RESUMEN
BACKGROUND: The function of hornerin (HRNR), a member of the S100 protein family, is poorly clarified in the development of human tumors. The role of HRNR in hepatocellular carcinoma (HCC) progression is investigated in the study. METHODS: The expression levels of HRNR were assessed in tumor samples from a cohort of 271 HCC patients. The effect of HRNR on proliferation, colony formation and invasion of tumor cells was examined. We further determined the role of HRNR in tumor growth in vivo by using xenograft HCC tumor models. The possible mechanism of the HRNR promotion of HCC progression was explored. RESULTS: We found that HRNR was overexpressed in HCC tissues. The high expression of HRNR in HCCs was significantly associated with vascular invasion, poor tumor differentiation, and advanced TNM stage. The disease-free survival (DFS) and overall survival (OS) of HCC patients with high HRNR expression were poorer than those in the low HRNR expression group. HRNR expression was an independent risk factor linked to both poor DFS (HR = 2.209, 95% CI = 1.627-2.998,P < 0.001) and OS (HR = 2.459,95% CI = 1.736-3.484, P < 0.001). In addition, the knockdown of HRNR by shRNAs significantly inhibited the proliferation, colony formation, migration and invasion of HCC tumor cells. HRNR silencing led to the decreased phosphorylation of AKT signaling. Notably, tumor growth was markedly inhibited by HRNR silencing in a xenograft model of HCC. CONCLUSIONS: HRNR promotes tumor progression and is correlated with a poor HCC prognosis. HRNR may contribute to HCC progression via the regulation of the AKT pathway.
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Proteínas de Unión al Calcio/genética , Carcinoma Hepatocelular/genética , Proliferación Celular/genética , Proteínas de Filamentos Intermediarios/genética , Neoplasias Hepáticas/genética , Adulto , Anciano , Animales , Carcinoma Hepatocelular/patología , Movimiento Celular/genética , Metilación de ADN/genética , Progresión de la Enfermedad , Supervivencia sin Enfermedad , Femenino , Regulación Neoplásica de la Expresión Génica , Humanos , Neoplasias Hepáticas/patología , Masculino , Ratones , Persona de Mediana Edad , Invasividad Neoplásica/genética , Invasividad Neoplásica/patología , Proteína Oncogénica v-akt/genética , Pronóstico , Transducción de Señal/genética , Ensayos Antitumor por Modelo de XenoinjertoRESUMEN
In liver transplant patients with type 2 diabetes mellitus (DM), the disease worsens after transplantation because of longterm use of diabetogenic immunosuppressive drugs, making management of those patients a great challenge. The objective of our study was to evaluate the safety and efficacy of a simplified multivisceral transplantation (SMT) procedure for the treatment of patients with end-stage liver disease and concurrent type 2 DM. Forty-four patients who had pretransplant type 2 DM were included. A total of 23 patients received SMT, and 21 patients received orthotopic liver transplantation (OLT). Patient and graft survivals, complications, diabetic control, and quality of life (QOL) were retrospectively analyzed in both groups. The 1-, 3-, and 5-year cumulative patient and graft survival rates were 91.5%, 75.4%, and 75.4% in the SMT group and were 94.4%, 64.4%, and 64.4% in the OLT group, respectively (P = 0.70). Interestingly, 95.7% (22/23) of patients achieved complete remission from DM after SMT compared with 16.7% (3/18) of patients after OLT. The occurrence of biliary complication was significantly higher in the OLT group than that in the SMT group (23.8% versus 0.0%; P = 0.01). Moreover, better QOL was observed in the SMT group than that in the OLT group. In conclusion, the SMT procedure we described here is a safe and viable option for patients with end-stage live disease and concurrent type 2 DM. This SMT procedure offers excellent transplant outcomes and QOL. Liver Transplantation 23 1161-1170 2017 AASLD.
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Diabetes Mellitus Tipo 2/cirugía , Enfermedad Hepática en Estado Terminal/cirugía , Inmunosupresores/efectos adversos , Trasplante de Hígado/métodos , Complicaciones Posoperatorias/epidemiología , Adulto , Anciano , Enfermedades de las Vías Biliares/epidemiología , Enfermedades de las Vías Biliares/etiología , Diabetes Mellitus Tipo 2/complicaciones , Diabetes Mellitus Tipo 2/mortalidad , Enfermedad Hepática en Estado Terminal/complicaciones , Enfermedad Hepática en Estado Terminal/mortalidad , Estudios de Factibilidad , Femenino , Estudios de Seguimiento , Rechazo de Injerto/prevención & control , Supervivencia de Injerto , Humanos , Trasplante de Hígado/efectos adversos , Masculino , Persona de Mediana Edad , Complicaciones Posoperatorias/etiología , Calidad de Vida , Estudios Retrospectivos , Encuestas y Cuestionarios , Tasa de Supervivencia , Resultado del TratamientoRESUMEN
Prognostic value of peripheral monocyte, as a member of inflammatory cells, was widely being investigated. The aim of this study was to evaluate the prognostic value of preoperative peripheral blood monocyte count for hepatocellular carcinoma (HCC) patients who underwent liver transplantation (LT) and the relationship between monocyte count and tumor-related characteristics. We retrospectively analyzed the clinical data of 101 HCC patients after LT. Preoperative monocyte count and demographic, clinical, and pathologic data were analyzed. The optimal cutoff value of monocyte count was 456/mm(3), with the sensitivity and specificity of 69.4 and 61.5 %, respectively. Elevated preoperative peripheral blood monocyte count was significantly associated with large tumor size. The 1-, 3-, and 5-year disease-free survival (DFS) (80.9, 70.1, and 53.3 % vs 55.1, 38.7, and 38.7 %, P = 0.007) and overall survival (OS) rates (95.7, 76.6, and 64.8 % vs 72.2, 44.1, and 36.1 %, P = 0.002) of HCC patients in the peripheral blood monocyte count ≤456/mm(3) group were higher than those in the peripheral blood monocyte count >456/mm(3) group. In conclusion, elevated preoperative peripheral blood monocyte count was significantly associated with advanced tumor stage and it can be considered as a prognostic factor for HCC patients after LT.
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Carcinoma Hepatocelular/patología , Leucocitos Mononucleares/patología , Neoplasias Hepáticas/patología , Monocitos/patología , Supervivencia sin Enfermedad , Femenino , Humanos , Recuento de Leucocitos/métodos , Trasplante de Hígado/métodos , Masculino , Persona de Mediana Edad , Periodo Preoperatorio , Pronóstico , Estudios Retrospectivos , Sensibilidad y EspecificidadRESUMEN
BACKGROUND: The occurrence and development of hepatocellular carcinoma (HCC) depends largely on such non-tumor factors as inflammatory condition, immune state, viral infection and liver fibrosis. Various inflammation-based prognostic scores have been associated with survival in patients with HCC, such as the neutrophil/lymphocyte ratio (NLR), the platelet/lymphocyte ratio (PLR) and the prognostic nutritional index (PNI). The aspartate aminotransferase/platelet count ratio index (APRI) is thought to be a biomarker of liver fibrosis and cirrhosis. This study aims to evaluate the ability of these indices to predict survival in HCC patients after curative hepatectomy, and probe the increased prognostic accuracy of APRI combined with established inflammation-based prognostic scores. METHODS: Data were collected retrospectively from 321 patients who underwent curative resection for HCC. Preoperative NLR, PLR, PNI, APRI and clinico-pathological variables were analyzed. Univariate and multivariate analyses were performed to identify the predictive value of the above factors for disease-free survival (DFS) and overall survival (OS). RESULTS: Univariate analysis showed that NLR, PLR, PNI and APRI were significantly associated with DFS and OS in HCC patients with curative resection. Multivariate analysis showed that NLR and APRI were superior to PLR and PNI, and both were independently correlated with DFS and OS. Preoperative NLR >2 or APRI >1.68 predicted poor prognosis of patients with HCC after hepatectomy. Furthermore, the predictive range of NLR combined with APRI was more sensitive than that of either measure alone. CONCLUSIONS: Preoperative NLR and APRI are independent predictors of DFS and OS in patients with HCC after surgical resection. Higher levels of NLR or APRI predict poorer outcomes in HCC patients. Intriguingly, combining NLR and APRI increases the prognostic accuracy of testing.
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Aspartato Aminotransferasas/metabolismo , Carcinoma Hepatocelular/patología , Neoplasias Hepáticas/patología , Linfocitos/inmunología , Neutrófilos/inmunología , Adulto , Anciano , Carcinoma Hepatocelular/metabolismo , Carcinoma Hepatocelular/mortalidad , Femenino , Humanos , Neoplasias Hepáticas/metabolismo , Neoplasias Hepáticas/mortalidad , Masculino , Persona de Mediana Edad , Evaluación Nutricional , Recuento de Plaquetas , Pronóstico , Análisis de Supervivencia , Adulto JovenRESUMEN
BACKGROUND: Tumor suppression of Transforming Growth Factor (TGF-ß) signaling pathway requires an adaptor protein, Embryonic Liver Fodrin (ELF). Disruption of ELF expression resulted in miscolocalization of Smad3 and Smad4, then disruption of TGF-ß signaling. However, the prognostic significance of ELF for hepatocellular carcinoma (HCC) hasn't been clarified. This study aimed to investigate whether measuring both TGF-ß1 and ELF provides a more powerful predictor for HCC prognosis than either marker alone. METHODS: TGF-ß1 and ELF protein were detected by immunohistochemistry. The relationship between TGF-ß1/ELF expression and patients' clinicopathologic factors was analyzed. The association between TGF-ß1/ELF expression and disease-free survival and overall survival was analyzed by Kaplan-Meier curves, the log-rank test, and Multivariate Cox regression analyses. RESULTS: The expression of TGF-ß1 in HCC tissues was significantly higher than that in normal liver tissues. Conversely, the expression of ELF in HCC tissues declined markedly. ELF protein was correlated with HBsAg, tumor size, tumor number, TNM and recurrence. Data also indicated a significant negative correlation between ELF and TGF-ß1. Patients with high TGF-ß1 expression or/and low ELF expression appeared to have a poor postoperative disease-free survival and overall survival compared with those with low TGF-ß1 expression or/and high ELF expression. Furthermore, the predictive range of ELF combined with TGF-ß1 was more sensitive than that of either one alone. CONCLUSIONS: TGF-ß1 and ELF protein are potential and reliable biomarkers for predicting prognosis in HCC patients after hepatic resection. Our current study has demonstrated that the prognostic accuracy of testing can be enhanced by their combination.
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Carcinoma Hepatocelular/metabolismo , Carcinoma Hepatocelular/mortalidad , Proteínas Portadoras/metabolismo , Neoplasias Hepáticas/metabolismo , Neoplasias Hepáticas/mortalidad , Proteínas de Microfilamentos/metabolismo , Factor de Crecimiento Transformador beta1/metabolismo , Adulto , Anciano , Biomarcadores de Tumor , Carcinoma Hepatocelular/patología , Carcinoma Hepatocelular/cirugía , Femenino , Estudios de Seguimiento , Expresión Génica , Humanos , Inmunohistoquímica , Estimación de Kaplan-Meier , Neoplasias Hepáticas/patología , Neoplasias Hepáticas/cirugía , Masculino , Persona de Mediana Edad , Clasificación del Tumor , Estadificación de Neoplasias , Pronóstico , Transducción de Señal , Carga Tumoral , Adulto JovenRESUMEN
BACKGROUND: Pancreatic fistula (PF) remains the most challenging complication after pancreaticoduodenectomy (PD). The purpose of this study was to identify the risk factors of PF and delineate its impact on patient outcomes. METHODS: We retrospectively reviewed clinical data of 532 patients who underwent PD and divided them into PF group and no PF group. Risk factors and outcomes of PF following PD were examined. RESULTS: PF was found in 65 (12.2%) cases, of whom 11 were classified into ISGPF grade A, 42 grade B, and 12 grade C. Clinically serious postoperative complications in the PF versus no PF group were mortality, abdominal bleeding, bile leak, intra-abdominal abscess and pneumonia. Univariate and multivariate analysis showed that blood loss ≥ 500 ml, pancreatic duct diameter ≤ 3 mm and pancreaticojejunostomy type were independent risk factors of PF after PD. CONCLUSIONS: Blood loss ≥ 500 ml, pancreatic duct diameter ≤ 3 mm and pancreatico-jejunostomy type were independent risk factors of PF after PD. PF was related with higher mortality rate, longer hospital stay, and other complications.
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Fístula Pancreática/etiología , Pancreaticoduodenectomía , Complicaciones Posoperatorias/etiología , Adulto , Anciano , Femenino , Humanos , Masculino , Auditoría Médica , Persona de Mediana Edad , Análisis Multivariante , Evaluación de Resultado en la Atención de Salud , Fístula Pancreática/mortalidad , Pancreatoyeyunostomía , Complicaciones Posoperatorias/mortalidad , Estudios Retrospectivos , Factores de RiesgoRESUMEN
BACKGROUND: There is conflicting evidence concerning platelet status and hepatocellular carcinoma (HCC) prognosis. We evaluated the prognostic value of platelet-based indices, including platelet count, platelet/lymphocyte ratio (PLR), and aspartate aminotransferase to platelet ratio index (APRI) in HCC after hepatic resection. METHODS: We retrospectively reviewed 332 patients with HCC treated with hepatectomy between 2006 and 2009. Preoperative platelet count, as well as demographic, clinical, and pathologic data, were analyzed. RESULTS: Both disease-free survival (DFS) and overall survival (OS) were significantly improved for patients with low platelet count, PLR, and APRI compared to patients with elevated values. On multivariate analysis, APRI, tumor size ≥5 cm, noncapsulation, and multiple tumors were all associated with both poor DFS and OS. The 1-, 3-, and 5-year DFS rates were 52, 36, and 32 % for patients with APRI <0.62 and were 35, 22, and 19 % for patients with APRI ≥0.62. Correspondingly, the 1-, 3-, and 5-year OS rates were 77, 51, and 42, and 63, 35, and 29 % for both groups. Both DFS and OS of patients with APRI <0.62 were significantly better compared to patients with an elevated APRI (P = 0.009 and 0.002, respectively). Patients with elevated APRI tended to have cirrhosis, hepatitis B virus (HBV) infection, surgical margin <1 cm, and noncapsulated tumors. CONCLUSIONS: Elevated platelets based inflammatory indices, especially APRI, was associated with adverse characteristic features and poor prognosis in HCC, especially for patients with HBV infection or cirrhosis. Antiplatelet treatment may represent a potential therapy for HBV-induced HCC recurrence.
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Aspartato Aminotransferasas/metabolismo , Biomarcadores de Tumor/análisis , Plaquetas/patología , Carcinoma Hepatocelular/patología , Hepatectomía/efectos adversos , Hepatitis B/complicaciones , Neoplasias Hepáticas/patología , Adulto , Anciano , Carcinoma Hepatocelular/enzimología , Carcinoma Hepatocelular/etiología , Carcinoma Hepatocelular/mortalidad , Femenino , Estudios de Seguimiento , Hepatitis B/cirugía , Hepatitis B/virología , Virus de la Hepatitis B/aislamiento & purificación , Humanos , Neoplasias Hepáticas/enzimología , Neoplasias Hepáticas/etiología , Neoplasias Hepáticas/mortalidad , Masculino , Persona de Mediana Edad , Estadificación de Neoplasias , Cuidados Preoperatorios , Pronóstico , Estudios Retrospectivos , Tasa de Supervivencia , Adulto JovenRESUMEN
BACKGROUNDS: Neutrophil-lymphocyte ratio (NLR) has recently been reported as a predictor of Hepatocellular carcinoma (HCC). However, its prognostic value in HCC still remains controversial. In this study, we aimed to evaluate the association between NLR and clinical outcome of HCC patients by performing meta-analysis. METHODS: A comprehensive literature search for relevant studies published up to August 2013 was performed by using PubMed, Ovid, the Cochrane Library and Web of Science databases. Meta-analysis was performed using hazard ratio (HR) or odds ratio (OR) and 95% confidence intervals (95% CIs) as effect measures. RESULTS: A total of 15 studies encompassing 3094 patients were included in this meta-analysis. Our pooled results showed that high NLR was associated with poor overall survival (OS) and disease free survival (DFS) in HCC initially treated by liver transplantation (HR = 3.42, 95% CI:2.41-4.85,P = 0.000; HR = 5.90, 95% CI:3.99-8.70,P = 0.000, respectively) and surgical resection (HR = 3.33, 95% CI:2.23-4.98, P = 0.000; HR = 2.10, 95% CI: 2.06-2.14, respectively). High NLR was also associated with poor OS in HCC treated by radiofrequency-ablation (HR = 1.28, 95%CI: 1.10-1.48, P = 0.000), TACE (HR = 2.52, 95% CI: 1.64-3.86, P = 0.000) and mixed treatment (HR = 1.85, 95% CI: 1.40-2.44, P = 0.000), respectively. In addition, high NLR was significantly correlated with the presence of vascular invasion (OR = 2.69, 95% CI: 2.01-3.59, P = 0.000), tumor multifocality (OR = 1.74, 95% CI: 1.30-2.34, P = 0.000) and higher incidence of AFP ≥ 400 ng/ml (OR = 1.46, 95% CI: 1.01-2.09, P = 0.04). CONCLUSION: Elevated NLR indicates a poor prognosis for patients with HCC. NLR may be a convenient, easily-obtained, low cost and reliable biomarker with prognostic potential for HCC.
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Carcinoma Hepatocelular/inmunología , Carcinoma Hepatocelular/patología , Neoplasias Hepáticas/inmunología , Neoplasias Hepáticas/patología , Linfocitos Infiltrantes de Tumor/inmunología , Infiltración Neutrófila , Neutrófilos/patología , Carcinoma Hepatocelular/mortalidad , Carcinoma Hepatocelular/terapia , Terapia Combinada , Humanos , Recuento de Leucocitos , Neoplasias Hepáticas/mortalidad , Neoplasias Hepáticas/terapia , Linfocitos Infiltrantes de Tumor/patología , Clasificación del Tumor , Neovascularización Patológica , Oportunidad Relativa , Modelos de Riesgos Proporcionales , Sesgo de Publicación , Carga TumoralRESUMEN
BACKGROUND: Peripheral blood monocyte count is an easily assessable parameter of systemic inflammatory response. The aim of this study was to determine whether monocyte count was prognostic in hepatocellular carcinoma (HCC) following hepatic resection. METHODS: We retrospectively reviewed 351 patients with HCC treated with hepatic resection from 2006 to 2009. Preoperative absolute peripheral monocyte count, demographics, and clinical and pathological data were analyzed. RESULTS: On univariate and multivariate analysis, elevated monocyte counts (≥ 545/mm(3)), tumor size ≥ 5 cm, non-capsulation, and multiple tumors were associated with poor disease-free survival (DFS) and overall survival (OS). The 1-, 3- and 5-year DFS rates were 58%, 41% and 35%, respectively, for patients with monocyte counts <545/mm(3), and 36%, 23% and 21% for patients with monocyte counts ≥ 545/mm(3). Correspondingly, the 1-, 3- and 5-year OS rates were 79%, 53% and 46% for monocyte counts <545/mm(3), and 64%, 36% and 29% for monocyte counts ≥ 545/mm(3). Subgroup analysis indicated that DFS after hepatic resection in hepatitis B virus (HBV)-infected patients was significantly better in those with a peripheral blood monocyte counts <545/mm(3), but it did not differ between patients without HBV infection. In addition, DFS was significantly better for patients with a peripheral blood monocyte count <545/mm(3), whether or not cirrhosis was present. Patients with elevated monocyte counts tended to have larger tumors. CONCLUSIONS: Elevated preoperative monocyte count is an independent predictor of worse prognosis for patients with HCC after hepatic resection, especially for those with HBV infection. Postoperative adjuvant treatment might be considered for patients with elevated preoperative monocyte counts.
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Carcinoma Hepatocelular/sangre , Carcinoma Hepatocelular/patología , Neoplasias Hepáticas/sangre , Neoplasias Hepáticas/patología , Monocitos/fisiología , Adulto , Anciano , Carcinoma Hepatocelular/cirugía , Supervivencia sin Enfermedad , Femenino , Humanos , Recuento de Leucocitos , Neoplasias Hepáticas/cirugía , Masculino , Persona de Mediana Edad , Análisis de Supervivencia , Adulto JovenRESUMEN
BACKGROUNDS: Glypican-3(GPC3) has been implicated in tumor development and progression for several years. However, the prognostic significance of GPC3 expression in patients with hepatocellular carcinoma (HCC) is controversial. We performed a meta-analysis of available studies to assess whether GPC3 can be used as a prognostic factor in patients with HCC. METHODS: We searched PubMed and Ovid EBM Reviews databases and evaluated the reference list of relevant articles for studies that assessed the prognostic relevance of GPC3 in patients with HCC. Meta-analysis was performed using hazard ratio (HR) or odds ratio (OR) and 95% confidence intervals (95% CIs) as effect measures. RESULTS: A meta-analysis of eight studies included 1070 patients was carried out to evaluate the association between GPC3 and overall survival (OS) and disease-free survival (DFS) in HCC patients. The relation between GPC3 and tumor pathological features was also assessed. Our analysis results indicated that high GPC3 expression predicted poor OS (HR: 1.96, 95% CI: 1.51-2.55) and DFS (HR: 1.99, 95% CI: 1.57-2.51) of patients with HCC. GPC3 overexpression was significantly associated with high tumor grade (OR: 3.30, 95% CI: 2.04-5.33), late TNM stage (OR: 2.26, 95% CI: 1.00-5.12), and the presence of vascular invasion (OR: 2.43, 95% CI: 1.23-4.82). CONCLUSIONS: GPC3 overexpression indicates a poor prognosis for patients with HCC, and it may also have predictive potential for HCC invasion and metastasis.
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Carcinoma Hepatocelular/genética , Glipicanos/genética , Neoplasias Hepáticas/genética , Pronóstico , Biomarcadores de Tumor/biosíntesis , Carcinoma Hepatocelular/patología , Supervivencia sin Enfermedad , Regulación Neoplásica de la Expresión Génica , Glipicanos/biosíntesis , Humanos , Neoplasias Hepáticas/patología , Persona de Mediana Edad , Invasividad Neoplásica , Estadificación de NeoplasiasRESUMEN
BACKGROUND: Conflicting results were found between radiofrequency-assisted liver resection (RF-LR) and clamp-crush liver resection (CC-LR) during liver surgery. We conducted a systematic review and meta-analysis that included randomized controlled trials (RCTs) and non-RCTs to compare the effectiveness and safety of RF-LR versus CC-LR during liver surgery. METHODS: Articles comparing RF-LR and CC-LR that were published before December 2012 were retrieved and subjected to a systematic review and meta-analysis. Data synthesis and statistical analysis were carried out by Review Manager Version 5.2 software. RESULTS: In all, four RCTs and five nonrandomized studies evaluating 728 patients were included. Compared with CC-LR, the RF-LR group had significantly reduced total intraoperative blood loss (weighted mean difference [WMD] = -187 mL; 95% confidence interval [CI] = -312, -62; data on 628 patients), and blood loss during liver transection (WMD = -143.7 mL; 95% CI = -200, -87; data on 190 patients). However, RF-LR is associated with a higher rate of intra-abdominal abscess than the clamp-crushing method (odds ratio = 3.61; 95% CI = 1.26, 10.32; data on 366 patients). No significant difference was observed between both the groups for the incidence of both blood transfusion and bile leak. CONCLUSIONS: There is currently not sufficient evidence to support or refute the use of RF-LR in liver surgery. RF-LR has advantages in terms of reducing blood loss. However, RF-LR may increase the rates of both bile leak and abdominal abscess. So, the safety of RF-LR has not been established. Future well-designed RCTs are awaited to further investigate the efficacy and safety of RF devices in liver resection.
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Ablación por Catéter/métodos , Hemostasis Quirúrgica/métodos , Hepatectomía/métodos , Hepatopatías/cirugía , Neoplasias Hepáticas/cirugía , Hepatectomía/instrumentación , Humanos , Ensayos Clínicos Controlados Aleatorios como Asunto , Instrumentos QuirúrgicosRESUMEN
BACKGROUND/AIMS: DNA-based tumor vaccine immunotherapy which elicits exclusively cellular immune response against cancer cells in an antigen-specific fashion has been documented to be an effective treatment for cancers in the past decade. Glypican 3 (GPC3) is especially overexpressed in hepatocellular carcinoma (HCC), but not in benign liver lesions and normal adult tissues, which makes it an ideal tumor antigen designed for HCC immunotherapy. METHODOLOGY: We constructed a GPC3 cDNA vaccine by using a recombinant plasmid encoding murine GPC3 cDNA for treatment of HCC in a C57BL/6 mouse model. The specificity and effectiveness of anti-tumor immunity were assessed in vitro and in vivo studies. RESULTS: In vitro studies showed that GPC3 DNA vaccine induced potent specific cytotoxic T lymphoctyes (CTLs) immune response against C57BL/6 homogenous HCC cell line Hepa 1-6 (GPC3+). However, there was no detectable immune response against GPC3-negative SP 2/0 cells and Sk-Hep-1 cells. In vivo study indicated that GPC3 DNA vaccine could significantly suppress homogenous tumor growth and prolong survival time of tumor bearing mice. CONCLUSIONS: This study demonstrated the first time that the GPC3 DNA vaccine could elicit specific and effective cellular antitumor immunity against GPC3 HCC. This may provide an alternative option for immunotherapy of HCC.
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Antígenos de Neoplasias/inmunología , Vacunas contra el Cáncer/inmunología , Carcinoma Hepatocelular/inmunología , Glipicanos/inmunología , Neoplasias Hepáticas/inmunología , Vacunas de ADN/inmunología , Adulto , Animales , Antígenos de Neoplasias/genética , Vacunas contra el Cáncer/genética , Carcinoma Hepatocelular/metabolismo , Carcinoma Hepatocelular/mortalidad , Carcinoma Hepatocelular/patología , Línea Celular Tumoral , Femenino , Glipicanos/análisis , Glipicanos/genética , Glipicanos/metabolismo , Humanos , Interferón gamma/análisis , Interferón gamma/metabolismo , Estimación de Kaplan-Meier , Neoplasias Hepáticas/metabolismo , Neoplasias Hepáticas/mortalidad , Neoplasias Hepáticas/patología , Ratones , Ratones Endogámicos C57BL , Linfocitos T Citotóxicos/inmunología , Vacunas de ADN/genéticaRESUMEN
Among the lymphatic system in the human body, the spleen is the most extensive one and has hematopoietic, hemofiltration, blood storage, and immune functions. As a new method of preserving the spleen, laparoscopic partial splenectomy (LPS) has been increasingly applied in clinical practice with people's deeper insights into minimally invasive treatment and the development of technical equipment. Compared with conventional open splenectomy, LPS can preserve normal spleen tissue as much as possible, decrease the occurrence of complications after total splenectomy, and reduce postoperative hospital stay. The bipolar radiofrequency excision hemostatic device used for LPS can solidify the splenic tissue and close the small blood vessels, which reduces the hemorrhage of the spleen cross-section and clears the operative field, thus achieving the ideal effect of "bloodless partial splenectomy". Therefore, under the premise of strictly mastering the indications and fully understanding the vascular anatomy of the spleen, the application of the bipolar radiofrequency excision hemostatic device in LPS is worthy of clinical promotion.
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Hemostáticos , Laparoscopía , Humanos , Esplenectomía/métodos , Lipopolisacáridos , Laparoscopía/métodos , Bazo/cirugíaRESUMEN
Hepatocellular carcinoma (HCC) is the sixth most commonly diagnosed malignancy and the third leading cause of cancer-related deaths worldwide. A 58-year-old man visited his local hospital due to abdominal discomfort and was diagnosed with lung metastasis. After admission to our hospital in April 2020, he received two cycles of transcatheter arterial embolization (TAE), hepatic arterial infusion chemotherapy (HAIC-Folfox), sorafenib, and camrelizumab every 3 weeks. Due to the end of HAIC treatment, he underwent drug-eluting transcatheter arterial chemoembolization (dTACE) once, sorafenib, and camrelizumab. However, because of worsening liver function, we interrupted TACE and only gave sorafenib and camrelizumab in August 2020. Although he received systemic therapy, the tumors still rapidly progressed and we considered the possibility of tumor resistance. Subsequently, regorafenib was given. In September, the patient underwent conventional TACE (cTACE) once, regorafenib, and camrelizumab. After half a year of comprehensive treatment, the treatment effect was not satisfactory, and he returned to the local hospital to received regorafenib every day and camrelizumab once every 3 weeks. The patient found that the tumor and lung metastasis had shrunk significantly after 1 year of the initial diagnosis, then he was admitted to our hospital and received surgery treatment, and now he has survived disease-free for 6 months.
RESUMEN
OBJECTIVE: To compare the outcomes between anterior versus conventional approach right hepatectomy for large hepatocellular carcinoma (HCC). METHODS: A total of 188 consecutive patients with large HCC ( > or =5 cm) undergoing right hepatectomy were reviewed retrospectively. Among them, 92 patients received anterior approach right hepatectomy (anterior group) while the other conventional right hepatectomy (conventional group). Their clinicopathologic data and survivals were compared. RESULTS: There were five surgical deaths (2.7%), two in the anterior group and three in the conventional group. The biochemical and tumor pathological data (except for tumor size) of these two groups were comparable. The mean intraoperative blood loss, the number of patients with massive hemorrhage ( >3000 ml) and the volume of blood transfusion of the anterior group were markedly less than those of conventional group. The 1-, 3-year disease-free survival rates of the anterior group were significantly better than those of the conventional group (56.2%, 30.9% vs. 39.1%, 13.0%, P = 0.043). The 1- & 3-year cumulative survival rates of the anterior group were also markedly higher than those of conventional group. The Cox regression model indicated that tumor size [P = 0.014, odd ratio (OD) = 1.074] and surgical procedure (P = 0.009, OD = 0. 468) were independent risk factors correlated with disease-free survival. And the surgical procedure (P = 0.003, OD = 0.369) was the only independent risk factor for postoperative cumulative survival. CONCLUSION: Anterior approach right hepatectomy can significantly decrease intraoperative blood loss. The postoperative survivals of large HCC patients are significantly improved by anterior approach right hepatectomy.
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Carcinoma Hepatocelular/cirugía , Hepatectomía/métodos , Neoplasias Hepáticas/cirugía , Adulto , Carcinoma Hepatocelular/patología , Supervivencia sin Enfermedad , Femenino , Humanos , Neoplasias Hepáticas/patología , Masculino , Persona de Mediana Edad , Estudios Retrospectivos , Resultado del TratamientoRESUMEN
The abnormal expression of long noncoding RNAs (lncRNAs) is associated with human carcinoma. The present study aimed to investigate the mechanisms underlying the function of lncRNA AK002107 in the progression of hepatocellular carcinoma (HCC). The differential expression of lncRNAs between HCC and paired nontumor tissues was identified using microarrays, and the correlation between the expression of lncRNA AK002107 and the clinical prognosis of HCC was analyzed. We investigated the role of lncRNA AK002107 in HCC tumor biology in vitro using 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl-tetrazolium bromide (MTT), colony formation, and Matrigel invasion assays and in vivo by assessing the growth of xenografted HCC tumors. The potential microRNAs that interact with lncRNA AK002107 were identified using online tools and were verified using PCR and luciferase reporter assay. The levels of TGFBR1, E-cadherin, and vimentin were determined using western blot assays. We then further investigated the correlation between expression of lncRNA AK002107 with miR-140-5p and TGFBR1 expression in HCC tissues. The expression of lncRNA AK002107 is frequently upregulated in HCC samples and cell lines. Patients with HCC who have elevated lncRNA AK002107 expression exhibit poorer overall survival and disease-free survival. Silencing lncRNA AK002107 expression significantly inhibited HCC cell proliferation, colony formation, and invasion both in vitro and in vivo. Furthermore, lncRNA AK002107 directly binds to miR-140-5p and significantly inhibits miR-140-5p expression. The functions of lncRNA AK002107 in cell growth and tumor invasion are mediated via miR-140-5p. lncRNA AK002107 upregulated TGFBR1 expression and then induced epithelial-mesenchymal transition (EMT) by inhibiting miR-140-5p expression. The expression of lncRNA AK002107 inversely correlated with miR-140-5p expression and positively correlated with TGFBR1 expression in HCC tissues. In summary, lncRNA AK002107 functions as an oncogene in tumors by inhibiting miR-140-5p, targeting TGFBR1, and then inducing EMT. The lncRNA AK002107/miR-140-5p/TGFBR1/EMT regulatory network may be a valuable target for the development of novel diagnostic and treatment methods for HCC.
Asunto(s)
Carcinoma Hepatocelular/metabolismo , Transición Epitelial-Mesenquimal , Neoplasias Hepáticas/metabolismo , MicroARNs/metabolismo , Proteínas de Neoplasias/metabolismo , ARN Largo no Codificante/metabolismo , ARN Neoplásico/metabolismo , Receptor Tipo I de Factor de Crecimiento Transformador beta/metabolismo , Carcinoma Hepatocelular/genética , Carcinoma Hepatocelular/patología , Femenino , Células Hep G2 , Humanos , Neoplasias Hepáticas/genética , Neoplasias Hepáticas/patología , Masculino , MicroARNs/genética , Proteínas de Neoplasias/genética , ARN Largo no Codificante/genética , ARN Neoplásico/genética , Receptor Tipo I de Factor de Crecimiento Transformador beta/genéticaRESUMEN
NEK2 is a member of the NIMA-related family of serine/threonine centrosomal kinases. We analyzed the relationship between differential expression of NEK2 and hepatocellular carcinoma (HCC) patient outcomes after liver transplants. We also studied the microRNAs that affect NEK2 expression. Analysis of multiple microarrays in the Oncomine database revealed that NEK2 expression was higher in HCC tissues than adjacent normal liver tissues. High NEK2 expression correlated with tumor size, pathological grade and macro- and microvascular invasion. Consequently, patients exhibiting high NEK2 expression had poorer prognosis. This was corroborated by our multivariate analysis that showed NEK2 to be an independent prognostic factor for HCC patient survival. Further, high NEK2 expression promoted proliferation, colony formation, migration and invasion of HCC cell lines. Tumor xenograft data from Balb/c nude mice demonstrated that HCC cells with high NEK2 expression formed larger tumors than those with low NEK2 expression. Finally, we showed that miR-486-5p suppressed NEK2 by directly binding to its transcript 3'UTR. We also demonstrated an inverse relationship between miR-486-5p and NEK2 expression in HCC patients. These findings suggest miR-486-5p negatively regulates NEK2, which is a critical prognostic indicator of HCC patient survival after liver transplantation.
RESUMEN
OBJECTIVES: Elevated plasma fibrinogen (Fib) correlated with patient's prognosis in several solid tumors. However, few studies have illuminated the relationship between preoperative Fib and prognosis of HCC after liver transplantation. We aimed to clarify the prognostic value of Fib and whether the prognostic accuracy can be enhanced by the combination of Fib and neutrophil-lymphocyte ratio (NLR). RESULTS: Fib was correlated with Child-pugh stage, alpha-fetoprotein (AFP), size of largest tumor, macro- and micro-vascular invasion. Univariate analysis showed preoperative Fib, AFP, NLR, size of largest tumor, tumor number, macro- and micro- vascular invasion were significantly associated with disease-free survival (DFS) and overall survival (OS) in HCC patients with liver transplantation. After multivariate analysis, only Fib and macro-vascular invasion were independently correlated with DFS and OS. Survival analysis showed that preoperative Fib > 2.345 g/L predicted poor prognosis of patients HCC after liver transplantation. Preoperative Fib showed prognostic value in various subgroups of HCC. Furthermore, the predictive range was expanded by the combination of Fib and NLR. MATERIALS AND METHODS: Data were collected retrospectively from 130 HCC patients who underwent liver transplantation. Preoperative Fib, NLR and clinicopathologic variables were analyzed. The survival analysis was performed by the Kaplan-Meier method, and compared by the log-rank test. Univariate and multivariate analyses were performed to identify the prognostic factors for DFS and OS. CONCLUSIONS: Preoperative Fib is an independent effective predictor of prognosis for HCC patients, higher levels of Fib predict poorer outcomes and the combination of Fib and NLR enlarges the prognostic accuracy of testing.
Asunto(s)
Carcinoma Hepatocelular/cirugía , Fibrinógeno/metabolismo , Neoplasias Hepáticas/cirugía , Neutrófilos/citología , Adolescente , Adulto , Anciano , Carcinoma Hepatocelular/sangre , Carcinoma Hepatocelular/metabolismo , Carcinoma Hepatocelular/patología , Femenino , Humanos , Neoplasias Hepáticas/sangre , Neoplasias Hepáticas/metabolismo , Neoplasias Hepáticas/patología , Trasplante de Hígado , Recuento de Linfocitos , Masculino , Persona de Mediana Edad , Periodo Preoperatorio , Pronóstico , Estudios Retrospectivos , Análisis de Supervivencia , Carga Tumoral , Adulto Joven , alfa-Fetoproteínas/metabolismoRESUMEN
Protein kinase C epsilon (PKCε), a member of the novel PKC family, is known to be a transforming oncogene and tumor biomarker for many human solid cancers including renal cell carcinoma (RCC). We isolated side population (SP) cells from the RCC 769P cell line, and proved that those cells possess cancer stem cell (CSC) characteristics. In this study, to identify the function of PKCε in cancer stemness of 769P SP cells, we reduced the expression of PKCε in those cells, following the results demonstrated that PKCε depletion had a negative correlation with the existence of SP cells in 769P cell line. Down-regulation of PKCε also suppresses the CSC potential of sorted 769P SP cells in several ways: proliferation potential, resistance to chemotherapeutics and in vivo tumor formation ability. Our study also reveals that PKCε is associated with ABCB1 and this association probably contributed to the SP cells isolation from 769P cell line. Furthermore, the expression of ABCB1 is directly regulated by PKCε. Additionally, after the depletion of PKCε, the phosphorylation of pAkt, pStat3 and pERK was apparently suppressed in 769P SP cells, whereas PKCε overexpression could promote the phosphorylation of AKT, STAT3 and ERK in 769P Non-SP cells. Overall, PKCε down-regulation suppresses sorting and the cancer stem-like phenotype of RCC 769P SP cells through the regulation of ABCB1 transporter and the PI3K/Akt, Stat3 and MAPK/ERK pathways that are dependent on the phosphorylation effects. Thus, PKCε may work as an important mediator in cancer stem cell pathogenesis of renal cell cancer.