected by many factors. AFP/TTV ratio has important predictive value for the tumor recurrence and the prognosis of patients with HCC after liver transplantation. AFP/TTV>2 is an independent risk factor for both early tumor recurrence and poor prognosis of patients with HCC after liver transplantation.


Assuntos
Carcinoma Hepatocelular , Neoplasias Hepáticas , Transplante de Fígado , Recidiva Local de Neoplasia , Veia Porta , alfa-Fetoproteínas/análise , Biomarcadores Tumorais/sangue , Carcinoma Hepatocelular/sangue , Carcinoma Hepatocelular/patologia , Carcinoma Hepatocelular/cirurgia , Intervalo Livre de Doença , Feminino , Humanos , Estimativa de Kaplan-Meier , Testes de Função Hepática/métodos , Neoplasias Hepáticas/sangue , Neoplasias Hepáticas/patologia , Neoplasias Hepáticas/cirurgia , Transplante de Fígado/efeitos adversos , Transplante de Fígado/métodos , Masculino , Pessoa de Meia-Idade , Recidiva Local de Neoplasia/diagnóstico , Recidiva Local de Neoplasia/epidemiologia , Veia Porta/diagnóstico por imagem , Veia Porta/patologia , Valor Preditivo dos Testes , Prognóstico , Medição de Risco/métodos , Fatores de Risco , Carga Tumoral
15.
Medicine (Baltimore) ; 100(22): e25984, 2021 Jun 04.
Artigo em Inglês | MEDLINE | ID: mdl-34087841

RESUMO

BACKGROUND: As one of the key factors, postoperative recurrence of hepatocellular carcinoma (HCC) influences the therapeutic effects and survival period of patients. Therefore, the early diagnosis of postoperative recurrence of HCC plays an important role in improving the therapeutic effects and prognosis. Contrast-enhanced ultrasound (CEUS) plays an important role in the early diagnosis of postoperative recurrence of HCC. However, the accuracy of CEUS in predicting postoperative recurrence of HCC is still controversial. Therefore, in this study, a meta-analysis was carried out to further evaluate the accuracy of CEUS in predicting postoperative recurrence of HCC, thus providing evidence support for the early diagnosis of HCC. METHODS: The literatures on the CEUS diagnosis of postoperative recurrence of HCC were collected by searching China National Knowledge Infrastructure, Wanfang, China Biology Medicine disc, PubMed, EMBASE, Cochrane Library, and Web of Science on computer. The retrieval time is set from the start of the database until April 2021. The meta-analysis of the literatures that meet the quality standards was conducted by Stata 16.0 software. RESULTS: The results of this meta-analysis will be submitted to a peer-reviewed journal for publication. CONCLUSION: This study will provide evidence support for the accuracy of CEUS in the diagnosis of postoperative recurrence of HCC. ETHICS AND DISSEMINATION: The private information from individuals will not be published. This systematic review also should not damage participants' rights. Ethical approval is not available. The results may be published in a peer-reviewed journal or disseminated in relevant conferences. OSF REGISTRATION NUMBER: DOI 10.17605/OSF.IO/HB46W.


Assuntos
Carcinoma Hepatocelular/diagnóstico por imagem , Carcinoma Hepatocelular/patologia , Neoplasias Hepáticas/diagnóstico por imagem , Neoplasias Hepáticas/patologia , Recidiva Local de Neoplasia/patologia , Carcinoma Hepatocelular/cirurgia , Diagnóstico Precoce , Humanos , Neoplasias Hepáticas/cirurgia , Prognóstico , Projetos de Pesquisa , Ultrassonografia/métodos
16.
Medicine (Baltimore) ; 100(22): e26194, 2021 Jun 04.
Artigo em Inglês | MEDLINE | ID: mdl-34087888

RESUMO

BACKGROUND: Long noncoding RNAs (lncRNAs) can work as microRNA (miRNA) sponges through a competitive endogenous RNA (ceRNA) mechanism. LncRNAs and miRNAs are important components of competitive endogenous binding, and their expression imbalance in hepatocellular carcinoma (HCC) is closely related to tumor development, diagnosis, and prognosis. This study explored the potential impact of the ceRNA regulatory network in HCC on the prognosis of HCC patients. METHODS: We thoroughly researched the differential expression profiles of lncRNAs, miRNAs, and mRNAs from 2 HCC Gene Expression Omnibus datasets (GSE98269 and GSE60502). Then, a dysregulated ceRNA network was constructed by bioinformatics. In addition, hub genes in the ceRNA network were screened by Cytoscape, these hub genes functional analysis was performed by gene set enrichment analysis, and the expression of these hub genes in tumors and their correlation with patient prognosis were verified with Gene Expression Profiling Interactive Analysis. RESULTS: A ceRNA network was successfully constructed in this study including 4 differentially expressed (DE) lncRNAs, 7 DEmiRNAs, and 166 DEmRNAs. Importantly, 4 core genes (CCNA2, CHEK1, FOXM1, and MCM2) that were significantly associated with HCC prognosis were identified. CONCLUSIONS: Our study provides comprehensive and meaningful insights into HCC tumorigenesis and the underlying molecular mechanisms of ceRNA. Furthermore, the specific ceRNAs can be further used as potential therapeutic targets and prognostic biomarkers for HCC.


Assuntos
Carcinoma Hepatocelular/genética , Biologia Computacional/métodos , Regulação Neoplásica da Expressão Gênica/genética , Neoplasias Hepáticas/patologia , RNA Longo não Codificante/genética , Adulto , Biomarcadores Tumorais/metabolismo , Carcinogênese/genética , Carcinoma Hepatocelular/diagnóstico , Quinase 1 do Ponto de Checagem/genética , Ciclina A2/genética , Feminino , Proteína Forkhead Box M1/genética , Perfilação da Expressão Gênica/métodos , Humanos , Masculino , MicroRNAs/genética , Pessoa de Meia-Idade , Componente 2 do Complexo de Manutenção de Minicromossomo/genética , Prognóstico , RNA Mensageiro/genética , Motivos de Ligação ao RNA/genética
17.
Int J Nanomedicine ; 16: 4001-4016, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34135585

RESUMO

Background: Tumor angiogenesis has been proven to potentiate tumor growth and metastasis; therefore, the strategies targeting tumor-related angiogenesis have great potentials in antitumor therapy. Methods: Here, the GA&Gal dual-ligand-modified liposomes co-loaded with curcumin and combretastatin A-4 phosphate (CUCA/GA&Gal-Lip) were prepared and characterized. A novel "BEL-7402+HUVEC" co-cultured cell model was established to mimic tumor microenvironment. The cytotoxicity and migration assays were performed against the novel co-cultured model. Angiogenesis ability was evaluated by tube formation test, and in vivo metastatic ability was evaluated by lung metastasis test. Results: The result demonstrated that dual-ligand-modified liposomes showed greater inhibition of tumor angiogenesis and metastasis in comparison with other combined groups. Significantly, the mechanism analysis revealed that curcumin and combretastatin A-4 phosphate could inhibit tumor angiogenesis and metastasis via down-regulation of VEGF and VEGFR2 expression, respectively, and that GA&Gal-Lip could improve antitumor effect by GA/Gal-mediated active-targeting delivery. Conclusion: CUCA/GA&Gal-Lip hold great potentials in hepatoma-targeting delivery of antitumor drugs and can achieve anti-angiogenic and anti-metastatic effects by simultaneously blocking VEGF/VEGFR2 signal pathway, therefore exhibiting superior anti-hepatoma efficacy.


Assuntos
Inibidores da Angiogênese/administração & dosagem , Antineoplásicos Fitogênicos/administração & dosagem , Lipossomos/farmacologia , Neovascularização Patológica/tratamento farmacológico , Inibidores da Angiogênese/farmacologia , Animais , Antineoplásicos Fitogênicos/farmacologia , Carcinoma Hepatocelular/tratamento farmacológico , Carcinoma Hepatocelular/patologia , Linhagem Celular Tumoral , Curcumina/administração & dosagem , Curcumina/farmacocinética , Liberação Controlada de Fármacos , Regulação Neoplásica da Expressão Gênica/efeitos dos fármacos , Células Endoteliais da Veia Umbilical Humana , Humanos , Ligantes , Lipossomos/administração & dosagem , Lipossomos/química , Neoplasias Hepáticas/tratamento farmacológico , Neoplasias Hepáticas/patologia , Neoplasias Pulmonares/tratamento farmacológico , Neoplasias Pulmonares/genética , Neoplasias Pulmonares/secundário , Camundongos Endogâmicos BALB C , Estilbenos/administração & dosagem , Estilbenos/farmacologia , Ensaios Antitumorais Modelo de Xenoenxerto
18.
J Int Med Res ; 49(6): 3000605211023351, 2021 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-34139869

RESUMO

BACKGROUND: Sorafenib is mainly used to treat patients with hepatocellular carcinoma (HCC) Barcelona Clinic Liver Cancer (BCLC) stage C, many of whom also have severe cirrhosis. However, hypersplenism and digestive tract hemorrhage are common complications of cirrhosis, which increase the risk and difficulty of treatment. METHODS: Nineteen patients with HCC BCLC stage C with hypersplenism were treated with sorafenib plus partial splenic embolism at Chongqing University Cancer Hospital, Chongqing, China, between January 2015 and June 2018. We analyzed the therapeutic effect and clinical safety of this treatment in these patients. RESULT: Hypersplenism was rectified in all patients. The incidence rates of hemorrhage and myelosuppression were 0%, and the mean survival time was 11.2 months. CONCLUSION: Sorafenib plus partial splenic embolism could relieve hypersplenism and prolong survival in patients with BCLC stage C HCC.


Assuntos
Antineoplásicos , Carcinoma Hepatocelular , Quimioembolização Terapêutica , Embolia , Hiperesplenismo , Neoplasias Hepáticas , Antineoplásicos/uso terapêutico , Carcinoma Hepatocelular/complicações , Carcinoma Hepatocelular/tratamento farmacológico , Carcinoma Hepatocelular/patologia , China , Humanos , Hiperesplenismo/complicações , Hiperesplenismo/tratamento farmacológico , Neoplasias Hepáticas/complicações , Neoplasias Hepáticas/tratamento farmacológico , Neoplasias Hepáticas/patologia , Estadiamento de Neoplasias , Compostos de Fenilureia/uso terapêutico , Sorafenibe/uso terapêutico , Resultado do Tratamento
19.
Toxins (Basel) ; 13(6)2021 05 27.
Artigo em Inglês | MEDLINE | ID: mdl-34072178

RESUMO

Hepatitis B virus (HBV) infection and aflatoxin B1 (AFB1) exposure have been recognized as independent risk factors for the occurrence and development of hepatocellular carcinoma (HCC), but their combined impacts and the potential metabolic mechanisms remain poorly characterized. Here, a comprehensive non-targeted metabolomic study was performed following AFB1 exposed to Hep3B cells at two different doses: 16 µM and 32 µM. The metabolites were identified and quantified by an ultra-performance liquid chromatography-mass spectrometry (UPLC-MS)-based strategy. A total of 2679 metabolites were identified, and 392 differential metabolites were quantified among three groups. Pathway analysis indicated that dynamic metabolic reprogramming was induced by AFB1 and various pathways changed significantly, including purine and pyrimidine metabolism, hexosamine pathway and sialylation, fatty acid synthesis and oxidation, glycerophospholipid metabolism, tricarboxylic acid (TCA) cycle, glycolysis, and amino acid metabolism. To the best of our knowledge, the alteration of purine and pyrimidine metabolism and decrease of hexosamine pathways and sialylation with AFB1 exposure have not been reported. The results indicated that our metabolomic strategy is powerful to investigate the metabolome change of any stimulates due to its high sensitivity, high resolution, rapid separation, and good metabolome coverage. Besides, these findings provide an overview of the metabolic mechanisms of the AFB1 combined with HBV and new insight into the toxicological mechanism of AFB1. Thus, targeting these metabolic pathways may be an approach to prevent carcinogen-induced cancer, and these findings may provide potential drug targets for therapeutic intervention.


Assuntos
Aflatoxina B1/toxicidade , Carcinoma Hepatocelular/metabolismo , Neoplasias Hepáticas/metabolismo , Metabolômica/métodos , Aminoácidos/metabolismo , Apoptose/efeitos dos fármacos , Carcinoma Hepatocelular/patologia , Humanos , Metabolismo dos Lipídeos/efeitos dos fármacos , Neoplasias Hepáticas/patologia , Redes e Vias Metabólicas , Estresse Oxidativo/efeitos dos fármacos , Purinas/metabolismo , Pirimidinas/metabolismo , Espectrometria de Massas em Tandem , Células Tumorais Cultivadas
20.
Aging (Albany NY) ; 13(12): 16267-16286, 2021 06 18.
Artigo em Inglês | MEDLINE | ID: mdl-34148029

RESUMO

Multiple studies have revealed that long non-coding RNA (lncRNAs) served as regulatory factors in modulating tumorigenesis of hepatocellular carcinoma (HCC). In the present study, we demonstrated that lncRNA HCP5 was overexpressed in HCC tissues and cell lines, and these findings were obvious even in metastatic and recurrent cases. Knockdown of HCP5 significantly alleviated cell growth, metastasis, and invasion both in vitro and in vivo through promoting apoptosis and by inactivating the epithelial-mesenchymal transition (EMT) progress. Moreover, miR-29b-3p has been identified as a negatively regulatory target gene of HCP5, and served as a tumor suppressor of HCC to prevent cell proliferation, migration, and invasion. Subsequently, DNMT3A was identified as a downstream regulatory factor of miR-29b-3p, and acted as a participated element of HCC progression by activating AKT phosphorylation. Taken together, our study elucidated for the first time that HCP5 plays a crucial role in HCC via the HCP5/miR-29b-3p/DNMT3A/AKT axis and our findings demonstrated a novel diagnostic and therapeutic strategy with potentiality to treat HCC.


Assuntos
Carcinoma Hepatocelular/genética , Carcinoma Hepatocelular/patologia , DNA (Citosina-5-)-Metiltransferases/genética , Neoplasias Hepáticas/genética , Neoplasias Hepáticas/patologia , MicroRNAs/metabolismo , RNA Longo não Codificante/metabolismo , Regulação para Cima/genética , Idoso , Apoptose/genética , Sequência de Bases , Linhagem Celular Tumoral , Movimento Celular/genética , Proliferação de Células/genética , DNA (Citosina-5-)-Metiltransferases/metabolismo , Progressão da Doença , Transição Epitelial-Mesenquimal/genética , Feminino , Regulação Neoplásica da Expressão Gênica , Humanos , Masculino , MicroRNAs/genética , Pessoa de Meia-Idade , Invasividade Neoplásica , Metástase Neoplásica , Fosforilação , Proteínas Proto-Oncogênicas c-akt/metabolismo , RNA Longo não Codificante/genética
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