fluorescent-laparoscopic-central-hepatectomy-for-liver-cancer-using

Fluorescent Laparoscopic Central Hepatectomy for Liver Cancer Using Indocyanine Green Negative Staining

Laparoscopic hepatectomy is an important treatment method for liver cancer. In the past, the resection boundary was usually determined by intraoperative ...

Sun Yat-sen University

Laparoscopic hepatectomy (LH), microwave ablation (MWA), and open hepatectomy (OH) are three widely used methods to treat small hepatocellular carcinoma (HCC). However, few studies have compared the short- and long-term outcomes of these three treatments. The aim of this study was to investigate their effectiveness.

Short-term and long-term outcomes of laparoscopic hepatectomy, microwave ablation, and open hepatectomy for small hepatocellular carcinoma: a 5-year experience in a single center.

Sorafenib has been globally approved as the standard treatment for patients with advanced hepatocellular carcinoma (HCC). However, the response rate of HCC patients to sorafenib is limited because of tumor recurrence and metastasis. Therefore, seeking combined therapeutic strategies with sorafenib is necessary to improve the antitumor efficiency. Here we demonstrated that expression of MMP-2 is positively correlated with the migration ability of HCC cells. Cells with a higher MMP-2 expression (SK-HEP-1 cells) were less sensitive to sorafenib than those with lower MMP-2 expression (HepG2 cells). Cotreatment of cells with SB-3CT and sorafenib more strongly inhibited migration ability than with sorafenib treatment alone in both HCC cells with high and low expression of MMP-2. In vivo cell metastasis experiments confirmed the synergistic effects of sorafenib and SB-3CT in reducing lung metastasis of SK-HEP-1 cells. Mechanistically, we showed that the synergistic antitumor effect may be attributed to inhibition of the PI3K/AKT/mTOR signaling pathway, but not the RAF/MEK/ERK signaling pathway. With these results taken together, the current study demonstrates that inhibiting MMP-2 expression can enhance the antitumor effect of sorafenib in HCC cells with a high MMP-2 expression, which may provide a novel strategy to improve therapeutic efficiency in HCC.

Inhibition of MMP-2 Expression Enhances the Antitumor Effect of Sorafenib in Hepatocellular Carcinoma by Suppressing the PI3K/AKT/mTOR Pathway.

The role of tumor necrosis factor alpha (TNF-α) in targeted therapy for hepatocellular carcinoma (HCC) remains largely unknown. The current study aimed to clarify the mechanistic effects of targeting TNF-α to overcome sorafenib resistance in HCC.

TNF-α is a potential therapeutic target to overcome sorafenib resistance in hepatocellular carcinoma.

: Sorafenib appears to increase the survival rate of hepatocellular carcinoma (HCC) patients, but its response rate is seriously limited due to drug resistance. Molecular mechanisms underlying sorafenib resistance are still unknown. Herein, we explored the possible role of miR-1226-3p in sorafenib resistance of HCC. : The miR-1226-3p expression level in HCC cell lines was evaluated by qRT-PCR. Cell viabilities to sorafenib were measured by CCK-8 assay. Cell apoptosis and proliferation were detected by flow cytometry and EdU proliferation assay. A luciferase reporter of DUSP4 3'-UTR was used for validation as a target gene of miR-1226-3p. Finally, the effects of  antitumor efficacy of miR-1226-3p combined with sorafenib were evaluated by HCC tumor xenografts in nude mice. : Bioinformatics analysis from Gene Expression Omnibus (GEO) datasets GSE56059 suggested that miR-1226-3p expression was downregulated in HCC patients who showed progressive disease (PD) after sorafenib treatment. SK-HEP-1 cells expressed lower levels of miR-1226-3p than HepG2 cells. We confirmed that SK-HEP-1 cells were more resistant to sorafenib compared to HepG2 cells. In addition, miR-1226-3p mimic increased cell apoptosis of SK-HEP-1 cells, whereas miR-1226-3p inhibitor significantly impaired cell apoptosis of HepG2 cells after sorafenib treatment. Moreover, we validated that miR-1226-3p directly targeted dual specificity phosphatase 4 (DUSP4), and further demonstrated that knockdown of DUSP4 reduced sorafenib resistance by regulating the JNK-Bcl-2 axis. : miR-1226-3p promotes sorafenib sensitivity of HCC through downregulation of DUSP4 expression, and targeting miR-1226-3p may be a novel therapeutic strategy for overcoming sorafenib resistance.

miR-1226-3p Promotes Sorafenib Sensitivity of Hepatocellular Carcinoma via Downregulation of DUSP4 Expression.

Laparoscopic common bile duct exploration (LCBDE) is one of the minimally invasive options for choledocholithiasis. Primary closure of the common bile duct (CBD) upon completion of laparoscopic choledochotomy is safe in selected patients. The present study aimed to evaluate the feasibility and safety of primary closure of CBD after LCBDE in patients aged 70 years or older.

Laparoscopic common bile duct exploration with primary closure is safe for management of choledocholithiasis in elderly patients.

Corrigendum to "TNF-α is a potential therapeutic target to overcome sorafenib resistance in hepatocellular carcinoma" [EBioMedicine 40 (2019) 446-456].

Article	Year
Short-term and long-term outcomes of laparoscopic hepatectomy, microwave ablation, and open hepatectomy for small hepatocellular carcinoma: a 5-year experience in a single center. Hepatology research : the official journal of the Japan Society of Hepatology\| PubMed ID: 27487979	2017
Inhibition of MMP-2 Expression Enhances the Antitumor Effect of Sorafenib in Hepatocellular Carcinoma by Suppressing the PI3K/AKT/mTOR Pathway. Oncology research\| PubMed ID: 28276313	2017
TNF-α is a potential therapeutic target to overcome sorafenib resistance in hepatocellular carcinoma. EBioMedicine\| PubMed ID: 30594557	2019
miR-1226-3p Promotes Sorafenib Sensitivity of Hepatocellular Carcinoma via Downregulation of DUSP4 Expression. Journal of Cancer\| PubMed ID: 31258782	2019
Laparoscopic common bile duct exploration with primary closure is safe for management of choledocholithiasis in elderly patients. Hepatobiliary & pancreatic diseases international : HBPD INT\| PubMed ID: 31474445	2019
Corrigendum to "TNF-α is a potential therapeutic target to overcome sorafenib resistance in hepatocellular carcinoma" [EBioMedicine 40 (2019) 446-456]. EBioMedicine\| PubMed ID: 35605430	2022

Jinyi Zhong

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