Abstract

Introduction. Serum chemokines are inflammatory mediators, which role is shown in the occurrence and progression of a number of malignant tumors. Produced by white blood cells, stem cells, tumor and endothelial cells, chemokines control their movement and positioning. Chronic inflammation underlies the progression of ovarian cancer (OC ). This increases the likelihood of chemokines stimulating or blocking tumor progression.The aim of the study was to evaluate the relationship between the blood levels of inflammatory cytokines in blood and the number of circulating tumor cells (CTC s) with the response to standard chemotherapy (CT ) in patients with cancer.Material and Methods. In patients with primary OC before and after 2–4 courses of chemotherapy and in patients with benign ovarian tumors (as a control), serum levels of CCL 2, CCL 3, CCL 4, CXCL 8 and CX3CL 1 were evaluated by multiplex xMAP analysis. The amount of CTC s (population CD 45-/ Epcam+/CK+) was determined using a flow cytometer. Patients with ovarian cancer were divided into 3 groups according to the platinum sensitivity criterion of GC JG 4th, and progression-free interval (PFI) was determined. Results. It was found that the levels of CCL 2, CCL 3, CCL 4, CXCL 8, and CX3CL 1 in case of OC did not significantly differ from that in the control, strongly negatively correlated with age (except for the CCL 2 level). CT significantly increased the level of CCL 2 in the group of refractory OC ; of CCL 3 – in the group of sensitive OC , of CCL 4 – in the groups of resistant and sensitive OC , and C XCL 8 level increased in the groups with resistant and sensitive OC and decreased in the group of refractory OC . The number of CTC s in patients with OC was significantly higher than in the control. After CT , a decrease in the amount of CTC s strongly and significantly correlated with a decrease in the level of CX3CL 1 in the groups of refractory andsensitive OC . The maximum PFI occurred with an increase in serum levels of CCL 3, CXCL 8, a decrease in CCL 4 and a constant level of CX3CL 1.Conclusion. Thus, no significant differences in the levels of CCL 2, CCL 3, CCL 4, and IL -8 between patients with OC and control groups were found. The levels of chemokines studied and the amount of CTC s differed in the groups divided by the tumor sensitivity to CT . We observed significant correlations between the amount of CTC s and the level of CX3CL 1 in the group of platinumsensitive OC .

Highlights

  • Serum chemokines are inflammatory mediators, which role is shown in the occurrence and progression of a number of malignant tumors

  • The aim of the study was to evaluate the relationship between the blood levels of inflammatory cytokines in blood and the number of circulating tumor cells (CTCs) with the response to standard chemotherapy (CT) in patients with cancer

  • In patients with primary ovarian cancer (OC) before and after 2–4 courses of chemotherapy and in patients with benign ovarian tumors, serum levels of CCL2, CCL3, CCL4, CXCL8 and CX3CL1 were evaluated by multiplex xMAP analysis

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Summary

After CT

Примечание: р – различия значимо отличаются по сравнению с показателями до ХТ. Note: p – statistically significantly different compared with corresponding data before CT. При анализе динамики уровней хемокинов на фоне платиносодержащей ХТ с позиций продолжительности периода до прогрессирования было выявлено, что при повышении уровня CCL3 после 3 курсов ХТ PFI статистически значимо увеличивался и составлял в среднем 315 дней (р=0,046) Induction of the MCP chemokine cluster cascade in the periphery by cancer cell-derived Ccl. Detection of circulating tumor cells in breast cancer patients utilizing multiparameter flow cytometry and assessment of the prognosis of patients in different CTCs levels. Hypoxia-inducible factor-1α induces CX3CR1 expression and promotes the epithelial to mesenchymal transition (EMT) in ovarian cancer cells. Identification of the chemokine CX3CL1 as a new regulator of malignant cell proliferation in epithelial ovarian cancer. Circulating levels of transforming growth factor-βeta (TGF-β) and chemokine (C-X-C motif) ligand-1 (CXCL1) as predictors of distant seeding of circulating tumor cells in patients with metastatic breast cancer.

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