Treatment of paclitaxel and doxorubicin changes the immune microenvironment of breast cancer and inhibits the growth of tumor cells in mice / 细胞与分子免疫学杂志

Objective To investigate the effects of paclitaxel and doxorubicin on the immune microenvironment of breast cancer in mice. Methods The CTR-DB database, a database for analysis of gene expression profiles and drug resistance characteristics related to tumor drug response, was used to analyze the effect of chemotherapeutic drugs on the immune microenvironment of breast cancer. Mouse models with breast cancer were established by in situ injection with 4T1 cells, a triple-negative breast cancer (TNBC) cells. Then they were treated with doxorubicin and paclitaxel, respectively. The sizes of tumor were recorded and analyzed by growth curve. The number of different types of immune cells was analyzed using flow cytometry. The expressions of Ki67, S100 calcium binding protein A9 (S100A9) and matrix metalloproteinase 9 (MMP9) were detected by immunohistochemistry. The cell cycles of 4T1 cells in paclitaxel group and doxorubicin group were analyzed by flow cytometry. Results The results of CTR_Microarray_75 analysis showed that the immune scores, and the number of cytotoxic lymphocytes, B lineages, CD8+ T cells, dendritic cells (DCs), monocytic lineages and natural killer (NK) cells in chemotherapy-sensitive breast cancer were higher than those in chemotherapy-insensitive breast cancer. Through growth curve analysis in mice with breast cancer, we found that both paclitaxel and doxorubicin could inhibit the increase of the tumor sizes, and the paclitaxel showed a higher inhibitory effect. The results of cytometry displayed that both paclitaxel and doxorubicin could restrain the expression of Ki67 and increase the number of breast cancer cells in G2/M phase, and in the paclitaxel group, the expression of Ki67 was lower and the number of breast cancer cells in G2/M phase was larger. Paclitaxel and doxorubicin enhanced the infiltration of CD45+ immune cells but decreased the infiltration of neutrophils. Additionally, paclitaxel promoted the infiltration of CD3+CD4+ T helper cells, CD3+CD8+ cytotoxic T cells and CD45+CD19+B cells, while doxorubicin increased the infiltration of CD4+CD25+ regulatory T cells (Tregs). The results of immunohistochemistry displayed that the paclitaxel significantly inhibited the expression of S100A9, while the doxorubicin significantly restrained the expression of MMP9. Conclusion Paclitaxel and doxorubicin can effectively inhibit the growth of breast cancer cells and change immune microenvironment of TNBC by regulating the different patterns of cell infiltration and the expression of different extracellular matrix components.

Maternal iron status in the first trimester is associated with gestational diabetes mellitus and macrosomia / 中华健康管理学杂志

Objective:To evaluate the association of maternal nutrition status in the first trimester with gestational diabetes mellitus (GDM) and macrosomia.Methods:378 pregnant women who took prenatal care in Shunyi Women′s and Children′s Hospital of Beijing Children′s Hospital were enrolled in the study. Blood samples were collected at first prenatal visit (<12 gestation weeks) to measure the level of hemoglobin and iron status indexes including serum iron, ferritin, transferrin, total iron binding capacity, iron saturation, transferrin saturation. The incidence of GDM and macrosomia were collected and Logistic regression was used to evaluate the associations of maternal nutrients status in the first trimester with GDM and macrosomia.Results:The incidence rate of GDM was16.9%,the incidence of anemia and iron deficiency in the first trimester were2.4% and 2.5%, respectively. After adjustment for variables such as maternal age, pre-pregnancy BMI, family history of diabetes, and parity, Logistic regression showed that in the first trimester, iron saturation>50% ( OR=0.238, 95% CI 0.068-0.831), transferrin saturation>50% ( OR=0.08, 95% CI 0.010-0.677) were protective factors of GDM; iron saturation 25%-50% ( OR=0.361, 95% CI 0.143-0.908); transferrin saturation 25%-50% ( OR=0.383, 95% CI 0.165-0.891); ferritin>30 ng/ml ( OR=0.418, 95% CI0.186-0.939) were protective factors of macrosomia. Conclusion:Maternal iron status in the first trimester might be associated with GDM and macrosomia. Thus, maternal iron status assessment in the first trimester is necessary.