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Objective To investigate the clinical efficacy and related adverse reactions of the combination of camrelizumab with anlotinib as the third-line therapy on advanced non-small cell lung cancer. Methods We retrospectively analyzed the clinical data of 84 patients with advanced non-small cell lung cancer after second-line treatment. According to different treatment methods, 44 patients who received camrelizumab combined with anlotinib were included in the observation group, and 40 patients who received anlotinib alone were included in the control group. The PFS, ORR, DCR and incidence of adverse reactions were analyzed and compared between the two groups. Results The median PFS of the observation group was longer than that of the control group (7.0 vs. 5.6 months, P=0.001). No statistically significant difference was observed in ORR, DCR, the incidence of adverse reactions or the incidence of adverse reactions above grade 3 between two groups (all P > 0.05). Conclusion The clinical efficacy of camrelizumab combined with anlotinib as third-line therapy on advanced non-small cell lung cancer is better than anlotinib alone, and the safety is good.
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Objective@#To investigate the effect of tumor-associated macrophages on the stemness of esophageal cancer cells and the potential mechanism of antiproliferative effects of aspirin (ASA).@*Methods@#The effects of aspirin on the stemness characteristics of KYSE-450 cells and KYSE-450 cells co-cultured with M2 macrophages (KYSE-450+ M2) were performed using spheroid formation assay. After treatment with aspirin, the expression of different chemokines, the core pluripotency gene Nanog and the stem cell marker CD90 in different cell groups were determined by real-time quantitative PCR, flow cytometry and Western blot.@*Results@#The number of spheres formed in the ASA and KYSE-450+ M2 cell groups were 7.00±1.23 and 34.33±2.33, respectively, showing statistically significant difference compared with that of control group (14.50±2.33, all P<0.05). The number of spheres in KYSE-450+ M2+ ASA cell group were 20.67±2.33, which was significantly lower than that of KYSE-450+ M2 group (P<0.05). The expression levels of Nanog gene in control and ASA groups were 1.00 and 0.50±0.10, respectively, and the difference was statistically significant (P<0.05). Moreover, the expression of Nanog gene in cells of KYSE-450+ M2 group and M2+ KYSE-450+ ASA group was 1.74±0.13 and 1.43±0.05, showing statistically significant difference (P<0.05). When chemokine CCL2 was knocked down, the levels of Nanog gene in M2+ shCCL2-KYSE450+ ASA group and M2+ shCCL2-KYSE450 group were decreased to 1.22±0.11 and 1.17±0.08, respectively, and there was no statistically significant difference between them (P=0.69). Flow cytometry analyses showed that the expression levels of CD90 in control and ASA cells were (2.93±0.52)% and (1.30±0.17)%, respectively, and the difference was statistically significant (P<0.05). Moreover, the expression levels of CD90 in M2+ shCCL2-KYSE450 cells and M2+ shCCL2-KYSE450+ ASA cells were (4.07±0.12)% and (4.73±0.38)%, respectively, showing no statistically significant difference (P=0.17).@*Conclusions@#Tumor-associated macrophages enhances the stemness of esophageal cancer cells, whereas aspirin attenuates the stemness by suppressing the expression of CCL2. Aspirin plays an anti-tumor effect in esophageal cancer cells.
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Objective: To analyze the correlation of miR-625 expression with clinicopathological characteristics in esophageal squa-mous cell carcinoma (ESCC) and to explore the effect of miR-625 on the migration and proliferation of ESCC cells. Methods:The expres-sion level of miR-625 was determined through real-time PCR in 86 paired human ESCC tissue specimens and tumor-adjacent normal esophageal tissue specimens, ESCC cell lines, and esophageal epithelial cell line. The associations of miR-625 expression with clinico-pathological characteristics and survival in ESCC patients were analyzed. Transwell and CCK-8 assays were performed to examine the effect of miR-625 expression on migration and proliferation of ESCC cells. Results:Compared with tumor-adjacent normal specimens, miR-625 was significantly downregulated in ESCC tissue specimens (P<0.05). MiR-625 expression was decreased in ESCC cell lines com-pared with human esophageal epithelial cell lines (P<0.05). Lower miR-625 expression was associated with poorer prognosis and sur-vival. The migration and proliferation abilities of ESCC cells were inhibited by miR-625 overexpression (P<0.05). Conclusion:MiR-625 acts as a tumor suppressor gene in the development and progression of ESCC, suggesting that miR-625 may serve as an efficient prog-nosis biomarker and a potential therapeutic target for ESCC.
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<p><b>OBJECTIVE</b>To investigate the expression and significance of CCL5 in patients with esophageal carcinoma.</p><p><b>METHODS</b>Using reverse transcriptase polymerase chain reaction (RT-PCR), the expressions of CCL5/CD8/granzyme B/perforin in tumor and corresponding adjacent tissues from esophageal carcinoma patients were examined. Flow cytometry (FACS) was used to detect the percentages of CD8(+) T cells and CCR5(+)CD8(+) T cells in TIL and PBMC from the patients. Transwell assay was performed to study the effect of CCL5 on the migration of T cells in vitro. T test and Spearman correlation analysis were performed.</p><p><b>RESULTS</b>The mRNA expressions of CCL5 and perforin were 0.348 2 ± 0.300 1 and 0.181 9 ± 0.118 6, respectively, in the tumor samples, while their expressions in adjacent samples were 0.279 6 ± 0.138 0 and 0.118 0 ± 0.109 8, respectively, with no statistically significant differences between them (P > 0.05 for both). The mRNA expressions of CD8 and granzyme B were significantly higher in the tumor tissues than in adjacent tissues (0.464 9 ± 0.300 8 vs. 0.279 0 ± 0.173 4, 0.648 7 ± 0.516 0 vs. 0.469 7 ± 0.259 1; P < 0.05 for both). The relative expression of CCL5 was positively correlated with that of CD8, perforin and granzyme B (r(CD8) = 0.272, P = 0.034; r(perforin) = 0.305, P = 0.026; r(granzymeB) = 0.108, P = 0.012) in the tumor sites. FACS data revealed that the proportions of CD8(+) T cells in TIL and PBMC were (45.86 ± 16.09)% and (34.05 ± 15.07)%, respectively, showing a significant difference (P = 0.022). Similarly, CCR5(+)CD8(+) T cells fraction in TIL (48.12 ± 26.75)% was much higher than that in PBMC (19.53 ± 13.67) % (P < 0.001). Transwell assay showed that CCL5 protein enhanced the migration of T cells, supporting that CCL5 is crucial for CD8(+) T cells recruitment in vivo. Intriguingly, CCL5 expression was down-regulated in advanced patients (stage IIb-IV). The accumulation of CD8(+) T cells and CCR5(+)CD8(+) T cells was strongly reduced in advanced patients, suggesting that CCL5 expression may be involved in the local control of the disease and its reduction may be involved in disease progression.</p><p><b>CONCLUSIONS</b>The current data indicate the involvement of CCL5 in the regulation of CD8(+) T cell entry into tumor lesions in esophageal carcinoma patients. This process may affect the disease status and potentially as a prognostic factor for cancer patients. Enhancing local CCL5 expression in tumor lesions may represent a novel strategy in esophageal cancer therapy.</p>