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1.
Anticancer Res ; 39(10): 5393-5401, 2019 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-31570434

RESUMO

BACKGROUND/AIM: Local recurrence of hepatocellular carcinoma (HCC) after thermal coagulation therapy may be associated with an aggressive phenotypic change. This study focused on the thermal effects on HCC cells and evaluated the heat shock response and phenotypic changes after heat treatment. MATERIALS AND METHODS: HepG2 and HuH7 cells were used. After heat treatment at 37-50°C for 5-30 min, we assessed their survival rate, induction of heat shock protein (HSP)70 promoter, proliferation rate, induction of the epithelial-mesenchymal transition (EMT) and cancer stem cell (CSC)-related markers. RESULTS: Induction of HSP70 promoter per surviving cell was maximized after 10 min of heat treatment at 48°C. Induction of EMT and CSC-related markers was also observed. CONCLUSION: Sub-lethal heat treatment causes large heat shock response to surviving HCC cells and induce EMT-like and CSC-like phenotypic changes that might contribute to increased aggressiveness.


Assuntos
Carcinoma Hepatocelular/genética , Carcinoma Hepatocelular/patologia , Resposta ao Choque Térmico/genética , Neoplasias Hepáticas/genética , Neoplasias Hepáticas/patologia , Linhagem Celular Tumoral , Sobrevivência Celular/genética , Transição Epitelial-Mesenquimal/genética , Proteínas de Choque Térmico HSP70/genética , Células Hep G2 , Temperatura Alta , Humanos , Recidiva Local de Neoplasia/genética , Recidiva Local de Neoplasia/patologia , Células-Tronco Neoplásicas/patologia , Taxa de Sobrevida
2.
Anticancer Res ; 39(10): 5639-5643, 2019 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-31570461

RESUMO

BACKGROUND/AIM: Diabetes mellitus (DM) is known as an important risk factor for hepatocellular carcinoma (HCC). However, surgical outcomes in patients with DM and HCC have not been evaluated in detail. PATIENTS AND METHODS: We retrospectively studied 177 patients with type 2 DM who underwent curative hepatectomy for HCC. Surgical outcomes after curative hepatectomy and prognostic factors were evaluated among 75 patients with DM and/or nonalcoholic steatohepatitis (NASH)-related HCC and 102 patients with DM and viral or alcoholic hepatitis (VAH)-related HCC. RESULTS: The 5-year survival rate and 5-year recurrence-free survival rate were significantly higher in the DM and/or NASH-related HCC group (87% and 51%) than in the DM and VAH-related HCC group (68%: p=0.0001 and 26%: p=0.0002). Multivariate analysis showed DM and/or NASH-related HCC to be significant independent prognostic factors for overall survival and recurrence-free survival. CONCLUSION: Patients with DM and/or NASH-related HCC showed more favorable surgical outcomes after hepatectomy in patients with DM and HCC.


Assuntos
Carcinoma Hepatocelular/mortalidade , Carcinoma Hepatocelular/cirurgia , Neoplasias Hepáticas/mortalidade , Hepatopatia Gordurosa não Alcoólica/mortalidade , Adulto , Idoso , Idoso de 80 Anos ou mais , Carcinoma Hepatocelular/etiologia , Carcinoma Hepatocelular/patologia , Diabetes Mellitus Tipo 2/complicações , Diabetes Mellitus Tipo 2/mortalidade , Diabetes Mellitus Tipo 2/patologia , Diabetes Mellitus Tipo 2/cirurgia , Intervalo Livre de Doença , Feminino , Hepatectomia/métodos , Humanos , Neoplasias Hepáticas/etiologia , Neoplasias Hepáticas/patologia , Neoplasias Hepáticas/cirurgia , Masculino , Pessoa de Meia-Idade , Hepatopatia Gordurosa não Alcoólica/patologia , Hepatopatia Gordurosa não Alcoólica/cirurgia , Prognóstico , Estudos Retrospectivos , Fatores de Risco , Taxa de Sobrevida , Resultado do Tratamento
3.
Anticancer Res ; 39(10): 5755-5760, 2019 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-31570478

RESUMO

BACKGROUND/AIM: After primary resection of hepatocellular carcinoma (HCC), the impact of patient's characteristics at the initial hepatectomy, on long-term remnant liver function has not been reported. The aim of this study was to identify factors associated with the deterioration of remnant liver function among patients who developed recurrent HCC. PATIENTS AND METHODS: A total of 51 patients with intrahepatic recurrence after initial hepatic resection for HCC were included. We retrospectively investigated the relation between patient characteristics and the degree of deterioration of remnant liver function upon recurrence. RESULTS: In univariate analysis, significant predictors of deterioration of remnant liver function consisted of preoperative gastro-esophageal varices (p=0.0101), preoperative transcatheter arterial chemoembolization (p=0.0230) and hepatectomy beyond Makuuchi's criteria (p=0.0101). In multivariate analysis, the only significant independent predictor of deterioration of remnant liver function was hepatectomy beyond Makuuchi's criteria (p=0.0498). CONCLUSION: Hepatectomy beyond Makuuchi's criteria at the initial hepatectomy may predict deterioration of remnant liver function upon recurrence of HCC.


Assuntos
Carcinoma Hepatocelular/patologia , Hepatectomia/efeitos adversos , Neoplasias Hepáticas/patologia , Fígado/patologia , Idoso , Idoso de 80 Anos ou mais , Carcinoma Hepatocelular/cirurgia , Quimioembolização Terapêutica/efeitos adversos , Quimioembolização Terapêutica/métodos , Feminino , Hepatectomia/métodos , Humanos , Fígado/cirurgia , Neoplasias Hepáticas/cirurgia , Masculino , Pessoa de Meia-Idade , Recidiva Local de Neoplasia/patologia , Recidiva Local de Neoplasia/cirurgia , Estudos Retrospectivos , Fatores de Risco
4.
Medicine (Baltimore) ; 98(42): e17412, 2019 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-31626095

RESUMO

BACKGROUND: Long non-coding RNA colon cancer-associated transcript 2 (CCAT2) is a 1752-bp lncRNA transcribed from m8q24 genomic region. A lot of investigations have confirmed the involvement of CCAT2 in the tumorigenesis of many cancer types. Previous studies found that over-expression of CCAT2 significantly promoted cell migration and proliferation, and inhibited apoptosis of HCC cells. In the present investigation, the clinical value and prognostic significance of CCAT2 were investigated. METHODS: The 122 pairs of HCC tissues and adjacent normal liver tissues were acquired between September 2013 and February 2018. The expression levels of CCAT2 in HCC tissues and their corresponding adjacent normal liver tissues were examined by RT-qPCR analysis. Survival was calculated using the Kaplan-Meier method and analyzed using the log-rank test. Independent prognostic indicators were determined in the multivariate analysis using Cox's proportional hazard model. RESULTS: CCAT2 expression levels were significantly increased in HCC tissues compared to that in their normal counterparts (P < .001). CCAT2 expression was significantly correlated with vascular invasion (P = .001), histopathologic grading (P = .001), distant metastasis (P = .002) and TNM stage (P = .018). A Kaplan-Meier survival curve showed that the overall survival rate of HCC patients in high CCAT2 expression group markedly decreased as compared with that of low CCAT2 expression group (P = .016). In addition, COX multivariate analysis showed that high expression of CCAT2 was an independent risk factor for predicting shorter overall survival time in HCC (HR = 2.126, 95%CI:1.273-8.775, P = .021). CONCLUSIONS: Taken together, this research revealed that lncRNA CCAT2 may serve as a potential biomarker for predicting overall survival time in HCC.


Assuntos
Carcinoma Hepatocelular/genética , Regulação Neoplásica da Expressão Gênica , Neoplasias Hepáticas/genética , RNA Longo não Codificante/genética , Adulto , Idoso , Biomarcadores Tumorais/genética , Carcinoma Hepatocelular/mortalidade , Carcinoma Hepatocelular/patologia , Feminino , Humanos , Estimativa de Kaplan-Meier , Neoplasias Hepáticas/mortalidade , Neoplasias Hepáticas/patologia , Masculino , Pessoa de Meia-Idade , Invasividade Neoplásica/genética , Modelos de Riscos Proporcionais , Reação em Cadeia da Polimerase Via Transcriptase Reversa , Regulação para Cima/genética
6.
Tumour Biol ; 41(10): 1010428319880080, 2019 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-31603389

RESUMO

Searching for new sources of safe nutraceuticals antitumor drugs is an important issue. Consequentially, this study designed to assess the antitumor activity of Pulicaria undulata extract in vitro in the treatment of hepatocellular carcinoma HepG2 cell line. Aerial parts of P. undulata plants were collected, used for phytochemical analysis, and assessed for anticancer activity. The antitumor activity was evaluated through studying the cell viability and apoptotic pathway. The gas chromatography-mass spectrometry phytochemical analysis revealed that P. undulata is a promising new source of several known antioxidant and antitumor compounds which could participate in drug development and exploration of alternative strategies to the harmful synthetic antitumor drugs. P. undulata stifled HepG2 cell viability in a concentration-dependent manner. Meanwhile, P. undulata tempted substantial apoptosis in HepG2 cells and enhanced the expression of miR-34a. However, the mRNA expression level of antiapoptotic B-cell lymphoma-2 was markedly decreased by P. undulata treatment. Moreover, P. undulata increased the protein expression of proapoptotic p53 and caspase 3/9 with reducing B-cell lymphoma-2 protein expression level. Thus, P. undulata induced apoptosis in the HepG2 cells by overexpression of miR-34a which regulates p53/B-cell lymphoma-2/caspases signaling pathway. These findings were well appreciated with morphological studies of cells treated with P. undulata. In conclusion, P. undulata could be a probable candidate agent for the initiation of cell apoptosis in HepG2 and thereby can serve as promising therapeutic agent for treatment of hepatocellular carcinoma which should attract further studies.


Assuntos
Apoptose/efeitos dos fármacos , Carcinoma Hepatocelular/patologia , Proliferação de Células/efeitos dos fármacos , Neoplasias Hepáticas/patologia , Extratos Vegetais/farmacologia , Pulicaria/química , Carcinoma Hepatocelular/tratamento farmacológico , Células Hep G2 , Humanos , Neoplasias Hepáticas/tratamento farmacológico , Transdução de Sinais
7.
Zhonghua Gan Zang Bing Za Zhi ; 27(9): 681-686, 2019 Sep 20.
Artigo em Chinês | MEDLINE | ID: mdl-31594092

RESUMO

Objective: Hepatocellular carcinoma (HCC) is one of the most common malignant tumor worldwide. Metastasis is a marker of cancer deterioration in patients with liver cancer and a major cause of death. In order to develop effective therapeutic strategies, it is urgent to study the molecular basis of liver cancer metastasis. Methods: Immunohistochemistry was used to detect the expression of fatty acid synthase (FASN) in HCC. Wound healing and transwell cell invasion assays was used to confirm the role of FASN in liver cancer migration and invasion. Proteins that interacted with FASN were identified using iTRAQ (isobaric tag for relative and absolute quantification). Co-immunoprecipitation (Co-IP) and cellular immunofluorescence analysis were used to assess the interaction between FASN and signal transduction and transcription activator 3 (STAT3). The expression of STAT3, p-STAT3, matrix metalloproteinase (MMP)-2 and MMP-9 was detected after FASN knockdown using Western blot method. Statistical analysis was performed using the t-test. Results: Immunohistochemistry showed that the expression of FASN in HCC tissue was higher than that in adjacent tissues. iTRAQ, Co-IP and immunofluorescence analysis revealed that FASN interacted with STAT3. Western blot analysis showed that the expression of p-STAT3, MMP-2 and MMP-9 decreased after FASN knockdown. Conclusion: FASN may promote the metastasis of liver cancer by interacting with STAT3 and affecting the expression of MMP-2/MMP-9.


Assuntos
Carcinoma Hepatocelular/patologia , Ácido Graxo Sintase Tipo I/metabolismo , Neoplasias Hepáticas/patologia , Fator de Transcrição STAT3/metabolismo , Linhagem Celular Tumoral , Movimento Celular , Ácido Graxo Sintases , Humanos , Metaloproteinase 2 da Matriz/metabolismo , Metaloproteinase 9 da Matriz/metabolismo
8.
Zhonghua Gan Zang Bing Za Zhi ; 27(9): 693-697, 2019 Sep 20.
Artigo em Chinês | MEDLINE | ID: mdl-31594094

RESUMO

Objective: To investigate the effect and mechanism of XTP4 gene in apoptotic hepatoblastoma HepG2 cell line. Methods: HepG2 cells were transiently transfected with small interfering RNA of XTP4 genes, plasmid pcDNA3.1/myc-His(-) A-XTP4, and hepatitis B virus X protein transactivated x gene 4 (HBX protein trans-activate gene4, XTP4) and their respective negative controls. After 48h, the overexpression and interference expression condition of XTP4 in HepG2 cells were detected by Western blot. HepG2 cells apoptosis was detected by flow cytometry. The expression levels of apoptosis-related proteins P53, Bcl-2, Bax and Caspase-3 in HepG2 cells were detected by Western blot, and Bcl-2/Bax ratio was calculated. The chemiluminescence assay was used to detect activity of caspase-3 in HepG2 cells. The measured data were presented as (x ± s), and independent sample t-test was used for comparison between the two groups. Results: HepG2 cells had successfully achieved the overexpression and interference expression of XTP4 protein. Compared with the control group, the overexpression of XTP4 in HepG2 cells had significantly decreased the number of apoptotic cells (P < 0.05), and increased Bcl-2/Bax (P < 0.05) ratio, but decreased the expression of P53 protein (P < 0.05). The protein expression of Caspase-3 and activity of caspase-3 was decreased (P < 0.05). However, interference with XTP4 expression in HepG2 cells had significantly increased the number of apoptotic cells (P < 0.05) and decreased Bcl-2/Bax (P < 0.05) ratio, but increased the expression of P53 protein (P < 0.05). The protein expression of Caspase-3 and activity of caspase-3 was increased (P<0.05). Conclusion: In HepG2 apoptosis XTP4 has inhibitory effect, and its effect on inhibiting HepG2 apoptosis may be achieved by regulating the Bcl-2/Bax ratio, and the P53 protein may be involved.


Assuntos
Apoptose , Carcinoma Hepatocelular/patologia , Neoplasias Hepáticas/patologia , Transativadores/metabolismo , Caspase 3/metabolismo , Células Hep G2 , Humanos , Proteínas Proto-Oncogênicas c-bcl-2/metabolismo , Transfecção , Proteína Supressora de Tumor p53/metabolismo , Proteína X Associada a bcl-2/metabolismo
9.
Medicine (Baltimore) ; 98(38): e17102, 2019 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-31567946

RESUMO

Combined hepatocellular-cholangiocarcinoma (CHCC) is a rare type of primary liver cancer (PLC). The aim of this study was to investigate the disease characteristics in CHCC patients and compare them with those in hepatocellular carcinoma (HCC) or intrahepatic cholangiocarcinoma (ICC).The perioperative and follow-up data of CHCC patients (n = 15), HCC patients (n = 577), and ICC patients (n = 61) were retrospectively analyzed, and the clinicopathological characteristics were compared among these 3 groups.In the CHCC group, the serum level of AFP was significantly higher than that of the ICC group (P = .002), and the CA19-9 level was higher than that of the HCC group (P = .011). The positive rates of CK7 and CK19 expression were higher in CHCC group than in HCC group (both P < .001), while the positive rates of Glypican-3 and Hepatocyte expression were higher in CHCC group than in ICC group (both P < .001). Meanwhile, the CHCC patients were likely to have undergone more MJH/LT than the HCC patients (P = .037) and the ICC patients (P = .011). Macrovascular invasion and lymph node metastasis in the CHCC group were significantly higher but satellite lesions were similar, compared to the HCC group. Both the 1-year disease-free survival (DFS) and the 1-year overall survival (OS) for the CHCC patients were worse than those for the HCC patients. AFP ≥ 400 ng/ml, tumor size ≥5 cm, tumor number ≥2, macro- and microvascular invasion, distant metastasis and positive margin were risk factors for both DFS and OS for the PLC patients. Multivariate analysis also confirmed that ICC and lymph node metastasis were risk factors for DFS and MJH/LT was risk factor for OS.CHCC patients appear to have intermediate clinical characteristics in comparison with the HCC and ICC patients, and the 1-year DFS and OS for the CHCC patients was worse than the HCC patients, but similar to the ICC patients.


Assuntos
Neoplasias dos Ductos Biliares/mortalidade , Carcinoma Hepatocelular/mortalidade , Colangiocarcinoma/mortalidade , Neoplasias Hepáticas/mortalidade , Neoplasias Primárias Múltiplas/mortalidade , Neoplasias dos Ductos Biliares/patologia , Neoplasias dos Ductos Biliares/cirurgia , Carcinoma Hepatocelular/patologia , Carcinoma Hepatocelular/cirurgia , China , Colangiocarcinoma/patologia , Colangiocarcinoma/cirurgia , Intervalo Livre de Doença , Feminino , Humanos , Neoplasias Hepáticas/patologia , Neoplasias Hepáticas/cirurgia , Metástase Linfática , Masculino , Pessoa de Meia-Idade , Neoplasias Primárias Múltiplas/cirurgia
10.
Medicine (Baltimore) ; 98(40): e16912, 2019 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-31577696

RESUMO

INTRODUCTION: Accessory liver lobe (ALL) is a rare congenital anomaly. ALL combined with hepatocellular carcinoma (HCC) is even rarer. Most ALLs with HCC are often located in the right liver, and are not supplied by the left hepatic artery. PATIENT CONCERNS: A 77-year-old man was referred to our hospital because of the level of serum alpha-fetoprotein (AFP) continually increased for 1 month. He had no history of chronic hepatitis, alcohol abuse, or cirrhosis of the liver. DIAGNOSES: Preoperative computed tomography (CT) scan revealed a 3.0 × 3.0 × 1.0 cm ovaloid-shaped solid mass in the left subphrenic area with isodensity. Magnetic resonance imaging (MRI) showed a mass with a heterogeneous signal on T1- and T2-weighted images. On contrast-enhanced CT and MRI, the mass showed a pattern of early enhancement and washout. Digital subtraction angiography (DSA) confirmed the mass was fed by the branch of left liver artery. INTERVENTIONS: The mass was treated by transatheter arterial embolization (TAE) followed by surgical resection. Histopathologically showed HCC, consistent with a moderately differentiated. OUTCOMES: Follow-up of 3 months after surgery, the level of AFP returned to normal gradually. CONCLUSIONS: In this report, we describe a rare case of ALL with HCC, located in the left subphrenic area, especially which was supplied by the branch of left hepatic artery has rarely been described. The clinical presentation, radiological features are described in the literature.


Assuntos
Carcinoma Hepatocelular/patologia , Artéria Hepática/patologia , Neoplasias Hepáticas/patologia , Fígado/anormalidades , Fígado/patologia , Idoso , Carcinoma Hepatocelular/diagnóstico por imagem , Carcinoma Hepatocelular/terapia , Embolização Terapêutica , Artéria Hepática/diagnóstico por imagem , Humanos , Fígado/efeitos dos fármacos , Neoplasias Hepáticas/diagnóstico por imagem , Neoplasias Hepáticas/terapia , Imagem por Ressonância Magnética , Masculino , Tomografia Computadorizada por Raios X
11.
Anticancer Res ; 39(9): 4787-4794, 2019 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-31519580

RESUMO

BACKGROUND/AIM: The aim of this study was to investigate the effects of the macrophage colony-stimulating factor (M-CSF) receptor antagonist on hepatic carcinogenesis in mice. MATERIALS AND METHODS: Mice were injected with diethylnitrosamine (DEN) and treated with M-CSF receptor antagonist GW2580 (GW) or a saline vehicle just after (early treated group) or 2 weeks after (late treated group) DEN injection. Animals were sacrificed after 28 weeks and incidence of tumor was assessed. Isolated Kupffer cells were co-cultured with M-CSF in the presence or absence of GW, and the concentration of VEGF was measured. RESULTS: The incidence of tumors was significantly blunted both in the early- and the late-treated groups. In addition, angiogenesis within the tumor was also suppressed in both groups. The concentration of VEGF increased in Kupffer cells treated with M-CSF compared to those cultured without M-CSF. This increase was blunted by GW. CONCLUSION: M-CSF and its receptor could be novel molecular targets for hepatocellular carcinoma.


Assuntos
Anisóis/farmacologia , Transformação Celular Neoplásica/efeitos dos fármacos , Pirimidinas/farmacologia , Receptor de Fator Estimulador de Colônias de Macrófagos/antagonistas & inibidores , Animais , Biomarcadores , Carcinoma Hepatocelular/tratamento farmacológico , Carcinoma Hepatocelular/metabolismo , Carcinoma Hepatocelular/patologia , Proliferação de Células/efeitos dos fármacos , Imuno-Histoquímica , Macrófagos do Fígado/efeitos dos fármacos , Macrófagos do Fígado/metabolismo , Neoplasias Hepáticas/tratamento farmacológico , Neoplasias Hepáticas/metabolismo , Neoplasias Hepáticas/patologia , Macrófagos/efeitos dos fármacos , Macrófagos/imunologia , Masculino , Camundongos , Carga Tumoral/efeitos dos fármacos
12.
Braz J Med Biol Res ; 52(10): e8631, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31531526

RESUMO

The long non-coding RNA (lncRNA) maternally expressed gene 3 (MEG3), a tumor suppressor, is critical for the carcinogenesis and progression of different cancers, including hepatocellular carcinoma (HCC). To date, the roles of lncRNA MEG3 in HCC are not well illustrated. Therefore, this study used western blot and qRT-PCR to evaluate the expression of MEG3, miR-9-5p, and Sex determining Region Y-related HMG-box 11 (SOX11) in HCC tissues and cell lines. RNA pull-down and luciferase reporter assay were used to evaluate these molecular interactions. 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide and flow cytometry detected the viability and apoptosis of HCC cells, respectively. The results showed that MEG3 and SOX11 were poorly expressed but miR-9-5p was highly expressed in HCC. The expression levels of these molecules suggested a negative correlation between MEG3 and miR-9-5p and a positive correlation with SOX11, confirmed by Pearson's correlation analysis and biology experiments. Furthermore, MEG3 could combine with miR-9-5p, and SOX11 was a direct target of miR-9-5p. Moreover, MEG3 over-expression promoted cell apoptosis and growth inhibition in HCC cells through sponging miR-9-5p to up-regulate SOX11. Therefore, the interactions among MEG3, miR-9-5p, and SOX11 might offer a novel insight for understanding HCC pathogeny and provide potential diagnostic markers and therapeutic targets for HCC.


Assuntos
Carcinoma Hepatocelular/genética , Neoplasias Hepáticas/genética , MicroRNAs/genética , RNA Longo não Codificante/genética , Fatores de Transcrição SOXC/genética , Apoptose/genética , Carcinoma Hepatocelular/metabolismo , Carcinoma Hepatocelular/patologia , Linhagem Celular Tumoral , Proliferação de Células/genética , Feminino , Regulação Neoplásica da Expressão Gênica , Humanos , Neoplasias Hepáticas/metabolismo , Neoplasias Hepáticas/patologia , Masculino , MicroRNAs/metabolismo , Pessoa de Meia-Idade , Estadiamento de Neoplasias , RNA Longo não Codificante/metabolismo , Reação em Cadeia da Polimerase em Tempo Real , Fatores de Transcrição SOXC/metabolismo , Ativação Transcricional , Transfecção , Regulação para Cima
13.
Zhonghua Zhong Liu Za Zhi ; 41(9): 659-666, 2019 Sep 23.
Artigo em Chinês | MEDLINE | ID: mdl-31550855

RESUMO

Objective: To explore the effects of lncRNA HULC on hepatocellular carcinoma (HCC) growth by down-regulating miR-29. Methods: The expression levels of HULC and miR-29 in HCC tissues and cells were detected by real-time quantitative PCR (RT-qPCR), and the correlation analysis was performed. After HCC cells were transfected with HULC overexpressed plasmid or siRNA, the expressions of miR-29 and its target gene SETDB1 were determinate by RT-qPCR. According to the bioinformatic prediction of the miR-29 binding site in the HULC sequence, the report gene plasmids were constructed. The HCC cells were co-transfected with miR-29 mimics or miR-29 inhibitor, and the HULC targeted regulation of miR-29 was verified by dual luciferase reporter assay. The effect of miR-29 on the HULC-mediated proliferation in HCC cells was detected by cell count kit 8 (CCK-8) experiment. Expression of tumor proliferation antigen Ki-67 was detected by RT-qPCR.The Hep3B cells were inoculated in mice and miR-29 mimics and miR-29 negative control (NC) further injected into the lesions. The tumor volume was observed, and the expressions of tumor proliferation antigen ki-67 in tumor tissues were detected by immunohistochemical staining. Results: The expression of HULC was significantly up-regulated while the expression of miR-29 was significantly down-regulated in HCC tissues and cells (P<0.01). The level of HULC was negatively correlated with miR-29 in tumor tissues (r=-0.754, P<0.01) and HCC cells (r=-0.865, P<0.05). The in vitro experiments showed that, compared with the blank control group, the expression of miR-29 in HULC overexpressed Huh7 cells was significantly reduced, while the mRNA level of miR-29 target gene SETDB1 was increased (P<0.01). The expression of miR-29 was significantly increased in HULC deleted Hep3B cells, while the mRNA expression of SETDB1 was decreased (P<0.01). Double luciferase reporter gene assay showed that miR-29 mimics significantly inhibited the luciferase activity of Hep3B cells transfected with HULC wide type (psi-HULC-WT) plasmid but had no effect on Hep3B cells transfected with mutant plasmid (psi-HULC-Mut). However, the miR-29 inhibitor antagonized the inhibitory effect of miR-29 mimics on luciferase activity of psi-HULC-WT (P<0.01). Cell proliferation experiments showed that, compared with the control group, the proliferation ability of miR-29 mimics overexpressed Huh7 cells was significantly reduced.After 24, 48 and 72 hours of treatment, the proliferation rates of Huh7 cells in the HULC overexpressed group were (43.87±3.82)%, (83.45±7.46)% and (123.34±8.67)%, respectively, significantly higher than (13.45±1.77)%, (23.54±1.37)% and (38.21±2.09)% of control group (P<0.05). After treatment for 48 and 72 hours, the proliferation rates of miR-29 mimics transfected Huh7 cells were (57.10±1.94)% and (73.76±3.46)%, respectively, significantly lower than (83.45±7.46)% and (123.34±8.67)% of control group (P<0.05). After treatment for 48 and 72 hours, the proliferation rates of Huh7 cells transfected with miR-29 mimics and miR-29 inhibitor group were (76.45±3.24)% and (89.37±4.37)%, respectively, significant higher than (57.10%±1.94)% and (73.76±3.46)% of the control group (P<0.05). After 48 h transfection, the expression of Ki-67 in Huh7 transfected with miR-29 mimics was significantly inhibited compared with the control group (P<0.01). However, the expression of Ki-67 mRNA was increased in Huh7 cells transfected with miR-29 inhibitor (P<0.01). The results of in vivo experiments showed that the tumor volumes of the control group, miR-29 mimics group and miR-29 mimics + miR-29 inhibitors group were (504.0±19.6) mm(3), (310.0±24.3) mm(3) and (483.7±21.2) mm(3), respectively. Injection of miR-29 mimics reduced while miR-29 inhibitor promoted tumorigenesis ability of Huh7 in nude mice (P<0.01). The immunohistochemical staining showed that the average optical density values of Ki-67 protein in tumor tissues of the control group, miR-29 mimics group and miR-29 analogue+ miR-29 inhibitor group were 0.65±0.08, 0.36±0.07 and 0.56±0.06, respectively. The expression level of Ki-67 protein in miR-29 mimics group was significantly reduced (P<0.01) while increased in the miR-29 mimics+ miR-29 inhibitor group (P<0.01). Conclusion: LncRNA HULC promotes HCC growth by down-regulating miR-29.


Assuntos
Carcinoma Hepatocelular/patologia , Proliferação de Células/genética , Regulação Neoplásica da Expressão Gênica/genética , Neoplasias Hepáticas/patologia , MicroRNAs/genética , RNA Longo não Codificante/genética , Animais , Carcinoma Hepatocelular/genética , Histona-Lisina N-Metiltransferase , Neoplasias Hepáticas/genética , Camundongos , Camundongos Nus , Reação em Cadeia da Polimerase em Tempo Real
14.
Zhonghua Zhong Liu Za Zhi ; 41(9): 667-674, 2019 Sep 23.
Artigo em Chinês | MEDLINE | ID: mdl-31550856

RESUMO

Objective: To investigate the effect of long-chain non-coding RNA Fez family zinc finger protein 1 antisense RNA1 (lncRNA FEZF1-AS1) on the biological function of hepatocellular carcinoma (HCC). Methods: SMMC771 and BEL-7402 cells were transfected with sh-FEZF1-AS1 and OE-FEZF1-AS1, respectively. The expression of lncRNA FEZF1-AS1 was detected by real-time quantitative PCR. Cell proliferation was detected by Cell Counting Kit-8 (CCK-8), and apoptosis was detected by flow cytometry. The effects of lncRNA FEZF1-AS1 on invasion and migration were detected by Transwell and wound healing assays. The expression levels of adhesion molecules were detected by Western blot. The effect of lncRNA FEZF1-AS1 on the in vivo growth was verified by nude mice xenograft experiments. Results: The silencing or ectopic expression of lncRNA FEZF1-AS1 inhibited or promoted the proliferation of hepatocellular carcinoma cells. CCK-8 assay showed that the proliferation abilities of SMMC7721 and BEL-7402 cells in sh-FEZF1-AS1 transfection group significantly decreased, achieving (35.43±4.06)% and (34.68±3.97)%, respectively, on the fifth day. There were significant differences between sh-FEZF1-AS1 group and sh-NC group [52.21±8.46)% and (53.76±7.64)%] (all P<0.05). In contrast, the proliferation ability of SMMC7721 and BEL-7402 cells transfected with OE-FEZF1-AS1 was significantly increased, achieving (83.49±6.92)% and (80.31±3.13)%, respectively, on the fifth day. There were significant differences between OE-FEZF1-AS1 and OE-NC group [53.03±8.84)% and (55.11±7.09)%] (all P<0.05). The subsequent flow cytometry results showed that cell apoptotic rates of SMMC7721 and BEL-7402 cells transfected with sh-FEZF1-AS1 were (13.02±1.38)% and (11.88±1.29)%, respectively, which were significantly higher than those in sh-NC groups [(5.57±1.46)% and (8.06±1.42)%, respectively, all P<0.05]. In contrast, the apoptotic rates of SMMC7721 and BEL-7402 cells transfected with OE-FEZF1-AS1 were (3.01±0.39)% and (3.22±0.43)%, which were significantly lower than those in OE-NC groups [(6.68±0.96)% and (6.63±0.45)%, all P<0.05]. In addition, knockdown or overexpression of lncRNA FEZF1-AS1 expression inhibited or enhanced the migration and invasion abilities as well as the levels of adhesion molecules in hepatocellular carcinoma cells. After 30 days of feeding under the same conditions, the tumor volumes of sh-FEZF1-AS1 and sh-NC SMMC7721 cells xenograft mice models were (0.26±0.03) cm(3) and (0.63±0.06) cm(3), respectively, showing significant difference (P<0.05). The tumor volumes of sh-FEZF1-AS1 and sh-NC BEL-7402 cells were (0.31±0.02) cm(3) and (0.72±0.08) cm(3), and the difference was statistically significant (P<0.05). Conclusion: lncRNA FEZF1-AS1 may strengthen the growth, migration and invasion of hepatocellular carcinoma cells.


Assuntos
Carcinoma Hepatocelular , Movimento Celular , Proliferação de Células , Neoplasias Hepáticas , RNA Longo não Codificante , Animais , Carcinoma Hepatocelular/genética , Carcinoma Hepatocelular/patologia , Proteínas de Ligação a DNA , Regulação Neoplásica da Expressão Gênica , Neoplasias Hepáticas/genética , Neoplasias Hepáticas/patologia , Camundongos , Camundongos Nus , Proteínas do Tecido Nervoso , Reação em Cadeia da Polimerase em Tempo Real , Fatores de Transcrição
15.
Chem Commun (Camb) ; 55(79): 11944-11947, 2019 Oct 01.
Artigo em Inglês | MEDLINE | ID: mdl-31531457

RESUMO

A novel hexanuclear copper(ii)-based complex, [Cu6(tpbb)2(NO3)12] (1), was synthesized, which shows potent cytotoxicity to hepatoma carcinoma cells by inducing apoptosis and apoptosis-related processes. Furthermore, mechanistic investigations based on proteomes revealed that the induced apoptosis was mediated by acting on several targets and multiple pathways in a pleiotropic way.


Assuntos
Apoptose/efeitos dos fármacos , Carcinoma Hepatocelular/tratamento farmacológico , Complexos de Coordenação/química , Cobre/química , Neoplasias Hepáticas/tratamento farmacológico , Carcinoma Hepatocelular/patologia , Linhagem Celular Tumoral , Permeabilidade da Membrana Celular , Sobrevivência Celular/efeitos dos fármacos , Complexos de Coordenação/farmacologia , Dano ao DNA/efeitos dos fármacos , Desenho de Drogas , Humanos , Ligantes , Neoplasias Hepáticas/patologia , Simulação de Acoplamento Molecular , Relação Estrutura-Atividade
16.
Yonsei Med J ; 60(9): 842-853, 2019 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-31433582

RESUMO

PURPOSE: Long intergenic non-protein coding RNA 665 (LINC00665) plays a vital role in the development of cancer. Its function in hepatocellular carcinoma (HCC), however, remains largely unknown. MATERIALS AND METHODS: The expressions of LINC00665, miR-186-5p, and MAP4K3 were determined by qRT-PCR. Cell viability and apoptosis were evaluated by MTT and flow cytometry, respectively. Autophagic puncta formation was observed by fluorescence microscopy. Bioinformatics analysis, luciferase reporter assay, RNA immunoprecipitation, and RNA pulldown were performed to identify associations among LINC00665, miR-186-5p, and MAP4K3. Western blot was utilized to examine the expressions of MAP4K3, Beclin-1, and LC3. Tumor growth was evaluated in a xenograft model. RESULTS: Elevations in LINC00665 were observed in HCC tissues and cells. The overall survival of HCC patients with high levels of LINC00665 was shorter than those with low levels. In vitro, LINC00665 depletion inhibited viability and induced apoptosis and autophagy. miR-186-5p interacted with LINC00665 and was downregulated in HCC tissues and cells. Upregulation of miR-186-5p inhibited viability and induced apoptosis and autophagy, which were attenuated by upregulation of LINC00665. MAP4K3 was found to possess binding sites with miR-186-5p and was upregulated in HCC tissues and cells. MAP4K3 depletion inhibited viability and induced apoptosis and autophagy, which were attenuated by miR-186-5p inhibitor. In vivo, miR-186-5p expression was negatively correlated with LINC00665 or MAP4K3 in HCC tissues, while LINC00665 was positively correlated with MAP4K3. LINC00665 knockdown suppressed tumor growth. CONCLUSION: LINC00665 was involved in cell viability, apoptosis, and autophagy in HCC via miR-186-5p/MAP4K3 axis, which may provide a new approach for HCC treatment.


Assuntos
Apoptose/genética , Autofagia/genética , Carcinoma Hepatocelular/patologia , Sobrevivência Celular/genética , Regulação Neoplásica da Expressão Gênica/genética , Neoplasias Hepáticas/patologia , Adulto , Idoso , Carcinoma Hepatocelular/genética , Linhagem Celular Tumoral , Proliferação de Células/genética , Regulação para Baixo , Feminino , Humanos , Neoplasias Hepáticas/genética , Masculino , MicroRNAs/genética , Pessoa de Meia-Idade , Proteínas Serina-Treonina Quinases , RNA Longo não Codificante/genética , Regulação para Cima
17.
Medicine (Baltimore) ; 98(31): e16660, 2019 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-31374039

RESUMO

INTRODUCTION: Primary hepatocellular carcinoma (HCC) is one of the most common malignancies, only 10% to 20% of HCC patients are surgically resectable as most of the patients are diagnosed at advanced stages at presentation. The efficiencies of transcatheter arterial chemoembolization (TACE), high-intensity focused ultrasound (HIFU), and three-dimensional conformal radiation therapy (3D-CRT) in patients with advanced HCC have been clinically confirmed. We here report a patient with HCC accompanied by venous tumor thrombus, who was treated with the combination of these 3 therapies. The patient survived for 16 months with good quality of life. PATIENT CONCERNS: The patient was a 72-year-old male with a primary multicentric HCC accompanied by tumor thrombus in the right hepatic vein. The patient had the symptoms of abdominal distention and liver pain. He refused sorafenib treatment because of personal reason. DIAGNOSIS: Primary multicentric HCC stage IIIB cT4N0M0, accompanied by tumor thrombus in the right hepatic vein; chronic viral hepatitis B; and hepatitis B virus-related decompensated liver cirrhosis. INTERVENTIONS: TACE + HIFU + 3D-CRT. OUTCOMES: The patient had an overall survival of 16 months with good quality of life. Compared with monotherapy, the combined therapy significantly prolonged patient survival time with improved clinical benefits. CONCLUSION: The combination of TACE, HIFU, and 3D-CRT is safe and effective in the treatment of advanced HCC, which provides a possible comprehensive treatment strategy for advanced HCC.


Assuntos
Carcinoma Hepatocelular/terapia , Quimioembolização Terapêutica/métodos , Tratamento por Ondas de Choque Extracorpóreas/métodos , Neoplasias Hepáticas/terapia , Radioterapia Conformacional/métodos , Idoso , Carcinoma Hepatocelular/complicações , Carcinoma Hepatocelular/patologia , Terapia Combinada , Humanos , Neoplasias Hepáticas/complicações , Neoplasias Hepáticas/patologia , Masculino , Estadiamento de Neoplasias , Trombose Venosa/etiologia
18.
Anticancer Res ; 39(8): 4219-4225, 2019 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-31366509

RESUMO

BACKGROUND/AIM: The aim of the study was to evaluate surgical outcomes of patients with high-signal intensity (SI) image hepatocellular carcinoma (HCC). PATIENTS AND METHODS: Between 2008 and 2013, 257 HCC patients were retrospectively evaluated. A total of 21 patients were diagnosed as high-SI image HCC, 215 as low-SI image HCC, and 21 patients as mixed (high and low)-SI image HCC in the hepatobiliary (HB) phase of MRI. Five-year overall survival (OS) and recurrence-free survival (RFS) were compared among patient groups. RESULTS: The 5-year OS and RFS rates were significantly higher in patients with high-SI image HCC (100% and 56%) than in patients with low-SI image HCC (71%; p=0.097 and 38%; p=0.0209) and in patients with mixed-SI image HCC (73%; p=0.0329 and 9%; p=0.0021). High-SI image was an independent prognostic factor for OS (relative risk 0.167, p=0.0178) and RFS (relative risk 0.471, p=0.0322) on multivariate analysis. CONCLUSION: Patients with high-SI image HCC showed favorable long-term survival after curative surgery.


Assuntos
Sistema Biliar/diagnóstico por imagem , Carcinoma Hepatocelular/diagnóstico por imagem , Neoplasias Hepáticas/diagnóstico por imagem , Recidiva Local de Neoplasia/diagnóstico por imagem , Idoso , Idoso de 80 Anos ou mais , Sistema Biliar/patologia , Carcinoma Hepatocelular/patologia , Meios de Contraste/administração & dosagem , Intervalo Livre de Doença , Feminino , Gadolínio DTPA/administração & dosagem , Humanos , Neoplasias Hepáticas/patologia , Imagem por Ressonância Magnética , Masculino , Pessoa de Meia-Idade , Recidiva Local de Neoplasia/patologia , Estudos Retrospectivos
19.
Anticancer Res ; 39(8): 4315-4324, 2019 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-31366523

RESUMO

BACKGROUND/AIM: This study aimed to obtain accurate differential diagnosis (DDx) of multicentric carcinogenesis (MC) and intrahepatic metastasis (IM) in recurrent lesions of hepatocellular carcinoma. MATERIALS AND METHODS: A total of 79 patients who underwent re-hepatectomy (2000-2013) were examined. PCR was used to analyze 13 chromosomal microsatellite loci by PCR. On the basis of this genetic analysis, the recurrent lesions were diagnosed as IM, MC or not determined (ND). Subsequently, DDx was compared with types of resection and outcome. RESULTS: The recurrent lesions were diagnosed as IM in 33 patients, MC in 44, and ND in 2. The anatomical resection group included 14 IM lesions (28%) and 36 MC lesions (72%), while the non-anatomical resection group included 19 IM lesions (70%) and 8 MC lesions (30%) (p<0.001). CONCLUSION: Anatomical resection at initial hepatectomy may reduce the likelihood of IM recurrence, leading to a better outcome for patients with HCC.


Assuntos
Carcinoma Hepatocelular/diagnóstico , Neoplasias Hepáticas/diagnóstico , Metástase Neoplásica/diagnóstico , Recidiva Local de Neoplasia/diagnóstico , Adulto , Idoso , Carcinogênese/genética , Carcinoma Hepatocelular/genética , Carcinoma Hepatocelular/patologia , Carcinoma Hepatocelular/cirurgia , Diagnóstico Diferencial , Feminino , Hepatectomia/métodos , Humanos , Neoplasias Hepáticas/genética , Neoplasias Hepáticas/patologia , Neoplasias Hepáticas/secundário , Masculino , Repetições de Microssatélites/genética , Pessoa de Meia-Idade , Metástase Neoplásica/genética , Metástase Neoplásica/patologia , Recidiva Local de Neoplasia/genética , Recidiva Local de Neoplasia/patologia , Recidiva Local de Neoplasia/cirurgia
20.
Gene ; 716: 144031, 2019 Oct 20.
Artigo em Inglês | MEDLINE | ID: mdl-31377314

RESUMO

Circular RNAs (circRNAs), a novel class of widespread and diverse endogenous RNAs, have been identified as critical regulators of various cancers, including hepatocellular carcinoma (HCC). However, the specific roles of circRNAs in HCC are largely unknown. In this study, we identified a novel circRNA, circ-IGF1R, in HCC tumour tissues and cell lines. Circ-IGF1R levels were found to be significantly upregulated in HCC tissues compared with levels in paired peritumoural tissues. The high expression levels of circ-IGF1R in HCC were associated with tumour size. Moreover, knocking down circ-IGF1R with siRNA significantly attenuated cell proliferation and induced cell apoptosis and cell cycle arrest in vitro. Further investigation revealed that PI3K/AKT signalling pathway activation was involved in the oncogenic functions of circ-IGF1R in HCC. Our study suggests that circ-IGF1R may be a potential target for the prevention and treatment of HCC.


Assuntos
Carcinoma Hepatocelular/genética , Neoplasias Hepáticas/genética , RNA/metabolismo , Apoptose , Carcinoma Hepatocelular/enzimologia , Carcinoma Hepatocelular/metabolismo , Carcinoma Hepatocelular/patologia , Ciclo Celular , Linhagem Celular , Linhagem Celular Tumoral , Proliferação de Células , Feminino , Humanos , Neoplasias Hepáticas/enzimologia , Neoplasias Hepáticas/metabolismo , Neoplasias Hepáticas/patologia , Masculino , Pessoa de Meia-Idade , Fosfatidilinositol 3-Quinase/antagonistas & inibidores , Fosfatidilinositol 3-Quinase/metabolismo , Proteínas Proto-Oncogênicas c-akt/antagonistas & inibidores , Proteínas Proto-Oncogênicas c-akt/metabolismo , Transdução de Sinais , Regulação para Cima
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