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Prostate cancer stem-like cells/cancer-initiating cells have an autocrine system of hepatocyte growth factor

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Page 431–6

Prostate cancer is one of the leading causes of cancer death in men. Current research is aimed at understanding the mechanisms behind prostate cancer development and progression. One proposed mechanism implicates a subpopulation of prostate cancer cells as the driving force behind disease progression. Nishida and coworkers have developed a method to isolate these cells, known as cancer stem-like cells/cancer-initiating cells. In their current work, the authors used a cell culture technique to isolate prostate cancer stem-like cells/cancer-initiating cells and searched for overexpression of certain genes. Interestingly, they found that two important growth factors, insulin-like growth factor 1 and hepatocyte growth factor (HGF), had high levels of expression in these cells. The researchers carried their study further by using siRNA gene knockdown to evaluate the importance of HGF in tumorigenicity in an in vivo model. These findings suggest the HGF pathway as a potential therapeutic target in prostate cancer. doi: 10.1111/cas.12104

Miniaturized antibodies for imaging membrane type-1 MMP in cancers

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Page 495–501

There are numerous barriers that tumor cells must overcome to gain the ability to metastasize; one such physical obstacle is the ECM. To degrade the ECM, some cancers may rely on MMPs, such as membrane type-1 (MT1)-MMP. Deranged activity of MT1-MMP could serve as a biomarker of potentially metastatic tumors, but it has been difficult to study in a research setting. Here, Kondo et al. present their novel method for detecting MT1-MMP as an improvement over prior approaches. The authors developed variants of an anti-MT1-MMP antibody that could be radiolabeled and applied either in vitro or in vivo. Through several experiments, they found specific uptake of their probes into cancer cells that could then be imaged non-invasively, such as with standard imaging techniques. This method for labeling MT1-MMP provides an exciting new tool that could be applicable to both research and clinical settings. doi: 10.1111/cas.12102

Anti-angiogenic and anti-tumor effects of TAK-593, a potent and selective inhibitor of vascular endothelial growth factor and platelet-derived growth factor receptor tyrosine kinase

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Page 486–94

As a tumor grows, it slowly begins to exhaust its own blood supply and requires angiogenesis for survival. In the same way that new blood vessels are generated under physiologic conditions, tumors often rely on growth factors, such as vascular endothelial growth factor and platelet-derived growth factor, to develop and expand their blood supply. In recent work, Awazu and colleagues showed the inhibitory effects of a small molecule, known as TAK-593, on angiogenesis and tumor progression. In the article presented here, the authors further their earlier work by showing that TAK-593 potently inhibited vascular endothelial growth factor, platelet-derived growth factor, and the downstream molecules Akt and ERK. Moreover, TAK-593 given orally to mice led to the inhibition of xenografts of various tumor types, including lung, breast, colon, and gastric cancer. These findings promote TAK-593 as a potentially broad-spectrum chemotherapeutic agent acting through its anti-angiogenic properties. doi: 10.1111/cas.12101

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