Current status of sorafenib nanoparticle delivery systems in the treatment of hepatocellular carcinoma.

Hepatocellular carcinoma (HCC) is the most common type of liver cancer and one of the leading causes of cancer-related death worldwide. Advanced HCC displays strong resistance to chemotherapy, and traditional chemotherapy drugs do not achieve satisfactory therapeutic efficacy. Sorafenib is an oral kinase inhibitor that inhibits tumor cell proliferation and angiogenesis and induces cancer cell apoptosis. It also improves the survival rates of patients with advanced liver cancer. However, due to its poor solubility, fast metabolism, and low bioavailability, clinical applications of sorafenib have been substantially restricted. In recent years, various studies have been conducted on the use of nanoparticles to improve drug targeting and therapeutic efficacy in HCC. Moreover, nanoparticles have been extensively explored to improve the therapeutic efficacy of sorafenib, and a variety of nanoparticles, such as polymer, lipid, silica, and metal nanoparticles, have been developed for treating liver cancer. All these new technologies have improved the targeted treatment of HCC by sorafenib and promoted nanomedicines as treatments for HCC. This review provides an overview of hot topics in tumor nanoscience and the latest status of treatments for HCC. It further introduces the current research status of nanoparticle drug delivery systems for treatment of HCC with sorafenib.

Protective effects of Eucommia lignans against hypertensive renal injury by inhibiting expression of aldose reductase.

AIM OF THE STUDY: To investigate the protective effects and the underlying mechanism of Eucommia lignans against hypertensive renal injury. MATERIAL AND METHODS: Ten-week-old Wistar Kyoto rats and age matched spontaneously hypertension rats were used in the study. The SHR were randomly divided into 4 groups (n=7 for each group) and received different treatment for 16 weeks, which including saline, Captopril, Epalrestat and Eucommia lignans, respectively. System blood pressures of the rats were monitored once every 4 weeks. N-Acetyl-ß-D-glucosaminidase (NAG) activity and the ratio of albumin and urinary creatinine were chosen as the indices of kidney function. Then the structure and renal collagen type III expression of glomerular basement membrane were observed by microscopy and the renal aldose reductase (AR) expression was measured by immunohistochemistry. In vitro, the proliferation of mesangial cells induced by AngII was assayed by MTT, and the mRNA expression of AR was measured by RT-real-time PCR. RESULTS: The renal function, evaluated by NAG enzyme activity and the ratio of albumin to urinary creatinine, was significantly ameliorated by Eucommia lignans treatment. Meanwhile, Eucommia lignans decreased both the protein (P<0.05) and the mRNA expressed lever of AR (P<0.05). Eucommia lignans also decreased the high expression of collagen type III in SHR (P<0.05) and inhibited the proliferation of renal mesangial cells induced by AngII (P<0.05). CONCLUSION: Eucommia lignans have protective effects against hypertensive renal injury, and the protective effects may be partly due to inhibition of aldose reductase.

[Effect of extract of ginkgo biloba leaves on the precondition of liver graft in rat liver transplantation].

OBJECTIVE: To explore the effect of extract of ginkgo biloba leaves on the precondition of liver graft in rat liver transplantation. METHODS: Male Sprague-Dawley rats were used as donors and recipients of orthotopic liver transplantation (OLT), and were randomly divided into extract of ginkgo biloba leaves group (Egb), NS control group (NS), and sham operation group (SO) according to whether the extract of ginkgo biloba leaves was injected by the venous (40 mg/kg) 1 h before the liver grafts harvesting. The rats were killed at 2 h, 6 h, and 24 h after the ischemia/reperfusion. The serum concentrations of ALT and AST were determined and the liver tissue were sampled to observe the expression of TNF-alpha and IL-1. RESULTS: After the ischemia/reperfusion the serum concentration of ALT and AST and expressions of TNF-alpha and IL-1 in the hepatic tissue in the NS group significantly increased (p<0.01), and the hepatocytic morphologic change was obvious compared with the SO group. The treatment of ginkgo biloba extract significantly decreased the serum concentration of ALT and AST and the expressions of TNF-alpha and IL-1 in the hepatic tissue in EGb group compared with the NS group (p<0.01), and relieved the hepatocyte swelling and necrosis. CONCLUSION: Ginkgo bilobA extract may decrease the release of TNF-alpha and IL-1 by inhibiting activation of kuffer cells and regulate the cell factors to protect the live.

Panax notoginseng saponins preconditioning protects rat liver grafts from ischemia/reperfusion injury via an antiapoptotic pathway.

BACKGROUND: Ischemia/reperfusion (I/R) injury is a major cause of primary graft dysfunction and renders an allograft more immunogenic in orthotopic liver transplantation (OLT). Panax notoginseng saponins (PNS) has been reported to exert protective effects against I/R injury to various organs. The objective of this study is to investigate whether PNS preconditioning protects rat liver grafts from I/R injury via an antiapoptotic pathway. METHODS: Male Sprague-Dawley rats were used as donors and recipients of orthotopic liver transplantation (OLT) and were divided into PNS preconditioning group(group P) and normal saline control group (group N) randomly according to whether PNS (50 mg/kg) was injected intravenously 1 hour before liver grafts harvesting, and sham group (group S). The animals were separately killed 2, 6 and 24 hours after reperfusion. Plasma samples were collected for test of alanine aminotransferase (ALT) and aspartate aminotransferase (AST). Liver tissues were collected to detect histological changes, apoptosis and the expression of TNF-alpha, Bcl-2 and Caspase-3 mRNA. RESULTS: The serum levels of ALT and AST and the apoptosis index (AI) of liver tissue in group P were lower than in group N significantly 2, 6 and 24 hours after reperfusion. Compared with group N, the expression of TNF-alpha and Caspase-3 mRNA was reduced significantly in group P 2 and 6 hours after reperfusion and the expression of Bcl-2 mRNA was enhanced significantly in group P 6 and 24 hours after reperfusion. CONCLUSIONS: PNS preconditioning protects liver grafts from I/R injury effectively in rat OLT via an antiapoptotic pathway. The antiapoptotic mechanisms of PNS may include inhibiting the expression of TNF-alpha and Caspase-3 and enhancing the expression of Bcl-2.