An updated meta-analysis of randomized controlled trial assessing the effect of neoadjuvant chemotherapy in advanced gastric cancer.

Patients with locally advanced gastric cancer (AGC) have a poor outcome. We performed an updated meta-analysis to assess the effect of neoadjuvant chemotherapy (NAC). By searching electronic databases (PubMed, Embase, Cochrane Library) and ASCO proceedings from 1990 to 2012, all randomized controlled trials (RCTs) which compared the effect of NAC combined surgery versus surgery alone in advanced gastric and gastroesophageal cancer would be included. All calculations and statistical tests were performed. Twelve RCTs with a total of 1,820 patients were included. All patients had resectable gastric or gastroesophageal cancer and received NAC. NAC can slightly improve the survival rate [OR = 1.32, 95% confidence interval (CI): 1.07-1.64, P = 0.01], little, or no significant benefits were suggested in subgroup analyses between different population and regimens either. It can significantly improved the 3-year progression-free survival (PFS) [OR: 1.85 (1.39, 2.46), p < .0001], tumor down-staging rate [OR: 1.71 (1.26, 2.33), p = .0006] and R0 resection rate [OR: 1.38 (1.08, 1.78) p = .01] of patients with AGC. There were no difference between the two arms, in terms of relapse rates [OR: 1.03 (0.60, 1.78), p = 0.92], operative complications [OR: 1.20 (0.90, 1.58), p = 0.21], perioperative mortality [OR: 1.14 (0.64, 2.05), p = 0.65], and grade 3/4 adverse effects. NAC can significantly down-stage the tumor and improve R0 resection rate of patients with gastric and gastroesophageal cancer. It is safe and feasible, and can be tolerated. NAC can slightly improve the survival rate. It needs further prospective multinational multicenter RCTs to define the clinical benefits of NAC and the most effective strategies for gastric and gastroesophageal cancer.

[Role of histone deacetylase in inhibiting invasion of human gastric carcinoma cell line SGC-7901 by PPARgamma-mediated pathway].

BACKGROUND AND OBJECTIVE: Histone deacetylase (HDAC) can attenuate the function of peroxisome proliferator-activated receptor gamma (PPARgamma) to drive adipocyte differentiation. PPARgamma activation is confirmed to inhibit the development and metastasis of a variety of malignant cells. This study was to investigate the role of HDAC in inhibiting the invasion of human gastric carcinoma SGC-7901 cells through PPARgamma-mediated pathway, and explore potential mechanism. METHODS: SGC-7901 cells were treated with different concentrations of Trichostatin A (TSA) and Rosiglitazone (ROZ) respectively to select the best combination through assessing cell proliferation by MTT assay. Then cells were randomly divided into control group, TSA group, ROZ group, and combination group. Cell proliferation was detected by MTT assay after 48 h; cell invasion was detected by Boyden chamber invasion test. The mRNA levels of PPARgamma and matrix metalloproteinase-2 (MMP-2) were assessed by reverse transcription-polymerase chain reaction (RT-PCR), and the protein level of MMP-2 was evaluated by Western blot. RESULTS: Both TSA and ROZ inhibited the proliferation of SGC-7901 cells in a dose-dependent manner. A combination of 20 nmol/L TSA and 5 mumol/L ROZ synergistically inhibited the invasion of SGC-7901 cells (q=1.41). ROZ down-regulated the mRNA and protein expression of MMP-2. TSA and ROZ in combination reduced MMP-2 expression more obviously than ROZ alone. TSA up-regulated the expression of PPARgamma mRNA. CONCLUSIONS: HDAC suppresses the activation of PPARgamma through a series of molecular mechanisms. The activity of ROZ in inhibiting invasion of human gastric carcinoma cells can be enhanced after the activity of HDAC is inhibited by TSA.

[Impact of chronic restraint stress on splenocyte immunity and growth of mouse forestomach carcinoma xenografts in Kunming mice].

BACKGROUND & OBJECTIVE: Recent study found psychosocial factors play some important roles in carcinogenesis and development of malignant tumors, but its mechanisms remain unclear. This study was to investigate the impact of chronic restraint stress on splenocyte immunity and growth of mouse forestomach carcinoma (MFC) xenografts in Kunming mice, and provide evidences for exploring the mechanisms of psychosocial factors function on malignant tumors. METHODS: A total of 60 Kunming mice were randomized into normal control group, restraint stress group, tumor-bearing group and tumor plus restraint stress group; each group contained 15 mice. Chronic restraint stress models were established in restraint stress group and tumor plus restraint stress group; MFC xenograft models were established in tumor-bearing group and tumor plus restraint stress group 4 weeks later. Mice were killed 10 days after inoculation of MFC cells. The weight of MFC xenografts were measured. The proliferation and cytotoxicity of splenocytes were detected by MTT assay. The level of interleukin-2 (IL-2) in splenocyte culture supernants was detected by enzyme-linked immunoabsorbent assay (ELISA). RESULTS: The weight of MFC xenografts was (1.39+/-0.39) g in tumor-bearing group and (2.10+/-0.52) g in tumor plus restraint stress group; MFC xenografts grew faster in tumor plus restraint stress group than in tumor-bearing group (P<0.01), with a tumor growth rate of 51.08%. In normal control group, restraint stress group, tumor-bearing group, and tumor plus restraint stress group, the stimulus indexes (SI) of T lymphocytes were 1.77+/-0.22, 1.70+/-0.17, 1.69+/-0.18, and 1.22+/-0.15, respectively; the SI of B lymphocytes were 1.73+/-0.14, 1.65+/-0.17, 1.64+/-0.21, and 1.33+/-0.11, respectively; the inhibition rate of MFC cell proliferation were (23.01+/-4.76)%, (19.47+/-3.70)%, (16.81+/-3.68)%, and (7.14+/-5.00)%, respectively, when the effector/target ratio was 5:1 and (33.03+/-3.91)%, (28.34+/-4.58)%, (24.94+/-2.97)%, and (13.49+/-7.94)%, respectively, when the effector/target ratio was 10:1; the levels of IL-2 in splenocyte culture supernatants were (260.03+/-14.96) pg/mL, (239.78+/-10.93) pg/mL, (238.11+/-13.50) pg/mL, and (186.34+/-10.42) pg/mL, respectively. Both chronic restraint stress and MFC xenografts impaired the proliferation, cytotoxicity, and IL-2 secretion of splenocytes; the two factors showed interactive effect (P<0.01), but the effect of chronic restraint stress was much more obvious. CONCLUSION: Chronic restraint stress may impair the immune function and promote the growth of MFC xenografts in mice.

RNA interference-mediated gene silencing of vascular endothelial growth factor in colon cancer cells.

AIM: To inhibit the expression of vascular endothelial growth factor (VEGF) in colon cancer cell line by RNA interference (RNAi). METHODS: Followed the service of E-RNAi, we designed and constructed two kinds of shRNA expression vectors aiming at the VEGF gene, then transfected them into colon cancer HT29 cells by lipofectamine(TM) 2000. The level of VEGF mRNA was investigated by RT-PCR and Northern blotting. The protein expression of VEGF was observed by immunofluoresence staining and Western blotting. RESULTS: We got two kinds of VEGF specific shRNA expression vectors which could efficiently inhibit the expression of VEGF in HT29 cells. RT-PCR, Northern blotting, immunofluoresence staining and Western blotting showed that inhibition rate for VEGF expression was up to 42%, 89%, 73% and 82%, respectively. CONCLUSION: The expression of VEGF can be inhibited by RNA interference in HT29 cells.

[Effects of glutamine granules on immunofunction in trauma patients: a double-blind randomized controlled, multi-center clinical trail with 120 patients].

OBJECTIVE: To evaluate the effect of glutamine granules on immunofunction in severe burns and trauma patients. METHODS: One hundred and twenty patients with severe burns, multiple trauma and post operation who met the requirements of the protocol joined this double-blind randomized controlled, multi-center clinical trail. Patients were randomly divided into two groups: placebo control group (P group, 60 patients) and glutamine granules treatment group (GLN group, 60 patients). There was isonitrogenous and isocaloric intake in both groups. GLN and P group patients had been given glutamine granules or placebo (glycine) at 0.5 g.kg(-1).d(-1) for 7 days, respectively. The level of plasma glutamine and some index of immunofunction were determined, and the complication and side effect were also observed. RESULTS: After 7 days of taking glutamine granules orally, plasma GLN concentration was significantly higher than that in P group [(593 +/- 185) micromol/L vs (407 +/- 190) micromol/L)] (P < 0.01). IL-2 level, CD(4)/CD(8) ratio, PMN swallow ratio in GLN group were significantly higher than those in P group (P < 0.05-0.01), but the concentration of IgG, IgM, C(3)/C(4) were not significantly different when compared with P group (P > 0.05). In addition, the occurrence of side effect in both groups was seldom. CONCLUSION: Taking glutamine granules could increase plasma GLN concentration, enhance body immunofunction, and using glutamine granules is safe.

[Analysis of the therapeutic effect and the safety of glutamine granules per os in patients with severe burns and trauma].

OBJECTIVE: To observe the therapeutic effect and possible side effects of glutamine granules per os in patients with trauma, burns and major operations. METHODS: Patients inflicted with severe burns, trauma and major operations were enrolled in the study. One hundred and twenty patients were randomly divided into two groups, 60 in control group (C) and 60 in glutamine group (Gln). Randomized double blind and placebo control methods were employed in the study. All the patients in both groups were given diet with equal calories and equal nitrogen content. The patients in Gln group received glutamine granules in dose of 0.5 g.kg(-1).d(-1) orally or by gavage, while those in C group received same dose of placebo (glycine) for 7 days. The changes in the intestinal mucosal barrier function, the protein metabolism, the immune function, hepatic and renal functions, and the incidence of side effects of the medication in both groups of patients were observed and compared before and after the supplementation of glutamine or glycine. RESULTS: The plasma contents of glutamine, proteins and interleukin 2 in both groups were all lower than normal values. But the plasma diamine oxidase (DAO) activity, endotoxin content, intestinal mucosal permeability (urine lactose/mannitol, L/M) and urine excretion of nitrogen increased obviously in both groups. The plasma glutamine concentration in Gln group increased by 38.04% after the administration of Gln for 7 days (P < 0.01). The plasma contents of pro-albumin, transferrin, and IL-2 were obviously higher than those in the C group (the increase rates were 21.19%, 51.11%, 57.54%, respectively, P < 0.01). The plasma DAO activity, L/M ratio, endotoxin content and urine nitrogen excretion in Gln group were evidently lower than those in C group (the decrease rates were 47.26%, 52.18, 22.22% and 27.78%, respectively, P < 0.05 or 0.01). There was no obvious difference in the plasma levels of total protein and albumin, the indices in blood and urine test, or the hepatic and renal functions between the two groups before and after the amino acid supplementation. Mild side effects such as nausea, diarrhea, constipation occurred in both groups, but all of them disappeared spontaneously afterwards (P > 0.05). CONCLUSION: Oral administration of glutamine could be helpful to increase plasma concentration of glutamine and to ameliorate obviously the intestinal mucosal injury, to promote systemic protein synthesis and to inhibit protein catabolism and to upgrade systemic immune function with little side effect in patients with severe injury.