ABSTRACT
OBJECTIVE@#To assess the activation function of specific tumor polypeptide for dendritic cell vaccine on lymphocytes proliferation, production of cytokines and killing activity in vitro by using dendritic cells as antigen presenting vector.@*METHODS@#Peripheral blood dendritic cells (DC) and cytokine-induced killer (CIK) were isolated and cultured by adherent culture method; CCK-8 method was used to assess the proliferation function of lymphocytes and the killing function of lymphocytes to tumor cells; enzyme-linked immunospot assay method was used to evaluate the secretion function of cytokines. The experiment was divided into tumor polypeptide group (peptide with DC-CIK), DC-CIK group and CIK group.@*RESULTS@#With presence of interleukin-2 (IL-2) in the culture system, the lymphocyte proliferation of the three groups was obvious. The absorbance at 450 nm of tumor polypeptide group was significantly higher than that of CIK group at the time points day 4 and day 6 (day 4: Z=-3.79, P < 0.001; day 6: Z =-2.95, P < 0.01). The absorbance at 450 nm of group tumor polypeptide was significantly higher than that of DC-CIK group on day 4 (Z=-2.02, P < 0.05). Without IL-2 in the culture system, lymphocytes proliferated slowly in all the three groups, and there was no significant difference in 450 nm absorbance at each time point. The levels of IL-4 (Z=-2.61, P < 0.01), granulocyte-macrophage colony-stimulation factor (GM-CSF, Z=-3.85, P < 0.001), interferon- γ (IFN- γ, Z=-3.56, P < 0.001) and tumor necrosis factor-α (TNF-ɑ, Z=-3.40, P < 0.001) of tumor polypeptide group were higher than those of CIK group. There was no significant difference in the production of cytokines except IL-4 (Z=-2.15, P < 0.05) when tumor polypeptide group was compared with DC-CIK group. The production of IFN-γ (Z=-2.44, P < 0.05), TNF-ɑ (Z=-2.26, P < 0.05) and GM-CSF (Z=-3.73, P < 0.001) in DC-CIK group were higher than those of CIK group. Although there was no significant difference in killing activity between tumor polypeptide group, DC-CIK group and CIK group at hour 18 and hour 24, and the killing activity of tumor polypeptide group was higher than that of the other two groups.@*CONCLUSION@#Tumor peptide combined with dendritic cells can improve the proliferation activity of CIK cells in vitro, and increase the secretion of several cytokines.
Subject(s)
Dendritic Cells , PeptidesABSTRACT
OBJECTIVE: To investigate whether the polymorphisms of cytochrome P450 3A5 (CYP3A5) gene and glutathione S-transferase P1 (GSTP1) gene are associated with the short-term efficacy of docetaxel plus thiotepa for Chinese patients with metastatic breast cancer. METHODS: All patients received docetaxel plus thiotepa chemotherapy. CYP3A5 and GSTP1 were genotyped by matrix assisted laser desorption ionization / time of flight (MALDI-TOF). Disease control rate (DCR) was evaluated every two chemotherapy cycles, and was compared between different genotypes. RESULTS: Among 93 enrolled patients, people with CYP3A5 A6986G GG genotype showed a statistically higher DCR than those with AG + GG genotype (77.8% versus 57.4%, P < 0.05), and the DCR of the patients with GSTP1 A313G AG + GG was statistically higher than that of patients with AA (81.6% versus 57.4%, P < 0.05). Combination analysis showed that patients with GSTP1 A313G AG + GG and CYP3A5 A6986G GG had the highest DCR (84.2%, P < 0.05). CONCLUSION: CYP3A5 and GSTP1 polymorphisms are associated with the short-term efficacy of docetaxel plus thiotepa. Higher DCRs were seen in patients carrying GSTP1 A313G AG + GG and / or CYP3A5 A6986G GG genotype, which might be a reference for clinical chemotherapy. Copyright 2012 by the Chinese Pharmaceutical Association.