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

RESUMO

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


Assuntos
Carcinoma Hepatocelular/diagnóstico , Carcinoma Hepatocelular/patologia , Neoplasias Hepáticas/diagnóstico , Neoplasias Hepáticas/patologia , Células Neoplásicas Circulantes/metabolismo , Biomarcadores Tumorais , Carcinoma Hepatocelular/sangue , Contagem de Células , Humanos , Neoplasias Hepáticas/sangue , Recidiva Local de Neoplasia , Células Neoplásicas Circulantes/patologia , Razão de Chances , Prognóstico , Modelos de Riscos Proporcionais , Curva ROC , Sensibilidade e Especificidade , Análise de Sobrevida
2.
Nat Commun ; 11(1): 4489, 2020 09 07.
Artigo em Inglês | MEDLINE | ID: mdl-32895384

RESUMO

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


Assuntos
Biomarcadores Tumorais/isolamento & purificação , Carcinoma Hepatocelular/diagnóstico , Detecção Precoce de Câncer/métodos , Vesículas Extracelulares/genética , Neoplasias Hepáticas/diagnóstico , Idoso , Biomarcadores Tumorais/genética , Carcinoma Hepatocelular/sangue , Carcinoma Hepatocelular/genética , Carcinoma Hepatocelular/patologia , Estudos de Casos e Controles , Química Click/instrumentação , Química Click/métodos , Química Computacional , Simulação por Computador , Diagnóstico Diferencial , Dimetilpolisiloxanos/química , Progressão da Doença , Detecção Precoce de Câncer/instrumentação , Feminino , Células Hep G2 , Humanos , Dispositivos Lab-On-A-Chip , Biópsia Líquida/instrumentação , Biópsia Líquida/métodos , Cirrose Hepática/sangue , Cirrose Hepática/patologia , Neoplasias Hepáticas/sangue , Neoplasias Hepáticas/genética , Neoplasias Hepáticas/patologia , Masculino , Técnicas Analíticas Microfluídicas/instrumentação , Técnicas Analíticas Microfluídicas/métodos , Pessoa de Meia-Idade , Nanoestruturas/química , Nanofios/química , Estadiamento de Neoplasias , RNA Mensageiro/genética , RNA Mensageiro/isolamento & purificação , Curva ROC , Reação em Cadeia da Polimerase Via Transcriptase Reversa/instrumentação , Reação em Cadeia da Polimerase Via Transcriptase Reversa/métodos
3.
Anticancer Res ; 40(9): 5271-5276, 2020 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-32878816

RESUMO

BACKGROUND/AIM: Hepatic encephalopathy is an adverse event resulting from lenvatinib use in patients with hepatocellular carcinoma (HCC). We analyzed the influence of lenvatinib on portal venous flow velocity (PVV) and serum ammonia concentration. PATIENTS AND METHODS: Eleven patients with unresectable HCC were enrolled, including three with modified albumin-bilirubin (mALBI) grade 1, three with grade 2a, and five with grade 2b. PVV was measured by Doppler ultrasound sonography before and on day 2 of administration. RESULTS: Out of 11 patients, one developed hepatic encephalopathy. PVV was reduced in 10 patients, and the change from baseline was significantly correlated with lenvatinib dosage. The increase in serum ammonia concentration was affected by lenvatinib dose and baseline hepatic function as a threshold between mALBI grade 2a and 2b statistically. There was no correlation between changes in PVV and serum ammonia concentration. CONCLUSION: Lenvatinib might directly disturb hepatocyte metabolism to result in increased serum ammonia concentration.


Assuntos
Antineoplásicos/efeitos adversos , Carcinoma Hepatocelular/complicações , Carcinoma Hepatocelular/tratamento farmacológico , Hiperamonemia/etiologia , Neoplasias Hepáticas/complicações , Neoplasias Hepáticas/tratamento farmacológico , Compostos de Fenilureia/efeitos adversos , Inibidores de Proteínas Quinases/efeitos adversos , Quinolinas/efeitos adversos , Idoso , Idoso de 80 Anos ou mais , Antineoplásicos/administração & dosagem , Antineoplásicos/uso terapêutico , Bilirrubina/sangue , Carcinoma Hepatocelular/diagnóstico , Suscetibilidade a Doenças , Feminino , Encefalopatia Hepática/diagnóstico , Encefalopatia Hepática/etiologia , Humanos , Hiperamonemia/diagnóstico , Testes de Função Hepática , Neoplasias Hepáticas/diagnóstico , Masculino , Pessoa de Meia-Idade , Gradação de Tumores , Estadiamento de Neoplasias , Compostos de Fenilureia/administração & dosagem , Compostos de Fenilureia/uso terapêutico , Veia Porta/fisiopatologia , Inibidores de Proteínas Quinases/administração & dosagem , Inibidores de Proteínas Quinases/uso terapêutico , Quinolinas/administração & dosagem , Quinolinas/uso terapêutico , Fatores de Risco
4.
Zhonghua Yu Fang Yi Xue Za Zhi ; 54(9): 998-1002, 2020 Sep 06.
Artigo em Chinês | MEDLINE | ID: mdl-32907292

RESUMO

Objective: To investigate the clinical value of glypican-3 (GPC3) detection in the diagnosis and therapy-monitoring of primary hepatocellular carcinoma (HCC). Methods: From March 2018 to May 2019, the patients with HCC were enrolled as the experimental group(n=166)from Fudan University Shanghai Cancer Centre, while the specimens from health control group(n=94) and benign control group (n=50) were analyzed. The serum of GPC3 and alpha fetoprotein (AFP)levels were respectively detected by ELISA and chemiluminescence. GPC3 detections combined with AFP etc. in accuracy of HCC diagnosis were explored by using Logistic regression analysis. Results: The serum GPC3 level in patients with HCC [0.210 (0.048, 0.801)mg/L] [Median (quartile Q1, Q3)] was significantly higher than those in healthy controls [0.029(0.019, 0.052)mg/L] and benign controls [0.033(0.021, 0.043) mg/L] (Z=-7.69, P<0.001).The serum levels of aspartate aminotransferase (AST), alanine aminotransferase (ALT) and AFP were significantly different among the three groups (Z=-7.02, -6.85, -8.36 respectively, P<0.001). Among the serological indicators, it was related to ALT and AST (Z=-3.77, -4.09 respectively, P<0.001).The Cut-off level of GPC3 was determined as 0.077 mg/L by ROC curve. The sensitivity of the combined detection of serum GPC3 with AFP for HCC was up to 87.82%, the specificity was 77.86%, the negative predictive value was 84.29%, and the positive predictive value was 82.53%.The HCC-GPC3 model was constructed by using Logistic regression analysis. The area under the ROC curve was 0.882, the total sensitivity was 91.10%, and the total specificity was 72.73%. Further analysis showed that the serum GPC3 of patients with HCC was significantly lower [0.454(0.019, 0.286) mg/L] than that before surgery[0.608(0.039, 0.554)mg/L](Z=-7.32, P<0.001). Conclusion: The detection of serum GPC3 can be applied to aid diagnosis and therapy-monitoring of HCC.The combination of GPC3 and AFP can improve the diagnostic efficiency of HCC.


Assuntos
Carcinoma Hepatocelular , Neoplasias Hepáticas/diagnóstico , Biomarcadores Tumorais , China , Glipicanas , Humanos
5.
Rev Med Suisse ; 16(704): 1554-1559, 2020 Sep 02.
Artigo em Francês | MEDLINE | ID: mdl-32880111

RESUMO

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


Assuntos
Adenoma de Células Hepáticas , Neoplasias Hepáticas , Adenoma de Células Hepáticas/diagnóstico , Adenoma de Células Hepáticas/genética , Adenoma de Células Hepáticas/patologia , Adenoma de Células Hepáticas/terapia , Feminino , Humanos , Neoplasias Hepáticas/diagnóstico , Neoplasias Hepáticas/genética , Neoplasias Hepáticas/patologia , Neoplasias Hepáticas/terapia , Imagem por Ressonância Magnética , Mutação
6.
Medicine (Baltimore) ; 99(31): e21210, 2020 Jul 31.
Artigo em Inglês | MEDLINE | ID: mdl-32756098

RESUMO

RATIONALE: Procalcitonin (PCT) has been identified as a tumor biomarker in medullary thyroid carcinoma. Other neuroendocrine carcinomas with elevated PCT levels are relatively rare, and are mainly reported in the lung, digestive tract, and pancreas. No studies in the literature have reported a case of primary hepatic carcinoma complicated with unexpectedly elevated PCT levels. PATIENT CONCERNS: A 78-year-old man with persistent fatigue and mild fever was complicated with an extremely high PCT level. Radiological examination revealed a single hypodense lesion in the left lobe of the liver with a "rapid enhancement and rapid washout" pattern. Pathological analysis showed a poorly differentiated neuroendocrine carcinoma (grade 3) with multiple genetic mutations. DIAGNOSIS: Primary hepatic neuroendocrine carcinoma. INTERVENTIONS: The patient received antibiotic therapy and subsequent transcatheter hepatic arterial chemoembolization; a PCT assessment and computed tomography were performed during the follow-up. OUTCOMES: The PCT level did not decline after antibiotic therapy but greatly declined in response to effective transcatheter hepatic arterial chemoembolization. The patient survived and is still being followed up. LESSONS: An extremely elevated PCT level may raise a suspicion of a neuroendocrine carcinoma and plays an indicative role as a biomarker during therapy.


Assuntos
Carcinoma Neuroendócrino/diagnóstico , Neoplasias Hepáticas/diagnóstico , Pró-Calcitonina/sangue , Idoso , Biomarcadores Tumorais/sangue , Carcinoma Neuroendócrino/sangue , Carcinoma Neuroendócrino/diagnóstico por imagem , Carcinoma Neuroendócrino/terapia , Quimioembolização Terapêutica , Diagnóstico Diferencial , Humanos , Neoplasias Hepáticas/sangue , Neoplasias Hepáticas/diagnóstico por imagem , Neoplasias Hepáticas/terapia , Masculino , Tomografia Computadorizada por Raios X
7.
Medicine (Baltimore) ; 99(31): e21211, 2020 Jul 31.
Artigo em Inglês | MEDLINE | ID: mdl-32756099

RESUMO

RATIONALE: Within a rapidly expanding therapeutic armamentarium, the combination of everolimus (Eve) plus exemestane (Exe) utility needs to be reinstated in hormone receptor positive (HR+), human epidermal growth factor receptor 2 negative (HER2-) metastatic breast cancer (MBC). PATIENT CONCERNS: We herein report on a patient affected by HR+ HER2- MBC treated with radical surgery after neoadjuvant chemotherapy, who relapsed early on adjuvant tamoxifen, progressed rapidly on first line anastrozole, and failed treatment with third line capecitabine. DIAGNOSES: Metastatic luminal breast cancer progressed under standard endocrine therapy and chemotherapy. INTERVENTIONS: Third line with Eve plus Exe was given after chemotherapy. OUTCOMES: Patient experienced a 5-year progression free interval. LESSONS: Eve plus Exe remains a valid option in HR+HER2- MBC.


Assuntos
Neoplasias da Mama/diagnóstico , Carcinoma Lobular/diagnóstico , Neoplasias Hepáticas/diagnóstico , Androstadienos/administração & dosagem , Androstadienos/uso terapêutico , Protocolos de Quimioterapia Combinada Antineoplásica , Neoplasias da Mama/tratamento farmacológico , Neoplasias da Mama/mortalidade , Neoplasias da Mama/patologia , Carcinoma Lobular/tratamento farmacológico , Carcinoma Lobular/mortalidade , Carcinoma Lobular/patologia , Everolimo/administração & dosagem , Everolimo/uso terapêutico , Feminino , Humanos , Neoplasias Hepáticas/tratamento farmacológico , Neoplasias Hepáticas/mortalidade , Neoplasias Hepáticas/secundário , Pessoa de Meia-Idade , Pré-Menopausa , Intervalo Livre de Progressão
8.
Zhonghua Liu Xing Bing Xue Za Zhi ; 41(7): 1126-1137, 2020 Jul 10.
Artigo em Chinês | MEDLINE | ID: mdl-32741183

RESUMO

Objective: The objective of the study was systematically summarized the current status of the hepatocellular carcinoma (HCC) screening guidelines, and evaluated the HCC screening guidelines according to the authoritative framework of cancer screening guidelines of authoritative institutions, which provided important value for the formulation of HCC screening evidence-based guidelines. Methods: Literature search was conducted in multiple databases from their inception dates to January 3, 2019. In addition, we sought relevant websites further was searched to identify potentially eligible studies. Two reviewers independently screened literature and extracted data. Qualitative description of the basic information, recommendations of HCC screening, source of evidence and update progress of the HCC screening guidelines was conducted. Results: At present, there were no independent HCC screening guidelines worldwide. There were only 17 clinical practice HCC guidelines briefly provided the recommendation of HCC screening. Current HCC screening guidelines only recommended screening for high-risk groups of HCC. All guidelines have identified patients with chronic hepatitis B, hepatitis C and cirrhosis as high-risk groups for HCC. Most of guidelines recommended screening intervals was 6 months. The latest guidelines in Europe and the United States recommended ultrasound for screening HCC. The combination of ultrasound and AFP was recommended in the Asian guidelines. Currently, HCC screening guidelines mainly recommended screening strategies based on factors such as risk of HCC, accuracy of screening modality, screening cost, etc.. The key factors such as screening efficacy and safety have not yet been considered comprehensively. Conclusions: There were no independent HCC screening guidelines worldwide. Only some clinical practice HCC guidelines briefly mentioned HCC screening. Currently, the guidelines only recommend screening for high-risk groups of HCC, with a screening interval of 6 months. There are differences in screening modalities recommended by European, American and Asian guidelines for screening HCC. It is suggested that the relevant institutions should formulate the evidence-based HCC screening guidelines by referring to the theoretical framework of other authoritative other cancer screening guidelines.


Assuntos
Carcinoma Hepatocelular/diagnóstico , Detecção Precoce de Câncer , Neoplasias Hepáticas/diagnóstico , Guias de Prática Clínica como Assunto , Ásia , Europa (Continente) , Humanos , Estados Unidos
9.
Medicine (Baltimore) ; 99(32): e21630, 2020 Aug 07.
Artigo em Inglês | MEDLINE | ID: mdl-32769926

RESUMO

RATIONALE: Hepatocellular carcinoma (HCC) with intracavitary metastasis extending to the heart, also known as inferior vena cava (IVC) tumor thrombus, is an extremely rare late-stage disease with no effective treatment. In fact, the median survival is reportedly less than 2 months; thus, there is an urgent need for better treatment. PATIENT CONCERNS: In this study, a 48-year-old patient was admitted to our hospital to seek medical treatment for advanced primary HCC with right atrial metastasis. DIAGNOSIS: The patient was diagnosed as primary HCC with a large mass in the right lobe of the liver and intracavitary metastasis to the right atrium. INTERVENTIONS: A new surgical treatment of right hemihepatectomy, complete resection of the involved IVC and the right atrium thrombus, plus reconstruction of the resected IVC using autologous pericardial tube graft were undertaken and successfully performed. OUTCOMES: The patient recovered rapidly, and 14 days after the surgical procedures, he was discharged from the hospital. Notably, serum levels of alpha-fetoprotein dropped to normal range and no clinical signs of recurrence were observed during follow-up. LESSONS: This report highlights an unusual case of right atrial metastasis from HCC. The surgical treatment appeared to be suitable and effective, together with postoperative administration of lenvatinib, a tyrosine kinase multitarget inhibitor selected by performing whole-exome sequencing. These therapies have offered favorable clinical outcomes such as prevention of recurrence and prolongation of patient survival. In addition, clinicians may benefit from our experience for their future treatment of patients with similar clinical conditions.


Assuntos
Carcinoma Hepatocelular/cirurgia , Átrios do Coração/anormalidades , Metástase Neoplásica/diagnóstico , Carcinoma Hepatocelular/complicações , Átrios do Coração/cirurgia , Hepatectomia/métodos , Humanos , Neoplasias Hepáticas/diagnóstico , Neoplasias Hepáticas/diagnóstico por imagem , Neoplasias Hepáticas/cirurgia , Masculino , Pessoa de Meia-Idade , Metástase Neoplásica/fisiopatologia , Metástase Neoplásica/terapia , Tomografia Computadorizada por Raios X/métodos , Resultado do Tratamento , Veia Cava Inferior/cirurgia
10.
Medicine (Baltimore) ; 99(32): e21652, 2020 Aug 07.
Artigo em Inglês | MEDLINE | ID: mdl-32769936

RESUMO

To investigate the diagnostic value of multimodal ultrasound imaging composed of conventional ultrasonography (US), contrast-enhanced ultrasonography (CEUS), and shear wave elastography (SWE) for liver tumors.Between October 2017 and October 2019, US, CEUS, and SWE examinations of a total of 158 liver tumors in 136 patients at The First Affiliated Hospital of Nanchang University were performed. The histopathological or imaging diagnostic results were used as controls to evaluate the sensitivity, specificity, accuracy, positive predictive value, and negative predictive value of US, CEUS, SWE, and multimodal ultrasound imaging, which combines these 3 modes, in the differential diagnosis of benign and malignant liver tumors.Among the 158 tumors, there were 64 benign tumors, including 55 cases of hepatic hemangioma, 3 cases of focal nodular hyperplasia of the liver, 4 cases of hepatic cyst, and 2 cases of focal nonuniform distribution of fat in the liver. There were 94 malignant tumors, including 32 cases of hepatocellular carcinoma, 22 cases of intrahepatic cholangiocellular carcinoma, 29 cases of metastatic liver cancer, and 11 cases of dysplastic nodules in cirrhotic liver. In the diagnosis of benign and malignant liver tumors, the sensitivity, specificity, accuracy, positive predictive value, and negative predictive value were 82.56%, 68.06%, 75.96%, 75.53%, and 76.56% for US; 92.39%, 86.36%, 89.87%, 90.43%, and 89.06% for CEUS; 87.14%, 76.81%, 82.91%, 82.98%, and 82.81% for SWE; and 97.85%, 95.38%, 96.83%, 96.81%, and 96.88% for multimodal ultrasound imaging, respectively. The sensitivity, specificity, accuracy, positive predictive value, and negative predictive value were all significantly higher for multimodal ultrasound imaging than those values for US, CEUS, and SWE (all P < .05). The areas under the receiver operating characteristic curve for US, CEUS, SWE, and multimodal ultrasound imaging in the diagnosis of benign and malignant liver tumors were 0.760, 0.897, 0.829, and 0.968, respectively.US, CEUS, and SWE all have diagnostic value in the diagnosis of benign and malignant liver tumors. Multimodal ultrasound imaging could significantly increase the accuracy of the diagnosis of benign and malignant liver tumors and has higher value for clinical application.


Assuntos
Neoplasias Hepáticas/diagnóstico por imagem , Ultrassonografia/métodos , Adulto , Idoso , Idoso de 80 Anos ou mais , China , Meios de Contraste/uso terapêutico , Técnicas de Imagem por Elasticidade/métodos , Feminino , Humanos , Fígado/diagnóstico por imagem , Neoplasias Hepáticas/diagnóstico , Masculino , Pessoa de Meia-Idade , Imagem Multimodal/instrumentação , Imagem Multimodal/métodos , Ultrassonografia/instrumentação
11.
J Infect Public Health ; 13(9): 1274-1289, 2020 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-32758393

RESUMO

Cancer is a fatal illness often caused by genetic disorder aggregation and a variety of pathological changes. Cancerous cells are abnormal areas often growing in any part of human body that are life-threatening. Cancer also known as tumor must be quickly and correctly detected in the initial stage to identify what might be beneficial for its cure. Even though modality has different considerations, such as complicated history, improper diagnostics and treatement that are main causes of deaths. The aim of the research is to analyze, review, categorize and address the current developments of human body cancer detection using machine learning techniques for breast, brain, lung, liver, skin cancer leukemia. The study highlights how cancer diagnosis, cure process is assisted using machine learning with supervised, unsupervised and deep learning techniques. Several state of art techniques are categorized under the same cluster and results are compared on benchmark datasets from accuracy, sensitivity, specificity, false-positive metrics. Finally, challenges are also highlighted for possible future work.


Assuntos
Aprendizado de Máquina , Neoplasias/diagnóstico , Neoplasias Encefálicas/diagnóstico , Neoplasias da Mama/diagnóstico , Feminino , Humanos , Processamento de Imagem Assistida por Computador , Neoplasias Hepáticas/diagnóstico , Neoplasias Pulmonares/diagnóstico , Imagem por Ressonância Magnética , Masculino , Neoplasias/terapia , Leucemia-Linfoma Linfoblástico de Células Precursoras/diagnóstico , Sensibilidade e Especificidade , Neoplasias Cutâneas/diagnóstico , Inquéritos e Questionários , Tomografia Computadorizada por Raios X
12.
Int J Nanomedicine ; 15: 4933-4941, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32764926

RESUMO

Purpose: The aim of this study was to develop an avidin-modified macromolecular lipid magnetic sphere and its application in differential diagnosis of liver disease and liver cancer. Materials and Methods: Lectin-modified macromolecular lipid magnetic spheres were prepared by thin-film hydration method using lentil lectin derivatives (LCA-HQ) and cholesterol as raw materials. Alpha-fetoprotein variants (AFP-L3) in serum from healthy people, liver disease and liver cancer patients were isolated using the prepared lectin-modified macromolecular lipid magnetic spheres, and alpha-fetoprotein (AFP) and AFP-L3 were detected by fully automatic time-resolved fluorescence immunoassay. Results: The lectin polymer lipid magnetic sphere prepared in this study was superparamagnetic and encapsulated by a lectin derivative. There was no significant difference in the recovery rate of AFP-L3 between avidin magnetic ball-automatic time-resolved fluorescence immunoassay and manual micro-affinity column method (p>0.05). We found that AFP-L3 can be used as a differential indicator between liver cancer and liver disease. The positive rate of AFP and AFP-L3 in liver cancer patients was higher than that in healthy people and liver disease patients (p<0.001). The AUC (95% CI) of AFP and AFP-L3 were 0.743 ± 0.031 and 0.850 ± 0.024, respectively. AFP-L3 AUC value is greater than AFP; therefore, AFP-L3 distinguishes liver cancer more accurately, and the difference is statistically different, p<0.05. Conclusion: We proposed a novel method for integration of the lectin polymer lipid magnetic spheres and time-resolved fluorescence immunoassay that enables simple, accurate and rapid determination of AFP-L3 in clinical samples. To be noted, fully automatic time-resolved fluorescence immunoassay compared with the commonly used techniques in clinical practice, the measurement procedure is simple and is expected to be used for the detection and accurate diagnosis of liver cancer.


Assuntos
Fluorescência , Lipossomos/química , Neoplasias Hepáticas/diagnóstico , Mutação , Polímeros/química , alfa-Fetoproteínas/genética , alfa-Fetoproteínas/metabolismo , Adulto , Área Sob a Curva , Automação , Biomarcadores Tumorais/sangue , Feminino , Humanos , Imunoensaio/métodos , Neoplasias Hepáticas/sangue , Imãs/química , Masculino , Pessoa de Meia-Idade , Fatores de Tempo
13.
PLoS One ; 15(8): e0237475, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32790728

RESUMO

BACKGROUND AND AIMS: Direct-acting antivirals (DAAs) against hepatitis C virus (HCV) exert high anti-HCV activity and are expected to show anti-inflammatory effects associated with HCV elimination. Furthermore, hepatocellular carcinoma (HCC) is known to dedifferentiate from hypovascular tumors, such as dysplastic nodules or well-differentiated HCC, to hypervascular tumors. We therefore explored whether or not DAAs can suppress the growth and hypervascularization of hypovascular tumors. METHODS: We enrolled 481 patients with HCV genotype 1 infection who were treated with Daclatasvir and Asunaprevir therapy. Of these, 29 patients had 33 hypovascular tumors, which were confirmed by contrast-enhanced MRI or CT before therapy. We prospectively analyzed the cumulative incidence of HCC, i.e. the growth or hypervascularization of hypovascular tumors, and compared the HCC development rates between patients with hypovascular tumors and those without any tumors. RESULTS: The mean size of the hypovascular tumors was 11.3 mm. Twenty seven of 29 patients who achieved an SVR had 31 nodules, 19 of 31 nodules (61.3%) showed tumor growth or hypervascularization, and 12 (38.7%) nodules showed no change or improvement. The cumulative incidence rates of tumor growth or hypervascularization were 19.4% at 1 year, 36.0% at 2 years, 56.6% at 3 years, and 65.3% at 4 years. Among the patients who achieved a sustained virologic response, the cumulative HCC development rates of patients with hypovascular tumors was significantly higher than in those without any tumors. A Cox proportional hazard analysis showed that a history of HCC therapy, the presence of a hypovascular tumor, and AFP >4.6 ng/mL at the end of treatment were independent risk factors for HCC development. CONCLUSION: Hypovascular tumors developed into HCC at a high rate despite the elimination of HCV by DAAs. As patients with hypovascular tumors were shown to have a high risk of HCC development, they should undergo strict HCC surveillance.


Assuntos
Antivirais/uso terapêutico , Carcinoma Hepatocelular/diagnóstico , Hepatite C Crônica/tratamento farmacológico , Neoplasias Hepáticas/diagnóstico , Idoso , Carcinoma Hepatocelular/complicações , Carcinoma Hepatocelular/epidemiologia , Feminino , Genótipo , Hepacivirus/genética , Hepacivirus/isolamento & purificação , Hepatite C Crônica/complicações , Hepatite C Crônica/virologia , Humanos , Imidazóis/uso terapêutico , Incidência , Isoquinolinas/uso terapêutico , Cirrose Hepática/diagnóstico , Neoplasias Hepáticas/complicações , Neoplasias Hepáticas/epidemiologia , Masculino , Pessoa de Meia-Idade , Modelos de Riscos Proporcionais , Fatores de Risco , Sulfonamidas/uso terapêutico , Resposta Viral Sustentada , alfa-Fetoproteínas/análise
16.
Life Sci ; 257: 118131, 2020 Sep 15.
Artigo em Inglês | MEDLINE | ID: mdl-32710948

RESUMO

AIMS: ATP-binding cassette (ABC) transporters constitute one of the largest families of membrane proteins in most organisms; however, their functions in hepatocellular carcinoma (HCC) remain unclear. MAIN METHODS: A set of bioinformatic tools was integrated to analyze the expression of 49 members of the ABC transporter family. The function of members which had prognostic values in HCC was explored by gene ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analysis. KEY FINDINGS: ABCA8 and ABCA9 were significantly down-regulated in HCC. Prognostic analysis indicated that HCC patients with low expression of ABCA8 and ABCA9 had significantly shorter survival time. On the contrary, ABCB6 was over-expressed in the disease and high expression of ABCB6 was associated with worse prognosis. Co-expression analysis, and subsequently GO and KEGG analysis indicated that ABCA8 and ABCA9 might participate in the catabolic processes of multiple metabolites, while ABCB6 might regulate ferroptosis. SIGNIFICANCE: This study reveals a previously unrecognized function of ABCB6 in HCC, by regulating ferroptosis. Since ABCB6 is over-expressed in HCC and ferroptosis involves in cancer development, ABCB6 might be a promising therapeutic target in the disease.


Assuntos
Transportadores de Cassetes de Ligação de ATP/metabolismo , Carcinoma Hepatocelular/metabolismo , Ferroptose , Neoplasias Hepáticas/metabolismo , Carcinoma Hepatocelular/diagnóstico , Carcinoma Hepatocelular/mortalidade , Regulação Neoplásica da Expressão Gênica , Humanos , Neoplasias Hepáticas/diagnóstico , Neoplasias Hepáticas/mortalidade , Prognóstico , Mapas de Interação de Proteínas , Análise de Sobrevida
17.
PLoS One ; 15(7): e0235623, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32614932

RESUMO

Pancreatic cancer is an aggressive, solid tumor, with a grave prognosis. Despite surgical treatment in patients with pancreatic cancer, the rate of recurrence is high. In addition, although tumor biomarkers are frequently used to confirm advanced pancreatic cancer, this is not accurate and the biomarkers currently used cannot indicate prognosis. This study sought to evaluate circulating tumor DNA as a tumor biomarker to prognosticate pancreatic cancer. Patients with advanced pancreatic cancer and liver metastasis (N = 104) were included, and blood samples were collected from all patients. The mutant allele frequency was measured using amplicon-based deep sequencing on a cell-free DNA panel covering 14 genes with > 240 hot spots. In patients with advanced pancreatic cancer, 50% (N = 52) had detectable ctDNA levels, with TP53 (45%, N = 47) and KRAS (42.3%, N = 44) mutations the most common. Patients with detectable circulating tumor DNA levels also had significantly worse overall survival and progression free survival than ctDNA negative patients (8.4 vs 16 months, P<0.0001 for overall survival; 3.2 vs 7.9 months, P<0.0001 for progression-free survival). In a multivariate analysis, ctDNA status was independently associated with overall survival and progression-free survival (HR = 3.1, 95%CI = 1.9-5.0, P<0.0001; HR 2.6, 95%CI = 1.7-4.0, P<0.0001, respectively). Moreover, circulating tumor DNA significantly correlated with a higher number of liver metastases, the presence of lung and/or peritoneal metastases, tumor burden, and higher carbohydrate antigen 19-9 levels. This study supports the use of circulating tumor DNA as an independent prognostic marker for advanced pancreatic cancer.


Assuntos
Biomarcadores Tumorais/sangue , DNA Tumoral Circulante/sangue , Neoplasias Hepáticas/diagnóstico , Neoplasias Pancreáticas/patologia , Adulto , Idoso , Idoso de 80 Anos ou mais , Antineoplásicos/uso terapêutico , Biomarcadores Tumorais/genética , Antígeno CA-19-9/sangue , Ácidos Nucleicos Livres/metabolismo , Feminino , Humanos , Estimativa de Kaplan-Meier , Neoplasias Hepáticas/secundário , Masculino , Pessoa de Meia-Idade , Estadiamento de Neoplasias , Neoplasias Pancreáticas/tratamento farmacológico , Neoplasias Pancreáticas/mortalidade , Prognóstico , Intervalo Livre de Progressão , Proteínas Proto-Oncogênicas p21(ras)/genética , Proteína Supressora de Tumor p53/genética
18.
Zhonghua Zhong Liu Za Zhi ; 42(6): 469-473, 2020 Jun 23.
Artigo em Chinês | MEDLINE | ID: mdl-32575942

RESUMO

Objective: To investigate the characteristics of contrast-enhanced ultrasound (CEUS) in alpha-fetoprotein (AFP)-negative recurrent small hepatocellular carcinoma (rsHCC). Methods: The imaging characteristics of CEUS were retrospectively analyzed in 132 lesions from 116 patients with rsHCC, including 59 lesions from 51 AFP-negative patients and 73 lesions from 65 AFP-positive patients. The hemodynamic parameters such as contrast-enhanced onset time, time-to-peak, isoenhancement start time, low-enhancement start time, and perfusion mode were compared between two groups. Results: The time-to-peak, isoenhancement start time, low-enhancement start time of AFP-negative group were significantly increased than those in AFP-positive group (23.22±5.08)s vs. (20.30±3.41)s, (59.44±39.75)s vs. (40.75±16.16)s, (102.89±44.45)s vs. (87.08±25.27)s (all of P<0.05). Meanwhile, the proportion of isoenhancement during the portal and late phases in AFP-negative group was significantly higher than those in AFP-positive group (59.3% vs. 37.0%, 16.9% vs. 4.1%; all of P<0.05). However, there was no significant difference between the two groups in the enhancement start time (14.87±6.00)s vs. (14.35±5.30)s (P>0.05) as well as isoenhancement proportion in the arterial phase (94.9% vs. 98.6%, P>0.05). Conclusions: The enhancement pattern of CEUS in AFP-negative rsHCC patients was "fast-in and slow-out" with a diverse and atypical trend. Recognizing its regular features will facilitate the early detection of AFP-negative rsHCC.


Assuntos
Carcinoma Hepatocelular/diagnóstico por imagem , Meios de Contraste , Neoplasias Hepáticas/diagnóstico por imagem , Ultrassonografia/métodos , Carcinoma Hepatocelular/diagnóstico , Humanos , Aumento da Imagem/métodos , Neoplasias Hepáticas/diagnóstico , Neoplasias Hepáticas/patologia , Estudos Retrospectivos , alfa-Fetoproteínas
19.
Eur J Endocrinol ; 183(3): R57-R73, 2020 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-32508312

RESUMO

Non-alcoholic fatty liver disease (NAFLD) is a growing health problem with a global prevalence of over 25% and prevalence rates of over 60% in high-risk populations. It is considered the hepatic component of the metabolic syndrome and is associated with an increased risk of the development of various liver-associated and cardiometabolic complications. Given the complexity of NAFLD and associated comorbidities and complications, treatment requires interventions from a variety of different healthcare specialties. However, many clinicians are currently insufficiently aware of the potential harm and severity of NAFLD and associated comorbidities, complications and the steps that should be taken when NAFLD is suspected. Recognizing which patients suffer from non-progressive simple steatosis, metabolically active NASH with high risk of developing cardiovascular disease and which patients have a high risk of developing cirrhosis and hepatocellular carcinoma is important. Unfortunately, this can be difficult and guidelines towards the optimal diagnostic and therapeutic approach are ambivalent. Here we review the pathogenesis, diagnostics and treatment of NAFLD and discuss how multidisciplinary care path development could move forward.


Assuntos
Doenças Cardiovasculares/diagnóstico , Doenças Cardiovasculares/patologia , Hepatopatia Gordurosa não Alcoólica/diagnóstico , Hepatopatia Gordurosa não Alcoólica/patologia , Animais , Carcinoma Hepatocelular/diagnóstico , Carcinoma Hepatocelular/tratamento farmacológico , Carcinoma Hepatocelular/patologia , Carcinoma Hepatocelular/cirurgia , Doenças Cardiovasculares/tratamento farmacológico , Doenças Cardiovasculares/cirurgia , Humanos , Fígado/patologia , Neoplasias Hepáticas/diagnóstico , Neoplasias Hepáticas/tratamento farmacológico , Neoplasias Hepáticas/patologia , Neoplasias Hepáticas/cirurgia , Hepatopatia Gordurosa não Alcoólica/tratamento farmacológico , Hepatopatia Gordurosa não Alcoólica/cirurgia
20.
Cancer Sci ; 111(9): 3338-3349, 2020 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-32506598

RESUMO

Exosomal long noncoding RNA (lncRNA) has been found to be associated with the development of cancers. However, the expression characteristics and the biological roles of exosomal lncRNAs in hepatocellular carcinoma (HCC) remain unknown. Here, by RNA sequencing, we found 9440 mRNAs and 8572 lncRNAs were differentially expressed (DE-) in plasma exosomes between HCC patients and healthy controls. Exosomal DE-lncRNAs displayed higher expression levels and tissue specificity, lower expression variability and splicing efficiency than DE-mRNAs. Six candidate DE-lncRNAs (fold change 6 or more, P ≤ .01) were high in HCC cells and cell exosomes. The knockdown of these candidate DE-lncRNAs significantly affected the migration, proliferation, and apoptosis in HCC cells. In particular, a novel DE-lncRNA, RP11-85G21.1 (lnc85), promoted HCC cellular proliferation and migration by targeted binding and regulating of miR-324-5p. More importantly, the level of serum lnc85 was highly expressed in both Alpha-fetoprotein (AFP)-positive and AFP-negative HCC patients and allowed distinguishing AFP-negative HCC from healthy control and liver cirrhosis (area under the receiver operating characteristic curve, 0.869; sensitivity, 80.0%; specificity, 76.5%) with high accuracy. Our finding offers a new insight into the association between the dysregulation of exosomal lncRNA and HCC, suggesting that lnc85 could be a potential biomarker of HCC.


Assuntos
Biomarcadores Tumorais , Carcinoma Hepatocelular/genética , Carcinoma Hepatocelular/metabolismo , Ácidos Nucleicos Livres , Exossomos/metabolismo , Neoplasias Hepáticas/genética , Neoplasias Hepáticas/metabolismo , RNA Longo não Codificante/genética , Adulto , Processamento Alternativo , Carcinoma Hepatocelular/diagnóstico , Feminino , Regulação Neoplásica da Expressão Gênica , Sequenciamento de Nucleotídeos em Larga Escala , Humanos , Neoplasias Hepáticas/diagnóstico , Masculino , MicroRNAs , Pessoa de Meia-Idade , Fenótipo , RNA Mensageiro , Curva ROC , Análise de Sequência de RNA
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