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<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>
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Humanos , Proliferação de Células , Interleucina-10 , Metabolismo , Interleucina-12 , Metabolismo , Fator Estimulador de Colônias de Macrófagos , Farmacologia , Macrófagos , Biologia Celular , Fenótipo , Neoplasias Gástricas , Patologia , Células Tumorais Cultivadas , ATPases Vacuolares Próton-Translocadoras , FarmacologiaRESUMO
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.
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Objective To summarize the clinicopathological characteristics and effects of surgical treatment on gastric stump cancer.Methods With meta- analysis, clinical data of 902 gastric stump cancer patients who were treated in our hospital or were reported in literatures were included for analysis.Age, gender, pathological types, TNM stages, surgical treatment, prognosis were evaluated.Results Gastric stump cancer developed mostly in male patients (4.1∶1) , and the median age was 61 years.Incidence of gastric stump cancer after digestive tract reconstruction with Billroth- Ⅱ operative modality was higher than that with Billroth- Ⅰ (81.6% vs.17.1%).50.5% of the cancers were present at the anastomotic site, 21.7% at the gastric lesser curvature, 18.5% at the gastric cardia, and less than 10% at other places.Resection and radical resection rates were 81.3% and 62.7% , while operation combined organ resection was carried out (36.5% ).The 1-, 3-, 5- year survival rate of the patients with radical resection were significantly better than those with palliative resection, which was 77.8% vs.36.4% , 58.2% vs.9.8% and 28.9% vs.3.9% (P＜0.01) respectively.Conclusions Distal gastrectomy and Billroth Ⅱ GI tract reconstruction was the most common type of previous operation.Gastric stump cancer occurs more frequently at anastomotic site and the majority of histological types was well-differentiated adenocarcinoma.Most cases were at the advanced TNM-stage when diagnosed.Radical resection is an effective way to prolong the postoperative survival time in gastric stump cancer patients, especially in early stage.
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Objective To investigate the possibility of human umbilical cord blood mesenchymal stem cells' migrating to the gastric carcinoma xenografts. Methods Gastric cancer cells SGC-7901 were injected subcutaneously into one side of the inguinal groove in the hairless mice to establish the animal model.Gastric cancer-bearing mice were divided randomly into two groups and five in each group (n =5). Then mesenchymal stem cells and the fibroblast HFL-Ⅰ labeled with fluorescent dye SP-DiI were injected at the opposite side. Ten days later, the mice were put to death, and the gastric carcinoma xenografts, liver, spleen,lung and the tissue of injected point were obtained. Cryosections from frozen tissues were processed for fluorescent microscopy and the distribution of MSC and fibroblasts in different organs were observed. Adjacent sections were stained with HE. Results Human umbilical cord blood mesenchymal stem cells were mainly distributed in gastric carcinoma xenografts (0.0150±0.0079), but were found only a little in liver (0.0010±0.0005), spleen (0.0015±0.0012), lung (0.0014±0.0008) and injected point (0.0043±0.0039). Fibroblasts were mainly observed in the tissue of injected point, but none in other tissues (P ＜0.01). Conclusion Human umbilical cord blood mesenchymal stem cells have the tendency of migrating to tumor sites, suggesting that it can be hopefully used in the diagnosis and treatment of gastric cancer.
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Objective To study lymph node metastasis in early gastric carcinoma. Methods From July 2001 to July 2007, 177 patients with early gastric carcinoma underwent radical gastrectomy and the clinicopathologic data were analyzed by binary logistic regression. Results The overall rate of lymph node metastasis in early gastric carcinoma was 13%, involving 13% and 3% in level I (NI) and level Ⅱlymph nodes (N2), respectively. The rate of lymph node metastasis was 22%(20/89) in cases of submucosal lesion (SM), which was significantly higher than 3%(3/88) in cases of mucosal lesion (M) (X2=14. 222, P<0.01). The rate of lymph node metastasis was 3%(4/117) when the primary tumor was ≤2cmin diameter compared with 32%(19/60) when the tumor was >2cm (X2=27.992, P<0.01). The lymph node metastasis rate was 4%(3/81) and 21%(20/96) in differentiated and undifferentiated lesion (X2=11.402, P=0.001), and it was 33%(2/6)、8%(7/99) and 19% (14/92) in macroscopic type I, Ⅱ and Ⅲ (X2=8.172, P=0.014). Binarylogistic analysis found that the tumour diameter greater than 2.0cm (OR=8.408, P<0.01), infiltration of the submucosal layer (OR=5.926, P=0.009) and undifferentiated lesion (OR=4.880, P=0.020) were the independent risk factors. Conclusion Lymph node metastasis in early gastric carcinoma is significantly cantingent on the depth of infiltration, tumor size and histological type.
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Objective To review the experience on the surgical management for advanced gastric carcinoma with portal hypertension. Methods In this study, 14 advanced gastric carcinoma with portal hypertension patients were analyzed retrospectively, liver cirrhosis was found in 13 cases. In 10 esophageal variceal patients, 5 had upper gastrointestinal bleeding history. All of those cases were associated with different degree of hypersplenism. The tumours situated at the upper third of the stomach in 2 patients, middle and upper third in 2 and lower third in 10. Five patients underwent curative distal subtotal gastrectomy and splenectomy, 2 cases did radical distal subtotal gatrectomy and pericardial devascularizaion, 2 curative distal subtotal gastrectomy combined with splenic artery ligation,2 did total gastrectomy and pericardial devascularizaion,2 cases did radical proximal gastrectomy and pericardial devascularization and 1 patient did distal subtotal gastrectomy only. Results Three died from extensive wound bleeding, jejunal fistula and liver failure respectively. 3 patients were complicated by left subdiaphragmatic abscess, hepatic dysfunction and massive ascites individually. The morbidity and mortality rate were 42.86% and 21.43% respectively. Conclusion The surgical procedures for patients of advanced gastric carcinoma with portal hypertension caused a considerably high postoperative mortality and morbidity rate.
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Objective:To investigate the inhibitory effect of cytokine-induced killer cells (CIK) against implanted gastric cancer cells. Methods:Gastric cancer SGC-7901 cells were subcutaneously injected into the inguina of nude mice to establish gastric cancer model. The tumor bearing mice were randomly divided into CIK group and fibroblasts group,in which mice were subcutaneously injected with fluorescence dye SP-DiI labeled CIK and fibroblasts HFL-I cells,respectively. Distribution of CIK and HFL-I cells in different tissues of gastric cancer bearing mice were observed. Meanwhile,tumor volume was measured after different treatments and tumor inhibitory rate was calculated. Tumor necrosis areas in different groups were observed. Results:SP-DiI labeled CIK was mainly located in the gastric cancer tissues 10 d after injection,and was hardly detected at the injection sites,liver,spleen and lung tissues (P