N-linoleyltyrosine resisted the growth of non-small cell lung cancer cells via the regulation of CB1 and CB2 involvement of PI3K and ERK pathways.

Background: N-linoleyltyrosine (NITyr), one of the anandamide analogs, exerts activity via the endocannabinoid receptors (CB1 and CB2), which showed anti-tumor effects in various tumors. Therefore, we speculated that NITyr might show anti-non-small cell lung cancer (NSCLC) effects via the CB1 or CB2 receptor. The purpose of the investigation was to reveal the anti-tumor ability of NITyr on A549 cells and its mechanisms. Methods: The viability of A549 cells was measured by MTT assay, and the cell cycle and apoptosis were both examined by flow cytometry; in addition, cell migration was tested by wound healing assay. Apoptosis-related markers were measured by immunofluorescence. The downstream signaling pathways (PI3K, ERK, and JNK) of CB1 or CB2 were examined through Western blotting. The expressions of CB1 and CB2 were detected by immunofluorescence. Finally, the AutoDock software was used to validate the binding affinity between the targets, such as CB1 and CB2, with NITyr. Results: We found that NITyr inhibited cell viability, hindered the cell cycle, resulted in apoptosis, and inhibited migration. The CB1 inhibitor, AM251, and the CB2 inhibitor, AM630, weakened the aforementioned phenomenon. The immunofluorescence assay suggested that NITyr upregulated the expression of CB1 and CB2. Western blot analysis indicated that NITyr upregulated the expression of p-ERK, downregulated the expression of p-PI3K, and did not affect p-JNK expression. In conclusion, NITyr showed a role in inhibiting NSCLC through the activation of CB1 and CB2 receptors involved in PI3K and ERK pathways.

A successful combined laparoscopic cholecystectomy and laparoscopic exploration of common bile duct for acute gangrenous cholecystitis and choledocholithiasis during pregnancy: A case report.

INTRODUCTION: Choledocholithiasis during pregnancy is relatively uncommon but it can be life-threatening. Therapeutic endoscopic retrograde cholangiopancreatography (ERCP) poses the risk of ionizing radiation exposure to the developing fetus. Other strategies are thus needed to tackle this problem. PRESENTATION OF CASE: A 38-year-old 8 weeks' pregnant lady presented with acute onset of right upper quadrant pain. Ultrasonography showed features of acute cholecystitis and choledocholithiasis, which was later confirmed by magnetic resonance cholangiogram. Emergency combined laparoscopic cholecystectomy (LC) and laparoscopic exploration of common bile duct (Lap ECBD) were performed. Lap ECBD through trans-cystic duct approach was adopted. The patient recovered uneventfully and was discharged on postoperative day 4. A healthy baby boy was delivered at 40 weeks' gestation without developmental problem. CONCLUSION: Lap ECBD avoided ionizing radiation for choledocholithiasis during pregnancy, and can combined with LC as an effective minimally invasive procedure for complicated gallstone disease.

[Nanogold inhibits angiogenesis and growth of liver cancer: experiment with mice].

OBJECTIVE: To investigate the effects of nanogold in inhibition of angiogenesis and growth of liver cancer cells. METHODS: Nanogold was co-incubated with VEGF165 and VDGF121 respectively. Atomic force microscopy (AFM) was used to observe the changes of the form of the particles. Human umbilical vascular endothelial cells (HUVEC) were serum-starved for 24 hours, then co-cultured with VEGF165 + nanogold or VEGF121 + nanogold for 24 h. ATM was used to observe the ultrastructure of the cells. Another HUVEC were serum-starved for 24 hours and then cultured with VEGF165 (10 microg/L) 100 microl + nanogold 125, 250, and 500 nmol/L 100 microl respectively for 5 min. Then Western blotting was used to detect the phosphorylation protein of phospholipase C (PLC)-gamma1 on VEGFR-2. Hepatocellular cancer cells of the line H22 were injected subcutaneously into the right armpit of 20 Balb/c nude mice. When the size of transplanted tumor reached about 8 mm, the mice were divided into 2 equal groups: experimental group undergoing injection of nanogold into the tumor once a day for 8 days, and control group injected with normal saline. On day 14 the mice were sacrificed with the liver tumors taken out to measure the size and weight. The microvascular density (MVD) of tumor was determined by immunohistochemical staining. RESULTS: ATM showed that acted with VEGF165, the size of nanogold became over 30 nm. Treated with VEGF165 the HUVEC became larger with obvious pseudopodium. However, such changes were obviously milder in those HUVEC treated with nanogold + VEGF165. The PLC-gamma1 phosphorylation level VEGF receptor-2 was decreased along with the increase of the concentration of nanogold. The MVD of liver cancer tissue in the experimental group was 14.27 +/- 1.08, significantly lower than that of the control group [(23.52 +/- 1.36), P < 0.01]. The mean weight and volume of tumor of the experimental group were (1.39 +/- 0.08) g and (1.37 +/- 0.34) cm(3) respectively, both significantly lower than those of the control group [(2.47 +/- 0.15) g and (2.49 +/- 0.78) cm(3) respectively, both P < 0.05] with a tumor growth inhibition rate of 43.72%. CONCLUSION: Nanogold significantly inhibits the angiogenesis and growth of liver cancer cells with the possible mechanism that nanogold inhibits the VEGF165-induced signaling.