The p53 gene is a potent determinant of chemosensitivity and radiosensitivity in gastric and colorectal cancers

Madoka Hamada, Toshiyoshi Fujiwara, Akio Hizuta, Akira Gochi, Yoshio Naomoto, Norihisa Takakura, Kenji Takahashi, Jack A. Roth, Noriaki Tanaka, Kunzo Orita

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112 Citations (Scopus)

Abstract

We previously reported that introduction of the wild-type p53 gene into human cancer cells with deleted p53 enhanced apoptosis induced by chemotherapy [Fujiwara et al. (1994) Cancer Res 54:2287]. This suggests that p53 status could be a potent determinant of the therapeutic efficacy of DNA-damaging cancer therapy. We analyzed 24 patients with gastric or colorectal cancer for p53 mutations and apoptotic changes in surgical specimens. Out of 11 patients with gastric cancer, 3 were treated with chemotherapeutic drugs before resection; 5 of 13 patients with colorectal cancer had 30 Gy radiation prior to surgery. p53 mutations were detected in 4 cases of gastric cancer (36.4%) and in 6 cases of colorectal cancer (46.2%) by immunohistochemical staining. The preoperative DNA-damaging therapies increased the number of apoptotic cells in wild-type-p53-expressing tumors; tumors with mutant p53, however, significantly showed fewer apoptotic cells compared with those expressing wild-type p53. The p53-inducible WAF1/CIP1 protein was immunohistochemically observed in wild-type-p53-containing tumors, whereas mutant-p53-expressing tumors expressed no detectable WAF1/CIP1. Taken together, we conclude that p53 mutations are associated with the poor response of chemotherapy and radiotherapy.

Original languageEnglish
Pages (from-to)360-365
Number of pages6
JournalJournal of cancer research and clinical oncology
Volume122
Issue number6
DOIs
Publication statusPublished - May 24 1996

Keywords

  • Apoptosis
  • Chemoradiosensitivity
  • Colorectal cancer
  • Gastric cancer
  • p53

ASJC Scopus subject areas

  • Oncology
  • Cancer Research

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  • Cite this

    Hamada, M., Fujiwara, T., Hizuta, A., Gochi, A., Naomoto, Y., Takakura, N., Takahashi, K., Roth, J. A., Tanaka, N., & Orita, K. (1996). The p53 gene is a potent determinant of chemosensitivity and radiosensitivity in gastric and colorectal cancers. Journal of cancer research and clinical oncology, 122(6), 360-365. https://doi.org/10.1007/BF01220804