mpatibility with HUVECs, but had no effect on L-929 cell viability. Principle Conclusions We report the development and characterization of a new, dual-functional embolization-visualization system for improving fluorescence-imaged endoscopic surgical resection of hypervascular tumors. © The author(s).Rationale Epigenetic mechanisms are fundamental processes that can modulate gene expression, allowing cellular adaptation to environmental conditions. Hypoxia is an important factor known to initiate the metastatic cascade in cancer, activating cell motility and invasion by silencing cell adhesion genes. G9a is a histone methyltransferase previously shown to accumulate in hypoxic conditions. While its oncogenic activity has been previously reported, not much is known about the role G9a plays in the hypoxia-mediated metastatic cascade. Methods The role of G9a in cell motility in hypoxic condition was determined by inhibiting G9a either by short-hairpin mediated knock down or pharmacologically using a small molecule inhibitor. Through gene expression profiling, we identified CDH10 to be an important G9a target that regulates breast cancer cell motility. Lung metastasis assay in mice was used to determine the physiological significance of G9a. Results We demonstrate that, while hypoxia enhances breast cancer migc biomarker for breast cancer. © The author(s).Recently, personal glucose meter (PGM) has been utilized for the detection of non-glucose targets for point-of-care (POC) testing. Aimed at this goal, we herein developed a new PGM-based label-free read-out method for polymerase chain reaction (PCR) based on our novel finding that cerium oxide nanoparticles (CeO2 NPs) exhibit glucose oxidase-like activity comparable to the natural glucose oxidase enzyme. Methods In principle, DNA amplicons produced by PCR in the presence of target DNA electrostatically bind to CeO2 NPs, leading to their aggregation and reducing the efficiency for CeO2 NP-catalyzed glucose oxidation reaction. Thus, glucose is hardly oxidized to gluconic acid, resulting in the maintenance of initial high glucose level. On the contrary, in the absence of target DNA or presence of non-target DNA, DNA amplicons are not produced and glucose is effectively oxidized by the glucose oxidase-like activity of CeO2 NPs, leading to the significant reduction of glucose level. Finally, the resulting glucose level is simply measured by using PGM. Results With this strategy, DNA amplicons were quantitatively examined within 5 min, realizing ultrafast analysis of PCR results without any cumbersome and labor-intensive procedures. In addition, the target genomic DNA derived from Escherichia coli (E. coli) was sensitively determined down to 10 copies with high selectivity. Conclusion Importantly, the use of PGM as a detection component enables its direct application in POC settings. Based on the meritorious features of PGM such as rapidity, simplicity, and cost-effectiveness, we expect that the devised system could serve as a core platform for the on-site read-out of PCR amplification. © The author(s).Purpose The tumor homing characteristics of mesenchymal stem cells (MSCs) make them attractive vehicles for the tumor-specific delivery of therapeutic agents, such as the sodium iodide symporter (NIS). NIS is a theranostic protein that allows non-invasive monitoring of the in vivo biodistribution of functional NIS expression by radioiodine imaging as well as the therapeutic application of 131I. To gain local and temporal control of transgene expression, and thereby improve tumor selectivity, we engineered MSCs to express the NIS gene under control of a heat-inducible HSP70B promoter (HSP70B-NIS-MSCs). Experimental Design NIS induction in heat-treated HSP70B-NIS-MSCs was verified by 125I uptake assay, RT-PCR, Western blot and immunofluorescence staining. HSP70B-NIS-MSCs were then injected i.v. into mice carrying subcutaneous hepatocellular carcinoma HuH7 xenografts, and hyperthermia (1 h at 41°C) was locally applied to the tumor. 0 - 72 h later radioiodine uptake was assessed by 123I-scintigraphy. The most effective uptake regime was then selected for 131I therapy. learn more Results The HSP70B promoter showed low basal activity in vitro and was significantly induced in response to heat. In vivo, the highest tumoral iodine accumulation was seen 12 h after application of hyperthermia. HSP70B-NIS-MSC-mediated 131I therapy combined with hyperthermia resulted in a significantly reduced tumor growth with prolonged survival as compared to control groups. Conclusions The heat-inducible HSP70B promoter allows hyperthermia-induced spatial and temporal control of MSC-mediated theranostic NIS gene radiotherapy with efficient tumor-selective and temperature-dependent accumulation of radioiodine in heat-treated tumors. © The author(s).Activation-induced cell death (AICD) is a complex immunoregulatory mechanism that causes the demise of a fraction of T-lymphocytes upon antigen-driven activation. In the present study we investigated the direct role of TNF in AICD of CD8 T lymphocytes. Methods Human peripheral mononuclear cells were isolated from healthy donors and fresh tumor-infiltrating lymphocytes were obtained from cancer patients undergoing surgery. T cells were activated with anti-CD3/CD28 mAbs or with a pool of virus peptides, in combination with clinical-grade TNF blocking agents. Results A portion of CD8 T cells undergoes apoptosis upon CD3/CD28 activation in a manner that is partially prevented by the clinically used anti-TNF agents infliximab and etanercept. TNF-mediated AICD was also observed upon activation of virus-specific CD8 T cells and tumor-infiltrating CD8 T lymphocytes. The mechanism of TNF-driven T cell death involves TNFR2 and production of mitochondrial oxygen free radicals which damage DNA. Conclusion The use of TNF blocking agents reduces oxidative stress, hyperpolarization of mitochondria, and the generation of DNA damage in CD8 T celss undergoing activation. The fact that TNF mediates AICD in human tumor-reactive CD8 T cells suggests that the use of TNF-blocking agents can be exploited in immunotherapy strategies. © The author(s).