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1.
Medicine (Baltimore) ; 99(40): e22242, 2020 Oct 02.
Artigo em Inglês | MEDLINE | ID: mdl-33019399

RESUMO

BACKGROUND: To evaluate the clinical value of circulating tumor cell (CTC) detection in peripheral blood for the diagnosis and prognosis of hepatocellular carcinoma (HCC). METHODS: Public databases were searched, and a meta-analysis was performed to determine the specificity, sensitivity, negative- likelihood ratio (NLR) and positive-likelihood ratio (PLR), and diagnostic odds ratio (dOR) of CTC detection for the diagnosis of HCC. Hazard ratios (HRs) and 95% confidence intervals (CIs) were analyzed for the association of CTC detection with overall survival (OS) and HCC recurrence. The Meta-DiSc 1.4 and Review Manager 5.2 software programs were used for statistical analysis. RESULTS: Meta-analysis of 20 studies including 1191 patients showed that the specificity, sensitivity, NLR, PLR, and dOR of CTC testing for HCC diagnosis were 0.60 (95% CI = 0.57-0.63), 0.95 (95%CI = 0.93-0.96), 0.36 (95%CI = 0.28-0.48), 11.64 (95%CI = 5.85-23.14), and 38.94 (95%CI = 18.33-82.75), respectively. Meta-analysis of 18 studies including 1466 patients indicated that the OS of CTC-positive HCC patients was less than that of CTC-negative patients (HR = 2.31; 95% CI = 1.55-3.42; P < .01). Meta-analysis of 5 studies including 339 patients revealed that the presence of CTCs in peripheral blood significantly increased the risk of HCC recurrence (HR = 3.03, 95% CI = 1.89-4.86; P < .01). CONCLUSION: CTCs in peripheral blood may be a useful marker for HCC diagnosis. In addition, the prognosis of CTC-positive HCC patients was significantly worse than that of CTC-negative HCC patients. Therefore, further studies are warranted to confirm the clinical potential of CTC detection in peripheral blood in patients with primary HCC.


Assuntos
Carcinoma Hepatocelular/diagnóstico , Carcinoma Hepatocelular/patologia , Neoplasias Hepáticas/diagnóstico , Neoplasias Hepáticas/patologia , Células Neoplásicas Circulantes/metabolismo , Biomarcadores Tumorais , Carcinoma Hepatocelular/sangue , Contagem de Células , Humanos , Neoplasias Hepáticas/sangue , Recidiva Local de Neoplasia , Células Neoplásicas Circulantes/patologia , Razão de Chances , Prognóstico , Modelos de Riscos Proporcionais , Curva ROC , Sensibilidade e Especificidade , Análise de Sobrevida
2.
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
3.
Medicine (Baltimore) ; 99(39): e22489, 2020 Sep 25.
Artigo em Inglês | MEDLINE | ID: mdl-32991488

RESUMO

RATIONALE: Primary sarcomatoid hepatocellular carcinoma (SHC) is a rare subtype of morphologic hepatocellular carcinoma reported on less than 1% of surgical pathology specimens. Herein, we report a rare case of SHC. The case in question was initially misdiagnosed as a liver abscess due to the clinical and radiological similarity between these 2 pathologies. Ultrasound(US)- and contrast-enhanced ultrasound (CEUS)- guided biopsies are helpful in making an accurate diagnosis under the appropriate biopsy area and angle of puncture. PATIENT CONCERNS: A 56-year old male presented to our hospital with a 2-month history of dull, upper abdominal pain without radiation. DIAGNOSES: Upon initial investigation with computed tomography, a cystic mass was found in the hepatic V segment and an infectious etiology was presumed. Further diagnostic examination with CEUS and magnetic resonance imaging suggested a hepatic abscess. However, a diagnosis of atypical intrahepatic cholangiocarcinoma was not excluded. The patient received the standard antibiotic treatment without alleviation of his symptoms. Through 3 diagnostic US-and CEUS-guided biopsies over a 3-month period, the pathological diagnosis of SHC was finally confirmed. INTERVENTIONS: The patient was diagnosed by 3 diagnostic US-and CEUS-guided biopsies, the pathological diagnosis of SHC was finally confirmed. OUTCOMES: Due to the delay in diagnosis, the patient was not a candidate for surgical resection, and showed dissemination of the lesion to the portal vein. Therefore, treatment with chemotherapy was initiated. After 4 courses of this regimen, tumor progression was found on enhanced magnetic resonance imaging. Therefore, the patient received immunotherapy and targeted therapy with limited response. The patient passed away 3 months later due to tumor progression. LESSONS: A hepatic abscess should be considered as a malignant lesion when clinical symptoms do not resolve upon standard treatment. US- and CEUS- guided biopsies are helpful in making an accurate diagnosis under the appropriate biopsy area and angle of puncture.


Assuntos
Carcinoma Hepatocelular/diagnóstico por imagem , Abscesso Hepático/diagnóstico , Neoplasias Hepáticas/diagnóstico por imagem , Fígado/patologia , Carcinoma Hepatocelular/patologia , Diagnóstico Diferencial , Evolução Fatal , Humanos , Neoplasias Hepáticas/patologia , Masculino , Pessoa de Meia-Idade , Ultrassonografia
4.
Nat Commun ; 11(1): 4489, 2020 09 07.
Artigo em Inglês | MEDLINE | ID: mdl-32895384

RESUMO

We report a covalent chemistry-based hepatocellular carcinoma (HCC)-specific extracellular vesicle (EV) purification system for early detection of HCC by performing digital scoring on the purified EVs. Earlier detection of HCC creates more opportunities for curative therapeutic interventions. EVs are present in circulation at relatively early stages of disease, providing potential opportunities for HCC early detection. We develop an HCC EV purification system (i.e., EV Click Chips) by synergistically integrating covalent chemistry-mediated EV capture/release, multimarker antibody cocktails, nanostructured substrates, and microfluidic chaotic mixers. We then explore the translational potential of EV Click Chips using 158 plasma samples of HCC patients and control cohorts. The purified HCC EVs are subjected to reverse-transcription droplet digital PCR for quantification of 10 HCC-specific mRNA markers and computation of digital scoring. The HCC EV-derived molecular signatures exhibit great potential for noninvasive early detection of HCC from at-risk cirrhotic patients with an area under receiver operator characteristic curve of 0.93 (95% CI, 0.86 to 1.00; sensitivity = 94.4%, specificity = 88.5%).


Assuntos
Biomarcadores Tumorais/isolamento & purificação , Carcinoma Hepatocelular/diagnóstico , Detecção Precoce de Câncer/métodos , Vesículas Extracelulares/genética , Neoplasias Hepáticas/diagnóstico , Idoso , Biomarcadores Tumorais/genética , Carcinoma Hepatocelular/sangue , Carcinoma Hepatocelular/genética , Carcinoma Hepatocelular/patologia , Estudos de Casos e Controles , Química Click/instrumentação , Química Click/métodos , Química Computacional , Simulação por Computador , Diagnóstico Diferencial , Dimetilpolisiloxanos/química , Progressão da Doença , Detecção Precoce de Câncer/instrumentação , Feminino , Células Hep G2 , Humanos , Dispositivos Lab-On-A-Chip , Biópsia Líquida/instrumentação , Biópsia Líquida/métodos , Cirrose Hepática/sangue , Cirrose Hepática/patologia , Neoplasias Hepáticas/sangue , Neoplasias Hepáticas/genética , Neoplasias Hepáticas/patologia , Masculino , Técnicas Analíticas Microfluídicas/instrumentação , Técnicas Analíticas Microfluídicas/métodos , Pessoa de Meia-Idade , Nanoestruturas/química , Nanofios/química , Estadiamento de Neoplasias , RNA Mensageiro/genética , RNA Mensageiro/isolamento & purificação , Curva ROC , Reação em Cadeia da Polimerase Via Transcriptase Reversa/instrumentação , Reação em Cadeia da Polimerase Via Transcriptase Reversa/métodos
5.
DNA Cell Biol ; 39(10): 1838-1849, 2020 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-32876480

RESUMO

The breast cancer gene 1 (BRCA1) is a tumor suppressor, and mutations or epigenetic inactivation will increase the risk of breast cancer oncogenesis. The current research aimed to explore the relationship between BRCA1 expression, prognosis, and tumor immunity in hepatocellular carcinoma (HCC). In this study, BRCA1 expression was analyzed via multiple online databases and its association with clinical characteristics, prognosis and genetic alterations was identified using the original The Cancer Genome Atlas-liver hepatocellular carcinoma cohorts. DNA methylation sites and their prognostic values were analyzed using MethSurv. The correlations between BRCA1 and immune infiltration were investigated via Tumor Immune Estimation Resource. As results, BRCA1 was significantly upregulated in tumor tissues in multiple HCC cohorts. Besides, high BRCA1 expression was correlated with race, advanced T stage, clinical stage, poor tumor grade, MSI status, and worse prognosis. Notably, BRCA1 expression was positively correlated with infiltration levels of B cells, CD4+ T cells, CD8+ T cells, neutrophils, macrophages, and dendritic cells. The current findings imply that BRCA1 is associated with prognosis and immune infiltration, laying foundations for in-depth research on the role of BRCA1 in HCC.


Assuntos
Proteína BRCA1/genética , Biomarcadores Tumorais/genética , Carcinoma Hepatocelular/genética , Neoplasias Hepáticas/genética , Proteína BRCA1/metabolismo , Biomarcadores Tumorais/metabolismo , Carcinoma Hepatocelular/imunologia , Carcinoma Hepatocelular/patologia , Movimento Celular , Metilação de DNA , Células Dendríticas/imunologia , Humanos , Neoplasias Hepáticas/imunologia , Neoplasias Hepáticas/patologia , Linfócitos/imunologia , Macrófagos/imunologia
6.
Anticancer Res ; 40(9): 5211-5219, 2020 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-32878809

RESUMO

BACKGROUND/AIM: CBP is a transcriptional coactivator in the Wnt/ß-catenin pathway that is related to cell kinetics and differentiation. This study aimed to characterize ß-catenin-activated hepatocellular carcinoma (HCC) and evaluate the direct effects of PRI-724 (a selective inhibitor of Wnt/ß-catenin/CBP signaling) on HCC. MATERIALS AND METHODS: Immunohistochemistry for ß-catenin was performed in 199 HCC resected samples. Moreover, using cultured HCC cell lines, cell kinetics and its related proteins were analyzed after treatment of cells with C-82 (active form of PRI-724). RESULTS: Nuclear ß-catenin expression was found in 18% of HCC cases and the tumor sizes in these positive samples were larger. In HCC cell lines with a constitutively activated ß-catenin, C-82 inhibited cell proliferation. C-82 led to an increase in the percentage of cells in the G0/G1 phase of the cell cycle. The percentage of cells in the sub-G1 phase also increased. Moreover, C-82 treatment significantly decreased the expression of cell proliferating markers and increased the expression of apoptosis-related proteins. CONCLUSION: PRI-724(C-82) may be a novel drug for ß-catenin-activated HCC therapy.


Assuntos
Antineoplásicos/farmacologia , Compostos Bicíclicos Heterocíclicos com Pontes/farmacologia , Carcinoma Hepatocelular/metabolismo , Neoplasias Hepáticas/metabolismo , Pirimidinonas/farmacologia , beta Catenina/metabolismo , Biomarcadores , Carcinoma Hepatocelular/tratamento farmacológico , Carcinoma Hepatocelular/genética , Carcinoma Hepatocelular/patologia , Ciclo Celular/efeitos dos fármacos , Linhagem Celular Tumoral , Proliferação de Células/efeitos dos fármacos , Expressão Gênica , Humanos , Imuno-Histoquímica , Neoplasias Hepáticas/tratamento farmacológico , Neoplasias Hepáticas/genética , Neoplasias Hepáticas/patologia , Proteínas Wnt/metabolismo , beta Catenina/antagonistas & inibidores
7.
Nat Commun ; 11(1): 4810, 2020 09 23.
Artigo em Inglês | MEDLINE | ID: mdl-32968061

RESUMO

Chimeric antigen receptor (CAR) therapy is a promising immunotherapeutic strategy for treating multiple refractory blood cancers, but further advances are required for solid tumor CAR therapy. One challenge is identifying a safe and effective tumor antigen. Here, we devise a strategy for targeting hepatocellular carcinoma (HCC, one of the deadliest malignancies). We report that T and NK cells transduced with a CAR that recognizes the surface marker, CD147, also known as Basigin, can effectively kill various malignant HCC cell lines in vitro, and HCC tumors in xenograft and patient-derived xenograft mouse models. To minimize any on-target/off-tumor toxicity, we use logic-gated (log) GPC3-synNotch-inducible CD147-CAR to target HCC. LogCD147-CAR selectively kills dual antigen (GPC3+CD147+), but not single antigen (GPC3-CD147+) positive HCC cells and does not cause severe on-target/off-tumor toxicity in a human CD147 transgenic mouse model. In conclusion, these findings support the therapeutic potential of CD147-CAR-modified immune cells for HCC patients.


Assuntos
Basigina/metabolismo , Carcinoma Hepatocelular/tratamento farmacológico , Carcinoma Hepatocelular/metabolismo , Imunoterapia Adotiva/métodos , Neoplasias Hepáticas/tratamento farmacológico , Receptores de Antígenos Quiméricos/efeitos dos fármacos , Animais , Basigina/genética , Carcinoma Hepatocelular/patologia , Linhagem Celular Tumoral , Modelos Animais de Doenças , Feminino , Células Hep G2 , Humanos , Células Matadoras Naturais , Fígado/patologia , Neoplasias Hepáticas/patologia , Masculino , Camundongos , Camundongos Knockout , Camundongos Transgênicos , Ensaios Antitumorais Modelo de Xenoenxerto
8.
Am J Clin Oncol ; 43(9): 640-647, 2020 09.
Artigo em Inglês | MEDLINE | ID: mdl-32889834

RESUMO

BACKGROUND: The incidence of liver cancer has more than tripled since 1980. Hepatectomy represents the major curative treatment for liver cancer. The risk factors associated with 90-day mortality after hepatectomy are not well understood and there are currently no good prediction models for this outcome. The objectives of the current study were to identify risk factors of 90-day mortality after hepatectomy in patients with hepatocellular carcinoma and to develop an integer-based risk score using the National Cancer Database. METHODS: Hepatectomies recorded in the National Cancer Database during 2004-2012 were reviewed for 90-day mortality. Risk factors were identified by multivariate logistic regression models. An integer-based risk score was developed using the ß coefficients derived from the logistic regression model and tested for discriminatory ability. According to the total risk score, patients were grouped into 4 risk groups. RESULTS: The overall 90-day mortality was 10.2%. Ten risk factors were identified, which included sex, age, race/ethnicity, insurance status, education, annual hospital volume, stage, tumor grade, Charlson-Deyo Score, and surgical procedure. The risk of 90-day mortality was stratified into 4 groups. The calculated 90-day mortality rates were 2.47%, 5.88%, 12.58%, and 24.67% for low-risk, medium-risk, high-risk, and excessive-risk groups, respectively. An area under the receiver operating characteristic curve of 0.69 was obtained for model discrimination. CONCLUSIONS: The integer-based risk score we developed could easily quantify each patient's risk level and predict 90-day mortality after hepatectomy. The stratified risk score could be a useful addition to perioperative risk management and a tool to improve 90-day mortality after hepatectomy.


Assuntos
Carcinoma Hepatocelular/mortalidade , Carcinoma Hepatocelular/cirurgia , Neoplasias Hepáticas/mortalidade , Neoplasias Hepáticas/cirurgia , Adolescente , Adulto , Idoso , Área Sob a Curva , Carcinoma Hepatocelular/patologia , Estudos Transversais , Bases de Dados Factuais , Feminino , Previsões/métodos , Hepatectomia/estatística & dados numéricos , Humanos , Neoplasias Hepáticas/patologia , Modelos Logísticos , Masculino , Pessoa de Meia-Idade , Período Pós-Operatório , Curva ROC , Estudos Retrospectivos , Medição de Risco/métodos , Fatores de Risco , Estados Unidos/epidemiologia , Adulto Jovem
9.
Anticancer Res ; 40(10): 5823-5828, 2020 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-32988911

RESUMO

AIM: Our aim was to confirm the utility of Indocyanine green (ICG) fluorescence imaging for intraoperative detection of adrenal hepatocellular carcinoma (HCC) metastasis. CASE REPORT: An 83-year-old man with a right adrenal HCC metastasis was admitted after complete remission of primary HCC and a metachronous left adrenal metastasis. He was treated with ICG fluorescence-guided limited resection to preserve adrenal function. ICG was administered intravenously at a dose of 0.5 mg/kg, 6 days before the operation. After removal of the entire suspicious metastatic HCC, ICG fluorescence imaging clearly demonstrated two illuminated lesions. The lesions were separately resected using an energy device. Finally, there were no ICG fluorescent lesions which meant residual tumor. Histopathological examination confirmed adrenal metastasis of moderately differentiated HCC in the initial specimen and the additional resected specimens. Three months after the operation, adrenal function was well preserved without recurrence of HCC. CONCLUSION: ICG fluorescence imaging is essential for complete resection of adrenal HCC metastasis.


Assuntos
Neoplasias das Glândulas Suprarrenais/cirurgia , Carcinoma Hepatocelular/cirurgia , Neoplasias Hepáticas/cirurgia , Imagem Óptica , Neoplasias das Glândulas Suprarrenais/diagnóstico por imagem , Neoplasias das Glândulas Suprarrenais/patologia , Neoplasias das Glândulas Suprarrenais/secundário , Idoso de 80 Anos ou mais , Carcinoma Hepatocelular/diagnóstico por imagem , Carcinoma Hepatocelular/patologia , Humanos , Verde de Indocianina/administração & dosagem , Neoplasias Hepáticas/diagnóstico por imagem , Neoplasias Hepáticas/patologia , Masculino , Metástase Neoplásica , Recidiva Local de Neoplasia/diagnóstico por imagem , Recidiva Local de Neoplasia/patologia , Recidiva Local de Neoplasia/cirurgia
10.
PLoS One ; 15(7): e0236491, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32735635

RESUMO

Selenoprotein P (SEPP1) is a kind of secretory glycoproteins with an antioxidant effect during the development of some diseases. In this study, we attempted to observe the expression of SEPP1 in livers from the patients with hepatocellular carcinoma (HCC) and explore its effect on HCC cells. All the tissues from patients with HCC were obtained from Affiliated Hospital of Nantong University. Western blot and immunohistochemical results showed that SEPP1 was reduced in HCC liver tissues. Its expression was negatively correlated with Ki67 expression in tissues. The expression of SEPP1 in normal liver cell line was significantly higher than those in the liver cancer cell lines. Serum starvation and release experiment demonstrated that SEPP1 expression was reduced and PCNA expression was increased, when the serum was re-added into cell culture system and the cells were on a proliferation state. After SEPP1 over-expression plasmid was transfected into HepG2 cells, cell proliferation of HepG2 cells and PCNA expression level were all inhibited by SEPP1. Results obtained via 8-isoprostane ELISA further indicated that inhibited ROS level was found in HepG2 cells transfected with SEPP1 over-expression plasmid. In addition, RT-qPCR results demonstrated that GPX1 expression levels increased in HepG2 cells transfected with SEPP1 over-expression plasmid. In conclusion, SEPP1 may inhibit the proliferation of HCC cells, accompanied by the reduction of ROS production and the increasing of GPX1 expression.


Assuntos
Carcinoma Hepatocelular/genética , Glutationa Peroxidase/genética , Neoplasias Hepáticas/genética , Selenoproteína P/genética , Carcinoma Hepatocelular/patologia , Proliferação de Células/genética , Feminino , Regulação Neoplásica da Expressão Gênica/genética , Células Hep G2 , Humanos , Antígeno Ki-67/genética , Fígado/metabolismo , Fígado/patologia , Neoplasias Hepáticas/patologia , Masculino
11.
J Environ Pathol Toxicol Oncol ; 39(2): 113-123, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32749121

RESUMO

Liver cancer or hepatocellular carcinoma is considered to be the third leading cause of death among all other cancers. The rate of liver cancer occurrence is high, and the rate of recovery is low. In this study, we investigated the therapeutic efficacy of vicenin-2 against the diethylnitrosamine-induced liver carcinoma in experimental rats. Diethylnitrosamine was widely employed as a carcinogenic agent to stimulate the cancer in animal models. Our results indicated that vicenin-2 administration effectively attenuates the diethylnitrosamine-induced physiological and pharmacological alterations in the experimental rats. Vicenin-2 treatment significantly enhanced the pathological lesions and decreased the levels of alanine aminotransferase (ALT), aspartate aminotransferase (AST), alkaline phosphatase (ALP), and α-fetoprotein (AFP) in serum. We also observed that vicenin-2 reduced the production of reactive oxygen species, decreased the liver weight, upregulated expression of apoptotic proteins, and decreased the histological changes in the liver, which are induced by the diethylnitrosamine in rats. Moreover, vicenin-2 downregulates antiapoptotic Bcl-2 and Bcl-xL, and upregulates the proapoptotic Bax and caspase. Hence, our results suggested that vicenin-2 had a highly therapeutic effect in reversing diethylnitrosamine-induced liver carcinoma in rats, which might be related to the apoptosis induced by vicenin-2. Therefore vicenin-2 could be a good candidate for future therapeutic use to inhibit chemically induced liver cancer.


Assuntos
Apigenina/farmacologia , Carcinoma Hepatocelular/tratamento farmacológico , Glucosídeos/farmacologia , Neoplasias Hepáticas Experimentais/tratamento farmacológico , 8-Hidroxi-2'-Desoxiguanosina/metabolismo , Animais , Antineoplásicos Fitogênicos/farmacologia , Antioxidantes/metabolismo , Apoptose/efeitos dos fármacos , Apoptose/fisiologia , Biomarcadores Tumorais/sangue , Proteínas Sanguíneas/análise , Peso Corporal/efeitos dos fármacos , Carcinoma Hepatocelular/induzido quimicamente , Carcinoma Hepatocelular/patologia , Dietilnitrosamina/toxicidade , Enzimas/sangue , Neoplasias Hepáticas Experimentais/induzido quimicamente , Neoplasias Hepáticas Experimentais/patologia , Masculino , Estresse Oxidativo/efeitos dos fármacos , Ratos Wistar , Soroglobulinas/análise
12.
J Environ Pathol Toxicol Oncol ; 39(2): 179-189, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32749126

RESUMO

Ginkgo biloba extract EGb761 conveys an anticancer effect, but little is known regarding its role in hepatocellular carcinoma (HCC). Our study aims to determine the anticancer effect of EGb761 on HCC cell lines and clarify the underlying molecular mechanism. We explore biological functions of EGb761 in HCC using morphological observation, the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay, and cytotoxic analysis. We investigate the effects of EGb761 on proliferation and apoptosis of HCC cells using plate clone formation, proliferating cell nuclear antigen, and terminal deoxynucleotidyl transferase d-untranslated protein nick end labeling assays. Protein expressions of the NF-κB/p53 signal pathway were detected and identified using immunohistochemistry. The effect of EGb761 on the p53 signaling pathway was further confirmed by adding pifithrin (PFT)-α, an inhibitor of p53. We determine that EGb761 inhibits cell growth, reduces cell viability, and promotes apoptosis of HCC cells. In addition, EGb761 reduces proliferation and increases apoptosis of human hepatocellular carcinomas (HepG2) cells in a dose-dependent manner. We also find that EGb761 exerts an anticancer effect on HepG2 cells by activating p53 and inhibiting nuclear factor (NF)-κB signaling pathways. This study confirms that EGb761 inhibits proliferation and triggers apoptosis of HCC cells through the NF-κB/p53 signaling pathway.


Assuntos
Antineoplásicos Fitogênicos/farmacologia , Carcinoma Hepatocelular/tratamento farmacológico , Neoplasias Hepáticas/tratamento farmacológico , Extratos Vegetais/farmacologia , Apoptose/efeitos dos fármacos , Carcinoma Hepatocelular/metabolismo , Carcinoma Hepatocelular/patologia , Proliferação de Células/efeitos dos fármacos , Células Hep G2 , Humanos , Neoplasias Hepáticas/metabolismo , Neoplasias Hepáticas/patologia , NF-kappa B/metabolismo , Transdução de Sinais/efeitos dos fármacos , Proteína Supressora de Tumor p53/metabolismo
13.
Medicine (Baltimore) ; 99(32): e21489, 2020 Aug 07.
Artigo em Inglês | MEDLINE | ID: mdl-32769883

RESUMO

For the treatment of huge unresectable hepatocellular carcinoma (HCC), transcatheter arterial chemoembolization (TACE) or transcatheter arterial embolization (TAE) generally had poor effects and high complication rates. Our previous study found that Hepatic arterial infusion chemotherapy (HAIC) is a safe procedure and provides better survival than symptomatic treatment for the patients with huge unresectable HCC. The aim of the study is to compare the effect of HAIC vs TAE in patients with huge unresectable HCC.Since 2000 to 2005, patients with huge (size > 8 cm) unresectable HCC were enrolled. Twenty-six patients received HAIC and 25 patients received TAE. Each patient in the HAIC group received 2.5 + 1.4 (range: 1-6) courses of HAIC and in the TAE group received 1.8 + 1.2 (range: 1-5) courses of TAE. Baseline characteristics and survival were compared between the HAIC and TAE group.The HAIC group and the TAE group were similar in baseline characteristics and tumor stages. The overall survival rates at 1 and 2 years were 42% and 31% in the HAIC group and 28% and 24% in the TAE group. The patients in the HAIC group had higher overall survival than the TAE group (P = .077). Cox-regression multivariate analysis revealed that HAIC is the significant factor associated with overall survival (relative risk: 0.461, 95% confidence interval: 0.218-0.852, P = .027). No patients died of the complications of HAIC but three patients (12%) died of the complications of TAE.In conclusion, HAIC is a safe procedure and provides better survival than TAE for patients with huge unresectable HCCs.


Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/administração & dosagem , Carcinoma Hepatocelular/terapia , Embolização Terapêutica/mortalidade , Infusões Intra-Arteriais/mortalidade , Neoplasias Hepáticas/terapia , Idoso , Carcinoma Hepatocelular/mortalidade , Carcinoma Hepatocelular/patologia , Embolização Terapêutica/métodos , Feminino , Artéria Hepática , Humanos , Infusões Intra-Arteriais/métodos , Neoplasias Hepáticas/mortalidade , Neoplasias Hepáticas/patologia , Masculino , Pessoa de Meia-Idade , Estadiamento de Neoplasias , Modelos de Riscos Proporcionais , Análise de Regressão , Resultado do Tratamento
14.
Medicine (Baltimore) ; 99(32): e21561, 2020 Aug 07.
Artigo em Inglês | MEDLINE | ID: mdl-32769898

RESUMO

In this study, we evaluated the feasibility and efficacy of stereotactic body radiation therapy (SBRT) in the treatment of Barcelona Clinic Liver Cancer (BCLC) stage C hepatocellular carcinoma (HCC).This retrospective study evaluated 139 patients with BCLC stage C HCC who underwent CyberKnife SBRT between January 2009 and September 2017. All patients had BCLC-C, Child-Turcotte-Pugh score A-B. In-field control, overall survival (OS), progression free survival (PFS), and prognostic factors were evaluated.An objective response rate was achieved in 81.5% patients (complete response, 36.2%, partial response, 45.3%). The median survival was 15.44 months, and the 1-, 3-, 5-year OS rates were 56%, 28%, and 20%, respectively. The median PFS was 6 months, the PFS rate at 1-, 3-, and 5-year were 35%, 14%, and 10%, respectively. In-field control of 1 to 2 years was achieved in 85.1% of patients. The major pattern of failure was out-field intrahepatic failure which comprised 42.9% of patients. Multivariate analysis revealed that the Child-Turcotte-Pugh score, macrovascular invasion, advance stage (III-IV), and tumor response rate were independent predictors of OS.The result of our study shows that SBRT is a safe and effective therapeutic option for BCLC stage C HCC lesions that are unsuitable for standard loco-regional therapies, Moreover, SBRT has acceptable local control rates and low-treatment toxicity.


Assuntos
Carcinoma Hepatocelular/radioterapia , Neoplasias Hepáticas/radioterapia , Radiocirurgia/mortalidade , Idoso , Carcinoma Hepatocelular/mortalidade , Carcinoma Hepatocelular/patologia , Feminino , Humanos , Neoplasias Hepáticas/mortalidade , Neoplasias Hepáticas/patologia , Masculino , Estadiamento de Neoplasias , Radiocirurgia/métodos , Estudos Retrospectivos , Taxa de Sobrevida
15.
Orv Hetil ; 161(35): 1441-1448, 2020 08.
Artigo em Húngaro | MEDLINE | ID: mdl-32822322

RESUMO

Chronic liver disorders are the main leading cause of morbidity and mortality data. Viral infection, toxic injury, metabolic, autoimmun, storage disorders, in the case of ongoing presence of the etiological factors, could result in fibrotic remodelling in the liver. The process is complex, not fully understood in details; cells, cytokines, chemokines release, altered secretion of hepatokines, lipotoxicity, innate immun system, gut microbiom, metal ions and free radical reactions all have a role in it. Chronic liver disorders are often symptomless, diagnosed in the stage of fibrotic tissue accumulation, liver failure or hepatocellular carcinoma formation, when the prognosis is poor, treatment options are narrow. Noninvasive, properly sensitive and specific biomarkers are the targets of studies, with them the necessity of liver biopsies can be decreased, through the follow-up of processes, progression and treatment efficacy. Authors review the processes taking part in the progression of the most frequent chronic liver disorders, emphasizing the parameters of pro/antioxidant balance, and the necessity of a combined reliable biomarker. Orv Hetil. 2020; 161(35): 1441-1448.


Assuntos
Carcinoma Hepatocelular/patologia , Neoplasias Hepáticas/patologia , Progressão da Doença , Radicais Livres , Humanos
16.
Orv Hetil ; 161(35): 1449-1455, 2020 08.
Artigo em Húngaro | MEDLINE | ID: mdl-32822323

RESUMO

Autophagy plays an important role in the homeostasis of the cells and it may be upregulated in response to several types of stresses. Deregulation of autophagy is a key mechanism in the pathogenesis and progression of several liver diseases. Deficient autophagy can contribute to liver steatosis, to endoplasmic reticulum stress and to the progression of non-alcoholic fatty liver disease. Chronic alcohol consumption inhibits autophagy. The accumulated mutant protein in the endoplasmic reticulum can be degraded by autophagy in alpha-1-antitrypsin deficiency. Hepatitis C and B viruses may exploit the autophagy pathway to promote the own replication. Hepatitis C virus non-structural protein 5A and 5B have roles in the induction of autophagosomes. MicroRNAs regulate multiple physiological, pathological functions and autophagy through the modulation of gene expression. MicroRNA-122 is involved in HCV replication. In HBV-infected livers, the microRNA pathways related to cell death, DNA damage, recombination and signal transduction were activated. MicroRNA-122 effects multiple important factors which regulate the lipid and carbohydrate metabolisms in human non-alcoholic fatty liver disease. Oxidative stress and free oxygen radicals generation involved in alcoholic liver diseases development are regulated by microRNAs through different pathways. MicroRNAs control autophagy process and autophagy regulates the expression of microRNA-s. The exploration of their interactions contributes to understanding the development of liver diseases. Orv Hetil. 2020; 161(35): 1499-1455.


Assuntos
Autofagia , Carcinoma Hepatocelular/patologia , Hepacivirus/patogenicidade , Hepatite C Crônica/patologia , Hepatite C , Fígado/virologia , MicroRNAs/genética , Carcinoma Hepatocelular/virologia , Estresse do Retículo Endoplasmático , Hepacivirus/fisiologia , Hepatite C Crônica/virologia , Hepatite Viral Humana/fisiopatologia , Humanos , Fígado/patologia , Neoplasias Hepáticas/patologia , Neoplasias Hepáticas/virologia , Estresse Oxidativo
17.
Int J Nanomedicine ; 15: 5203-5215, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32801686

RESUMO

Introduction: Metformin is an ideal candidate to treat the liver tumor with insulin resistance because of its good performance in the treatment of type 2 diabetes and the advantage in cancer therapy. We aim to develop a delivery system with higher efficiency than free drug. Methods: Metformin-bovine serum albumin (met-BSA) nanoparticles (NPs) were prepared using the anti-solvent precipitation method with a stabilizer of BSA for particle growth. The therapeutic effect of the drug was tested by the insulin-resistant HepG2 cells and C57BL/6J mice at a glucose starvation condition. The interaction mechanism of the drug and the protein during the formation of the NPs was tested using a series of spectroscopy. Results: Metformin and BSA formed nonporous and spherical particles of about 200 nm with proper lognormal distribution and thermostability. The cellular uptake, as well as the anti-liver cancer activities of met-BSA, was enhanced dramatically compared with the free drug. The thermodynamic studies suggested that the weak binding of metformin to BSA was governed by hydrogen bonds and van der Waals forces. Moreover, the results of synchronous, circular dichroism (CD) and three-dimensional fluorescence demonstrated that the BSA skeleton and chromophore microenvironments were changed in the presence of metformin. Conclusion: Therefore, met-BSA has been proved as a simple yet effective therapeutic agent for cancer with insulin resistance, promising for future clinic translations in cancer treatment.


Assuntos
Sistemas de Liberação de Medicamentos/métodos , Resistência à Insulina , Metformina/farmacologia , Nanopartículas/administração & dosagem , Soroalbumina Bovina/farmacologia , Animais , Carcinoma Hepatocelular/tratamento farmacológico , Carcinoma Hepatocelular/patologia , Dicroísmo Circular , Diabetes Mellitus Tipo 2 , Células Hep G2 , Humanos , Ligação de Hidrogênio , Neoplasias Hepáticas/tratamento farmacológico , Neoplasias Hepáticas/patologia , Masculino , Metformina/administração & dosagem , Metformina/química , Camundongos Endogâmicos C57BL , Nanopartículas/química , Soroalbumina Bovina/química , Termodinâmica , Ensaios Antitumorais Modelo de Xenoenxerto
19.
PLoS One ; 15(8): e0238078, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32845895

RESUMO

BACKGROUNDS AND AIMS: Because of the known limitations of ultrasonography (US) alone, we re-evaluated whether complimentary testing for serum alpha-fetoprotein (AFP) is helpful in surveilling for hepatocellular carcinoma (HCC) in high-risk populations. METHODS: We included, from a hospital-based cancer registry, 1,776 asymptomatic adults who were surveilled biannually with the AFP test and US and eventually diagnosed with HCC between 2007 and 2015. Based on the screening results, these patients were divided into three groups: AFP (positive for AFP only; n = 298 [16.8%]), US (positive for US only; n = 978 [55.0%]), and AFP+US (positive for both; n = 500 [28.2%]). We compared the outcomes of the three groups, calculating the survival of the AFP group both as observed survival and as survival corrected for lead-time. RESULTS: In terms of tumor-related factors, the separate AFP and US groups were more likely to have early stage HCC and to receive curative treatments than the combined AFP+US group (Ps<0.05). The AFP group had significantly better overall and cancer-specific survival than the AFP+US group after adjusting for covariates (adjusted hazard ratios [HRs] 0.68 and 0.62, respectively). In analyses correcting for lead-time in the AFP group (doubling time 120 days), the respective adjusted HRs for the AFP group were unchanged (0.74 and 0.67), but they were no longer significant after additional adjustment for tumor stage and curative treatment (0.87 and 0.81). CONCLUSIONS: HCC cases detected by the AFP test without abnormal ultrasonic findings appear to have better survival, possibly as a result of stage migration and the resulting cures. Complementary AFP surveillance, together with US, could be helpful for at-risk patients.


Assuntos
Carcinoma Hepatocelular/patologia , Neoplasias Hepáticas/patologia , alfa-Fetoproteínas/análise , Antineoplásicos/uso terapêutico , Carcinoma Hepatocelular/tratamento farmacológico , Carcinoma Hepatocelular/mortalidade , Detecção Precoce de Câncer , Feminino , Hepatite B/patologia , Humanos , Cirrose Hepática/complicações , Cirrose Hepática/diagnóstico , Neoplasias Hepáticas/tratamento farmacológico , Neoplasias Hepáticas/mortalidade , Masculino , Pessoa de Meia-Idade , Estadiamento de Neoplasias , Razão de Chances , Modelos de Riscos Proporcionais , Sistema de Registros , Fatores de Risco , Taxa de Sobrevida , Ultrassonografia
20.
Nat Protoc ; 15(9): 2956-2979, 2020 09.
Artigo em Inglês | MEDLINE | ID: mdl-32737464

RESUMO

Bottom-up mass spectrometry-based proteomics relies on protein digestion and peptide purification. The application of such methods to broadly available clinical samples such as formalin-fixed and paraffin-embedded (FFPE) tissues requires reversal of chemical crosslinking and the removal of reagents that are incompatible with mass spectrometry. Here, we describe in detail a protocol that combines tissue disruption by ultrasonication, heat-induced antigen retrieval and two alternative methods for efficient detergent removal to enable quantitative proteomic analysis of limited amounts of FFPE material. To show the applicability of our approach, we used hepatocellular carcinoma (HCC) as a model system. By combining the described protocol with laser-capture microdissection, we were able to quantify the intra-tumor heterogeneity of a tumor specimen on the proteome level using a single slide with tissue of 10-µm thickness. We also demonstrate broader applicability to other tissues, including human gallbladder and heart. The procedure described in this protocol can be completed within 8 d.


Assuntos
Formaldeído , Espectrometria de Massas , Inclusão em Parafina , Proteômica/métodos , Fixação de Tecidos , Carcinoma Hepatocelular/patologia , Humanos , Neoplasias Hepáticas/patologia
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