Cancer letters
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Celecoxib is a paradigmatic selective inhibitor of cyclooxygenase-2 (COX-2). This anti-inflammatory drug has potent anti-tumor activity in a wide variety of human epithelial tumor types, such as colorectal, breast, non-small cell lung, and prostate cancers. Up to now, the drug found application in cancer prevention in patients with familial adenomatous polyposis. ⋯ Consequently, the use of Celecoxib may be of specific value for the treatment of apoptosis-resistant tumors with overexpression of Bcl-2, Mcl-1, or survivin as single drug or in combination with radiotherapy, chemotherapy, or targeted pro-apoptotic drugs that are inhibited by survivin, Bcl-2 or Mcl-1. As COX-2 inhibition has been associated with cardiovascular toxicity, the value of drug derivatives without COX-2 inhibitory action should be validated for prevention and treatment of human epithelial tumors to reduce the risk for heart attack or stroke. However, its additional COX-2 inhibitory action may qualify Celecoxib for a cautious use in COX-2-dependent epithelial tumors, where the drug could additionally suppress COX-2-mediated growth and survival promoting signals from the tumor and the stromal cells.
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Review
Tumor-associated macrophages as potential diagnostic and prognostic biomarkers in breast cancer.
Breast cancer development largely depends upon the essential contributions from the tumor microenvironment, where several inflammatory cell populations (e.g. macrophages) orchestrate breast cancer development. The majority of tumor-associated macrophages (TAMs) exhibit alternatively activated M2 properties, produce abundant anti-inflammatory factors and facilitate tumor development. ⋯ The pan-macrophage marker CD68 is now generally utilized to identify TAMs in diagnostic biopsy samples, and some other TAM-related biomarkers are also utilized in prognosis prediction, including CD163, vascular endothelial growth factor (VEGF), hypoxia-inducible factors (HIFs), proliferating cellular nuclear antigen (PCNA), ferritin light chain (FTL) and C-C motif chemokine ligand 18 (CCL18). In this review, we highlight the recent progress made in understanding the relationship between TAMs and clinicopathological parameters in human breast cancer and address the potential value of TAMs as diagnostic and prognostic biomarkers.
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This study explores the impact of Hsp90 inhibitors NVP-AUY922 and NVP-BEP800 in combination with ionizing radiation (IR) on the migration and invasion of lung carcinoma A549 and glioblastoma SNB19 cells, under normoxia or hypoxia. Independent of oxygen concentration, both drugs decreased the migration and invasion rates of non-irradiated tumor cells. ⋯ Decreased migration of cells correlated with altered expression of several matrix-associated proteins (FAK/p-FAK, Erk2, RhoA) and impaired F-actin modulation. The anti-metastatic efficacy of the Hsp90 inhibitors could be useful in combinational therapies of cancer.