Magnetic anchoring device assisted-laparoscopic sleeve gastrectomy versus conventional laparoscopic sleeve gastrectomy: A retrospective cohort study.

Background: Bariatric surgeries, including the sleeve gastrectomy, have been recognized as the most effectively treatment strategy for severe obesity. Magnetic devices have been successfully used in bariatric surgeries. Here, we intended to evaluate the safety and efficiency of magnetic anchoring device assisted-laparoscopic sleeve gastrectomy (MLSG), and to make a comparison of the short-term results between conventional laparoscopic sleeve gastrectomy (CLSG) and MLSG. Methods: The retrospective cohort study was carried out by analyzing and summarizing the data from a database of routinely collected data. The cohort included the patients who underwent either CLSG (n = 120) or MLSG (n = 115) at a single center between January 2018 and December 2020 with a two-year follow-up. The effects of these two surgeries on the weight loss, resolution of comorbidities and quality of life (QOL) were analyzed. Results: The two groups were similar in gender, age, body mass index, abdominal girth, as well as the type and proportion of comorbidities. And the cases in MLSG group had a markedly shorter time of operation (MLSG, 72.59 min vs. CLSG, 76.67 min; P = 0.003). Length of stay in hospital was significantly shorter in the MLSG group than that in the CLSG group (MLSG, 5.59 days vs. CLSG, 5.96 days; P = 0.016). Neither fatal event nor conversion to open surgery happened among all cases. There were no differences in terms of the postoperative complications between the two groups. Magnetic device-related mild hepatic lacerations occurred and were handled by hemostatic treatments in 3 cases. The QOL of patients in MLSG was better at 6-month after surgery, but there was no significant difference between the two groups at 1-year or 2-year after surgery. Conclusion: Both MLSG and CLSG prove safe and effective, and the patients underwent MLSG have a shorter length of stay in hospital, and a better QOL during 6 months after surgery.

YAP1-activated ZNF131 promotes hepatocellular carcinoma cell proliferation through transcriptional regulation of PAIP1.

Zinc finger protein 131 (ZNF131), a member of BTB-ZF transcription factors, has been previously reported as an oncogene in several human cancers. However, the function and underlying mechanism of ZNF131 in hepatocellular carcinoma (HCC) are still unclear. In our study, the upregulated expression of ZNF131 mRNA was confirmed in HCC tissues by analyzing the TCGA and GEO datasets. The immunohistochemical staining data also revealed the overexpression of ZNF131 protein in HCC samples. High expression of ZNF131 predicted poor overall survival and disease-free survival in HCC patients. ZNF131 knockdown inhibited the proliferation and colony formation and led to G2/M phase arrest of HCC cells, while its overexpression promoted HCC cell proliferation, cell cycle progression and colony formation. Moreover, ZNF131 silencing repressed the growth of HCC cells in nude mice. Yes-associated protein 1 (YAP1) was recognized as an upstream regulator of ZNF131. Both YAP1 knockdown and inactivation reduced ZNF131 expression in HCC cells, and YAP1 overexpression enhanced ZNF131 level. Interestingly, we found that poly(A) binding protein interacting protein 1 (PAIP1) was a novel target of ZNF131. ZNF131 silencing downregulated while ZNF131 overexpression upregulated PAIP1 expression in HCC cells. The luciferase reporter assay demonstrated that ZNF131 regulated PAIP1 expression at the transcription level. Notably, we revealed that ZNF131 activated the AKT signaling by enhancing PAIP1 expression in HCC cells. AKT inhibitor markedly attenuated ZNF131-enhanced HCC cell proliferation. Restoring PAIP1 expression abrogated the inhibitory effects of ZNF131 knockdown on HCC cell proliferation and colony formation. To conclude, ZNF131 was highly expressed and acted as an oncogene in HCC. ZNF131, which was activated by YAP1, promoted HCC cell proliferation through transcriptional regulation of PAIP1.

METTL3-induced lncRNA GBAP1 promotes hepatocellular carcinoma progression by activating BMP/SMAD pathway.

BACKGROUND: Hepatocellular carcinoma (HCC) is one of the most common and challenging cancers in the world. N6-methyladenosine (m6A) modification and long non-coding RNAs (lncRNAs) play critical roles in the progression of HCC. However, there are few reports on genome-wide screening and functional annotations of m6A-methylated lncRNAs in HCC. METHODS: The expression levels of m6A methyltransferase METTL3 and the association with the prognosis in HCC were determined by RT-qPCR, public dataset platforms. Then, RNA-seq, Pearson correlation analysis, MeRIP-qPCR, RNA half-life assay, gene site-directed mutation, RIP assay and RT-qPCR analysis were employed to determine the downstream target of METTL3 in HCC. Subsequently, the expression levels and roles of lncRNA glucosylceramidase beta pseudogene 1 (GBAP1) in HCC were determined by Kaplan-meier curves, RT-qPCR, in vitro functional experiments and in vivo tumorigenesis and lung metastasis models. Then, the downstream target and pathway of GBAP1 were explored by GO biological process, KEGG pathway enrichment, luciferase reporter assay, RIP assay and rescue experiments and so on. RESULTS: METTL3 was upregulated in HCC and closely related to HCC prognosis. And METTL3 induced GBAP1 expression by acting as the m6A writer of GBAP1 and IGF2BP2 worked as its m6A reader. Clinically, GBAP1 expression was significantly associated with tumor size, venous infiltration, TNM stage and prognosis of HCC, Functionally, GBAP1 promoted HCC metastasis and growth both in vitro and in vivo. Furthermore, GBAP1 acted as the molecular sponge for miR-22-3p to increase the expression of bone morphogenetic protein receptor type 1A (BMPR1A), which then activated BMP/SMAD pathway in HCC cells. CONCLUSIONS: Our findings demonstrated that METTL3-induced GBAP1 promoted migration, invasion and proliferation of HCC cells via GBAP1/miR-22-3p/BMPR1A/SMAD axis. GBAP1 could be a potential prognosis indicator and therapeutic target for HCC.

[Corrigendum] BCL­3 promotes the tumor growth of hepatocellular carcinoma by regulating cell proliferation and the cell cycle through cyclin D1.

Subsequently to the publication of the above article, the authors have alerted the Editorial Office to the fact that they identified a small number of errors concerning the assembly of Figs. 3A, 6B and 7A in their paper. Specifically, the western blotting results for the BCL­3 and GAPDH experiments in Fig. 3A, the cyclin D1 blots in Fig. 6B and the cyclin D1 blots shown in Fig. 7A were selected erroneously when choosing images from the total pool of data due to the similarity in the appearance of the data. However, the authors retained their access to the raw data, and were able to make the appropriate corrections required for these figures. The corrected versions of Figs. 3, 6 and 7, showing the correct BLC­3/GAPDH and cyclin D1 data in Fig. 3A and 6B respectively, and the correct cyclin D1 data in Fig. 7A, are shown on the next two pages. Note that these errors did not adversely affect the major conclusions reported in the study. The authors all agree to the publication of this corrigendum, and thank the Editor of Oncology Reports for allowing them the opportunity to publish this. The authors also apologize for any inconvenience caused. [Oncology Reports 35: 2382­2390, 2016; DOI: 10.3892/or.2016.4616].

Tube feeding associated postoperative intussusceptions: A single center case series study.

RATIONALE: Postoperative intussusception in adults is a rare but serious complication after gastrointestinal anastomosis surgery. Postoperative intussusception in adults caused by tube feeding was rarely been reported before. The aim of the current study was to summarize the clinical data on a group of patients with tube feeding associated postoperative intussusceptions. The possible etiology and preventive measures will also be discussed. PATIENT CONCERNS: During the period from May 2013 to January 2018, patients who received gastrointestinal anastomosis in our center were retrospectively reviewed. Preoperative variables including standard demographic and pathological characteristics as well as the treatment and prognosis were also analyzed. DIAGNOSES: Tube feeding associated postoperative intussusceptions. INTERVENTIONS: 7 patients were identified with tube feeding associated postoperative intussusceptions with a prevalence of 0.38%. Intussusceptions occurred from 10 to 69 days (median 25.7 days) postoperatively in an acute form. OUTCOMES: None of the patients had spontaneous reduction and all patients underwent surgery. Antegrade efferent limb intussusceptions were found in all the cases. Intussusception occurred at efferent loop at 23.6 cm (range 15-60) from the gastrointestinal or Braun anastomosis. None of the patients was found recurrence throughout the follow-up period. LESSONS: In contrast with other postoperative intussusceptions, the tube feeding associated postoperative intussusceptions have special clinical manifestations. It is more likely to occur in early period of time after the surgery and in an acute form. Surgical correction is recommended for most of patients. Several measures have been proposed to prevent such complications after gastrointestinal surgery, however more research and information are still needed.

MicroRNA-519c-3p promotes tumor growth and metastasis of hepatocellular carcinoma by targeting BTG3.

Tumor recurrence and metastasis after surgical resection are the major causes for the cancer-related death of hepatocellular carcinoma (HCC). Thus, better understanding the mechanisms involved in tumor progression will benefit to improve HCC treatment. Accumulating evidence demonstrates that microRNAs (miRNAs) play critical roles in the development and progression of HCC. However, the function of miR-519c-3p in HCC and its related mechanism remain unexplored. Here, we reported that miR-519c-3p was strongly overexpressed in HCC tissues, which was significantly correlated with poor prognosis and clinicopathological features including tumor size ≥5 cm, vascular invasion and advanced tumor-node-metastasis (TNM) stages (III + IV). Furthermore, the elevated levels of miR-519c-3p were observed in HCC cell lines. Subsequently, gain- or loss-of-function assays demonstrated that miR-519c-3p promoted HCC cell proliferation, migration as well as invasion in vitro, and facilitated the growth and metastasis of HCC cells in vivo. Mechanistically, B-cell translocation gene 3 (BTG3) was identified as a direct downstream target of miR-519c-3p. The level of BTG3 mRNA was downregulated in HCC and negatively correlated with miR-519c-3p expression. Western blotting confirmed that BTG3 was negatively regulated by miR-519c-3p in HCC cells. Luciferase reporter assays illustrated the direct interaction between miR-519c-3p and the 3'UTR of BTG3 mRNA. Recuse experiments demonstrated that BTG3 mediated the promoting effects of miR-519c-3p on the proliferation and motility of HCC cells. Collectively, our results suggest that miR-519c-3p functions as a tumor promotor in regulating the growth and metastasis of HCC by targeting BTG3, and potentially serves as a novel therapeutic target for HCC.

ZNF503 accelerates aggressiveness of hepatocellular carcinoma cells by down-regulation of GATA3 expression and regulated by microRNA-495.

Zinc finger protein ZNF503 is an important regulator during developmental process and tumor initiation. ZNF503 drives tumor development and process and was cancer-specific dysregulated in cancers. However, its expression and function in hepatocellular carcinoma (HCC) still need to be studied and elucidated. In this study, we demonstrated for the first time that ZNF503 mRNA and protein was up-regulated in HCC tissues and cell lines. Clinical data showed that high ZNF503 was significantly correlated with poor prognostic features, including advanced TNM stage and venous invasion. Moreover, ZNF503 was identified as a potential 5-year prognostic marker of HCC patients. Notably, ZNF503 promoted migration, invasion and EMT progress. ZNF503 was recruited to GATA3 promoter and inhibited its expression. GATA3 inhibited HCC cells migration, invasion and EMT process. Furthermore, we demonstrated that ZNF503 expression was regulated by miR-495. In HCC tissues. MiR-495 has an inverse correlation with ZNF503 expression. Conclusively, our data revealed that ZNF503 promoted migration, invasion and EMT process through regulating GATA3 expression, which was regulated by miR-495, suggesting the potential therapeutic value for HCC.

MicroRNA-645 represses hepatocellular carcinoma progression by inhibiting SOX30-mediated p53 transcriptional activation.

Amount of evidence demonstrate that aberrant microRNAs (miRNAs) are involved in tumorigenesis and progression in hepatocellular carcinoma (HCC). Among them, miR-645 is recently recognized as cancer-related miRNA and its significance in HCC remains largely unknown. In this study, we reported for the first that miR-645 expression was markedly elevated in HCC tissues and cell lines, and its up-regulation was associated with malignant clinical features, including tumor size and venous infiltration and poor prognosis. Our data revealed that miR-645 promoted cell proliferation, colony formation and inhibited apoptosis by gain- and loss-of function experiments in vitro. In vivo assays showed that miR-645 overexpression enhanced tumor growth. Moreover, miR-645 directly bound to the SOX30 3'-UTR and post-transcriptionally repressed SOX30 expression in HCC cells. Furthermore, miR-645 inversely correlated with SOX30 expression in HCC tissues. Restoration of SOX30 expression at least partially abolished the biological effects of miR-645 on HCC cells. SOX30 regulated HCC progression through aberrant activation of p53 by directly binding to its promoter. Taken together, this research supports the first evidence that miR-645 exerts an oncogenic role in HCC progression and may be a therapeutic target for HCC treatment.

lncRNA A1BG-AS1 suppresses proliferation and invasion of hepatocellular carcinoma cells by targeting miR-216a-5p.

Extensive evidence indicate that long noncoding RNAs (lncRNAs) regulates the tumorigenesis and progression of hepatocellular carcinoma (HCC). However, the expression and biological function of lncRNA A1BG antisense RNA 1 (A1BG-AS1) were poorly known in HCC. Here, we found the underexpression of A1BG-AS1 in HCC via analysis of The Cancer Genome Atlas database. Further analyses confirmed that A1BG-AS1 expression in HCC was markedly lower than that in noncancerous tissues based on our HCC cohort. Clinical association analysis revealed that low A1BG-AS1 expression correlated with poor prognostic features, such as microvascular invasion, high tumor grade, and advanced tumor stage. Follow-up data indicated that low A1BG-AS1 level evidently correlated with poor clinical outcomes of HCC patients. Moreover, forced expression of A1BG-AS1 repressed proliferation, migration, and invasion of HCC cells in vitro. Conversely, A1BG-AS1 knockdown promoted these malignant behaviors in HepG2 cells. Mechanistically, A1BG-AS1 functioned as a competing endogenous RNA by directly sponging miR-216a-5p in HCC cells. Notably, miR-216a-5p restoration rescued A1BG-AS1 attenuated proliferation, migration and invasion of HCCLM3 cells. A1BG-AS1 positively regulated the levels of phosphatase and tensin homolog and SMAD family member 7, which were reduced by miR-216a-5p in HCC cells. Altogether, we conclude that A1BG-AS1 exerts a tumor suppressive role in HCC progression.

miR-23c suppresses tumor growth of human hepatocellular carcinoma by attenuating ERBB2IP.

MicroRNAs (miRNAs) regulate a variety of development and physiologic processes, and play prominent roles in the initiation and progression of human cancers including hepatocellular carcinoma (HCC). MiR-23c is recently emerging as a cancer-associated miRNA, while its expression status and functional role in HCC are unrevealed yet. Here, we found that miR-23c underexpression was associated with the tumorigenesis of HCC based on TCGA data. qRT-PCR analysis revealed that miR-23c expression was reduced in HCC tissues and cell lines. Clinical analysis indicated that low miR-23c expression was correlated with large tumor size, high tumor grade, advanced tumor stage and poor survival of HCC patients. Our in vitro experiments found that overexpression of miR-23c inhibited cell proliferation and induced apoptosis of HCC cells. While miR-23c knockdown led to HCC cell growth arrest and apoptosis. Additionally, miR-23c overexpression repressed tumor growth of HCC in vivo. Mechanistically, erbb2 interacting protein (ERBB2IP) was identified as a direct target of miR-23c in HCC cells. miR-23c suppressed ERBB2IP expression in HCC cells and inversely correlated with ERBB2IP mRNA expression in HCC tissues. Notably, ERBB2IP silencing restrained HCC cell proliferation and induced apoptosis. ERBB2IP restoration reversed the inhibitory effects of miR-23c on HCC cell growth. In conclusion, our observations suggested that miR-23c inhibited cell proliferation and accelerated apoptosis by attenuating ERBB2IP. Targeting miR-23c might open a new avenue for HCC treatment.

MicroRNA-876-5p inhibits epithelial-mesenchymal transition and metastasis of hepatocellular carcinoma by targeting BCL6 corepressor like 1.

Our previous study has reported that BCL6 corepressor like 1 (BCORL1) plays an oncogenic role in hepatocellular carcinoma (HCC) via promoting epithelial-mesenchymal transition (EMT) and tumor metastasis. However, the regulation of BCORL1 mediated by microRNAs (miRNAs) remains poorly known. The analysis of our clinical samples indicated that BCORL1 expression was markedly higher in HCC tissues than that in tumor-adjacent normal tissues. The Cancer Genome Atlas (TCGA) and Gene Expression Omnibus (GEO) datasets revealed that high BCORL1 expression associated with high tumor grade, advanced tumor stage and poor survival of HCC patients. miR-875-5p expression was down-regulated and negatively correlated with BCORL1 mRNA expression in HCC tissues. Furthermore, miR-876-5p inversely regulated BCORL1 abundance in HCC cells by directly targeting the 3'-untranslated region (3'-UTR) of BCORL1. Ectopic expression of miR-876-5p suppressed cell migration and invasion in both HCCLM3 and MHCC97H cells. In accordance, miR-876-5p knockdown promoted the metastatic behaviors of Hep3B cells. Mechanistically, miR-876-5p suppressed the EMT progression of HCC cells. HCC tissues with high miR-876-5p level showed a higher E-cadherin staining compared to cases with low miR-876-5p level. Moreover, the repression of cell metastasis mediated by miR-876-5p was rescued by BCORL1 restoration in HCCLM3 cells. Notably, low miR-876-5p expression associated with venous infiltration, high tumor grade and advanced tumor stage. HCC patients with low miR-876-5p expression had a significant poorer overall survival and disease-free survival. To conclude, miR-876-5p inhibits EMT progression, migration and invasion of HCC cells by targeting BCORL1. Therefore, miR-876-5p/BCORL1 axis may represent as a novel therapeutic target for HCC treatment.

Perioperative outcome of elderly versus younger patients undergoing major hepatic or pancreatic surgery.

OBJECTIVE: The aim of this study was to determine the safety of elderly cancer patients (≥70 years) undergoing hepatic resection (HR) or pancreaticoduodenectomy (PD) in comparison with younger adults (<70 years). METHODS: A total of 1,012 consecutive patients undergoing HR or PD were included. The incidence and severity of morbidity were documented within 30 days postoperatively and compared between elderly and younger groups. Risk factors associated with postoperative morbidity were investigated by multivariate logistic regression analysis. RESULTS: Elderly patients (n=111, 11.0%) had more comorbidities and worse preoperative general condition and liver function versus younger patients (n=901, 89.0%), and thus were more likely to develop infectious (eg, systemic sepsis and urinary tract infection, both p<0.01) and technical-associated complications (intraperitoneal bleeding and biliary/pancreatic fistula, p=0.029 and p=0.074, respectively). However, the incidence and severity of complications were comparable between elderly and younger patients in the whole cohort, and also in HR and PD surgery groups separately. Preoperative hemoglobin (odds ratio [OR] 1.4, p=0.007) and intraoperative blood transfusion (OR 1.9, p=0.002), rather than age, were independently associated with postoperative morbidity. Hepatitis (OR 2.9, p=0.001), preoperative hemoglobin (OR 1.6, p=0.036), and pancreatic versus hepatic surgery (OR 2.3, p=0.005) were independently associated with postoperative infectious. For elderly patients only, American Society of Anesthesiologists (ASA) score III (OR 2.1, p=0.033) and intraoperative blood transfusion (OR 3.2, p=0.030) were independently associated with postoperative morbidity. CONCLUSION: HR and PD can be safely performed in selected elderly patients versus younger patients. Elderly patients with ASA score III or above should be cautiously selected for major surgeries.

Inhibition of CIP2A attenuates tumor progression by inducing cell cycle arrest and promoting cellular senescence in hepatocellular carcinoma.

CIP2A is a recent identified oncogene that inhibits protein phosphatase 2A (PP2A) and stabilizes c-Myc in cancer cells. To investigate the potential oncogenic role and prognostic value of CIP2A, we comprehensively analyzed the CIP2A expression levels in pan-cancer and observed high expression level of CIP2A in majority cancer types, including hepatocellular carcinoma (HCC). Based on a validation cohort including 60 HCC and 20 non-tumorous tissue samples, we further confirmed the high mRNA and protein expression levels of CIP2A in HCC, and found high CIP2A mRNA expression level was associated with unfavorable overall and recurrence-free survival in patients with HCC. Mechanistic investigations revealed that inhibition of CIP2A significantly attenuated cellular proliferation in vitro and tumourigenicity in vivo. Bioinformatic analysis suggested that CIP2A might be involved in regulating cell cycle. Our experimental data further confirmed CIP2A knockdown induced cell cycle arrest at G1 phase. We found accumulated cellular senescence in HCC cells with CIP2A knockdown, companying expression changes of senescence associated proteins (p21, CDK2, CDK4, cyclin D1, MCM7 and FoxM1). Mechanistically, CIP2A knockdown repressed FoxM1 expression and induced FoxM1 dephosphorylation. Moreover, inhibition of PP2A by phosphatase inhibitor rescued the repression of FoxM1. Taken together, our results showed that CIP2A was highly expressed in HCC. Inhibition of CIP2A induced cell cycle arrest and promoted cellular senescence via repressing FoxM1 transcriptional activity, suggesting a potential anti-cancer target for patients with HCC.

MiR-324-3p promotes tumor growth through targeting DACT1 and activation of Wnt/ß-catenin pathway in hepatocellular carcinoma.

Recently, it has been reported that miR-324-3p participates in regulation of the carcinogenesis and tumor progression in various cancers. However, the expression and function of miR-324-3p in hepatocellular carcinoma (HCC) remain unclear. In the current study, miR-324-3p expression was significantly up-regulated in HCC tissues and cell lines. HCC patients with high miR-324-3p level showed poor prognostic features and shorter overall survival and disease-free survival. And in vitro and in vivo experiments revealed that miR-324-3p promoted cell viability, colony formation, proliferation and cell cycle progression of HCC cells. Further studies demonstrated that miR-324-3p could directly target DACT1 (dishevelled binding antagonist of beta catenin 1) and negatively regulated its expression in HCC cells. And rescue experiments revealed that DACT1 could reverse the effects of miR-324-3p on HCC cells. Furthermore, the accumulation of both cytoplasmic and nuclear ß-catenin as well as its downstream targets including c-Myc and cyclin D1 could be positively regulated by miR-324-3p. The regulatory effects of miR-324-3p on ß-catenin, c-Myc and cyclin D1 levels could be reversed by DACT1. Overall, we concluded that miR-324-3p could promote tumor growth through targeting DACT1 and activation of Wnt/ß-catenin pathway in HCC. MiR-324-3p may be a ponderable and promising therapeutic target for HCC.

MicroRNA-340 promotes the tumor growth of human gastric cancer by inhibiting cyclin G2.

Aberrant expression and function of microRNAs (miRNAs) play a critical role in the development and progression of various human cancers including gastric cancer. However, the clinical significance and underlying mechanisms of miR-340 remain largely unknown in gastric cancer. In the present study, we demonstrated that the expression of miR-340 was aberrantly elevated in both gastric cancer tissues and cells. Moreover clinical association analyses disclosed that the elevated level of miR-340 was significantly associated with unfavorable clinicopathological characteristics of the gastric cancer patients, such as poor differentiation, large tumor size and advanced tumor-node-metastasis (TNM) stage. Gastric cancer patients with high expression of miR-340 had prominently shorter overall survival and disease-free survival. Functionally, forced expression of miR-340 promoted cell viability, proliferation, colony formation and cell cycle progression in the SGC-7901 cells, while miR-340 silencing reduced cell viability, proliferation, colony formation and cell cycle progression in MGC-803 cells. Furthermore, in vivo experiments indicated that miR-340 knockdown suppressed the tumor growth of MGC-803 cells. Notably, alteration of miR-340 expression affected the luciferase activity of wild-type 3'-UTR of cyclin G2 (CCNG2) and regulated CCNG2 abundance in gastric cancer cells, indicating that CCNG2 is a direct target of miR-340. Moreover, CCNG2 knockdown eradicated the effects of miR-340 silencing on gastric cancer cells. In conclusion, our data suggest that miR-340 may potentially serve as a novel prognostic biomarker and therapeutic target for gastric cancer.

BCORL1 is an independent prognostic marker and contributes to cell migration and invasion in human hepatocellular carcinoma.

BACKGROUND: The deregulation of E-cadherin has been considered as a leading cause of hepatocellular carcinoma (HCC) metastasis. BCL6 corepressor-like 1 (BCORL1) is a transcriptional corepressor and contributes to the repression of E-cadherin. However, the clinical significance of BCORL1 and its role in the metastasis of HCC remain unknown. METHODS: Differentially expressed BCORL1 between HCC and matched tumor-adjacent tissues, HCC cell lines and normal hepatic cell line were detected by Western blot. The expression of BCORL1 was altered by siRNAs or lentivirus-mediated vectors. Transwell assays were performed to determine HCC cell invasion and migration. RESULTS: Increased expression of BCORL1 protein was detected in HCC specimens and cell lines. Clinical association analysis showed that BCORL1 protein was expressed at significant higher levels in HCC patients with multiple tumor nodes, venous infiltration and advanced TNM tumor stage. Survival analysis indicated that high expression of BCORL1 protein conferred shorter overall survival (OS) and recurrence-free survival (RFS) of HCC patients. Multivariate Cox regression analysis disclosed that BCORL1 expression was an independent prognostic marker for predicting survival of HCC patients. Our in vitro studies demonstrated that BCORL1 prominently promoted HCC cell migration and invasion. Otherwise, an inverse correlation between BCORL1 and E-cadherin expression was observed in HCC tissues. BCORL1 inversely regulated E-cadherin abundance and subsequently facilitated epithelial-mesenchymal transition (EMT) in HCC cells. Notably, the effect of BCORL1 knockdown on HCC cells was abrogated by E-cadherin silencing. CONCLUSIONS: BCORL1 may be a novel prognostic factor and promotes cell migration and invasion through E-cadherin repression-induced EMT in HCC.

BCL-3 promotes the tumor growth of hepatocellular carcinoma by regulating cell proliferation and the cell cycle through cyclin D1.

Previous studies have demonstrated the aberrant expression and oncogenic role of B-cell CLL/lymphoma-3 (BCL-3) in human malignancies. However, the clinical significance of BCL-3 and its biological function in human hepatocellular carcinoma (HCC) remain unknown. In the present study, the expression levels of BCL-3 protein and mRNA in 90 pairs of HCC and matched non-tumor tissues were analyzed using immunohistochemistry and reverse transcription­quantitative polymerase chain reaction (RT­qPCR). We found that the expression levels of BCL-3 protein and mRNA in HCC tissues were significantly higher than those in the matched tumor-adjacent tissues. In addition, positive expression of BCL-3 was associated with adverse clinicopathological characteristics of the HCC patients including hepatitis B virus (HBV) infection, tumor size, cirrhosis and advanced tumor-node-metastasis (TNM) stage. Moreover, HCC patients with positive expression of BCL-3 had significantly decreased 5-year overall survival and recurrence-free survival. Importantly, BCL-3 expression was an independent prognostic factor for indicating the survival of the HCC patients. Functionally, BCL-3 knockdown markedly inhibited cell viability, proliferation and cell cycle progression in HepG2 cells, while BCL-3 overexpression promoted these cellular processes in Huh7 cells. Accordingly, in vivo experiments indicated that BCL-3 knockdown prominently suppressed the tumor growth of HepG2 cells in nude mice. Mechanistically, we revealed that the expression of cyclin D1 was decreased after BCL-3 knockdown in the HepG2 cells and was increased after BCL-3 overexpression in the Huh7 cells. Cyclin D1 silencing was found to abrogate the functional effects of BCL-3 on cellular processes in Huh7 cells. Taken together, our data suggest that BCL-3 may serve as a promising biomarker and an effective therapeutic target of HCC.

Does Braun enteroenterostomy reduce delayed gastric emptying after pancreaticoduodenectomy?

Whether an additional Braun enteroenterostomy is necessary in reducing delayed gastric emptying (DGE) after pancreaticoduodenectomy (PD) has not yet been well investigated. Herein, in this retrospective study, 395 consecutive cases of patients undergoing classic PD from 2009 to 2013 were reviewed. Patients with and without Braun enteroenterostomy were compared in preoperative baseline characteristics, surgical procedure, postoperative diagnosis, and morbidity including DGE. The DGE was defined and classified by the International Study Group of Pancreatic Surgery recommendation. The incidence of DGE was similar in patients with or without Braun enteroenterostomy following PD (37/347, 10.7% vs 8/48, 16.7%, P = 0.220). The patients in the 2 groups were not different in patient characteristics, lesions, surgical procedure, or postoperative complications, although patients without Braun enteroenterostomy more frequently presented postoperative vomiting than those with Braun enteroenterostomy (33.3% vs 15.3%, P = 0.002). Bile leakage, pancreatic fistula, and intraperitoneal abscess were risk factors for postoperative DGE (all P < 0.05). Prokinetic agents and acupuncture were effective in symptom relief of DGE in 24 out of 45 patients and 12 out of 14 patients, respectively.The additional Braun enteroenterostomy following classic PD was not associated with a decreased rate of DGE. Postoperative abdominal complications were strongly correlated with the onset of DGE. Prokinetic agents and acupuncture could be utilized in some patients with DGE.

[Downregulation of HSP70 gene expression and apoptosis in human hepatocellular carcinoma SMMC-7721 cells induced by nimesulide in vitro].

AIM: To investigate the effect of nimesulide on cell apoptosis and possible mechanism in human hepatocellular carcinoma SMMC-7721 cells. METHODS: SMMC-7721 cells were treated with nimesulide at different concentrations. Cell viability was assessed by MTT assay. Cell apoptosis rate was determined with flow cytometry. The cleavage activity of PARP and caspase-9 and the expression of HSP70 were evaluated using RT-PCR and Western blotting. The influence of HSP70 on cell apoptosis was observed using RNA interference silencing HSP70 expression. RESULTS: Nimesulide significantly inhibited cell growth in SMMC-7721 cells in a time- and concentration-dependent manner, and induced cell apoptosis in a concentration-dependent manner. Moreover, nimesulide promoted the cleavage of caspase-9 and PARP and inhibited the mRNA and protein expression of HSP70. Through the specific inhibition on HSP70 gene with siRNA, cell apoptosis increased, and the apoptosis was enhanced by the cleavage activity of caspase-9 and PARP. CONCLUSION: Nimesulide could inhibit cell growth and induce apoptosis in human hepatocellular carcinoma SMMC-7721 cells via the downregulation of HSP70.