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1.
BMC Cancer ; 24(1): 227, 2024 Feb 16.
Artículo en Inglés | MEDLINE | ID: mdl-38365630

RESUMEN

BACKGROUND: Most patients with intrahepatic cholangiocarcinoma (ICC) have developed distant metastasis at the time of diagnosis, while there is rear related nomogram to predict the prognosis. METHODS: Clinical data of patients pathologically diagnosed of ICC with distant metastasis were retrospectively collected from the Surveillance, Epidemiology, and End Results (SEER) database during 2005 to 2019. Finally, patients diagnosed as ICC in the Second Affiliated Hospital of Nanchang University from 2014 to 2019 were collected for external verification. All data were divided into training cohort and validation cohort in a ratio of 7:3. The nomogram was established based on independent prognostic factors using Cox univariate and multivariate analyses. The area under the receiver operating characteristic (ROC) curves (AUC), the calibration curve and the decision curve analysis (DCA) were used to determine the prediction accuracy of the nomogram. RESULTS: This study finally included 572 ICC with distant metastasis patients, another 32 patients collected by the author's hospital were used as external verification. Results showed that age, surgery, radiotherapy and chemotherapy were independent prognostic factors, and nomogram was established. The AUC of predicting 3, 6, 9-month overall survival were 0.866, 0.841 and 0.786. The ROC curves and calibration curves showed that the nomogram had good predictive accuracy, and DCA showed that the nomogram had good clinical applicability. CONCLUSIONS: The nomogram has good accuracy in predicting prognosis of DM-ICC patients, which would be of good significance to improve the prognosis of these patients.


Asunto(s)
Neoplasias de los Conductos Biliares , Colangiocarcinoma , Humanos , Nomogramas , Estudios Retrospectivos , Pronóstico , Colangiocarcinoma/terapia , Neoplasias de los Conductos Biliares/terapia , Conductos Biliares Intrahepáticos
2.
Langenbecks Arch Surg ; 408(1): 357, 2023 Sep 13.
Artículo en Inglés | MEDLINE | ID: mdl-37704787

RESUMEN

OBJECTIVE: To explore the surgical risk factors of laparoscopic left-sided hepatectomy for hepatolithiasis and establish and validate a nomogram to estimate the corresponding surgical risks. METHODS: Patients with hepatolithiasis who underwent laparoscopic left-sided hepatectomy were retrospectively enrolled. Demographic data, clinicopathological parameters, and surgical factors were collected. Three hundred fifty-three patients were enrolled and randomly divided into training set (n=267) and validation set (n=86) by 3:1. Conversion to laparotomy was used as a surrogate index to evaluate the surgical risk. Univariate analysis was used to screen potential surgical risk factors, and multivariate analysis using logistic regression model was used to screen independent surgical risk factors. Nomogram predicting the surgical risks was established based on the independent risk factors. Discrimination, calibration, decision curve, and clinical impact analyses were used to evaluate the performance of the nomogram on the statistical and clinical aspects both in the training and validation sets. RESULTS: Five independent surgical risk factors were identified in the training set, including recurrent abdominal pain, bile duct stricture, ASA classification ≥2, extent of liver resection, and biliary tract T tube drainage. No collinearity was found among these five factors, and a nomogram was established. Performance analyses of the nomogram showed good discrimination (AUC=0.850 and 0.817) and calibration (Hosmer-Lemeshow test, p=0.530 and 0.930) capabilities both in the training and validation sets. Decision curve and clinical impact analyses also showed that the prediction performance was clinically valuable. CONCLUSIONS: A nomogram was established and validated to be effective in evaluating and predicting the surgical risk of patients undergoing laparoscopic left-sided hepatectomies for hepatolithiasis.


Asunto(s)
Laparoscopía , Litiasis , Hepatopatías , Humanos , Hepatectomía , Nomogramas , Estudios Retrospectivos , Hepatopatías/cirugía
3.
J Cell Physiol ; 236(4): 2572-2591, 2021 04.
Artículo en Inglés | MEDLINE | ID: mdl-32853412

RESUMEN

Changes in immune responses to hepatocellular carcinoma (HCC) are closely related to the occurrence, development, and prognosis of this disease. Exploring the role of immune-related genes (IRGs) in HCC would provide insights into the mechanisms regulating this disease. The Cancer Genome Atlas (TCGA) and International Cancer Genome Consortium (ICGC) provide a platform for such research, owing to a large number of HCC samples available for comprehensive and systematic immunogenomics analyses. We analyzed the IRGs expression profile and clinical information of patients with HCC based on the TCGA and ICGC database. Potential molecular mechanisms and properties of the screened IRGs were analyzed across multiple databases. And we analyzed the correlation between IRGs, single-nucleotide polymorphisms, and copy number variation. A novel prognostic index, based on IRGs, was developed using the LASSO Cox regression algorithm, followed by univariate and multivariate Cox regression analyses to analyze the prognostic index. Information in the ICGC database was used to verify the reliability of the prognostic index. A total of 54 differentially expressed IRGs were found to be significantly associated with HCC prognosis, and there is a significant correlation between their expression level and copy number variation. Functional enrichment analyses indicated that the genes play active roles in tumor and immune-related signaling pathways. In addition, five potential biomarkers namely IRG, MAPK3, HSP90AA1, HSP90AB1, HSPA4, and CDK4, were identified. Finally, a novel prognostic index, based on IRGs (PSMD14, FABP6, ISG20L2, HGF, BIRC5, IL17D, and STC2), was found useful as an independent prognostic factor, not only for prognosis but also to reflect levels of infiltration in a variety of immune cells. Our team conducted a genomics study of IRGs in HCC and screened several clinically significant IRGs, and our model provides an effective approach for stratification and characterization of patients using IRG-based immunolabeling tools to monitor the prognosis of HCC.


Asunto(s)
Carcinoma Hepatocelular/genética , Perfilación de la Expresión Génica , Fenómenos Inmunogenéticos , Neoplasias Hepáticas/genética , Transcriptoma , Anciano , Carcinoma Hepatocelular/inmunología , Carcinoma Hepatocelular/patología , Carcinoma Hepatocelular/terapia , Variaciones en el Número de Copia de ADN , Bases de Datos Genéticas , Femenino , Dosificación de Gen , Regulación Neoplásica de la Expresión Génica , Redes Reguladoras de Genes , Humanos , Neoplasias Hepáticas/inmunología , Neoplasias Hepáticas/patología , Neoplasias Hepáticas/terapia , Masculino , Persona de Mediana Edad , Polimorfismo de Nucleótido Simple , Valor Predictivo de las Pruebas , Pronóstico , Microambiente Tumoral
4.
Exp Cell Res ; 383(1): 111493, 2019 10 01.
Artículo en Inglés | MEDLINE | ID: mdl-31310747

RESUMEN

Recent studies have shown that the expression levels of glucose-regulated protein 78 (GRP78) and homeobox B9 (HOXB9) are both upregulated in hepatocellular carcinoma (HCC) and are closely related to HCC invasion and metastasis. However, whether there is a regulatory relationship between GRP78 and HOXB9 is unclear. In this study, we examined the expression of GRP78 and HOXB9 in HCC tissues and adjacent nontumor tissues. Correlation analysis indicated that GRP78 and HOXB9 expression were positively correlated. High levels of GRP78 and HOXB9 expression are closely related to worse clinicopathological features. Knockdown of GRP78 in HCC cells decreased the mRNA and protein expression of HOXB9, but increase HOXB9 expression reversed the decrease in invasion and metastasis induced by knocking down GRP78. Further experiments showed that GRP78 regulates HOXB9 through the Wnt signaling pathway by chaperoning low-density lipoprotein receptor-related protein 6 (LRP6). Importantly, we found that GPR78 promoted maturation of LRP6, while knockdown of GRP78 led to LRP6 misfolding and endoplasmic reticulum-associated degradation (ERAD). Consequently, the levels of mature LRP6 were reduced, and Wnt/HOXB9 signaling was inhibited. Our data suggest that the GRP78-LRP6-HOXB9 axis regulates the invasion and metastasis of HCC and may represent a potential therapeutic target for the treatment of HCC.


Asunto(s)
Carcinoma Hepatocelular/secundario , Regulación Neoplásica de la Expresión Génica , Proteínas de Choque Térmico/metabolismo , Proteínas de Homeodominio/metabolismo , Neoplasias Hepáticas/patología , Proteína-6 Relacionada a Receptor de Lipoproteína de Baja Densidad/metabolismo , Proteína Wnt1/metabolismo , Animales , Apoptosis , Biomarcadores de Tumor/genética , Biomarcadores de Tumor/metabolismo , Carcinoma Hepatocelular/genética , Carcinoma Hepatocelular/metabolismo , Movimiento Celular , Proliferación Celular , Chaperón BiP del Retículo Endoplásmico , Degradación Asociada con el Retículo Endoplásmico , Femenino , Proteínas de Choque Térmico/genética , Proteínas de Homeodominio/genética , Humanos , Neoplasias Hepáticas/genética , Neoplasias Hepáticas/metabolismo , Proteína-6 Relacionada a Receptor de Lipoproteína de Baja Densidad/genética , Masculino , Ratones , Ratones Endogámicos BALB C , Ratones Desnudos , Persona de Mediana Edad , Chaperonas Moleculares , Invasividad Neoplásica , Pronóstico , Tasa de Supervivencia , Células Tumorales Cultivadas , Proteína Wnt1/genética , Ensayos Antitumor por Modelo de Xenoinjerto
5.
Exp Cell Res ; 365(1): 1-11, 2018 04 01.
Artículo en Inglés | MEDLINE | ID: mdl-29458176

RESUMEN

Glucose-regulated protein 78(GRP78) and the ubiquitin-like protein FAT10 each promote proliferation in hepatocellular carcinoma(HCC). However, the relationship of GRP78 and FAT10 in HCC proliferation are still not known. In this study, we found that GRP78 and FAT10 were significantly overexpressed in HCC tissues compare with adjacent non-cancerous tissues, and a positive correlation was found between their expression and associated proliferation characteristics. High expression of GRP78 and FAT10 were positively correlated with tumor proliferation and poor prognosis in HCC. Moreover, GRP78 knockdown reduced FAT10 expression and suppressed HCC proliferation in vitro and in vivo. The effects of GRP78 knockdown were rescued by FAT10 up-regulation, whereas FAT10 knockdown reduced HCC proliferation enhanced by GRP78 up-regulation. Furthermore, GRP78 modulated FAT10 expression by regulating the NF-κB pathway, direct activation of the NF-κB pathway increased the expression of FAT10, a gene counteracting the tumor suppressor p53. Taken together, these results suggest that this newly identified GRP78-NF-κB-FAT10 axis will provide novel insight into the understanding of the regulatory mechanisms of proliferation in human HCC.


Asunto(s)
Carcinoma Hepatocelular/genética , Proliferación Celular/genética , Proteínas de Choque Térmico/genética , Neoplasias Hepáticas/genética , FN-kappa B/genética , Ubiquitinas/genética , Carcinoma Hepatocelular/patología , Línea Celular Tumoral , Chaperón BiP del Retículo Endoplásmico , Regulación Neoplásica de la Expresión Génica/genética , Células Hep G2 , Humanos , Neoplasias Hepáticas/patología , Transducción de Señal/genética , Regulación hacia Arriba/genética
6.
Pharm Biol ; 56(1): 643-648, 2018 Dec.
Artículo en Inglés | MEDLINE | ID: mdl-31070541

RESUMEN

CONTEXT: d-Glucaro-1,4-lactone (1,4-GL) exists in many vegetables and fruits. Metabonomics has not been used to investigate the role of 1,4-GL in preventing liver cancer. OBJECTIVE: The pharmacological effects and metabolite alterations of 1,4-GL on the prevention of diethylnitrosamine (DEN)-induced liver cancer were investigated. MATERIALS AND METHODS: Ten healthy Sprague-Dawley rats served as control and 46 were used to establish rat liver cancer model. 1HNMR-based metabonomics was used to compare the effects of oral 1,4-GL (50 mg/kg) in liver cancer rats (n = 26) after 10 consecutive weeks of intervention. The amino acids in rat serum were quantified by HPLC-UV, and the changes in Fischer's ratio were calculated. RESULTS: The 20-week survival rate of DEN-induced liver cancer rats administered with oral 1,4-GL was increased from 45.0 to 70.0% with reduced carcinogenesis of the liver and significantly lowered serum α-fetoprotein level (14.28 ± 2.89 ng/mL vs. 18.56 ± 4.65 ng/mL, p = 0.012). The serum levels of leucine, valine, 3-hydroxybutyrate, lactate, acetate and glutamine in the DEN + 1,4-GL group returned to normal levels compared with those of the DEN group on week 20. Fischer's ratio in the rat serum of DEN group was 1.62 ± 0.21, which was significantly lower than that in healthy rats (2.3 ± 0.12). However, Fischer's ratio increased to 1.89 ± 0.22 in the DEN + 1,4-GL group. DISCUSSION AND CONCLUSIONS: 1,4-GL exerted positive effects on liver carcinogenesis in rats by pathological examination and metabonomic analysis. Its mechanism may be related to the restoration of amino acid and energy metabolism.


Asunto(s)
Dietilnitrosamina/toxicidad , Ácido Glucárico/análogos & derivados , Neoplasias Hepáticas Experimentales/tratamiento farmacológico , Neoplasias Hepáticas Experimentales/metabolismo , Metabolómica/métodos , Alquilantes/toxicidad , Animales , Ácido Glucárico/metabolismo , Ácido Glucárico/uso terapéutico , Neoplasias Hepáticas Experimentales/inducido químicamente , Ratas , Ratas Sprague-Dawley
7.
World J Surg Oncol ; 14(1): 218, 2016 Aug 17.
Artículo en Inglés | MEDLINE | ID: mdl-27535234

RESUMEN

BACKGROUND: Synchronous development of primary hepatocellular carcinoma (HCC) and intrahepatic cholangiocarcinoma (ICC) in different sites of the liver have rarely been reported before. The purpose of this study is to investigate the clinicopathological characteristics of synchronous double cancer of HCC and ICC. CASE PRESENTATION: A 56-year-old Chinese man without obvious liver cirrhosis was preoperation diagnosed with multiple HCC in segments VI (SVI) and VII (SVII) by the abdominal computed tomography (CT) and contrast-enhanced ultrasonography (CEUS). We performed hepatic resection of both segments. The tumors in SVI and SVII were pathologically diagnosed as ICC and HCC, respectively. Immunohistochemically, the HCC in SVII was positive for HepPar-1 and negative for CK19, while the ICC in SVI tumor was positive for CK19 and negative for HepPar-1. Interestingly, the immunohistochemical results also showed that the classic hepatic progenitor cell (HPCs) markers CD34 and CD117 were both positive of the two tumors. The patient still survived and at a 1-year follow-up did not show evidence of metastasis or new recurrent lesions. We speculate that the two masses may have originated from HPCs based on the findings of this patient. CONCLUSIONS: Synchronous development of HCC and ICC is very rare with unique clinical and pathological features. The correct preoperative diagnosis of double hepatic cancer of HCC and ICC is difficult. Hepatitis B virus (HBV) and hepatitis C virus (HCV) infection were both the independent risk factor to the development of double liver cancer. Hepatic resection is the preferred and most effective treatment choice. The prognosis of synchronous occurrence of double hepatic cancer was poorer than for either HCC or ICC, and the origin of it needs further study.


Asunto(s)
Neoplasias de los Conductos Biliares/patología , Carcinoma Hepatocelular/patología , Colangiocarcinoma/patología , Neoplasias Hepáticas/patología , Neoplasias Primarias Múltiples/patología , Neoplasias de los Conductos Biliares/cirugía , Carcinoma Hepatocelular/cirugía , Colangiocarcinoma/cirugía , Humanos , Neoplasias Hepáticas/cirugía , Masculino , Persona de Mediana Edad , Neoplasias Primarias Múltiples/cirugía , Pronóstico
8.
Zhong Nan Da Xue Xue Bao Yi Xue Ban ; 41(11): 1163-1167, 2016 Nov 28.
Artículo en Zh | MEDLINE | ID: mdl-27932761

RESUMEN

OBJECTIVE: To systematically review the potential value of long noncoding RNA (lncRNA) metastasis-associated lung adenocarcinoma transcript 1 (MALAT1) as a potential novel prognostic biomarker in cancers.
 Methods: Databases including Cochrane Library, Medline, Embase, PubMed databases were searched for all English studies, which explored the correlation between lncRNA MALAT1 expression and overall survival in tumors. The retrieval time was from inception to August 1, 2015. Two reviewers independently screened literature according to the inclusion and exclusion criteria, extracted data, and assessed methodological quality. Then, Meta-analysis was performed using RevMan 5.3 software.
 Results: Ten studies covered a total of 1 016 patients. Meta-analysis showed that high expression of MALAT1 was significantly correlated to poor overall survival (OS) in patients with tumor (HR= 2.08, 95% CI 1.74 to 2.48, P<0.001). 
 Conclusion: LncRNA MALAT1 might be a potential novel prognostic biomarker in tumor.


Asunto(s)
Biomarcadores de Tumor/genética , Neoplasias/genética , Neoplasias/mortalidad , ARN Largo no Codificante , Humanos , Pronóstico , Tasa de Supervivencia
9.
Surg Today ; 43(12): 1371-81, 2013 Dec.
Artículo en Inglés | MEDLINE | ID: mdl-23184324

RESUMEN

PURPOSES: The primary concern regarding laparoscopic hepatectomy in hepatolithiasis patients is surgical safety, which may be high in current practice. METHODS: Hepatolithiasis patients who underwent laparoscopic and laparotomic hepatectomies were retrospectively studies after being matched for age, location of gallstones, liver resection and underlying liver conditions at a ratio of 1:1 (n = 44 in each group). The rates of intraoperative incidents and postoperative complications were examined using validated classification and grading systems. The primary outcome measure was the procedure-related complication/mortality rate. RESULTS: Laparoscopy was converted to open surgery in three patients (6.8 %). The length of the operation for laparoscopic hepatectomy was significantly longer than that for laparotomic hepatectomy (277.5 min [range, 190-410 min] vs. 212.5 min [140-315 min], P < 0.001). The two groups had similar intraoperative blood loss (367.5 mL [150-1200 mL] vs. 392.5 mL [200-1400 mL], P > 0.05) and transfusion frequencies (13.6 vs. 18.2 %, P > 0.05). The laparoscopy group had a higher percentage of patients with at least one intraoperative incident compared with the laparotomy group (22.7 vs. 6.8 %; P < 0.05). Vascular events occurred in nine patients (20.5 %) undergoing laparoscopy and two patients (4.5 %) undergoing laparotomy (OR 5.4 [95 %CI, 1.1-26.7], P < 0.05). CONCLUSIONS: Laparoscopic hepatectomy is associated with a higher risk of intraoperative vascular incidents in hepatolithiasis patients compared wit laparotomy.


Asunto(s)
Hepatectomía/efectos adversos , Hepatectomía/estadística & datos numéricos , Complicaciones Intraoperatorias/epidemiología , Laparoscopía/efectos adversos , Laparoscopía/estadística & datos numéricos , Litiasis/cirugía , Hepatopatías/cirugía , Complicaciones Posoperatorias/epidemiología , Adulto , Anciano , Estudios de Casos y Controles , Femenino , Estudios de Seguimiento , Hepatectomía/métodos , Humanos , Incidencia , Laparoscopía/métodos , Laparotomía/efectos adversos , Laparotomía/estadística & datos numéricos , Masculino , Persona de Mediana Edad , Cuidados Posoperatorios , Estudios Retrospectivos , Riesgo , Resultado del Tratamiento , Adulto Joven
10.
Yao Xue Xue Bao ; 48(5): 635-41, 2013 May.
Artículo en Zh | MEDLINE | ID: mdl-23888683

RESUMEN

Ras is best known for its ability to regulate cell growth, proliferation and differentiation. Mutations in Ras are associated with the abnormal cell proliferation which can result in incidence of all human cancers. Extracellular signal-regulated kinase (ERK) is a downstream effector of Ras and plays important roles in prognosis of tumors. Recently, evidence has gradually accumulated to demonstrate that there are other effectors between Ras and ERK, these proteins interact each other and constitute the thorough Ras/Raf/MEK/ERK signaling pathway. The pathway has profound effects on incidence of esophageal carcinoma and clinical applications of some chemotherapeutic drugs targeting the pathway. Further understanding of the relevant molecular mechanisms of Ras/Raf/MEK/ERK signaling pathway can be helpful for the development of efficient targeting therapeutic approaches which contribute to the treatment of esophageal cancer. In this article, roles of Ras/Raf/MEK/ERK signaling pathway in esophageal carcinoma as well as pharmacological targeting point in the pathway are reviewed.


Asunto(s)
Antineoplásicos , Carcinoma de Células Escamosas/tratamiento farmacológico , Neoplasias Esofágicas/tratamiento farmacológico , Quinasas MAP Reguladas por Señal Extracelular/metabolismo , Quinasas de Proteína Quinasa Activadas por Mitógenos/metabolismo , Proteínas Proto-Oncogénicas c-raf/metabolismo , Proteínas ras/metabolismo , Animales , Antineoplásicos/farmacología , Antineoplásicos/uso terapéutico , Carcinoma de Células Escamosas/enzimología , Carcinoma de Células Escamosas/patología , Línea Celular Tumoral , Activación Enzimática/efectos de los fármacos , Neoplasias Esofágicas/enzimología , Neoplasias Esofágicas/patología , Carcinoma de Células Escamosas de Esófago , Quinasas MAP Reguladas por Señal Extracelular/antagonistas & inhibidores , Humanos , Quinasas de Proteína Quinasa Activadas por Mitógenos/antagonistas & inhibidores , Proteínas Proto-Oncogénicas c-raf/antagonistas & inhibidores , Transducción de Señal/efectos de los fármacos , Proteínas ras/antagonistas & inhibidores
11.
Hepatol Int ; 17(1): 180-189, 2023 Feb.
Artículo en Inglés | MEDLINE | ID: mdl-36258065

RESUMEN

PURPOSE: Probing efficacy and safety of lusutrombopag in Chinese chronic liver disease (CLD) and severe thrombocytopenia (PLT < 50 × 109/L) patients undergoing elective invasive procedures. METHODS: In this double-blind, parallel-group phase 3 study, 66 patients with CLD and severe thrombocytopenia were randomized 2:1 to lusutrombopag or placebo arm treatment regimens for seven days at 9 centers in China. Responders (PLT ≥ 50 × 109/L that increased to ≥ 20 × 109/L from the baseline and not received rescue therapy for bleeding) on Day 8 (the day after seven-day treatment) were assessed. PLT ≥ 50 × 109/L on or after Day 8 and within 2 days before invasive procedure (alternative criteria for not requiring platelet transfusion) were also analyzed. Adverse events (AEs) were recorded. RESULTS: The proportion of responders on Day 8 was evidently higher (p = 0.0011) in the lusutrombopag group (43.2%, 19/44) versus placebo (4.5%, 1/22). And 72.7% (32/44) patients receiving lusutrombopag met the alternative criteria for not requiring platelet transfusion, while 18.2% (4/22) in the placebo group. The median maximum PLT in lusutrombopag group increased to 80.5 × 109/L, and median time to reach maximum was 14.5 days. Compared with placebo, the lusutrombopag group had a lower incidence of bleeding events (6.8% versus 13.6%), and only one patient had thrombotic-related AE. Overall, the incidence of treatment-emergent AEs was comparable between two groups. CONCLUSIONS: Lusutrombopag was effective in raising PLT, diminishing platelet transfusion requirement, and documented a safety profile like the placebo in CLD and severe thrombocytopenia patients in a Chinese cohort undergoing elective invasive procedures. Chinese clinical trial registration number: CTR20192384.


Asunto(s)
Hepatopatías , Trombocitopenia , Humanos , Pueblos del Este de Asia , Hepatopatías/complicaciones , Hepatopatías/tratamiento farmacológico , Trombocitopenia/tratamiento farmacológico , Tiazoles/uso terapéutico
12.
Bioengineered ; 13(3): 5737-5755, 2022 03.
Artículo en Inglés | MEDLINE | ID: mdl-35184652

RESUMEN

Metastasis and chemoresistance are the leading causes of death in patients with hepatocellular carcinoma (HCC). microRNAs (miRNAs or miRs) may be useful as diagnostic, therapeutic and prognostic markers for HCC. In this study, we set out to investigate the possible role of miR-381 in HCC development and chemoresistance along with the related mechanism. Microarray-based gene expression profiling was carried out to analyze the expression of SET domain bifurcated 1 (SETDB1) and histone methyltransferase enhancer of zeste homolog 2 (EZH2) followed by validation in clinical HCC tissues and cells. The potential binding between miR-381 and SETDB1 was found and verified. Then, the role of SETDB1 in HCC in relation to miR-381 and protein kinase B (AKT) pathway was explored through gain- and loss-of-function approaches. After expression determination of EZH2, SETDB1, miR-381, and AKT pathway-related factors, their reactions were analyzed and their functional roles in HCC progression and chemoresistance were investigated in vitro and in vivo. SETDB1 was aberrantly upregulated in clinical HCC tissues and cells. This upregulation activated AKT pathway by promoting its tri-methylation on K64. SETDB1 promoted the proliferation, migration and chemoresistance through the AKT pathway in HCC cells. In a xenograft mouse model, SETDB1 promoted HCC cell tumorigenesis in vivo by activating the AKT pathway. Furthermore, EZH2 suppressed miR-381 by catalyzing the activity of H3K27me3 on its promoter region. In conclusion, EZH2 suppressed miR-381 expression by promoting H3K27me3 activity on its promoter region to facilitate SETDB1 expression, thereby activating the AKT pathway to promote hepatocarcinogenesis and chemoresistance.


Asunto(s)
Carcinoma Hepatocelular , Proteína Potenciadora del Homólogo Zeste 2 , N-Metiltransferasa de Histona-Lisina , Neoplasias Hepáticas , MicroARNs , Animales , Carcinogénesis/genética , Carcinoma Hepatocelular/metabolismo , Línea Celular Tumoral , Proliferación Celular/genética , Resistencia a Antineoplásicos/genética , Proteína Potenciadora del Homólogo Zeste 2/genética , Proteína Potenciadora del Homólogo Zeste 2/metabolismo , Regulación Neoplásica de la Expresión Génica , N-Metiltransferasa de Histona-Lisina/genética , N-Metiltransferasa de Histona-Lisina/metabolismo , Histonas/genética , Histonas/metabolismo , Humanos , Neoplasias Hepáticas/metabolismo , Ratones , Ratones Desnudos , MicroARNs/genética , Proteínas Proto-Oncogénicas c-akt/genética , Proteínas Proto-Oncogénicas c-akt/metabolismo
13.
Front Surg ; 8: 659422, 2021.
Artículo en Inglés | MEDLINE | ID: mdl-34079814

RESUMEN

Background: This study aims to establish an effective nomogram to predict the overall survival of patients with intrahepatic cholangiocarcinoma (ICC). Patients and Methods: Data used to build the nomogram comes from the Surveillance, Epidemiology, and End Results (SEER) database. Patients diagnosed with ICC between 2005 and 2016 were retrospectively collected. Prediction accuracy and discrimination ability of the nomogram was evaluated by concordance index (C-index) and calibration curve. The area under receiver operating characteristic (ROC) curve (AUC) and decision curve analysis (DCA) were used to compare the precision of the 1-, 3-, and 5-year survival of the nomogram with 8th American Joint Commission on Cancer (AJCC) tumor-node-metastasis (TNM) staging system. Finally, it was verified in a prospective study of patients diagnosed with ICC in the Second Affiliated Hospital of Nanchang University from 2013 to 2020 by bootstrap resampling. Result: The study contains two parts of data; we establish a nomogram using external data, and we conducted internal verification and external verification. The nomogram that we have established has good calibration, with a concordance index (C-index) of 0.75 (95% CI, 0.74-0.76) for overall survival (OS) prediction. The AUC value of the nomogram predicting 1-, 3-, and 5-year OS rates were 0.821, 0.828, and 0.836, which were higher than those of the 8th AJCC TNM staging systems. The calibration curve for the probability of survival between prediction by nomogram and actual observation shows good agreement. The nomogram showed better accuracy than the 8th edition AJCC TNM staging. Conclusion: The nomogram established can provide a more accurate prognosis for patients with intrahepatic cholangiocarcinoma.

14.
Front Surg ; 8: 675661, 2021.
Artículo en Inglés | MEDLINE | ID: mdl-34778352

RESUMEN

Background: The aim of this study based on log odds of positive lymph nodes (LODDS) is to develop and validate an effective prognostic nomogram for patients with T3 and T4 gallbladder cancer (GBC) after resection. Patients and Methods: A total of 728 T3 and T4 gallbladder cancer patients after resection from the Surveillance, Epidemiology, and End Results (SEER) database, randomly divided into training cohort and validation cohort according to 7:3. Another 128 patients from The Second Affiliated Hospital of Nanchang University for external validation. The nomograms were built by the Cox regression model and the Fine and Grey's model. Concordance index (C-index), calibration curve and the area under receiver operating characteristic (ROC) curve (AUC) were used to evaluate the nomogram and internal verification. The decision curve analysis (DCA) was used to measure clinical applicability. Result: LODDS was independent prognostic predictor for overall survival (OS) and cancer-specific survival (CSS), and established the nomograms on this basis. The nomogram we have established has a good evaluation effect, with a C-index of 0.719 (95%CI, 0.707-0.731) for OS and 0.747 (95%CI, 0.733-0.760) for CSS. The calibration curves of OS and CSS both showed good calibration capability, and the AUC for predicting 1-, 2-, and 3-year 0.858, 0.848 were and 0.811 for OS, and 0.794, 0.793, and 0.750 for CSS. The DCA of nomograms both showed good clinical applicability. Conclusion: The nomogram can provide effective OS and CSS prediction for patients with advanced gallbladder cancer after surgery.

15.
Surg Laparosc Endosc Percutan Tech ; 30(5): 467-470, 2020 Oct.
Artículo en Inglés | MEDLINE | ID: mdl-32496345

RESUMEN

BACKGROUND: Remnant cystic duct (RCD) may be responsible for postcholecystectomy syndrome. We present our experience with the management of remnant cystic duct disease (RCDD) after cholecystectomy. METHODS: Over a period of 5 years, 10 patients underwent reoperation for RCDD in our hospital. Cystic duct was identified by intraoperative exploration. RESULTS: There were 4 men and 6 women ranging in age from 37 to 76 years (median, 60.40 y). All 10 had biliary pain, 5 had jaundice, and 2 had pancreatitis. The time from initial cholecystectomy to reoperation ranged from 4 to 28 years (median, 12.22 y). Eight patients had an abnormal liver function. Six of these 8 patients (75%) were diagnosed by magnetic resonance cholangiopancreatography. In 7 patients treated by completed cholecystectomy (6 by laparoscopy and 1 by laparotomy), pathology proved the presence of an RCD and chronic cholecystitis. The other 3 patients were treated by removing stones. All patients had 6- to 14-day hospital stays after reoperation, except for 1 patient with a 3-day stay. CONCLUSIONS: RCDD may be a more reasonable explanation for a source of postcholecystectomy syndrome. Magnetic resonance cholangiopancreatography has a role in the diagnosis of RCDD. We believe that excision of diseased RCD is necessary and that laparoscopic surgery is feasible.


Asunto(s)
Enfermedades de los Conductos Biliares , Colecistectomía Laparoscópica , Adulto , Anciano , Enfermedades de los Conductos Biliares/cirugía , Pancreatocolangiografía por Resonancia Magnética , Colecistectomía/efectos adversos , Colecistectomía Laparoscópica/efectos adversos , Conducto Cístico/cirugía , Femenino , Humanos , Masculino , Persona de Mediana Edad
16.
Clin Chim Acta ; 472: 64-68, 2017 Sep.
Artículo en Inglés | MEDLINE | ID: mdl-28729135

RESUMEN

MAIN PROBLEM: The tumor-stroma ratio (TSR) has been reported as a prognosis predictor in multiple cancers. The aim of this meta-analysis was to investigate the potential value of TSR as a prognostic predictor of cancer in the digestive system. METHODS: We searched PubMed, Embase, Elsevier and Web of Science. All studies exploring the association of TSR with overall survival (OS) or disease-free survival (DFS), and lymph node metastasis (LNM) were identified. RESULTS: In total, eight studies were eligible for analysis, and they included 1959 patients. Meta-analysis showed that the low TSR in the tumor could predict poor overall survival (OS) in multiple cancers (pooled Hazard Ratio [HR]: 2.15, 95%CI: 1.80-2.57, P<0.00001, fixed effects). For disease-free survival (DFS), low TSR was also a significant predictor (pooled Hazard Ratio [HR]: 2.31, 95%CI: 1.88-2.83, P<0.00001, fixed effects). In addition, low TSR was correlated with tumor stage. DISCUSSION: The tumor-stroma ratio (TSR) may potentially serve as a poor prognostic predictor for the metastasis and prognosis of cancer.


Asunto(s)
Neoplasias del Sistema Digestivo/diagnóstico , Neoplasias del Sistema Digestivo/patología , Medicina Basada en la Evidencia , Humanos , Pronóstico
17.
Sci Rep ; 7: 46601, 2017 04 18.
Artículo en Inglés | MEDLINE | ID: mdl-28417972

RESUMEN

The lymphocyte-to-monocyte ratio (LMR) has been reported to predict clinical outcomes in multiple malignancies. The aim of this study was to assess the prognostic role of pretreatment LMR in hepatocellular carcinoma (HCC). A total of seven studies comprising 2,738 patients were included in the meta-analysis. Pooled results showed that elevated LMR was significantly associated with increased overall survival (OS) (HR: 0.31, 95% CI: 0.20-0.47, p < 0.001), disease-free survival (DFS)/recurrence-free survival (RFS) (HR: 0.57, 95% CI: 0.49-0.67, p < 0.001). The favorable prognostic impact of high LMR on OS was observed in all subgroup with different sample size, type of publication, NOS score, and the cut-off value of LMR. In addition, low LMR was significantly correlated with TNM stage and BCLC stage. We therefore conclude that elevated pretreatment LMR could be a favorable prognostic factor for clinical outcomes in patients with HCC.


Asunto(s)
Carcinoma Hepatocelular , Neoplasias Hepáticas , Linfocitos , Monocitos , Anciano , Carcinoma Hepatocelular/sangre , Carcinoma Hepatocelular/mortalidad , Supervivencia sin Enfermedad , Femenino , Humanos , Neoplasias Hepáticas/sangre , Neoplasias Hepáticas/mortalidad , Recuento de Linfocitos , Masculino , Persona de Mediana Edad , Tasa de Supervivencia
18.
PLoS One ; 12(6): e0178762, 2017.
Artículo en Inglés | MEDLINE | ID: mdl-28575033

RESUMEN

BACKGROUND: Recently, the preoperative platelet to lymphocyte ratio (PLR) has been found reported to predict oncologic outcomes in multiple malignancies. However, its prognostic value in patients with pancreatic cancer (PC) remains controversial. The aim of this study was to assess the prognostic value of preoperative PLR in PC. METHODS: MEDLINE, EMBASE, and Cochrane databases were searched to identify studies evaluating the prognostic significance of preoperative PLR in PC. Pooled hazard ratios (HRs) for overall survival (OS) were calculated using fixed-effects/random-effects models. RESULTS: A total of eight studies comprising 1,904 patients with PC were included in the meta-analysis. The pooled analysis demonstrated that elevated PLR had an association with decreased OS (HR: 1.22, 95% CI: 1.04-1.43, p = 0.02). Subgroup analysis showed that a high PLR significantly predicted poor OS in Asian studies (HR: 1.25, 95% CI: 1.03-1.52, p = 0.02), patients with metastatic disease (HR: 1.34, 95% CI: 1.01-1.77, p = 0.04) and patients with PLR >150 (HR: 1.73, 95% CI: 1.21-2.49, p = 0.003). CONCLUSIONS: The preoperative PLR may be a significant independent prognostic factor in patients with PC.


Asunto(s)
Plaquetas/patología , Linfocitos/patología , Neoplasias Pancreáticas/sangre , Humanos , Pronóstico
19.
Sci Rep ; 7(1): 15372, 2017 11 13.
Artículo en Inglés | MEDLINE | ID: mdl-29133895

RESUMEN

The purpose of this study was to evaluate the safety and feasibility of laparoscopic common bile duct exploration (LCBDE) in patients with previous abdominal surgery (PAS). The outcomes were compared in 139 patients (103 upper and 36 lower abdominal surgeries) with PAS and 361 without PAS who underwent LCBDE. The operative time, hospital stay, rate of open conversion, postoperative complications, duct clearance, and blood loss were compared. Patients with PAS had longer operative times (P = 0.006), higher hospital costs (P = 0.043), and a higher incidence of wound complications (P = 0.011) than those without PAS. However, there were no statistically significant in the open conversion rate, blood loss, hospital stay, bile leakage, biliary strictures, residual stones, and mortality between patients with and without PAS (P > 0.05). Moreover, compared with those without PAS, patients with previous upper abdominal surgery (PUAS) had longer operative times (P = 0.005), higher hospital costs (P = 0.030), and a higher open conversion rate (P = 0.043), but patients with previous lower abdominal surgery (PLAS) had a higher incidence of wound complications (P = 0.022). LCBDE is considered safe and feasible for patients with PAS, including those with PUAS.


Asunto(s)
Conducto Colédoco/cirugía , Laparoscopía/métodos , Tiempo de Internación , Adulto , Anciano , Pérdida de Sangre Quirúrgica/prevención & control , Femenino , Humanos , Laparoscopía/efectos adversos , Masculino , Persona de Mediana Edad , Complicaciones Posoperatorias/epidemiología , Estudios Retrospectivos
20.
Oncotarget ; 8(52): 90301-90307, 2017 Oct 27.
Artículo en Inglés | MEDLINE | ID: mdl-29163829

RESUMEN

Expression of ZFAS1, a newly identified long noncoding RNA (lncRNA), is dysregulated in several types of cancer. Here we assessed the prognostic value of ZFAS1 in solid tumors. A comprehensive literature search was performed by screening the PubMed, EMBASE, MEDLINE, Cochrane Library, CNKI, and Wanfang databases. A total of 874 patients from 10 studies were included. The pooled analysis demonstrated that patients with high ZFAS1 expression had a significantly shorter overall survival (OS) (HR, 1.58; 95% CI, 1.28-1.97; P < 0.001) and recurrence-free survival (RFS) (HR, 1.90; 95% CI, 1.29-2.79; P = 0.001). Moreover, elevated ZFAS1 expression correlated with tumor size, tumor-node-metastasis (TNM) stage, and lymph node metastasis (LNM). These results demonstrate that increased ZFAS1 expression correlates with a poor prognosis in cancer patients, which suggests ZFAS1 might be useful as a potential prognostic biomarker in patients with solid tumors.

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