Cytotoxic function of gamma delta (ϒ/δ) T cells against pamidronate- treated cervical cancer cells.

The cytotoxic function of polyclonal expanded ϒ/δ T cells against pamidronate-treated cervical cancer cells in vitro and in vivo were determined. The ϒ/δ T cells were isolated and purified from PBMCs by using miniMACS and were later treated with 10 μM pamidronate. The expansion of ϒ/δ T cells was 15 times more than the non-stimulated cells. Among the expanded ϒ/δ T cells, 47% were Vϒ9/Vδ2 T cells with a purity of 87%. Analyzing the cytotoxic function of ϒ/δ T cells against 3 cervical cancer cells in vitro by LDH cytotoxicity test revealed that the killing efficacy increased if the cervical cancer cells (HeLa, SiHa and CaSki) were pretreated with pamidronate. The presence of CD107 on ϒ/δ T cells indicated the degranulation of perforin and granzyme pathway is one of the mechanisms used by the ϒ/δ T cells to kill cancer cells. The killing ability of ϒ/δ T cells against cancer cells in vivo was preliminary assessed by using mouse baring HeLa cells. The results demonstrated that ϒ/δ T cells induce apoptosis in tumor cells. Our study supports the usefulness of ϒ/δ T cells in future development of immunotherapy for cervical cancer.

Downregulation of p-ERK1/2 and p-AKT expression by curcumin and tetrahydrocurcumin in hepatocellular carcinoma-induced tumors in nude mice.

Background: Curcumin (CUR) and tetrahydrocurcumin (THC) inhibits tumor angiogenesis. It is suggested that tumor progress may be related to the pathway of extracellular signal-regulated kinase 1/2 (ERK1/2) and serine/ threonine kinase AKT, but the mechanism remains unclear. Objective: Investigate the effects of CUR and THC on the expression of ERK1/2 and AKT in hepatocellula carcinoma (HepG2)-induced tumors in nude mice. Methods: The curcuminoid mixture was obtained from the rhizomes of Curcuma longa, which was subjected to silica gel column chromatography to afford CUR as the major constituent. THC was prepared by hydrogenation of curcumin with palladium on charcoal as a catalyst. HepG2-implanted nude mice model was used to study of angiogenesis and tumor progression. Expressions of phospho-ERK1/2 (p-ERK1/2) and phopho-AKT (p-AKT) in HepG2-implated tissue were measured by immunohistochemistry. Tumor area, area of expression and expression ratio of pERK1/2 and p-AKT were determined. Results: Increases in p-ERK1/2 and p-AKT expression in HepG2 group was related to changes in tumor growth in control, CUR, and THC groups. THC-treatment could attenuate the p-ERK1/2, p-AKT expression, tumor area, and ratio of expression in HepG2-implanted nude mice significantly, compared to CUR-treatment. Conclusion: HepG2-induced tumor progression may be inhibited by THC in part through the inhibition of mitogen-activated protein kinase (MEK)/ERK and phosphoinositide 3-kinase (PI3K)/AKT.

Curcumin as a therapeutic agent against cancer.

Background: Curcumin is an important chemopreventive agent against cancer. Recently, it has been reported that curcumin has also anti-angiogenic effects in tumor. Objective: This article reviews the effect of curcumin against tumor angiogenesis from view-points of cancer microcirculation and biomarkers. Results and conclusion. We demonstrated an anti-angiogenic effect of curcumin in tumors using nude mice. We studied the inhibitory effects of curcumin on tumor-induced neocapillaries and proangiogenic factors, based on our intravital fluorescent observation. Finally, we hypothesized a possible mechanism for curcumin effect in tumor.

Leukocyte-endothelial cell interaction is attenuated by low-intensity exercise training and vitamin C supplementation in diabetic rats.

Objective: To determine the effects of vitamin C supplementation and low-intensity exercise training on diabetesinduced endothelial dysfunction. Methods: Male Spraque-Dawley rats were randomly divided into five groups: control (Con), diabetes (DM) (streptozotocin; 50 mg/kg BW, i.v.), diabetes with supplemented vitamin C (DM+Vit.C; 1 g/L mixed in drinking water), diabetes with low-intensity exercise-trained (DM+Ex; running 5 times/week with 13-15 m/min velocity for 30 minutes) and diabetes with supplemented vitamin C and exercisetrained (DM+Vit.C+Ex) groups. The number of leukocyte-endothelial cell (EC) interactions in mesenteric postcapillary venules was monitored using intravital fluorescence videomicroscopy. Liver malondialdehyde (MDA) level, an indicator for oxidative stress, was determined by using the thiobarbituric acid reaction. Results: At 24 weeks, the plasma vitamin C level was significantly increased (p<0.05) in DM+Vit.C and DM+Vit.C+Ex rats when compared with DM rats. DM+Ex and DM+Vit.C+Ex rats had lower triglyceride levels and heart weights when compared with DM rats (P<0.05). Mean arterial pressures were significantly decreased in all treatment groups. DM rats had significantly higher malondialdehyde (MDA) levels and lower activities of superoxide dismutase (SOD) than Con. The number of adherent leukocytes and levels of MDA were significantly lower in DM+Vit.C, DM+Ex and DM+Vit.C+Ex than those of DM rats. Conclusion: The increased leukocyte-EC adherence in diabetic rats is significantly related to increased ROS, based on lower MDA levels. Vitamin C supplementation and regular low-intensity exercise training can prevent these deleterious effects, including hypertension, cardiac hypertrophy, hypertriglyceridemia, and leukocyte-EC adherence. Vitamin C supplementation combined with low-intensity exercise training is highly effective in preventing diabetic cardiovascular complications.

Effects of N-acetylcysteine on oxidative stress in rats with non-alcoholic steatohepatitis.

OBJECTIVE: Prove the attenuated effects of N-acetylcysteine (NAC) on oxidative stress in rats with nonalcoholic steatohepatitis (NASH). MATERIAL AND METHOD: Male Sprague-Dawley rats were randomly divided into five groups. Group I (normal control) was fed regular dry rat chow (RC) for 6 weeks. Group 2 (NASH) was fed 100% fat diet for 6 weeks. Group 3-5 were fed 100% fat diet for 6 weeks, and then switched to RC alone (NASH + diet ; group 3), to RC + 20 mg/kg/day of NAC orally (NASH + diet + NAC20; group 4) or to RC + 500 mg/kg/day of NAC orally (NASH + diet + NAC500; group 5) for 4 weeks, respectively. They were sacrificed to collect blood and liver samples at the end of the present study. RESULTS: Levels of total glutathione (GSH), serum cholesterol, and hepatic malondialdehyde (MDA) were increased significantly in the NASH group compared with normal control. Liver histopathology from group 2 showed moderate to severe macrovesicular steatosis, hepatocyte ballooning, and necroinflammation. Treatment with diet or diet plus NAC reduced the levels of GSH, cholesterol, and hepatic MDA back to normal. Liver sections from group 3-5 showed a decrease in fat deposition and necroinflammation in hepatocytes. However, no differences on all variables existed between diet alone and diet plus NAC groups. CONCLUSION: Our data indicate that diet or diet plus NAC treatment could attenuate oxidative stress and improve liver histopathology of NASH. However the addition of NAC is not better than diet treatment alone.