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1.
Rev Med Suisse ; 16(704): 1554-1559, 2020 Sep 02.
Artigo em Francês | MEDLINE | ID: mdl-32880111

RESUMO

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


Assuntos
Adenoma de Células Hepáticas , Neoplasias Hepáticas , Adenoma de Células Hepáticas/diagnóstico , Adenoma de Células Hepáticas/genética , Adenoma de Células Hepáticas/patologia , Adenoma de Células Hepáticas/terapia , Feminino , Humanos , Neoplasias Hepáticas/diagnóstico , Neoplasias Hepáticas/genética , Neoplasias Hepáticas/patologia , Neoplasias Hepáticas/terapia , Imagem por Ressonância Magnética , Mutação
2.
Anticancer Res ; 40(9): 5059-5069, 2020 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-32878794

RESUMO

BACKGROUND/AIM: Liver cancer is the fourth leading cause of cancer-related mortality globally, of which hepatocellular carcinoma (HCC) accounts for 85-90% of total primary liver cancer. A drug shortage for HCC therapy triggered us to screen the small-molecule database with a high-throughput cellular screening system. Herein, we examined whether cetyltrimethylammonium bromide (CTAB) inhibits cellular mobility and invasiveness of Mahlavu HCC cells. MATERIALS AND METHODS: The effects of CTAB on cell viability were assessed using WST-1 assay, cell-cycle distribution using flow cytometric analysis, migration/invasion using woundhealing and transwell assays, and associated protein levels using western blotting. RESULTS: Treatment of Mahlavu cells with CTAB transformed its mesenchymal spindle-like morphology. In addition, CTAB exerted inhibitory effects on the migration and invasion of Mahlavu cells dose-dependently. CTAB also reduced the protein levels of matrix metalloproteinase-2 (MMP2), MMP9, RAC family small GTPase 1, SNAIL family transcriptional repressor 1 (SNAI1), SNAI2, TWIST family basic helix-loop-helix transcription factor 1 (TWIST1), vimentin, N-cadherin, phospho-fibroblast growth factor (FGF) receptor, phospho-phosphoinositide 3-kinase, phospho-v-Akt murine thymoma viral oncogene and phospho-signal transducer and activator of transcription 3 but increased the protein levels of tissue inhibitor of metalloproteinases-1/2 and E-cadherin. Rescue experiments proved that CTAB induced mesenchymal-epithelial transition in Mahlavu cells and this was significantly dose-dependently mitigated by basic FGF. CONCLUSION: CTAB suppressed the migration and invasion of Mahlavu cells through inhibition of the FGF signaling pathway. CTAB seems to be a potential agent for preventing metastasis of hepatic cancer.


Assuntos
Antineoplásicos/farmacologia , Cetrimônio/farmacologia , Fatores de Crescimento de Fibroblastos/metabolismo , Transdução de Sinais/efeitos dos fármacos , Animais , Biomarcadores , Ciclo Celular/efeitos dos fármacos , Linhagem Celular Tumoral , Movimento Celular/efeitos dos fármacos , Sobrevivência Celular/efeitos dos fármacos , Modelos Animais de Doenças , Humanos , Neoplasias Hepáticas/tratamento farmacológico , Neoplasias Hepáticas/metabolismo , Neoplasias Hepáticas/patologia , Camundongos , Ensaios Antitumorais Modelo de Xenoenxerto
3.
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
4.
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
5.
BMC Bioinformatics ; 21(1): 396, 2020 Sep 07.
Artigo em Inglês | MEDLINE | ID: mdl-32894041

RESUMO

BACKGROUND: MicroRNAs are a class of important small noncoding RNAs, which have been reported to be involved in the processes of tumorigenesis and development by targeting a few genes. Existing studies show that the imbalance between cell proliferation and apoptosis is closely related to the initiation and development of cancers. However, the impact of miRNAs on this imbalance has not been studied systematically. RESULTS: In this study, we first construct a cell fate miRNA-gene regulatory network. Then, we propose a systematical method for calculating the global impact of miRNAs on cell fate genes based on the shortest path. Results on breast cancer and liver cancer datasets show that most of the cell fate genes are perturbed by the differentially expressed miRNAs. Most of the top-identified miRNAs are verified in the Human MicroRNA Disease Database (HMDD) and are related to breast and liver cancers. Function analysis shows that the top 20 miRNAs regulate multiple cell fate related function modules and interact tightly based on their functional similarity. Furthermore, more than half of them can promote sensitivity or induce resistance to some anti-cancer drugs. Besides, survival analysis demonstrates that the top-ranked miRNAs are significantly related to the overall survival time in the breast and liver cancers group. CONCLUSION: In sum, this study can help to systematically study the important role of miRNAs on proliferation and apoptosis and thereby uncover the key miRNAs during the process of tumorigenesis. Furthermore, the results of this study will contribute to the development of clinical therapy based miRNAs for cancers.


Assuntos
Apoptose/genética , Proliferação de Células/genética , MicroRNAs/metabolismo , Biomarcadores/metabolismo , Neoplasias da Mama/genética , Neoplasias da Mama/mortalidade , Neoplasias da Mama/patologia , Bases de Dados Genéticas , Feminino , Redes Reguladoras de Genes , Humanos , Neoplasias Hepáticas/genética , Neoplasias Hepáticas/mortalidade , Neoplasias Hepáticas/patologia , MicroRNAs/genética , RNA Mensageiro/metabolismo , Análise de Sobrevida
6.
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
7.
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
8.
Anticancer Res ; 40(10): 5393-5397, 2020 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-32988858

RESUMO

BACKGROUND/AIM: We established a new patient-derived orthotopic xenograft (PDOX) model of gastric cancer liver metastasis and evaluated the efficacy of a novel combination chemotherapy, gemcitabine (GEM) plus 5-fluorouracil (5-FU), compared to a standard regimen of oxaliplatinum (L-OHP) plus 5-FU on the liver metastasis. MATERIALS AND METHODS: Patient-derived gastric cancer was established in nude mice from the patient' s surgical tumor specimen. A single tumor fragment was implanted in the liver of nude mice. The mice with tumors were treated by GEM plus 5-FU or L-OHP plus 5-FU. RESULTS: GEM plus 5-FU or L-OHP plus 5-FU significantly and similarly inhibited tumor growth on the liver compared to the untreated control (p=0.007, p=0.02, respectively). CONCLUSION: GEM plus 5-FU could be a novel future clinical alternative to L-OHP plus 5-FU in gastric cancer patients who cannot tolerate platinum drugs.


Assuntos
Desoxicitidina/análogos & derivados , Fluoruracila/farmacologia , Neoplasias Hepáticas/tratamento farmacológico , Neoplasias Gástricas/tratamento farmacológico , Animais , Protocolos de Quimioterapia Combinada Antineoplásica/farmacologia , Desoxicitidina/farmacologia , Modelos Animais de Doenças , Humanos , Neoplasias Hepáticas/patologia , Camundongos , Oxaliplatina/farmacologia , Estômago/efeitos dos fármacos , Estômago/patologia , Neoplasias Gástricas/patologia , Ensaios Antitumorais Modelo de Xenoenxerto
9.
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
10.
Z Gastroenterol ; 58(9): 847-854, 2020 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-32947630

RESUMO

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


Assuntos
Técnicas de Imagem por Elasticidade/métodos , Neoplasias Hepáticas/diagnóstico por imagem , Fígado/diagnóstico por imagem , Adulto , Idoso , Meios de Contraste , Diagnóstico Diferencial , Humanos , Fígado/patologia , Neoplasias Hepáticas/patologia , Masculino , Pessoa de Meia-Idade , Sensibilidade e Especificidade , Ultrassonografia , Viscosidade , Adulto Jovem
12.
Medicine (Baltimore) ; 99(36): e22077, 2020 Sep 04.
Artigo em Inglês | MEDLINE | ID: mdl-32899078

RESUMO

RATIONALE: Hepatic epithelioid hemangioendothelioma (HEH) is a rare vascular tumor of the liver with malignant potential. It can be of solitary type, multifocal type, or diffuse type. Although there are some characteristic features on radiologic imaging, the definitive diagnosis of HEH is based on histopathology. The surgical treatment of HEH includes liver resection and transplant. PATIENT CONCERNS: A middle-aged woman presented with easy fatiguability and anorexia for 1 month was found to have multifocal lesions on radiological imaging. DIAGNOSIS: HEH was diagnosed by needle biopsy. It can be seen from imaging that this case is a multifocal form. The largest lesion increased from 3 to 3.3 cm within 2 months, with an increase of 9.45%; no other relevant literatures have been reported. INTERVENTIONS: The possibility of liver transplantation was suggested to the patient. However, the patient refused transplantation and was successfully treated by radical right hepatectomy and resection of the left lobe lesion. OUTCOMES: She remained disease-free throughout a year follow-up period. CONCLUSION: HEH is a rare disease with characteristic radiological and pathological features. Although liver transplantation is the preferred treatment for multifocal HEH, surgical excision represents one alternative when the lesions can be guaranteed to be completely excised.


Assuntos
Hemangioendotelioma Epitelioide/patologia , Neoplasias Hepáticas/patologia , Feminino , Hemangioendotelioma Epitelioide/cirurgia , Hepatectomia , Humanos , Neoplasias Hepáticas/cirurgia , Pessoa de Meia-Idade
13.
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
14.
Medicine (Baltimore) ; 99(31): e21174, 2020 Jul 31.
Artigo em Inglês | MEDLINE | ID: mdl-32756095

RESUMO

Congenital hepatoblastoma (CHB) is the most common hepatic malignant tumor of fetus or neonates, but few studies focusing on the radiological characteristics of CHB have been reported to date.To investigate the characteristic clinical and computed tomography (CT) findings of CHB to facilitate recognition and noninvasive diagnosis.Medical records of 7 patients with CHB were retrospectively reviewed. The demographic, clinical, and laboratory data were extracted from the electronic medical records. Two pediatric radiologists evaluated the abdominal CT examinations for the hepatic tumor location, size, enhancement characteristics, vascular invasion, and intra-/extra-hepatic metastasis.Among the included 7 patients (3 males and 4 females), only 1 had an elevated serum alpha-fetoprotein level. All patients had solitary intrahepatic mass with a mean size of 4.7 cm (range: 2.9-10.2 cm), of which liver SV-VII were most involved. 4/7 tumors were round while 3/7 irregular or lobulated. 6/7 tumors were well-defined. Microhemorrhage, cystic necrosis, and coarse calcification were present in 5/7, 4/7, and 1/7 tumors, respectively. All lesions showed inhomogeneously significant enhancement, with multiple nodular or striped appearance in the center and periphery of the tumors on the arterial phase, and then the enhancement area showed progressive expansion and fusion filling over time but the attenuation gradually declined on the portal and delayed phases, and finally the majority (6/7) of tumors presented multiple band- or island-like characteristics with prominently peripheral enhancement on the delayed phase while the remaining 1 relatively small tumor showed nearly complete but inhomogenous enhancement. In addition, only 1/7 tumor had hilar hepatic bile duct and portal vein invasion and secondary intra-hepatic bile duct dilation. No metastatic lesions were identified in all patients at diagnosis. The abdominal aorta distal to the coeliac trunk was significantly narrowed in 3/7 patients. Pathological examinations suggested that 6/7 tumors showed fetal histology with only 1 containing mesenchymal elements.The relationship between serum alpha-fetoprotein and CHB could be more complicated and yet to be determined. Dynamic contrast-enhanced CT can facilitate recognition and noninvasive diagnosis of CHB, presenting a pattern of progressive expansion and fusion filling but inhomogeneously significant enhancement.


Assuntos
Hepatoblastoma/diagnóstico por imagem , Neoplasias Hepáticas/diagnóstico por imagem , Feminino , Hepatoblastoma/congênito , Hepatoblastoma/secundário , Humanos , Recém-Nascido , Neoplasias Hepáticas/congênito , Neoplasias Hepáticas/patologia , Masculino , Registros Médicos , Metástase Neoplásica , Estudos Retrospectivos , Tomografia Computadorizada por Raios X
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.
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
18.
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
19.
Medicine (Baltimore) ; 99(32): e21702, 2020 Aug 07.
Artigo em Inglês | MEDLINE | ID: mdl-32769939

RESUMO

Hepatocellular carcinoma (HCC) is a malignant tumor with unsatisfactory prognosis. The abnormal genes expression is significantly associated with initiation and poor prognosis of HCC. The aim of the present study was to identify molecular biomarkers related to the initiation and development of HCC via bioinformatics analysis, so as to provide a certain molecular mechanism for individualized treatment of hepatocellular carcinoma.Three datasets (GSE101685, GSE112790, and GSE121248) from the GEO database were used for the bioinformatics analysis. Differentially expressed genes (DEGs) of HCC and normal liver samples were obtained using GEO2R online tools. Gene ontology term and Kyoto Encyclopedia of Gene and Genome (KEGG) pathway analysis were conducted via the Database for Annotation, Visualization, and Integrated Discovery online bioinformatics tool. The protein-protein interaction (PPI) network was constructed by the Search Tool for the Retrieval of Interacting Genes database and hub genes were visualized by Cytoscape. Survival analysis and RNA sequencing expression were conducted by UALCAN and Gene Expression Profiling Interactive Analysis.A total of 115 shared DEGs were identified, including 30 upregulated genes and 85 downregulated genes in HCC samples. P53 signaling pathway and cell cycle were the major enriched pathways for the upregulated DEGs whereas metabolism-related pathways were the major enriched pathways for the downregulated DEGs. The PPI network was established with 105 nodes and 249 edges and 3 significant modules were identified via molecular complex detection. Additionally, 17 candidate genes from these 3 modules were significantly correlated with HCC patient survival and 15 of 17 genes exhibited high expression level in HCC samples. Moreover, 4 hub genes (CCNB1, CDK1, RRM2, BUB1B) were identified for further reanalysis of KEGG pathway, and enriched in 2 pathways, the P53 signaling pathway and cell cycle pathway.Overexpression of CCNB1, CDK1, RRM2, and BUB1B in HCC samples was correlated with poor survival in HCC patients, which could be potential therapeutic targets for HCC.


Assuntos
Biomarcadores Tumorais/análise , Carcinoma Hepatocelular/diagnóstico , Biologia Computacional/estatística & dados numéricos , Programas de Rastreamento/normas , Prognóstico , Carcinoma Hepatocelular/mortalidade , Carcinoma Hepatocelular/fisiopatologia , China/epidemiologia , Análise por Conglomerados , Expressão Gênica/genética , Humanos , Neoplasias Hepáticas/epidemiologia , Neoplasias Hepáticas/mortalidade , Neoplasias Hepáticas/patologia , Programas de Rastreamento/métodos , Mapas de Interação de Proteínas/genética , Análise de Sobrevida
20.
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
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