| Part Ⅰ The impact of neoadjuvant chemotherapy with FLEP regimen on the therapeutic effects of gastric carcinoma patientsObjective:Giving FLEP neoadjuvant chemotherapy to gastric cancer patients, and comparing the changes of tumor tissue pathology and imaging before and after chemotherapy, to evaluate the therapeutic effects of FLEP neoadjuvant chemotherapy for gastric cancer.Methods and materials:Collecting36cases of advanced gastric cancer admitted in general surgery fron Guangdong Medical college affiliated hospital(July2012to June2013). Randomly dividing them into two groups (18cases in each group):the experimental group (FLEP NACT+surgery+postoperative adjuvant chemotherapy group, the CSC group) and control group (surgery+postoperative adjuvant chemotherapy group, the group S). FLEP-based NACT for2～4cycles, and evaluating the clinical stage after2or4cycles of NACT. Routine postoperative adjuvant chemotherapy after surgery.Results:In18cases from group CSC, four people were complete remission,10 people partially alleviated and four people had no progress. The effective rate was77.8%(14/18). The clinical stage of gastric cancer reduced in group CSC. Compared with S group, the RO resection rate increased significantly, lymph node metastasis reduced and tumor infiltrating significantly narrowed down in group CSC. According to the grading evaluation criterion of NCI-CTC adverse reactions, the numbers of leucocytes were on the low side in2patients after chemotherapy, skin pigmentation occured in1case, belonging to the adverse reaction grade Ⅰ. No patient had Ⅲ magnitude adverse reactions.Conclusions:FLEP-based neoadjuvant chemotherapy can significantly reduce the clinical stage of gastric cancer, reduce lymph node metastasis, and improve the radical resection opportunities of gastric cancer. At the same time, FLEP-based neoadjuvant chemotherapy do not increase the risk of surgical complications, the difficulty of gastric cancer surgery and has no obvious effects on the recovery of postoperative patients.Part Ⅱ The impact of neoadjuvant chemotherapy FLEP on biological behavior of gastric cancer tumor cellsObjective:Giving FLEP neoadjuvant chemotherapy to gastric cancer patients, and detecting tumor cell apoptosis index (AI), MVD and PCNA expression level, to discusses the effects of FLEP neoadjuvant chemotherapy on apoptosis induction, cell proliferation inhibition and tumor angiogenesis and help evaluate and judging treatment effects and prognosis.Methods and materials:Collecting36cases of advanced gastric cancer admitted in general surgery fron Guangdong Medical college affiliated hospital(July2012to June2013). Randomly dividing them into two groups (18cases in each group):the experimental group (FLEP NACT+surgery+postoperative adjuvant chemotherapy group, the CSC group) and control group (surgery+postoperative adjuvant chemotherapy group, the group S). FLEP-based NACT for2-4cycles, and evaluating the clinical stage after2or4cycles of NACT. Routine postoperative adjuvant chemotherapy after surgery.Results:There are significant differences between AI of gastric cancer tumor cells in group CSC and S, indicating higher AI of gastric cancer tumor cells after neoadjuvant chemotherapy. There are also significant differences between the positive rate of PCNA expression of gastric cancer tumor cells in group CSC and S, indicating lower PCNA expression of gastric cancer tumor cells after neoadjuvant chemotherapy.Detecting MVD of group CSC and S showed significant differences, suggesting lower MVD after neoadjuvant chemotherapy.Conclusions:FLEP neoadjuvant chemotherapy can induce apoptosis of advanced gastric cancer tumor cells, inhibit gastric cancer tumor cell proliferation and tumor angiogenesis, reaching effective treatment. Tumor microvascular formation and cell proliferation can be important indexes for judging therapeutic effects prognosis of FLEP-based neoadjuvant chemotherapy for malignant tumor.Part Ⅲ The impact of neoadjuvant chemotherapy FLEP on CD4+CD25+regulatory T cells in the peripheral blood of patients with gastric cancerObjective:Giving FLEP neoadjuvant chemotherapy to gastric cancer patients, and analyzing the ratio of CD4+CD25+regulatory T (Treg) cells peripheral blood, the ability of CD4+CD25+Treg cells suppressing T cell proliferation and immune suppression secreted factors of CD4+CD25+Treg cells, to clear the association between CD4+CD25+Treg cells and clinical stage of gastric cancer, and its role in FLEP neoadjuvant chemotherapy for gastric cancer.Methods and materials:Collecting peripheral blood of healthy people and patients in group CSC and S for separation of peripheral blood mononuclear cells (PBMCs). Then testing proportions of CD4+CD25+Treg cells in peripheral blood by flow cytometry and separating CD4+CD25+Treg cells from peripheral blood by MACs. Detecting the purity of sorted CD4+CD25+Treg cells, the cell vitality by trypan blue staining, and proliferation in vitro by H mixed method. Analyzingthe ability of CD4+CD25+Treg cells suppressing T cell proliferation in vitro by mixed lymphocyte reaction. Detecting immune suppression secreted factors of CD4+CD25+Treg cells by flow cytometry and ELISA.Results:Compared with Ⅰ, Ⅱ stage gastric cancer, the proportion of CD4+CD25+Treg cells in peripheral blood from Ⅲand IVgastric cancer patients increased significantly, the proportion of CD4+CD25+Treg cells in peripheral blood from gastric cancer patients is higher than healthy people; the proportion in group CSC after neoadjuvant chemotherapy decreased; compared with the group S, the proportion in group CSC also decreased, suggesting that neoadjuvant chemotherapy can significantly reduce the proportion of CD4+CD25+Treg cells in peripheral blood from gastric cancer patients. CD4+CD25+Treg cells can significantly inhibit the CD4+CD25"T cells proliferation, and the ability increased accordingly with the increasing number of CD4+CD25+Treg cells; after neoadjuvant chemotherapy, the ability of CD4+CD25+Treg cells suppressing T cell proliferation dropped significantly. CD4+CD25+Treg cells from gastric cancer could secrete higher TGF-P, IL-4and IL-10level than healthy people; after neoadjuvant chemotherapy, immune suppression secreted factors of CD4+CD25+Treg cellsdecreased.Conclusions:The higher the staging of gastric cancer is associated with higher proportion of CD4+CD25+Treg cells in peripheral blood. Neoadjuvant chemotherapy can significantly lower the ratio of CD4+CD25+Treg cells in gastric cancer patients, inhibit the ability of CD4+CD25+Treg cells suppressing T cell proliferation, and impair immune suppression secreted factors of CD4+CD25+Treg cells, indicating an important mechanism for neoadjuvant chemotherapy to achieve therapeutic effects by modulating the immune responses. |
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