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1.
Anticancer Res ; 40(1): 245-252, 2020 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-31892573

RESUMO

AIM: It has been shown that the integration of hepatitis B virus (HBV) gene into the host genome is a high-risk factor for development of hepatocellular carcinoma (HCC). However, the relationship between HBV S-integrated human extra spindle pole bodies-like 1 (ESPL1) gene and HCC is unknown. This study was designed to detect HBV S-integrated human ESPL1 fusion gene in patients with HCC for potentially using this fusion gene as a biomarker for HCC diagnosis. PATIENTS AND METHODS: Nineteen and 70 patients with chronic hepatitis B (CHB) were recruited to the experimental and control groups, respectively, and both groups underwent an effective nucleoside/nucleotide analog therapy and follow-up for HCC occurrence for up to 11 years. HCC tissues were obtained by surgical resection from the experimental group, while liver tissues were collected by liver biopsy in the control group prior to treatment with nucleoside/nucleotide analogs. Alu polymerase chain reaction was used to assess HBV S gene integration in the liver tissues from both groups. HBV S-integrated human ESPL1 fusion gene was then detected in patients with HBV S gene integration using a gene database. RESULTS: All patients in the experimental group developed HCC, whereas no HCC was diagnosed in the control group. HBV S gene integration was identified in 12 out of 19 HCC tissues in the experimental group, giving a detection rate of 63.2%, which was significantly greater than that of 15.7% (11/70) in the control group (p<0.001). We further showed that HBV S-integrated human ESPL1 fusion gene was detected in eight patients (rate of 66.7%) among the 12 patients with HCC with HBV S gene integration in the experimental group, whereas the fusion gene was not detectable in any of the patients in the control group (p=0.001). CONCLUSION: This research demonstrates a high detection rate of HBV S-integrated human ESPL1 fusion gene in patients with HBV-related HCC and shows that this fusion gene appears to be associated with HCC development in patients with CHB. These findings suggest that HBV S-integrated human ESPL1 fusion gene may potentially serve as a biomarker for early detection of HCC in HBV-infected populations.


Assuntos
Grupo com Ancestrais do Continente Asiático , Vírus da Hepatite B/genética , Neoplasias Hepáticas/genética , Proteínas de Fusão Oncogênica/genética , Separase/genética , Carcinoma Hepatocelular/genética , Carcinoma Hepatocelular/patologia , Estudos de Casos e Controles , Feminino , Regulação Neoplásica da Expressão Gênica , Hepatite B Crônica/genética , Humanos , Neoplasias Hepáticas/patologia , Masculino , Pessoa de Meia-Idade , Proteínas de Fusão Oncogênica/metabolismo , Separase/metabolismo , Proteínas do Envelope Viral/genética , Proteínas do Envelope Viral/metabolismo
2.
Zhonghua Wai Ke Za Zhi ; 58(1): 13-16, 2020 Jan 01.
Artigo em Chinês | MEDLINE | ID: mdl-31902163

RESUMO

Large hepatocellular carcinoma (HCC) is one of the most common malignancies and was mistaked as "advanced and unresectable" . Liver resection is still the best curable treatment for HCC.The resection of large HCC is very difficult, which seriously restrict the progress of liver surgery.Our study proved that solitary large HCC (SLHCC) has unique clinicopathological and molecular biological characteristics.No matter how big the tumor size is, it belongs to early stage if there is no vascular invasion.Liver resection should be aggressively recommended for the patients with SLHCC, in which they can obtain good outcome, with 40% 5-year survival rate.We has also defined the borderline resectable hepatocellular carcinoma, and suggested that strictly master and correctly judge the surgical indications, syntheticly evaluate the surgical safety and patient's tolerability for liver resection.After that, with hands of experienced surgeons, liver resection for SLHCC can be safely and reliablely performed.


Assuntos
Carcinoma Hepatocelular/cirurgia , Hepatectomia/métodos , Neoplasias Hepáticas/cirurgia , Carcinoma Hepatocelular/patologia , Hepatectomia/tendências , Humanos , Neoplasias Hepáticas/patologia
3.
Gut ; 69(1): 168-176, 2020 01.
Artigo em Inglês | MEDLINE | ID: mdl-30878947

RESUMO

OBJECTIVE: Hepatocellular carcinoma (HCC) is a major cause of death worldwide and its incidence is expected to increase globally. Aim of this study was to assess whether the implementation of screening policies and the improvement of treatment options translated into a real-world survival benefit in HCC patients. DESIGN: 4078 patients diagnosed with HCC between 1998 and 2016 from the Munich Cancer Registry were analysed. Tumour characteristics and outcome were analysed by time period and according to age and presence of metastases at diagnosis. Overall survival (OS) was analysed using Kaplan-Meier method and relative survival (RS) was computed for cancer-specific survival. Cox proportional hazard models were conducted to control for prognostic variables. RESULTS: While incidence of HCC remained substantially stable, tumours were diagnosed at increasingly earlier stages, although the median age at diagnosis increased. The 3 years RS in HCC improved from 19.8% in 1998-2002, 22.4% in 2003-2007, 30.6% in 2008-2012 up to 31.0% in 2013-2016. Median OS increased from 6 months in 1998-2002 to 12 months in 2008-2016. However, analysis according to the metastatic status showed that survival improved only in patients without metastases at diagnosis whereas the prognosis of patients with metastatic disease remained unchanged. CONCLUSION: These real-world data show that, in contrast to the current assumptions, the incidence of HCC did not increase in a representative German region. Earlier diagnosis, likely related to the implementation of screening programmes, translated into an increasing employment of effective therapeutic options and a clear survival benefit in patients without metastases at diagnosis, irrespective of age.


Assuntos
Carcinoma Hepatocelular/mortalidade , Carcinoma Hepatocelular/secundário , Detecção Precoce de Câncer/mortalidade , Neoplasias Hepáticas/mortalidade , Neoplasias Hepáticas/patologia , Idoso , Idoso de 80 Anos ou mais , Carcinoma Hepatocelular/diagnóstico , Carcinoma Hepatocelular/terapia , Feminino , Alemanha/epidemiologia , Humanos , Incidência , Estimativa de Kaplan-Meier , Neoplasias Hepáticas/diagnóstico , Neoplasias Hepáticas/terapia , Masculino , Pessoa de Meia-Idade , Estadiamento de Neoplasias , Prognóstico , Modelos de Riscos Proporcionais , Taxa de Sobrevida/tendências
4.
Br J Radiol ; 93(1105): 20190375, 2020 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-31670572

RESUMO

OBJECTIVES: We aimed to identify dynamic CT features that can be used for prediction of local recurrence of hepatocellular carcinoma (HCC) after proton beam therapy (PBT). METHODS: We retrospectively retrieved CT scans of patients with PBT-treated HCC, taken between January 2004 and December 2016. 17 recurrent lesions and 34 non-recurrent lesions were retrieved. The attenuation difference between irradiated tumor and irradiated parenchyma (ADHCC-IP) was compared in the two groups by using the Mann-Whitney U test. Cut-off value of ADHCC-IP was estimated by using the Youden index. RESULTS: The follow-up time after PBT initiation ranged from 374 to 2402 days (median, 1069 days) in recurrent lesions, and 418 to 2923 days (median, 1091.5 days) in non-recurrent lesions (p = 0.892). The time until appearance of local recurrence after PBT initiation ranged from 189 to 2270 days (median, 497 days). ADHCC-IP of recurrent lesions [mean, -21.8 Hounsfield units (HU); from -95 to -31 HU] was significantly greater than that of non-recurrent lesions (mean, -51.7 HU; from -117 to -12 HU) at 1-2 years in portal venous phase (p = 0.039). 5-year local tumor control rates were 0.93 and 0.56 in lesions with ADHCC-IP at 1-2 years in PVP < -55 and ≥ -55 HU, respectively. CONCLUSION: The attenuation difference between irradiated HCC and irradiated liver parenchyma in portal venous phase at 1-2 years after PBT can predict long-term local recurrence of HCC after treatment. ADVANCES IN KNOWLEDGE: We identified a cut-off value for contrast enhancement of HCC after PBT that could predict future local recurrence.


Assuntos
Carcinoma Hepatocelular/radioterapia , Neoplasias Hepáticas/radioterapia , Recidiva Local de Neoplasia/diagnóstico por imagem , Recidiva Local de Neoplasia/patologia , Terapia com Prótons , Tomografia Computadorizada por Raios X/métodos , Idoso , Carcinoma Hepatocelular/patologia , Meios de Contraste , Feminino , Humanos , Neoplasias Hepáticas/patologia , Masculino , Estudos Retrospectivos
6.
Anticancer Res ; 39(11): 6325-6332, 2019 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-31704863

RESUMO

BACKGROUND/AIM: We aimed to assess surgical outcome and long-term survival after elective hepatic resection for hepatocellular carcinoma (HCC) and colorectal liver metastasis (CRLM) in patients aged 80 years or older. PATIENTS AND METHODS: This study included 100 patients aged 70 years or older, who underwent hepatic resection for HCC or CRLM between January 2000 and December 2012. Outcomes and clinicopathological data were compared between the elderly (aged 70-79 years; n=84) and extremely elderly groups (aged 80 years or older; n=16). RESULTS: Incidence of postoperative complications, in-hospital mortality, and postoperative OS in the extremely elderly group were comparable with those of the elderly group. In patients with HCC, the extremely elderly group was associated with shorter DFS (p=0.030) in univariate analysis, while multivariate analysis showed significant and independent factors of cancer recurrence. CONCLUSION: Hepatic resection for HCC and CRLM in patients aged 80 years and older may be safe and acceptable with appropriate selection. For HCC in patients aged 80 years and older, hepatic resection may be effective when negative surgical margins can be achieved.


Assuntos
Carcinoma Hepatocelular/cirurgia , Neoplasias Colorretais/patologia , Hepatectomia , Neoplasias Hepáticas/cirurgia , Fatores Etários , Idoso , Idoso de 80 Anos ou mais , Análise de Variância , Carcinoma Hepatocelular/mortalidade , Carcinoma Hepatocelular/patologia , Comorbidade , Intervalo Livre de Doença , Feminino , Hepatectomia/mortalidade , Hepatectomia/estatística & dados numéricos , Mortalidade Hospitalar , Humanos , Estimativa de Kaplan-Meier , Neoplasias Hepáticas/mortalidade , Neoplasias Hepáticas/patologia , Neoplasias Hepáticas/secundário , Masculino , Margens de Excisão , Complicações Pós-Operatórias , Análise de Sobrevida , Resultado do Tratamento
7.
Medicine (Baltimore) ; 98(45): e17920, 2019 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-31702672

RESUMO

There is little information concerning the predictive ability of the preoperative platelet to albumin ratio (PAR) in hepatocellular carcinoma (HCC) patients after liver resection. In the current study, we aimed to assess the prognostic power of the PAR in HCC patients without portal hypertension (PH) following liver resection.Approximately 628 patients were included in this study. A receiver operating characteristic (ROC) curve analysis was performed to evaluate the predictive value of the PAR for both recurrence-free survival (RFS) and overall survival (OS). Univariate and multivariate analyses were used to identify the independent risk factors for both RFS and OS.During the follow-up period, 361 patients experienced recurrence, and 217 patients died. ROC curve analysis suggested that the best cut-off value of the PAR for RFS was greater than 4.8. The multivariate analysis revealed that microvascular invasion (MVI), tumor size >5 cm, high aspartate aminotransferase-to-platelet count ratio index (APRI) and high PAR were four independent risk factors for both RFS and OS. Patients with a low PAR had significantly better RFS and OS than those with a high PAR.The PAR may be a useful marker to predict the prognosis of HCC patients after liver resection. HCC patients with a high preoperative PAR had a higher recurrent risk and lower long-term survival rate than those with a low preoperative PAR.


Assuntos
Albuminas/metabolismo , Plaquetas/metabolismo , Carcinoma Hepatocelular/mortalidade , Neoplasias Hepáticas/mortalidade , Recidiva Local de Neoplasia/epidemiologia , Adulto , Biomarcadores/sangue , Carcinoma Hepatocelular/patologia , Carcinoma Hepatocelular/cirurgia , Feminino , Hepatectomia/mortalidade , Hepatectomia/estatística & dados numéricos , Humanos , Neoplasias Hepáticas/patologia , Neoplasias Hepáticas/cirurgia , Estudos Longitudinais , Masculino , Pessoa de Meia-Idade , Recidiva Local de Neoplasia/patologia , Valor Preditivo dos Testes , Período Pré-Operatório , Intervalo Livre de Progressão , Curva ROC
8.
Zhonghua Gan Zang Bing Za Zhi ; 27(10): 766-771, 2019 Oct 20.
Artigo em Chinês | MEDLINE | ID: mdl-31734990

RESUMO

Objective: To investigate the prognostic relationship between the expression levels of periostin (POSTN) in hepatocellular carcinoma (HCC) tissues as well as its effect in invasion and metastasis. Methods: The expression levels of POSTN in liver cancer tissues were detected with real-time quantitative PCR (QPCR) and immunohistochemistry (IHC). Kaplan-Meier method and Log-rank test were used to analyze the relationship between POSTN expression level and postoperative prognosis in patients with liver cancer. The expression of POSTN in hepatocellular carcinoma cells with different metastasis characteristics were detected in vitro and the overexpression of POSTN in low metastatic hepatocellular carcinoma cells was mediated through plasmid transfection techniques. The effects of POSTN on invasion and metastasis of hepatocellular carcinoma cells were determined by transwell migration and matrigel invasion assay. The comparative expression level of POSTN was analyzed by t-test. Results: The expression levels of POSTN in tissues from high to low was in the order of metastatic liver cancer tissues, non-metastatic liver cancer tissues and normal liver tissues (P = 0.006). The median survival time and 3-year survival rate in postoperative patients with hepatocellular carcinoma of high POSTN expression level were significantly lower than the low expression group (10.00 months, 44.44%; 59.00 months, 53.13%, P = 0.031 2). In in vitro testing, the expression of POSTN was highest in MHCC97H cells with high metastatic characteristics as compared with Huh7 and MHCC97L cells with low and medium metastatic characteristics. After overexpression of POSTN in MHCC97L cells, the migration and invasion capacity of MHCC97L cells was increased. Conclusion: POSTN is associated with pathological processes such as metastasis and invasion of liver cancer, which may promote the migration and invasion of liver cancer cells. It is expected to be an important prognostic biomarker of tumor recurrence and a therapeutic target for inhibiting the occurrence of metastasis in postoperative patients with hepatocellular carcinoma.


Assuntos
Carcinoma Hepatocelular/patologia , Moléculas de Adesão Celular/metabolismo , Neoplasias Hepáticas/patologia , Carcinoma Hepatocelular/metabolismo , Linhagem Celular Tumoral , Regulação Neoplásica da Expressão Gênica , Humanos , Neoplasias Hepáticas/metabolismo , Invasividade Neoplásica , Metástase Neoplásica , Recidiva Local de Neoplasia , Prognóstico
9.
Anticancer Res ; 39(11): 5973-5982, 2019 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-31704822

RESUMO

BACKGROUND/AIM: Lenvatinib is a potent inhibitor of receptor tyrosine kinases, targeting vascular endothelial growth factor receptors (VEGFR1-3), fibroblast growth factor receptors (FGFR1-4), KIT, and RET. Here, we investigated the antiproliferative effects of lenvatinib in liver cancer cells in vitro and in vivo. MATERIALS AND METHODS: Eleven hepatocellular carcinoma cell lines and two combined hepatocellular/cholangiocarcinoma cell lines were treated with 0-30 µM lenvatinib. Cell growth, apoptosis and the expression of FGFR1-4, FGF19, fibroblast growth factor receptor substrate (FRS)2α and RET were examined. Two HCC cell lines were subcutaneously implanted on nude mice and mice were treated with 3, 10, 30 mg/kg/day of lenvatinib or vehicle for 14 consecutive days. Tumor volume was measured every 3 days. Mice were sacrificed on day 15 and tumors were processed for histological examination. Blood vessels, microvessel density, necrosis, and apoptosis were also examined. RESULTS: Lenvatinib dose- and time-dependently inhibited growth of all cell lines; however, sensitivity to lenvatinib varied. Apoptosis was not observed in any cell line, and expression of FGFR1, -2, -3 and -4, FGF19, FRS2α, and RET were observed in these cell lines. Cell lines with high expression of these factors showed higher response to lenvatinib. In mice, lenvatinib dose-dependently suppressed tumor growth. Blood vessels and microvessel density were significantly reduced and the rate of necrosis was significantly increased by lenvatinib; apoptosis was not observed. CONCLUSION: Antiproliferative effects of lenvatinib on liver cancer cells were observed in vitro and in vivo. Lenvatinib may suppress tumor formation by inhibiting angiogenesis, and via an additional direct antiproliferative effect in some liver cancer cells.


Assuntos
Antineoplásicos/farmacologia , Apoptose/efeitos dos fármacos , Carcinoma Hepatocelular/patologia , Proliferação de Células/efeitos dos fármacos , Neoplasias Hepáticas/patologia , Compostos de Fenilureia/farmacologia , Quinolinas/farmacologia , Animais , Biomarcadores Tumorais/metabolismo , Carcinoma Hepatocelular/tratamento farmacológico , Carcinoma Hepatocelular/metabolismo , Feminino , Humanos , Técnicas In Vitro , Neoplasias Hepáticas/tratamento farmacológico , Neoplasias Hepáticas/metabolismo , Camundongos , Camundongos Endogâmicos BALB C , Camundongos Nus , Células Tumorais Cultivadas , Ensaios Antitumorais Modelo de Xenoenxerto
10.
Anticancer Res ; 39(11): 6025-6033, 2019 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-31704828

RESUMO

BACKGROUND/AIM: Carbohydrate antigen 19-9 (CA19-9) is a poor prognostic marker in intrahepatic cholangiocarcinoma (IHCC). Previous studies have shown a link between hypoxia and CA19-9 in cancer, and we have previously demonstrated a correlation between HDAC1 and HIF-1α in IHCC. Here, we evaluated the expression and correlation of CA19-9 with HIF-1 and HDAC in IHCC. PATIENTS AND METHODS: This study included 62 patients with IHCC who underwent primary hepatectomy at our department. Clinicopathological characteristics were examined. Immunohistochemical expression of HIF-1 and HDAC1 in specimens was quantitatively evaluated. RESULTS: Patients with high preoperative serum CA19-9 levels showed clinicopathological characteristics associated with tumour progression. High CA19-9 levels were associated with worse overall and recurrence-free survival. Univariate and multivariate analysis detected high CA19-9 levels as an independent poor prognostic factor for IHCC. Serum CA19-9 was significantly correlated with both HIF-1α and HDAC1 expression. CONCLUSION: High serum CA19-9 level is a poor prognostic factor for overall survival in IHCC and correlates with HIF-1α and HDAC1 expression.


Assuntos
Neoplasias dos Ductos Biliares/patologia , Antígeno CA-19-9/metabolismo , Colangiocarcinoma/patologia , Histona Desacetilase 1/metabolismo , Subunidade alfa do Fator 1 Induzível por Hipóxia/metabolismo , Neoplasias Hepáticas/patologia , Recidiva Local de Neoplasia/patologia , Idoso , Neoplasias dos Ductos Biliares/metabolismo , Neoplasias dos Ductos Biliares/cirurgia , Biomarcadores Tumorais/metabolismo , Colangiocarcinoma/metabolismo , Colangiocarcinoma/cirurgia , Feminino , Seguimentos , Regulação Neoplásica da Expressão Gênica , Humanos , Neoplasias Hepáticas/metabolismo , Neoplasias Hepáticas/cirurgia , Masculino , Recidiva Local de Neoplasia/metabolismo , Recidiva Local de Neoplasia/cirurgia , Prognóstico , Taxa de Sobrevida
11.
Can Assoc Radiol J ; 70(4): 434-440, 2019 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-31585824

RESUMO

PURPOSE: To determine negative predictive value (NPV) of contrast-enhanced ultrasound (CEUS) to demonstrate local tumour progression (LTP) at thermal ablation (TA) sites. METHODS: Our institutional review board approved this retrospective study; acquisition of consent was waived. Consecutive CEUS examinations performed between 2004-2014 for TA site evaluation on patients who could not undergo enhanced computed tomography (CT) or magnetic resonance imaging (MRI), or had inconclusive CT or MRI, were retrospectively reviewed. Those reported as no abnormal enhancement in or surrounding TA site were included. CEUS examination was considered true-negative based on stability or lack of enhancement/washout on follow-up imaging for at least 1 year, and false-negative (FN), if there was an arterially enhancing focus with wash-out at or surrounding TA site on subsequent follow-up imaging. RESULTS: Study population included 56 tumours in 54 patients, 11 women, 43 men; mean age 71 years. Two patients had TA of two different hepatocellular carcinomas. Thirty-six examinations were for hepatic TA and twenty for renal TA. Lesion sizes ranged from 1 cm to 7 cm (mean 3.1 ± 1.2). Mean diameter of 7 recurrences was 13.8 mm. Overall FN rate was 12.5% (7/56). Corresponding numbers were 0% (0/20) for renal TA and 19.4% (7/36) for hepatic TA. Overall NPV of CEUS was 87.5% (49/56) (confidence interval [CI]: 78.8%-96.2%). NPV for renal TA was 100% (20/20) (CI: 100%-100%) and for hepatic TA 81.5% (29/36) (CI: 67.6 %-93.5%). CONCLUSION: In this cohort, CEUS showed high NPV for exclusion of LTP at renal TA sites. NPV for hepatic TA sites was high but lower than renal TA.


Assuntos
Neoplasias Renais/diagnóstico por imagem , Neoplasias Hepáticas/diagnóstico por imagem , Ultrassonografia/métodos , Idoso , Idoso de 80 Anos ou mais , Ablação por Cateter , Meios de Contraste , Progressão da Doença , Feminino , Seguimentos , Humanos , Neoplasias Renais/patologia , Neoplasias Renais/cirurgia , Neoplasias Hepáticas/patologia , Neoplasias Hepáticas/cirurgia , Estudos Longitudinais , Masculino , Pessoa de Meia-Idade , Valor Preditivo dos Testes , Estudos Retrospectivos
12.
Expert Opin Investig Drugs ; 28(11): 941-949, 2019 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-31590579

RESUMO

Introduction: Hepatocellular carcinoma (HCC) is the most common primary liver cancer and the burden of disease is increasing globally. Until recently, systemic therapies for HCC were limited and prognosis for advanced disease generally poor.Area covered: This article describes some recent phase I and II clinical trials for the treatment of HCC. We performed a search on Pubmed with keywords hepatocellular carcinoma, phase I clinical trial, phase II clinical trial, and immunotherapy. We also searched https://clinicaltrials.gov and identified relevant trials listed as active. Studies in progress or recently reported were conducted using novel therapies based on targets identified through molecular profiling of tumors or based on insights into immune system dysregulation in HCC. We also identified studies using drugs targeting recently discovered biomarkers such as endoglin or aldo-keto reductase 1c3. The major outcomes were safety and efficacy as measured by response rate, progression-free survival or overall survival.Expert opinion: HCC is a heterogeneous disease resulting from aberrations in intracellular signaling and immune system dysregulation. Thus, a multisystem approach will be required to deliver personalized therapy. Combination therapies are likely to be future options; it is also possible that modulation of the microbiome might form part of future treatment paradigms.


Assuntos
Antineoplásicos/administração & dosagem , Carcinoma Hepatocelular/tratamento farmacológico , Neoplasias Hepáticas/tratamento farmacológico , Animais , Antineoplásicos/efeitos adversos , Antineoplásicos/farmacologia , Biomarcadores Tumorais/metabolismo , Carcinoma Hepatocelular/patologia , Drogas em Investigação/administração & dosagem , Drogas em Investigação/efeitos adversos , Drogas em Investigação/farmacologia , Humanos , Imunoterapia , Neoplasias Hepáticas/patologia , Terapia de Alvo Molecular , Sobrevida
13.
Medicine (Baltimore) ; 98(41): e17533, 2019 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-31593128

RESUMO

BACKGROUND: With the improvements of surgical instruments and surgeons' experience, laparoscopic liver resection has been applied for recurrent tumors. However, the value of laparoscopic repeat liver resection (LRLR) is still controversial nowadays, which compelled us to conduct this meta-analysis to provide a comprehensive evidence about the efficacy of LRLR for recurrent liver cancer. METHODS: A computerized search was performed to identify all eligible trials published up to April 2019. This meta-analysis was conducted to estimate the perioperative data and oncological outcomes of LRLR by compared with open repeat liver resection (ORLR) and laparoscopic primary liver resection (LPLR). A fixed or random-effect modal was established to collect the data. RESULTS: A total of 1232 patients were included in this meta-analysis (LRLR: n = 364; ORLR: n = 396; LPLR: n = 472). LRLR did not increase the operative time compared to ORLR (WMD = 15.92 min; 95%CI: -33.53 to 65.37; P = .53). Conversely, LRLR for patients with recurrent tumors was associated with less intraoperative blood loss (WMD = -187.33 mL; 95%CI: -249.62 to -125.02; P < .00001), lower transfusion requirement (OR = 0.24; 95%CI: 0.06-1.03; P = .05), fewer major complications (OR = 0.42; 95%CI: 0.23-0.76; P = .004), and shorter hospital stays (WMD = -2.31; 95%CI: -3.55 to -1.07; P = .0003). In addition, the oncological outcomes were comparable between the two groups. However, as for the safety of LRLR compared with LPLR, although the operative time in LRLR group was longer than LPLR group (WMD = 58.63 min; 95%CI: 2.99-114.27; P = .04), the blood loss, transfusion rates, R0 resection, conversion, postoperative complications, and mortality were similar between the two groups. CONCLUSIONS: LRLR for recurrent liver cancer could be safe and feasible in selected patients when performed by experienced surgeons.


Assuntos
Laparoscopia/efeitos adversos , Neoplasias Hepáticas/cirurgia , Recidiva Local de Neoplasia/cirurgia , Reoperação/efeitos adversos , Adulto , Idoso , Idoso de 80 Anos ou mais , Perda Sanguínea Cirúrgica/estatística & dados numéricos , Feminino , Hepatectomia/efeitos adversos , Hepatectomia/métodos , Hepatectomia/tendências , Humanos , Laparoscopia/métodos , Tempo de Internação/tendências , Neoplasias Hepáticas/patologia , Masculino , Pessoa de Meia-Idade , Duração da Cirurgia , Seleção de Pacientes , Período Perioperatório , Complicações Pós-Operatórias/epidemiologia , Complicações Pós-Operatórias/mortalidade , Reoperação/métodos , Resultado do Tratamento
14.
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
15.
Neoplasma ; 66(6): 918-929, 2019 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-31607134

RESUMO

Protein arginine methyltransferase 1 (PRMT1) is dysregulated in a number of human cancers. Herein, we report that PRMT1 expression is directly associated with epithelial-mesenchymal transition (EMT) in hepatic carcinoma cells. Firstly, we find that PRMT1 expression is higher in hepatic carcinoma tissues than that in normal liver tissues at both mRNA and protein levels, and higher expression of PRMT1 correlates with poor survival in liver tumors. The data in vitro reveals that PRMT1 knockdown inhibits the abilities of proliferation, migration and invasion, while PRMT1 overexpression promotes the above behaviors in hepatic carcinoma cells. Further studies indicate that PRMT1 knockdown remarkably decreases the expression of mesenchymal markers including Vimentin, Snail and N-cadherin, and upregulates expression of epithelial markers E-cadherin. Conversely, PRMT1 overexpression results in the opposite effects. Additionally, we identified that PRMT1 knockdown resulted in downregulation of TGF-ß1, p-Smad2 and p-Smad3, while PRMT1 overexpression activated TGF-ß1, p-Smad2 and p-Smad3. These findings suggest that PRMT1 promotes EMT in hepatic carcinoma cells probably via TGF-ß1/Smad pathway, and might represent a novel anti-liver cancer strategy.


Assuntos
Carcinoma Hepatocelular/metabolismo , Transição Epitelial-Mesenquimal , Neoplasias Hepáticas/metabolismo , Proteína-Arginina N-Metiltransferases/metabolismo , Proteínas Repressoras/metabolismo , Carcinoma Hepatocelular/patologia , Linhagem Celular Tumoral , Movimento Celular , Técnicas de Silenciamento de Genes , Humanos , Neoplasias Hepáticas/patologia , Transdução de Sinais , Proteína Smad2/metabolismo , Proteína Smad3/metabolismo , Fator de Crescimento Transformador beta1/metabolismo
16.
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
17.
Life Sci ; 236: 116933, 2019 Nov 01.
Artigo em Inglês | MEDLINE | ID: mdl-31614146

RESUMO

AIMS: Hepatocellular carcinoma (HCC) pathogenesis involves the interplay of multiple signalling pathways. Notch and Hedgehog (Hh) are two major developmental pathways that act in concert to regulate adult cell repair. CK2α -serine-threonine kinase-down-regulation enhanced apoptotic activity and was proven beneficial for HCC patients. Quercetin is a bioactive flavonoid and has been shown to protect against HCC through its antioxidant activity. This study was carried out to elucidate the antineoplastic effect of quercetin through regulating both Notch and Hh pathways, apoptosis, cell proliferation and CK2α activity. MAIN METHODS: Hepatocellular carcinoma was induced in male Sprague Dawley rats by thioacetamide. Quercetin was administered in both protective and curative doses. Parameters of liver function and oxidative stress were assessed. CK2α, Notch and Hh pathways were evaluated using RT-PCR and ELISA. Apoptosis was investigated by detecting caspase-3, caspase-8 and p53. Proliferative and cell cycle markers as cyclin D1 and Ki-67 were detected immunohistochemically. KEY FINDINGS: Quercetin inhibited CK2α and downregulated mRNA and protein expression of Notch1 and Gli2. Quercetin also suppressed caspase-3 expression but not caspase-8. Quercetin elevated p53 expression whereas proliferative and cell cycle markers cyclin D1 and Ki-67 were downregulated. Markers of hepatic cellular integrity such as AST, ALT, ALP, GGT, albumin and bilirubin were significantly ameliorated. This was confirmed by histological examination. Quercetin also alleviated oxidative stress as shown by SOD, GSH, MDA and NO levels. SIGNIFICANCE: We can conclude that in addition to its antioxidant power, quercetin blocked Notch, Hedgehog, regulated the apoptotic and proliferative pathways and inhibited CK2α in HCC.


Assuntos
Antioxidantes/farmacologia , Carcinoma Hepatocelular/metabolismo , Regulação Neoplásica da Expressão Gênica/efeitos dos fármacos , Neoplasias Hepáticas/metabolismo , Quercetina/farmacologia , Transdução de Sinais/efeitos dos fármacos , Animais , Apoptose/efeitos dos fármacos , Carcinoma Hepatocelular/tratamento farmacológico , Carcinoma Hepatocelular/patologia , Caseína Quinase II/antagonistas & inibidores , Caseína Quinase II/metabolismo , Proliferação de Células/efeitos dos fármacos , Proteínas Hedgehog/antagonistas & inibidores , Proteínas Hedgehog/metabolismo , Neoplasias Hepáticas/tratamento farmacológico , Neoplasias Hepáticas/patologia , Masculino , Estresse Oxidativo , Ratos , Ratos Sprague-Dawley , Receptores Notch/antagonistas & inibidores , Receptores Notch/metabolismo
18.
Chem Commun (Camb) ; 55(87): 13148-13151, 2019 Oct 29.
Artigo em Inglês | MEDLINE | ID: mdl-31617549

RESUMO

Cu2ZnSnS4 nanocrystals (CZTS NCs) have been demonstrated to be effective in tumor therapy as a novel susceptible agent for microwave thermal and microwave dynamic therapy. CZTS NCs intensify the heating effect of microwaves with a significant temperature increase of about 15 °C compared to the control group and showed remarkable anti-tumor performance after 5 min of microwave irradiation. For the first time, we report the microwave absorption performance and singlet oxygen production of CZTS NCs used in microwave therapy, which reveals new opportunities for novel combined mechanisms of microwave thermal and microwave dynamic tumor therapies.


Assuntos
Antineoplásicos/uso terapêutico , Cobre/uso terapêutico , Neoplasias Hepáticas/tratamento farmacológico , Micro-Ondas , Nanopartículas/uso terapêutico , Sulfetos/uso terapêutico , Temperatura Ambiente , Estanho/uso terapêutico , Zinco/uso terapêutico , Animais , Antineoplásicos/química , Proliferação de Células/efeitos dos fármacos , Terapia Combinada , Cobre/química , Relação Dose-Resposta a Droga , Ensaios de Seleção de Medicamentos Antitumorais , Neoplasias Hepáticas/patologia , Neoplasias Hepáticas Experimentais/tratamento farmacológico , Neoplasias Hepáticas Experimentais/patologia , Camundongos , Nanopartículas/química , Tamanho da Partícula , Relação Estrutura-Atividade , Sulfetos/química , Propriedades de Superfície , Estanho/química , Zinco/química
20.
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
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