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Gastric cancer is a serious malignancy that endangers human health. Increased rates of chemotherapy-resistant cancer have led to a decrease in the efficacy of treatment. Recent studies found that the presence of hypoxia in the tumor microenvironment was a notable cause of gastric cancer resistance to chemotherapy drugs. The abnormal structure and function of blood vessels in the tumor and the rapid proliferation of tumor cells increase the oxygen consumption of tumor cells, which results in tumor tissue hypox-ia. Hypoxic conditions make tumor cells more aggressive, more likely to metastasize and develop resistance to chemotherapy. In this paper, we have reviewed the progress of research into hypoxia-induced chemotherapeutic drug resistance in gastric cancer. The review has covered the causes of hypoxia and the characteristics of the hypoxic microenvironment in gastric cancer, the current situation and causes of hypoxia-induced chemotherapeutic drug resistance in gastric cancer, and the measures to overcome the hypoxia-induced re-sistance to chemotherapy drugs.
RÉSUMÉ
Objective To identify the imbalance of T cell-specific transcription factors T-bet/GATA-3,and to explore the modulation with dexamethasone and imiquimod in CD4+T cells from ovalbumin (OVA)sensitized mice.Methods CD4+T cells were obtained fromsingled-cell suspension of spleen(after lysis of RBC).ELISA assay was used to detect the concentrations of IL-4,IL-5 and IFN-γin superna tants and cell pellets,and the expression of T-bet and GATA-3 was detected by Western blot.Resuits In the control group,tIle low levels of IFN-γ were detected in the supernatants during 24 h.In OVA treatment group,the concentrations of IL-4,IL-5 were increased significantly,and the concentrations of IFN-γ were always low in the supernatants.In the dexamethasone treatment group,the concentrations of IFN-γ,IL-4 and IL-5 were all low in the supernatants during 24 h.In the imiquimod treatment group,the concentrations of IFN-γ were increased significantly,and the concentrations of IL-4 and IL-5 were decreased in the super natants.It worked at 6 h,and achieved the peak at 12 h,lasted over 24 h.In the control group,the expres sions of T-bet and GATA-3 were detected in CD4+T cells during 24 h.In OVA treatment group,the expressions of T-bet were decreased,and that of GATA-3 were increased rapidly in CD4+T cells.In dexam ethasone treatment group,the expressions of T-bet were always low in CD4+T cells,and that ofGATA-3 were no change during 24 h.In imiquimod treatment group,the expressions of T-bet were increased,andthat of GATA-3 were decreased in CD4+T cells.The protein expressions worked at 6 h.and achieved the peak at 12 h,lasted over 24 h.Conclusion The imbalance T cell-specific transcription factors T-bet/GA-TA-3 contributes to both high expression of GATA-3 and low expression of T-bet in CD4+T cells from OVA sensitized mice.Dexamethasone treatment inhibits the expression of T-bet in CD4+T cells and has no func tion in GATA-3.Imiquimod treatment modulates key master switches GATA-3 and T-bet that results in com mitting T helper cell to a TH 1 phenotype and imiquimod may play a key role in the regulation of TH2 cytokine responses in asthma.
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OBJECTIVE The diagnosis of drug allergy is difficult and is usually based on clinical history,skin tests(for some drugs) and,in a few specialized allergy centers,provocation tests.To establish the method for analyzing basophil activation test(BAT) by flow cytometry(FCM) and evaluate its clinical significance in the diagnosis of drug allergy.METHODS The protocol for FCM analysis of basophil degranulation in allergy dustmite by CD63,CD203c and CD45 combination was established.The clinical significance of activated basophil by FCM was evaluated by comparing with the results of sIgE by fluorescence enzyme-linked absorbent assay(FELISA),regarding the skin prick test as the gold standard.RESULTS Pure basophils were got by CD45 and CD203c gating,CD63 was the best marker for activated basophil;Spearman′s correlation coefficients indicated a moderate positive correlation between SIgE class categorized by Unicap class and activated basophil;there was no significant difference between activated basophil by FCM and sIgE by FELISA in the diagnosis of allergic reaction,but the former was better than the latter in specificity and positive likelihood ratio.CONCLUSIONS Quantification of activated basophil by CD63 expression with FCM is a valuable new and safe method in vitro for diagnosis of immediate type hypersensitization.
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OBJECTIVE To investigate the association between 592C/A and-819C/T of interleukin-10 gene polymorphism in patients with immediate ?-lactam drug allergy in Chinese Han population.METHODS The genotype and allele frequency of interleukin-10 gene were studied by polymerase chain reaction-restriction fragment length polymorphism(PCR-RFLP)in 44 Chinese Han patients with evidence of immediate ?-lactam drug allergy and 44 controls subjects.They all matched for sex and atopy,the production was investigated by sequence analysis.RESULTS Our analysis did reveal differences in the distribution of the single nucleotide polymorphism(SNP)between female allergic patients and controls.Among allergy subjects,we found two distinct significant associations between immediate drug allergy women and two linked IL-10 promoter genes polymorphism,-592C/A and-819C/T(P