Publications by authors named "Chengyou Du"

19 Publications

  • Page 1 of 1

H/ACA snoRNP Gene Family as Diagnostic and Prognostic Biomarkers for Hepatocellular Carcinoma.

Pharmgenomics Pers Med 2021 19;14:1331-1345. Epub 2021 Oct 19.

Department of Pathology, Chongqing Medical University, Chongqing, 400016, People's Republic of China.

Background: The H/ACA small nucleolar ribonucleoprotein (snoRNP) gene family, including GAR1 ribonucleoprotein (GAR1), NHP2 ribonucleoprotein (NHP2), NOP10 ribonucleoprotein (NOP10), and dyskerin pseudouridine synthase 1 (DKC1), play important roles in ribosome biogenesis. However, the potential clinical value of the H/ACA snoRNP gene family in hepatocellular carcinoma (HCC) has not yet been reported.

Methods: Bioinformation databases were used to analyze the expression and roles of the H/ACA snoRNP gene family in HCC. Survival analysis, Gene Ontology (GO), and Kyoto Encyclopedia of Genes and Genomes enrichment pathway (KEGG) analyses were performed using software. Tumor Immune Estimation Resource (TIMER) was used to analyze the correlation between the expression of the H/ACA snoRNP gene family and immune infiltration in HCC. Finally, immunohistochemistry and Western blotting were performed to verify the protein expression of the H/ACA snoRNP gene family in HCC tissues and adjacent tissues.

Results: The expression of the H/ACA snoRNP gene family was significantly increased in HCC samples compared to normal tissues, and the area under the curve (AUC) of GAR1, NHP2, NOP10, and DKC1 was 0.898, 0.962, 0.884, and 0.911, respectively. Increased expression of the H/ACA snoRNP gene family was associated with poor prognosis in HCC patients (Hazard Ratio, HR = 1.44 [1.02-2.04], 1.70 [1.20-2.40], 1.53 [1.09-2.17], and 1.43 [1.02-2.03], respectively; log-rank = 0.036, 0.003, 0.014, 0.039, respectively). GO and KEGG analyses showed that co-expressed genes were primarily enriched in ribosome biogenesis. In addition, upregulated expression of H/ACA snoRNP gene family was related to the infiltration of various immune cells and multiple T cell exhaustion markers in HCC patients. Immunohistochemical analysis and Western blotting showed that the protein expression of H/ACA snoRNP gene family was higher in HCC tissues than in adjacent tissues of clinical samples.

Conclusion: H/ACA snoRNP gene family expression was higher in HCC tissues than in normal or adjacent tissues and was highly associated with poor prognosis of HCC patients and, therefore, has the potential to serve as diagnostic and prognostic biomarkers for HCC.
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http://dx.doi.org/10.2147/PGPM.S333838DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8541795PMC
October 2021

Is a Prognostic Biomarker Correlated With Immune Infiltration in Hepatocellular Carcinoma.

Front Oncol 2021 14;11:713017. Epub 2021 Sep 14.

Department of Pathology, Chongqing Medical University, Chongqing, China.

Background: Recently, it has been reported that angiotensin II receptor-associated protein () plays a substantial role in tumor progression. Nevertheless, the possible role of in hepatocellular carcinoma (HCC) remains unrecognized.

Methods: The metabolic gene rapid visualizer, Cancer Cell Line Encyclopedia, Human Protein Atlas, and Hepatocellular Carcinoma Database were used to analyze the expression of in HCC tissues and normal liver tissues or adjacent tissues. Kaplan-Meier plotter and UALCAN analysis were used to assess the prognostic and diagnostic value of LinkedOmics and cBioPortal were used to explore the genes co-expressed with in HCC. To further understand the potential mechanism of in HCC, Gene Ontology and Kyoto Encyclopedia of Genes and Genomes enrichment pathway analyses were performed using software, the protein-protein interaction (PPI) network was established using the STRING database, and the immune infiltration and T-cell exhaustion related to were explored Timer and GEPIA. In addition, immunohistochemistry was used to detect the expression of AGTRAP protein in HCC tissues and paired adjacent tissues from clinical specimens.

Results: This study found that the mRNA and protein levels of AGTRAP in HCC tissues were higher than those in normal liver tissues and adjacent tissues, and higher mRNA levels of were associated with higher histological grade and a poor overall survival in HCC patients. The area under the receiver operating characteristic curve (AUC) of was 0.856, suggesting that it could be a diagnostic marker for HCC. Moreover, the alteration rate of in HCC was 8%, and was involved in HCC probably through the NF-κB and MAPK signaling pathways. Furthermore, was positively correlated with the infiltration of CD8 T cells, CD4 T cells, B cells, macrophages, dendritic cells, and neutrophils, and the levels of were significantly correlated with T-cell exhaustion biomarkers. The immunohistochemistry results confirmed that the protein levels of AGTRAP were consistently higher in HCC tissues than in paired adjacent tissues.

Conclusion: The clinical value of and its correlation with immune infiltration in HCC was effectively identified in clinical data from multiple recognized databases. These findings indicate that could serve as a potential biomarker in the treatment of HCC, thereby informing its prognosis, diagnosis, and even immunotherapy.
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http://dx.doi.org/10.3389/fonc.2021.713017DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8477650PMC
September 2021

A Novel Nomogram Based on Hepatic and Coagulation Function for Evaluating Outcomes of Intrahepatic Cholangiocarcinoma After Curative Hepatectomy: A Multi-Center Study of 653 Patients.

Front Oncol 2021 12;11:711061. Epub 2021 Jul 12.

Department of Liver Surgery & Liver Transplantation, State Key Laboratory of Biotherapy and Cancer Center, West China Hospital, Sichuan University and Collaborative Innovation Center of Biotherapy, Chengdu, China.

Background And Aims: Hepatic and coagulation function are routine laboratory tests prior to curative hepatectomy. The prognostic value of gamma-glutamyl transpeptidase (GGT) to platelet ratio (GPR) and international normalized ratio (INR) in surgically treated patients with intrahepatic cholangiocarcinoma (ICC) remains unclear.

Methods: ICC patients received curative hepatectomy in two west China centers were included. Time-dependent ROC curves were conducted to compare established indexes with prognostic value for ICC. GPR-INR score was introduced and evaluated using the Time-dependent AUC curve and Kaplan-Meier survival analysis. A novel nomogram based on the GPR-INR score was proposed; Harrell's C-index, calibration curve and decision curve analysis were used to assess this nomogram.

Results: A total of 653 patients were included. The areas under ROC curves of GPR and INR in OS and RFS were superior to other indexes. Patients with a high GPR-INR score (1,2) presented significantly decreased overall survival (OS) and recurrence-free survival (RFS); GPR-INR sore, along with several clinicopathological indexes were selected into the nomogram, the calibration curve for OS probability showed good coincidence between the nomogram and the actual surveillance. The C-index of the nomogram was 0.708 (derivation set) and 0.746 (validation set), which was more representative than the C-indexes of the GPR-INR score (0.597, 0.678). In decision curve analysis, the net benefits of the nomogram in derivation and validation set were higher than Barcelona Clinic Liver Cancer staging (BCLC) classification and American Joint Committee on Cancer (AJCC) TNM 8 staging system.

Conclusions: The proposed nomogram generated superior discriminative ability to established staging systems; it is profitable to applicate this nomogram in clinical practice.
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http://dx.doi.org/10.3389/fonc.2021.711061DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8311735PMC
July 2021

Sintilimab plus a bevacizumab biosimilar (IBI305) versus sorafenib in unresectable hepatocellular carcinoma (ORIENT-32): a randomised, open-label, phase 2-3 study.

Lancet Oncol 2021 07 15;22(7):977-990. Epub 2021 Jun 15.

Live Surgery Ward, Peking Union Medical College Hospital, Beijing, China.

Background: China has a high burden of hepatocellular carcinoma, and hepatitis B virus (HBV) infection is the main causative factor. Patients with hepatocellular carcinoma have a poor prognosis and a substantial unmet clinical need. The phase 2-3 ORIENT-32 study aimed to assess sintilimab (a PD-1 inhibitor) plus IBI305, a bevacizumab biosimilar, versus sorafenib as a first-line treatment for unresectable HBV-associated hepatocellular carcinoma.

Methods: This randomised, open-label, phase 2-3 study was done at 50 clinical sites in China. Patients aged 18 years or older with histologically or cytologically diagnosed or clinically confirmed unresectable or metastatic hepatocellular carcinoma, no previous systemic treatment, and a baseline Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1 were eligible for inclusion. In the phase 2 part of the study, patients received intravenous sintilimab (200 mg every 3 weeks) plus intravenous IBI305 (15 mg/kg every 3 weeks). In the phase 3 part, patients were randomly assigned (2:1) to receive either sintilimab plus IBI305 (sintilimab-bevacizumab biosimilar group) or sorafenib (400 mg orally twice daily; sorafenib group), until disease progression or unacceptable toxicity. Randomisation was done using permuted block randomisation, with a block size of six, via an interactive web response system, and stratified by macrovascular invasion or extrahepatic metastasis, baseline α-fetoprotein, and ECOG performance status. The primary endpoint of the phase 2 part of the study was safety, assessed in all patients who received at least one dose of study drug. The co-primary endpoints of the phase 3 part of the study were overall survival and independent radiological review committee (IRRC)-assessed progression-free survival according to Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1 in the intention-to-treat population. The study is registered with ClinicalTrials.gov, NCT03794440. The study is closed to new participants and follow-up is ongoing for long-term outcomes.

Findings: Between Feb 11, 2019 and Jan 15, 2020, we enrolled 595 patients: 24 were enrolled directly into the phase 2 safety run-in and 571 were randomly assigned to sintilimab-bevacizumab biosimilar (n=380) or sorafenib (n=191). In the phase 2 part of the trial, 24 patients received at least one dose of the study drug, with an objective response rate of 25·0% (95% CI 9·8-46·7). Based on the preliminary safety and activity data of the phase 2 part, in which grade 3 or worse treatment-related adverse events occurred in seven (29%) of 24 patients, the randomised phase 3 part was started. At data cutoff (Aug 15, 2020), the median follow-up was 10·0 months (IQR 8·5-11·7) in the sintilimab-bevacizumab biosimilar group and 10·0 months (8·4-11·7) in the sorafenib group. Patients in the sintilimab-bevacizumab biosimilar group had a significantly longer IRRC-assessed median progression-free survival (4·6 months [95% CI 4·1-5·7]) than did patients in the sorafenib group (2·8 months [2·7-3·2]; stratified hazard ratio [HR] 0·56, 95% CI 0·46-0·70; p<0·0001). In the first interim analysis of overall survival, sintilimab-bevacizumab biosimilar showed a significantly longer overall survival than did sorafenib (median not reached [95% CI not reached-not reached] vs 10·4 months [8·5-not reached]; HR 0·57, 95% CI 0·43-0·75; p<0·0001). The most common grade 3-4 treatment-emergent adverse events were hypertension (55 [14%] of 380 patients in the sintilimab-bevacizumab biosimilar group vs 11 [6%] of 185 patients in the sorafenib group) and palmar-plantar erythrodysaesthesia syndrome (none vs 22 [12%]). 123 (32%) patients in the sintilimab-bevacizumab biosimilar group and 36 (19%) patients in the sorafenib group had serious adverse events. Treatment-related adverse events that led to death occurred in six (2%) patients in the sintilimab-bevacizumab biosimilar group (one patient with abnormal liver function, one patient with both hepatic failure and gastrointestinal haemorrhage, one patient with interstitial lung disease, one patient with both hepatic faliure and hyperkalemia, one patient with upper gastrointestinal haemorrhage, and one patient with intestinal volvulus) and two (1%) patients in the sorafenib group (one patient with gastrointestinal haemorrhage and one patient with death of unknown cause).

Interpretation: Sintilimab plus IBI305 showed a significant overall survival and progression-free survival benefit versus sorafenib in the first-line setting for Chinese patients with unresectable, HBV-associated hepatocellular carcinoma, with an acceptable safety profile. This combination regimen could provide a novel treatment option for such patients.

Funding: Innovent Biologics.

Translation: For the Chinese translation of the abstract see Supplementary Materials section.
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http://dx.doi.org/10.1016/S1470-2045(21)00252-7DOI Listing
July 2021

Construction of a five-gene prognostic model based on immune-related genes for the prediction of survival in pancreatic cancer.

Biosci Rep 2021 07;41(7)

Department of Oncology, Clinical Medical College and The First Affiliated Hospital of Chengdu Medical College, Chengdu, Sichuan, China.

Purpose: To identify differentially expressed immune-related genes (DEIRGs) and construct a model with survival-related DEIRGs for evaluating the prognosis of patients with pancreatic cancer (PC).

Methods: Six microarray gene expression datasets of PC from the Gene Expression Omnibus (GEO) and Immunology Database and Analysis Portal (ImmPort) were used to identify DEIRGs. RNA sequencing and clinical data from The Cancer Genome Atlas Program-Pancreatic Adenocarcinoma (TCGA-PAAD) database were used to establish the prognostic model. Univariate, least absolute shrinkage and selection operator (LASSO) and multivariate Cox regression analyses were applied to determine the final variables of the prognostic model. The median risk score was used as the cut-off value to classify samples into low- and high-risk groups. The prognostic model was further validated using an internal validation set of TCGA and an external validation set of GSE62452.

Results: In total, 142 DEIRGs were identified from six GEO datasets, 47 were survival-related DEIRGs. A prognostic model comprising five genes (i.e., ERAP2, CXCL9, AREG, DKK1, and IL20RB) was established. High-risk patients had poor survival compared with low-risk patients. The 1-, 2-, 3-year area under the receiver operating characteristic (ROC) curve of the model reached 0.85, 0.87, and 0.93, respectively. Additionally, the prognostic model reflected the infiltration of neutrophils and dendritic cells. The expression of most characteristic immune checkpoints was significantly higher in the high-risk group versus the low-risk group.

Conclusions: The five-gene prognostic model showed reliably predictive accuracy. This model may provide useful information for immunotherapy and facilitate personalized monitoring for patients with PC.
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http://dx.doi.org/10.1042/BSR20204301DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8252190PMC
July 2021

GBP2 as a potential prognostic biomarker in pancreatic adenocarcinoma.

PeerJ 2021 11;9:e11423. Epub 2021 May 11.

Department of Oncology, Clinical Medical College and The First Affiliated Hospital of Chengdu Medical College, Chengdu, China.

Background: Pancreatic adenocarcinoma (PAAD) is a disease with atypical symptoms, an unfavorable response to therapy, and a poor outcome. Abnormal guanylate-binding proteins (GBPs) play an important role in the host's defense against viral infection and may be related to carcinogenesis. In this study, we sought to determine the relationship between GBP2 expression and phenotype in patients with PAAD and explored the possible underlying biological mechanism.

Method: We analyzed the expression of GBP2 in PAAD tissues using a multiple gene expression database and a cohort of 42 PAAD patients. We evaluated GBP2's prognostic value using Kaplan-Meier analysis and the Cox regression model. GO and KEGG enrichment analysis, co-expression analysis, and GSEA were performed to illustrate the possible underlying biological mechanism. CIBERSORT and the relative expression of immune checkpoints were used to estimate the relationship between GBP2 expression and tumor immunology.

Result: GBP2 was remarkably overexpressed in PAAD tissue. The overexpression of GBP2 was correlated with an advanced T stage and poor overall survival (OS) and GBP2 expression was an independent risk factor for OS in PAAD patients. Functional analysis demonstrated that positively co-expressed genes of GBP2 were closely associated with pathways in cancer and the NOD-like receptor signaling pathway. Most of the characteristic immune checkpoints, including PDCD1, PDCDL1, CTLA4, CD80, TIGIT, LAG3, IDO2, and VISTA, were significantly expressed in the high-GBP2 expression group compared with the low-GBP2 expression group.

Conclusion: GBP2 acted as a potential prognostic biomarker and was associated with immune infiltration and the expression of immune checkpoints in PAAD.
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http://dx.doi.org/10.7717/peerj.11423DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8121056PMC
May 2021

Immune Checkpoint Inhibitors in Patients with Recurrent Hepatocellular Carcinoma after Liver Transplantation: A Case Report and Literature Review.

Curr Cancer Drug Targets 2020 ;20(9):720-727

Department of Hepatobiliary Surgery, The First Affiliated Hospital of Chongqing Medical University, Chongqing 400016, China.

Background: Immune checkpoint modulators, such as the programmed death protein-1 (PD-1)/programmed death ligand-1 (PD-L1) inhibitor, cytotoxic T-Lymphocyte-associated antigen 4 (CTLA-4) inhibitor have been investigated with encouraging results for hepatocellular carcinoma (HCC). However, the safety of this strategy in patients with previous liver transplantation (LT) is not well studied.

Objective: To explore the safety and feasibility of immune checkpoints inhibitors in recurrent and metastatic HCC patients on a background of LT.

Methods: A case of recurrent, refractory, metastatic HCC after LT, where PD-1 inhibitor was initiated, was described and related literature was reviewed.

Results: There was complete remission in lung metastases and the partial radiological response of metastatic retroperitoneal lymph node to the drug with no liver graft rejection after 13 cycles of PD- 1 inhibitor injection. PD-1inhibitor, at least in this patient, was verified to play an important role in controlling tumor progression and prolonging patient survival.

Conclusion: This novel drug might be a useful method to allow doctors to guarantee a better chance for long-term survival in recurrent, metastatic HCC patients with the previous LT. However, it should be used with caution in allograft recipients due to the risk of acute graft rejection, further larger, prospective studies are needed to determine optimal immunomodulatory therapy to achieve optimal anti-tumor efficacy with transplant liver preservation.
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http://dx.doi.org/10.2174/1568009620666200520084415DOI Listing
September 2021

Antecolic reconstruction is associated with a lower incidence of delayed gastric emptying compared to retrocolic technique after Whipple or pylorus-preserving pancreaticoduodenectomy.

Medicine (Baltimore) 2019 Aug;98(34):e16663

Department of Hepatobiliary Surgery, The First Affiliated Hospital of Chongqing Medical University, Chongqing, China.

Background: The aim of present study is to investigate the relationship between the antecolic (AC) route of gastrojejunostomy (GJ) after pancreaticoduodenectomy (PD) or duodenojejunostomy (DJ) reconstruction after pylorus-preserving pancreaticoduodenectomy (PPPD), and the incidence of delayed gastric emptying (DGE).

Methods: An electronic search of 4 databases to identify all articles comparing AC and retrocolic (RC) reconstruction after PD or PPPD was performed.

Results: Fifteen studies involving 2270 patients were included for final pooled analysis. The overall incidence of DGE was 27.2%. Meta-analysis results showed AC group had lower incidence of DGE (odds ratio, 0.29; 95% confidence interval [CI], 0.16-0.52, P < .0001) and shorter hospital length of stay (weight mean difference, -3.29; 95% CI, -5.2 to -1.39, P = .0007). Days until to liquid and solid diet in the AC group were also significantly earlier than that in the RC group (P = .0006 and P < .0001). There was no difference in operative time, incidence of pancreatic fistula and bile leakage, and mortality, respectively.

Conclusions: AC route of GJ after PD or DJ after PPPD is associated with a lower incidence of DGE. However, the preferred route for GJ or DJ reconstruction remains to be investigated in well-powered, randomized, controlled trial.
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http://dx.doi.org/10.1097/MD.0000000000016663DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6716732PMC
August 2019

The potential value of CDV3 in the prognosis evaluation in Hepatocellular carcinoma.

Genes Dis 2018 Jun 31;5(2):167-171. Epub 2018 Jan 31.

Department of Hepatobiliary Surgery, The First Affiliated Hospital of Chongqing Medical University, People's Republic of China.

CDV3 is correlated with tumorigenesis and may affect some biological process in cancer. In this study, we explore the role of CDV3 in HCC. According to the TCGA data base, CDV3 is over-expressed in HCC tissues. Up-regulation of CDV3 is correlated with lower over-all survival rate in HCC patients. In HCC samples from our hospital, CDV3 is also enriched in cancer tissues and CDV3 expression associated with HCC pathological T stage. What is more, higher CDV3 expression could forecast poor survival rate in HCC patients. In conclusion, CDV3 is a biomarker of HCC and could be a potential therapeutic target.
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http://dx.doi.org/10.1016/j.gendis.2018.01.003DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6147043PMC
June 2018

Pancreatogastrostomy Versus Pancreatojejunostomy for RECOnstruction After PANCreatoduodenectomy (RECOPANC, DRKS 00000767): Perioperative and Long-term Results of a Multicenter Randomized Controlled Trial.

Ann Surg 2017 12;266(6):e63-e64

Department of Hepatobiliary Surgery, The First Affiliated Hospital of Chongqing Medical University, Chongqing, China.

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http://dx.doi.org/10.1097/SLA.0000000000001503DOI Listing
December 2017

[Hepatic stellate cells inhibit the proliferation and invasion of HepG2 hepatocellular carcinoma via activating γδ T cells].

Xi Bao Yu Fen Zi Mian Yi Xue Za Zhi 2017 Jul;33(7):870-874

Department of Hepatobiliary Surgery, First Affiliated Hospital, Chongqing Medical University, Chongqing 400016, China. *Corresponding author, E-mail:

Objective To investigate the effects of γδ T cells co-cultured with human hepatic stellate cells (HSCs) on the proliferation and invasion of hepatocellular carcinoma (HCC) cells. Methods Peripheral γδ T cells of healthy volunteers and HCC patients were separated and collected by density gradient centrifugation and flow cytometry. Transwell chambers were used to co-culture LX-2 cells and γδ T cells. The concentration of IFN-γ in γδ T cell supernatant was detected by ELISA. The proliferation of HepG2 cells was analyzed by CCK-8 assay, and the invasion ability of HepG2 cells was evaluated by Transwell chamber assay. Results After co-cultured with LX-2 cells, the IFN-γ secretion in γδ T cells increased obviously, and the level of IFN-γ was higher in healthy volunteer group than in HCC patient group. The inhibitory effects of γδ T cells on the proliferation and invasion of HepG2 cells were enhanced after the co-culture, and the enhancement of inhibitory abilities was more obvious in healthy volunteer group than in HCC patient group. Conclusion HSC could activate γδ T cells and promote IFN-γ secretion of γδ T cells, thus enhancing the inhibitory effects of γδ T cells on the proliferation and invasion of hepatoma cells.
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July 2017

[Hepatic stellate cell conditioned medium induces proliferation and epithelial-mesenchymal transition via activating ERK1/2 signaling pathway in hepatoma cells].

Xi Bao Yu Fen Zi Mian Yi Xue Za Zhi 2017 Feb;33(2):210-4

Objective: To investigate the influence of hepatic stellate cells( HSCs) on malignant biological behavior of hepatoma cells and related mechanisms.

Methods: Human hepatoma cell lines SMMC-7721 and Hep G2,and hepatic stellate cell line LX-2 were cultured separately. HSC conditioned medium( LX2-CM),MAPK specific inhibitor U0126 were used to treat hepatoma cells,separately or together. The invasion and migration abilities of hepatoma cells were detected by TranswellTMassay,and cell proliferation was analyzed by CCK-8 assay. The mRNA and protein expression levels of p-ERK1 /2,ERK1 /2,c-Myc,vimentin and E-cadherin were determined by real-time PCR and Western blot analysis,respectively.

Results: LX2-CM promoted the proliferation,invasion and migration of SMMC-7721 and Hep G2 cells,and these effects were inhibited by U0126. LX2-CM up-regulated the expression levels of p-ERK1 /2,c-Myc,vimentin and down-regulated the expression level of E-cadherin. Conversely,after U0126 treatment,the expression levels of p-ERK1 /2,c-Myc and vimentin decreased significantly,while E-cadherin expression level increased.

Conclusion: LX2-CM could activate c-Myc via ERK1 /2signaling pathway in hepatoma cells,and consequently promote cell proliferation,invasion and migration,and also induce epithelial-mesenchymal transition.
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February 2017

The prognostic value of a classification system for centrally located liver tumors in the setting of hepatocellular carcinoma after mesohepatectomy.

Surg Oncol 2016 Dec 8;25(4):441-447. Epub 2016 Mar 8.

Department of Hepatobiliary Surgery, The First Affiliated Hospital of Chongqing Medical University, Chongqing 400016, China. Electronic address:

Background: A classification system of centrally located liver tumors (CLLTs) was proposed by our group in 2013, which divided CLLTs into four subtypes by focusing on the involvement of resected segments and the anatomical location of lesions relative to the principal hepatic vascular structures. The current study aimed to analyze the clinical characteristics and compare the surgical outcomes of the different CLLTs classification system for patients with hepatocelluar carcinoma (HCC) underwent mesohepatectomy (MH). Moreover, we sought to validate the prognostic value of the new classification system.

Methods: Data from 353 consecutive patients with centrally located HCC who were treated with MH between 2005 and 2013 were prospectively collected and retrospectively reviewed.

Results: The 1-, 3-, and 5-y overall recurrence rates were 21.4%, 41.3%, and 55.6%, respectively. The 1-, 3-, and 5-y overall (OS) and corresponding recurrence-free survival rates (RFS) were 82.5%, 61.6%, 40.2%, and 68.8%, 42.5%, 30.7%, respectively. According the CLLTs classification system, 106 patients were classified as type I, 68 as type II, 94 as type III and 85 as type IV. There were no significant differences in RFS rate among the CLLTs groups, however, a significant decrease in OS rates was observed in the type IV classification, respectively. Multivariate analysis reveal that patients with microvascular invasion, portal vein thrombosis, the largest tumor size≥5 cm, tumor number≥3, liver cirrhosis, hepatic inflow occlusion ≥60 min, intraoperative blood loss≥1500 ml, pTNM staging and CLLTs classification of Type IV to be independent adverse factors for long-term survivals.

Conclusion: The classification system of CLLTs is meant to help clinicians in defining the extent of resection, providing a risk assessment and predicting prognosis. However, it is need to be validated in more HCC patients and medical centers.
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http://dx.doi.org/10.1016/j.suronc.2016.03.001DOI Listing
December 2016

A systematic review of robotic-assisted liver resection and meta-analysis of robotic versus laparoscopic hepatectomy for hepatic neoplasms.

Surg Endosc 2016 Mar 20;30(3):862-75. Epub 2015 Jun 20.

Department of Hepatobiliary Surgery, The First Affiliated Hospital of Chongqing Medical University, Chongqing, 400016, China.

Background: Robotic-assisted liver resection (RALR) was introduced as procedures of overcoming the limitations of traditional laparoscopic liver resection (LLR). The aim of this review was to evaluate the surgical results of RALR from all published studies and the results of comparative studies of RALR versus LLR for hepatic neoplasm.

Methods: Eligible studies involved RALR that published between January 2001 and December 2014 were reviewed systematically. Comparisons between RALS and LLR were pooled and analyzed by meta-analytical techniques using random- or fixed-effects models, as appropriate.

Results: In total, 29 studies, involving 537 patients undergoing RALR, were identified. The most common RALR procedure was a wedge resection and segmentectomy (28.67%), followed by right hepatectomy (17.88%), left lateral sectionectomy (13.22%), and bisegmentectomy (9.12%). The conversion and complication rates were 5.59 and 11.36%, respectively. The most common reasons for conversion were bleeding (46.67%) and unclear tumor margin (33.33%). Intracavitary fluid collections and bile leaks (40.98%) were the most frequently occurring morbidities. Nine studies, involving 774 patients, were included in meta-analysis. RALR had a longer operative time compared with LLR [mean difference (MD) 48.49; 95% confidence interval (CI) 22.49-74.49 min; p = 0.0003]. There were no significant differences between the two groups in blood loss [MD 31.53; 95% CI -14.74 to 77.79 mL; p = 0.18], hospital stay [MD 0.13; 95% CI -0.54 to 0.80 days; p = 0.18], postoperative overall morbidity [odds ratio (OR) 0.76; 95% CI 0.49-1.19; p = 0.23], and surgical margin status (OR 0.61; 95% CI 0.33-1.12; p = 0.11); cost was greater than robotic surgery (p = 0.001).

Conclusion: RALR and LLR display similar safety, feasibility, and effectiveness for hepatectomies, but further studies are needed before any final conclusion can be drawn, especially in terms of oncologic and cost-effectiveness outcomes.
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http://dx.doi.org/10.1007/s00464-015-4306-7DOI Listing
March 2016

Era of liver transplantation: combined anatomic splenectomy and anticoagulant therapy in prevention of portal vein thrombosis after splenectomy.

Hepatogastroenterology 2015 Mar-Apr;62(138):405-9

Background/aims: Portal vein thrombosis (PVT) is a common complication following splenectomy in patients with liver cirrhosis and portal hypertension, which also brings difficulties to future possible liver transplantation. This paper retrospectively analyzes the preventive effect of combined anatomic splenectomy and early anticoagulant therapy on post-splenectomy portal vein thrombosis in patients with portal hypertension.

Methodology: We retrospectively analyzed 136 patients who underwent splenectomy at our hospital between January 2010 and December 2013 due to liver cirrhosis and portal hypertension. Patient conditions, such as coagulation function, splenic and portal vein thrombosis, intra-abdominal hemorrhage, pancreatic leakage and intra-abdominal infections, are observed postoperatively.

Results: Despite the presence of liver cirrhosis and portal hypertension in patients, early postoperative anticoagulant therapy has no significant impact on coagulation function and intra-abdominal hemorrhage of these patients (p > 0.05). Anatomic splenectomy can reduce the occurrence of complications such as postoperative bleeding, pancreatic leakage and intra-abdominal infections (p < 0.05).

Conclusion: Combined anatomic splenectomy and early postoperative anticoagulant therapy can reduce post-splenectomy portal vein thrombosis in patients with portal hypertension, and is conducive to the future liver transplantation therapy may be needed by the patients.
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June 2015

TAZ regulates cell proliferation and epithelial-mesenchymal transition of human hepatocellular carcinoma.

Cancer Sci 2015 Feb 30;106(2):151-9. Epub 2015 Jan 30.

Division of Hepatobiliary and Pancreatic Surgery, Department of Surgery, First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, China.

The transcriptional coactivator with PDZ binding motif (TAZ) has been reported to be one of the nuclear effectors of Hippo-related pathways. TAZ is expressed in many primary tumors and could regulate many biological processes. However, little is known about the role of TAZ in hepatocellular carcinoma (HCC). In the current study, we show that TAZ regulates cellular proliferation and epithelial-mesenchymal transition (EMT) of HCC. TAZ is overexpressed in HCC tissues and cell lines and upregulation of TAZ correlates with a lower overall survival rate of HCC patients after hepatic resection. TAZ knockdown results in inhibition of cancer cell proliferation through decreases in expression of stem cell markers (OCT4, Nanog, and SOX2). Reduction in HCC cell migration and invasion is also evident through reversal of EMT by increases E-cadherin expression, decreases in N-cadherin, vimentin, Snail, and Slug expression, and suppression of MMP-2 and MMP-9 expression. In a xenograft tumorigenicity model, TAZ knockdown could effectively inhibit tumor growth and metastasis through reversal of the EMT pathway. In conclusion, TAZ is associated with the proliferation and invasiveness of HCC cells, and the TAZ gene may contribute to a novel therapeutic approach against HCC.
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http://dx.doi.org/10.1111/cas.12587DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4399022PMC
February 2015

Augmenter of liver regeneration promotes hepatic regeneration depending on the integrity of Kupffer cell in rat small-for-size liver transplantation.

J Surg Res 2013 Aug 13;183(2):922-8. Epub 2013 Mar 13.

Department of Hepatobiliary Surgery, Second Affiliated Hospital of Chongqing Medical University, Chongqing, China.

Background: Augmenter of liver regeneration (ALR) can promote hepatocyte proliferation and thereby augment liver mass restoration. This study was performed to further explore the mechanism of ALR on liver regeneration in small-for-size liver transplanted rats.

Methods: Donor Sprague-Dawley rats were divided into a Kupffer cell (KC)-depleted group (pretreated with GdCl3) and KC-competent group and then further divided into two subgroups: the ALR subgroup (infused with 100 μg/kg ALR through the portal vein) and non-ALR subgroup. Only the median lobe was retained to establish the small-for-size liver transplantation model. Ten rats from each subgroup were used for the 7 d survival study. In addition, the nuclear factor κB activity, reperfusion injury, regeneration of the remnant liver, and tumor necrosis factor α and interleukin 6 expression levels were evaluated.

Results: ALR could accelerate graft regeneration by increasing nuclear factor κB activity to induce tumor necrosis factor α and interleukin 6 expression in the KC-competent rats, which resulted in a higher 7 d survival rate.

Conclusions: ALR could enhance the hepatocellular proliferation of small-for-size liver grafts, and these effects appeared to deeply depend on the integrity of KCs.
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http://dx.doi.org/10.1016/j.jss.2013.02.033DOI Listing
August 2013

The effect of fibroblast activation on vascularization in transplanted pancreatic islets.

J Surg Res 2013 Jul 20;183(1):450-6. Epub 2013 Jan 20.

Department of Hepatobiliary Surgery, The First Affiliated Hospital of Chong Qing Medical University, Chong Qing, PR China.

Background: Insufficient revascularization of transplanted pancreatic islets is an important reason why the long-term effects of pancreatic islet transplantation on type I diabetes patients have been so limited. The goal of this study was to investigate the role of fibroblasts (FBs) activated by tumor cell supernatants on the vascularization of transplanted pancreatic islets.

Materials And Methods: Pancreatic islets and activated or inactivated FBs were used for subrenal capsule transplantation. Mouse melanoma cell supernatants were used to activate FBs; the tests of the purity of the pancreatic islet cells of the donor, survival rate, and function of insulin secretion were performed to ensure high-quality transplants. Mice receiving the allogeneic transplantation were given tacrolimus and sirolimus to prevent rejection. The diabetic model was induced by streptozotocin.

Results: Conditioned medium made of tumor cell supernatants was found to stimulate the expression of α-smooth muscle actin and vascular endothelial growth factor A to an extent notably greater than that of pancreatic islet transplantation alone or pancreatic islet transplantation combined with inactivated FBs. FBs from the recipient were associated with capillary density in the transplanted pancreatic islet most closely to that observed in isogenically transplanted pancreatic islets and the original pancreatic islet. In this way, activated FBs derived from the recipient combined with pancreatic transplantation were able to treat diabetes, and long-term survival was achieved.

Conclusions: The current research sheds new light on the revascularization of transplanted pancreatic islets: activated FBs derived from the recipients, when transplanted alongside pancreatic tissue, can promote revascularization inside the transplanted pancreatic islet.
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http://dx.doi.org/10.1016/j.jss.2012.12.044DOI Listing
July 2013

Tumor necrosis factor alpha 308 G/A polymorphism and hepatocellular carcinoma risk in a Chinese population.

Genet Test Mol Biomarkers 2011 Jul-Aug;15(7-8):569-72. Epub 2011 Mar 14.

Department of Hepatobiliary Surgery, The First Affiliated Hospital, Chongqing Medical University, Chongqing, China.

Background: The genetic basis of susceptibility to hepatocellular carcinoma (HCC) is poorly understood. Tumor necrosis factor alpha (TNF-α) is a cytokine that may act as an endogenous tumor promoter. The association between TNF-α 308 G/A polymorphism and HCC risk remains unclear.

Aim: The aim of this study was to investigate the association between TNF-α 308 G/A polymorphism and HCC risk in a Chinese population.

Methods: The study population consisted of 88 patients with documented HCC and 88 healthy controls. The gene polymorphism of TNF-α was analyzed by polymerase chain reaction-restriction fragment length polymorphism assay.

Results: HCC patients had a significantly lower frequency GG (odds ratio=0.36; 95% confidence interval=0.13, 0.94; p=0.04) and G allele (odds ratio=0.58; 95% confidence interval=0.37, 0.90; p=0.01) than healthy controls. When stratifying for tumor size and cirrhosis, no statistically significant results were found.

Conclusion: This study suggested that TNF-α -308GG and G allele were associated with a modest decrease in the risk of HCC in Chinese population.
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http://dx.doi.org/10.1089/gtmb.2011.0008DOI Listing
November 2011
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