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Science 4 November 1994:
Vol. 266. no. 5186, pp. 807 - 810
DOI: 10.1126/science.7973635
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Articles

Science, Vol 266, Issue 5186, 807-810
Copyright © 1994 by American Association for the Advancement of Science

articles

p53 status and the efficacy of cancer therapy in vivo

SW Lowe, S Bodis, A McClatchey, L Remington, HE Ruley, DE Fisher, DE Housman, and T Jacks

Center for Cancer Research, Massachusetts Institute of Technology, Cambridge 02139.

The therapeutic responsiveness of genetically defined tumors expressing or devoid of the p53 tumor suppressor gene was compared in immunocompromised mice. Tumors expressing the p53 gene contained a high proportion of apoptotic cells and typically regressed after treatment with gamma radiation or adriamycin. In contrast, p53-deficient tumors treated with the same regimens continued to enlarge and contained few apoptotic cells. Acquired mutations in p53 were associated with both treatment resistance and relapse in p53-expressing tumors. These results establish that defects in apoptosis, here caused by the inactivation of p53, can produce treatment-resistant tumors and suggest that p53 status may be an important determinant of tumor response to therapy.


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Eur. Respir. J. 19, 134-140
   Abstract »    Full Text »    PDF »
Identification of a Novel Synthetic Triterpenoid, Methyl-2-cyano-3,12-dioxooleana-1,9-dien-28-oate, That Potently Induces Caspase-mediated Apoptosis in Human Lung Cancer Cells.
K. B. Kim, R. Lotan, P. Yue, M. B. Sporn, N. Suh, G. W. Gribble, T. Honda, G. S. Wu, W. K. Hong, and S.-Y. Sun (2002)
Mol. Cancer Ther. 1, 177-184
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Induction and apoptotic regression of lung adenocarcinomas by regulation of a K-Ras transgene in the presence and absence of tumor suppressor genes.
G. H. Fisher, S. L. Wellen, D. Klimstra, J. M. Lenczowski, J. W. Tichelaar, M. J. Lizak, J. A. Whitsett, A. Koretsky, and H. E. Varmus (2001)
Genes & Dev. 15, 3249-3262
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Age and TP53 Mutation Frequency in Childhood Malignant Gliomas: Results in a Multi-institutional Cohort.
I. F. Pollack, S. D. Finkelstein, J. Burnham, E. J. Holmes, R. L. Hamilton, A. J. Yates, J. L. Finlay, and R. Sposto (2001)
Cancer Res. 61, 7404-7407
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Correlation of p53 Mutations with Resistance to Platinum-based Chemotherapy and Shortened Survival in Ovarian Cancer.
A. Reles, W. H. Wen, A. Schmider, C. Gee, I. B. Runnebaum, U. Kilian, L. A. Jones, A. El-Naggar, C. Minguillon, I. Schonborn, et al. (2001)
Clin. Cancer Res. 7, 2984-2997
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Synergistic Inhibition of Human Lung Cancer Cell Growth by Adenovirus-mediated Wild-Type p53 Gene Transfer in Combination with Docetaxel and Radiation Therapeutics in Vitro and in Vivo.
M. Nishizaki, R. E. Meyn, L. B. Levy, E. N. Atkinson, R. A. White, J. A. Roth, and L. Ji (2001)
Clin. Cancer Res. 7, 2887-2897
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Signaling pathways activated by daunorubicin.
G. Laurent and J.-P. Jaffrezou (2001)
Blood 98, 913-924
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Loss of p53 Function Confers High-Level Multidrug Resistance in Neuroblastoma Cell Lines.
N. Keshelava, J. J. Zuo, P. Chen, S. N. Waidyaratne, M. C. Luna, C. J. Gomer, T. J. Triche, and C. P. Reynolds (2001)
Cancer Res. 61, 6185-6193
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