0447, Mantal-Cox test). We further monitored the growth of the metastatic tumor foci by in vivo imaging (Figure 6B, 6C). Indeed, the ascending luminescence signal as observed in the control mice was well suppressed in the CNHK600-IL24 group. Figure 6 Inhibition of breast tumor metastasis by CNHK600-IL24. (A) Survival curves of mice in the metastatic

model created by tail vein injection of Temsirolimus cancer cells. (N = 8 for each group) (B, C) In vivo imaging of the control and the CNHK600-IL24 group in the metastatic model created by tail vein injection. (D, E) In vivo imaging of the control and CNHK600-IL24 group in the metastatic model generated by left ventricular injection. We also assessed the anti-proliferative activity of CNHK600-IL24 in a metastatic model by left ventricular injection. Similarly, two of the three mice in control group died on days 36 and 41, but the three CNHK600-IL24-treated mice all survived more see more than 45 days. From the 10th day on, all of the mice were tested using IVIS 50 every seven days. There was an obvious difference in metastases between the control group and treatment group (Figure 6D, 6E). On day 45, surviving mice were sacrificed and the metastases were detected ex vivo. There were extensive metastases in the only surviving mouse of the control group. Tumors were

visible in the skull, mandible, scapula, clavicle, femur, brain, lung and liver. In contrast, metastases in the treatment groups were significantly reduced (data not show). Discussion Breast cancer is the most frequently diagnosed neoplasm in women. Although great progress has been made in treatment of breast cancer, very STI571 manufacturer limited options are available for metastatic breast cancer. Indeed, micrometastases within bone marrow or other tissues can lead to relapse and metastasis and significantly accelerate the progression of disease[17]. Targeted oncolytic adenovirus brought new options for novel strategies to tackle these difficult problems. Compared with small triclocarban molecule drug or recombinant proteins, viruses

have their unique properties, i.e., they can replicate and spread in addition to carrying anti-tumoral therapeutic genes, and may be targeted specifically to tumor cells. In recent years, the synergistic anti-tumor effects of IL-24, including apoptosis-inducing and immune-stimulating effects have gained increasing attention. Zheng et al. found that Adenovirus transduction of IL-24 causes G2/M cell cycle arrest and apoptotic cell death and this effect could be antagonized by IL-10[18]. Patani et al. showed that recombinant IL-24 reduced the motility and migration of MDA-MB-231 using wound healing and electric cell impedance sensing assay. Furthermore, significantly lower expression of IL-24 was also noted in tumors from patients who died of breast cancer compared to those who remained disease free. Low levels of MDA-7 were significantly correlated with a shorter disease free survival[19].