Effect of synergistic polarization macrophage modulated by N-terminal domain of a2 vacuolar ATPase and macrophage colony stimulating factor on proliferation of gastric cancer cells / 中华胃肠外科杂志

<p><b>OBJECTIVE</b>To investigate the synergistic effect between the N-terminus domain of the a2 isoform of vacuolar ATPase (a2NTD) and macrophage colony-stimulating factor (M-CSF) on modulating macrophage polarization and the impact of polarized macrophages on proliferation of gastric cancer cells.</p><p><b>METHODS</b>Peripheral blood mononuclear cells were derived from healthy donor and induced into macrophages. Then macrophages were randomly divided into four groups: the control group (RPMI 1640), the experimental group I (M-CSF 100 μg/L), the experimental group II (a2NTD 500 μg/L) and the experimental group III (a2NTD 500 μg/L plus M-CSF 100 μg/L). After stimulation for 48 hours, double color immunofluorescence cytochemistry was adopted to detect the expression of cell membrane molecules on macrophages; ELISA was used to measure the secretion of cytokines IL-10 and IL-12; CCK-8 assay was used to evaluate the impact of macrophages on proliferation ability of gastric cancer cell strain SGC-7901.</p><p><b>RESULTS</b>The expression of CD68, also known as macrophage surface antigen, was detected on macrophage membrane in all four groups (+). The mean absorbance (A) was 0.092 ± 0.005 in control group, 0.095 ± 0.006 in group I, 0.094 ± 0.005 in group II, 0.094 ± 0.005 in group III, and no significant differences were observed among 4 groups (all P>0.05). Meanwhile, the expression of CD206, which mainly exists on M2 macrophage membrane, was hard to detect in control group (-) with A 0.025 ± 0.004; it was normal in groupI and group II (+) with A 0.191 ± 0.012 in group I and 0.197 ± 0.136 in group II (P=0.212), and it was up-regulated significantly in group III (+++) with A 0.285 ± 0.011. There were significant differences between either two groups except group I and group II (all P<0.01). Secretion of IL-10 in group I and group II [(85.65 ± 13.64) ng/L and (87.77 ± 14.25) ng/L] was significantly higher compared with control group [(71.67 ± 7.56) ng/L, P<0.01]. Secretion of IL-12 in group I and group II [(9.91 ± 1.50) ng/L and (10.15 ± 1.80) ng/L] was significantly lower compared with control group [(16.87 ± 1.10) ng/L, P<0.01]. Secretion of IL-10 in group III [(116.98 ± 14.27) ng/L] was the highest, and secretion of IL-12 [(5.31 ± 0.88) ng/L] was the lowest (all P<0.01). There was a synergistic effect between a2NTD and M-CSF on the secretion of both IL-10 and IL-12. Elevated proliferation of gastric cancer cell strain SGC-7901 was detected in all four groups, in which group III showed the greatest impact compared with other 3 groups (P<0.01).</p><p><b>CONCLUSIONS</b>a2NTD and M-CSF show a synergistic effect in modulating macrophage phenotype and the secretion of IL-10 and IL-12. The polarized macrophage can significantly enhance proliferation of gastric cancer cell strain SGC-7901.</p>

The effect of expressions of ERCC1on neoadjuvant chemotherapy and prognosis in advanced gastric cancer / 中华普通外科杂志

ObjectiveTo investigate theeffectof expression of excision repair cross complementing 1(ERCC1) on adjuvant chemotherapy and prognnsis in advanced gastric cancer.MethodsIn this study 88 advanced gastric cancer cases were divided into initial neoadjuvant chemotherapy group (45 patients) and upfront surgical group (43 cases).In neoadjuvant chemotherapy group two courses neoadjuvant chemotherapy with XELOX were given before an interval standard radical gastrectomy.Postoperatively another four cycles of chemotherapy with XELOX were given; In upfront surgical group standard radical gastrectomy was done followed by 6 cycles of postoperative chemotherapy with XELOX;Patients in the two groups were followed up for 3 years.ResultsERCC1positive expression were 49％ and 44％ in neoadjuvant group and surgical patients; Response rate in neoadjuvant chemotherapy group was 49％.Patients with ERCClnegative expression were more sensitive to chemotherapy (P ＜0.05 ); 3-year recurrence-free survival rate in patients with ERCC1negative expression was 64％,which was significantly higher than 30％ in patients with positive expression,the difference was statistically significant (P ＜ 0.05 ) ;3-year recurrence-free survival rate in initial surgical group patients with ERCCl-negative expression was 79％,significantly higher than in patients with positive expression (38％),the difference was statistically significant (P ＜0.05) ; Cox regression analysis revealed that ERCC1expression is closely related to 3-year disease-free survival ( P ＜ 0.05 ). ConclusionsERCC1expression in patients with advanced gastric cancer is related to chemosensitivity and prognosis,it can forecast the prognosis and chemotherapy sensitivity.