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1.
Medicine (Baltimore) ; 100(16): e25627, 2021 Apr 23.
Artigo em Inglês | MEDLINE | ID: mdl-33879737

RESUMO

ABSTRACT: The aim of the current study was to explore the value of tumor attenuation and quantitative analysis of perfusion parameters obtained from traditional tri-phasic CT scans in grading hepatocellular carcinoma (HCC).Totally 39 patients (42 lesion samples) with pathologically confirmed HCC who underwent tri-phasic CT scans were enrolled. HCC lesions were divided into non-poorly differentiated HCC (NP-HCC; n = 31) and poorly differentiated HCC (pHCC; n = 11). All lesions were divided into 5 groups according to the attenuation on different CT enhancement phase. The values of tumor attenuation on different scanning phases were measured. The following parameters were calculated: arterial enhancement fraction (AEF), portal venous supply coefficient (PVC), and hepatic arterial supply coefficient (HAC). The relationship of perfusion parameters with the histological grade of HCC was analyzed. Receiver operating characteristic curves were generated.No significant correlation was observed between the perfusion parameters and tumor grading. Only HAC showed a non-significant trend in different grades of HCC (pHCC < NP-HCC; P = .07). The pHCC cases had significantly decreased values of tumor attenuation on the unenhanced phase (TAu), tumor attenuation on the portal phase portal phase (TAp), and equilibrium phase (TAe) (P < .01). The difference of tumor attenuation between the portal phase and the unenhanced phase (TAp-TAu) of the pHCC cases was decreased than that of the NP-HCC cases (P < .01), whereas the difference of attenuation between the equilibrium phase and portal phase (TAe-TAp) was significantly higher in the pHCC cases than that in the NP-HCC cases (P < .01). TAe-TAp had the highest area under the curve. The number of tumor enhancement pattern in Group 5 of HCCs with a diameter of 3 cm or more was significantly more than that of HCCs with a diameter of less than 3 cm or with other different enhancement patterns (P < .01).Histological HCC grading cannot be predicted by the perfusion parameters derived from traditional tri-phasic CT scans, whereas the tumor attenuation on different phases and the tumor attenuation differences among different phases, especially the mean value of TAe-TAp, might be useful for non-invasive prediction on the degree of HCC differentiation.


Assuntos
Carcinoma Hepatocelular/irrigação sanguínea , Carcinoma Hepatocelular/diagnóstico por imagem , Neoplasias Hepáticas/irrigação sanguínea , Neoplasias Hepáticas/diagnóstico por imagem , Gradação de Tumores/métodos , Imagem de Perfusão/métodos , Tomografia Computadorizada por Raios X/métodos , Idoso , Idoso de 80 Anos ou mais , Carcinoma Hepatocelular/patologia , Feminino , Artéria Hepática/patologia , Humanos , Fígado/irrigação sanguínea , Fígado/patologia , Neoplasias Hepáticas/patologia , Masculino , Pessoa de Meia-Idade , Variações Dependentes do Observador , Perfusão , Veia Porta/patologia , Valor Preditivo dos Testes , Curva ROC , Estatísticas não Paramétricas
2.
Life Sci ; 273: 119184, 2021 May 15.
Artigo em Inglês | MEDLINE | ID: mdl-33577844

RESUMO

OBJECTIVE: It has been already accepted that hepatocellular carcinoma (HCC) cells-derived exosomes mediate HCC development partially through transferring microRNAs (miRNAs). Illuminated by that, this work pivoting on HCC specifically starts from miR-378b in HepG2 cells-derived exosomes, involving with transforming growth factor ß receptor III (TGFBR3). METHODS: HCC tissue and normal tissue specimens were resected, in which miR-378b and TGFBR3 expression were tested. The connection between miR-378b and TGFBR3 was assessed. HepG2 cells were transfected with miR-378b and TGFBR3-related sequences to explore their functions in HCC cell progression. The extracted exosomes from HepG2 cells were identified and co-cultured with human umbilical vein endothelial cells to explore their roles in HCC cell progression and angiogenesis. Tumorigenesis in mice was conducted for further validation of the findings in cells. RESULTS: Up-regulated miR-378b and down-regulated TGFBR3 presented in HCC, and miR-378b targeted TGFBR3. Depleted miR-378b disturbed HCC cell migration and promoted apoptosis. Knockdown of TGFBR3 reversed the effects of down-regulated miR-378b on HCC cells. HepG2 cells-derived exosomes promoted angiogenesis in vitro and tumor growth in vivVo, which would be further enhanced by miR-378b overexpression while impaired by miR-378b down-regulation. CONCLUSION: It is elucidated that HepG2 cells-derived exosomal miR-378b enhances HCC cell progression and angiogenesis, which may be linked with TGFBR3, providing therapeutic agents for HCC curing.


Assuntos
Biomarcadores Tumorais/genética , Carcinoma Hepatocelular/irrigação sanguínea , Exossomos/genética , Regulação Neoplásica da Expressão Gênica , Neoplasias Hepáticas/irrigação sanguínea , MicroRNAs/genética , Neovascularização Patológica/patologia , Adulto , Idoso , Animais , Apoptose , Carcinoma Hepatocelular/genética , Carcinoma Hepatocelular/patologia , Proliferação de Células , Feminino , Humanos , Neoplasias Hepáticas/genética , Neoplasias Hepáticas/patologia , Masculino , Camundongos , Camundongos Nus , Pessoa de Meia-Idade , Prognóstico , Células Tumorais Cultivadas , Ensaios Antitumorais Modelo de Xenoenxerto
3.
Mol Carcinog ; 60(2): 151-163, 2021 02.
Artigo em Inglês | MEDLINE | ID: mdl-33428809

RESUMO

Regorafenib is approved for patients with unresectable hepatocellular carcinoma (HCC) following sorafenib. However, the effect of regorafenib on HCC metastasis and its mechanism are poorly understood. Here, our data showed that regorafenib significantly restrained the migration, invasion and vasculogenic mimicry (VM) of HCC cells, and downregulated the expression of epithelial-to-mesenchymal transition (EMT)/VM-related molecules. Using RNA-seq and cellular thermal shift assays, we found that inhibitor of differentiation 1 (ID1) was a key target of regorafenib. In HCC tissues, the protein expression of ID1 was positively correlated with EMT and VM formation (CD34- /PAS+ ). Functionally, ID1 knockdown inhibited HCC cell migration, invasion, metastasis, and VM formation in vitro and in vivo, with upregulation of E-cadherin and downregulation of Snail and VE-cadherin. Moreover, Snail overexpression promoted the migration, invasion, and VM formation of ID1 knockdown cells. Snail knockdown reduced the migration, invasion, and VM formation of ID1 overexpression cells. Finally, regorafenib suppressed VM formation and decreased the expression of ID1, VE-cadherin and Snail in HCC PDX model. In conclusion, we manifested that regorafenib distinctly inhibited EMT in HCC cells via targeting ID1, leading to the suppression of cell migration, invasion and VM formation. These findings suggest that regorafenib may be developed as a suitable therapeutic agent for HCC metastasis.


Assuntos
Carcinoma Hepatocelular/prevenção & controle , Movimento Celular/efeitos dos fármacos , Transição Epitelial-Mesenquimal/efeitos dos fármacos , Proteína 1 Inibidora de Diferenciação/antagonistas & inibidores , Neoplasias Hepáticas/prevenção & controle , Neovascularização Patológica/prevenção & controle , Compostos de Fenilureia/farmacologia , Piridinas/farmacologia , Ensaios Antitumorais Modelo de Xenoenxerto/métodos , Animais , Carcinoma Hepatocelular/irrigação sanguínea , Carcinoma Hepatocelular/genética , Linhagem Celular Tumoral , Movimento Celular/genética , Transição Epitelial-Mesenquimal/genética , Regulação Neoplásica da Expressão Gênica/efeitos dos fármacos , Células Hep G2 , Humanos , Proteína 1 Inibidora de Diferenciação/genética , Proteína 1 Inibidora de Diferenciação/metabolismo , Neoplasias Hepáticas/irrigação sanguínea , Neoplasias Hepáticas/genética , Masculino , Camundongos Endogâmicos BALB C , Camundongos Nus , Invasividade Neoplásica , Neovascularização Patológica/genética , Carga Tumoral/efeitos dos fármacos , Carga Tumoral/genética
4.
J Vasc Interv Radiol ; 32(2): 204-210, 2021 02.
Artigo em Inglês | MEDLINE | ID: mdl-33358329

RESUMO

PURPOSE: This pilot study aims to evaluate the effect of hepatic intraarterial norepinephrine injection in vasculature modulation for hepatocellular carcinoma (HCC) tumors. MATERIALS AND METHODS: This is a single-center prospective study of patients with HCC with proven single-lobe tumors > 3 cm. Eight patients were included, with a mean age of 63 y ± 8. All patients had Barcelona Clinic Liver Cancer stage B HCC and an Eastern Cooperative Oncology Group performance status of 0. Mean tumor size was 6.1 cm ± 1.8; all tumors were hypervascular. Patients underwent CT hepatic perfusion before and after injection of 24 µg of norepinephrine intraarterially (4 µg/mL; total 6 mL injected at a rate of 1 mL/s). Color-coded perfusion maps were used to assess the effects of local therapy on hepatic perfusion values. Tumor-to-liver ratio (TLR) was calculated from the ratio of tumor perfusion to background liver perfusion value. RESULTS: Seven of 8 patents had significant (P = .04) absolute increase in tumor perfusion vs background liver, varying from incremental (-2 mL/min/100 mL) to 290 mL/min/100 mL. There was a nonsignificant increase in TLR from 2.7 ± 1.3 to 2.9 ± 1.4 after norepinephrine injection (P = .8). Mean peak time to maximal increase in tumor perfusion after injection was 6.1 s (range, 4.5-9.1 s). Norepinephrine injection was well tolerated without major adverse events. CONCLUSIONS: Norepinephrine causes increased blood flow toward HCC tumors, but with a corresponding smaller increase in blood flow to noncancerous liver tissue, with no observed systemic side effects.


Assuntos
Carcinoma Hepatocelular/irrigação sanguínea , Carcinoma Hepatocelular/diagnóstico por imagem , Artéria Hepática/efeitos dos fármacos , Artéria Hepática/diagnóstico por imagem , Neoplasias Hepáticas/irrigação sanguínea , Neoplasias Hepáticas/diagnóstico por imagem , Tomografia Computadorizada Multidetectores , Norepinefrina/administração & dosagem , Imagem de Perfusão , Vasoconstritores/administração & dosagem , Idoso , Carcinoma Hepatocelular/terapia , Feminino , Artéria Hepática/fisiopatologia , Humanos , Injeções Intra-Arteriais , Neoplasias Hepáticas/terapia , Masculino , Pessoa de Meia-Idade , Projetos Piloto , Valor Preditivo dos Testes , Estudos Prospectivos , Fluxo Sanguíneo Regional
5.
Microvasc Res ; 133: 104094, 2021 01.
Artigo em Inglês | MEDLINE | ID: mdl-33011171

RESUMO

BACKGROUND: Hepatocellular carcinoma (HCC) is one of the most vascularized tumor types, and is characterized by development of heterogeneous immature vessels with increased permeability. Here, we analyzed morphology and vascular permeability-related structures in endothelial cells of HCC microvessels. METHODS: Small (Type I) and large (Type II) peritumoral blood microvessels were assessed in HCC-bearing mice. By transmission electron microscopy, endothelial cell cytoplasm area, free transport vesicles, vesiculo-vacuolar organelles and clathrin-coated vesicles were measured. RESULTS: The phenotypic changes in the HCC microvessels included presence of sinusoidal capillarization, numerous luminal microprocesses and abnormal luminal channels, irregular dilatations of interendothelial junctions, local detachment of basement membranes and widened extracellular space. Endothelial cells Type I microvessels showed increased vesicular trafficking-related structures. CONCLUSION: Ultrastructural characteristics of microvessels Type I can associate with HCC new-formed microvessels. The morphological changes observed in HCC microvessels might explain the increased transcellular and paracellular permeability in HCC endothelial cells.


Assuntos
Carcinoma Hepatocelular/irrigação sanguínea , Células Endoteliais/ultraestrutura , Neoplasias Hepáticas/irrigação sanguínea , Microvasos/ultraestrutura , Vesículas Transportadoras/ultraestrutura , Animais , Transporte Biológico , Permeabilidade Capilar , Linhagem Celular Tumoral , Células Endoteliais/metabolismo , Masculino , Camundongos Endogâmicos CBA , Microscopia Eletrônica de Transmissão , Microvasos/metabolismo , Vesículas Transportadoras/metabolismo
6.
Anticancer Res ; 40(7): 3953-3960, 2020 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-32620637

RESUMO

BACKGROUND/AIM: To examine the factors influencing the introduction of the second-line chemotherapy and discuss the selection of first-line agent for hepatocellular carcinoma (HCC). PATIENTS AND METHODS: We retrospectively studied 154 patients with HCC who received sorafenib therapy. RESULTS: A total of 109 (70.8%) patients, maintained Child-Pugh grade A and Eastern Cooperative Oncology Group performance status (ECOG-PS) ≤1 upon sorafenib discontinuation. Multivariate analysis revealed that the up-to-seven criteria status in the hepatic lesion [p=0.019; odds ratio=OR, 2.685], albumin-bilirubin (ALBI) grade (p=0.002; OR=3.589), and macroscopic vascular invasion (MVI) (p=0.008; OR=2.972) were significant factors at sorafenib initiation that influenced the maintenance of Child-Pugh grade A and ECOG-PS ≤1 upon therapy discontinuation. CONCLUSION: Not only ALBI grade and MVI, but also up-to-seven criteria status in the hepatic lesion influence the introduction of second-line therapy, and could affect the selection of the first-line therapy.


Assuntos
Carcinoma Hepatocelular/tratamento farmacológico , Neoplasias Hepáticas/tratamento farmacológico , Sorafenibe/uso terapêutico , Adulto , Idoso , Idoso de 80 Anos ou mais , Antineoplásicos/uso terapêutico , Carcinoma Hepatocelular/irrigação sanguínea , Carcinoma Hepatocelular/patologia , Feminino , Humanos , Neoplasias Hepáticas/irrigação sanguínea , Neoplasias Hepáticas/patologia , Masculino , Pessoa de Meia-Idade , Gradação de Tumores , Estudos Retrospectivos , Índice de Gravidade de Doença , Resultado do Tratamento , Carga Tumoral
7.
Oncol Rep ; 44(4): 1727-1735, 2020 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-32700752

RESUMO

Hepatocellular carcinoma (HCC) is a common hypervascular tumor disease. Endothelial cells, as a crucial component of the tumor microenvironment, have been reported to participate in angiogenesis and influence the development of tumors, including HCC. Recent studies have demonstrated that circulating RNAs (circRNAs) participate in the functional regulation of endothelial cells. However, the expression and function of circRNAs in endothelial cells under the HCC microenvironment is still unclear. In the present study, we analyzed the expression profiles and investigated the role of circRNAs in human umbilical vein endothelial cells (HUVECs) co­cultured with human primary hepatoma cells. Based on an RNA­sequencing assay, we screened 19 significantly downregulated circRNAs in HUVECs under an HCC microenvironment. Subsequently, we validated the expression of the candidate circRNAs using RT­qPCR, and selected two of the most downregulated circRNAs among them, circ_4911 and circ_4302. Next, through circRNA overexpression experiments, we demonstrated that overexpression of circ_4911 and circ_4302 both inhibited the proliferation and migration of HUVECs, and arrested cells at the GO/G1 stage, while promoting adhesion. Overall, in the present study, we identified the roles of circ_4911 and circ_4302 in regulating functions of HUVECs under an HCC microenvironment.


Assuntos
Carcinoma Hepatocelular/genética , Ácidos Nucleicos Livres/genética , Endotélio Vascular/patologia , Neoplasias Hepáticas/genética , Carcinoma Hepatocelular/sangue , Carcinoma Hepatocelular/irrigação sanguínea , Carcinoma Hepatocelular/patologia , Ciclo Celular/fisiologia , Proliferação de Células/fisiologia , Ácidos Nucleicos Livres/sangue , Técnicas de Cocultura , Endotélio Vascular/metabolismo , Feminino , Sequenciamento de Nucleotídeos em Larga Escala , Células Endoteliais da Veia Umbilical Humana , Humanos , Neoplasias Hepáticas/sangue , Neoplasias Hepáticas/irrigação sanguínea , Neoplasias Hepáticas/patologia , Masculino , Pessoa de Meia-Idade , Análise de Sequência de RNA , Células Tumorais Cultivadas , Microambiente Tumoral
8.
Medicine (Baltimore) ; 99(26): e20795, 2020 Jun 26.
Artigo em Inglês | MEDLINE | ID: mdl-32590762

RESUMO

To explore different posttreatment changes between multimode tumor ablation therapy (MTAT) and radiofrequency ablation (RFA) using intravoxel incoherent motion diffusion-weighted imaging (IVIM-DWI) and diffusion kurtosis imaging (DKI) in patients with hepatic malignancies.Eighty - seven patients with one hundred and twenty eight hepatic lesions receiving MTAT or RFA underwent IVIM-DWI and DKI before and after treatment. The mean value of apparent diffusion coefficient (ADC), IVIM-DWI parameters, including true diffusion coefficient (D), pseudo-diffusion coefficient (DP), perfusion fraction (f), and DKI parameters including diffusion coefficient (DK), apparent diffusional kurtosis (K) were retrospectively compared prior to and following treatment as well as between treatment groups. The degree of parameters change after ablation was compared between 2 treatment modalities.The mean value of ADC, D, and DK increased while f, and K decreased significantly in MTAT group. In RFA group, just ADC and K showed significantly change following treatment. The ADC and D value were higher in MTAT group than in RFA group 1 month after treatment. While f was lower in MTAT group after treatment compared with RFA group. The ADC, D and DK increased (21.89 ±â€Š24.95% versus 8.76 ±â€Š19.72%, P = .04 for ADC, 33.78 ±â€Š54.01% versus 7.91 ±â€Š25.16%, P = .03 for D, 25.91 ±â€Š36.28% versus 1.75 ±â€Š46.42%, P = .01 for DK) while f declined (-32.62 ±â€Š41.48% versus 6.51 ±â€Š44.16%, P < .001) more in MTAT group.The MTAT induced different posttreatment changes on water molecule diffusion and microvasculature related functional MR parameters compared to RFA in patients with liver tumors.


Assuntos
Ablação por Cateter , Imagem de Difusão por Ressonância Magnética/métodos , Neoplasias Hepáticas , Imagem por Ressonância Magnética/métodos , Microvasos/diagnóstico por imagem , Ablação por Cateter/efeitos adversos , Ablação por Cateter/métodos , Feminino , Humanos , Neoplasias Hepáticas/irrigação sanguínea , Neoplasias Hepáticas/diagnóstico por imagem , Neoplasias Hepáticas/patologia , Masculino , Pessoa de Meia-Idade , Avaliação de Resultados em Cuidados de Saúde , Ablação por Radiofrequência/métodos
9.
Radiol Med ; 125(10): 971-980, 2020 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-32270335

RESUMO

PURPOSE: Quantification of post-interventional adverse events of outpatient SIRT leading to hospitalization and quantification of radiation exposure. MATERIALS AND METHODS: In this single-center, retrospective cohort study, we reviewed 212 patients treated with SIRT (90Y-microspheres) for primary and secondary liver malignancies. We searched for adverse events (AEs) and serious adverse events (SAEs), defined as AE's causing hospitalization. Additionally, radiation exposure was measured in 36 patients. RESULTS: Seven patients had an SAE (3.3%), four patients had AE without readmission/hospitalization (1.9%) and 201 patients had no complications (94.8%). The mean ambient dose rate at 1 m distance from the source after administration of 90Y-microspheres was 1.88 µSv/h ± 0.74 (± SD) with a range from 4.3 to 0.2 µSv/h. CONCLUSION: Outpatient radioembolization with 90Y-microspheres is safe and requires hospitalization only in a very small number of patients. The mean dose rate was low and met the national conditions for outpatient treatment (< 5 µSv/h).


Assuntos
Assistência Ambulatorial , Embolização Terapêutica/métodos , Hospitalização , Neoplasias Hepáticas/terapia , Microesferas , Radioisótopos de Ítrio/administração & dosagem , Angiografia , Embolização Terapêutica/efeitos adversos , Feminino , Hospitalização/estatística & dados numéricos , Humanos , Neoplasias Hepáticas/irrigação sanguínea , Neoplasias Hepáticas/secundário , Masculino , Pessoa de Meia-Idade , Pacientes Ambulatoriais , Exposição à Radiação/análise , Pneumonite por Radiação/prevenção & controle , Estudos Retrospectivos , Tomografia Computadorizada com Tomografia Computadorizada de Emissão de Fóton Único , Radioisótopos de Ítrio/efeitos adversos
10.
Cochrane Database Syst Rev ; 3: CD009498, 2020 03 12.
Artigo em Inglês | MEDLINE | ID: mdl-32163181

RESUMO

BACKGROUND: The liver is affected by two of the most common groups of malignant tumours: primary liver tumours and liver metastases from colorectal carcinoma or other extrahepatic primary cancers. Liver metastases are significantly more common than primary liver cancer, and long-term survival rate after radical surgical treatment is approximately 50%. However, R0 resection (resection for cure) is not feasible in the majority of people; therefore, other treatments have to be considered. One possible option is based on the concept that the blood supply to hepatic tumours originates predominantly from the hepatic artery. Transarterial chemoembolisation (TACE) of the hepatic artery can be achieved by administering a chemotherapeutic drug followed by vascular occlusive agents, and can lead to selective necrosis of the liver tumour while it may leave normal parenchyma virtually unaffected. This can also be performed without chemotherapy, which is called bland transarterial embolisation (TAE). OBJECTIVES: To assess the beneficial and harmful effects of TAE or TACE compared with no intervention or placebo in people with liver metastases. SEARCH METHODS: We searched the Cochrane Hepato-Biliary Group Controlled Trials Register, CENTRAL, MEDLINE, Embase, and four more databases (December 2019). We also searched two trials registers and the US Food and Drug Administration database (September 2019). SELECTION CRITERIA: Randomised clinical trials assessing beneficial and harmful effects of TAE or TACE compared with no intervention or placebo for liver metastases. DATA COLLECTION AND ANALYSIS: We followed standard Cochrane methodological procedures. We extracted information on participant characteristics, interventions, study outcomes, study design, and trial methods. Two review authors independently extracted data and assessed risk of bias. We assessed the certainty of evidence with GRADE. We resolved disagreements by discussion. MAIN RESULTS: We included one randomised clinical trial with 61 participants (43 male and 18 female) with colorectal cancer with liver metastases: 22 received transarterial embolisation (TAE; hepatic artery embolisation), 19 received transarterial chemoembolisation (TACE; 5-fluorouracil hepatic artery infusion chemotherapy with degradable microspheres), and 20 received 'no active therapeutic intervention' as a control. Most tumours were synchronous, unresectable metastases involving up to 75% of the liver. Participants were followed for a minimum of seven months. The trial was at high risk of bias. Very-low-certainty evidence found inconclusive results for mortality at 44 months between the TAE and TACE versus no intervention groups (risk ratio (RR) 0.88, 95% confidence interval (CI) 0.74 to 1.06; 61 participants). Local recurrence was reported in 10 participants without any details about the group allocation. Very-low-certainty evidence found little or no difference in mortality between the TAE and no intervention groups (RR 0.91, 95% CI 0.75 to 1.10; 42 participants). Median survival was 7 months from trial entry (range 2 to 44 months) in the TAE group and 7.9 months (range 1 to 26 months) in the control group, and 8.7 months after diagnosis (range 2 to 49 months) in the TAE group and 9.6 months (range 1 to 27 months) in the control group. The trial authors reported the differences were not statistically significant. There were no reported side effects in the control group. In the TAE group, 18 participants experienced short-term symptoms of 'post-embolisation syndrome', which were relieved with symptomatic treatment; one participant also had a local puncture site haematoma. Very-low-certainty evidence found little or no difference in mortality between the TACE and no intervention groups (RR 0.83, 95% CI 0.65 to 1.07; 39 participants). Median survival in the TACE group was 10.7 months (range 3 to 38 months) from trial entry, and 13.0 months (range 3 to 38 months) after diagnosis. The trial authors reported that differences between groups were not statistically significant. All participants experienced short-term nausea, with or without vomiting, immediately after treatment; one participant developed a wound infection, and one developed deep vein thrombosis. The trial did not measure failure to clear liver metastases, time to progression of liver metastases, tumour response measures, or health-related quality of life. Cancer Research Campaign, a non-profit organisation, provided a grant for the trial; Pharmacia Ltd. delivered the Port-a-Cath arterial delivery systems and degradable starch microspheres. We identified one ongoing trial comparing TACE plus chemotherapy versus chemotherapy alone in people with unresectable colorectal liver metastases who failed with first-line chemotherapy (NCT03783559). AUTHORS' CONCLUSIONS: Based on one, small randomised trial at high risk of bias, the evidence is very uncertain about the effect of TAE or TACE versus no active therapeutic intervention on mortality for people with liver metastases as the true effect may be substantially different. The trial did not measure failure to clear liver metastases, time to progression of liver metastases, tumour response measures, or health-related quality of life. Short-term, minor adverse events were recorded in the intervention groups only. Large trials, following current standards of conduct and reporting, are required to explore the benefits and harms of TAE or TACE compared with no intervention or placebo in people with resectable and unresectable liver metastasis.


Assuntos
Neoplasias Colorretais , Embolização Terapêutica/métodos , Artéria Hepática , Neoplasias Hepáticas/secundário , Neoplasias Hepáticas/terapia , Antimetabólitos Antineoplásicos/administração & dosagem , Quimioembolização Terapêutica/métodos , Quimioembolização Terapêutica/mortalidade , Embolização Terapêutica/mortalidade , Feminino , Fluoruracila/administração & dosagem , Humanos , Infusões Intra-Arteriais/métodos , Neoplasias Hepáticas/irrigação sanguínea , Masculino , Microesferas , Ensaios Clínicos Controlados Aleatórios como Assunto
11.
J Surg Oncol ; 122(1): 70-77, 2020 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-32215927

RESUMO

The preferential blood supply from the hepatic artery to liver tumors allows for the regional delivery of chemotherapy, commonly referred to as hepatic artery infusion chemotherapy via a subcutaneous pump. Hepatic artery infusion chemotherapy has been demonstrated to improve overall survival in select patients with colorectal liver metastasis and is a promising treatment for unresectable intrahepatic cholangiocarcinoma. This review focuses on the technical aspects of hepatic artery infusion pump placement.


Assuntos
Antineoplásicos/administração & dosagem , Quimioterapia do Câncer por Perfusão Regional/instrumentação , Artéria Hepática , Bombas de Infusão Implantáveis , Neoplasias Hepáticas/irrigação sanguínea , Neoplasias Hepáticas/tratamento farmacológico , Quimioterapia do Câncer por Perfusão Regional/métodos , Neoplasias Colorretais/tratamento farmacológico , Neoplasias Colorretais/patologia , Humanos , Infusões Intra-Arteriais , Curva de Aprendizado , Neoplasias Hepáticas/diagnóstico por imagem , Neoplasias Hepáticas/secundário , Ensaios Clínicos Controlados Aleatórios como Assunto
12.
PLoS One ; 15(2): e0227475, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32074102

RESUMO

Conventional transarterial chemoembolization (cTACE), drug-eluting beads (DEB-TACE) and transarterial radioembolization (TARE) are alternative strategies for unresectable hepatocellular carcinoma (HCC). However, which of these strategies is the best is still controversial. This meta-analysis was performed to evaluate the effects of DEB-TACE, TARE and cTACE in terms of overall survival (OS), tumor response and complications. A literature search was conducted using the EMBASE, PubMed, Google Scholar, and Cochrane databases from inception until July 2019 with no language restrictions. The primary outcome was overall survival, and the secondary outcomes included complete response and local recurrence. The comparison of DEB-TACE with cTACE indicated that DEB-TACE has a better OS at 1 year (RR 0.79, 95% CI 0.67-0.93, p = 0.006), 2 years (RR 0.89; 95% CI 0.81-0.99, p = 0.046), and 3 years (RR 0.89; 95% CI 0.81-0.99, p = 0.035). The comparison of TARE with cTACE indicated that TARE has a better OS than cTACE at 2 years (RR 0.87; 95% CI 0.80-0.95, p = 0.003) and 3 years (RR 0.90; 95% CI 0.85-0.96, p = 0.001). The comparison of DEB-TACE with TARE indicated that DEB-TACE has a better OS than TARE at 2 years (RR 0.40; 95% CI 0.19-0.84, p = 0.016). The current meta-analysis suggests that DEB-TACE is superior to both TARE and cTACE in terms of OS. TARE has significantly lower complications than both DEB-TACE and cTACE for patients with HCC. Further multicenter, well-designed randomized controlled trials are needed, especially for evaluating DEB-TACE versus TARE.


Assuntos
Carcinoma Hepatocelular/irrigação sanguínea , Artéria Hepática/patologia , Neoplasias Hepáticas/irrigação sanguínea , Carcinoma Hepatocelular/patologia , Quimioembolização Terapêutica/efeitos adversos , Intervalo Livre de Doença , Humanos , Neoplasias Hepáticas/patologia , Modelos de Riscos Proporcionais , Viés de Publicação , Análise de Sobrevida
13.
Sci Rep ; 10(1): 2964, 2020 02 19.
Artigo em Inglês | MEDLINE | ID: mdl-32076049

RESUMO

Transcatheter arterial embolization (TAE) plays an important role in clinical liver tumor therapy. However, hypoxia after TAE limit the medium-long term efficacy of TAE. Thus, in our study, we explored the treatment effect and mechanism of combining transcatheter arterial embolization with adopted iodized oil containing Apatinib on suppressing tumor growth and metastasis. We simulated the changing of tumor microenvironment before and after TAE both in vitro and in vivo models. The anti-angiogenic effect of Apatinib was explored by bioassays in human umbilical vein endothelial cells (HUVECs), including cell migration, invasion and apoptosis, tube formation, and wound healing. Further experiments showed that Apatinib inhibited tumor microangiogenesis to achieve the aims of inhibiting tumor growth and recurrence by means of down-regulating the phosphorylation of the RAF-mek-erk, PI3K-akt and P38MAPK pathways. The antitumor growth and anti-angiogenic effect of Apatinib was further validated by the animal experiment. Taken together, we concluded that Apatinib inhibits the angiogenesis and growth of liver cancer by down-regulating the PI3K-akt, RAF-mek-erk and P38MAPK pathways, and has a stronger inhibitory effect in hypoxic environments. Combining TAE with adopted iodized oil containing Apatinib has a stronger inhibitory effect in VX2 liver tumor growth and metastasis, which suggesting such combinations may provide a new target and strategy for interventional therapy of liver cancer.


Assuntos
Antineoplásicos/administração & dosagem , Carcinoma Hepatocelular/terapia , Quimioembolização Terapêutica/métodos , Neoplasias Hepáticas/terapia , Piridinas/administração & dosagem , Animais , Apoptose/efeitos dos fármacos , Carcinoma Hepatocelular/irrigação sanguínea , Carcinoma Hepatocelular/genética , Movimento Celular/efeitos dos fármacos , Proliferação de Células/efeitos dos fármacos , Regulação Neoplásica da Expressão Gênica/efeitos dos fármacos , Células Hep G2 , Células Endoteliais da Veia Umbilical Humana , Humanos , Óleo Iodado/administração & dosagem , Neoplasias Hepáticas/irrigação sanguínea , Neoplasias Hepáticas/genética , Sistema de Sinalização das MAP Quinases/efeitos dos fármacos , Camundongos , Neovascularização Patológica/terapia , Fosforilação/efeitos dos fármacos , Microambiente Tumoral/efeitos dos fármacos , Ensaios Antitumorais Modelo de Xenoenxerto
15.
FASEB J ; 34(1): 66-81, 2020 01.
Artigo em Inglês | MEDLINE | ID: mdl-31914639

RESUMO

Angiogenesis is critical for the development, progression, and metastasis of hepatocellular carcinoma (HCC), but the roles of miR-3064-5p in HCC angiogenesis are still unknown. In this study, the roles of miR-3064-5p in HCC angiogenesis were studied in 192 HCC patients, xenograft mouse models, and HCC cell lines. The results showed that miR-3064-5p expression was significantly decreased in HCC tissues and cells, and downregulated miR-3064-5p was associated with upregulated angiogenic potential of HCC. MiR-3064-5p inhibited proangiogenic VEGFA and angiogenin expressions but induced antiangiogenic endostatin and MMP12 expressions, finally leading to suppression of HCC angiogenesis, as shown by the decline in intratumoral microvessel density (MVD). Moreover, miR-3064-5p was inversely correlated with lncRNA MALAT1 and FOXA1. FOXA1 bound to and interacted with CD24 and then regulated Src phosphorylation. MiR-3064-5p played an antiangiogenic role by inhibiting the FOXA1/CD24/Src pathway, whereas oncogenic MALAT1 functioned as a competing endogenous RNA (ceRNA) by sponging miR-3064-5p to alleviate the suppressive effect on the FOXA1 pathway. HCC patients with high miR-3064-5p, low MALAT1, or low FOXA1 expression had a better prognosis with longer overall survival and recurrence-free survival. In univariate and multivariate analyses, miR-3064-5p was identified as the independent prognostic predicator for HCC progression and patient survival. Taken together, miR-3064-5p exerts an antiangiogenic role by targeting the FOXA1/CD24/Src pathway but oncogenic lncRNA MALAT1 acts as a ceRNA to sponge miR-3064-5p. MiR-3064-5p is of great clinical significance and is a novel prognostic indicator and an attractive therapeutic target for HCC.


Assuntos
Carcinoma Hepatocelular/irrigação sanguínea , Fator 3-alfa Nuclear de Hepatócito/metabolismo , Neoplasias Hepáticas/irrigação sanguínea , MicroRNAs/metabolismo , Neovascularização Patológica/metabolismo , RNA Longo não Codificante/metabolismo , Animais , Antígeno CD24/genética , Antígeno CD24/metabolismo , Carcinoma Hepatocelular/patologia , Linhagem Celular Tumoral , Proliferação de Células , Feminino , Fator 3-alfa Nuclear de Hepatócito/genética , Humanos , Neoplasias Hepáticas/patologia , Camundongos , MicroRNAs/genética , Neoplasias Experimentais , RNA Longo não Codificante/genética , Quinases da Família src/genética , Quinases da Família src/metabolismo
16.
Int J Radiat Biol ; 96(6): 759-766, 2020 06.
Artigo em Inglês | MEDLINE | ID: mdl-31977276

RESUMO

Purpose: Hepatocellular carcinoma (HCC) involving the inferior vena cava (IVC) and/or right atrium (RA) can affect systemic circulation, causing fatal complications. Standard treatment is yet to be established due to its rarity and intractability. We sought to determine the clinical efficacy of external beam radiotherapy (EBRT) in HCC treatment.Patients and methods: Our group designed this multicenter trial and recruited patients with HCC and IVC and/or RA involvement. Forty-nine patients from six institutions received EBRT with median dose of 46.7 (range: 35.4-71.5) Gy during 2009-2016. The primary outcome was overall survival (OS), and relevant predictors were evaluated.Results: Median follow-up length was 9.3 (range: 1.1-119) months. Median survival, 1-, and 2- year OS rates were 10.1 months (95% confidence interval [CI]: 7.5-12.7 months), 43.5%, and 30.1%, respectively. Significant factors affecting OS were alpha-fetoprotein level ≥300 ng/mL (risk ratio [RR]: 2.34, p = .025), tumor multiplicity (RR: 2.56, p = .028), and patient volume of institutions (high- vs. middle volume centers) (RR: 3.58, p = .001). Local control rates were 88.7% and 74.5% at 1 and 2 years, respectively. The most common first failure site was the lung (21/49, 42.9%) followed by liver outside the EBRT field (17/49, 34.7%). One case of possible radiation-induced liver disease was noted, with transient alkaline phosphatase elevation.Conclusion: EBRT can yield favorable local control in HCC with IVC and/or RA involvement. Systemic treatment may be more indicated as factors reflecting tumor aggressiveness were significant, and first distant failure is common.


Assuntos
Carcinoma Hepatocelular/irrigação sanguínea , Carcinoma Hepatocelular/radioterapia , Átrios do Coração/efeitos da radiação , Neoplasias Hepáticas/irrigação sanguínea , Neoplasias Hepáticas/radioterapia , Veia Cava Inferior/efeitos da radiação , Intervalo Livre de Doença , Estudos de Viabilidade , Feminino , Átrios do Coração/patologia , Humanos , Estimativa de Kaplan-Meier , Masculino , Pessoa de Meia-Idade , República da Coreia , Veia Cava Inferior/patologia
17.
J Clin Ultrasound ; 48(4): 231-234, 2020 May.
Artigo em Inglês | MEDLINE | ID: mdl-31721219

RESUMO

Hepatic hemangioma is the most common hepatic tumor with a prevalence of approximately 3%. It is typically supplied by the hepatic artery as evident from findings of abdominal angiography, contrast-enhanced ultrasonography (CEUS), contrast-enhanced computed tomography (CT), and contrast-enhanced magnetic resonance imaging. However, few cases of hepatic hemangioma supplied by the portal vein have been reported. In this paper, we report a rare case of hepatic hemangioma supplied by the portal vein as shown on CEUS and CT arterioportography.


Assuntos
Hemangioma/irrigação sanguínea , Neoplasias Hepáticas/irrigação sanguínea , Veia Porta/diagnóstico por imagem , Angiografia , Meios de Contraste , Diagnóstico Diferencial , Feminino , Hemangioma/diagnóstico por imagem , Hemangioma/patologia , Artéria Hepática/diagnóstico por imagem , Humanos , Neoplasias Hepáticas/diagnóstico por imagem , Neoplasias Hepáticas/patologia , Imagem por Ressonância Magnética , Tomografia Computadorizada por Raios X , Ultrassonografia , Adulto Jovem
18.
Folia Morphol (Warsz) ; 79(1): 71-78, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-31106843

RESUMO

BACKGROUND: The aim of the study was to investigate the changes of blood flow signal in residual cancer after ultrasound-guided radiofrequency ablation (RFA) treatment of rabbit liver cancer over time, and to analyse the correlation between changes in blood flow signal and changes in hypoxia-inducible factor 1-alpha (HIF-1α), vascular endothelial growth factor (VEGF), and matrix metalloproteinase-9 (MMP-9) in residual cancer tissue after RFA. MATERIALS AND METHODS: One hundred and ten rabbits were randomly selected, VX2 tumour cells were implanted subcutaneously, tumour cells were implanted in liver. Ninety rabbits were divided into three groups: Group 1 - untreated controls, Group 2 - RFA group, Group 3 - surgical resection group. Tumour size, blood flow signal, microvessel density (MVD) in liver cancer were assessed. RESULTS: Correlation of HIF-1a, VEGF, MMP-9 mRNA and protein expressions with blood flow signal in residual cancer were observed. Liver tumour was 2.3 ± 0.32 cm, significant differences in the grade of blood flow signal were noted among different time points (days 0, 3, 7, and 14; p < 0.05). Significant differences were also observed between the surgical resection and RFA groups at the same time points (p < 0.05). The MVD in the RFA group was lower than that in the control group, but higher than that in the surgical resection group. The immunohistochemical scores for VEGF and MMP-9 in the RFA group were lower than those in the control group, but higher than those in the surgical resection group. The grade of ultrasound blood flow signal was positively correlated with the expression of two angiogenesis-related factors, VEGF and MMP-9, and the MVD in the control, RFA, and surgical resection groups. CONCLUSIONS: There is a higher risk of tumour recurrence with RFA than with surgical resection.


Assuntos
Carcinoma Hepatocelular/irrigação sanguínea , Neoplasias Hepáticas/irrigação sanguínea , Neoplasia Residual/irrigação sanguínea , Neovascularização Patológica/patologia , Animais , Carcinoma Hepatocelular/patologia , Feminino , Hepatectomia , Subunidade alfa do Fator 1 Induzível por Hipóxia/metabolismo , Neoplasias Hepáticas/patologia , Masculino , Metaloproteinase 9 da Matriz/metabolismo , Coelhos , Ablação por Radiofrequência , Fator A de Crescimento do Endotélio Vascular/metabolismo
19.
Int J Cancer ; 146(5): 1383-1395, 2020 03 01.
Artigo em Inglês | MEDLINE | ID: mdl-31286509

RESUMO

Hepatocellular carcinoma (HCC) is an aggressive malignancy with increasing mortality in China. Angiogenesis is crucial for tumor formation, development and metastasis in HCC. Previous studies indicated that high expression levels of elongation factor 2 kinase (eEF2K), a protein kinase that negatively regulates the elongation stage of translation, were associated with poor prognosis of HCC. Here, we show that pharmacological inhibition or knockdown of eEF2K in highly metastatic liver cancer cells inhibits their colony forming and migratory capacities, as well as reducing their invasiveness. Importantly, knocking down eEF2K by lentiviral directed shRNA prevented tumor growth and angiogenesis of HCC in mice. Silencing of eEF2K in endothelial cells (HUVECs) led to a reduction in vascularization, evidenced by a decrease in capillary-like structures in the matrigel. Notably, knocking down eEF2K reduced the expression of angiogenesis-related growth factors in liver cancer cells and the expression of growth factor receptors on HUVECs, and thus restricted signaling crosstalk that promotes angiogenesis between HCC cells and endothelial cells. We also showed that silencing of eEF2K effectively reduced protein levels of SP1/KLF5 transcription factors and hence decreased the levels of bound SP1/KLF5 to the VEGF promoter, resulted in a decrease in VEGF mRNA expression. Knocking down eEF2K also led to a striking decrease in the phosphorylation of PI3K/Akt and STAT3, indicating inactivation of these tumorigenic pathways. Taken together, our data suggest that eEF2K contributes to angiogenesis and tumor progression in HCC via SP1/KLF5-mediated VEGF expression, as well as the subsequent stimulation of PI3K/Akt and STAT3 signaling.


Assuntos
Carcinoma Hepatocelular/irrigação sanguínea , Quinase do Fator 2 de Elongação/metabolismo , Neoplasias Hepáticas/irrigação sanguínea , Fosfatidilinositol 3-Quinases/metabolismo , Proteínas Proto-Oncogênicas c-akt/metabolismo , Fator de Transcrição STAT3/metabolismo , Animais , Carcinoma Hepatocelular/metabolismo , Linhagem Celular Tumoral , Movimento Celular , Proliferação de Células , Células Hep G2 , Xenoenxertos , Células Endoteliais da Veia Umbilical Humana , Humanos , Neoplasias Hepáticas/metabolismo , Masculino , Camundongos , Camundongos Endogâmicos BALB C , Camundongos Nus , Invasividade Neoplásica , Neovascularização Patológica/metabolismo , Neovascularização Patológica/patologia , Transdução de Sinais
20.
Appl Biochem Biotechnol ; 190(1): 305-324, 2020 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-31346920

RESUMO

Current estimates indicate that hepatocarcinoma is the leading cause of death globally. There is interest in utilizing nanomedicine for cancer therapy to overcome side effects of chemo-interventions. Ribavirin, an antiviral nucleoside inhibitor, accumulates inside red blood cells, causing anemia. Its analog, viramidine, can concentrate within hepatocytes and spare red blood cells, thus limiting anemia. Hepatocarcinoma cells have a large number of asialoglycoprotein receptors on their membranes that can bind galactosyl-terminating solid lipid nanoparticles (Gal-SLN) and internalize them. Here, viramidine, 5-fluorouracil, and paclitaxel-loaded Gal-SLN were characterized inside cells. Cytotoxicities of free-drug, nano-void, and drug-loaded Gal-SLN were evaluated using HepG2 cells; over 3 days, cell viability was measured. To test the mechanistic pathway, we investigated in vitro apoptosis using flow cytometry and in ovo angiogenesis using the CAM assay. Results showed that 1 and 2 µM of the viramidine-encapsulated Gal-SLN had the highest cytotoxic effect, achieving 80% cell death with a steady increase over 3 days, with induction of apoptosis and reduction of necrosis and angiogenesis, compared to free-drugs. Gal-SLN application on breast cancer MCF-7 cells confirmed its specificity against liver cancer HepG2 cells. We conclude that viramidine-encapsulated Gal-SLN has anticancer and anti-angiogenic activities against hepatocarcinoma.


Assuntos
Inibidores da Angiogênese/administração & dosagem , Apoptose/efeitos dos fármacos , Galactose/química , Nanopartículas/química , Neovascularização Patológica/prevenção & controle , Ribavirina/análogos & derivados , Inibidores da Angiogênese/química , Inibidores da Angiogênese/farmacologia , Neoplasias da Mama/irrigação sanguínea , Neoplasias da Mama/patologia , Carcinoma Hepatocelular/irrigação sanguínea , Carcinoma Hepatocelular/patologia , Células Hep G2 , Humanos , Neoplasias Hepáticas/irrigação sanguínea , Neoplasias Hepáticas/patologia , Células MCF-7 , Ribavirina/administração & dosagem , Ribavirina/química , Ribavirina/farmacologia
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