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  • Title: p14(ARF) modulates the cytolytic effect of ONYX-015 in mesothelioma cells with wild-type p53.
    Author: Yang CT, You L, Uematsu K, Yeh CC, McCormick F, Jablons DM.
    Journal: Cancer Res; 2001 Aug 15; 61(16):5959-63. PubMed ID: 11507034.
    Abstract:
    ONYX-015 has been reported to kill selectively tumor cells lacking functional p53. Genetic alterations of INK4a/ARF locus, which is a predominant event in malignant pleural mesothelioma, may result in loss of p14(ARF) and subsequent disruption of p53 pathway in cancer cells. In the present study, ONYX-015 was able to kill three mesothelioma cell lines (H28, H513, and 211H) with wild-type p53 but lacking p14(ARF). In contrast, MS-1 mesothelioma cells, which expressed both p53 and p14(ARF), were resistant to ONYX-015. Introducing p14(ARF) gene into the H28 cell, a mesothelioma cell without p14(ARF) expression, significantly increased the resistance of this cell line to the cytolytic effect of ONYX-015. Our results suggest that human mesotheliomas with wild-type p53 yet lacking p14(ARF) are potential candidates for ONYX-015 therapy.
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