An open-labeled, randomized, multicenter phase IIa study of gambogic acid injection for advanced malignant tumors.

BACKGROUND: Gambogic acid is a pure active compound isolated from the traditional Chinese medicinal plant gamboge (Garcinia morella Desv.). Based on the preliminary results of a phase I study, this phase IIa study compared the efficacy and safety of different dosage schedules of gambogic acid in patients with advanced malignant tumors. METHODS: Patients with advanced or metastases cancer who had not received any effective routine conventional treatment or who had failed to respond to the existing conventional treatment were randomly assigned to receive either 45 mg/m(2) gambogic acid intravenously from Days 1 to 5 of a 2-week cycle (Group A), or 45 mg/m(2) every other day for a total of five times during a 2-week cycle (Group B). The primary endpoint was objective response rate (ORR). RESULTS: Twenty-one patients assigned to Group A and 26 to Group B were included in the final analysis. The ORRs were 14.3% in Group A and 0% in Group B. It was not possible to analyze the significant difference because one of the values was zero. The disease control rates (DCRs) were 76.2% in Group A and 61.5% in Group B (P = 0.0456). The observed adverse reactions were mostly Grades I and II, and occurred in most patients after administration of the trial drug. There was no significant difference in the incidence of adverse reactions between the two arms. CONCLUSIONS: The preliminary results of this phase IIa exploratory study suggest that gambogic acid has a favorable safety profile when administered at 45 mg/m(2). The DCR was greater in patients receiving gambogic acid on Days 1 - 5 of a 2-week cycle, but the incidence of adverse reactions was similar irrespective of the administration schedule.

[Effect of early enteral nutrition supplemented with glutamine on postoperative intestinal mucosal barrier function in patients with gastric carcinoma].

OBJECTIVE: To investigate the effect of early enteral nutrition (EEN) supplemented with glutamine on postoperative intestinal mucosal barrier function of patients with gastric carcinoma. METHODS: Eighty patients with gastric carcinoma who underwent intraoperative peritoneal hyperthermic chemotherapy(IPHC) were randomized into two groups: EEN+glutamine (EEN+Gln) group(n=40) and EEN group(n=40). Intestinal mucosal barrier function was evaluated by serum diamine oxidase (DAO), ratio of lactulose to mannitol(L/M), endotoxin lipopolysaccharides(LPS), and tumor necrosis factor-α(TNF-α) at 1 day before operation, 1 day, 7 days, 12 days after operation. Time to first flatus and tolerance to EEN were recorded as well. RESULTS: There were no significant differences in the two groups in demographics(all P>0.05). Two cases(5%) in the EEN+Gln group and 1 case (2.5%) in the EEN group could not tolerate well(P>0.05). On postoperative day 1, there were no differences in serum DAO, L/M ratio, LPS, TNF-α between the two groups (P>0.05). On postoperative day 7, all the parameters for mucosal barrier function were significantly lower in the EEN+Gln group. On postoperative day 12, the urinary L/M and DAO, LPS, and TNF-α were still significantly lower in the EEN+Gln group, however, urinary L/M was comparable between the two groups. There were no differences between the two groups in the time to first flatus (P>0.05). CONCLUSION: The immunologic tolerance of enteral nutrition supplemented with glutamine is favorable, which provides protective effect on intestinal mucosal barrier in patients with gastric carcinoma undergoing IPHC.

[Nutritional therapy of duodenocutaneous fistula].

OBJECTIVE: To summarize the experience in nutritional support for the management of duodenocutaneous fistula. METHODS: Data of 32 patients with duodenocutaneous fistula in Zhejiang provincial people's hospital from January 1999 to December 2009 were analyzed retrospectively. RESULTS: The mean duration of nutritional support was 35.6 days (range, 8-82 days). Eight received total parenteral nutrition, 2 total enteral nutrition, and 22 parenteral nutrition combined with enteral nutrition respectively. Succus entericus reinfusion with enteral nutrition was used in 11 cases, glutamine-enriched nutritional support in 28 cases, somatostatin in 12 cases. In these patients, the healing rate was 75.0% after conservative treatment. In the 8 patients who underwent surgery, 6 were cured and 2 died (due to severe abdominal infection and multiple organ failure). A total of 30 patients had the fistulas cured and discharged. CONCLUSIONS: Parenteral nutrition combined with enteral nutrition, succus entericus reinfusion combined with enteral nutrition, glutamine-enriched nutritional support and somatostatin are important factors for the healing of duodenocutaneous fistulas.

[Studies on effect enhancement of the Schistosoma japonicum DNA vaccine pVIV02-IL12-Sj23 by vegetal polysaccharides].

OBJECTIVE: To enhance the immunogenicity of the recombinant pVIVO2-IL12-Sj23 vaccine of Schistosoma japonicum by using mixed vegetal polysaccharides as adjuvant. METHODS: The plasmid pVIVO2-IL12-Sj23 was constructed. 3 groups of BALB/C mice were injected intramuscularly with normal saline (Group A), pVIVO2-IL12-Sj23 plasmid DNA (B), and pVIVO2-IL12-Sj23 plus mixed vegetal polysaccharides (C) respectively, and challenged with S. japonicum cercariae on the 4th week after immunization. Mice were killed to calculate the worm reduction rate and egg reduction rate in liver tissue on the 6th week after infection. Before and 4 weeks after immunization blood samples were collected. RESULTS: The worm reduction rate and egg reduction rate were 64.3% and 79.9%, respectively in group C, 45.5% and 58.4%, respectively in group B, showing a remarkable difference hetween them (P < 0.05). ELISA analysis showed a significantly higher level of IgG specific for Sj23 4 weeks after vaccination in groups B and C (P < 0.05). However, there was no significant difference in IgG level between groups C and B (P > 0.05). CONCLUSION: When mixed vegetal polysaccharides are used as adjuvant, the effect of the vaccine pVIVO2-IL12-Sj23 can he considerably enhanced.

[Protective effect of Gastrodia elata and E-gelatin on lead-induced damage to the structure and function of rat hippocampus].

OBJECTIVE: To observe the counteraction of Gastrodia elata and E-gelatin on the effect of subchronic lead poisoning on the ability of learning and memory and the ultrastructure in hippocampus. METHODS: Subchronic lead acetate exposure was given to rats (0.2 g x kg(-1) x d(-1)). Single and combined administration of Gastrodia elata (4 g x kg(-1) x d(-1)) and E-gelatin (1 g x kg(-1) x d(-1)) were conducted at the same time. Pb concentration in blood, and the ability of learning and memory (Y-maze test) of rats were measured. Ultrastructure of CA3 pyramidal cells in hippocampus under transmission electron microscope was observed. RESULTS: Blood Pb concentrations in each group (Pb group: 690.6 micro g/L, Pb + Gastodiae eleta group: 688.8 micro g/L, Pb + E-gelatin group: 663.8 micro g/L, Pb + combined group: 667.2 micro g/L) were higher than that in the control (28.24 micro g/L, P < 0.01). But there was no significant difference (P > 0.05) among these groups. In Y-maze test, the number of electric stroke in Pb group is higher than that in control (P < 0.01). Gastrodia elata or E-gelatin used singly could significantly reduce the number of electric stroke of lead-exposed groups (P < 0.05 in the first month and P < 0.01 in the second and third month). And the effect of combined use of them was more efficient than single use (P < 0.01). Under electron microscope, no anomaly was seen in the pyramidal cells of CA3 area in hippocampus of control group. But there was significant anomaly such as neucleus separation in the cells of Pb exposed group. In Pb-Gastrodia elata group, there were some stress response phenomena such as the occurrence of huge mitochondria while in Pb-E-gelatin group, the anomaly was mild. The cells in the CA3 area in hippocampus of the pb-Gastrodia-E-gelatin group were almost normal, and also showed some stress response phenomena. CONCLUSION: Gastrodia elata and E-gelatin may protect the neurons in CA3 area of hippocampus against damage induced by lead to improve the ability of learning and memory, and they have synergistic effect.

[The antagonistic action of Gastrodia elata combined with E-gelatin on lead-induced down regulation of c-fos expression in rat brain].

OBJECTIVE: To observe the effect of lead on the expression of c-fos mRNA in hippocampus and cerebellum and the ability of learning and memory in rat, and to observe the antagonistic action of Gastrodia elata and E-gelatin on the effect mentioned above. METHODS: Rats were exposed to lead acetate (0.2 g x kg(-1) x d(-1) and 0.1 g x kg(-1) x d(-1)). The single and combined administration of Gastrodia elata (4 g x kg(-1) x d(-1)) and E-gelatin (1 g x kg(-1) x d(-1)) were conducted at the same time. Blood lead concentration in rats were measured. The ability of learning and memory by Y-maze test were examined. The expression of c-fos mRNA in hippocampus and cerebellum during Y-maze test were observed by in situ hybridization (ISH). RESULTS: (1) Blood lead concentrations were significantly increased in both high and low doses of lead-exposed rats (P < 0.01). But there were no differences among high dose groups or low dose groups (P > 0.05). (2) In Y-maze test, the number of electric stroke during learning in lead-exposed group was significantly increased (P < 0.01) while that in Gastrodia elata and E-gelatin groups was significantly decreased (P < 0.05), and that in combined use group was more significantly decreased (P < 0.01). (3) There were much more deep-colored c-fos positive cells in CA3 area of hippocampus in low dose of Pb-exposed with Gastrodia elata + E-gelatin group. These cells were also found in high Pb with combined use or single use group, but which were not so densely distributed as the former. And they were hardly found in high and low doses of Pb alone groups. The changes of expression of c-fos cells in cerebellam were similar to those in hippocampus. CONCLUSION: The down regulation of c-fos expression may be one of the molecular mechanism of lead-induced impairment of learning and memory. Gastrodia elata and E-gelatin may antagonize the effect of lead on c-fos expression, and combined use of both drugs may potentiate the antagonism.