BackgroundExtracellular matrix protein 1 (ECM1) and vascular endothelial growth factor-C (VEGF-C) are secretory glycoproteins that are associated with lymphangiogenesis; these proteins could, therefore, play important roles in the lymphatic dissemination of tumors. However, very little is known about their potential roles in lymphangiogenesis. The aim of this study was to investigate whether correlations exist between ECM1 and VEGF-C in human breast cancer, lymphangiogenesis, and the clinicopathological characteristics of the disease.MethodsECM1 and VEGF-C mRNA and protein expression levels in 41 patients were investigated using real-time reverse transcriptase polymerase chain reaction (RT-PCR), or immunohistochemical (IHC) staining of breast cancer tissue, matched noncancerous breast epithelial tissues, and suspicious metastatic axillary lymph nodes. D2-40 labelled lymph vessels and lymphatic microvessel density (LMVD) were counted. Correlations between ECM1 or VEGF-C protein expression levels, LMVD, and clinicopathological parameters were statistically tested.ResultsThe rate of ECM1 positive staining in breast cancer tissues was higher (31/41, 75.6%) than that in the corresponding epithelial tissues (4/41, 9.8%, P < 0.001) and lymph nodes (13/41, 31.7%, P < 0.001). Similarly, the VEGF-C expression rate in cancer specimens was higher (33/41, 80.5%) than in epithelial tissues (19/41, 46.3%, P < 0.01) or lymph nodes (15/41, 36.6%, P < 0.01). Higher ECM1 and VEGF-C mRNA expression levels were also detected in the tumor tissues, compared to the non-cancerous tissue types or lymph nodes (P < 0.05). ECM1 protein expression was positively correlated with the estrogen receptor status (P < 0.05) and LMVD (P < 0.05). LMVD in the ECM1- and VEGF-C-positive tumor specimens was higher than that in the tissue types with negative staining (P < 0.05).ConclusionsBoth ECM1 and VEGF-C were overexpressed in breast cancer tissue samples. ECM1 expression was positively correlated with estrogen responsiveness and the metastatic properties of breast cancer. We conclude, therefore, that ECM1 and VEGF-C may have a synergistic effect on lymphangiogenesis to facilitate lymphatic metastasis of breast cancer.

BackgroundMatrix metalloproteinase 9 (MMP-9) is a type-IV collagenase that is highly expressed in breast cancer, but its exact role in tumor progression and metastasis is unclear.Methods MMP-9 mRNA and protein expression was examined by real-time reverse transcriptase PCR and immunohistochemical staining, respectively, in 41 breast cancer specimens with matched peritumoral benign breast epithelial tissue and suspicious metastatic axillary lymph nodes. Lymph vessels were labeled with D2-40 and lymphatic microvessel density (LMVD) was calculated. Correlation of MMP-9 protein expression with clinicopathological parameters and LMVD was also evaluated.ResultsMMP-9+ staining in breast cancer specimens (35/41, 85.4%) was higher than in matched epithelium (21/41, 51.2%; P<0.05) and lymph nodes (13/41, 31.7%; P<0.001). Higher MMP-9 mRNA expression was also detected in tumor specimens compared with matched epithelial tissues and lymph nodes (P<0.05). Elevated MMP-9 expression was correlated with lymph node metastasis and LMVD (P<0.05).ConclusionMMP-9 was overexpressed in breast cancer specimens compared with peritumoral benign breast epithelium and lymph nodes. Moreover, its expression in the matched epithelium and lymph nodes was positively associated with lymph node metastasis, and its expression in lymph nodes was positively associated with lymphangiogenesis in breast cancer. Thus, MMP-9 is a potential marker for breast cancer progression.

Breast cancer is one of the most common malignant tumors in women and it is the most frequently diagnosed cancer in the world. Ampelopsin (AMP) is a purified component from the root of Ampelopsis grossedentata. It is reported that AMP could significantly inhibit the proliferation of breast cancer cells. However, the antitumor mechanism against breast cancer has not yet been fully elucidated. The purpose of this work was to study the role of AMP against breast cancer MDA-MB-231 cells and to further investigate the underlying mechanism. PI3K/AKT/mTOR plays a very important role in tumor cell growth and proliferation and we hypothesize that AMP may inhibit this pathway. In the present work, the results showed that AMP could significantly inhibit the growth of breast cancer MDA-MB-231 cells in vitro and in vivo. In addition, treatment with AMP decreased the levels of PI3K, AKT and mTOR, as well as cyclin B1 expression, followed by p53/p21 pathway activation to arrest the cell cycle at G2/M. Moreover, it demonstrated a positive association between cyclin B1 and PI3K/AKT/mTOR levels. Importantly, this pathway was found to be regulated by cyclin B1 in MDA-MB-231 cells treated with AMP. Also, it was observed that cyclin B1 overexpression attenuated cell apoptosis and weakened the inhibitory effects of AMP on cell proliferation. Together, AMP could inhibit breast cancer MDA-MB-231 cell proliferation in vitro and in vivo, due to cell cycle arrest at G2/M by inactivating PI3K/AKT/mTOR pathway regulated by cyclin B1.

Objective. To investigate the effect of stereotactic radiotherapy (SBRT) combined with thermoplastic fixation on set-up error in breast cancer (BC) patients undergoing radiotherapy. Methods. Ninety BC patients undergoing radiotherapy who were treated in our hospital (May 2019-May 2020) were selected as the research objects and equally divided into the experimental group and control group according to the order of hospitalization, with 45 patients in each group. The control group received conventional radiotherapy combined with breast bracket, and the experimental group received SBRT combined with thermoplastic fixation. The incidences of adverse reactions, 1-year survival rates, and set-up errors were compared between the two groups. Results. Compared with the control group, the experimental group had much lower total incidence of adverse reactions and remarkably higher 1-year survival rate. The translational errors ( X direction, Y direction, and Z direction), translational errors after rotation ( X direction, Y direction, and Z direction), and rotation errors ( X direction, Y direction, and Z direction) in the experimental group were obviously lower compared with those in the control group. Conclusion. Implementing SBRT combined with thermoplastic fixation in BC patients undergoing radiotherapy can effectively improve set-up efficiency and treatment accuracy and reduce set-up errors. Compared with the breast bracket, the combination of SBRT and thermoplastic fixation has higher application value, and further studies are conducive to providing patients with a better solution plan.

Purpose: To evaluate the in vitro and in vivo effects of the combination therapy of histone deacetylases (HDAsC) inhibitor, chidamide, and bromodomain-containing proteins (BETs) inhibitor, PFI-1, on triplenegative breast cancer (TNBC). Methods: Four distinct breast cancer cell lines and one TNBC mouse model were treated with vehicle, chidamide, PFI-1 alone, or chidamide and PFI-1. The inhibitory effect of chidamide or PFI-1 on HDACs and BETs was assessed by HDAC enzyme inhibition and AlphaScreen assays. Cell viability was determined by MTT assay while protein expression of p-STAT3 was evaluated by western blotting and immunohistochemistry (IHC) staining assay. Results: Chidamide exerted inhibitory effect on HDACs while PFI-1 inhibited BET proteins. The threedimensional model demonstrated the interactions between chidamide and HDAC2, and between PFI-1 and BRD4. Chidamide or PFI-1 exerted inhibitory effects on breast cancer cell proliferation in vitro. However, the combination of PFI-1 and chidamide significantly inhibit MDA-MB-231 cell viability, and decrease the expression of p-STAT3, when compared to that treated with chidamide or PFI-1 alone. Moreover, the combined inhibitory effect of PFI-1 and chidamide on tumor growth was also found in the in vivo mice experiments. Conclusion: The combination of chidamide and PFI-1 is a potential is a potential therapeutic strategy for the management of TNBC. Keywords: Triple-negative breast cancer, Histone deacetylases, Bromodomain