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1.
Adv Exp Med Biol ; 1287: 69-80, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-33034027

RESUMO

Interactions between liver cells are closely regulated by Notch signaling. Notch signaling has been reported clinically related to bile duct hypogenesis in Alagille syndrome, which is caused by mutations in the Jagged1 gene. Notch activation and hepatocarcinogenesis are closely associated since cancer signaling is affected by the development of liver cells and cancer stem cells. Gene expression and genomic analysis using a microarray revealed that abnormalities in Notch-related genes were associated with the aggressiveness of liver cancer. This pattern was also accompanied with α-fetoprotein- and EpCAM-expressing phenotypes in vitro, in vivo, and in clinical tissues. Hepatitis B or C virus chronic infection or alcohol- or steatosis-related liver fibrosis induces liver cancer. Previous reports demonstrated that HBx, a hepatitis B virus protein, was associated with Jagged1 expression. We found that the Jagged1 and Notch1 signaling pathways were closely associated with the transcription of covalently closed circular hepatitis B virus DNA, which regulated cAMP response element-binding protein, thereby affecting Notch1 regulation by the E3 ubiquitin ligase ITCH. This viral pathogenesis in hepatocytes induces liver cancer. In conclusion, Notch signaling exerts various actions and is a clinical signature associated with hepatocarcinogenesis and liver context-related developmental function.


Assuntos
Neoplasias Hepáticas , Receptores Notch/metabolismo , Transdução de Sinais , Hepatite/metabolismo , Hepatite/virologia , Vírus da Hepatite B/patogenicidade , Humanos , Neoplasias Hepáticas/metabolismo , Neoplasias Hepáticas/virologia , Proteínas Repressoras/metabolismo , Ubiquitina-Proteína Ligases/metabolismo
2.
Zhong Nan Da Xue Xue Bao Yi Xue Ban ; 45(9): 1053-1060, 2020.
Artigo em Inglês, Chinês | MEDLINE | ID: mdl-33051418

RESUMO

OBJECTIVES: Hepatocellular carcinoma (HCC) is one of the most common malignant tumors worldwide, especially in Asia and Africa. However, the underlying mechanism is still unclear. Consequently, it is important to explore its key genes and prognosis-related genes via bioinformatics. This study aimed to explore the molecular mechanism of HCC by using bioinformatics analysis for HCC gene chip data. METHODS: Microarray data of HCC genes were downloaded from public GEO database and screened for differentially expressed genes (DEGs) by GEO2R analysis. Then DAVID online tool was used for GO annotation and KEGG pathway enrichment analysis. STRING-DB online database and Cytoscape software were used for protein interaction network analysis.GEPIA and Ualcan were applied to evaluate prognosis and promoter methylation level. RESULTS: A total of 87 DEGs of HCC were screened, of which 15 genes were up-regulated and 72 genes were down-regulated. GO annotation indicated that most of the genes were involved in oxidation reduction,cellular amino acid derivative metabolic process, carboxylic acid catabolic process, and response to wounding. KEGG pathways were enriched in linoleic acid metabolism, retinol metabolism, complement and coagulation cascades,steroid hormone biosynthesis, drug metabolism, and other pathways. Two key modules and key genes AURKA and SPP2 were obtained by protein interaction network analysis. Prognostic analysis showed that the 2 genes were significantly correlated with the total survival time of patients with HCC. There was no significant difference in the methylation level of AURKA promoter between the primary tumor group and the normal group (P=0.296) and the methylation level of SPP2 promoter was significantly lower in the primary tumor group than that in the normal group (P<0.001). CONCLUSIONS: HCC-relevant AURKA and SPP2 are obtained via bioinformatics analysis, which are closely related to the prognosis of patients with HCC. Gene promoter methylation is not the main factor for AURKA and SPP2 expression levels.


Assuntos
Carcinoma Hepatocelular , Neoplasias Hepáticas , Carcinoma Hepatocelular/genética , Biologia Computacional , Perfilação da Expressão Gênica , Regulação Neoplásica da Expressão Gênica , Redes Reguladoras de Genes , Humanos , Neoplasias Hepáticas/genética , Análise de Sequência com Séries de Oligonucleotídeos , Fosfoproteínas
3.
Zhong Nan Da Xue Xue Bao Yi Xue Ban ; 45(9): 1009-1014, 2020.
Artigo em Inglês, Chinês | MEDLINE | ID: mdl-33051413

RESUMO

OBJECTIVES: To investigate the effect of HBV infection on PTEN expression, and to explore the possible molecular mechanisms. METHODS: HepG2 cells and HepG2.2.15 cells were cultured under suitable conditions for 48 hours, and the expressions of PTEN, Nrf2 and pGSK3ß in HepG2 and HepG2.2.15 cells were detected by Western blotting. After the blank plasmid (EV) and the plasmid pWXL-Nrf2 were transiently transfected into HepG2 and HepG2.2.15 cells, respectively, the HepG2 and HepG2.2.15 cells were treated with the selective inhibitor of GSK3ß (25 nmol/L LiCl). After 48 h, the expressions of Nrf2, pGSK3ß and PTEN in HepG2 and HepG2.2.15 cells were examined by Western blotting. RESULTS: Expression of PTEN was reduced and the levels of Nrf2 and pGSK3ß were increased in HepG2.2.15 cells compared with those in the HepG2 cells (all P<0.05). After transfection with pWXL-Nrf2, the protein expression of Nrf2 and pGSK3ß in cells were significantly increased while the protein expression of PTEN was decreased (all P<0.05). Furthermore, LiCl treatment up-regulated the protein expression of Nrf2 and pGSK3ß, and eventually suppressed the production of PTEN (all P<0.05). CONCLUSIONS: HBV may down-regulate PTEN expression via Nrf2/GSK3ß signaling pathway, which may provide new ideas for the targeting therapy of hepatocellular carcinoma.


Assuntos
Neoplasias Hepáticas , Fator 2 Relacionado a NF-E2 , PTEN Fosfo-Hidrolase , Glicogênio Sintase Quinase 3 beta/genética , Glicogênio Sintase Quinase 3 beta/metabolismo , Vírus da Hepatite B/genética , Humanos , Fator 2 Relacionado a NF-E2/genética , PTEN Fosfo-Hidrolase/fisiologia , Transdução de Sinais
4.
Nihon Shokakibyo Gakkai Zasshi ; 117(10): 914-918, 2020.
Artigo em Japonês | MEDLINE | ID: mdl-33041303

RESUMO

A fifty-year-old man with a liver metastasis of a duodenal gastrointestinal stromal tumor (GIST) previously treated with imatinib. Thirty-three months following initiation of the therapy, he visited the emergency room of our hospital presenting with an upper abdominal pain. Dynamic CT scan revealed a ruptured liver metastasis of duodenal GIST. We used transcatheter arterial embolization to stop the bleeding. Due to the rarity of this condition, we herein report this case with an article review.


Assuntos
Embolização Terapêutica , Tumores do Estroma Gastrointestinal , Neoplasias Hepáticas , Duodeno , Tumores do Estroma Gastrointestinal/diagnóstico por imagem , Tumores do Estroma Gastrointestinal/tratamento farmacológico , Humanos , Mesilato de Imatinib/uso terapêutico , Neoplasias Hepáticas/diagnóstico por imagem , Neoplasias Hepáticas/tratamento farmacológico , Masculino , Pessoa de Meia-Idade
5.
Medicine (Baltimore) ; 99(41): e22118, 2020 Oct 09.
Artigo em Inglês | MEDLINE | ID: mdl-33031259

RESUMO

It is controversial regarding the treatment allocation for patients with stage I hepatocellular carcinoma (SI-HCC). The aim of the present study was to compare the long-term survival in SI-HCC patients undergoing liver transplantation (LT), liver resection (LR), local tumor destruction (LTD), or none. SI-HCC patients diagnosed between 2004 and 2015 were extracted from the SEER 18 registry database. Multivariable Cox models and propensity score matching (PSM) method were used to explore the association between surgical methods and long-term prognosis. A total of 5165 patients with stage I (AJCC, 6th or 7th) HCC were included in the study. Only 36.9% of patients diagnosed with HCC in stage I received surgical therapy. The incidence of LT was decreased over time (P < .001). In the multivariable-adjusted cohort (n = 5165), after adjusting potential confounding factors, a clear prognostic advantage of LT was observed in OS (P < .0001) compared with patients after LR. Patients undergoing LTD had a worse OS in comparison with patients who underwent LR (P < .0001). Patients who received no surgical treatment had the worst OS (P < .0001) among 4 treatment groups. In stratified analyses, the salutary effects of LT vs LR on OS were consistent across all subgroups except for a similar result in the noncirrhotic subgroup (P = .4414). The inferior survival effects of LTD vs LR on OS were consistent across all subgroups, and even in the subgroup with tumor size < 3 cm (P = .0342). In the PSM cohort, patients in LT group showed a better OS (P < .001) than patients in LR group (P < .0001) and patients undergoing LTD had a worse OS compared with patients who underwent LR (P = .00059). In conclusion, LT offered a survival advantage compared with LR among patients with Stage I HCC. LT is the best surgical treatment for stage I HCC in patients with advanced fibrosis, whereas LR provides comparable long-term outcomes to LT in patients without advanced fibrosis and should be considered as the first-line surgical option. LTD can be used as an alternative method when LR and LT are unavailable.


Assuntos
Carcinoma Hepatocelular/mortalidade , Carcinoma Hepatocelular/terapia , Neoplasias Hepáticas/mortalidade , Neoplasias Hepáticas/terapia , Feminino , Hepatectomia , Humanos , Transplante de Fígado , Masculino , Pessoa de Meia-Idade , Estadiamento de Neoplasias , Prognóstico , Pontuação de Propensão , Programa de SEER , Análise de Sobrevida
6.
Medicine (Baltimore) ; 99(41): e22486, 2020 Oct 09.
Artigo em Inglês | MEDLINE | ID: mdl-33031282

RESUMO

RATIONALE: Prostate-specific membrane antigen positron emission tomography-computed tomography (F-PSMA-1007 PET/CT) imaging is an emerging method for the diagnosis of prostate cancer (PC), but its efficiency in detecting other accompanying diseases has rarely been investigated. PATIENT CONCERNS: A 77-year-old man presented with a complaint of bone pain throughout his entire body lasting for 2 weeks. Routine preoperative whole-body bone scanning revealed multiple osteogenic metastases. His alpha-fetoprotein and prostate-specific antigen levels were 108.2 ng/mL and 53.32 ng/mL, respectively. F-PSMA-1007 PET/CT imaging revealed high tracer uptake in the primary lesion in the liver and the peripheral zone of the prostate. DIAGNOSES: Due to the results from imaging and pathological examinations, a diagnosis of PC with multiple bone metastases accompanied by primary hepatocellular carcinoma was made. INTERVENTIONS: Taking into consideration the patient's age, interventional therapy was performed for the liver lesion, whereas the prostate and bone lesions were treated with endocrine therapy. OUTCOMES: The patient recovered well and was discharged uneventfully postoperatively. The patient was also doing well at the 6-month follow-up. LESSONS: PSMA-PET/CT imaging results must be interpreted cautiously when the uptake of PSMA increases in a single lesion instead of the most common sites of PC metastasis. Pathological examination of the suspected lesions is also recommended.


Assuntos
Carcinoma Hepatocelular/diagnóstico por imagem , Neoplasias Hepáticas/diagnóstico por imagem , Neoplasias Primárias Múltiplas/diagnóstico por imagem , Tomografia Computadorizada com Tomografia por Emissão de Pósitrons/métodos , Idoso , Antígenos de Superfície , Radioisótopos de Flúor , Glutamato Carboxipeptidase II , Humanos , Achados Incidentais , Masculino , Neoplasias da Próstata
7.
Medicine (Baltimore) ; 99(41): e22565, 2020 Oct 09.
Artigo em Inglês | MEDLINE | ID: mdl-33031303

RESUMO

BACKGROUND: Kangai injection, a well-known insect-derived traditional Chinese medicine preparation, has been widely applied as a promising adjunctive drug for hepatitis B virus (HBV)-related hepatocellular carcinoma (HCC). However, its exact clinical efficacy and safety is still not well investigated. In this study, we aimed to summarize the efficacy and safety of Kangai injection for patients with HBV-related HCC through the meta-analysis. METHODS: All available randomized controlled trials (RCTs) and high-quality prospective cohort studies that investigated the efficacy and safety of Kangai injection for patients with HBV-related HCC were searched from ten electronic databases including Google Scholar, PubMed, Excerpt Medica Database (Embase), Cochrane Library, Medline, Web of Science (WOS), China National Knowledge Infrastructure (CNKI), China Scientific Journal Database (CSJ) Chinese, Biomedical Literature Database (CBM) and Wanfang Database. Papers in Chinese or English published from January 2000 to September 2020 will be included without any restrictions.Study selection and data extraction will be performed independently by 2 researchers. The clinical outcomes including overall response rate (ORR), disease control rate (DCR), quality of life (QoL), clinical symptoms, virological indicators, immune function and adverse events, were systematically evaluated. Review Manager 5.3 and Stata 14.0 were used for data analysis, and the quality of the literatures was also evaluated. RESULTS: The results of this study will be published in a peer-reviewed journal, and provide a helpful evidence for clinicians to formulate the best postoperative adjuvant treatment strategy for HBV-related HCC patients. CONCLUSION: Our study will draw an objective conclusion of the efficacy of Kangai injection on curative effect (ORR and DCR), clinical symptoms, virological indicators, QoL, and immune function in patients with HBV-related HCC. INPLASY REGISTRATION NUMBER: INPLASY202090014.


Assuntos
Carcinoma Hepatocelular/terapia , Carcinoma Hepatocelular/virologia , Quimioembolização Terapêutica , Medicamentos de Ervas Chinesas/uso terapêutico , Vírus da Hepatite B , Neoplasias Hepáticas/terapia , Neoplasias Hepáticas/virologia , Projetos de Pesquisa , Humanos , Metanálise como Assunto
8.
Medicine (Baltimore) ; 99(41): e22568, 2020 Oct 09.
Artigo em Inglês | MEDLINE | ID: mdl-33031305

RESUMO

The effect of intraoperative blood transfusion on the immune function and prognosis of hepatocellular carcinoma (HCC) has not been fully investigated. The aim of this study was to evaluate the effects of intraoperative autologous blood transfusion and allogeneic blood transfusion on immune function and prognosis in surgically treated HCC patients. One hundred fourteen primary hepatic carcinoma patients who would undergo selective operations were divided into two groups, 35 patients in the experimental group received intraoperative autologous blood transfusion and 79 patients in the control group received allogeneic blood transfusion. The amount of serum T lymphocyte subsets, natural killer (NK) cells and immunoglobulin before and after operation, as well as the recurrence-free survival (RFS) were compared. Results shown that, there was no significant difference in the level of immunocytes and immunoglobulin between the two groups before treatment (P > .05). At 1 day after surgery, there were significant differences in T lymphocyte, NK cells and immunoglobulin levels before and after transfusion. CD3+, CD4+, CD4+/CD8+, and NK cells in autologous transfusion group were significantly higher than those in allogeneic transfusion group (P < .05); the level of IgG, IgM, and IgA in allogeneic transfusion group were significantly lower than those before operation (P < .05), the level of IgG, IgM, and IgA in autologous transfusion group did not significantly fluctuate, and significantly higher than those of allogeneic transfusion group (P < .05). At 5 days after surgery, all indexes of autologous transfusion group recovered to the preoperative level, the levels of CD3+, CD4+, CD4+/CD8+, NK cells, IgG, IgM, and IgA were significantly higher than those of allogeneic transfusion group (P < .05). The follow-up results showed that the RFS of autologous transfusion group was significantly higher than that of allogeneic transfusion group (P < .05). In conclusion, compared with allogeneic blood transfusion, intraoperative autologous blood transfusion possessed less impact on immune function, it may even improve immune function and RFS in HCC patients after surgery. Therefore, HCC patients should be recommended to receive autologous blood transfusion instead of allogeneic blood transfusion when they need blood transfusion during the perioperative period.


Assuntos
Transfusão de Sangue , Carcinoma Hepatocelular/imunologia , Carcinoma Hepatocelular/cirurgia , Cuidados Intraoperatórios , Neoplasias Hepáticas/imunologia , Neoplasias Hepáticas/cirurgia , Transfusão de Sangue Autóloga , Feminino , Humanos , Imunoglobulinas/imunologia , Células Matadoras Naturais/imunologia , Masculino , Pessoa de Meia-Idade , Prognóstico , Subpopulações de Linfócitos T/imunologia
9.
Medicine (Baltimore) ; 99(41): e22580, 2020 Oct 09.
Artigo em Inglês | MEDLINE | ID: mdl-33031307

RESUMO

RATIONALE: Mycobacterium tuberculosis (TB) remains a serious threat in developing countries. Primary isolated hepatic tuberculosis is extremely rare. Because of its non-specific imaging features, noninvasive preoperative imaging diagnosis of isolated hepatic tuberculoma remains challenging. PATIENT CONCERNS: A 48-year-old man was admitted to our hospital due for suspected liver neoplasm during health examination. DIAGNOSES: The tests for blood, liver function, and tumor markers were within normal range. Preoperative ultrasonography (US) showed a hypoechoic lesion with a longitudinal diameter of 2.5 cm in segment six of liver. It exhibited early arterial phase hyperenhancement and late arterial phase rapid washout in contrast-enhanced US. It demonstrated hyperintensity in T2-weighted magnetic resonance imaging and partly restricted diffusion in diffusion-weighted imaging. For this nodule, the preoperative diagnosis was small hepatocellular carcinoma (HCC). INTERVENTIONS: Laparoscopic hepatectomy was performed. Intraoperative extensive adhesion in the abdominal cavity and liver was found. The lesion had undergone expansive growth. OUTCOMES: Microscopically, a granuloma with some necrosis was detected. With both acid-fast staining and TB fragment polymerase chain reaction showing positive results, TB was the final histology diagnosis. After surgery, the patient declined any anti-TB medication. During the follow-up, he had no symptoms. In the sixth month after surgery, he underwent an upper abdominal US. It showed no lesions in the liver. LESSONS: Because of non-specific imaging findings and non-specific symptoms, a diagnosis of isolated hepatic TB is difficult to make, especially for small lesions. A diagnosis of HCC should be made cautiously when small isolated lesions in the liver are encountered, especially in patients without a history of hepatitis and with negative tumor markers.


Assuntos
Tuberculose Hepática/diagnóstico por imagem , Tuberculose Hepática/cirurgia , Carcinoma Hepatocelular/diagnóstico por imagem , Meios de Contraste , Diagnóstico Diferencial , Hepatectomia , Humanos , Neoplasias Hepáticas/diagnóstico por imagem , Imagem por Ressonância Magnética , Masculino , Pessoa de Meia-Idade , Ultrassonografia
10.
Medicine (Baltimore) ; 99(41): e22594, 2020 Oct 09.
Artigo em Inglês | MEDLINE | ID: mdl-33031312

RESUMO

BACKGROUND: Hepatocellular carcinoma (HCC) is an aggressive cancer associated with poor prognosis. Early diagnosis is crucial to improve its prognosis. Blood-based liquid biopsies are promising methods in detecting HCC. However, their accuracies have not been systematically assessed, so it is essential to conduct a meta-analysis to evaluate the diagnostic performance of blood-based liquid biopsies in detecting HCC. METHODS: We will search PubMed, EMBASE, Cochrane Library, Web of Science, Medline, China National Knowledge Infrastructure(CNKI) for the relevant studies that assessed the diagnostic performance of blood-based liquid biopsies including circulating tumor cells(CTCs), circulating tumor DNA(ctDNA), and exosomes(EVs) in HCC patients from inception to September 2020. Two researchers will independently extract the data and use Quality Assessment of Diagnostic Accuracy Studies-2 (QUADAS-2) to evaluate the quality of included literature. We will also conduct the pool diagnostic value, heterogeneity across studies and reporting bias. All the statistical analysis will be conducted by Stata V.15.0 and Meta-disc V.1.4. RESULTS: This review will evaluate the pooled diagnostic value of blood-based liquid biopsies in HCC. CONCLUSION: This review will summarize the current published evidence of blood-based liquid biopsies in diagnosing HCC, which may provide a great opportunity for promotion and application of them. OPEN SCIENCE FRAMEWORK(OSF) REGISTRATION NUMBER: September 3, 2020. https://osf.io/9n4yz.


Assuntos
Carcinoma Hepatocelular/patologia , Biópsia Líquida , Neoplasias Hepáticas/patologia , Projetos de Pesquisa , Humanos , Metanálise como Assunto , Revisões Sistemáticas como Assunto
11.
Medicine (Baltimore) ; 99(40): e21503, 2020 Oct 02.
Artigo em Inglês | MEDLINE | ID: mdl-33019382

RESUMO

Hepatitis B virus (HBV) infection is a leading cause of hepatocellular carcinoma (HCC), but HBV-HCC related prognosis signature remains rarely investigated. This study was to identify an integrated long non-coding RNAs-messenger RNAs (lncRNA-mRNA) signature for prediction of overall survival (OS) and explore their underlying functions.One RNA-sequencing dataset (training set, n = 95) and one microarray dataset E-TABM-36 (validation set, n = 44) were collected. Least absolute shrinkage and selection operator analysis was performed to identify an lncRNA-mRNA prognosis signature. The OS difference of patients in the high-risk and low-risk risk groups was evaluated by Kaplan-Meier curve. Area under the receiver operating characteristic curve (AUC), Harrell concordance index (C-index) calculation, and multivariate analyses with clinical characteristics were used to determine the prognostic ability. Furthermore, a coexpression network was constructed to interpret the functions.Nine signature genes (3 lncRNAs and 6 mRNAs) were selected to generate the risk score model. Patients belonging to the high-risk group showed a significantly shorter survival than those of the low-risk group. The prediction accuracy of the risk score for 5-year OS was 0.936 and 0.905 for the training set and validation set, respectively. Also, this risk score was independent of various clinical variables for the prognosis prediction. Incorporation of the risk score remarkably increased the predictive power of the routine clinical prognostic factors (vascular invasion status, tumor recurrence status) (AUC = 0.942 vs 0.628; C-index = 0.7997 vs 0.6908). Furthermore, LncRNA insulin-like growth factor 2 antisense RNA (IGF2-AS) and long intergenic non-protein coding RNA 342 (LINC00342) were predicted to exert tumor suppression effects by regulating homeobox D1 (HOXD1) and secreted frizzled related protein 5 (SFRP5), respectively; while lncRNA rhophilin Rho GTPase binding protein 1 antisense RNA 1 (RHPN1-AS1) may possess carcinogenic potential by promoting the transcription of chromobox 2 (CBX2), cell division cycle 20 (CDC20), matrix metallopeptidase 12 (MMP12), stratifin (SFN), tripartite motif containing 16 (TRIM16), and uroplakin 3A (UPK3A). These mRNAs may be associated with cell proliferation or apoptosis related pathways.This study may provide a novel, effective prognostic biomarker, and some therapeutic targets for HBV-HCC patients.


Assuntos
Carcinoma Hepatocelular/genética , Hepatite B/genética , Neoplasias Hepáticas/genética , RNA Longo não Codificante/genética , RNA Mensageiro/genética , Idoso , Biomarcadores Tumorais/genética , Carcinoma Hepatocelular/mortalidade , Carcinoma Hepatocelular/virologia , Estudos de Casos e Controles , Feminino , Regulação Neoplásica da Expressão Gênica , Humanos , Neoplasias Hepáticas/mortalidade , Neoplasias Hepáticas/virologia , Masculino , Pessoa de Meia-Idade , Modelos de Riscos Proporcionais , Medição de Risco
12.
Medicine (Baltimore) ; 99(40): e22435, 2020 Oct 02.
Artigo em Inglês | MEDLINE | ID: mdl-33019424

RESUMO

Given that evidence supporting chronic hepatitis C (CHC) infection developed chance for hepatocellular carcinoma (HCC) following antiviral agents therapy is controversial. We conducted a meta-analysis to examine the risk.We evaluated 20 retrospective and prospective cohort studies published up to 31 December 2017 which investigated the association between sustained virological response (SVR) and incidence of HCC patients treated with monotherapy interferon (IFN) or IFN plus ribavirin (RBV) therapy. The primary outcome of the study was the cumulative incidence of HCC. Odds ratio (OR) was used to evaluate the index of effect size for the association between SVR and treatment with IFN alone or IFN/RBV in CHC patients.SVR patients demonstrated a lower incidence of HCC compared to non-SVR patients. Non-SVR patients had greater odds of HCC incidence compared to SVR patients in the treatment of IFN plus RBV (pooled OR = 7.405, 95% CI = 4.689 to 11.694, P < .001). Non-SVR patients had greater odds of HCC incidence compared to SVR patients in the treatment of IFN monotherapy (pooled OR = 4.135, 95% CI = 3.009 to 5.682, P < .001). Lack of SVR to IFN therapy was significantly associated with greater risk of HCC incidence (pooled OR = 5.035, 95% CI = 3.915 to 6.474, P < .001).SVR could be as a predictor of HCC in CHC patients treated with IFN or IFN plus RBV, and have important implications during HCC screening, whereby patients who fail to achieve SVR need to be screened more rigorously.


Assuntos
Antivirais/uso terapêutico , Hepatite C Crônica/tratamento farmacológico , Interferon-alfa/uso terapêutico , Resposta Viral Sustentada , Carcinoma Hepatocelular/virologia , Feminino , Humanos , Neoplasias Hepáticas/virologia , Masculino , Pessoa de Meia-Idade , Estudos Observacionais como Assunto
15.
Zhongguo Zhong Yao Za Zhi ; 45(16): 3945-3951, 2020 Aug.
Artigo em Chinês | MEDLINE | ID: mdl-32893593

RESUMO

In order to observe the anti-tumor effect of cinobufotalin on H22 liver cancer mice and to explore its regulatory mechanism, 50 Kunming mice were subcutaneously inoculated with H22 intraperitoneal passage cells under the armpit to establish H22 hepatocellular carcinoma model. They were then randomly divided into model group, cinobufotalin low dose group, cinobufotalin high dose group, cisplatin group and cisplatin+cinobufotalin group, which received 0.01% ethanol solution, 1 mg·kg~(-1) cinobufotalin, 5 mg·kg~(-1) cinobufotalin, 5 mg·kg~(-1) cisplatin, 5 mg·kg~(-1)cisplatin + 5 mg·kg~(-1) cinobufotalin respectively for 10 days. The general condition of mice during the intervention was observed, and the inhibition rate, tumor mass, thymus index, histopathological changes of the tumors, apoptotic rate of the tumors, the expressions of phosphatidylinositol 3-kinase(PI3 K), protein kinase B(Akt), apoptosis related gene(Fas), Fas ligand(FasL) mRNA and protein phosphorylated Akt(pAkt) protein in the tumors of each group were compared. The results showed that during the modeling period, the mice showed a decline in food intake, dark fur, poor mental status, and gradually worsened over time. The mental status of mice in each intervention group was improved gradually, especially in the cisplatin+cinobufotalin group. As compared with the model group, the tumor mass of each intervention group was lower(P<0.05). As compared with the cinobufotalin low dose group, the tumor mass was lower and inhibition rate was higher in the cinobufotalin high dose group, cisplatin group and cisplatin+cinobufotalin group(P<0.05). As compared with the cinobufotalin high dose group and the cisplatin group, the tumor mass was lower and the inhibition rate was higher in cisplatin+cinobufotalin group(P<0.05). As compared with the model group, the thymus index was higher in cinobufotalin high dose group and cisplatin + cinobufotalin group, while was lower in cisplatin group(P<0.05). As compared with the cinobufotalin low dose group, the thymus index was higher in the cinobufotalin high dose group and lower in the cisplatin group(P<0.05). As compared with the cinobufotalin high dose group, the thymus index was lower in cisplatin group(P<0.05). As compared with cisplatin group, the thymus index was higher in cisplatin+cinobufotalin group(P<0.05). Pathological staining showed that a large number of heterogeneous cells and mitotic phenomena were observed in the model group. Cell fragments and neutrophils were observed in the tumor tissues of the intervention groups, showing diffuse necrosis, and the diffuse necrosis was more obvious in the cisplatin+cinobufotalin group. As compared with the model group, the apoptotic rate of the tumors and the relative expressions of Fas mRNA and protein were higher in the intervention groups, while the relative expressions of PI3 K, FasL mRNA and protein and the relative expression of pAkt protein were lower in the intervention groups(P<0.05). As compared with the cinobufotalin low dose group, the apoptotic rate of the tumors and relative expression of Fas and protein were higher in the cinobufotalin high dose group, cisplatin group and cisplatin+cinobufotalin group, while the relative expressions of PI3 K, FasL mRNA and protein and pAkt protein were lower(P<0.05). As compared with the cinobufotalin high dose group and the cisplatin group, apoptotic rate of the tumors and the relative expression of Fas mRNA and protein were higher in the cisplatin+cinobufotalin group, while the relative expressions of PI3 K, FasL mRNA and protein and pAkt protein were lower in the cisplatin+cinobufotalin group(P<0.05). In summary, cinobufotalin has significant anti-tumor effect on H22 liver cancer mice, and can enhance the immune function of mice and synergistically enhance the effect of chemotherapy. Its mechanism may be associated with regulating PI3 K/Akt/Fas/FasL signaling pathway related genes and protein expression.


Assuntos
Bufanolídeos , Carcinoma Hepatocelular , Neoplasias Hepáticas , Animais , Apoptose , Cisplatino , Proteína Ligante Fas , Camundongos
16.
Rev Med Suisse ; 16(704): 1554-1559, 2020 Sep 02.
Artigo em Francês | MEDLINE | ID: mdl-32880111

RESUMO

Hepatocellular adenomas (HA) are rare benign liver tumors known to affect mainly women of reproductive age taking oral contraception. They can be complicated by hemorrhage or malignant transformation to hepatocellular carcinoma, especially when the size of the lesion exceeds 5 cm. Magnetic resonance imaging is the most specific tool for the non-invasive characterization of HA. The discovery of mutations underlying different specific HA phenotypes has allowed the establishment of a molecular classification that modified the management of this pathology.


Assuntos
Adenoma de Células Hepáticas , Neoplasias Hepáticas , Adenoma de Células Hepáticas/diagnóstico , Adenoma de Células Hepáticas/genética , Adenoma de Células Hepáticas/patologia , Adenoma de Células Hepáticas/terapia , Feminino , Humanos , Neoplasias Hepáticas/diagnóstico , Neoplasias Hepáticas/genética , Neoplasias Hepáticas/patologia , Neoplasias Hepáticas/terapia , Imagem por Ressonância Magnética , Mutação
17.
Z Gastroenterol ; 58(9): 847-854, 2020 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-32947630

RESUMO

BACKGROUND: The aim of our study is to analyze viscosity characteristics of focal liver lesions (FLLs) and the diagnostic performance of shear wave dispersion (SWD) in differentiating benign and malignant FLLs. METHODS: Between January 2018 and April 2018, 58 consecutive patients (median age 57, age range 21-74 years, 37 males) with 58 FLLs located on the right lobe of liver were prospectively studied. The Aplio i900 series diagnostic ultrasound system (Canon Medical systems) equipped with a curvilinear PV1-475BX transducer (1-8 MHz) was used. SWD slope and viscosity measurements were expressed as mean ± standard deviation for both liver tumors and background liver parenchyma. Histopathological results after surgery were regarded as the gold standard for diagnosis. RESULTS: Final diagnosis included 40 cases of malignant and 18 cases of benign FLLs. The mean viscosity value were 14.78 ±â€Š1.86 m/s/kHz for hepatocellular carcinoma (n = 30), 14.81 ±â€Š2.35 m/s/kHz for liver metastasis lesions (n = 10), 13.23 ±â€Š1.31 m/s/kHz for hemangioma (n = 13), and 13.67 ± 2.72 m/s/kHz for focal nodular hyperplasia (n = 5). Malignant FLLs showed higher mean viscosity values (14.79 ±â€Š3.15 m/s/KHz) than benign FLLs (13.36 ±â€Š2.76 m/s/KHz) (p < 0.05). The best performing cut-off value of lesion viscosity was 13.15 m/s/kHz (sensitivity 83.3 %; specificity 56.5 %; area under the curve (AUC) 0.71) for malignancy) (p < 0.05). CONCLUSIONS: The analysis of SWD slope and liver viscosity parameters provide additional viscoelastic information about FLLs before operation.


Assuntos
Técnicas de Imagem por Elasticidade/métodos , Neoplasias Hepáticas/diagnóstico por imagem , Fígado/diagnóstico por imagem , Adulto , Idoso , Meios de Contraste , Diagnóstico Diferencial , Humanos , Fígado/patologia , Neoplasias Hepáticas/patologia , Masculino , Pessoa de Meia-Idade , Sensibilidade e Especificidade , Ultrassonografia , Viscosidade , Adulto Jovem
18.
Nat Commun ; 11(1): 4383, 2020 09 01.
Artigo em Inglês | MEDLINE | ID: mdl-32873799

RESUMO

Mongolia has the highest incidence of hepatocellular carcinoma (HCC) in the world, but its causative factors and underlying tumor biology remain unknown. Here, we describe molecular characteristics of HCC from 76 Mongolian patients by whole-exome and transcriptome sequencing. We present a comprehensive analysis of mutational signatures, driver genes, and molecular subtypes of Mongolian HCC compared to 373 HCC patients of different races and ethnicities and diverse etiologies. Mongolian HCC consists of prognostic molecular subtypes similar to those found in patients from other areas of Asia, Europe, and North America, as well as other unique subtypes, suggesting the presence of distinct etiologies linked to Mongolian patients. In addition to common driver mutations (TP53, CTNNB1) frequently found in pan-cancer analysis, Mongolian HCC exhibits unique drivers (most notably GTF2IRD2B, PNRC2, and SPTA1), the latter of which is associated with hepatitis D viral infection. These results suggest the existence of new molecular mechanisms at play in Mongolian hepatocarcinogenesis.


Assuntos
Biomarcadores Tumorais/genética , Carcinoma Hepatocelular/genética , Regulação Neoplásica da Expressão Gênica , Hepatite D/genética , Neoplasias Hepáticas/genética , Idoso , Carcinogênese/genética , Carcinoma Hepatocelular/epidemiologia , Carcinoma Hepatocelular/cirurgia , Carcinoma Hepatocelular/virologia , Análise Mutacional de DNA , Feminino , Perfilação da Expressão Gênica , Hepatectomia , Hepatite D/epidemiologia , Hepatite D/cirurgia , Hepatite D/virologia , Vírus Delta da Hepatite/isolamento & purificação , Humanos , Incidência , Fígado/patologia , Fígado/cirurgia , Fígado/virologia , Neoplasias Hepáticas/epidemiologia , Neoplasias Hepáticas/cirurgia , Neoplasias Hepáticas/virologia , Masculino , Pessoa de Meia-Idade , Mongólia/epidemiologia , Mutação , Prognóstico , Sequenciamento Completo do Exoma
20.
Medicine (Baltimore) ; 99(38): e22312, 2020 Sep 18.
Artigo em Inglês | MEDLINE | ID: mdl-32957395

RESUMO

RATIONALE: Immunotherapy and targeted therapy have attracted widespread attention in current clinical research, which could be considered as a good therapeutic option for treatment of refractory liver cancer. PATIENT CONCERNS: The patient was a 37-year-old man with hepatitis B virus (HBV) infection. He was presented with hepatalgia and discomfort. DIAGNOSIS: The computed tomography showed multiple intrahepatic masses, indicating primary liver cancer with multiple intrahepatic metastases. INTERVENTIONS: After failed transarterial chemoembolization therapy, he was initially treated with immunotherapy pembrolizumab plus angiogenesis inhibitor lenvatinib, and after 3 months of treatment, the condition improved. However, the disease subsequently progressed. The next-generation sequencing identified a BRCA2 germline mutation in this patient. A poly (ADP-ribose) polymerase inhibitor, olaparib, plus nivolumab therapy was started and achieved stable disease. OUTCOMES: The patient achieved stable disease and improvement in hepatalgia for 3 months after the combination treatment of Olaparib and nivolumab. CONCLUSION: We identified a BRCA2 germline mutation in a patient with liver cancer. Our findings could offer an alternative management for patients with liver cancer harboring germline BRCA2 mutation.


Assuntos
Antineoplásicos Imunológicos/uso terapêutico , Neoplasias Hepáticas/tratamento farmacológico , Nivolumabe/uso terapêutico , Ftalazinas/uso terapêutico , Piperazinas/uso terapêutico , Adulto , Protocolos de Quimioterapia Combinada Antineoplásica , Evolução Fatal , Genes BRCA2 , Mutação em Linhagem Germinativa , Sequenciamento de Nucleotídeos em Larga Escala , Humanos , Neoplasias Hepáticas/diagnóstico por imagem , Neoplasias Hepáticas/genética , Masculino
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