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Inhibition of lymphatic metastasis in neuroblastoma by a novel neutralizing antibody to vascular endothelial growth factor-D


Page 2144–52

In this experiment, Kashima and colleagues generated a novel monoclonal antibody, cVE199, against vascular endothelial growth factor-D (VEGF-D), a known lymphangiogenic factor. Lymphangiogenesis is of interest in metastases of malignant neoplasms because the induction of new lymphatic vessels increases the chance a cancer will metastasize via the lymph system. cVE199 was tested in vitro and found to have specific inhibitory activity against human VEGF-D. The ability of this monoclonal antibody to work in vivo was then tested in a xenograft mouse model using the SK-N-DZ neuroblastoma cell line. This cell line was shown to natively express VEGF-D. Repeated administration with cVE199 was successful in decreasing the metastasis of lymph nodes through reduction in lymphangiogenesis. This is as VEGF-D expression was noted in over one-third of human neuroblastoma tissues. Together these results suggest that monoclonal antibody cVE199 could be an important therapeutic agent in the treatment of neuroblastoma.doi: 10.1111/cas.12010

ASK1 inhibitor as a potent therapeutic drug for the treatment of gastric cancer


Page 2181–85

Although the curative rate for early-stage gastric cancer (GC) has been increased by improvements in endoscopic and surgical techniques, the prognosis of advanced and non-resectable GC remains poor. Currently, the only targeted therapy for GC is trastuzumab, which is directed again human epidermal growth factor receptor-2 (HER2). However, only 20% GCs express HER2 receptors leaving the majority of GCs without targeted therapy. In this experiment, Hayakawa et al., targeted the MAP3K apoptosis signal-regulating kinase (ASK-1), which has been shown to be elevated in human GC tissues. Using an ASK1 inhibitor, K811, the group showed there was a decrease in proliferation of GC cells. Further, they showed that HER2 can activate ASK1 and that even in cells overexpressing HER2, treatment with K811 decreased the proliferation of these cells. These results were then confirmed in vivo using a mouse model. This series of experiments suggests that ASK1 may be a useful new therapy target in advanced GC.doi: 10.1111/cas.12024

Multi-walled carbon nanotubes translocate into the pleural cavity and induce visceral mesothelial proliferation in rats


Page 2045–50

Multi-walled carbon nanotubes (MWCNT) closely mimic the structure of asbestos and various experiments have been performed to demonstrate their ability to induce cellular changes similar to that of asbestos. One implication of past studies has been the potential for MWCNTs to induce pleural mesothelioma, a rare form of cancer that is almost always associated with chronic asbestos exposure. There is motivation to study the negative health effects of MWCNTs because these synthetic compounds are being used in many industries without regulations on exposure. In this article, Xu and coworkers describe their experiment where rats inhaled MWCNTs and lung tissues were later sampled and found to have mesothelial proliferation. The authors went on to demonstrate the involvement of macrophages in a mechanism similar to that seen with asbestos exposure. These findings offer direct evidence that MWCNTs induce pleural mesothelioma and highlight the need to address regulations on exposure to these compounds.doi: 10.1111/cas.12005