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Expression And Significance Of CD4~+CD25~+,COX-2 And NF-κB In Human Gastric Tumor

Posted on:2008-07-23Degree:DoctorType:Dissertation
Country:ChinaCandidate:Y YouFull Text:PDF
GTID:1114360218955999Subject:Surgery
Abstract/Summary:PDF Full Text Request
Like all the other cancers, the oncogenesis of gastric cancer is alsoa complicated pathological process involves many factors, many genes andmany stages. As a common cancer with a yearly increasing occurrence rate, gastric cancer presents unsatisfied outcomes of current therapies and anextremely poor prognosis, due to its high malignancy and a lack of earlyspecific diagnostic methods. To solve the problem, the essential way isto find new therapeutic targets and diagnostic markers.In order to investigate the changes in peripheral CD4~+CD25~+ regulatoryT cells(CD4~+CD25~+ T reg), and discuss their relationship in patients withgastric cancer before and after operation. From 80 patients 4 ml venousblood was obtained, the blood samples were evaluated with the flowcytometry for lymphocyte subsets and T reg cells. We found that theexpressive rates of CO4,CD16 and the ratio of CD4/CD8 in peripheral bloodwere lower significantly than that in normal volunteers(P<0.05) in theadvanced stages. On the other hand, Cancer patients had a higherproportion of CD4~+CD25~+ T reg cells than those of the healthy volunteers(P<0.05). The relative increase in CD4~+CD25~+ regulatory T cells may berelated to immunosuppression and tumor progression in patients withgastric cancer. This finding suggests that the deletion of the CD4~+CD25~+Treg cells to treat gastric cancer patients may be an effective strategy.In order to investigate the expression of COX-2,VEGF and VEGF-C inhuman gastric cancer, the relationship between their expression and theclinicopathological features, as well as the relationship between theseparameter expression and lymphangiogenesis and angiogenesis. COX-2 andVEGF,VEGF-C expressions were detected in 86 gastric cancer samples by immunostaining. CD34-stained microvessel density and LYVE-1-stainedLymphanigovessel density were detected by immunohistochemical methods inspecimens. The correlations among COX-2 expression, MVD,LVD andclinicopathological features were analyzed. The COX-2 and VEGF,VEGF-Cpositive rate and MVD,LVD in gastric cancer were significantly higherthan those in the normal gastric mucosa. The expression of all in thepatients with stageⅢandⅣand with lymph node metastasis weresignificantly higher (P<0.01). The Spearman rank correlation test showeda significant correlation between COX-2 expression and tumor MVD,LVD(P<0.01). This finding suggests in gastric cancer, the expression ofCOX-2,VEGF and VEGF-C are significantly associated with angiogenesisand lymphangiogenesis. COX-2 may up-regulate the expression of VEGF andVEGF-C, which induces lymphangiogenesis and accordingly contributes totumor invasion and lymph node metastasis.In order to investigate whether there is constitutive activation ofNF-κB and study expression of COX-2, MMP-7 and NF-κB in the gastriccancer and their relation with pathological grades and clinical stages.Gastric tissue specimens were obtained from 46 cases with normal gastricmucosa and gastric cancer. The protein expression of NF-κB p50, p65 weredectected by Western blot. The mRNA expression of COX-2, MMP-7 and NF-κB p65, p50 mRNA were determined by RT-PCR. We can confirmed that therewas constitutive activation by the protein expression of NF-κB p50, p65in cell nucler. The relationship between the COX-2, MMP-7 and NF-κBp65, p50 and clinicopathological should be analyzed. Positive rate ofCOX-2,MMP-7 and NF-κB p50, p65 in GC were high significantly than NGMcontrols (P<0.01).There was a significiant difference between GC and NGMon the expression of mRNA and protein; Expression of COX-2,MMP-7 andNF-κB p50, p65 were closely correlated with TNM's classification andlymphnode and distal metastasis. This finding suggests there was constitutive activation in human GC. Expression levels of COX-2, MMP-7and NF-κB may be helpful for evaluating maglignant degree of GC andlymphnode metastasis.
Keywords/Search Tags:Gastric tumor, Clinical, VEGF, VEGF-C, Immunohistochemmistry CD4~+CD25~+ regulatory T cells, Cyclooxygenase-2, NF-κB, Real-time RT-PCR
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