Hongwei Xu

Expression of P-Glycoprotein and Multidrug Resistance-Associated Protein is Associated with Multidrug Resistance in Gastric Cancer

This study evaluated the sensitivities of gastric cancer cells to various chemotherapy drugs, and investigated the relationship between the expression of P-glycoprotein (P-gp) and multidrug resistance-associated protein (MRP) and multidrug resistance. Drug sensitivities were determined using a methyltetrazolium assay: expression levels of P-gp and MRP were measured using immunohistochemistry. On purification culture, gastric cancer cells were found to be most sensitive to cisplatin, mitomycin and adriamycin, moderately sensitive to etoposide and 5-fluorouracil, and less sensitive to homocamptothecin and methotrexate, with sensitivities of 76.7%, 70.0%, 66.7%, 60.0%, 56.7%, 43.3% and 30.0%, respectively. Positive expression for P-gp and MRP in gastric cancer tissues was 41.7% and 29.2%, respectively;co-expression of P-gp and MRP in cancer tissue was 23%. The drug-resistant groups had higher positive expression of P-gp and MRP compared with the drug-sensitive groups. In conclusion, expression of P-gp and MRP seems to be associated with multidrug resistance in gastric cancer.

Synthetic chenodeoxycholic acid derivative, HS-1200, induces apoptosis of human hepatoma cells via a mitochondrial pathway.

We investigated whether HS-1200 has anti-proliferation effects on human hepatoma cells in vitro. Here, chromatin condensation, DNA ladder formation and proteolytic cleavage of poly (ADP-ribose) polymerase (PARP) were observed after treatment of HS-1200, indicating the occurrence of apoptotic cell death, which was associated with up-regulation of Bax, cleaved-caspase-3 and cleaved-caspase-9. Inhibition of caspase-9 rescued HS-1200-induced apoptosis. Furthermore, cells treated with HS-1200 showed a reduction in mitochondrial membrane potential (Deltapsi(m)) and caused cytochrome c release into the cytosol. The results indicated that synthetic chenodeoxycholic acid HS-1200 could induce cell apoptosis in BEL7402 human hepatoma cell line, via a Bax/cytochrome c/caspase-9 independent pathway. This study suggested that HS-1200 is potentially useful as an apoptosis inducer for the treatment of hepatocellular carcinoma.

Submucosal tunneling endoscopic resection for tumors of the esophagogastric junction

Abstract Background: For submucosal tumors (SMTs) originating from the muscularis propria (MP) layer of the esophagogastric junction (EGJ), submucosal tunneling endoscopic resection (STER) is now widely used, and it shows promise in overcoming the limitations of endoscopic submucosal dissection. Aims: This study aimed to evaluate the efficacy and safety of the STER technique for treating SMTs of the EGJ originating from the MP layer. Material and methods: From October 2011 to February 2014, 20 patients were enrolled for STER surgery. Results: The patients were categorized into three groups according to the tumor location. The esophagocardiac group had a lower complication rate (0/7) compared with the cardiac group (3/6) and the gastrocardiac group (3/7). The mean operation time in the esophagocardiac (83 ± 24 min) and cardiac (83 ± 55 min) groups was significantly shorter than that of the gastrocardiac group (145 ± 44 min) (P < 0.05). The en bloc resection rate was 100%, with no severe complications and no recurrence during the follow-up period. Conclusions: The STER technique appears to be a feasible and safe minimally invasive approach for SMTs originating from the MP layer of the EGJ, with satisfying en bloc resection, a short operation time, and low rates of severe complications.

Ursodeoxycholic acid induces apoptosis in hepatocellular carcinoma xenografts in mice

AIM To evaluate the efficacy of ursodeoxycholic acid (UDCA) as a chemotherapeutic agent for the treatment of hepatocellular carcinoma (HCC). METHODS BALB/c nude mice were randomized into four groups 24 h before subcutaneous injection of hepatocarcinoma BEL7402 cells suspended in phosphate buffered saline (PBS) into the right flank. The control group (n = 10) was fed a standard diet while treatment groups (n = 10 each) were fed a standard daily diet supplemented with different concentrations of UDCA (30, 50 and 70 mg/kg per day) for 21 d. Tumor growth was measured once each week, and tumor volume (V) was calculated with the following equation: V = (L × W(2)) × 0.52, where L is the length and W is the width of the xenograft. After 21 d, mice were killed under ether anesthesia, and tumors were excised and weighed. Apoptosis was evaluated through detection of DNA fragmentation with gel electrophoresis and the terminal deoxynucleotidyl transferase-mediated dUTP-biotin nick end labeling (TUNEL) assay. Western blot analysis was performed to determine the expression of apoptosis-related proteins BAX, BCL2, APAF1, cleaved caspase-9, and cleaved caspase-3. RESULTS UDCA suppressed tumor growth relative to controls. The mean tumor volumes were the following: control, 1090 ± 89 mm(3); 30 mg/kg per day, 612 ± 46 mm(3); 50 mg/kg per day, 563 ± 38 mm(3); and 70 mg/kg per day, 221 ± 26 mm(3). Decreased tumor volumes reached statistical significance relative to control xenografts (30 mg/kg per day, P < 0.05; 50 mg/kg per day, P < 0.05; 70 mg/kg per day, P < 0.01). Increasing concentrations of UDCA led to increased DNA fragmentation observed on gel electrophoresis and in the TUNEL assay (control, 1.6% ± 0.3%; 30 mg/kg per day, 2.9% ± 0.5%; 50 mg/kg per day, 3.15% ± 0.7%, and 70 mg/kg per day, 4.86% ± 0.9%). Western blot analysis revealed increased expression of BAX, APAF1, cleaved-caspase-9 and cleaved-caspase-3 proteins, which induce apoptosis, but decreased expression of BCL2 protein, which is an inhibitor of apoptosis, following administration of UDCA. CONCLUSION UDCA suppresses growth of BEL7402 hepatocellular carcinoma cells in vivo, in part through apoptosis induction, and is thus a candidate for therapeutic treatment of HCC.

Protective effects of saizen in combination with stilamin on intestinal mucosa of a rabbit model of severe acute pancreatitis.

Objectives The objective of this study was to investigate whether the regimen of Saizen, a recombinant human somatropin, in combination Stilamin, a somatostatin analog, exerts synergistic effect on intestinal mucosa of a rabbit model of severe acute pancreatitis. Methods The rabbits were randomly divided into 3 groups: group A without any treatment, group B with single treatment of Stilamin, and group C with treatment of Saizen combined with Stilamin. The blood levels of D-lactate, insulinlike growth factor 1, prealbumin, and albumin were detected at the 6th, 12th, 24th, 48th, and 72nd hours after modeling. The pathological changes in terms of the villus height, crypt depth, and mucosal thickness were observed. The caspase 3 expression and apoptotic indices were evaluated. Results The blood levels of D-lactate at the 48th hour; insulinlike growth factor 1 at the 24th and 48th hours; prealbumin at the 24th, 48th, and 72nd hours; and albumin at the 48th hour in group C were significantly higher than these in the other 2 groups. Pathological changes in group C were slighter; the level of caspase 3 and apoptotic index in group C were significantly lower than those in the other 2 groups. Conclusions The combination of Saizen with Stilamin can enhance intestinal mucosa barrier function.

Successful endoscopic removal of three embedded esophageal self-expanding metal stents

In the report, we describe a case of refractory benign esophageal strictures from esophageal cancer after an operation for the placement of three partially covered self-expanding metal stents (SEMSs), which were all embedded in the esophageal wall. Using the stent-in-stent technique, the three embedded SEMSs were successfully removed without significant complications. To the best of our knowledge, few cases of the successful removal of multiple embedded esophageal SEMSs have been reported in the literature. This case also highlights that the stent-in-stent technique is effective for removing multiple embedded esophageal SEMSs.