Cancer letters
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Undifferentiated nasopharyngeal carcinoma (NPC) is an Epstein-Barr virus-associated malignant tumor. A consistent elevation in EBV antibody titers is a well-established risk factor for the development of NPC. The pathophysiological relationship and molecular mechanisms of EBV-mediated carcinogenesis have not been fully elucidated. ⋯ Some BART1 miRNAs are considered to negatively regulate LMP1 protein expression. LMP1 is secreted via exosomes, is incorporated into EBV-uninfected cells by endocytosis, and affects the environment surrounding the tumor. Here we reviewed the contribution of EBV gene products to NPC pathogenesis in relation with LMP1.
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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.
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Glioblastoma multiforme (GBM) is one of the most aggressive human tumors with poor prognosis. Current standard treatment includes chemotherapy using DNA alkylating agent temozolomide (TMZ) concomitant with surgical resection and/or irradiation. However, GBM patients exhibit various levels of the elevated expression of DNA repair enzyme, due to MGMT causing resistance to TMZ. ⋯ This bystander effect was observed in vitro using conditioned medium of TMZ-damaged GBM cells, and PCR array analysis indicated that the conditioned medium stimulated stress and toxicity pathway and upregulated anti-oxidants genes expression such as catalase and SOD2 in TMZ-resistant cells. In addition, the reduction of the activity of anti-stress mechanism by using inhibitor of GSH synthesis potentiated TMZ-induced bystander effect. These results suggest that GSH inhibitor might be one of the candidates for combination therapy with TMZ for TMZ-resistant GBM patients.