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1.
Adv Exp Med Biol ; 1164: 63-71, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31576540

RESUMO

Gankyrin (also called PSMD10, p28, or p28GANK) is a crucial oncoprotein that is upregulated in various cancers and assumed to play pivotal roles in the initiation and progression of tumors. Although the in vitro function of gankyrin is relatively well characterized, its role in vivo remains to be elucidated. We have investigated the function of gankyrin in vivo by producing mice with liver parenchymal cell-specific gankyrin ablation (Alb-Cre;gankyrinf/f) and gankyrin deletion both in liver parenchymal and in non-parenchymal cells (Mx1-Cre;gankyrinf/f). Gankyrin deficiency both in non-parenchymal cells and parenchymal cells, but not in parenchymal cells alone, reduced STAT3 activity, interleukin-6 production, and cancer stem cell marker expression, leading to attenuated tumorigenic potential in the diethylnitrosamine hepatocarcinogenesis model. Essentially similar results were obtained by analyzing mice with intestinal epithelial cell-specific gankyrin ablation (Villin-Cre;Gankyrinf/f) and gankyrin deletion both in myeloid and epithelial cells (Mx1-Cre;Gankyrinf/f) in the colitis-associated cancer model. Clinically, gankyrin expression in the tumor microenvironment was negatively correlated with progression-free survival in patients undergoing treatment with Sorafenib for hepatocellular carcinomas. These findings indicate important roles played by gankyrin in non-parenchymal cells as well as parenchymal cells in the pathogenesis of liver cancers and colorectal cancers, and suggest that by acting both on cancer cells and on the tumor microenvironment, anti-gankyrin agents would be promising as therapeutic and preventive strategies against various cancers, and that an in vitro cell culture models that incorporate the effects of non-parenchymal cells and gankyrin would be useful for the study of human cell transformation.


Assuntos
Carcinoma Hepatocelular , Neoplasias Hepáticas , Complexo de Endopeptidases do Proteassoma , Animais , Carcinoma Hepatocelular/genética , Carcinoma Hepatocelular/fisiopatologia , Carcinoma Hepatocelular/terapia , Neoplasias Colorretais/genética , Neoplasias Colorretais/fisiopatologia , Modelos Animais de Doenças , Sistemas de Liberação de Medicamentos , Deleção de Genes , Humanos , Neoplasias Hepáticas/genética , Neoplasias Hepáticas/fisiopatologia , Neoplasias Hepáticas/terapia , Camundongos , Complexo de Endopeptidases do Proteassoma/genética , Complexo de Endopeptidases do Proteassoma/metabolismo , Fator de Transcrição STAT3/metabolismo , Microambiente Tumoral
2.
Medicine (Baltimore) ; 98(40): e17460, 2019 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-31577775

RESUMO

BACKGROUND: This study aimed to perform a network meta-analysis to evaluate the therapeutic effect and safety of various modalities in treating advanced hepatocellular carcinoma (HCC). Typically, the modalities of interest were comprised of sorafenib, transarterial chemoembolization (TACE), sorafenib combined with TACE, TACE combined with traditional Chinese medicine (TCM), and sorafenib combined with hepatic arterial infusion chemotherapy (HAIC). METHODS: Potentially eligible studies were systemically retrieved from the electronic databases (including PubMed and Cochrane Library) up to September 2018. The overall survival (OS) associated with the 5 modalities of interest enrolled in this study was compared by means of network meta-analysis. Meanwhile, major adverse events (AEs) were also evaluated. RESULTS: The current network meta-analysis enrolled 7 published randomized controlled trials (RCTs), and the pooled results indicated that the TACE-TCM regimen displayed the highest efficacy in treating advanced HCC, followed by HAIC-sorafenib. By contrast, the TACE alone and sorafenib alone regimens had the least efficacy. Relative to other regimens of interest, the TACE-TCM regimen was associated with less incidence of treatment-associated AEs. CONCLUSION: The TACE-TCM regimen was associated with higher treatment responses in advanced HCC patients than those of the other regimens of interest.


Assuntos
Carcinoma Hepatocelular/terapia , Neoplasias Hepáticas/terapia , Humanos , Meta-Análise em Rede , Ensaios Clínicos Controlados Aleatórios como Assunto , Resultado do Tratamento
3.
Medicine (Baltimore) ; 98(40): e16912, 2019 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-31577696

RESUMO

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


Assuntos
Carcinoma Hepatocelular/patologia , Artéria Hepática/patologia , Neoplasias Hepáticas/patologia , Fígado/anormalidades , Fígado/patologia , Idoso , Carcinoma Hepatocelular/diagnóstico por imagem , Carcinoma Hepatocelular/terapia , Embolização Terapêutica , Artéria Hepática/diagnóstico por imagem , Humanos , Fígado/efeitos dos fármacos , Neoplasias Hepáticas/diagnóstico por imagem , Neoplasias Hepáticas/terapia , Imagem por Ressonância Magnética , Masculino , Tomografia Computadorizada por Raios X
4.
Medicine (Baltimore) ; 98(40): e17393, 2019 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-31577747

RESUMO

RATIONALE: Bacteremia caused by polymicrobial infections are rare but dangerous. We report a case of hepatic abscess combined with polymicrobial bacteremia in a 49-year-old male patient after surgery and transcatheter arterial chemoembolization (TACE). PATIENT CONCERNS: The patient was admitted to hospital with metastatic liver cancer for periodic chemotherapy and developed a high fever and tenderness to the liver following surgery and TACE. DIAGNOSIS: Hepatic abscess combined with polymicrobial bacteremia. INTERVENTIONS: The clinician formulated a therapy in accordance with the drug susceptibility test and the empirical drug use for anaerobic bacteria. A comprehensive treatment plan was adopted, on the basis of the combination of nitrazole and imipenem as anti-infection drugs as well as continuous abscess drainage. OUTCOMES: After comprehensive therapy, the patient was ultimately discharged without any residual symptoms. LESSONS: Bloodstream infection caused by multiple bacteria increases the difficulty of anti-infection treatments, leading to poor treatment outcome and high mortality. Therefore, a fast and accurate diagnosis of polymicrobial bacteremia is key for initiation of an effective antimicrobial treatment. Additionally, pre-operative prophylactic antibiotics are advisable when patients have a history of abdominal surgery and are immune-compromised.


Assuntos
Bacteriemia/etiologia , Carcinoma Hepatocelular/terapia , Quimioembolização Terapêutica/efeitos adversos , Abscesso Hepático/etiologia , Neoplasias Hepáticas/terapia , Antibacterianos/uso terapêutico , Bacteriemia/tratamento farmacológico , Bacteriemia/microbiologia , Carcinoma Hepatocelular/cirurgia , Coinfecção , Drenagem , Humanos , Abscesso Hepático/tratamento farmacológico , Abscesso Hepático/microbiologia , Neoplasias Hepáticas/cirurgia , Masculino , Pessoa de Meia-Idade , Metástase Neoplásica
5.
Zhonghua Gan Zang Bing Za Zhi ; 27(9): 732-736, 2019 Sep 20.
Artigo em Chinês | MEDLINE | ID: mdl-31594104

RESUMO

The treatment of late stage hepatocellular carcinoma (HCC) presently remains a great challenge. A very few drugs have been recently approved for clinical use except sorafenib and lenvatinib. After decades of failure and experience with molecular targeted and immunosuppressive therapy, immune checkpoint inhibitors are becoming one of the potentially effective therapies for patients with HCC, whose tumor is in the middle and late stages. Moreover, immune checkpoint is one of the main mechanisms of tumor immune evasion; of which programmed cell death protein 1 and its ligand (PD1/PD-L1) are important immune checkpoint targets, and its related pathway has shown to have an antitumor effect in a variety of solid or hematologic tumors and its inhibitors can effectively exert antitumor immunosuppressive effects. This review summarizes the current role of PD1/PD-L1 inhibitors in the treatment of late stage HCC, and explores the forecasting value of combined therapy strategy for HCC.


Assuntos
Antígeno B7-H1/antagonistas & inibidores , Carcinoma Hepatocelular/terapia , Neoplasias Hepáticas/terapia , Receptor de Morte Celular Programada 1/antagonistas & inibidores , Antígeno B7-H1/metabolismo , Humanos , Receptor de Morte Celular Programada 1/metabolismo
6.
Acta Cir Bras ; 34(7): e201900710, 2019 Sep 16.
Artigo em Inglês | MEDLINE | ID: mdl-31531530

RESUMO

PURPOSE: To investigate the prognostic value of 17 platelet-based prognostic scores in patients with malignant hepatic tumors after TACE therapy. METHODS: In total, 92 patients were divided into death group and survival group according to long-term follow-up results. The AUC was calculated to determine the optimal cut-off values for predicting prognosis. To determine better prognostic models, platelet-based models were analyzed separately after being showed as binary according to cut-off values. Cumulative survival rates of malignant hepatic tumors were calculated using Kaplan-Meier curves and differences were analyzed by the log-rank test. Univariate and multivariate analyses were performed to identify platelet-based prognostic scores associated with overall survival. RESULTS: Univariate analysis showed that APGA, APRI, FIB-4, FibroQ, GUCI, King's score, Lok index, PAPAS, cirrhosis, number of tumors, vascular cancer embolus, AFP, ALP and APTT were significantly related to prognosis. A multivariate analysis showed that the APGA, number of tumors, ALP and APTT were independently associated with overall survival. CONCLUSION: This study showed that the APGA, a platelet-based prognostic score, was an independent marker of prognosis in patients with malignant hepatic tumors after TACE and was superior to the other platelet-based prognostic scores in terms of prognostic ability.


Assuntos
Aspartato Aminotransferases/sangue , Plaquetas/química , Carcinoma Hepatocelular/terapia , Quimioembolização Terapêutica/métodos , Neoplasias Hepáticas/terapia , Adulto , Idoso , Idoso de 80 Anos ou mais , Biomarcadores Tumorais/sangue , Carcinoma Hepatocelular/sangue , Carcinoma Hepatocelular/mortalidade , Feminino , Humanos , Estimativa de Kaplan-Meier , Neoplasias Hepáticas/sangue , Neoplasias Hepáticas/mortalidade , Masculino , Pessoa de Meia-Idade , Contagem de Plaquetas , Prognóstico , Curva ROC , Estudos Retrospectivos
7.
Zhonghua Yi Xue Za Zhi ; 99(33): 2581-2585, 2019 Sep 03.
Artigo em Chinês | MEDLINE | ID: mdl-31510716

RESUMO

Objective: To explore clinical application value of prognostic nutrition index(PNI) and apparent diffusion coefficient(ADC) in treating hepatic arterial chemoembolization (TACE) of patients with hepatic cell carcinoma (HCC). Methods: A total of 77 patients with HHC of BCLC B were retrospectively analyzed in Dalian Medical University Affiliated Second Hospital who were diagnosed for the first time and received TACE treatment from October 2017 to December 2018, of whom 64 Males, 13 females, mean age was 54±13 years.At 1 month after surgery, TACE efficacy was evaluated according to revised solid tumor evaluation criteria (mRECIST), the enrolled patients were divided into TACE effective group (41 cases, 53.2%) and TACE ineffective group (36 cases, 46.8%) to compare ability of PNI and ability of ADC alone or in combination in evaluating efficacy of TACE and the relationship between these two groups. Results: Overall postoperative PNI of enrolled patients was decreased compared with preoperative PNI, 47.7±6.6 vs 48.3±5.9 (P<0.05), preoperative and postoperative PNI of TACE effective group were all higher than that of TACE ineffective group (49.9±6.0 vs 46.6±5.3, 50.6±5.4 vs 44.4±5.1,all P<0.05), there was no significant difference in PNI between the treatment groups (P>0.05). The value of ADC in postoperative tumor region increased compared with that in preoperative tumor region ((1.43±0.15) ×10(-3) vs (1.28±0.08) ×10(-3) mm(2)/s, P<0.05), the difference between postoperative tumor region ADC value and postoperative normal liver parenchyma had no statistical significance(P>0.05). Overall postoperative PNI and tumor region ADC value of enrolled patients had linear correlation (P<0.05).Threshold value of PNI and ADC value in preoperative prediction were 51.05 and 1.32×10(-3) mm(2)/s; postoperative evaluation threshold value were 50.11 and 1.41×10(-3) mm(2)/s.Postoperative combination of PNI and ADC had the highest value in evaluating TACE efficacy. Conclusions: TACE postoperative PNI and tumor region ADC are related. PNI and tumor region ADC could be used in predicting and evaluating TACE efficacy in HCC patients, combination of these two could further increase the efficiency.


Assuntos
Carcinoma Hepatocelular , Quimioembolização Terapêutica , Neoplasias Hepáticas , Adulto , Idoso , Carcinoma Hepatocelular/terapia , Feminino , Humanos , Neoplasias Hepáticas/terapia , Masculino , Pessoa de Meia-Idade , Avaliação Nutricional , Prognóstico , Estudos Retrospectivos
8.
Medicine (Baltimore) ; 98(31): e16660, 2019 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-31374039

RESUMO

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


Assuntos
Carcinoma Hepatocelular/terapia , Quimioembolização Terapêutica/métodos , Tratamento por Ondas de Choque Extracorpóreas/métodos , Neoplasias Hepáticas/terapia , Radioterapia Conformacional/métodos , Idoso , Carcinoma Hepatocelular/complicações , Carcinoma Hepatocelular/patologia , Terapia Combinada , Humanos , Neoplasias Hepáticas/complicações , Neoplasias Hepáticas/patologia , Masculino , Estadiamento de Neoplasias , Trombose Venosa/etiologia
9.
J Surg Oncol ; 120(6): 956-965, 2019 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-31373009

RESUMO

BACKGROUND: Videolaparoscopic (VL) microwave ablation (MWA) is not included in most of the international guidelines as a therapeutic option for hepatocellular carcinoma (HCC). Aim of this study was to assess the safety of VL MWA in patients with HCC for whom resection or percutaneous ablation is unsuitable. METHODS: A retrospective analysis was performed on a prospective database of patients with HCC treated with VL MWA at our institution from 2009 to 2016. Patient demographics, operational characteristics, and complications were recorded. Statistical analysis was performed to identify safety profile, overall survival and recurrence rate. RESULTS: A total of 815 VL MWA were performed in 674 patients with a mean age of 64 years. Patients had a mean Model for End-stage Liver Disease score of 10 (±3); 32.8% were Child B, 44.1% Barcelona Clinic Liver Cancer B-C. Perioperative mortality was 0.4%. Overall morbidity was 30.8%, with Dindo-Clavien complications ≥3 in 2%. The median length of stay was 2 days. In 43.1% VL MWA was the first-line therapy. Overall 1-, 3-, and 5-year survival rates were 81.9%, 54.9%, and 35.9%. CONCLUSIONS: The present is the largest series of VL ablation and the bigger number of patients with HCC treated with MW reported nowadays. It confirms the safety of a minimally invasive procedure for patients with HCC when resection or percutaneous ablation is not feasible.


Assuntos
Carcinoma Hepatocelular/terapia , Ablação por Cateter/mortalidade , Hospitais com Alto Volume de Atendimentos/estatística & dados numéricos , Laparoscopia/mortalidade , Neoplasias Hepáticas/terapia , Micro-Ondas/uso terapêutico , Cirurgia Vídeoassistida/mortalidade , Adulto , Idoso , Idoso de 80 Anos ou mais , Carcinoma Hepatocelular/patologia , Europa (Continente) , Feminino , Seguimentos , Humanos , Neoplasias Hepáticas/patologia , Estudos Longitudinais , Masculino , Pessoa de Meia-Idade , Prognóstico , Estudos Prospectivos , Estudos Retrospectivos , Taxa de Sobrevida
10.
Medicine (Baltimore) ; 98(35): e17007, 2019 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-31464957

RESUMO

Poor outcomes of hepatocellular carcinomas (HCC) in chronic kidney disease (CKD) patients are well described. Transarterial therapy is the standard treatment for HCC, following which regular contrast-enhanced imaging for residual disease is recommended. CKD is considered a relative contraindication for transarterial therapy owing to renal failure.This retrospective study investigated the outcomes of transarterial therapy in HCC patients with CKD. In total, 132 HCC patients who received transarterial therapy were enrolled, of whom 36 had CKD. Most CKD patients were elderly, with mean age of diagnosis of 69.7 ±â€Š11.4 years. Hypertension (odds ratio [OR]; 5.06; 95% confidence interval [Cl]; 1.83-13.94), hepatitis C virus carrier rate (OR; 4.12, 95% CI; 1.13-14.99) and diabetes (OR; 3.62, 95% CI; 1.22-10.72) were significant predictors for CKD in HCC patients. Post therapy, the estimated glomerular filtration rate significantly decreased 13.7% from baseline in the CKD patients (P = .03). There were more post-therapy complications than in the non-CKD group, e.g. acute renal failure and sepsis (P < .01 vs P < .01). Overall survival in the CKD group was significantly poor (10.9 ±â€Š8.5 vs 23.5 ±â€Š16.3 months, P < .01).The lower survival of CKD patients was unrelated to treatment modality or less contrast-enhanced imaging follow-up. Further research on patient care and factors leading to poor outcomes for CKD is needed.


Assuntos
Carcinoma Hepatocelular/epidemiologia , Carcinoma Hepatocelular/terapia , Quimioembolização Terapêutica/métodos , Neoplasias Hepáticas/epidemiologia , Neoplasias Hepáticas/terapia , Insuficiência Renal Crônica/epidemiologia , Fatores Etários , Idoso , Idoso de 80 Anos ou mais , Carcinoma Hepatocelular/mortalidade , Quimioembolização Terapêutica/efeitos adversos , Diabetes Mellitus/epidemiologia , Feminino , Taxa de Filtração Glomerular , Hepatite C/epidemiologia , Humanos , Hipertensão/epidemiologia , Neoplasias Hepáticas/mortalidade , Masculino , Pessoa de Meia-Idade , Complicações Pós-Operatórias/epidemiologia , Estudos Retrospectivos , Fatores de Risco
11.
J Cancer Res Clin Oncol ; 145(11): 2761-2769, 2019 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-31428932

RESUMO

PURPOSE: This study aims to examine the health-related quality of life in patients with hepatocellular carcinoma. METHODS: 181 patients attending a tertiary center outpatient clinic were interviewed and completed the short form 36 (SF36) questionnaire. The SF36 was used to assess health-related QoL. Cross-sectional analyses by group (age, gender, clinical scores, systemic, and local interventions) as well sequel questionnaires were conducted. RESULTS: Participants included were 79% (143/181) men [mean age at first SF36: 63.8 (± 12.3; 18.4-85.8) years]. Barcelona Clinic Liver Cancer (BCLC) stadium C was associated with significantly lower SF36 total scores, and elevated initial alpha-fetoprotein (AFP) concentrations were associated with lower SF36 functional and mental health sum scores throughout the course of the third questionnaire. Patients treated with sorafenib had within the sub-dimension scores a significantly lower result for role limitations due to physical health compared to patients without sorafenib treatment. Patients who underwent a transarterial chemoembolization (TACE) had within the sub-dimension scores a significantly higher result for control of pain compared to patients without TACE. Kaplan-Meier analysis revealed significant survival benefits for patients who underwent any intervention at the first SF36 (mean survival in years 4.3 vs. 1.6; P < 0.01) as well as for patients who underwent hepatic resection (mean survival in years 6.3 vs. 2.7; P < 0.0001). CONCLUSION: Advanced tumor stages marked by BCLC stadium C and elevated initial AFP concentrations were associated with lower SF36 total scores and functional sum scores, respectively. During the course of sorafenib treatment, the sub-dimensional score for role limitations due to physical health decreased significantly, whereas TACE performance was associated with a significant improvement of the control of body pain.


Assuntos
Carcinoma Hepatocelular/terapia , Quimioembolização Terapêutica/mortalidade , Neoplasias Hepáticas/terapia , Qualidade de Vida , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Carcinoma Hepatocelular/patologia , Carcinoma Hepatocelular/psicologia , Estudos Transversais , Intervenção Médica Precoce , Feminino , Seguimentos , Humanos , Neoplasias Hepáticas/patologia , Neoplasias Hepáticas/psicologia , Masculino , Pessoa de Meia-Idade , Estadiamento de Neoplasias , Estudos Prospectivos , Inquéritos e Questionários , Taxa de Sobrevida , Resultado do Tratamento , Adulto Jovem
12.
J Biomed Nanotechnol ; 15(10): 2025-2044, 2019 Oct 01.
Artigo em Inglês | MEDLINE | ID: mdl-31462369

RESUMO

In this study we employed self-designed PDLLA-PEG-PDLLA (PLEL) thermosensitive hydrogel to blend with norcantharidin (NCTD), a hydrophilic chemotherapeutic drug possessing curative effect on primary hepatocellular carcinoma (HCC) and adverse effects, then utilized the composite in HCC interstitial chemotherapy. PLEL copolymer was synthesized by ring-opening polymerization, NCTD-loaded PLEL hydrogel was prepared in a simple and reasonable way. The addition of NCTD had no significant effect on the temperature-dependent rheological properties of PLEL hydrogel. The pH values of NCTD-loaded gel solutions (13 wt%) and free NCTD solutions with three drug concentrations of 0.4 mg/mL, 0.8 mg/mL and 1.2 mg/mL under different storage conditions met the pH requirement of small-volume injection. There was no significant difference among the drug release behaviors of NCTD-loaded gels with drug concentrations of 0.4 mg/mL, 0.8 mg/mL and 1.2 mg/mL, they fitted first-order dynamics, exhibited significantly slower drug release than free drug solutions and the release was mainly based on drug diffusion. Drug-loaded gel solution (13 wt%) could evenly distribute throughout tumor tissue before converting into gel after being intratumorally injected and was able to significantly prolong retention time of the drug in tumor compared to free drug solution. The sustained-release performance of NCTD-loaded gel (13 wt%) was confirmed from the perspective of pharmacodynamics in vitro. The in vivo evaluation demonstrated that intratumoral injection of NCTD-loaded PLEL gel (13 wt%) was capable of improving curative effect of the drug and reducing its toxicity.


Assuntos
Carcinoma Hepatocelular , Neoplasias Hepáticas , Compostos Bicíclicos Heterocíclicos com Pontes , Carcinoma Hepatocelular/terapia , Humanos , Hidrogéis , Injeções Intralesionais , Neoplasias Hepáticas/terapia , Poliésteres , Polietilenoglicóis
13.
Cancer Radiother ; 23(5): 385-394, 2019 Sep.
Artigo em Francês | MEDLINE | ID: mdl-31300328

RESUMO

PURPOSE: The purpose of the study was to evaluate the outcomes of stereotactic radiation therapy for primary and secondary liver tumours in Jean-Perrin cancer centre (Clermont-Ferrand, France) in terms of efficacy and safety. MATERIALS AND METHODS: Between December 2013 and June 2016, 25 patients were included. Treatment was performed on a linear accelerator Novalis TX®. The prescription dose was 42 to 60Gy in three to five fractions. Local control at 1 year was evaluated with modified Response Evaluation Criteria in Solid Tumours (mRECIST) and RECIST criteria. Acute and late toxicity were evaluated with Common Terminology Criteria for Adverse Events (CTCAE) v4.0 criteria. RESULTS: Median follow-up was 10.5 months. Treatment tolerance was good with few side effects grade 3 or above, no acute toxicity and only one late toxicity. We have highlighted that hepatic artery haemorrhage was associated with the presence of a biliary prosthesis in contact with the artery (P=0.006) and in the irradiation field. There was no correlation with the dose delivered to the artery and hepatic artery haemorrhage. CONCLUSION: Stereotactic radiation therapy for liver tumours allows a good local control with few secondary effects. Caution should be exercised when treating patients with biliary prostheses in the vicinity of the target volume because there is a risk of haemorrhage of the hepatic artery in contact with the prosthesis.


Assuntos
Neoplasias Hepáticas/radioterapia , Hipofracionamento da Dose de Radiação , Lesões por Radiação/etiologia , Radiocirurgia/efeitos adversos , Radioterapia de Intensidade Modulada/métodos , Idoso , Idoso de 80 Anos ou mais , Antineoplásicos/uso terapêutico , Carcinoma/radioterapia , Carcinoma/secundário , Carcinoma/terapia , Carcinoma Hepatocelular/radioterapia , Carcinoma Hepatocelular/terapia , Colangiocarcinoma/radioterapia , Colangiocarcinoma/terapia , Terapia Combinada , Intervalo Livre de Doença , Embolização Terapêutica , Feminino , Seguimentos , França/epidemiologia , Hemorragia/etiologia , Hepatectomia , Artéria Hepática/efeitos da radiação , Humanos , Neoplasias Hepáticas/secundário , Neoplasias Hepáticas/terapia , Masculino , Pessoa de Meia-Idade , Polietileno/efeitos da radiação , Polímeros/efeitos da radiação , Lesões por Radiação/epidemiologia , Planejamento da Radioterapia Assistida por Computador , Estudos Retrospectivos , Stents
14.
Medicine (Baltimore) ; 98(30): e16150, 2019 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-31348228

RESUMO

We evaluated the post-treatment overall survival (OS) of elderly hepatocellular carcinoma (HCC) patients.The archived records of 10,578 HCC patients registered at the Korean Central Cancer Registry from 2008 through 2014 were retrospectively analyzed. In this registry, we selected Barcelona Clinic Liver Cancer (BCLC) 0, A, or B staged HCC patients (n = 4744) treated by surgical resection (SR), local ablation therapy (LAT), or locoregional therapy (LRT). OSs in nonelderly (<70 years) and elderly (≥70 years) patients were compared after propensity score matching (PSM).In BCLC 0-A staged HCC, the cumulative OS rates of elderly patients were poorer than those of nonelderly patients after PSM (P < .001), but not in those with BCLC stage B (P > .05). In BCLC 0-A staged elderly patients, OS after SR was significantly better than after LAT (P = .005) or LRT (P < .001). In BCLC B staged elderly patients, SR achieved better OS than LRT (P = .006). Multivariable analysis showed that LAT (hazard ratio [HR] 1.52, P = .048) or LRT (HR, 2.01, P < .001) as compared with SR, and large (>3 cm) tumor size (HR1.49, P = .018) were poor predictors of OS for elderly patients with BCLC stage 0-A, and that LRT (HR, 2.64, P = .042) was a poor predictor for those with BCLC stage B.SR provided a better OS rate than LAT or LRT in elderly HCC patients with BCLC stage 0-A, than LRT in those with BCLC stage B. SR should be considered the first therapeutic option even in elderly HCC patients with these stages.


Assuntos
Carcinoma Hepatocelular/epidemiologia , Carcinoma Hepatocelular/terapia , Neoplasias Hepáticas/epidemiologia , Neoplasias Hepáticas/terapia , Fatores Etários , Idoso , Idoso de 80 Anos ou mais , Consumo de Bebidas Alcoólicas/epidemiologia , Antineoplásicos/uso terapêutico , Carcinoma Hepatocelular/mortalidade , Carcinoma Hepatocelular/patologia , Ablação por Cateter/estatística & dados numéricos , Quimioembolização Terapêutica/estatística & dados numéricos , Comorbidade , Feminino , Comportamentos Relacionados com a Saúde , Hepatectomia/estatística & dados numéricos , Hepatite B/epidemiologia , Hepatite C/epidemiologia , Humanos , Testes de Função Hepática , Neoplasias Hepáticas/mortalidade , Neoplasias Hepáticas/patologia , Masculino , Estadiamento de Neoplasias , Pontuação de Propensão , Sistema de Registros , República da Coreia/epidemiologia , Estudos Retrospectivos , Fatores Sexuais , Fatores Socioeconômicos , Análise de Sobrevida , Carga Tumoral
15.
Medicine (Baltimore) ; 98(30): e16579, 2019 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-31348291

RESUMO

In this study, we aim to explore the values of serum dickkopf-1 (DKK1) and circulating tumor cells (CTCs) in predicting the efficacy and prognosis of transcatheter arterial chemoembolization (TACE) treatment on patients with hepatocellular carcinoma (HCC). We did a retrospective analysis on 155 HCC patients who underwent TACE treatment. The patients were divided into response group (complete response and partial response) and nonresponse group (stable disease and progressive disease), and their changes in serum DKK1 and CTCs after TACE were recorded. Receiver operating characteristic curve and survival analysis were used to assess the predictive values of DKK1 and CTCs for TACE efficacy and long-term prognosis of HCC. We found that the levels of preoperative DKK1 and CTCs in patients with HCC had a moderate positive correlation (r = 0.54). After TACE treatment, the serum DKK1 and CTCs in the response group were significantly decreased compared to pretreatment levels (P < .05), whereas the nonresponse group showed significantly increased serum DKK1 and CTCs levels (P < .05). The largest area under the curve (AUC) was achieved when using >0.02 µg/L reduction in DKK1 level after 4 weeks of TACE to predict the efficacy of TACE treatment (AUC = 0.913, 95% confidence interval: 0.856-0.952, P < .001), with the sensitivity of 78.26% and the specificity of 88.07%. The overall survival, disease-free survival, and 5-year survival rates were all significantly lower in the patients with positive preoperative levels of serum DKK1 and CTCs. COX multivariate regression analysis showed that Eastern Cooperative Oncology Group score, and preoperative levels of serum DKK1 and CTCs are independent influencing factors for the prognosis of patients with HCC. Overall, our results demonstrated that serum DKK1 and CTCs levels were good biomarkers for predicting the efficacy and prognosis of TACE treatment in patients with HCC. Moreover, these parameters exhibited different characteristics, and might have different potential applications.


Assuntos
Carcinoma Hepatocelular/terapia , Quimioembolização Terapêutica/métodos , Peptídeos e Proteínas de Sinalização Intercelular/sangue , Neoplasias Hepáticas/terapia , Células Neoplásicas Circulantes/patologia , Adulto , Idoso , Idoso de 80 Anos ou mais , Biomarcadores Tumorais , Carcinoma Hepatocelular/patologia , Intervalo Livre de Doença , Feminino , Humanos , Estimativa de Kaplan-Meier , Neoplasias Hepáticas/patologia , Masculino , Pessoa de Meia-Idade , Recidiva Local de Neoplasia , Prognóstico , Curva ROC , Estudos Retrospectivos
16.
Medicine (Baltimore) ; 98(26): e15682, 2019 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-31261491

RESUMO

To compare the efficacy of drug-eluting bead transarterial chemoembolization combined with radiofrequency ablation (DEB-TACE+RFA) versus DEB-TACE alone in Chinese hepatocellular carcinoma (HCC) patients.The 28 patients receiving DEB-TACE+RFA and 74 HCC patients receiving DEB-TACE were recruited in this study. Treatment responses, progression-free survival (PFS), and overall survival (OS) were evaluated.One to 3 months after treatments, the proportion of patients achieving complete response (CR) (78.6% vs 33.8%, P <.001) and objective response rate (ORR) (92.9% vs 78.4%, P =.010) were elevated in DEB-TACE+RFA group compared with DEB-TACE group. Multivariate logistic regression displayed that DEB-TACE+RFA was an independently predicting factor for better CR (P = .006). Subgroup analysis of CR achievement illuminated that DEB-TACE+RFA disclosed better CR achievement in patients with history of cirrhosis (P <.001), tumor located in right liver (P = .003), bilobar disease (P = .013), tumor size <3.3 cm (P = .001), no portal vein invasion (P = .001), no hepatic vein invasion (P <.001), Child-pugh stage A (P <.001), Barcelona Clinic Liver Cancer (BCLC) stage 0, A-B (P <.001), abnormal alpha-fetoprotein (AFP) (P = .001) and normal AFP (P = .016). The PFSs were similar between 2 groups (P = .112), however, the OS was more prolonged in DEB-TACE+RFA group (P = .025) compared with DEB-TACE group. And subgroup analysis displayed that PFS of patients with largest nodule size >3.3 cm (P = .025) was longer and patients with unilobar disease (P = .009), and patients with no hepatic invasion (P = .019) and Child-pugh stage A (P = .037) had more favorable OS in DEB-TACE+RFA group compared with DEB-TACE group.DEB-TACE+RFA achieved better treatment responses and OS compared with DEB-TACE alone in Chinese HCC patients.


Assuntos
Carcinoma Hepatocelular/terapia , Quimioembolização Terapêutica , Neoplasias Hepáticas/terapia , Ablação por Radiofrequência , Carcinoma Hepatocelular/mortalidade , Quimioembolização Terapêutica/métodos , China , Terapia Combinada , Sistemas de Liberação de Medicamentos , Feminino , Humanos , Neoplasias Hepáticas/mortalidade , Masculino , Pessoa de Meia-Idade , Análise de Sobrevida , Resultado do Tratamento
17.
Medicine (Baltimore) ; 98(26): e16084, 2019 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-31261522

RESUMO

Heme oxygenase-1 (HO-1) is an important catalytic enzyme in heme degradation, which increases during stressful conditions. It plays a major role in antioxidative and antiapoptotic processes and is associated with tumor growth and metastasis.This study aimed to evaluate the degree of HO-1 expressions in hepatocellular carcinoma (HCC) surgical specimens and the correlation between HO-1 expression and patient prognosis. Formalin-fixed, paraffin-embedded HCC tissue samples (n = 96) were included in the analysis, and the expression of HO-1 was evaluated by immunohistochemical staining. We reviewed clinical features of patients and evaluated the prognostic role of HO-1 in patient survival and recurrence.Positive HO-1 expression was identified in 43 cases (44.8%) and was frequently found in patients with advanced histology (Edmondson-Steiner [E-S] grade 2, 3, 4), α-fetoprotein (AFP) level of more than 200 IU/mL, and the presence of microvascular and capsular invasion (P < .05). In the univariate analysis, the overall survival (OS) and disease-free survival (DFS) of patients with HO-1-positive HCC were not statistically different from those with HO-1-negative HCC. Moreover, HO-1 expression was not associated with patient survival and recurrence based on the multivariate analysis. In the subgroup analysis of patients without preoperative transarterial chemoembolization (TACE) (n = 61), HO-1 was not also associated with tumor recurrence (P = .681).The clinical implication of HO-1 activity is controversial in various malignancies. However, HO-1 expression did not seem to influence the prognosis of HCC patients.


Assuntos
Carcinoma Hepatocelular/enzimologia , Heme Oxigenase-1/metabolismo , Neoplasias Hepáticas/enzimologia , Biomarcadores Tumorais/metabolismo , Carcinoma Hepatocelular/mortalidade , Carcinoma Hepatocelular/patologia , Carcinoma Hepatocelular/terapia , Feminino , Expressão Gênica , Humanos , Imuno-Histoquímica , Neoplasias Hepáticas/mortalidade , Neoplasias Hepáticas/patologia , Neoplasias Hepáticas/terapia , Masculino , Pessoa de Meia-Idade , Prognóstico , Recidiva , Estudos Retrospectivos , Análise de Sobrevida
18.
Cell Mol Life Sci ; 76(21): 4203-4219, 2019 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-31300868

RESUMO

Hepatocellular carcinoma (HCC) is one of the most common malignancies worldwide, with a high mortality rate. Its dismal prognosis is attributed to late diagnosis, high risk of recurrence and drug resistance. To improve the survival of patients with HCC, new approaches are required for early diagnosis, real-time monitoring and effective treatment. Exosomes are small membranous vesicles released by most cells that contain biological molecules and play a great role in intercellular communication under physiological or pathological conditions. In cancer, exosomes from tumor cells or non-tumor cells can be taken up by neighboring or distant target cells, and the cargoes in exosomes are functional to modulate the behaviors of tumors or reshape tumor microenvironment (TME). As essential components, non-coding RNAs (ncRNAs) are selectively enriched in exosomes, and exosomal ncRNAs participate in regulating specific aspects of tumor development, including tumorigenesis, tumor metastasis, angiogenesis, immunomodulation and drug resistance. Besides, dysregulated exosomal ncRNAs have emerged as potential biomarkers, and exosomes can serve as natural vehicles to deliver tumor-suppressed ncRNAs for treatment. In this review, we briefly summarize the biology of exosomes, the functions of exosomal ncRNAs in HCC development and their potential clinical applications, including as biomarkers and therapeutic tools.


Assuntos
Carcinoma Hepatocelular/genética , Exossomos/genética , Neoplasias Hepáticas/genética , RNA Neoplásico/fisiologia , RNA não Traduzido/fisiologia , Animais , Biomarcadores Tumorais/fisiologia , Carcinoma Hepatocelular/diagnóstico , Carcinoma Hepatocelular/patologia , Carcinoma Hepatocelular/terapia , Sistemas de Liberação de Medicamentos , Exossomos/metabolismo , Regulação Neoplásica da Expressão Gênica , Terapia Genética/métodos , Humanos , Neoplasias Hepáticas/diagnóstico , Neoplasias Hepáticas/patologia , Neoplasias Hepáticas/terapia , Terapia de Alvo Molecular/métodos , RNA Neoplásico/metabolismo , RNA não Traduzido/metabolismo
19.
Egypt J Immunol ; 26(1): 69-78, 2019 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-31332997

RESUMO

Hepatocellular carcinoma (HCC) is a primary malignancy of the liver. Tumors can recruit and promote the expansion of regulatory T cells (Tregs) to suppress antitumor immune responses for survival and progression. Furthermore, there is a strong evidence for the potential roles of cytokines in promoting HCC carcinogenesis and progression. We aimed to evaluate the frequency of Treg cells and serum levels of IL6 and IL10 before and after transarterial chemoembolization (TACE). We carried out a cross-sectional study at Assiut University hospitals that included 34 HCC patients and 10 matched apparently healthy controls. Peripheral Treg frequency was evaluated by Flow cytometry. IL6 and IL10 serum levels were evaluated by ELISA before and after TACE. HCC patients had a significantly higher level of IL6 and IL10 when compared to the control group (P=0.0002, P < 0.0001), respectively. However, after treatment, there was an elevation in the levels of IL6 and IL10 followed by a decrease to the baseline levels. Patients with large tumors (≥5 cm) showed higher levels of both IL 6 and IL 10 than those with smaller tumors. Moreover, HCC patients showed a higher frequency of Treg cells in comparison to the controls (P=0.002). No significant correlation was observed between the frequency of Treg cells and IL10 before and after treatment (r=0.38, P=0.30). In conclusion, HCC patients have significantly higher levels of IL 6, IL 10 and a higher percentage of Tregs than control individuals. Treg levels are altered after chemoembolization. IL 6 have a potential in reflecting the patient's condition after treatment, thus, can help in monitoring therapy.


Assuntos
Carcinoma Hepatocelular/imunologia , Quimioembolização Terapêutica , Hepatite C/imunologia , Interleucina-10/sangue , Interleucina-6/sangue , Neoplasias Hepáticas/imunologia , Linfócitos T Reguladores/imunologia , Carcinoma Hepatocelular/terapia , Carcinoma Hepatocelular/virologia , Estudos Transversais , Humanos , Neoplasias Hepáticas/terapia , Neoplasias Hepáticas/virologia , Resultado do Tratamento
20.
Zhonghua Liu Xing Bing Xue Za Zhi ; 40(7): 805-809, 2019 Jul 10.
Artigo em Chinês | MEDLINE | ID: mdl-31357803

RESUMO

Objective: To explore an effective long non-coding RNA (lncRNA) signature in predicting the prognosis of hepatocellular carcinoma through the analysis on RNA sequencing data of hepatocellular carcinoma patients and peritumoral tissues in the Cancer Genome Atlas (TCGA) database. Methods: The clinical characteristics and RNA sequencing data of 377 hepatocellular carcinoma patients were obtained from TCGA database by the end of February 2018. Then, differentially expressed lncRNAs between 50 pairs of tumor and peritumoral tissues were explored using student's t-test. Next, a lncRNA signature was established through LASSO Cox regression analysis. All the patients were divided into four groups (

Assuntos
Carcinoma Hepatocelular/genética , Neoplasias Hepáticas/genética , RNA Longo não Codificante , Carcinoma Hepatocelular/terapia , Bases de Dados Genéticas , Humanos , Neoplasias Hepáticas/terapia , Prognóstico
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