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BACKGROUND: To evaluate the long-term efficacy of single-balloon enteroscopy endoscopic retrograde cholangiography (SBE-ERC) for the treatment of biliary obstruction and to analyze the factors affecting the recurrence of benign bilioenteric anastomotic stricture after SBE-ERC treatment. METHODS: The clinical data of patients with biliary diseases treated with SBE-ERC after choledochojejunostomy in our hospital from January 2015 to December 2021 were analyzed retrospectively for the success rates of diagnosis and treatment and the incidence of complications. Patients who were diagnosed with benign bilioenteric anastomotic stricture were followed up. The independent factors affecting recurrence were obtained by univariate and multivariate analyses using the KaplanâMeier method and Cox proportional hazard regression model. RESULTS: A total of 289 SBE-ERCs were performed in 165 patients. The overall success rate was 83.0% (240/289). The incidence of postoperative complications was 5.2% (15/289). The 108 successfully treated patients diagnosed with benign bilioenteric anastomotic stricture were followed up. Twenty-six percent (29/108) of patients had recurrent stricture after SBE-ERC. The biliary patency rates at 1 year, 2 years and 5 years after SBE-ERC were 90.1%, 69.3%, and 53.9%, respectively. Single-factor analysis revealed the absence of intrahepatic biliary gas imaging during endoscopy ( χ 2 =5.366, P = 0.021), a diameter of balloon dilatation during the last endoscopic treatment less than 0.8 cm ( χ 2 =4.552, P = 0.033), and the presence of a thread in the anastomosis ( χ 2 =8.921, P = 0.003) as risk factors for recurrence. A non-indwelling biliary plastic stent ( χ 2 =14.868, P < 0.001) and undergoing only one ERCP treatment ( χ 2 =13.313, P = 0.001) were risk factors for the recurrence of benign stricture after SBE-ERC resection. Multivariate analysis revealed that the absence of a stent (HR = 0.15, 95% CI 0.06-0.40, P = 0.001), absence of intrahepatic biliary gas imaging during endoscopy (HR = 0.39, 95% CI 0.17-0.91, P = 0.03) and the presence of a thread in the anastomosis (HR = 3.69, 95% CI 1.59-8.57, P = 0.002) were independent risk factors for stricture recurrence. CONCLUSIONS: Treating biliary disease after choledochojejunostomy with SBE-ERC is safe and effective, with a good immediate technical success rate and an acceptable incidence of complications. SBE-ERC has long-term efficacy in the treatment of benign bilioenteric anastomotic stricture. The absence of intrahepatic biliary gas imaging during endoscopy, non-indwelling biliary stents and the existence of anastomotic threads are independent risk factors for the recurrence of benign bilioenteric anastomotic stricture.
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Background: Pancreatic fistula (PF) is the main complication in patients undergoing pancreaticoduodenectomy. Computed tomography (CT) value can reflect pancreatic tissue characteristics which is related to PF. This study was designed to study the relationship between the preoperative CT value and pancreatic fistula. Methods: We retrospectively reviewed the clinical and medical data of patients undergoing pancreaticoduodenectomy from 2017 to 2021. The pancreatic CT value and the CT value ratios of the pancreas and abdominal aorta (PCT/ACT) were measured and compared between the PF group and non-PF group. The values in different PF severity groups were compared using variance analysis. A cut-off value was selected by receiver operating characteristic (ROC) curve. Single-factor and multiple-factor analysis were performed to evaluate Correlation between PF and CT. Results: One hundred and twenty-seven cases were included in this study. The PCT/ACT in the PF group was significantly lower than that in the non-PF group (P<0.001), and the PCT/ACT value was correlatively lower in the severe PF group than in the mild PF group (P=0.008). A cutoff value of 0.99 was selected by ROC curves analysis. Further multifactor analysis identified PCT/ACT <0.99 to be an independent preoperative predictor [odds ratio (OR): 11.3, P<0.01]. Conclusions: The preoperative pancreatic CT value can indirectly reflect the histological condition of the pancreas and thus may related to postoperative PF after pancreaticoduodenectomy and provide useful information for surgeons in deciding upon the pancreaticojejunostomy method.
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Background: Pancreaticojejunal anastomotic stenosis (PJS) after pancreaticoduodenectomy (PD) is difficult to treat. Single-balloon enteroscope-assisted endoscopic retrograde pancreatography (SBE-assisted ERP) is a safe way to treat PJS with the strength of minimally invasion and repeatability, but since its technical difficulty and few patient number, data on long-term outcomes remain limited. The optimal treatment is still unknown. We aim to study the safety, effectiveness, and long-term outcome of single balloon enteroscopy-assisted (SBE-assisted) therapeutic ERP in patients with PJS in this study. Methods: The clinical information of patients undergoing SBE-assisted therapeutic ERP from March 2016 to March 2021 were retrospectively analyzed. All patients were diagnosed as PJS and without any contraindication for therapeutic endoscopy. Treatment details, postoperative complications, factors influencing technical success rate were evaluated. Long-term outcomes results were obtained by clinical or telephone follow-up. Results: Sixteen patients with median age of 51 years were included in this study, surgical reconstruction methods including PD with Whipple reconstruction, PD with Child reconstruction, pylorus-preserving pancreaticoduodenectomy (PpPD) with Whipple reconstruction. Eight patients were successfully treated. No serious complications happened. Risk factors for the failure of pancreaticojejunal anastomotic site identification include the digestive tract reconstruction sequence, pancreaticojejunostomy method, pancreatic duct tube implantation, pancreatic duct width before surgery, and pancreatic fistula during perioperative period. The median follow-up time was 77.2 months, the mean indwelling time of the stent was 62.3 months [interquartile range (IQR), 6.8-153.7 months]. Two of eight patients developed recurrent PJS. The variation in body mass index (BMI) was +2.46 in the non-recurrence group compared to -1.09 in the recurrence group and -2.12 in the endoscopic retrograde cholangiopancreatography (ERCP) treatment failure group. Conclusions: ERP intervention should be carried out early once PJS occurs in order to increase success rate. BMI is a crucial indicator which can reflex PJS rehabilitation degree during follow-up. In order to reduce PJS recurrence rate, a wider pancreatic stent and a longer stent indwelling time are recommended.
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BACKGROUND: Long non-coding RNA (lncRNA) H19 has been reported to involve in many kinds of human cancers and functions as an oncogene. Our previous study found that H19 was over-expressed in gallbladder cancer (GBC) and was shown to promote tumor development in GBC. However, the competing endogenous RNA (ceRNA) regulatory network involving H19 in GBC progression has not been fully elucidated. We aim to detect the role of H19 as a ceRNA in GBC. METHODS AND RESULTS: In this study, the expression of H19 and miR-342-3p were analyzed in 35 GBC tissues and matched normal tissues by using quantitative polymerase chain reaction (qRT-PCR). We demonstrated H19 was overexpressed and negatively correlated with miR-342-3p in GBC. By dual-luciferase reporter assays, RNA-binding protein immunoprecipitation (RIP) and RNA pull-down assays, we verified that H19 was identified as a direct target of miR-342-3p. QRT-PCR and Western-blotting assays demonstrated that H19 silencing down-regulated, whereas over-expression enhanced the expression of miR-342-3p targeting FOXM1 through competitively 'sponging' miR-342-3p. Furthermore, transwell invasion assays and cell cycle assays indicated that H19 knockdown inhibited both cells invasion and proliferation, but this effects was attenuated by co-transfection of siRNA-H19 and miR-342-3p inhibitor in GBC cells. In vivo, tumor volumes were decreased significantly in H19 silenced group compared to the control group, but was attenuated by co-transfection of shRNA-H19 and miR-342-3p inhibitor, which were stablely constructed through lenti-virus vector. CONCLUSION: Our results suggest a potential ceRNA regulatory network involving H19 regulates FOXM1 expression by competitively binding endogenous miR-342-3p in GBC. This mechanism may contribute to a better understanding of GBC pathogenesis and provides potential therapeutic strategy for GBC.
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Proteína Forkhead Box M1/genética , Neoplasias de la Vesícula Biliar/genética , MicroARNs/genética , ARN Largo no Codificante/genética , Regiones no Traducidas 3' , Animales , Línea Celular Tumoral , Neoplasias de la Vesícula Biliar/patología , Regulación Neoplásica de la Expresión Génica , Técnicas de Silenciamiento del Gen , Humanos , Ratones , Trasplante de NeoplasiasRESUMEN
Long noncoding RNAs (lncRNA) are being implicated in the development of many cancers. Here, we report the discovery of a critical role for the lncRNA GCASPC in determining the progression of gallbladder cancer. Differentially expressed lncRNAs and mRNAs between gallbladder cancer specimens and paired adjacent nontumor tissues from five patients were identified and validated by an expression microarray analysis. Quantitative real-time PCR was used to measure GCASPC levels in tissues from 42 gallbladder cancer patients, and levels of GCASPC were confirmed further in a separate cohort of 89 gallbladder cancer patients. GCASPC was overexpressed or silenced in several gallbladder cancer cell lines where molecular and biological analyses were performed. GCASPC levels were significantly lower in gallbladder cancer than adjacent nontumor tissues and were associated with tumor size, American Joint Committee on Cancer tumor stage, and patient outcomes. GCASPC overexpression suppressed cell proliferation in vitro and in vivo, whereas GCASPC silencing had opposite effects. By RNA pull-down and mass spectrometry, we identified pyruvate carboxylase as an RNA-binding protein that associated with GCASPC. Because GCASPC is a target of miR-17-3p, we confirmed that both miR-17-3p and GCASPC downregulated pyruvate carboxylase level and activity by limiting protein stability. Taken together, our results defined a novel mechanism of lncRNA-regulated cell proliferation in gallbladder cancer, illuminating a new basis for understanding its pathogenicity. Cancer Res; 76(18); 5361-71. ©2016 AACR.
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Neoplasias de la Vesícula Biliar/genética , Neoplasias de la Vesícula Biliar/patología , MicroARNs/genética , ARN Largo no Codificante/genética , Western Blotting , Proliferación Celular/fisiología , Neoplasias de la Vesícula Biliar/mortalidad , Técnicas de Silenciamiento del Gen , Humanos , Inmunohistoquímica , Inmunoprecipitación , Estimación de Kaplan-Meier , Espectrometría de Masas , Análisis de Secuencia por Matrices de Oligonucleótidos , Piruvato Carboxilasa/metabolismo , Reacción en Cadena en Tiempo Real de la PolimerasaRESUMEN
LncRNA-ROR has been reported to be involved in many kinds of human cancers. However, whether LncRNA-ROR is involved in gallbladder cancer progression remains largely unknown. The objective of this study is to investigate the role of LncRNA-ROR in gallbladder cancer. We found that LncRNA-ROR expression level was upregulated in gallbladder cancer tissues (P < 0.05) and was significantly associated with tumor sizes (P < 0.05) and lymph node metastasis (P < 0.05). High expression of LncRNA-ROR was significantly associated with poor prognosis in gallbladder cancer patients (P < 0.05). Moreover, knockdown of LncRNA-ROR inhibited cell proliferation, migration, and invasion. The epithelial-mesenchymal transition (EMT) phenotype induced by TGF-ß1 was reversed after LncRNA-ROR knocking down in SGC-996 and Noz cells. LncRNA-ROR plays an important role in the development of gallbladder cancer and mediates the EMT in gallbladder cancer. LncRNA-ROR might act as a marker of prognosis and therapeutic target for gallbladder cancer.
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Movimiento Celular/genética , Proliferación Celular/genética , Neoplasias de la Vesícula Biliar/genética , ARN Largo no Codificante/genética , Biomarcadores de Tumor/genética , Western Blotting , Cadherinas/genética , Cadherinas/metabolismo , Línea Celular Tumoral , Transición Epitelial-Mesenquimal/efectos de los fármacos , Transición Epitelial-Mesenquimal/genética , Femenino , Neoplasias de la Vesícula Biliar/metabolismo , Neoplasias de la Vesícula Biliar/patología , Regulación Neoplásica de la Expresión Génica , Humanos , Estimación de Kaplan-Meier , Masculino , Persona de Mediana Edad , Invasividad Neoplásica , Valor Predictivo de las Pruebas , Pronóstico , Interferencia de ARN , Reacción en Cadena de la Polimerasa de Transcriptasa Inversa , Factor de Crecimiento Transformador beta1/farmacología , Vimentina/genética , Vimentina/metabolismoRESUMEN
Gallbladder carcinoma (GBC) is an aggressive neoplasm, and the treatment options for advanced GBC are limited. Recently, long non-coding RNAs (lncRNAs) have emerged as new gene regulators and prognostic markers in several cancers. In this study, we found that metastasis-associated lung adenocarcinoma transcript 1 (MALAT1) expression was up-regulated in GBC tissues (P < 0.05). Luciferase reporter assays and RNA pull down assays showed that MALAT1 is a target of miR-363-3p. Real-time quantitative PCR and Western blot analysis indicated that MALAT1 regulated Myeloid cell leukaemia-1 (MCL-1) expression as a competing endogenous RNA (ceRNA) for miR-363-3p in GBC cells. Furthermore, MALAT1 silencing decreased GBC cell proliferation and the S phase cell population and induced apoptosis in vitro. In vivo, tumour volumes were significantly decreased in the MALAT1 silencing group compared with those in the control group. These data demonstrated that the MALAT1/miR-363-3p/MCL-1 regulatory pathway controls the progression of GBC. Inhibition of MALAT1 expression may be to a novel therapeutic strategy for gallbladder cancer.
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Neoplasias de la Vesícula Biliar/genética , Regulación Neoplásica de la Expresión Génica , MicroARNs/metabolismo , Proteína 1 de la Secuencia de Leucemia de Células Mieloides/genética , ARN Largo no Codificante/metabolismo , Animales , Apoptosis/genética , Secuencia de Bases , Ciclo Celular/genética , Línea Celular Tumoral , Proliferación Celular/genética , Regulación hacia Abajo/genética , Neoplasias de la Vesícula Biliar/patología , Técnicas de Silenciamiento del Gen , Masculino , Ratones Desnudos , MicroARNs/genética , Proteína 1 de la Secuencia de Leucemia de Células Mieloides/metabolismo , ARN Largo no Codificante/genética , Carga Tumoral/genéticaRESUMEN
The regulation of MYC-regulated long non-coding RNAs has been reported to contribute to certain types of cancers. However, the role of MYC-induced long non-coding RNA (MINCR) in the tumorigenesis of gallbladder cancer (GBC) is still largely unknown. In this study, we discovered that MINCR was markedly upregulated in GBC tissues compared with adjacent normal tissues. High MINCR expression levels in GBC were positively associated with tumor volume and lymph node metastasis and were negatively correlated with overall survival (OS). Upregulation of MINCR and enhancer of zeste homolog 2 (EZH2) in GBC coincided with the downregulation of miR-26a-5p in GBC. Mechanistically, MINCR/miR-26a-5p/EZH2 axis was found to be involved in cell proliferation, cell invasive and apoptosis in GBC cells. Moreover, knockdown of MINCR suppressed cell proliferation, decreased S-phase cell numbers, increased cell apoptosis, and inhibited cell invasion by inhibiting the epithelial-mesenchymal transition (EMT) phenomenon in GBC cells. In vivo, tumor volumes were significantly decreased in the MINCR silencing group compared with those in the control group. These results demonstrated that MINCR could potentially be a therapeutic target as well as a prognostic marker in GBC.
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Proteína Potenciadora del Homólogo Zeste 2/metabolismo , Neoplasias de la Vesícula Biliar/metabolismo , ARN Largo no Codificante/metabolismo , Apoptosis , Puntos de Control del Ciclo Celular , Línea Celular , Movimiento Celular , Proliferación Celular , Progresión de la Enfermedad , Proteína Potenciadora del Homólogo Zeste 2/genética , Transición Epitelial-Mesenquimal , Neoplasias de la Vesícula Biliar/genética , Neoplasias de la Vesícula Biliar/mortalidad , Neoplasias de la Vesícula Biliar/cirugía , Regulación Neoplásica de la Expresión Génica , Humanos , Metástasis Linfática , MicroARNs/genética , MicroARNs/metabolismo , Interferencia de ARN , ARN Largo no Codificante/genética , Transducción de Señal , Factores de Tiempo , Transfección , Carga Tumoral , Regulación hacia ArribaRESUMEN
Long non-coding RNA (lncRNA) metastasis-associated lung adenocarcinoma transcript 1 (Malat1) functions as an oncogene in many types of human cancer. In this study, we show that Malat1 is overexpressed in gallbladder cancer (GBC) tissue and cells. The high Malat1 levels correlated positively with tumor size and lymphatic metastasis, and correlated negatively with overall survival. We also show that Malat1 functions as a competing endogenous RNA (ceRNA) for miR-206. Because miR-206 directly suppresses expression of ANXA2 and KRAS, which are thought to promote GBC progression, Malat1 binding of miR-206 in GBC tissue and cells has an oncogenic effect. Conversely, Malat1 knockdown inhibits proliferation and invasion by GBC cells while increasing apoptosis. In vivo, silencing Malat1 decreases tumor volume. These results suggest Malat1 could potentially serve as a therapeutic target and prognostic marker for GBC.
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Carcinoma/metabolismo , Neoplasias de la Vesícula Biliar/metabolismo , MicroARNs/genética , ARN Largo no Codificante/genética , Anciano , Anexina A2/metabolismo , Apoptosis , Carcinoma/genética , Ciclo Celular , Proliferación Celular , Progresión de la Enfermedad , Femenino , Neoplasias de la Vesícula Biliar/genética , Células HEK293 , Humanos , Metástasis Linfática , Masculino , Persona de Mediana Edad , Invasividad Neoplásica , Proteínas Proto-Oncogénicas p21(ras)/metabolismo , ARN Largo no Codificante/metabolismo , Resultado del Tratamiento , Regulación hacia ArribaRESUMEN
[This corrects the article on p. 15 in vol. 6, PMID: 27073719.].
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The imprinted oncofetal long non-coding RNA H19 has been reported to be involved in many kinds of human cancers. However, whether lncRNA H19 implicate in oncogenesis and cancer progression in gallbladder cancer remain largely unknown. In the present study, compared with adjacent normal tissues, the level of H19 was significantly upregulated in gallbladder cancer tissues and was positively associated with lymphatic metastasis and tumor size. The overall survival is shorter in those who had higher H19 expression among GBC patients. In vitro, both TGF-ß1 and IL-6 treatment induced upregulation of H19, downregulated the protein level of E-cadherin while increased Vimentin, indicating an epithelial-mesenchymal transition (EMT) phenotype in GBC. The overexpression of H19 in GBC cells enhanced tumor invasion and promoted EMT by upregulated transcription factor Twist1. On the contrary, Loss of function studies indicated that H19 interference in GBC suppressed tumor cell invasion and promoted mesenchymal-epithelial transition (MET) via suppressing Twist expression. In vivo, the volume of the tumors in H19-inteference group was significantly decreased compared to those in the control group of nude mice. Both western-blot and immunohistochemistry confirmed that a MET phenotype existed in the H19 interference group when compared to control group. These results defined H19 as a novel prognostic factor for GBC, and indicated that it might play important regulatory roles in the EMT process.
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It has been shown that long noncoding RNAs (lncRNAs) play a critical role in the regulation of cellular processes including cancer progression and metastasis. However, the biological functions and clinical significance of lncRNA AFAP1-AS1 in hepatocellular carcinoma (HCC) remain unclear. Expression of AFAP1-AS1 was analyzed in 78 HCC tissues by real-time PCR. The effect of AFAP1-AS1 on cell proliferation was examined by MTT assay, cell apoptosis was detected by flow cytometric analysis and cell invasion was determined by Transwell assay. RhoA/Rac2 signaling and downstream factors were verified by western blotting. HCC cells infected with si-AFAP1-AS1 were injected into nude mice to investigate the effect of AFAP1-AS1 on the tumorigenesis in vivo. We found that increased expression of AFAP1-AS1 was significantly correlated with pathological staging (P=0.024) and lymph-vascular space invasion (LVSI) in HCC patients (P=0.007). Multivariate analyses indicated that AFAP1-AS1 represented an independent predictor for overall survival of HCC (P=0.029). Further experiments showed that knockdown of AFAP1-AS1 by si-AFAP1-AS1 decreased the proliferation and invasion in vitro and in vivo, induced cell apoptosis and blocked cell cycle in S phase via inhibition of the RhoA/Rac2 signaling. Taken together, our findings indicate that AFAP1-AS1 may promote the HCC development through upregulation of RhoA/Rac2 signaling and provide a potential therapeutic target for HCC.
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Carcinoma Hepatocelular/patología , Neoplasias Hepáticas/patología , ARN Largo no Codificante/genética , Regulación hacia Arriba , Proteínas de Unión al GTP rac/metabolismo , Proteína de Unión al GTP rhoA/metabolismo , Animales , Carcinoma Hepatocelular/genética , Carcinoma Hepatocelular/metabolismo , Línea Celular Tumoral , Movimiento Celular , Proliferación Celular , Femenino , Regulación Neoplásica de la Expresión Génica , Células Hep G2 , Humanos , Neoplasias Hepáticas/genética , Neoplasias Hepáticas/metabolismo , Masculino , Ratones , Trasplante de Neoplasias , Pronóstico , Transducción de Señal , Análisis de Supervivencia , Proteína RCA2 de Unión a GTPRESUMEN
Gallbladder cancer (GBC) is a highly malignant cancer with poor prognosis. Although long noncoding RNA (lncRNA) H19 has been reported to play vital role in many human cancers, whether it is involved in GBC proliferation is still unknown. This study was designed to explore the effect of H19 in GBC cell proliferation. The expression of H19 and AKT2 were significantly elevated in GBC tissues, and the level of miR-194-5p is markedly decreased. Moreover, the RNA levels of H19 and AKT2 were positively correlated, and H19 elevation was significantly associated with tumor size. Cell proliferation decreased significantly after knockdown of H19 in GBC-SD and NOZ cells and after knockdown of AKT2 in NOZ cells. Results from cell cycle studies indicated that the S phase were significantly decreased after knockdown of H19 in NOZ cells but significantly elevated after overexpression of H19 in GBC-SD cells. Furthermore, knockdown of H19 upregulated miR-194-5p levels, yet significantly decreased miR-194-5p targeting AKT2 gene expression in NOZ cells. Inhibitor against miR-194-5p reversed these effects. In addition, overexpression of H19 in GBC-SD cells downregulated miR-194-5p and markedly increased AKT2 expression, and miR-194-5p mimic reversed these effects. Eventually, GBC cells were arrested in G0/G1-phase after H19 knockdown, inhibition of miR-194-5p markedly promoted cells into S-phase and co-transfection of siH19, and miR-194-5p inhibitor exerted mutually counter-regulated effects on cell cycle. These results suggested that H19/miR-194-5p/AKT2 axis regulatory network might modulate cell proliferation in GBC.
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Biomarcadores de Tumor/metabolismo , Proliferación Celular , Neoplasias de la Vesícula Biliar/patología , MicroARNs/genética , Proteínas Proto-Oncogénicas c-akt/metabolismo , ARN Largo no Codificante/genética , Apoptosis , Biomarcadores de Tumor/genética , Western Blotting , Estudios de Casos y Controles , Ciclo Celular , Movimiento Celular , Femenino , Estudios de Seguimiento , Neoplasias de la Vesícula Biliar/genética , Neoplasias de la Vesícula Biliar/metabolismo , Humanos , Técnicas para Inmunoenzimas , Metástasis Linfática , Masculino , Persona de Mediana Edad , Clasificación del Tumor , Invasividad Neoplásica , Estadificación de Neoplasias , Pronóstico , Proteínas Proto-Oncogénicas c-akt/genética , ARN Mensajero/genética , Reacción en Cadena en Tiempo Real de la Polimerasa , Reacción en Cadena de la Polimerasa de Transcriptasa Inversa , Células Tumorales CultivadasRESUMEN
BACKGROUND: Two types of pancreatic duct stents are used to improve postoperative outcomes of pancreatic anastomosis. The aim of this meta-analysis was to evaluate and compare the postoperative outcomes of patients with internal or external stenting during pancreaticoduodenectomy (PD). METHODS: We searched PubMed, EMBASE, the Cochrane Library and Web of Science databases until the end of December, 2014. Studies comparing outcomes of external vs. internal stent placement in PD were eligible for inclusion. Included literature was extracted and assessed by two independent reviewers. RESULTS: Seven articles were identified for inclusion: three randomized controlled trials (RCTs) and four observational clinical studies (OCS). The meta-analyses revealed that use of external stents had advantage on reducing the incidences of pancreatic fistula (PF) in total [odds ratio (OR) =0.69; 95% confidence interval (CI), 0.48-0.99; P=0.04], PF in soft pancreas (OR =0.30; 95% CI, 0.16-0.56; P=0.0002) and delayed gastric emptying (DGE) (OR =0.58; 95% CI, 0.38-0.89; P=0.01) compared with internal stents. There were no significant differences in other postoperative outcomes between two stenting methods, including postoperative morbidity (OR =0.93; 95% CI, 0.39-2.23; P=0.88), overall mortality (OR =0.70; 95% CI, 0.22-2.25; P=0.55), and intra-abdominal collections (OR =0.67; 95% CI, 0.26-1.71; P=0.40). CONCLUSIONS: Based upon this meta-analysis, the use of external pancreatic stents might have potential benefit in reducing the incidence of PF and DGE. Due to the limited number of original studies, more RCTs are needed to further support our result and clarify the issue.
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The identification of cancer-associated long non-coding RNAs (lncRNAs) and the investigation of their molecular and biological functions are vital for understanding the molecular biology and progression of cancer. The lncRNA-LET, a newly identified lncRNA, was demonstrated to be down-regulated in hepatocellular cancer. However, little is known about its role in gallbladder cancer. In the present study, an obvious down-regulation of lncRNA-LET was observed in gallbladder cancer compared to their adjacent normal tissues. Meanwhile, patients with low expression of lncRNA-LET have significantly poorer prognosis than those with high expression. We confirmed that hypoxia decreased lncRNA-LET levels in gallbladder cancer cells. Moreover, lncRNA-LET overexpression was further validated to inhibit the invasion of gallbladder cancer cells under hypoxic or normoxic conditions in vitro. We demonstrated that lncRNA-LET overexpression conferred a proliferative advantage to tumor cells under hypoxic conditions. The ectopic expression of lncRNA-LET led to the promotion of cell cycle arrest at G0/G1 phase and to the induction of apoptosis under hypoxic conditions. Ectopic expression of LncRNA-LET also suppressed gallbladder tumor growth in vivo. Our findings indicate that lncRNA-LET may represent a prognostic marker and a potential therapeutic target for gallbladder cancer.
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Neoplasias de la Vesícula Biliar/genética , ARN Largo no Codificante/genética , Animales , Apoptosis/genética , Biomarcadores de Tumor/genética , Línea Celular Tumoral , Regulación hacia Abajo/genética , Femenino , Puntos de Control de la Fase G1 del Ciclo Celular/genética , Neoplasias de la Vesícula Biliar/patología , Regulación Neoplásica de la Expresión Génica/genética , Humanos , Masculino , Ratones , Ratones Desnudos , Persona de Mediana Edad , Pronóstico , Fase de Descanso del Ciclo Celular/genéticaRESUMEN
BACKGROUND: Recent studies have demonstrated that side population (SP) cells isolated from various cancer cell lines and primary tumors possess stem cell-like properties. Sesamin, a food-derived agent, possesses anti-cancer activities both in vitro and in vivo. The present study was designed to determine whether sesamin also have effects on cancer stem-like SP cells from gallbladder cancer (GBC). METHODS: In this study, we sorted SP cells by flow cytometry. SP cells were cultured and treated with sesamin. Tumor-sphere formation, colony formation, Matrigel invasion and tumorigenic potential were determined. Expression of nuclear NF-κB, IL-6, p-Stat3, Twist, E-cadherin and Vimentin was measured by Western blot, immunofluorescence staining or RT-PCR analysis. Nuclear NF-κB activity and IL-6 protein level were assessed with ELISA. Xenograft tumors were generated in nude mice. RESULTS: After treated with sesamin, SP cells differentiated into cells expressing the epithelial marker (E-cadherin). Sesamin effectively affected SP cells stem cell-like characteristics (i.e., tumor-sphere formation, colony-formation, Matrigel invasion), weakened the drug-resistance of SP cells and inhibited tumor growth both in vitro and in vivo. Treatment with sesamin significantly reduced the expression of nuclear NF-κB, IL-6, p-Stat3, Twist and Vimentin (a mesenchymal marker) in SP cells. Nuclear NF-κB activity and IL-6 level were also decreased after treatment with sesamin. CONCLUSION: Food-derived sesamin directs the epithelial differentiation of cancer stem-like SP cells from GBC, which is associated with attenuation of NF-κB-IL-6-Stat3-Twist signal pathway.
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Dioxoles/farmacología , Neoplasias de la Vesícula Biliar/tratamiento farmacológico , Neoplasias de la Vesícula Biliar/patología , Lignanos/farmacología , Células Madre Neoplásicas/efectos de los fármacos , Células de Población Lateral/efectos de los fármacos , Análisis de Varianza , Animales , Cadherinas/metabolismo , Carcinoma/tratamiento farmacológico , Carcinoma/metabolismo , Carcinoma/patología , Diferenciación Celular/efectos de los fármacos , Línea Celular Tumoral , Femenino , Neoplasias de la Vesícula Biliar/metabolismo , Humanos , Interleucina-6/metabolismo , Ratones , Ratones Desnudos , FN-kappa B/metabolismo , Células Madre Neoplásicas/metabolismo , Células Madre Neoplásicas/patología , Células de Población Lateral/metabolismo , Células de Población Lateral/patología , Transducción de Señal/efectos de los fármacos , Ensayos Antitumor por Modelo de XenoinjertoRESUMEN
BACKGROUND: Protein coding genes account for only about 2% of the human genome, whereas the vast majority of transcripts are non-coding RNAs including long non-coding RNAs. A growing volume of literature has proposed that lncRNAs are important players in cancer. HOTAIR was previously shown to be an oncogene and negative prognostic factor in a variety of cancers. However, the factors that contribute to its upregulation and the interaction between HOTAIR and miRNAs are largely unknown. METHODS: A computational screen of HOTAIR promoter was conducted to search for transcription-factor-binding sites. HOTAIR promoter activities were examined by luciferase reporter assay. The function of the c-Myc binding site in the HOTAIR promoter region was tested by a promoter assay with nucleotide substitutions in the putative E-box. The association of c-Myc with the HOTAIR promoter in vivo was confirmed by chromatin immunoprecipitation assay and Electrophoretic mobility shift assay. A search for miRNAs with complementary base paring with HOTAIR was performed utilizing online software program. Gain and loss of function approaches were employed to investigate the expression changes of HOTAIR or miRNA-130a. The expression levels of HOTAIR, c-Myc and miRNA-130a were examined in 65 matched pairs of gallbladder cancer tissues. The effects of HOTAIR and miRNA-130a on gallbladder cancer cell invasion and proliferation was tested using in vitro cell invasion and flow cytometric assays. RESULTS: We demonstrate that HOTAIR is a direct target of c-Myc through interaction with putative c-Myc target response element (RE) in the upstream region of HOTAIR in gallbladder cancer cells. A positive correlation between c-Myc and HOTAIR mRNA levels was observed in gallbladder cancer tissues. We predicted that HOTAIR harbors a miRNA-130a binding site. Our data showed that this binding site is vital for the regulation of miRNA-130a by HOTAIR. Moreover, a negative correlation between HOTAIR and miRNA-130a was observed in gallbladder cancer tissues. Finally, we demonstrate that the oncogenic activity of HOTAIR is in part through its negative regulation of miRNA-130a. CONCLUSION: Together, these results suggest that HOTAIR is a c-Myc-activated driver of malignancy, which acts in part through repression of miRNA-130a.
Asunto(s)
Neoplasias de la Vesícula Biliar/genética , MicroARNs/genética , Proteínas Proto-Oncogénicas c-myc/genética , ARN Largo no Codificante/genética , Adulto , Anciano , Sitios de Unión , Línea Celular Tumoral , Proliferación Celular , Neoplasias de la Vesícula Biliar/patología , Regulación Neoplásica de la Expresión Génica , Humanos , Masculino , MicroARNs/metabolismo , Persona de Mediana Edad , Invasividad Neoplásica/genética , Regiones Promotoras Genéticas , Activación TranscripcionalRESUMEN
BACKGROUND: A better understanding of the molecular mechanisms in liver regeneration holds promise for exploring the new potential therapy for liver failure. The present study was to investigate the role of zinc finger and BTB domain-containing protein 20 (ZBTB20), a potential factor associated with liver regeneration, in a model of 70% hepatectomy in mice. METHODS: Parameters for liver proliferation such as liver/body ratio and BrdU positivity were obtained via direct measurement and immunohistochemistry. The levels of zinc fingers and homeoboxes 2 (ZHX2), ZBTB20, alpha-fetoprotein (AFP) and glypican 3 (GPC3) transcripts in the regenerating liver tissue of a 70% hepatectomy rodent model were monitored by real-time PCR analysis at different time points. Knockdown of ZBTB20 was performed to characterize its regulatory function. RESULTS: A negatively regulating relationship between ZHX2, ZBTB20 and AFP, GPC3 was revealed from 24 to 72 hours after 70% hepatectomy. ZBTB20 appears to negatively regulate AFP and GPC3 transcription since the knockdown of ZBTB20 promoted the proliferation of hepatocytes and the expression of AFP and GPC3. CONCLUSION: In addition to AFP, GPC3 and ZHX2, ZBTB20 is a new regulator in liver regeneration and the decrease of ZBTB20 expression following 70% hepatectomy promotes AFP and GPC3 expression.
Asunto(s)
Hepatectomía/métodos , Regeneración Hepática/fisiología , Hígado/fisiología , Hígado/cirugía , Factores de Transcripción/fisiología , Animales , Línea Celular , Proliferación Celular , Glipicanos/fisiología , Hepatocitos/patología , Proteínas de Homeodominio/fisiología , Ratones , Ratones Endogámicos C57BL , Modelos Animales , ARN Interferente Pequeño/farmacología , Factores de Tiempo , Factores de Transcripción/efectos de los fármacos , Factores de Transcripción/genética , Transfección , alfa-Fetoproteínas/fisiologíaRESUMEN
BACKGROUND: The diagnostic and prognostic value of microRNA (miRNA) expression aberrations in pancreatic ductal adenocarcinoma (PDAC) has been studied extensively in recent years. However, differences in measurement platforms and lab protocols as well as small sample sizes can render gene expression levels incomparable. METHODS: A comprehensive meta-review of published studies in PDAC that compared the miRNA expression profiles of PDAC tissues and paired neighbouring noncancerous pancreatic tissues was performed to determine candidate miRNA biomarkers for PDAC. Both a miRNA vote-counting strategy and a recently published Robust Rank Aggregation method were employed. In this review, a total of 538 tumour and 206 noncancerous control samples were included. RESULTS: We identified a statistically significant miRNA meta-signature of seven up- and three down-regulated miRNAs. The experimental validation results showed that the miRNA expression levels were in accordance with the meta-signature. The results from the vote-counting strategy were consistent with those from the Robust Rank Aggregation method. The experimental validation confirmed that the statistically unique profiles identified by the meta-review approach could discriminate PDAC tissues from paired nonmalignant pancreatic tissues. In a cohort of 70 patients, the high expression of miR-21 (p=0.018, HR=2.610; 95% CI=1.179-5.777) and miR-31 (p=0.039, HR=2.735; 95% CI=1.317-6.426), the low expression of miR-375 (p=0.022, HR=2.337; 95% CI=1.431-5.066) were associated with poor overall survival following resection, independent of clinical covariates. CONCLUSIONS: The identified miRNAs may be used to develop a panel of diagnostic and prognostic biomarkers for PDAC with sufficient sensitivity and specificity for use in a clinical setting.