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1.
Oncology ; 98(11): 779-786, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32877911

RESUMO

BACKGROUND AND AIMS: Lenvatinib is an oral anticancer drug for patients with unresectable advanced hepatocellular carcinoma (HCC). We evaluated whether a reduction in tumor stain at 2 weeks after lenvatinib treatment in patients with unresectable HCC is a predictor of early treatment efficacy at 12 weeks. PATIENTS AND METHODS: Of the 23 patients who initiated lenvatinib treatment between April 2018 and January 2019, treatment efficacy was measured in 15 patients for more than 12 weeks after treatment. Changes in tumor stain, tumor size on contrast-enhanced computed tomography (CT), and serum levels of tumor markers were evaluated 2 weeks after lenvatinib treatment. Therapeutic efficacy was assessed by tumor stain and tumor size by contrast-enhanced CT within the first 12 weeks, according to the modified Response Evaluation Criteria in Solid Tumors (mRECIST) guidelines. RESULTS: At 12 weeks, efficacy evaluation of 15 patients revealed that 11 of them experienced partial responses, for a response rate of 73.3%. In the first 2 weeks, 13 patients (86.7%) experienced a decreased tumor stain, including 10 responders (90.9%) and 3 non-responders (75.0%). All patients in the non-responder group had required a lenvatinib dose reduction due to adverse events within 12 weeks. On contrast-enhanced CT, the change rate of tumor stain to HCC at 2 weeks after treatment was <0.8 among 10 responders (90.9%) and 1 non-responder (25.0%; p = 0.033). No significant differences between responders and non-responders were observed with regard to most characteristics at baseline and at 2 weeks after treatment initiation. However, significant differences were observed between groups in the presence or absence of a dose suspension period, the presence or absence of lenvatinib dose reduction from the maximum value during the first 2 weeks, and decreased tumor stain at 2 weeks after treatment initiation. CONCLUSION: Reduction in tumor stain at 2 weeks after lenvatinib treatment may be an early biomarker of efficacy at 12 weeks in patients with unresectable HCC.


Assuntos
Carcinoma Hepatocelular/tratamento farmacológico , Carcinoma Hepatocelular/patologia , Neoplasias Hepáticas/tratamento farmacológico , Neoplasias Hepáticas/patologia , Compostos de Fenilureia/uso terapêutico , Quinolinas/uso terapêutico , Idoso , Idoso de 80 Anos ou mais , Antineoplásicos/uso terapêutico , Biomarcadores/sangue , Carcinoma Hepatocelular/sangue , Carcinoma Hepatocelular/diagnóstico por imagem , Feminino , Humanos , Neoplasias Hepáticas/sangue , Neoplasias Hepáticas/diagnóstico por imagem , Masculino , Pessoa de Meia-Idade , Estudos Prospectivos , Inibidores de Proteínas Quinases/uso terapêutico , Precursores de Proteínas/sangue , Protrombina , Critérios de Avaliação de Resposta em Tumores Sólidos , Coloração e Rotulagem/métodos , Tomografia Computadorizada por Raios X , alfa-Fetoproteínas/metabolismo
2.
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
3.
J Cancer Res Clin Oncol ; 146(10): 2439-2446, 2020 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-32725355

RESUMO

Hepatocellular carcinoma (HCC) is one of the most common malignant tumors in the world. Alpha-fetoprotein (AFP) is considered as a diagnostic and prognostic tumorous marker for HCC, and up to 70% of HCC patients showed elevated serum levels of AFP. In the past two decades, evidences have shown that AFP not only is a tumorous biomarker for diagnosing HCC, but also plays a very complicated role in regulating proliferation, apoptosis, and autophagy and inhibiting the immune response of cells. Because AFP is significantly elevated during hepatocarcinogenesis, the role of AFP in the development of HCC is a scientific problem worthy of further exploration. In this review, we reviewed the effects of AFP on hepatocyte malignant transformation and the underlying mechanisms involved in the progression of HCC.


Assuntos
Carcinoma Hepatocelular/metabolismo , Carcinoma Hepatocelular/patologia , Neoplasias Hepáticas/metabolismo , Neoplasias Hepáticas/patologia , alfa-Fetoproteínas/metabolismo , Apoptose/fisiologia , Carcinoma Hepatocelular/genética , Transformação Celular Neoplásica , Progressão da Doença , Humanos , Neoplasias Hepáticas/genética , alfa-Fetoproteínas/biossíntese , alfa-Fetoproteínas/genética
4.
Gulf J Oncolog ; 1(33): 64-67, 2020 May.
Artigo em Inglês | MEDLINE | ID: mdl-32476652

RESUMO

BACKGROUND: Alpha-fetoprotein (AFP) is a serum tumor marker used in the past for surveillance and screening of hepatocellular carcinoma (HCC) in patients with cirrhosis. Its prognostic value is still debated in the literature. The aim of this study was to evaluate the prognostic impact of the AFP rate at diagnosis on the overall survival of patients with a small HCC (<3cm) in patients with cirrhosis. PATIENTS AND METHODS: Among the 122 patients diagnosed with HCC during the study period, 49 patients had a small HCC at diagnosis, including 40,8% (N 20) patients with a negative AFP (group I) and 59,18% (N 29) with an AFP >10 ng / ml (group II). Both groups of patients were comparable for age and WHO status (World Health Organization). Patient survival was assessed by the Kaplan-Meier method. The survival at 5 years was 35.7% in group 1 vs 12.3% in group 2. The AFP level was identified as an independent prognostic factor of survival. CONCLUSION: Alpha-fetoprotein serum positivity seems to have prognostic value in patients with single small HCC.


Assuntos
Carcinoma Hepatocelular/diagnóstico , Neoplasias Hepáticas/diagnóstico , alfa-Fetoproteínas/metabolismo , Carcinoma Hepatocelular/mortalidade , Feminino , Humanos , Neoplasias Hepáticas/mortalidade , Masculino , Pessoa de Meia-Idade , Prognóstico , Estudos Retrospectivos
5.
Am J Gastroenterol ; 115(10): 1642-1649, 2020 10.
Artigo em Inglês | MEDLINE | ID: mdl-32530829

RESUMO

INTRODUCTION: The value of hepatocellular carcinoma (HCC) surveillance is defined by the balance of benefits, i.e., early tumor detection, and potential harms, related to false positive and indeterminate results. Although physical harms can be observed in 15%-20% of patients with cirrhosis undergoing HCC surveillance, previous cost-effectiveness analyses have not incorporated costs of harms. We aimed to evaluate the cost-effectiveness of HCC surveillance including both benefits and harms. DESIGN: We constructed a Markov model to compare surveillance strategies of ultrasound (US) alone, US and alpha fetoprotein (AFP), and no surveillance in 1 million simulated patients with compensated cirrhosis. Harms included imaging and biopsy in patients undergoing surveillance for HCC. Model inputs were based on literature review, and costs were derived from the Medicare fee schedule, with all costs inflated to 2018 dollars. The primary outcome was the incremental cost-effectiveness ratio per incremental quality-adjusted life-year. RESULTS: In the base case analysis, US with AFP was the dominant strategy over both US alone and no surveillance. In a probabilistic sensitivity analysis, US with AFP was the most cost-effective strategy in 80.1% of simulations at a willingness-to-pay threshold of $100,000 per quality-adjusted life-year. In our threshold analyses, an HCC incidence >0.4% per year and surveillance adherence >19.5% biannually were necessary for US with AFP to be cost-effective compared with no surveillance. DISCUSSION: Accounting for both surveillance-related benefits and harms, US and AFP is more cost-effective for HCC surveillance than US alone or no surveillance in patients with compensated cirrhosis.


Assuntos
Carcinoma Hepatocelular/diagnóstico , Detecção Precoce de Câncer/métodos , Cirrose Hepática/terapia , Neoplasias Hepáticas/diagnóstico , Ultrassonografia/métodos , alfa-Fetoproteínas/metabolismo , Carcinoma Hepatocelular/economia , Carcinoma Hepatocelular/etiologia , Carcinoma Hepatocelular/metabolismo , Análise Custo-Benefício , Técnicas de Apoio para a Decisão , Detecção Precoce de Câncer/economia , Humanos , Fígado/diagnóstico por imagem , Fígado/patologia , Cirrose Hepática/complicações , Neoplasias Hepáticas/economia , Neoplasias Hepáticas/etiologia , Neoplasias Hepáticas/metabolismo , Cadeias de Markov , Dano ao Paciente , Anos de Vida Ajustados por Qualidade de Vida , Ultrassonografia/economia , Estados Unidos
6.
Zhonghua Zhong Liu Za Zhi ; 42(5): 396-402, 2020 May 23.
Artigo em Chinês | MEDLINE | ID: mdl-32482029

RESUMO

Objective: To investigate the differential gene expression profiles of alpha-fetoprotein (AFP) high- and low-expressing hepatocellular carcinoma (HCC), and to provide a theoretical basis for the molecular mechanism and prognosis analysis of HCC. Methods: The transcriptome data and related clinical information from 368 HCC cases were obtained from the Cancer Gene Atlas (TCGA) public database. The samples were divided into AFP high expression (AFP(high)) group and low expression (AFP(low)) group according to the quartile of AFP mRNA expression, with 92 cases in each group. The differential gene analysis was carried out using the DEseq2 package in the R software. The functional and KEGG pathway enrichment analysis of the differential genes was performed using ClusterProfiler package. The protein-protein interaction network was constructed to screen hub genes using the String database and Cytoscape software. The single-sample GSEA analysis was performed to enrich and score signature gene sets using the GSVA package. And then RNAseq data and real-time quantitative polymerase chain reaction (RT-qPCR) were used for independent dataset validation and tissue validation. Results: The clinical analysis showed that high expression of AFP was significantly associated with poor pathological differentiation and ethnicity (P<0.05 for both). A total of 1 382 differential genes were obtained by bioinformatics analysis, of which 931 genes were up-regulated and 451 genes were down-regulated in AFP(high) group. GO enrichment analysis showed that the highly expressed genes were mainly correlated with the processes of appendage development, limb development, and skeletal system development, while lowly expressed genes were related to metabolic-related processes such as xenobiotic metabolism, steroid metabolism, and cellular response to xenobiotic stimuli. KEGG pathway enrichment analysis revealed that highly expressed genes were mainly involved in primary immunodeficiency, neuroactive ligand-receptor interaction, and cytokine-cytokine receptor interaction, while lowly expressed genes were mainly involved in retinol metabolism, chemical carcinogenesis, steroid hormone biosynthesis and other pathways. A prognostic related gene set that was consisted of AURKB, TTK, CENPA, UBE2C, HJURP, and KIF15 was identified. And the high expression of this gene set was related to the shorter recurrence-free survival and overall survival time in HCC patients, and its enrichment score was positively correlated with AFP expression (r=0.475, P<0.001). The validation results of RNAseq data were basically consistent with the TCGA data. The RT-qPCR results showed that AURKB, KIF15, and UBE2C were significantly overexpressed in HCC tissues with high AFP expression. Although the expression of AURKB, TTK, KIF15, and UBE2C was not related to recurrence-free survival and overall survival of HCC patients, there was a tendency that the patients with high AFP levels showed relatively shorter recurrence-free survival time and overall survival time. Conclusions: There is a large difference in gene expression profiles between AFP(high) and AFP(low) HCC. The prognostic signature may cooperate with AFP to promote the initiation and development of HCC. It also may explain the tumorigenesis in HCC with different AFP levels, and provide new clues for the prognosis of HCC.


Assuntos
Carcinoma Hepatocelular/genética , Regulação Neoplásica da Expressão Gênica , Neoplasias Hepáticas/genética , alfa-Fetoproteínas/genética , Carcinoma Hepatocelular/patologia , Perfilação da Expressão Gênica , Humanos , Cinesina , Neoplasias Hepáticas/patologia , Reação em Cadeia da Polimerase em Tempo Real , Transcriptoma , Enzimas de Conjugação de Ubiquitina , alfa-Fetoproteínas/metabolismo
7.
PLoS One ; 15(5): e0232247, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32374744

RESUMO

BACKGROUND: Hepatocellular carcinoma (HCC) continues to be a leading challenge in modern oncology. Early detection via blood-based screening tests has the potential to cause a stage-shift at diagnosis and improve clinical outcomes. Tumor associated autoantibodies (TA-AAbs) have previously shown the ability to distinguish HCC from patients with high-risk liver disease. This research aimed to further show the utility of TA-AAbs as biomarkers of HCC and assess their use in combination with Alpha-fetoprotein (AFP) for detection of HCC across multiple tumor stages. METHODS: Levels of circulating G class antibodies to 44 recombinant tumor associated antigens and circulating AFP were measured in the serum of patients with HCC, non-cancerous chronic liver disease (NCCLD) and healthy controls via enzyme-linked immunosorbent assay (ELISA). TA-AAb cut-offs were set at the highest Youden's J statistic at a specificity ≥95.00%. Panels of TA-AAbs were formed using net reclassification improvement. AFP was assessed at a cut-off of 200 ng/ml. RESULTS: Sensitivities ranged from 1.01% to 12.24% at specificities of 95.96% to 100.00% for single TA-AAbs. An ELISA test measuring a panel of 10 of these TA-AAbs achieved a combined sensitivity of 36.73% at a specificity of 89.89% when distinguishing HCC from NCCLD controls. At a cut-off of 200 ng/ml, AFP achieved a sensitivity of 31.63% at a specificity of 100.00% in the same cohort. Combination of the TA-AAb panel with AFP significantly increased the sensitivity for stage one (40.00%) and two (55.00%) HCC over the TA-AAb panel or AFP alone. CONCLUSIONS: A panel of TA-AAbs in combination with AFP could be clinically relevant as a replacement for measuring levels of AFP alone in surveillance and diagnosis strategies. The increased early stage sensitivity could lead to a stage shift with positive prognostic outcomes.


Assuntos
Antígenos de Neoplasias/imunologia , Autoanticorpos/sangue , Carcinoma Hepatocelular/diagnóstico , Carcinoma Hepatocelular/patologia , Neoplasias Hepáticas/diagnóstico , Neoplasias Hepáticas/patologia , alfa-Fetoproteínas/metabolismo , Adulto , Idoso , Idoso de 80 Anos ou mais , Autoanticorpos/imunologia , Carcinoma Hepatocelular/imunologia , Carcinoma Hepatocelular/metabolismo , Feminino , Humanos , Neoplasias Hepáticas/imunologia , Neoplasias Hepáticas/metabolismo , Masculino , Pessoa de Meia-Idade , Estadiamento de Neoplasias
8.
Artigo em Inglês | MEDLINE | ID: mdl-32326594

RESUMO

The magnitude of the effect of fetuin-A and fetuin-B on non-alcoholic fatty liver disease (NAFLD) remains undefined. Therefore, the aim of this study was to synthesize previous findings to obtain a reliable estimation of this relationship. This study was registered in PROSPERO with the number CRD42019126314. Studies published not later than March 2019, examining the relationship between fetuin-A, fetuin-B, and NAFLD, were identified by a systematic search in the electronic databases of the Web of Science, PubMed, Embase, and Cochrane Library. Pooled estimates of standardized mean difference (SMD), calculated using the random-effects model in a meta-analysis, were applied to estimate the strength of the association between fetuin-A, fetuin-B, and NAFLD. Thirty publications were identified and analyzed based on specified inclusion criteria. Collectively, they consisted of 3800 NAFLD participants and 3614 controls. Compared with the controls, significant higher values of the fetuin-A (SMD = 0.83, 95% CI: 0.59 to 1.07, Z = 6.82, p < 0.001) and fetuin-B (SMD = 0.18, 95% CI: 0.02 to 0.33, Z = 2.27, p = 0.023) were observed in NAFLD patients. Meanwhile, in the subgroup analysis, the effect value of fetuin-A in the NASH group was significantly higher than that in the NAFL group (p = 0.036). The findings of this study suggest that elevated fetuin-A and fetuin-B may independently indicate the occurrence of NAFLD. Nevertheless, further research is needed to confirm these results.


Assuntos
Fetuína-B , Hepatopatia Gordurosa não Alcoólica , alfa-Fetoproteínas , Biomarcadores/metabolismo , Fetuína-B/metabolismo , Humanos , Hepatopatia Gordurosa não Alcoólica/metabolismo , alfa-2-Glicoproteína-HS/metabolismo , alfa-Fetoproteínas/metabolismo
9.
Anticancer Res ; 40(4): 2225-2229, 2020 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-32234918

RESUMO

BACKGROUND: Primary hepatic carcinosarcoma is a rare subtype of liver malignancy, with only a small number of cases described in the English literature. CASE REPORT: We report the case of a 72-year-old man with a history of hepatitis C, who presented with complaints of abdominal pain. The patient's alpha fetoprotein (AFP) level was highly elevated at 7,406 ng/ml. His albumin, total bilirubin, aspartate aminotransferase, alanine aminotransferase, and alkaline phosphatase levels were within normal ranges. Computer tomographic scans discovered a 12×9×8 cm mass in the left lobe of the liver, extending to the anterior gastric wall. A partial hepatectomy of segments 2 and 3 with en bloc distal gastrectomy and omentectomy, a Roux-en-Y gastrojejunostomy, and a cholecystectomy were performed. Pathology revealed the mass to be a hepatic carcinosarcoma composed of collision tumor of four malignant components: hepatocellular carcinoma, cholangiocarcinoma, osteosarcoma and rhabdomyosarcoma. One and half month post-surgery, the patient was found to have a mass confirmed by biopsy as hepatocellular carcinoma in the right lobe, nodules in his lung and bone, and his AFP level elevated to 51,027.6 ng/ml. He died after two months during hospice care. CONCLUSION: To the best of our knowledge, this is the first documented case of primary hepatic carcinosarcoma with collision tumor of four malignant entities (hepatocellular carcinoma, cholangiocarcinoma, osteosarcoma and rhabdomyosarcoma). The pathogenesis, diagnosis, treatment and prognosis of this disease are discussed.


Assuntos
Carcinoma Hepatocelular/parasitologia , Carcinossarcoma/patologia , Colangiocarcinoma/patologia , Neoplasias Hepáticas/patologia , Fígado/patologia , Idoso , Neoplasias dos Ductos Biliares/diagnóstico por imagem , Neoplasias dos Ductos Biliares/patologia , Neoplasias dos Ductos Biliares/cirurgia , Biópsia/métodos , Neoplasias Ósseas/diagnóstico por imagem , Neoplasias Ósseas/patologia , Neoplasias Ósseas/cirurgia , Carcinoma Hepatocelular/diagnóstico por imagem , Carcinoma Hepatocelular/cirurgia , Carcinossarcoma/diagnóstico por imagem , Carcinossarcoma/cirurgia , Colangiocarcinoma/diagnóstico por imagem , Colangiocarcinoma/cirurgia , Colecistectomia/métodos , Evolução Fatal , Gastrectomia/métodos , Derivação Gástrica/métodos , Hepatectomia/métodos , Humanos , Fígado/diagnóstico por imagem , Fígado/cirurgia , Neoplasias Hepáticas/diagnóstico por imagem , Neoplasias Hepáticas/cirurgia , Masculino , Osteossarcoma/diagnóstico por imagem , Osteossarcoma/patologia , Osteossarcoma/cirurgia , Prognóstico , Rabdomiossarcoma/diagnóstico por imagem , Rabdomiossarcoma/patologia , Rabdomiossarcoma/cirurgia , Tomografia Computadorizada por Raios X , alfa-Fetoproteínas/metabolismo
10.
J Med Life ; 13(1): 68-74, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32341704

RESUMO

AFP (alpha-fetoprotein) levels are increased during the development of HCC (hepatocellular carcinoma); nonetheless, it can also be produced by non-tumoral hepatocytes in conditions of high cell turnover. Our study aims to provide additional data regarding the causes of elevated AFP in patients with liver cirrhosis due to hepatitis C virus (HCV) infection. We conducted an observational prospective cohort study that included 2068 patients with compensated cirrhosis and chronic hepatitis C genotype 1b infection. The two main inclusion criteria were the presence of advanced liver fibrosis - Metavir stage F4 - diagnosed by FibroMax testing, Fibroscan or liver biopsy, and the presence of detectable HCV RNA in the serum. Plasmatic AFP levels were determined through the electrochemiluminescence method, with a standard value ranging from 0 to 7 ng/ml. All data were obtained from the Romanian National Health Agency. The average AFP serum levels in patients with compensated cirrhosis without HCC were 9.4 ng/ml (range 0.5 ÷ 406 ng/ml); 30.1% of patients had significantly increased levels of AFP (>15 ng/ml). High values of serum AFP in patients with compensated liver cirrhosis without HCC was correlated with more advanced age (p<0.001), severe necroinflammatory activity detected by FibroMax (p<0.001), severe NASH (p<0.001), severe steatosis (p<0.001), low platelets (p<0.001), increased values of AST and ALT (p<0.001).


Assuntos
Carcinoma Hepatocelular/sangue , Hepacivirus/fisiologia , Cirrose Hepática/sangue , Neoplasias Hepáticas/sangue , alfa-Fetoproteínas/metabolismo , Adulto , Idoso , Idoso de 80 Anos ou mais , Carcinoma Hepatocelular/patologia , Feminino , Hepatite C/sangue , Hepatite C/virologia , Humanos , Neoplasias Hepáticas/patologia , Masculino , Pessoa de Meia-Idade , Estudos Prospectivos
11.
Cancer Control ; 27(1): 1073274820915520, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32216575

RESUMO

Noninvasive tools for the prognosis of α-fetoprotein negative hepatocellular carcinoma (HCC) are urgently needed. The present study proposed a prognostic system based on preoperative plasma prothrombin time and fibrinogen (PT/Fbg system). With respect to α-fetoprotein (AFP)-negative HCC, we compared the prognostic value in PT/Fbg system, Glasgow Prognostic Score, and aminotransferase/aspartate aminotransferase ratio. The present study retrospectively analyzed patient characteristics, clinicopathological factors, and the level of pretreatment biomarkers in 628 patients with HCC. Patients with increased PT and Fbg levels were allocated a score of 2, patients with only one of these abnormalities were assigned score 1, and patients with neither of these abnormalities were allocated a score of 0. The following distributions of the PT/Fbg system scores were observed: 187 (29.78%) patients had a score of 0, 305 (30.65%) had a score of 1, and 134 (22.69%) patients had a preoperative score of 2. The prognostic significance of the PT/Fbg system was determined using univariate and multivariate Cox hazard analyses in AFP-negative HCC. Multivariate analysis revealed that patients with a higher PT/Fbg system exhibited worse overall survival (OS) than patients with a lower PT/Fbg system. Our study proposes preoperative evaluation of the plasma PT/Fbg system to predict the OS of patients with AFP-negative HCC.


Assuntos
Carcinoma Hepatocelular/genética , Fibrinogênio/metabolismo , Neoplasias Hepáticas/genética , Tempo de Protrombina/métodos , alfa-Fetoproteínas/metabolismo , Carcinoma Hepatocelular/patologia , Feminino , Humanos , Neoplasias Hepáticas/patologia , Masculino , Pessoa de Meia-Idade , Prognóstico
12.
Nat Rev Urol ; 17(4): 201-213, 2020 04.
Artigo em Inglês | MEDLINE | ID: mdl-32157202

RESUMO

Testicular germ cell tumours (TGCTs) are the most frequent cancer type in young men and originate from the common precursor germ cell neoplasia in situ (GCNIS). For decades, clinical management of patients with TGCT has relied on classic serum tumour markers: α-fetoprotein, human chorionic gonadotropin subunit-ß and lactate dehydrogenase. In the past 10 years, microRNAs have been shown to outperform classic serum tumour markers in the diagnosis of primary tumours and in follow-up monitoring and prediction of relapse. miR-371a-3p is the most consistent marker and exhibits >90% diagnostic sensitivity and specificity in TGCT. However, miR-371a-3p cannot be used to diagnose GCNIS or mature teratoma. Future efforts must technically standardize the microRNA-based methods internationally and introduce miR-371a-3p as a molecular liquid biopsy-based marker for TGCTs in the clinic.


Assuntos
Biomarcadores Tumorais/metabolismo , MicroRNAs/metabolismo , Recidiva Local de Neoplasia/diagnóstico , Neoplasias Embrionárias de Células Germinativas/diagnóstico , Neoplasias Testiculares/diagnóstico , Assistência ao Convalescente , Biomarcadores Tumorais/genética , Gonadotropina Coriônica Humana Subunidade beta/metabolismo , Humanos , L-Lactato Desidrogenase/metabolismo , Biópsia Líquida , Masculino , Recidiva Local de Neoplasia/metabolismo , Neoplasias Embrionárias de Células Germinativas/genética , Neoplasias Embrionárias de Células Germinativas/metabolismo , Neoplasias Embrionárias de Células Germinativas/terapia , Seminoma/diagnóstico , Seminoma/genética , Seminoma/metabolismo , Seminoma/terapia , Sensibilidade e Especificidade , Teratoma/diagnóstico , Teratoma/genética , Teratoma/metabolismo , Teratoma/terapia , Neoplasias Testiculares/genética , Neoplasias Testiculares/metabolismo , Neoplasias Testiculares/terapia , alfa-Fetoproteínas/metabolismo
13.
Int J Mol Sci ; 21(3)2020 Jan 30.
Artigo em Inglês | MEDLINE | ID: mdl-32019136

RESUMO

Alpha-fetoprotein (AFP) is a major embryo- and tumor-associated protein capable of binding and transporting a variety of hydrophobic ligands, including estrogens. AFP has been shown to inhibit estrogen receptor (ER)-positive tumor growth, which can be attributed to its estrogen-binding ability. Despite AFP having long been investigated, its three-dimensional (3D) structure has not been experimentally resolved and molecular mechanisms underlying AFP-ligand interaction remains obscure. In our study, we constructed a homology-based 3D model of human AFP (HAFP) with the purpose of molecular docking of ERα ligands, three agonists (17ß-estradiol, estrone and diethylstilbestrol), and three antagonists (tamoxifen, afimoxifene and endoxifen) into the obtained structure. Based on the ligand-docked scoring functions, we identified three putative estrogen- and antiestrogen-binding sites with different ligand binding affinities. Two high-affinity binding sites were located (i) in a tunnel formed within HAFP subdomains IB and IIA and (ii) on the opposite side of the molecule in a groove originating from a cavity formed between domains I and III, while (iii) the third low-affinity binding site was found at the bottom of the cavity. Here, 100 ns molecular dynamics (MD) simulation allowed us to study their geometries and showed that HAFP-estrogen interactions were caused by van der Waals forces, while both hydrophobic and electrostatic interactions were almost equally involved in HAFP-antiestrogen binding. Molecular mechanics/Generalized Born surface area (MM/GBSA) rescoring method exploited for estimation of binding free energies (ΔGbind) showed that antiestrogens have higher affinities to HAFP as compared to estrogens. We performed in silico point substitutions of amino acid residues to confirm their roles in HAFP-ligand interactions and showed that Thr132, Leu138, His170, Phe172, Ser217, Gln221, His266, His316, Lys453, and Asp478 residues, along with two disulfide bonds (Cys224-Cys270 and Cys269-Cys277), have key roles in both HAFP-estrogen and HAFP-antiestrogen binding. Data obtained in our study contribute to understanding mechanisms underlying protein-ligand interactions and anticancer therapy strategies based on ERα-binding ligands.


Assuntos
Estradiol/metabolismo , Moduladores de Receptor Estrogênico/metabolismo , Receptor alfa de Estrogênio/metabolismo , Estrogênios/metabolismo , alfa-Fetoproteínas/metabolismo , Sequência de Aminoácidos , Substituição de Aminoácidos , Sítios de Ligação , Receptor alfa de Estrogênio/agonistas , Receptor alfa de Estrogênio/antagonistas & inibidores , Feminino , Humanos , Ligantes , Modelos Moleculares , Simulação de Acoplamento Molecular , Simulação de Dinâmica Molecular , Mutagênese , Alinhamento de Sequência
14.
Drugs ; 80(3): 315-322, 2020 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-32034692

RESUMO

Ramucirumab (Cyramza®), a fully human anti-VEGFR-2 monoclonal antibody, has been approved as monotherapy for the treatment of patients with hepatocellular carcinoma (HCC) and α-fetoprotein levels ≥ 400 ng/mL who have been treated with sorafenib. Ramucirumab significantly prolonged overall survival (OS) and progression-free survival (PFS) relative to placebo in this population in the randomized, double-blind phase 3 REACH 2 trial. These benefits were seen in key prespecified subgroups based on demographic and disease characteristics. Ramucirumab had an acceptable tolerability profile and manageable safety profile in these patients, with the majority of treatment-related adverse events being mild or moderate in severity. The safety profile of ramucirumab was consistent with that expected for agents targeting the VEGF/VEGFR axis. Currently, ramucirumab is the only therapy specifically tested in patients with α-fetoprotein levels ≥ 400 ng/mL, which is associated with an aggressive disease and poor prognosis. Therefore, ramucirumab is an important treatment option for patients with HCC and α-fetoprotein levels ≥ 400 ng/mL who have been treated with sorafenib.


Assuntos
Anticorpos Monoclonais Humanizados/farmacologia , Antineoplásicos/farmacologia , Carcinoma Hepatocelular/tratamento farmacológico , Neoplasias Hepáticas/tratamento farmacológico , alfa-Fetoproteínas/antagonistas & inibidores , Anticorpos Monoclonais Humanizados/administração & dosagem , Anticorpos Monoclonais Humanizados/uso terapêutico , Antineoplásicos/administração & dosagem , Carcinoma Hepatocelular/metabolismo , Humanos , Neoplasias Hepáticas/metabolismo , alfa-Fetoproteínas/metabolismo
15.
Jpn J Radiol ; 38(5): 472-479, 2020 May.
Artigo em Inglês | MEDLINE | ID: mdl-32078123

RESUMO

PURPOSE: The goal of this study was to assess the value of whole-body 18F-FDG PET/CT in detecting the cause of rising serum alpha-fetoprotein (AFP) level after the treatment of hepatocellular carcinoma (HCC). MATERIALS AND METHODS: 18F-FDG PET/CT studies were performed for 100 patients (76 men and 24 women), ranged in age from 40 to 76 years who had underwent either surgical resection or interventional therapy for HCC, but were subsequently noted to have rising AFP serum level on routine follow-up examinations. The 18F-FDG PET/CT results were correlated with histological findings or radiological and clinical follow-up. RESULTS: According to patient-based analysis, 18F-FDG PET/CT demonstrated 74 true-positives, four false-negatives, 16 true-negative, and 6 false-positive results, with sensitivity, specificity, positive predictive value, negative predictive value, and accuracy of 95%, 72.7%, 92.5%, 80%, and 90%, respectively. According to Lesion-based analysis, 18F-FDG PET/CT demonstrated 202 true-positive lesions, 8 false-negatives, and 16 true-negative and 6 false-positive results, with sensitivity, specificity, positive predictive value, negative predictive value, and accuracy of 98%, 72.7%, 97%, 80%, and 95.6%, respectively. CONCLUSION: 18F-FDG PET/CT is a valuable imaging tool investigating patients who have a rising serum AFP level after HCC treatment. It accurately detects residual or recurrent tumor as well as extrahepatic metastasis.


Assuntos
Carcinoma Hepatocelular/diagnóstico por imagem , Fluordesoxiglucose F18 , Neoplasias Hepáticas/diagnóstico por imagem , Tomografia Computadorizada com Tomografia por Emissão de Pósitrons/métodos , Imagem Corporal Total/métodos , alfa-Fetoproteínas/metabolismo , Adulto , Idoso , Carcinoma Hepatocelular/sangue , Carcinoma Hepatocelular/terapia , Feminino , Seguimentos , Humanos , Neoplasias Hepáticas/sangue , Neoplasias Hepáticas/terapia , Masculino , Pessoa de Meia-Idade , Estudos Prospectivos , Compostos Radiofarmacêuticos , Sensibilidade e Especificidade , Resultado do Tratamento
16.
J Oncol Pharm Pract ; 26(6): 1505-1510, 2020 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-32041468

RESUMO

INTRODUCTION: Hepatoid adenocarcinoma of the lung is an extremely rare type of the non-small cell lung cancer. Treatment principles and prognosis are similar to that of lung adenocarcinoma. CASE REPORT: A 62-year-old female smoker presented with a huge mass in the left upper lobe. After diagnostic biopsy, she underwent left pneumonectomy and mediastinal lymph node dissection. A diagnosis of stage T4N1M0 hepatoid adenocarcinoma of the lung with positive surgical margins was made. MANAGEMENT AND OUTCOME: After the operation, the level of serum alpha fetoprotein was 9010 ng/ml (N: <10). The level of serum alpha fetoprotein was decreased with concurrent chemoradiotherapy and chemotherapy. Disease progression was detected at 11 months after diagnosis. No response was obtained to other therapies. The patient died at 14 months from the time of diagnosis. DISCUSSION: Usually, patients with hepatoid adenocarcinoma of the lung are male smokers. Hepatoid adenocarcinoma tends to settle in the upper lobes of the lung. The most important prognostic factor of the hepatoid adenocarcinoma of the lung is the disease stage at the diagnosis and patients with metastatic disease have poor survival.


Assuntos
Adenocarcinoma/terapia , Carcinoma Pulmonar de Células não Pequenas/terapia , Neoplasias Pulmonares/terapia , Adenocarcinoma/patologia , Adenocarcinoma de Pulmão/patologia , Adenocarcinoma de Pulmão/terapia , Carcinoma Pulmonar de Células não Pequenas/patologia , Feminino , Humanos , Neoplasias Pulmonares/patologia , Pessoa de Meia-Idade , Prognóstico , alfa-Fetoproteínas/metabolismo
17.
World J Surg Oncol ; 18(1): 41, 2020 Feb 24.
Artigo em Inglês | MEDLINE | ID: mdl-32093729

RESUMO

BACKGROUND: The indications for the surgical treatment of gastric cancer liver metastases (GCLMs) remain controversial. In addition, the outcome of surgery for the treatment of liver metastases of alpha-fetoprotein-producing gastric cancer (AFP-GC) has not yet been reported. We assessed the clinicopathologic features, including AFP-GC, and the surgical results of these patients. METHODS: This retrospective study analyzed 20 patients who underwent hepatectomy for GCLM at Odawara Municipal Hospital between April 2006 and January 2016. RESULTS: The actuarial 1-, 3-, and 5-year overall survival (OS) rates after primary hepatectomy were 80.0%, 55.5%, and 31.7%, respectively, with a median OS of 42 months. Four patients survived for more than 5 years after their final hepatectomy procedures. A multivariate analysis showed multiple metastases in the liver, the elevated level of carbohydrate antigen 19-9 (CA19-9), and an age of less than 70 years to be independently associated with a poor prognosis in terms of OS. No significant differences were noted between the AFP-GC and AFP-negative GC groups. CONCLUSION: Surgical treatment is therefore considered to be a feasible option for GCLM. The findings of the present study showed the number of metastatic liver tumors, the level of CA19-9, and the patient age to be prognostic indicators for the surgical treatment of GCLM.


Assuntos
Gastrectomia , Hepatectomia , Neoplasias Hepáticas/cirurgia , Recidiva Local de Neoplasia/epidemiologia , Neoplasias Gástricas/patologia , Fatores Etários , Idoso , Idoso de 80 Anos ou mais , Antígenos Glicosídicos Associados a Tumores/sangue , Intervalo Livre de Doença , Estudos de Viabilidade , Feminino , Mucosa Gástrica/patologia , Humanos , Estimativa de Kaplan-Meier , Fígado/patologia , Fígado/cirurgia , Neoplasias Hepáticas/sangue , Neoplasias Hepáticas/mortalidade , Neoplasias Hepáticas/secundário , Masculino , Pessoa de Meia-Idade , Recidiva Local de Neoplasia/prevenção & controle , Prognóstico , Estudos Retrospectivos , Fatores de Risco , Neoplasias Gástricas/sangue , Neoplasias Gástricas/mortalidade , Neoplasias Gástricas/cirurgia , Taxa de Sobrevida , alfa-Fetoproteínas/análise , alfa-Fetoproteínas/metabolismo
18.
PLoS One ; 15(2): e0228857, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32053643

RESUMO

OBJECTIVE: Hepatocellular carcinoma (HCC) has become a pressing health problem facing the world today due to its high morbidity, high mortality, and late discovery. As a diagnostic criteria of HCC, the exact threshold of Alpha-fetoprotein (AFP) is controversial. Therefore, this study was aimed to systematically estimate the performance of AFP in diagnosing HCC and to clarify its optimal threshold. METHODS: Medline and Embase databases were searched for articles indexed up to November 2019. English language studies were included if both the sensitivity and specificity of AFP in the diagnosis of HCC were provided. The basic information and accuracy data included in the studies were extracted. Combined estimates for sensitivity and specificity were statistically analyzed by random-effects model using MetaDisc 1.4 and Stata 15.0 software at the prespecified threshold of 400 ng/mL, 200 ng/mL, and the range of 20-100 ng/mL. The optimal threshold was evaluated by the area under curve (AUC) of the summary receiver operating characteristic (SROC). RESULTS: We retrieved 29,828 articles and included 59 studies and 1 review with a total of 11,731 HCC cases confirmed by histomorphology and 21,972 control cases without HCC. The included studies showed an overall judgment of at risk of bias. Four studies with AFP threshold of 400 ng/mL showed the summary sensitivity and specificity of 0.32 (95%CI 0.31-0.34) and 0.99 (95%CI 0.98-0.99), respectively. Four studies with AFP threshold of 200 ng/mL showed the summary sensitivity and specificity of 0.49 (95%CI 0.47-0.50) and 0.98 (95%CI 0.97-0.99), respectively. Forty-six studies with AFP threshold of 20-100 ng/mL showed the summary sensitivity and specificity of 0.61 (95%CI 0.60-0.62) and 0.86 (95%CI 0.86-0.87), respectively. The AUC of SROC and Q index of 400 ng/mL threshold were 0.9368 and 0.8734, respectively, which were significantly higher than those in 200 ng/mL threshold (0.9311 and 0.8664, respectively) and higher than those in 20-100 ng/mL threshold (0.8330 and 0.7654, respectively). Furthermore, similar result that favored 400 ng/mL were shown in the threshold in terms of AFP combined with ultrasound. CONCLUSION: AFP levels in serum showed good accuracy in HCC diagnosis, and the threshold of AFP with 400 ng/mL was better than that of 200 ng/mL in terms of sensitivity and specificity no matter AFP is used alone or combined with ultrasound.


Assuntos
Carcinoma Hepatocelular/diagnóstico , alfa-Fetoproteínas/análise , alfa-Fetoproteínas/metabolismo , Área Sob a Curva , Biomarcadores Tumorais/sangue , Biometria , Carcinoma Hepatocelular/metabolismo , Estudos de Casos e Controles , Confiabilidade dos Dados , Bases de Dados Factuais , Humanos , Testes Imunológicos , Neoplasias Hepáticas/diagnóstico , Neoplasias Hepáticas/metabolismo , Curva ROC , Sensibilidade e Especificidade
19.
BMC Cancer ; 20(1): 6, 2020 Jan 02.
Artigo em Inglês | MEDLINE | ID: mdl-31898536

RESUMO

BACKGROUND: Hepatocellular carcinoma (HCC) is a major health problem worldwide. However, the popular tumor marker, AFP, lacks sensitivity although its specificity is high. Tissue biopsy is an invasive operation and may increase the risk of needle-track metastases. Heat shock protein 90 (HSP90) is a potential biomarker for tumor diagnosis and prognosis. This study aims to determine whether levels of plasma HSP90α in HCC patients can be used as a cost-effective and simple test for the initial diagnosis of the disease. METHODS: Plasma samples were collected from 659 HCC patients, 114 secondary hepatic carcinoma (SHC) patients, 28 hepatic hemangioma patients and 230 healthy donors. The levels of HSP90α were measured by ELISA. RESULTS: The levels of plasma HSP90α in HCC patients were significantly higher than in healthy donors and in patients with hepatic hemangioma or SHC (144.08 ± 4.98, 46.81 ± 1.11, 61.56 ± 8.20 and 111.96 ± 10.08 ng/mL, respectively; p < 0.05 in all cases). The levels were associated with age (p = 0.001), BCLC stage (p < 0.001), levels of AFP (p < 0.001), tumor size (p < 0.001), tumor number (p < 0.001), PVTT (p < 0.001), EHM (p < 0.001) and Child-Pugh stage in the HCC cohort. In addition, the levels of plasma HSP90α showed an upward trend along with the progression of the BCLC stage. ROC curve analysis showed that compared to AFP (AUC 0.922, 95%CI 0.902-0.938) or HSP90α (AUC 0.836, 95%CI 0.810-0.860), the combination of HSP90α and AFP (AUC0.943, 95%CI 0.925-0.957) significantly improved the diagnostic efficiency for HCC patients. CONCLUSION: The results suggest that plasma Hsp90 α levels can be used as an initial diagnosis for patients with HCC in both rural and cosmopolitan settings.


Assuntos
Carcinoma Hepatocelular/sangue , Carcinoma Hepatocelular/diagnóstico , Proteínas de Choque Térmico HSP90/sangue , Neoplasias Hepáticas/sangue , Neoplasias Hepáticas/diagnóstico , Adulto , Idoso , Biomarcadores Tumorais , Ensaio de Imunoadsorção Enzimática , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Estadiamento de Neoplasias , Prognóstico , Curva ROC , Carga Tumoral , alfa-Fetoproteínas/metabolismo
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