Treatment of terminal peritoneal carcinomatosis by a transducible p53-activating peptide.
Treatment of terminal peritoneal carcinomatosis by a transducible p53-activating peptide.
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DOI：
10.1371/journal.pbio.0020036
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发表时间：
2004-02
期刊：
影响因子：
9.8
通讯作者：
Dowdy SF
中科院分区：
文献类型：
--
作者：
Snyder EL;Meade BR;Saenz CC;Dowdy SF
Advanced-stage peritoneal carcinomatosis is resistant to current chemotherapy treatment and, in the case of metastatic ovarian cancer, results in a devastating 15%–20% survival rate. Therapeutics that restore genes inactivated during oncogenesis are predicted to be more potent and specific than current therapies. Experiments with viral vectors have demonstrated the theoretical utility of expressing the p53 tumor suppressor gene in cancer cells. However, clinically useful alternative approaches for introducing p53 activity into cancer cells are clearly needed. It has been hypothesized that direct reactivation of endogenous p53 protein in cancer cells will be therapeutically beneficial, but few tests of this hypothesis have been carried out in vivo. We report that a transducible D-isomer RI-TATp53C′ peptide activates the p53 protein in cancer cells, but not normal cells. RI-TATp53C′ peptide treatment of preclinical terminal peritoneal carcinomatosis and peritoneal lymphoma models results in significant increases in lifespan (greater than 6-fold) and the generation of disease-free animals. These proof-of-concept observations show that specific activation of endogenous p53 activity by a macromolecular agent is therapeutically effective in preclinical models of terminal human malignancy. Our results suggest that TAT-mediated transduction may be a useful strategy for the therapeutic delivery of large tumor suppressor molecules to malignant cells in vivo. Specific activiation of the tumor suppressor protein p53, using a transducible p53 C-terminal peptide, dramatically increases survival in a mouse model of peritoneal carcinomatosis. This peptide offers therapeutic potential for tumors in which p53 is mutated
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影响因子：
56.9
作者：
Schwarze, SR;Ho, A;Dowdy, SF
通讯作者：
Dowdy, SF
影响因子：
82.9
作者：
Fulda, S;Wick, W;Debatin, KM
通讯作者：
Debatin, KM
影响因子：
56.9
作者：
Bunz, F;Dutriaux, A;Vogelstein, B
通讯作者：
Vogelstein, B
DOI：
10.1016/s0889-8588(05)70476-7
发表时间：
1997-10-01
影响因子：
2.4
作者：
Lam, KS;Zhao, ZG
通讯作者：
Zhao, ZG
影响因子：
8
作者：
Rippin, TM;Bykov, VJN;Fersht, AR
通讯作者：
Fersht, AR