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1.
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
2.
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
3.
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
4.
Khirurgiia (Mosk) ; (10): 88-90, 2019.
Artigo em Russo | MEDLINE | ID: mdl-31626245

RESUMO

Cardiovascular diseases and malignancies are leading causes of mortality in the world. Two categories of advanced age patients with cancer are observed in clinical practice. These are patients with cardiovascular diseases as comorbidities and patients with cardiovascular diseases as a complications of targeted therapy for cancer. Cardiac toxicity of chemotherapeutic drugs results myocardial dysfunction, occurrence or progression of heart valve disease, coronary artery disease, arterial hypertension and thromboembolism. A patient who underwent aortic valve replacement and coronary artery bypass surgery is discussed in the article. Aortic valve disease and coronary artery disease were complications of targeted radio- and chemotherapy for sigmoid colon cancer followed by lung and liver metastases. Questions of timely diagnosis and treatment of advanced age patients in multi-field surgical clinic are also analyzed.


Assuntos
Antineoplásicos/efeitos adversos , Cardiopatias/etiologia , Radioterapia/efeitos adversos , Neoplasias do Colo Sigmoide/terapia , Valva Aórtica/efeitos dos fármacos , Valva Aórtica/efeitos da radiação , Valva Aórtica/cirurgia , Estenose da Valva Aórtica/etiologia , Estenose da Valva Aórtica/cirurgia , Ponte de Artéria Coronária , Doença da Artéria Coronariana/etiologia , Doença da Artéria Coronariana/cirurgia , Cardiopatias/cirurgia , Implante de Prótese de Valva Cardíaca , Humanos , Neoplasias Hepáticas/secundário , Neoplasias Hepáticas/terapia , Neoplasias Pulmonares/secundário , Neoplasias Pulmonares/terapia , Neoplasias do Colo Sigmoide/patologia
5.
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
6.
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
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.
Anticancer Res ; 39(9): 5089-5096, 2019 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-31519620

RESUMO

BACKGROUND/AIM: We evaluated the clinical impact of FOLFOXIRI regimen aiming for conversion surgery in patients with unresectable multiple colorectal liver metastasis (CRLM). PATIENTS AND METHODS: A total of 42 patients with unresectable multiple CRLM who received chemotherapy with molecular agents were included in the analysis. The clinical results of FOLFOXIRI with other regimens were compared. RESULTS: The total conversion rate of 42 unresectable CRLM was 48.1%, and conversion cases had a better prognosis. Clinicopathological characteristics of conversion cases were more frequent in FOLFOXIRI induction, liver limited disease and maximum diameter × number (MDN) over 70. FOLFOXIRI achieved a higher conversion rate compared to other regimens (72.2% vs. 37.5%, p=0.0334), and significantly reduced the medication period until conversion surgery (median 5.8 courses) with a higher tumour necrotic rate. Consequently, the overall survival of conversion cases with FOLFOXIRI was better than that with other regimens (p=0.0055). CONCLUSION: FOLFOXIRI plus molecular agents might provide a higher probability of conversion surgery with a prognostic benefit.


Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Camptotecina/análogos & derivados , Neoplasias Colorretais/patologia , Neoplasias Hepáticas/secundário , Neoplasias Hepáticas/terapia , Protocolos de Quimioterapia Combinada Antineoplásica/efeitos adversos , Camptotecina/efeitos adversos , Camptotecina/uso terapêutico , Neoplasias Colorretais/diagnóstico , Terapia Combinada , Conversão para Cirurgia Aberta , Feminino , Fluoruracila/efeitos adversos , Fluoruracila/uso terapêutico , Hepatectomia , Humanos , Estimativa de Kaplan-Meier , Leucovorina/efeitos adversos , Leucovorina/uso terapêutico , Neoplasias Hepáticas/diagnóstico , Neoplasias Hepáticas/mortalidade , Masculino , Gradação de Tumores , Estadiamento de Neoplasias , Compostos Organoplatínicos/efeitos adversos , Compostos Organoplatínicos/uso terapêutico , Prognóstico , Resultado do Tratamento , Carga Tumoral
9.
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
11.
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
12.
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
13.
Int J Nanomedicine ; 14: 4397-4412, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31417251

RESUMO

Background: Graphene magnetite nanocomposites (G/Fe3O4) exhibit light photothermal conversion upon enhancement by 808 nm IR laser excitation. We evaluated the cytotoxic and photothermal effects of G/Fe3O4 on a HepG2 human liver cancer cell model. Methods: Graphene nanosheets (rGO), magnetite nanoparticles (Fe3O4), and G/Fe3O4 were prepared by chemical methods and characterized using transmission electron microscopy, Raman spectroscopy, zeta analysis, and vibrating sample magnemeter. Dark and light cytotoxicity were screened with colorimetric Sulforhodamine B cell viability assay after 24 and 48 hours. DNA fragmentation and some apoptotic genes on a transcriptional RNA level expression were performed. All prepared nanomaterials were evaluated for their photothermal effect at concentrations of 10 and 50 µg/mL. The power density incident on the cells by 300 mW 808 IR diode laser was 0.597 W/cm2. Results: Treatment of HepG2 with 400 µg/mL of rGO, Fe3O4, and G/Fe3O4 showed alteration in cell morphology after 24 hours of cell treatment and revealed toxic effects on cellular DNA. Evaluation of the cytotoxic effects showed messenger RNA (mRNA) in ß-actin and Bax apoptotic genes, but no expression of mRNA of caspase-3 after 24 hours of cell exposure, suggesting the involvement of an intrinsic apoptotic caspase-independent pathway. A photothermal effect was observed for G/Fe3O4 after irradiation of the HepG2 cells. A marked decrease was found in cell viability when treated with 10 and 50 µg/mL G/Fe3O4 from 40% to 5% after 48 hours of cell treatment. Conclusion: Results indicate that G/Fe3O4 nanocomposite was effective at transformation of light into heat and is a promising candidate for cancer therapy.


Assuntos
Grafite/química , Hipertermia Induzida , Raios Infravermelhos , Neoplasias Hepáticas/terapia , Nanopartículas de Magnetita/química , Modelos Biológicos , Nanocompostos/química , Fototerapia , Apoptose/genética , Sobrevivência Celular/genética , Fragmentação do DNA , Regulação Neoplásica da Expressão Gênica , Células Hep G2 , Humanos , Neoplasias Hepáticas/genética , Neoplasias Hepáticas/patologia , Nanopartículas de Magnetita/ultraestrutura , Nanocompostos/ultraestrutura , Oxirredução , Análise Espectral Raman , Eletricidade Estática , Difração de Raios X
14.
DNA Cell Biol ; 38(10): 1143-1146, 2019 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-31464522

RESUMO

Cervical carcinoma is associated with high-risk human papillomavirus (HPV) DNA integration and usually occurs after age 21 (peak 45 years), as reflected in screening guidelines. Between 1999 and 2008, cervical carcinoma rate in adolescents aged 15-19 years was 0.15 per 100,000. HPV-negative cervical carcinoma is rare in adolescents. The youngest previously reported case was 15 years old. Treatment options for cervical carcinoma are limited after first-line therapy. Immune checkpoint inhibitors blocking programmed death receptor (PD-1) and its ligand, PD-L1, have shown objective clinical responses and are tolerable in adults with gynecologic cancers. This class of agents is well tolerated in pediatric patients. PD-1/PD-L1 is commonly expressed in gynecologic cancers but its expression may not predict clinical response. We describe an exceptional response to single agent nivolumab postradiation therapy in a 13-year-old adolescent with poorly differentiated cervical carcinoma and widespread metastatic disease.


Assuntos
Antineoplásicos Imunológicos/uso terapêutico , Carcinoma/terapia , Neoplasias Hepáticas/terapia , Neoplasias Pulmonares/terapia , Nivolumabe/uso terapêutico , Neoplasias do Colo do Útero/terapia , Adolescente , Carboplatina/uso terapêutico , Carcinoma/secundário , Carcinoma/cirurgia , Feminino , Raios gama/uso terapêutico , Humanos , Histerectomia , Neoplasias Hepáticas/secundário , Neoplasias Hepáticas/cirurgia , Neoplasias Pulmonares/secundário , Neoplasias Pulmonares/cirurgia , Excisão de Linfonodo , Ovariectomia , Paclitaxel/uso terapêutico , Papillomaviridae , Salpingectomia , Resultado do Tratamento , Neoplasias do Colo do Útero/patologia , Neoplasias do Colo do Útero/cirurgia
15.
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
16.
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
17.
Nat Commun ; 10(1): 3051, 2019 07 11.
Artigo em Inglês | MEDLINE | ID: mdl-31296864

RESUMO

Treatment of liver metastasis experiences slow progress owing to the severe side effects. In this study, we demonstrate a strategy capable of eliminating metastatic cancer cells in a selective manner. Nucleus-targeting W18O49 nanoparticles (WONPs) are conjugated to mitochondria-selective mesoporous silica nanoparticles (MSNs) containing photosensitizer (Ce6) through a Cathepsin B-cleavable peptide. In hepatocytes, upon the laser irradiation, the generated singlet oxygen species are consumed by WONPs, in turn leading to the loss of their photothermally heating capacity, thereby sparing hepatocyte from thermal damage induced by the laser illumination. By contrast, in cancer cells, the cleaved peptide linker allows WONPs and MSNs to respectively target nucleus and mitochondria, where the therapeutic powers could be unleashed, both photodynamically and photothermally. This ensures the energy production of cancer cells can be abolished. We further assess the underlying molecular mechanism at both gene and protein levels to better understand the therapeutic outcome.


Assuntos
Portadores de Fármacos/metabolismo , Neoplasias Hepáticas/terapia , Fotoquimioterapia/métodos , Fármacos Fotossensibilizantes/administração & dosagem , Animais , Catepsina B/metabolismo , Núcleo Celular/metabolismo , Portadores de Fármacos/química , Feminino , Células HCT116 , Hepatócitos/citologia , Hepatócitos/metabolismo , Humanos , Injeções Intravenosas , Lasers , Fígado/citologia , Fígado/metabolismo , Fígado/patologia , Neoplasias Hepáticas/patologia , Neoplasias Hepáticas/secundário , Camundongos , Camundongos Endogâmicos BALB C , Camundongos Nus , Mitocôndrias/metabolismo , Nanopartículas/química , Nanopartículas/metabolismo , Fosforilação Oxidativa , Óxidos/química , Fotoquimioterapia/instrumentação , Espécies Reativas de Oxigênio , Dióxido de Silício/química , Resultado do Tratamento , Tungstênio/química , Ensaios Antitumorais Modelo de Xenoenxerto
18.
Nat Commun ; 10(1): 2993, 2019 07 05.
Artigo em Inglês | MEDLINE | ID: mdl-31278269

RESUMO

Activated hepatic stellate cell (aHSC)-mediated liver fibrosis is essential to the development of liver metastasis. Here, we discover intra-hepatic scale-up of relaxin (RLN, an anti-fibrotic peptide) in response to fibrosis along with the upregulation of its primary receptor (RXFP1) on aHSCs. The elevated expression of RLN serves as a natural regulator to deactivate aHSCs and resolve liver fibrosis. Therefore, we hypothesize this endogenous liver fibrosis repair mechanism can be leveraged for liver metastasis treatment via enforced RLN expression. To validate the therapeutic potential, we utilize aminoethyl anisamide-conjugated lipid-calcium-phosphate nanoparticles to deliver plasmid DNA encoding RLN. The nanoparticles preferentially target metastatic tumor cells and aHSCs within the metastatic lesion and convert them as an in situ RLN depot. Expressed RLN reverses the stromal microenvironment, which makes it unfavorable for established liver metastasis to grow. In colorectal, pancreatic, and breast cancer liver metastasis models, we confirm the RLN gene therapy results in significant inhibition of metastatic progression and prolongs survival. In addition, enforced RLN expression reactivates intra-metastasis immune milieu. The combination of the RLN gene therapy with PD-L1 blockade immunotherapy further produces a synergistic anti-metastatic efficacy. Collectively, the targeted RLN gene therapy represents a highly efficient, safe, and versatile anti-metastatic modality, and is promising for clinical translation.


Assuntos
Terapia Genética/métodos , Cirrose Hepática Experimental/terapia , Neoplasias Hepáticas/terapia , Hepatopatia Gordurosa não Alcoólica/terapia , Relaxina/genética , Animais , Antígeno B7-H1/antagonistas & inibidores , Antígeno B7-H1/imunologia , Tetracloreto de Carbono/administração & dosagem , Tetracloreto de Carbono/toxicidade , Linhagem Celular Tumoral/transplante , Progressão da Doença , Feminino , Técnicas de Transferência de Genes , Vetores Genéticos/genética , Células Estreladas do Fígado/metabolismo , Células Estreladas do Fígado/patologia , Humanos , Fígado/patologia , Cirrose Hepática Experimental/induzido quimicamente , Cirrose Hepática Experimental/patologia , Neoplasias Hepáticas/imunologia , Neoplasias Hepáticas/secundário , Camundongos , Nanopartículas/administração & dosagem , Nanopartículas/química , Hepatopatia Gordurosa não Alcoólica/etiologia , Hepatopatia Gordurosa não Alcoólica/patologia , Plasmídeos/genética , Receptores Acoplados a Proteínas-G/metabolismo , Relaxina/metabolismo , Resultado do Tratamento , Microambiente Tumoral/genética , Regulação para Cima
19.
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
20.
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
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