Objective:To explore the association of tumor associated macrophages (TAM) with tumor invasiveness, metastasis and prognosis in cardia carcinoma tissues.Methods:The cancer tissues and pericarcinomatous tissues of 100 patients with cardia carcinoma who underwent D2 radical operation in the First Hospital of Putian City from January 2014 to January 2015 were collected. M2-type TAM was marked with CD163. The tissue microarray was made and the expression of CD163 in microarray tissues was detected by using immunohistochemistry. The median number of CD163 positive cells in all cancer tissues was taken as the cut-off value. The patients with the mean number of CD163 positive cells ≥ the cut-off value were those with high TAM infiltration, and vice versa. The association of TAM infiltration with clinicopathological features and prognosis was analyzed, and Cox proportional hazards model was used for multivariate analysis of survival.Results:The positive cell median number of CD163 in cardia carcinoma tissues was higher than that in adjacent tissues [the median number ( P25, P75): 32/high power field (HP) (16/HP, 46/HP) vs. 6/HP (4/HP, 11/HP)], and the difference was statistically significant ( Z = -35.044, P < 0.01). There were 48 cases in low invasive group (< 32/HP) and 52 cases in high invasive group (≥32/HP). The proportion of patients with high TAM infiltration in serosa and extraserosa was higher than that in mucosa and muscle [60.9% (39/64) vs. 36.1% (13/36)], and the proportion of patients with high TAM infiltration for patients with lymph node metastasis was higher than that for patients without lymph node metastasis [61.8% (42/68) vs. 31.3% (10/32)], and the proportion of patients with high TAM infiltration for those with TNM stage Ⅲ-Ⅳ was higher than that for those with TNM stage Ⅰ-Ⅱ [64.4% (38/59) vs. 34.1% (14/41)], and the differences were statistically significant (all P < 0.05). The median overall survival time of high TAM group was shorter than that of low TAM group [24.00 months (95% CI 17.25-43.50 months) vs. 62.00 months (95% CI 34.00-68.00)], and the difference in overall survival was statistically significant (χ 2 = 18.137, P < 0.01). Lymph node metastasis ( HR = 0.301, 95% CI 0.105-0.862, P = 0.025), TNM staging ( HR = 8.404, 95% CI 2.810-25.133, P < 0.01) and TAM infiltration level in cancer tissues ( HR = 4.277, 95% CI 2.372-7.712, P < 0.01) were independent influencing factors for overall survival of patients. Conclusions:TAM plays an important role in the invasion and metastasis of cardia carcinoma and can be used as an independent predictor of biological behavior and prognosis in cardia carcinoma.

Objective To explore the relationship of the methylation levels of tissue inhibitor of metalloproteinases 3 (TIMP-3) gene promoter CpG islands with the invasiveness and prognosis in cardia carcinoma. Methods The tumors tissues were collected from 65 patients with cardia carcinoma. The methylation levels of the promoter of TIMP-3 gene were detected by methylation-specific PCR (MSP), the mRNA expression levels of TIMP-3 gene were detected by RT-PCR. The relationship of TIMP-3 gene ectopic methylation with invasiveness and prognosis of the cardia carcinoma patients was analyzed. Results The positive expression rates of TIMP-3 mRNA in gastric cancer and normal gastric tissues were 53.8 % (35/65) and 96.9 % (63/65), respectively. The difference was not statistically significant(Fisher exact test, P=0.912). The positive rate of TIMP-3 mRNA was negatively correlated with the depth of tumor invasion and lymph node metastasis [mucosa and muscular vs. serosa and mucosa outside of the serosa and muscula: 83.3 % (10/12) vs. 45.3 % (24/53); with lymph node metastasis vs. without lymph node metastasis: 73.9 % (17/23) vs. 40.5 %(17/42)] (both P<0.05). There was a negative correlation between TIMP-3 gene promoter methylation and TIMP-3 mRNA expression (r=-0.276, P=0.026). The size of tumor and TIMP-3 gene promoter methylation were both the independent influencial factors of prognosis in cardia carcinoma (both P<0.05). Conclusion The methylation of promoter region in CpG islands plays an important role in the invasion and metastasis of cardia carcinoma, and it can be used as an independent predictor of biological behavior and prognosis.

Objective To explore the relations among the promoter methylation of tissue inhibitor of metalloproteinase-3 (TIMP-3) gene and its protein expression, and the clinicopathological features in the gastric cardia carcinoma. Methods The tumor tissues and the adjacent normal mucosal tissues were collected from 65 patients with cardia carcinoma. The promoter methylation levels and the protein expression of TIMP-3 gene were detected by methylation-specific PCR (MSP) and immunohistochemistry respectively. Results The TIMP-3 methylation rates was 78.5 % (51/65) in the tumor tissues and 13.8 % (9/65) in the incisal edge of normal tissues, the methylation rates of TIMP-3 had positive correlation with the size of tumor, invasion depth, lymphatic metastasis and the stage of tumor. The protein expression of TIMP-3 was 26.2 %(17/65) in the tumor tissues and 95.4 % (62/65) in the incisal edge of normal tissues (P = 0.016), the protein expression of TIMP-3 was negatively correlated with the size of tumor, invasion depth, lymphatic metastasis and the stage of tumor. Conclusion The methylation of promoter region in CpG islands is a main mechanism of reduced and loss expression of TIMP-3 gene, which may play an important role in the invasion and metastasis of cardia carcinoma.

AIM:To explore the mechanism by which over-expression of enhancer of zeste homolog 2 (EZH2) in a panel of gastric cancer cell lines is involved in tumorigenesis of gastric cancer .METHODS: Real-time PCR and Western blot were employed to examine the mRNA and protein levels of EZH 2, respectively.MTS assay, cell migration and soft agar assay were performed to investigate the role of EZH 2 in the regulation of stomach cancer behaviors .The effect of EZH2 on NF-κB target gene expression was determined by Luciferase reporter and real-time PCR.Co-immunoprecipitati-on was used to analyze the interaction of EZH 2 and p65 in HEK293T cells.RESULTS: The expression levels of EZH2 were significantly increased in the gastric cancer cells compared with normal gastric epithelial cells .Pharmacological inhibi-tion by DZNep or knockdown of EZH2 significantly compromised AGS and SNU-16 cell activity , cell migration and anchor-age-independent cell growth.Moreover, siRNA knockdown of EZH2 impaired NF-κB downstream targets, such as IL-8, CXCL5 and CCL20.In addition, the interaction of EZH2 and p65 was detected.CONCLUSION: EZH2 mediates the growth of gastric cancer cells through the regulation of NF-κB downstream gene expression .

BACKGROUNDTo evaluate the effect of ⁸⁹SrCl₂ and/or Bonefos in the treatment of bone metastasis from pulmonary carcinoma.

METHODSA total of sixty-seven lung cancer patients with bone metastasis were enrolled in this study, who were divided into three groups: nineteen cases were treated with ⁸⁹SrCl₂; twenty-eight cases with Bonefos; and twenty cases combined ⁸⁹SrCl₂ with Bonefos.

RESULTSThe total relief rate of the bone pain: the ⁸⁹SrCl₂ group was 84.2%, and the Bonefos group was 80.4%, the combination group was 90.0%. There was no statistical difference among three groups (P > 0.05). The effective rate of the bone metastasis: the ⁸⁹SrCl₂ group was 15.7%, the Bonefos group was 10.7%, and the combination group was 45.0%. The combination group had significantly higher effective rate than that of the ⁸⁹SrCl₂ group or the Bonefos group alone (P < 0.05). The rate of improvement of quality of life: the ⁸⁹SrCl₂ group was 47.3%, the Bonefos group was 42.8%, and the combination group was 80.0%. The combination group had significantly higher effective rate than that of the ⁸⁹SrCl₂ group or the Bonefos group alone (P < 0.05). The side effects of three groups were minimal.

CONCLUSIONS⁸⁹SrCl₂ and Bonefos are two effective and safe drugs on relief of pain. Combined ⁸⁹SrCl₂ and Bonefos might be a better therapy for bone metastasis and improvement of quality of life than the single one, and the side effect is slight and tolerable.

Objective     To explore the correlation between the quantitative and qualitative features of CT images and the invasiveness of pulmonary ground-glass nodules, providing reference value for preoperative planning of patients with ground-glass nodules. Methods    The patients with ground-glass nodules who underwent surgical treatment and were diagnosed with pulmonary adenocarcinoma from September 2020 to July 2022 at the Third Affiliated Hospital of Kunming Medical University were collected. Based on the pathological diagnosis results, they were divided into two groups: a non-invasive adenocarcinoma group with in situ and minimally invasive adenocarcinoma, and an invasive adenocarcinoma group. Imaging features were collected, and a univariate logistic regression analysis was conducted on the clinical and imaging data of the patients. Variables with statistical difference were selected for multivariate logistic regression analysis to establish a predictive model of invasive adenocarcinoma based on independent risk factors. Finally, the sensitivity and specificity were calculated based on the Youden index. Results     A total of 555 patients were collected. The were 310 patients in the non-invasive adenocarcinoma group, including 235 females and 75 males, with a meadian age of 49 (43, 58) years, and 245 patients in the invasive adenocarcinoma group, including 163 females and 82 males, with a meadian age of 53 (46, 61) years. The binary logistic regression analysis showed that the maximum diameter (OR=4.707, 95%CI 2.060 to 10.758), consolidation/tumor ratio (CTR, OR=1.027, 95%CI 1.011 to 1.043), maximum CT value (OR=1.025, 95%CI 1.004 to 1.047), mean CT value (OR=1.035, 95%CI 1.008 to 1.063), spiculation sign (OR=2.055, 95%CI 1.148 to 3.679), and vascular convergence sign (OR=2.508, 95%CI 1.345 to 4.676) were independent risk factors for the occurrence of invasive adenocarcinoma (P<0.05). Based on the independent predictive factors, a predictive model of invasive adenocarcinoma was constructed. The formula for the model prediction was: Logit(P)=–1.293+1.549×maximum diameter of lesion+0.026×CTR+0.025×maximum CT value+0.034×mean CT value+0.72×spiculation sign+0.919×vascular convergence sign. The area under the receiver operating characteristic curve of the model was 0.910 (95%CI 0.885 to 0.934), indicating that the model had good discrimination ability. The calibration curve showed that the predictive model had good calibration, and the decision analysis curve showed that the model had good clinical utility. Conclusion     The predictive model combining quantitative and qualitative features of CT has a good predictive ability for the invasiveness of ground-glass nodules. Its predictive performance is higher than any single indicator.