Breast cancer is the second leading cause of cancer-related deaths among women worldwide. Many patients suffer from bone metastasis. Sclerostin, a key regulator of normal bone remodeling, is critically involved in osteolytic bone diseases. However, its role in breast cancer bone metastasis remains unknown. Here, we found that sclerostin was overexpressed in breast cancer tumor tissues and cell lines. Inhibition of sclerostin by antibody (Scl-Ab) significantly reduced migration and invasion of MDA-MB-231 and MCF-7 cells in a time-and dose-dependent manner. In xenograft model, sclerostin inhibition improved survival of nude mice and prevented osteolytic lesions resulting from tumor metastasis. Taken together, sclerostin promotes breast cancer cell migration, invasion and bone osteolysis. Inhibition of sclerostin may serve as an efficient strategy for interventions against breast cancer bone metastasis or osteolytic bone diseases.Breast cancer is the second leading cause of cancer-related deaths among women worldwide. 75-80% of patients with advanced disease develop bone metastasis 1, 2 . As an end-stage complication of breast cancer, bone metastasis frequently leads to detrimental skeletal-related events associated with significant morbidity 3-5 . Since current treatment for bone metastasis has limited efficacy, development of an effective therapeutic strategy is urgently needed. To improve the prognosis of breast cancer bone metastasis (BCBM), molecular mechanisms involved in breast cancer proliferation, invasion, metastasis and osteolytic lesions should be further explored.Sclerostin, a key regulator of normal bone remodeling, inhibits bone formation through inhibition of Wnt signaling 6,7 . Recent studies have revealed a vital role of sclerostin in multiple myeloma with osteolytic bone lesions [8][9][10][11][12] . BCBM patients exhibit a high level of circulating sclerostin, which correlates with disease stage and fractures, however, the origin and impact of sclerostin on BCBM remains to be defined. Thus, the purpose of our study was to evaluate the expression level of sclerostin in tumor tissue derived from BCBM patients and explore its association with clinical outcome and tumor characteristics, including the presence of lytic bone disease.Activation of Wnt signaling pathway has been indicated to participate in both initiation and progression of cancer metastasis 13,14 . During multiple-steps of metastasis to bone, breast cancer cells successfully induce a sequence of changes, for instance, secreting cytokines to inhibit differentiation and maturation of osteoblasts whereas to enhance the activity of osteoclasts. As such, we hypothesized that decreased sclerostin would suppress osteolytic bone lesions and reduce tumor burden, which may represent a target for inhibiting cancer-induced bone diseases and facilitating restoration of normal bone homeostasis. ResultsSclerostin is up-regulated in tumor tissues derived from patients with BCBM. To assess the expression of sclerostin in BCBM, paraffin sections of tissu...
Currently, one sixth of triple-negative breast cancer (TNBC) patients who receive docetaxel (T) and epirubicin (E) as neoadjuvant chemotherapy achieve a pathologic complete response (pCR). This study evaluates the impact of adding lobaplatin (L) to the TE regimen. Here, we show data from 125 patients (63 TE and 62 TEL patients). Four patients did not complete all the cycles. Two-sided P values show that the addition of L (38.7% vs. 12.7%, P = 0.001) significantly increases the rate of pCR in the breast and the axilla (TpCR) and the overall response rate (ORR; 93.5% vs. 73.0%, P = 0.003). The occurrence of grade 3–4 anemia and thrombocytopenia is higher in the TEL group (52.5% vs. 10.0% and 34.4% vs. 1.7% respectively). These results demonstrate that the addition of L to the TE regimen as neoadjuvant chemotherapy improves the TpCR and the ORR rates of TNBC but with increased side effects.
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