The Golgi apparatus is responsible for transporting, processing, and sorting numerous proteins in the cell, including cell surfaceexpressed receptor tyrosine kinases (RTK). The small-molecule compound M-COPA [2-methylcoprophilinamide (AMF-26)] disrupts the Golgi apparatus by inhibiting the activation of Arf1, resulting in suppression of tumor growth. Here, we report an evaluation of M-COPA activity against RTK-addicted cancers, focusing specifically on human gastric cancer (GC) cells with or without MET amplification. As expected, the MET-addicted cell line MKN45 exhibited a better response to M-COPA than cell lines without MET amplification. Upon M-COPA treatment, cell surface expression of MET was downregulated with a concurrent accumulation of its precursor form. M-COPA also reduced levels of the phosphorylated form of MET along with the downstream signaling molecules Akt and S6. Similar results were obtained in additional GC cell lines with amplification of MET or the FGF receptor FGFR2. MKN45 murine xenograft experiments demonstrated the antitumor activity of M-COPA in vivo. Taken together, our results offer an initial preclinical proof of concept for the use of M-COPA as a candidate treatment option for MET-addicted GC, with broader implications for targeting the Golgi apparatus as a novel cancer therapeutic approach. Cancer Res; 76(13); 3895-903. Ó2016 AACR.
the nursing image of nursing-related content, positive images weremost with 30(42.9%), followed by negative images with 21(30.0%), and neutral images with 19(27.1%). Conclusion: Nursing-related content was dealt with too little, and dependent nursing activities such as medication, and assisting roles for doctor's examinations and treatments mainly appeared. Also, the main activity place was a hospital. To introduce proper and adequate nursing activities to the students, various types of nursing-related data and material should be distributed to front line schools, teachers, main authors, and publishing companies.
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