Usefulness of Hexamethylenetetramine as an Adjuvant to Radiation and Cisplatin in the Treatment of Solid Tumors: its Independency of p53 Status

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概要

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• The usefulness of hexamethylenetetramine as an adjuvant to radiation and cisplatin in the treatment of solid tumors and its dependency on the p53 status of tumor cells were examined. Human head and neck squamous cell carcinoma cells transfected with mutant TP53 (SAS/mp53), or with neo vector as a control (SAS/neo), were inoculated subcutaneously into both the hind legs of Balb/cA nude mice. The tumor-bearing mice received 5-bromo-2-deoxyuridine (BrdU) continuously to label all proliferating (P) cells in the tumors. Then, they received hexamethylenetetramine (HMTA), intraperitoneally or continuously, combined with or without γ-ray irradiation or cisplatin treatment. Immediately after treatment following HMTA, the response of quiescent (Q) cells was assessed in terms of the micronucleus frequency using immunofluorescence staining for BrdU. The response of the total (= P + Q) tumor cells was determined from the BrdU non-treated tumors. A higher toxicity of HMTA to Q cells than total cells, especially in SAS/neo, was made less clear by continuous administration. There was no apparent difference in the radio- and cisplatin-sensitivity enhancing effects by HMTA combination between SAS/neo and SAS/mp53 tumors, with a slightly greater effect in SAS/mp53. In both SAS/neo and SAS/mp53 tumors, continuous HMTA administration produced higher radio- and cisplatin-sensitivity enhancing effects than intraperitoneal single administration. Therefore, the use of HMTA as an adjuvant to radiation or cisplatin might be promising in curing solid tumors with large fraction of hypoxic cells and also with frequent loss-of-function in p53.

著者

• ONO Koji

  Particle Radiation Oncology Research Center, Research Reactor Institute, Kyoto University

• Watanabe Masami

  Particle Radiation Biology Res. Reactor Inst. Kyoto Univ.

• Ono Koji

  Particle Radiation Oncology Research Center Kyoto University

• Masunaga Shin-ichiro

  Particle Radiation Oncology Research Center Kyoto University

• Tano Keizo

  Particle Radiation Biology Res. Reactor Inst. Kyoto Univ.

• TANAKA Hiroki

  Radiation Medical Physics, Research Reactor Institute, Kyoto University

• Ohnishi Takeo

  Department Of Biology Nara Medical University

• Kashino Genro

  Particle Radiation Oncology Research Center Kyoto University

• Liu Yong

  Particle Radiation Oncology Res. Center Res. Reactor Inst. Kyoto Univ.

• Kinashi Yuko

  Radiation Oncology Research Laboratory Research Reactor Institute Kyoto University

• Takahashi Akihisa

  Department Of Biology Nara Medical University

• Ohnishi Ken

  Department Of Biology Faculty Of Science Okayama University

• Nakamura Jun

  Department Of Environmental Sciences And Engineering University Of North Carolina

• Suzuki Minoru

  Particle Oncology Research Center Research Reactor Institute Kyoto University

• KINASHI Yuko

  Radiation Safety and Control, Research Reactor Institute, Kyoto University

• MASUNAGA Shin-ichiro

  Particle Radiation Oncology Research Center, Research Reactor Institute, Kyoto University

• TANO Keizo

  Particle Radiation Biology, Research Reactor Institute, Kyoto University

• KASHINO Genro

  Particle Radiation Oncology Research Center, Research Reactor Institute, Kyoto University

• WATANABE Masami

  Particle Radiation Biology, Research Reactor Institute, Kyoto University

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