1.Interventional therapy for biliary restenosis occurring after surgical T-tube drainage: preliminary investigation
Zhen LI ; Bingtao SHI ; Ya LI ; Xin LI ; Jiaxiang WANG ; Xinwei HAN
Journal of Interventional Radiology 2017;26(8):739-743
Objective To evaluate the curative effect,safety and feasibility of interventional therapy for biliary restenosis occurring after surgical T-tube drainage.Methods The clinical data of 25 patients with biliary restenosis that occurred after surgical T-tube drainage,who were admitted to authors' hospital during the period from June 2014 to March 2016,were retrospectively analyzed.The primary diseases included bile duct carcinoma (n=6),gallbladder carcinoma (n=3),biliary stone (n=13),hepatocellular carcinoma (n=2)and gastric cancer after surgery (n=1).Abnormal junction of pancreatic duct and biliary duct was observed in 4 patients.Interventional procedure via T-tube route was carried out in 22 patients,and T-tube radiography with subsequent percutaneous transhepatic cholangial drainage (PTCD) was conducted in 3 patients.Biliary balloon expansion combined with biliary drainage was performed in 21 patients,and biliary metal stent implantation was adopted in 4 patients.For patients with benign biliary stricture,the drainage tube was retained for 2-3 months before it was removed.All the patients were followed up for 3-24 months at outpatient clinic or by the telephone.The curative effect was evaluated with drainage-tube radiography.Results The interventional operation was successfully accomplished in all patients,no procedure-related complications occurred,the technical success rate was 100%.In 15 patients with benign biliary stricture,biliary plasty with balloon expansion via the T-tube fistula was conducted,then a 10.2-12 F drainage catheter was placed in the biliary tract and the T-tube was pulled out.During the follow-up period,one patient with anastomotic stricture of bile duct carcinoma died of pulmonary infection at 8 months after treatment.Of the 10 patients with malignant stricture,the biliary obstruction was located above the T-tube level in 3,and all the 3 patients received PTCD.Among the 3 patients,2 patients had hepatocellular carcinoma complicated by biliary invasion,as the extent of the cancerous thrombus was very large,both internal drainage tube and external drainage tube had to be implanted.After jaundice regression,the two patients died of hepatic failure at one month and 2.2 months after the operation respectively.One patient with gallbladder carcinoma complicated by invasion of bile duct received implantation of biliary stent,and the patient died of tumor deterioration at 2.5 months after the procedure.In 7 patients,the biliary obstruction was located below the T-tube level.hnplantation of internal drainage tube and external drainage tube via the Ttube fistula was performed in 4 patients,and implantation of metal stent was adopted in 3 patients.Among them,2 patients with gallbladder carcinoma died of tumor deterioration at 3.8 months and 5 months after the operation respectively.In 5 patients with cholangiocarcinoma,biliary stent restenosis occurred in 2 at 3 months after the treatment,and PTCD was adopted.Three patients died of tumor deterioration complicated by organ function failure at 3.6 months,5.2 months and 9.0 months after the operation respectively.Conclusion For the treatment of biliary restenosis occurring after surgical T-tube drainage,interventional therapy is safe and feasible with reliable curative effect,it can significantly improve the life quality of patients.
2.Investigation and experimental validation of curcumin-related mechanisms against hepatocellular carcinoma based on network pharmacology.
Yang CHEN ; Qian LI ; Sisi REN ; Ting CHEN ; Bingtao ZHAI ; Jiangxue CHENG ; Xiaoyan SHI ; Liang SONG ; Yu FAN ; Dongyan GUO
Journal of Zhejiang University. Science. B 2022;23(8):682-698
OBJECTIVES:
To determine the potential molecular mechanisms underlying the therapeutic effect of curcumin on hepatocellular carcinoma (HCC) by network pharmacology and experimental in vitro validation.
METHODS:
The predictive targets of curcumin or HCC were collected from several databases. the identified overlapping targets were crossed with Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) analyses using the Database for Annotation, Visualization, and Integrated Discovery (DAVID) platform. Two of the candidate pathways were selected to conduct an experimental verification. The 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide tetrazolium (MTT) assay was used to determine the effect of curcumin on the viability of HepG2 and LO2 cells. The apoptosis and autophagy of HepG2 cells were respectively detected by flow cytometry and transmission electron microscopy. Besides, western blot and real-time polymerase chain reaction (PCR) were employed to verify the p53 apoptotic pathway and adenosine 5'-monophosphate (AMP)-activated protein kinase (AMPK) autophagy pathway. HepG2 cells were pretreated with pifithrin-α (PFT-α) and GSK690693 for further investigation.
RESULTS:
The 167 pathways analyzed by KEGG included apoptosis, autophagy, p53, and AMPK pathways. The GO enrichment analysis demonstrated that curcumin was involved in cellular response to drug, regulation of apoptotic pathway, and so on. The in vitro experiments also confirmed that curcumin can inhibit the growth of HepG2 cells by promoting the apoptosis of p53 pathway and autophagy through the AMPK pathway. Furthermore, the protein and messenger RNA (mRNA) of the two pathways were downregulated in the inhibitor-pretreated group compared with the experimental group. The damage-regulated autophagy modulator (DRAM) in the PFT-α-pretreated group was downregulated, and p62 in the GSK690693-pretreated group was upregulated.
CONCLUSIONS
Curcumin can treat HCC through the p53 apoptotic pathway and the AMPK/Unc-51-like kinase 1 (ULK1) autophagy pathway, in which the mutual transformation of autophagy and apoptosis may occur through DRAM and p62.
AMP-Activated Protein Kinases/pharmacology*
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Apoptosis
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Carcinoma, Hepatocellular/pathology*
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Curcumin/pharmacology*
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Humans
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Liver Neoplasms/pathology*
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Network Pharmacology
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Tumor Suppressor Protein p53/metabolism*