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1.
Anticancer Res ; 39(10): 5695-5701, 2019 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-31570469

RESUMO

Large tumor size and arterioportal shunt are poor prognostic factors for hepatocellular carcinoma. Lenvatinib is a novel and potent multi-tyrosine kinase inhibitor developed in Japan. A 66-year-old woman with hepatocellular carcinoma and untreated hepatitis C was referred to our hospital. She was judged as unresectable and was treated with four sessions of transarterial chemoembolization; however, the therapeutic effect was unsatisfactory because of major arterioportal shunt. Lenvatinib was sequentially administered for 4 months. Thereafter, we observed tumor shrinkage, complete disappearance of arterioportal shunt, and obvious improvement in liver function. A curative conversion hepatectomy was successfully accomplished. The extremely high levels of tumor markers almost normalized; the pretreatment levels were 1,008,021 ng/ml for alpha-fetoprotein. At 1 year after the primary treatment, the patient has not experienced recurrence. To our knowledge, this is the first case of a patient with initially unresectable hepatocellular carcinoma with arterioportal shunt who underwent conversion hepatectomy after multidisciplinary treatment, including lenvatinib.


Assuntos
Carcinoma Hepatocelular/tratamento farmacológico , Carcinoma Hepatocelular/cirurgia , Hepatectomia/métodos , Neoplasias Hepáticas/tratamento farmacológico , Neoplasias Hepáticas/cirurgia , Compostos de Fenilureia/uso terapêutico , Quinolinas/uso terapêutico , Idoso , Biomarcadores Tumorais/metabolismo , Carcinoma Hepatocelular/metabolismo , Quimioembolização Terapêutica/métodos , Feminino , Humanos , Neoplasias Hepáticas/metabolismo , Recidiva Local de Neoplasia/tratamento farmacológico , Recidiva Local de Neoplasia/cirurgia , alfa-Fetoproteínas/metabolismo
2.
Medicine (Baltimore) ; 98(31): e16557, 2019 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-31374020

RESUMO

BACKGROUND: Post-treatment alpha-fetoprotein (AFP) response has been reported to be associated with prognosis of hepatocellular carcinoma (HCC) patients, but the results were not consistent. This meta-analysis aimed to explore the relationship between AFP response and clinical outcomes of HCC. METHODS: PubMed, Embase, Medline and Cochrane library were searched for relevant articles published before March 20, 2019. The data were analyzed using RevMan5.3 software. RESULTS: Twenty-nine articles with 4726 HCC patients were finally included for analysis. The pooled results showed that post-treatment AFP response was significantly associated with overall survival (OS) (hazard ratio (HR) = 0.41, 95% confidence interval (CI): 0.35-0.47, P <.001), progression free survival (PFS) (HR = 0.46, 95% CI: 0.39-0.54, P <.001) and recurrence free survival (RFS) (HR = 0.41, 95% CI: 0.29-0.56, P <.001) of HCC patients. CONCLUSION: post-treatment AFP response might be a useful prognostic marker for HCC patients.


Assuntos
Neoplasias Hepáticas/tratamento farmacológico , Prognóstico , alfa-Fetoproteínas/metabolismo , Humanos , alfa-Fetoproteínas/uso terapêutico
3.
J Agric Food Chem ; 67(28): 8007-8019, 2019 Jul 17.
Artigo em Inglês | MEDLINE | ID: mdl-31268702

RESUMO

Cow and human milk have been reported to contain dioxins ranging from 0.023 to 26.46 and 0.88 to 19 pg/g of fat, respectively. However, the toxic effects of the dioxins in the milk in this range of concentrations were not explored. Therefore, considering the outbred livestock tissues as better models than inbred laboratory animals, the present study targeted to study the effect of dioxins present in the milk on three-dimensionally (3D) cultured buffalo primary hepatocyte spheroids. The spheroids were treated with a model dioxin, 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD), directly and also through milk fat at different concentrations (i.e, 0.02-20 pg/mL) for 24 h. Among the liver-cell-specific (ALB, HNF4α, and AFP) genes, a similar ALB and upregulated HNF4α expression at all treatments indicated the functional and transcriptionally active hepatocyte spheroids. Supportingly, no significant difference in the antiapoptotic gene expression between the treatments of milk fat and milk fat containing dioxins indicated the survivability of the spheroids during dioxin treatments. Among the selected TCDD responsive (CYP1A1, CYP1A2, AHR, CYP1B1, and TIPARP) genes, a nonsignificant increasing trend of the CYP1A1 expression was observed from 0.2 to 10 pg/mL of TCDD concentration through milk fat. This pattern was similar to the reported insensitive response of human primary hepatocytes toward dioxins than that of rat primary hepatocytes. This may indicate that the buffalo hepatocyte spheroids could be better models than rats for TCDD hepatotoxic studies. Further, TCDD in the milk in the range of 0.02-20 pg/mL concentration may not be very hepatotoxic.


Assuntos
Dioxinas/farmacologia , Hepatócitos/efeitos dos fármacos , Leite/química , Animais , Búfalos , Células Cultivadas , Citocromo P-450 CYP1A1/genética , Citocromo P-450 CYP1A1/metabolismo , Citocromo P-450 CYP1A2/genética , Citocromo P-450 CYP1A2/metabolismo , Dioxinas/análise , Contaminação de Alimentos/análise , Fator 4 Nuclear de Hepatócito/genética , Fator 4 Nuclear de Hepatócito/metabolismo , Hepatócitos/metabolismo , Fígado/citologia , Fígado/efeitos dos fármacos , Fígado/metabolismo , Modelos Animais , Ratos , Esferoides Celulares/efeitos dos fármacos , Esferoides Celulares/metabolismo , alfa-Fetoproteínas/genética , alfa-Fetoproteínas/metabolismo
5.
Cancer Immunol Immunother ; 68(8): 1223-1233, 2019 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-31201473

RESUMO

Plasmacytoid dendritic cells (pDCs) are present in various primary and metastatic human neoplasms; however, their clinical significance in hepatocellular carcinoma (HCC) is unclear. In this study, we investigated the distribution, prognostic value, and potential function of pDCs in HCC patients undergoing curative resection. We performed immunohistochemical analyses of whole tumor sections from 224 patients to assess the expression of BDCA2, CD3, CD4, CD8, Foxp3, granzyme B, IL-17, and CD34. The findings were validated using tissue microarrays from another two independent cohorts totaling 841 HCC patients undergoing curative resection. Our results demonstrated that high numbers of BDCA2+ pDCs within tumors correlated with high alpha-fetoprotein levels, greater vascular invasion, advanced tumor-node-metastasis stage, shorter overall survival, and a higher recurrence rate. However, patient outcomes were not associated with pDCs in peritumoral stromal or nontumor tissues. Furthermore, an increase in intratumoral pDCs was associated with increased intratumoral infiltration of Foxp3+ regulatory T cells and IL-17-producing cells and correlated with tumor vascular density. Univariate and multivariate analyses revealed that the presence of intratumoral pDCs alone or in combination with regulatory T and/or IL-17-producing cells was an independent predictor of time to recurrence and overall survival. In conclusion, our study demonstrated that intratumoral infiltration by pDCs is a novel indicator for poor prognosis in patients with HCC, possibly through the induction of an immune tolerogenic and inflammatory tumor microenvironment comprising regulatory T and IL-17-producing cells. An assessment of the combination of these cells represents a superior predictor of patient outcome.


Assuntos
Carcinoma Hepatocelular/diagnóstico , Células Dendríticas/imunologia , Interleucina-17/metabolismo , Neoplasias Hepáticas/diagnóstico , Linfócitos T Reguladores/imunologia , Adulto , Idoso , Carcinoma Hepatocelular/imunologia , Carcinoma Hepatocelular/mortalidade , Progressão da Doença , Feminino , Seguimentos , Fatores de Transcrição Forkhead/metabolismo , Hepatectomia , Humanos , Lectinas Tipo C/metabolismo , Neoplasias Hepáticas/imunologia , Neoplasias Hepáticas/mortalidade , Masculino , Glicoproteínas de Membrana/metabolismo , Pessoa de Meia-Idade , Metástase Neoplásica , Prognóstico , Receptores Imunológicos/metabolismo , Análise de Sobrevida , alfa-Fetoproteínas/metabolismo
6.
Oncology ; 97(2): 75-81, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31242488

RESUMO

AIM: This study investigated early tumor marker response and treatment response in patients with advanced hepatocellular carcinoma (HCC) treated with lenvatinib. METHODS: Twenty patients with advanced HCC who received lenvatinib were enrolled in this retrospective study. α-Fetoprotein (AFP) and des-γ-carboxyprothrombin (DCP) levels were measured before treatment as well as 2 and 4 weeks after treatment. The objective response rate was evaluated by mRECIST at 6 weeks. RESULTS: The response rate was 30% (complete response/partial response/stable disease/progressive disease: n = 0/6/6/8 cases) by mRECIST. At 4 weeks, the AFP levels of 12 patients (80%) were lower than at baseline. The AFP levels of 9 patients (60%) continued decreasing from 2 weeks to 4 weeks (sustained-reduction group). In this group, the response rate was 67%. The median AFP change rate was -39% at 4 weeks. In imaging responders, the AFP change rate significantly decreased (p = 0.02). The DCP change rate had no significant correlation with imaging response. The AFP-sustained-reduction group had significantly higher adherence to lenvatinib than the non-sustained-reduction group (p = 0.02). CONCLUSION: With lenvatinib therapy for HCC, the AFP levels of most patients had declined at 2 weeks, and at 4 weeks the AFP-sustained-reduction group demonstrated a higher objective response.


Assuntos
Antineoplásicos/uso terapêutico , Biomarcadores Tumorais/metabolismo , Biomarcadores/metabolismo , Carcinoma Hepatocelular/tratamento farmacológico , Neoplasias Hepáticas/tratamento farmacológico , Compostos de Fenilureia/uso terapêutico , Precursores de Proteínas/metabolismo , Protrombina/metabolismo , Quinolinas/uso terapêutico , alfa-Fetoproteínas/metabolismo , Idoso , Idoso de 80 Anos ou mais , Carcinoma Hepatocelular/diagnóstico por imagem , Carcinoma Hepatocelular/metabolismo , Quimioembolização Terapêutica , Feminino , Humanos , Neoplasias Hepáticas/diagnóstico por imagem , Neoplasias Hepáticas/metabolismo , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos , Resultado do Tratamento
7.
Cell Mol Biol (Noisy-le-grand) ; 65(4): 23-28, 2019 Apr 30.
Artigo em Inglês | MEDLINE | ID: mdl-31078148

RESUMO

In recent years, most related studies have found that chronic hepatitis B virus infection is the main cause of hepatocellular carcinoma (HCC), but the specific pathogenesis is still unclear. To investigate the function of HDAC in hepatocellular carcinoma (HCC), this study used qRT-PCR to determine the expression levels of miR-376a and HDAC9 mNRA in HCC and para-cancerous tissues. The clinical significance of HDAC9 in HCC was assessed in a study cohort containing 37 patients with HCC using immunohistochemistry. The expression level of miR-376a in liver cancer tissues was significantly lower than that in para-cancerous tissues, while the expression level of HDAC9 mRNA in liver cancer tissue was significantly higher than that in para-cancerous tissues. The expression of HDAC9 occurred mainly in the nucleus. There was a significant correlation between tumor differentiation and HDAC9. Survival analysis showed that HCC patients with higher HDAC9 expression had poorer prognosis, and subsequent multivariate analysis showed that HDAC9 expression level was an independent predictor. There was a definite correlation between HDAC9 and the expressions of AFP and Ki67. These results suggest that the expression level of HDAC9 in HCC is abnormally high while the expression level of miR-376a is significantly decreased, indicating that HDAC9 may be a potential prognostic indicator of HCC.


Assuntos
Carcinoma Hepatocelular/enzimologia , Histona Desacetilases/metabolismo , Neoplasias Hepáticas/enzimologia , Proteínas Repressoras/metabolismo , Carcinoma Hepatocelular/genética , Carcinoma Hepatocelular/patologia , Feminino , Regulação Neoplásica da Expressão Gênica , Histona Desacetilases/genética , Humanos , Antígeno Ki-67/metabolismo , Neoplasias Hepáticas/genética , Neoplasias Hepáticas/patologia , Masculino , MicroRNAs/genética , MicroRNAs/metabolismo , Pessoa de Meia-Idade , Análise Multivariada , Prognóstico , Proteínas Repressoras/genética , Análise de Sobrevida , alfa-Fetoproteínas/metabolismo
8.
Medicine (Baltimore) ; 98(20): e15755, 2019 05.
Artigo em Inglês | MEDLINE | ID: mdl-31096541

RESUMO

RATIONALE: Hepatocellular carcinoma (HCC), one of the most common cancers worldwide, is an aggressive tumor with very poor prognosis. Regorafenib was the first agent to show a survival benefit over placebo in patients who showed progression while being treated with sorafenib, but it remains an unsatisfactory agent owing to its serious side effects. Therefore, more efficient and milder therapies are needed. PATIENT CONCERNS: Herein, we report a patient with advanced HCC with many lung metastases who showed progression during sorafenib treatment. DIAGNOSES: HCC with lung metastases (stage IVB). INTERVENTIONS: SHR-1210 alone was used as second-line treatment. OUTCOMES: Although the lung metastases did not decrease 3 months after the treatment, they decreased significantly at 6 months after the treatment and partially disappeared. The tumor response indicated partial response. Furthermore, all of the lung metastases continued to decrease at about 17 months after treatment. The alpha-fetoprotein levels showed a similar trend. After a follow up of 19 months, the patient remains in good health. LESSONS: SHR-1210 alone as a second-line treatment for a patient with HCC showed excellent antitumor effects. We think that SHR-1210 may exert its antitumor effects through a late-onset model, which persist for a long time. The side effects were mild and well tolerated.


Assuntos
Antineoplásicos Imunológicos/administração & dosagem , Carcinoma Hepatocelular/tratamento farmacológico , Neoplasias Hepáticas/tratamento farmacológico , Neoplasias Pulmonares/tratamento farmacológico , Antineoplásicos Imunológicos/farmacologia , Carcinoma Hepatocelular/metabolismo , Resistencia a Medicamentos Antineoplásicos/efeitos dos fármacos , Humanos , Neoplasias Hepáticas/metabolismo , Neoplasias Pulmonares/metabolismo , Neoplasias Pulmonares/secundário , Masculino , Pessoa de Meia-Idade , Receptor de Morte Celular Programada 1/antagonistas & inibidores , Sorafenibe , Resultado do Tratamento , alfa-Fetoproteínas/metabolismo
9.
Anal Bioanal Chem ; 411(14): 3009-3019, 2019 May.
Artigo em Inglês | MEDLINE | ID: mdl-31076819

RESUMO

The N-glycosylation of proteins is one of the most important post-translational modifications relevant to various biological functions. The identification and quantification of N-glycoproteins in liquid chromatography-mass spectrometry (LC-MS) is challenging because of their low analytical sensitivity and selectivity. This is due to their microheterogeneity and the difficulty of synthesizing N-glycopeptides as an internal standard. Parallel reaction monitoring (PRM) is widely used in targeted LC-MS. The key advantage of LC-PRM is that it can identify N-glycopeptides using tandem mass spectrometry (MS/MS) fragmentation, even without an internal standard. We investigated the feasibility of analyzing N-glycoproteins using multiplex immunoprecipitation to improve sensitivity and selectivity. We targeted N-glycoproteins [α-fetoprotein (AFP), vitronectin (VTN), and α-1-antichymotrypsin (AACT)] that are abnormally glycosylated in hepatocellular carcinoma (HCC). Their tryptic N-glycopeptides were selected to determine the percentages of fucosylated N-glycopeptides using Y ions, which include glycopeptide fragments with amino acid sequences. Finally, we confirmed that the area under the receiver operating characteristic curve (AUC = 0.944) for the combination of AFP and VTN increased more so than for a single glycopeptide (AUC = 0.889 for AFP and 0.792 for VTN) with respect to discriminating between HCC and cirrhosis serum. This study shows that an LC-PRM method using multiplex N-glycoproteins immunoprecipitated from serum could be applied to develop and verify cancer biomarkers. Graphical abstract.


Assuntos
Biomarcadores Tumorais/sangue , Carcinoma Hepatocelular/diagnóstico , Cromatografia Líquida/métodos , Glicoproteínas/sangue , Imunoprecipitação/métodos , Neoplasias Hepáticas/diagnóstico , Espectrometria de Massas em Tandem/métodos , Sequência de Aminoácidos , Calibragem , Carcinoma Hepatocelular/sangue , Estudos de Casos e Controles , Estudos de Viabilidade , Fucose/química , Glicoproteínas/química , Glicoproteínas/normas , Glicosilação , Humanos , Limite de Detecção , Neoplasias Hepáticas/sangue , Curva ROC , Padrões de Referência , Vitronectina/sangue , alfa 1-Antiquimotripsina/sangue , alfa-Fetoproteínas/metabolismo
10.
Gastroenterology ; 157(1): 54-64, 2019 07.
Artigo em Inglês | MEDLINE | ID: mdl-30986389

RESUMO

Hepatocellular cancer (HCC) is the fourth leading cause of cancer-related deaths worldwide and the fastest growing cause of cancer deaths in the United States. The overall prognosis of HCC remains dismal, except for the subset of patients who are diagnosed at early stage and receive potentially curative therapies, such as surgical resection and liver transplantation. Given this, expert society guidelines recommend HCC surveillance every 6 months in at-risk individuals. Despite these recommendations, the effectiveness of HCC surveillance remains a subject of debate. We discuss current best practices for HCC surveillance and the evidence that support these recommendations. We also describe several initiatives that are underway to improve HCC surveillance and outline areas that may serve as high-yield targets for future research. Overall, we believe these efforts will help the field move toward precision surveillance, where surveillance tests and intervals are tailored to individual HCC risk. Doing so can maximize surveillance benefits, minimize surveillance harms, and optimize overall value for all patients.


Assuntos
Carcinoma Hepatocelular/diagnóstico , Detecção Precoce de Câncer/métodos , Hepatite B Crônica/epidemiologia , Cirrose Hepática/epidemiologia , Neoplasias Hepáticas/diagnóstico , Carcinoma Hepatocelular/epidemiologia , Carcinoma Hepatocelular/metabolismo , Humanos , Neoplasias Hepáticas/epidemiologia , Neoplasias Hepáticas/metabolismo , Imagem por Ressonância Magnética , Lectinas de Plantas , Guias de Prática Clínica como Assunto , Medição de Risco , Tomografia Computadorizada por Raios X , Ultrassonografia , alfa-Fetoproteínas/metabolismo
11.
Future Oncol ; 15(15): 1771-1780, 2019 May.
Artigo em Inglês | MEDLINE | ID: mdl-30997850

RESUMO

Aim: MTHFD1 was the enzyme providing one-carbon derivatives of tetrahydrofolate. We sought to investigate the impact of MTHFD1 on hepatocellular carcinoma (HCC). Methods: Bioinformatic analysis, western blot and immunohistochemistry were conducted to detect MTHFD1 expression in HCC. The relationships between MTHFD1 and prognosis of 172 HCCs were analyzed by Kaplan-Meier method and Cox proportional hazards model. Results: High MTHFD1 expression in HCC represented poor prognosis (overall survival p = 0.025; time to recurrence p = 0.044). Combining MTHFD1 with serum AFP, survival analysis demonstrated the prognosis of the MTHFD1 low expression and AFP ≤20 ng/ml group was better than that of the MTHFD1 high expression or AFP >20 ng/ml group and the MTHFD1 high expression and AFP >20 ng/ml group (overall survival p < 0.0001; time to recurrence p < 0.0001). Conclusion: High MTHFD1 expression in HCC indicated poorer prognosis. Combining MTHFD1 with serum AFP improved the accuracy of prognostic prediction.


Assuntos
Biomarcadores Tumorais , Carcinoma Hepatocelular/genética , Carcinoma Hepatocelular/mortalidade , Expressão Gênica , Neoplasias Hepáticas/genética , Neoplasias Hepáticas/mortalidade , Metilenotetra-Hidrofolato Desidrogenase (NADP)/genética , Antígenos de Histocompatibilidade Menor/genética , Adulto , Idoso , Carcinoma Hepatocelular/patologia , Feminino , Humanos , Imuno-Histoquímica , Estimativa de Kaplan-Meier , Neoplasias Hepáticas/patologia , Masculino , Metilenotetra-Hidrofolato Desidrogenase (NADP)/metabolismo , Pessoa de Meia-Idade , Antígenos de Histocompatibilidade Menor/metabolismo , Recidiva Local de Neoplasia , Estadiamento de Neoplasias , Prognóstico , Curva ROC , Reprodutibilidade dos Testes , Fatores de Risco , Carga Tumoral , alfa-Fetoproteínas/metabolismo
12.
Medicine (Baltimore) ; 98(17): e15414, 2019 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-31027143

RESUMO

Alpha-fetoprotein (AFP), as the most widely used biomarker of hepatocellular carcinoma (HCC), was correlated with ongoing liver damage. The aim of this study was to evaluate the ability of inflammatory correction-based AFP to identify HCC from other liver diseases.From March 2012 to March 2017, among 926 participants, a total of 501 patients whose transaminases were higher than the upper limit of normal range, including 166 treatment-naïve HCC patients were enrolled in our retrospective study. The liver function, white blood cell (WBC) count and serum AFP level of all patients were collected at the initial stage of admission. The area under the receiver-operating curve (AUROC) of AFP, AFP/(Aspartate aminotransferase*Alanine aminotransferase) [AFP/(AST*ALT)] and AFP/WBC were compared between the HCC group and the control groups for the quantifying diagnostic efficacy.AUROCs of our novel index AFP/(AST*ALT) were up to 0.853 (95% confidence interval, CI 0.818-0.887, P < .001) and 0.825 (95% CI 0.782-0.868, P < .001), respectively, when differentiating HCC from non-HCC patients and from cirrhosis patients, which was superior to AFP and AFP/WBC. Diagnostic performance of AFP/(AST*ALT) could be verified in hepatitis B virus (HBV)- or hepatitis C virus (HCV)-associated HCC patients as well. What's more, AFP/(AST*ALT) had a significant positive and moderate correlation with tumor diameter and presence of cancerous emboli or not (Spearman correlation coefficients were 0.323 and 0.305, respectively; both P < .001). For predicting HCC, the optimal cut-off value of AFP/(AST*ALT) is 1.603, and the sensitivity and specificity were 82.8% and 72.7%, respectively, which were significantly higher than the AFP and AFP/WBC.The serum AFP levels based on correction of liver inflammation can effectively improve the diagnostic performance of HCC, providing a new indicator that is simple, economical and pervasive for clinic.


Assuntos
Carcinoma Hepatocelular/sangue , Neoplasias Hepáticas/sangue , Transaminases/sangue , alfa-Fetoproteínas/metabolismo , Adulto , Área Sob a Curva , Biomarcadores Tumorais/sangue , Carcinoma Hepatocelular/enzimologia , Carcinoma Hepatocelular/imunologia , Feminino , Humanos , Inflamação/sangue , Inflamação/enzimologia , Inflamação/imunologia , Contagem de Leucócitos , Fígado/enzimologia , Fígado/imunologia , Neoplasias Hepáticas/enzimologia , Neoplasias Hepáticas/imunologia , Masculino , Pessoa de Meia-Idade , Curva ROC , Estudos Retrospectivos
13.
Medicine (Baltimore) ; 98(14): e15053, 2019 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-30946350

RESUMO

RATIONALE: Hepatoid adenocarcinoma of lung (HAL) is a rare malignant tumor, which can be defined as a primary alpha-fetoprotein (AFP)-producing lung carcinoma. The majority of hepatoid adenocarcinoma (HAC) expressed AFP in tumor cells, but AFP expression is not required for its diagnosis according to the modified diagnostic criteria. Despite that HAC exhibits a poor prognosis and ineffective treatment options, early diagnosis and aggressive treatment can result in long-term survival. PATIENT CONCERNS: We report a 70-year-old Chinese male patient with alcoholic intake over 30 years and smoking history of 60 cigarettes per day for 40 years. He sought medical consultation for productive cough and hemoptysis sputum. DIAGNOSES AND INTERVENTIONS: Chest CT scan revealed a mass (6.4 × 5.5 cm) in the left lower lobe of the lung. The patient underwent curative surgical resection, and subsequently diagnosed as HAL. OUTCOMES: Eighteen months after primary diagnosis, the patient died of multiple organ failure caused by distant metastases. LESSONS: Familiarizing with the clinical features and modified diagnostic criteria of this rare tumor may increase awareness of the disease among clinicians and pathologists, thereby avoiding misdiagnosis and mistreatment.


Assuntos
Adenocarcinoma/patologia , Neoplasias Pulmonares/patologia , Adenocarcinoma/metabolismo , Idoso , Biomarcadores Tumorais/metabolismo , Evolução Fatal , Humanos , Neoplasias Pulmonares/metabolismo , Masculino , Tomografia Computadorizada por Raios X , alfa-Fetoproteínas/metabolismo
14.
Medicine (Baltimore) ; 98(14): e15090, 2019 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-30946366

RESUMO

The aim of this study was to evaluate the effects of polymorphisms in excision repair cross-complementation group 1 (ERCC1) and alpha-fetoprotein (AFP) genes and their haplotypes on the susceptibility to hepatocellular carcinoma (HCC), and to decipher the association between single-nucleotide polymorphisms (SNPs) and clinicopathologic characteristics of HCC.Peripheral blood DNA was extracted from 206 subjects. SNaPshot technique was used for genotyping 5 SNP sites of the ERCC1 rs735482, rs1046282, rs3212948, and AFP rs737241, rs4024 genotypes. Chi-squared test and logistic regression model were used to analyze the relationship of different genotypes or haplotype and the susceptibility and clinicopathologic characteristics of HCC.The frequency of GG.GA and AA genotypes at the AFP rs737241 site in the case and control groups showed statistically significant differences (P < .05). The risk of HCC in subjects carrying mutated allele A (GA+AA) was increased by 0.543-times (P < .05) compared to that in the subjects with the GG genotype. Significant differences were observed in the linkage disequilibrium between 2 of the five SNPs (P < .05); the frequency of ERCC1 C-C and AFP A-A haplotypes was significantly lower in the case group than in the control group (P < .05). The results of clinicopathologic analysis showed that A allele at the rs737241 locus could increase the expression level of AFP (P = .007), the rs1046282 mutation C allele could increase the AFP expression level (P = .011), rs4024 locus mutation A allele could reduce the risk of vascular invasion (P = .013), rs3212948 locus mutation T allele could reduce the differentiation of liver cancer (P = .022), rs1046282 locus C allele could reduce the DNA load of hepatitis B virus (P = .035), and rs735482 A allele could increase the tumor size in HCC (P = .037).The SNPs in rs737241 for AFP gene may correlate with the occurrence of HCC. The SNPs in ERCC1 and AFP genes may affect the prognosis of HCC, offering reliable information for early prediction of tumor progression and diagnosis of HCC.


Assuntos
Carcinoma Hepatocelular/genética , Proteínas de Ligação a DNA/genética , Endonucleases/genética , Neoplasias Hepáticas/genética , alfa-Fetoproteínas/genética , Adulto , Alelos , Biomarcadores Tumorais/genética , Estudos de Casos e Controles , Distribuição de Qui-Quadrado , Proteínas de Ligação a DNA/metabolismo , Endonucleases/metabolismo , Feminino , Predisposição Genética para Doença , Humanos , Modelos Logísticos , Masculino , Pessoa de Meia-Idade , Polimorfismo de Nucleotídeo Único , alfa-Fetoproteínas/metabolismo
15.
Biomed Pharmacother ; 114: 108732, 2019 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-30925457

RESUMO

Pretreatment of mesenchymal stem cells (MSCs) with melatonin (Mel) improves their potential therapeutic effect on chronic diseases and cancers. However, this preconditioning strategy may direct the effect of Mel toward MSCs alone and deprive cancer cells of the oncostatic effect of Mel. Herein, we hypothesized that Mel given before transplantation of non-preconditioned MSCs may maximize the therapeutic outcome via the oncostatic effect of Mel by preparing a suitable tumor microenvironment for MSCs. Female rats (n = 60) were equally divided into 6 groups; normal control, diethylnitrosamine (DEN), DEN + Mel, DEN + MSCs, DEN + MSCs preconditioned with Mel, and DEN + MSCs + Mel. The obtained data revealed that administration of Mel before MSCs treatment without preconditioning yielded a better ameliorative effect against DEN-induced hepatocellular carcinoma (HCC) as evidenced by: 1) reduced serum levels of alpha fetoprotein and gamma-glutamyl transferase; 2) decreased number and area of glutathione S-transferase placental positive foci; 3) induced apoptosis (as indicated by increased cleaved caspase-3 activity, upregulated expression of proapoptotic genes Bax and caspase 3 and downregulated expression of anti-apoptotic genes Bcl2, survivin); 4) decreased malondialdehyde level and increased activities of superoxide dismutase, catalase, and glutathione peroxidase enzymes; and 5) reduced inflammation, angiogenesis and metastasis as indicated by downregulated expression of interleukin 1 beta, nuclear factor kappa B, vascular endothelial growth factor, and matrix metallopeptidase 9 genes and upregulated expression of metalloproteinase inhibitor 1 gene. Thus, administration of Mel before MSCs (without preconditioning) fostered the survival and therapeutic potential of MSCs in HCC, possibly through induction of apoptosis and inhibition of inflammation and oxidative stress. This new strategy showed better therapeutic outcomes and may improve MSC-based therapies for HCC.


Assuntos
Carcinoma Hepatocelular/induzido quimicamente , Carcinoma Hepatocelular/tratamento farmacológico , Dietilnitrosamina/farmacologia , Neoplasias Hepáticas/induzido quimicamente , Neoplasias Hepáticas/tratamento farmacológico , Melatonina/farmacologia , Células-Tronco Mesenquimais/efeitos dos fármacos , Animais , Apoptose/efeitos dos fármacos , Carcinoma Hepatocelular/metabolismo , Modelos Animais de Doenças , Regulação para Baixo/efeitos dos fármacos , Feminino , Glutationa Peroxidase/metabolismo , Glutationa Transferase/metabolismo , Inflamação/tratamento farmacológico , Inflamação/metabolismo , Fígado/efeitos dos fármacos , Fígado/metabolismo , Neoplasias Hepáticas/metabolismo , Masculino , Células-Tronco Mesenquimais/metabolismo , Estresse Oxidativo/efeitos dos fármacos , Ratos , Regulação para Cima/efeitos dos fármacos , alfa-Fetoproteínas/metabolismo , gama-Glutamiltransferase/metabolismo
16.
J Gastrointestin Liver Dis ; 28(1): 63-71, 2019 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-30851174

RESUMO

BACKGROUND AND AIMS: Direct-acting antiviral agents (DAAs) and the risk of hepatocellular carcinoma (HCC) is controversially reported in the literature. The primary endpoints of this study were to clarify the cumulative incidence and recurrence rate of HCC after DAA treatment. The secondary endpoints were to identify the factors associated with the occurrence or recurrence of HCC after DAAs treatment. METHODS: Of 234 HCV patients, 211 with no history of HCC (no-HCC-history group) and 23 with previous treated HCC history (HCC-history group) were treated with DAAs and followed for more than 24 weeks to determine the incidence of HCC. Platelet count, albumin, α-fetoprotein (AFP) level, L3%, the FIB-4 index and APRI scores were analyzed as possible factors associated with HCC occurrence and recurrence. An intergroup comparison was made of the cumulative incidence of HCC. Cox proportional hazards regression was used to determine associations between blood test values and risk of HCC. RESULTS: The median observation period was 21 months. Cumulative incidence of HCC was higher in the HCC-history group than in the no-HCC-history group (p < 0.0001, 19.0 and 0.52 per 100 patient-years, respectively). Univariate analysis revealed platelet count, albumin, α-fetoprotein (AFP) level, AFP-L3%, and FIB-4 index and APRI scores at the end of DAA treatment as being significantly associated with occurrence/recurrence of HCC. Multivariate analysis revealed that AFP levels before and after the administration of DAAs and AFP-L3% after DAA were independently associated with the occurrence/recurrence of HCC (p = 0.045, 0.043, 0.005, respectively). CONCLUSION: The HCC occurrence rate after DAA treatment was very low, and the recurrence rate lower than that in previous interferon reports. The AFP level and AFP-L3% were identified as important factors in predicting occurrence/recurrence of HCC. Careful observation is needed when increased levels of AFP or AFP-L3% after DAAs treatment are observed.


Assuntos
Antivirais/uso terapêutico , Carcinoma Hepatocelular/prevenção & controle , Hepatite C Crônica/tratamento farmacológico , Neoplasias Hepáticas/prevenção & controle , Adulto , Idoso , Idoso de 80 Anos ou mais , Carcinoma Hepatocelular/diagnóstico por imagem , Carcinoma Hepatocelular/epidemiologia , Carcinoma Hepatocelular/virologia , Feminino , Hepatite C Crônica/diagnóstico , Hepatite C Crônica/epidemiologia , Hepatite C Crônica/virologia , Humanos , Incidência , Neoplasias Hepáticas/diagnóstico por imagem , Neoplasias Hepáticas/epidemiologia , Neoplasias Hepáticas/virologia , Masculino , Pessoa de Meia-Idade , Fatores de Proteção , Recidiva , Estudos Retrospectivos , Medição de Risco , Fatores de Risco , Fatores de Tempo , Tóquio/epidemiologia , Resultado do Tratamento , alfa-Fetoproteínas/metabolismo
17.
Medicine (Baltimore) ; 98(11): e14534, 2019 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-30882620

RESUMO

RATIONALE: Hepatoid adenocarcinoma (HAC) of the fallopian tubes is a rare malignant tumor in the female reproductive system. PATIENT CONCERNS: An 81-year-old Chinese woman presented with an elevated serum alpha-fetoprotein (AFP) level. DIAGNOSIS: Positron emission tomography-computed tomography (PET-CT) scan revealed a mass of approximately 47 × 27 mm located in the right adnexa. The tumor was diagnosed as a HAC arising from fallopian tube by immunohistochemical and histochemical technique. INTERVENTIONS: This patient underwent surgical treatment including a bilateral adnexectomy and appendectomy. In addition, the patient underwent 5 cycles of postoperative chemotherapy. OUTCOMES: The disease has recurred approximately six months after surgery and therefore, this patient will continue to be observed. LESSONS: Up to this point, only 4 known cases of HAC originating in fallopian tube have been published in the English literature. Further studies are needed to better understand the clinical characteristics, the prognosis, and the pathological mechanism of HAC development in the fallopian tubes.


Assuntos
Adenocarcinoma/patologia , Adenocarcinoma/terapia , Neoplasias das Tubas Uterinas/patologia , Neoplasias das Tubas Uterinas/terapia , Recidiva Local de Neoplasia , Adenocarcinoma/diagnóstico por imagem , Idoso de 80 Anos ou mais , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Apendicectomia , Quimioterapia Adjuvante , Neoplasias das Tubas Uterinas/diagnóstico por imagem , Feminino , Humanos , Tomografia por Emissão de Pósitrons , Salpingectomia , alfa-Fetoproteínas/metabolismo
18.
BMC Cancer ; 19(1): 278, 2019 Mar 28.
Artigo em Inglês | MEDLINE | ID: mdl-30922327

RESUMO

BACKGROUND: Codrituzumab, a humanized monoclonal antibody against Glypican-3 (GPC3), which is expressed in hepatocellular carcinoma (HCC), was tested in a randomized phase II trial in advanced HCC patients who had failed prior systemic therapy. Biomarker analysis was performed to identify a responder population that benefits from treatment. METHODS: A novel statistical method based on the Indian buffet process (IBP) was used to identify biomarkers predictive of response to treatment with Codrituzumab. The IBP is a novel method that allows flexibility in analysis design, and which is sensitive to slight, but meaningful between-group differences in biomarkers in very complex datasets RESULTS: The IBP model identified several subpopulations of patients having defined biomarker values. Tumor necrosis and viable cell content in the tumor were identified as prognostic markers of disease progression, as were the well-known HCC prognostic markers of disease progression, alpha-fetoprotein and Glypican-3 expression. Predictive markers of treatment response included natural killer (NK) cell surface markers and parameters influencing NK cell activity, all related to the mechanism of action of this drug CONCLUSIONS: The Indian buffet process can be effectively used to detect statistically significant signals with high sensitivity in complex and noisy biological data TRIAL REGISTRATION: NCT01507168 , January 6, 2012.


Assuntos
Anticorpos Monoclonais Humanizados/administração & dosagem , Biomarcadores Tumorais/metabolismo , Carcinoma Hepatocelular/tratamento farmacológico , Neoplasias Hepáticas/tratamento farmacológico , Anticorpos Monoclonais Humanizados/farmacologia , Carcinoma Hepatocelular/metabolismo , Estudos de Casos e Controles , Progressão da Doença , Feminino , Regulação Neoplásica da Expressão Gênica/efeitos dos fármacos , Glipicanas/metabolismo , Humanos , Neoplasias Hepáticas/metabolismo , Masculino , Modelos Estatísticos , Análise de Sobrevida , Resultado do Tratamento , alfa-Fetoproteínas/metabolismo
20.
Niger J Clin Pract ; 22(3): 342-349, 2019 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-30837421

RESUMO

Background: Primary malignant mediastinal germ cell tumors (PMMGCTs) including seminomas and nonseminomatous germ cell tumors (NSGCTs) are rare, and sometimes the diagnosis is very difficult. Purpose: The purpose of this study is to compare the clinical characteristics, biomarkers, and imaging findings of seminomas and NSGCTs and to determine whether these features could help distinguish these two types of PMMGCT. Material and Methods: A retrospective study of 24 male patients with histopathologically proven PMMGCT was performed. We collected the information of computed tomography (CT) (the scan area ranged from the apex of lung to the costophrenic angles) and magnetic resonance imaging blood test and histology characteristics of these patients. Results: Twelve of 24 cases were confirmed to be seminomas, whereas the other 12 cases were NSGCTs. Alfa-fetoprotein (AFP) was found to be elevated in all patients with NSGCT, whereas none of the patients with seminomas had elevated AFP level. Beta-human chorionic gonadotropin (ß-HCG) level was elevated in all the patients with seminomas (seven/seven), whereas in NSGCT only two of seven patients had elevated ß-HCG. Lactate dehydrogenase level was increased in five of the nine patients with seminomas, as well as in the eight patients with NSGCT. CT imaging revealed that 12 masses from the seminoma group were homogeneous, soft tissue opacity and showed minimal contrast enhancement. On the contrary, all 12 NSGCT cases showed cystic and solid masses; on contrast-enhanced CT, heterogeneous enhancement was found on the capsule of the tumor, septum, and solid masses. Conclusion: Seminomas and NSGCT showed different profiles of tumor biomarkers and radiographic features. Evidence from serum test, histopathological analysis, and imaging should be combined to ensure the accurate diagnosis of these two types of PMMGCT.


Assuntos
Biomarcadores Tumorais/sangue , Gonadotropina Coriônica Humana Subunidade beta/sangue , L-Lactato Desidrogenase/sangue , Neoplasias do Mediastino/diagnóstico por imagem , Neoplasias Embrionárias de Células Germinativas/diagnóstico por imagem , Seminoma/diagnóstico por imagem , Neoplasias Testiculares/diagnóstico por imagem , Tomografia Computadorizada por Raios X/métodos , alfa-Fetoproteínas/metabolismo , Adulto , Humanos , Masculino , Neoplasias do Mediastino/sangue , Neoplasias do Mediastino/patologia , Pessoa de Meia-Idade , Neoplasias Embrionárias de Células Germinativas/sangue , Neoplasias Embrionárias de Células Germinativas/patologia , Estudos Retrospectivos , Seminoma/sangue , Seminoma/patologia , Neoplasias Testiculares/sangue , Neoplasias Testiculares/patologia
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