BACKGROUND Tetrandrine, a bisbenzylisoquinoline alkaloid, has cancer cell cytotoxicity. The effects of combined tetrandrine and radiation, alone or combined, on human SH-SY5Y neuroblastoma cells were examined. MATERIALS AND METHODS A combination treatment, using either concomitant irradiation at the beginning or end of the tetrandrine treatment (designated as the RT-Tet and Tet-RT protocols, ...

BACKGROUND Survivin is overexpressed in cancer cells and plays a crucial role in apoptosis evasion. YM155, a small-molecule inhibitor of survivin, could enhance the cytotoxicity of various DNA-damaging agents. Here, we evaluated the radiosensitizaion potential of YM155 in human esophageal squamous cell carcinoma (ESCC). METHODS Cell viability was determined by CCK8 assay. The radiosensitizati...

PURPOSE The aim of this work was to study changes in the tumor microenvironment early after an antiangiogenic treatment using thalidomide (a promising angiogenesis inhibitor in a variety of cancers), with special focus on a possible "normalization" of the tumor vasculature that could be exploited to improve radiotherapy. EXPERIMENTAL DESIGN Tumor oxygenation, perfusion, permeability, intersti...

Hypoxia inducible factor-1 (HIF-1) promotes tumor cell adaptation to microenvironmental stress. HIF-1 is up-regulated in irradiated tumors and serves as a promising target for radiosensitization. We initially confirmed that the orally bioavailable HIF-1 inhibitor PX-478 reduces HIF-1 protein levels and signaling in vitro in a dose-dependent manner and provides direct radiosensitization of hypox...

Our earlier studies have shown that simultaneous inhibition of glycolysis and pentose phosphate pathway using 2-deoxy-d-glucose (2-DG, an inhibitor of glycolysis) and 6-aminonicotinamide (6-AN, an inhibitor of pentose phosphate pathway) lead to metabolic oxidative stress (MOS), resulting in radiosensitization in malignant cells. Present study was carried out to investigate the effects of 2-DG a...

UNLABELLED Ionizing radiation (IR) is a key therapeutic regimen for many head and neck cancers (HNC). However, the 5-year overall survival rate for locally advanced HNCs is approximately 50% and better therapeutic efficacy is needed. NAD(P)H quinone oxidoreductase 1 (NQO1) is overexpressed in many cancers, and β-lapachone (β-lap), a unique NQO1 bioactivatable drug, exploits this enzyme to rel...

Hsp90, the 90 kDa heat shock protein, is a highly expressed molecular chaperone that modulates the stability and/or transport of a diverse set of critical cellular regulatory proteins. Among Hsp90 clients are a number of proteins, which in a cell type-dependent manner, contribute to tumor cell radioresistance. Exposure of a variety of solid tumor cell lines to clinically relevant Hsp90 inhibito...

We have shown that 2',2'-difluoro-2'-deoxycytidine (dFdCyd; Gemcitabine), a deoxycytidine analogue, is a potent radiation sensitizer when cells are exposed to it continuously for >16 h in low concentrations (in the range of 10 nM). However, the most common method of clinical administration is by short-term infusion (30-90 min). Therefore, we wished to determine under what conditions dFdCyd coul...

Auranofin (AF) is an anti-arthritic drug considered for combined chemotherapy due to its ability to impair the redox homeostasis in tumor cells. In this study, we asked whether AF may in addition radiosensitize tumor cells by targeting thioredoxin reductase (TrxR), a critical enzyme in the antioxidant defense system operating through the reductive protein thioredoxin. Our principal findings in ...