The Relationship Between Microbial Community and Breast Cancer.

Breast cancer (BC) is the most common cancer in women and the leading cause of cancer-related deaths in women worldwide. Recent research studies have shown that the intestinal flora is related to the occurrence and progression of BC. Notably, some evidence identifies a unique microbial community in breast tissue, a site previously thought to be sterile. In addition, breast tumors have their own specific microbial community, distinct from normal mammary gland tissue, and all of them may result from intestinal flora. Some microbial community in breast tissue may lead to the occurrence and development of BC. This review focuses on the relationship between the microbial community and breast cancer, which will lay a solid theoretical foundation for further understanding the local microenvironment of BC and developing effective targeted therapeutic drugs.

The Signaling Pathways Associated With Breast Cancer Bone Metastasis.

Background: Breast cancer (BC) is now the leading cause of cancer in women, and bone is the primary site of distant BC metastasis. BC bone metastasis seriously affects the quality of life of patients and increases the mortality rate. However, the mechanism of BC bone metastasis is not fully understood. Main Body: Paget's "seed and soil" hypothesis led experts to explore the relationship between surface markers and receptors in breast tumors and various growth factors in bone. The relevant breast tumor markers serve as "seeds", and the bone microenvironment that is suitable for the survival of the tumor serves as the "soil". These factors interact to make up an entire system and form feedback pathways that accelerate the production of various cytokines, attracting BC cells to migrate to bone tissue, which worsens the development of BC and seriously affects the prognosis of patients. This process is a vicious cycle. At present, there are seven major signaling pathways involved in BC bone metastasis: the OPG/RANK/RANKL signaling pathway, TGF-ß signaling pathway, IGF system, PI3K-AKT-mTOR signaling pathway, Wnt signaling pathway and Hippo signaling pathway. In addition, FGF-FGFR signaling pathway, androgen-AR/LSD1-target gene pathway, Notch signaling pathway, JAK-STAT signaling pathway and CaN/NFATC1 signaling pathway also seem to be associated with BC bone metastasis. Conclusion: This review focuses on the signaling pathways related to BC bone metastasis and explores the interactions among these pathways, which will lay a solid theoretical foundation for further understanding the mechanism of BC bone metastasis and developing effective targeted therapeutic drugs.

Association between γδ T cells and clinicopathological features of breast cancer.

BACKGROUND: The roles of γδ T cells in patients with breast cancer (BC) have not been fully clarified, although the efficacy of gamma delta (γδ) T cells, which combine both innate and adaptive potential have extraordinary properties, such as recognizing tumor cells without the need for major histocompatibility complex (MHC) antigen presentation, as well as killing a broad range of tumor cells through their strong cytotoxic and pro-inflammatory activity, has been suggested in the majority of patients with some certain cancers. PURPOSE: To understand and dissect the association between γδ T cells and the clinical pathology of BC by measuring and analyzing the γδ T cell populations in the patients with BC. METHODS: On the one hand, γδ T cells were measured and analyzed by extracting from peripheral blood mononuclear cells (PBMC) of patients with BC. On the other hand, γδ T cells were measured and analyzed by performing enzymatic digestion in primary BC tissues, cancer adjacent tissues, and distant normal breast tissues from patients with different stages of cancer progression. In addition, patients with breast benign tumors and healthy volunteers were also collected as controls for this study. RESULTS: The proportion of γδ T cells in PBMC was significantly correlated with tumor histological grade, ER status, the proportional value of Ki-67, and lymph node (LN) metastasis. The decrease and exhaustion of γδ T cells were a general feature in the PBMC of BC patients. In addition, the primary BC tissue infiltration of γδ T cells was significantly associated with tumor histological grade, ER status, the proportional value of Ki-67, and LN metastasis. CONCLUSION: These findings suggest that γδ T cell populations are crucial for understanding the clinicopathological features of patients with BC, and may serve as a valuable and independent biomarker, as well as a potential therapeutic target for human BC.

The potential role and status of IL-17 family cytokines in breast cancer.

Breast cancer (BC) is currently the most common malignant tumor of women in the world. At present, the development of BC is accelerating and showing a younger trend, which may be due to the known and/or unknown risk factors (RFs) for BC are increasing. It has been reported that inflammatory factors promote the occurrence and development of BC. No doubt chronic inflammation could trigger a series of molecular events, which will lead to the malignant transformation of differentiated cells, inhibition of anti-tumor immunity, and finally, lead to the occurrence and metastasis of tumors. With the deepening of research, it has been found that pro-inflammatory cytokine-interleukin-17 (IL-17) is closely related to BC. It not only plays an important role in promoting tumor proliferation, invasion and metastasis, but also has a significant correlation with poor prognosis. Recently, it was reported that IL-17 is closely related to programmed death ligand 1 (PD-L1) in BC. Therefore, starting with the role of IL-17 family cytokines in BC, this paper briefly discusses the potential role and status of IL-17 and seeks to contribute to the development of targeted drugs for BC-related treatments and to the identification of prediction factors for the early detection and prognosis prediction of BC for laying a solid theoretical foundation.

Sacubitril/valsartan inhibits ox­LDL­induced MALAT1 expression, inflammation and apoptosis by suppressing the TLR4/NF­κB signaling pathway in HUVECs.

The therapeutic effect of sacubitril/valsartan (S/V) on heart failure has been confirmed, while its role in atherosclerosis remains largely unexplored. The present study aimed to investigate the effects of S/V on the expression of metastasis­associated lung adenocarcinoma transcript 1 (MALAT1), inflammation and apoptosis in human umbilical vein endothelial cells (HUVECs) induced by oxidized low­density lipoprotein (ox­LDL) and to elucidate its possible mechanism. Cell Counting Kit­8 assay was used to detect cell viability. Reverse transcription­quantitative PCR was performed to detect the MALAT1 expression. ELISA was performed to detect the levels of IL­1ß, IL­6 and TNF­α. Flow cytometry was conducted to detect the apoptotic rate of cells. A nitric oxide (NO) detection kit was used to determine the concentration of NO. Western blotting analysis was performed to determine the levels of intercellular cell adhesion molecule (ICAM)­1, vascular cell adhesion molecule (VCAM)­1, endothelin­1, caspase­3, Bax, Bcl­2, Toll­like receptor 4 (TLR4), p65 and p­p65. Compared with the ox­LDL group, S/V treatment significantly increased the cell viability, NO concentration and Bcl­2 expression, decreased the levels of IL­1ß, IL­6 and TNF­α and reduced the expressions of MALAT1, ICAM­1, VCAM­1, cleaved­caspase­3, Bax, TLR4 and p­p65. Overall, the findings suggested that S/V could downregulate the expression of MALAT1, inhibit inflammation and apoptosis and improve endothelial function in ox­LDL­induced HUVECs via inactivating the TLR4/NF­κB signaling pathway. Therefore, S/V might be utilized as a promising therapeutic strategy for the prevention and treatment of atherosclerosis.