Mesenchymal stem cell-derived interleukin-6 and vascular endothelial growth factor promote breast cancer cell migration.

Several different cytokines and growth factors secreted by mesenchymal stem cells (MSCs) have been hypothesized to play a role in breast cancer progression. By using a small panel of breast cancer cell lines (MCF-7, T47D, and SK-Br-3 cells), we analyzed the role of interleukin-6 (IL-6) and vascular endothelial growth factor A (VEGF) in the cross-talk between MSCs and breast cancer cells. We performed migration assays in which breast cancer cells were allowed to migrate in response to conditioned medium from MSCs (MSCs-CM), in absence or in presence of the anti-VEGF antibody bevacizumab or an anti-IL-6 antibody, alone or in combination.

Pharmacokinetic evaluation of zoledronic acid.

Introduction: Increased bone resorption is associated with several diseases, including osteoporosis, bone metastases and Paget's disease of bone. Zoledronic acid (ZA) is the most potent of the clinically available bisphosphonates. In addition to its antiresorptive activity, there has been increasing evidence to suggest that it also has anticancer properties.

Role of the EGFR ligand/receptor system in the secretion of angiogenic factors in mesenchymal stem cells.

Increasing evidence suggests that bone marrow-derived mesenchymal stem cells (MSCs) are recruited into the stroma of developing tumors where they contribute to cancer progression. MSCs produce different growth factors that sustain tumor-associated neo-angiogenesis. Since the majority of carcinomas secrete ligands of the epidermal growth factor receptor (EGFR), we assessed the role of EGFR signaling in regulating the release of angiogenic factors in MSCs.

Anticancer effect of bisphosphonates: new insights from clinical trials and preclinical evidence.

Bisphosphonates (BPs) are cornerstones in the treatment of patients with compromised skeletal integrity (either cancer related or not). However, a major indication for BPs use remains the treatment of patients with advanced cancer metastatic to the bone. Recently, several observations derived from clinical trials, primarily aimed at establishing the impact of BPs on the bone health of cancer patients, suggested a potential role for these agents as direct anti-tumor drugs.

Effects of the combined blockade of EGFR and ErbB-2 on signal transduction and regulation of cell cycle regulatory proteins in breast cancer cells.

Treatment of breast cancer cells with a combination of the EGFR-tyrosine kinase inhibitor (EGFR-TKI) gefitinib and the anti-ErbB-2 monoclonal antibody trastuzumab results in a synergistic antitumor effect. In this study, we addressed the mechanisms involved in this phenomenon. The activation of signaling pathways and the expression of cell cycle regulatory proteins were studied in SK-Br-3 and BT-474 breast cancer cells, following treatment with EGFR and/or ErbB-2 inhibitors.

Prognostic applications of gene expression signatures in breast cancer.

Analysis by DNA microarrays has led to the identification of molecular subtypes of breast carcinomas that show a distinct expression profile. Several studies have demonstrated that this 'intrinsic subtype' classification has a strong prognostic value. In addition, gene expression profiling techniques have been used to identify gene signatures that could be associated with the outcome of breast cancer patients.