Adverse effect of mild temperature hyperthermia combined with hexamethylenetetramine compared to its effect combined with tirapazamine in the treatment of solid tumors

Masunaga,Shin-Ichiro; Tano,Keizo; Nakamura,Jun; Watanabe,Masami; Kashino,Genro; Suzuki,Minoru; Kinashi,Yuko; Ono,Koji

doi:10.3892/etm_00000027

January-February 2010 Volume 1 Issue 1

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January-February 2010 Volume 1 Issue 1

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Article

Adverse effect of mild temperature hyperthermia combined with hexamethylenetetramine compared to its effect combined with tirapazamine in the treatment of solid tumors

Authors:
- Shin-Ichiro Masunaga
- Keizo Tano
- Jun Nakamura
- Masami Watanabe
- Genro Kashino
- Minoru Suzuki
- Yuko Kinashi
- Koji Ono
View Affiliations / Copyright

Affiliations: Particle Radiation Oncology Research Center, Research Reactor Institute, Kyoto University, Osaka 590-0494, Japan. smasuna@rri.kyoto-u.ac.jp
Pages: 169-174
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Published online on: January 1, 2010

https://doi.org/10.3892/etm_00000027
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Abstract

This study aimed to assess the effect on solid tumors of mild temperature hyperthermia (MTH) combined with hexamethylenetetramine (HMTA) or tirapazamine (TPZ). Squamous cell carcinoma (SCC VII) tumor-bearing mice were continuously administered 5-bromo-2'-deoxyuridine (BrdU) to label intratumor proliferating (P) cells. Mice received HMTA or TPZ through intraperitoneal single or subcutaneous continuous administration, with or without MTH (40°C, 60 min), followed or not by γ-ray irradiation or cisplatin treatment. After HMTA or TPZ administration without γ-ray irradiation or cisplatin treatment, immediately after γ-ray irradiation, or 1 h after cisplatin treatment, the response of quiescent (Q) cells was assessed in terms of micronucleus frequency using immunofluorescence staining for BrdU. The response of the total (P + Q) tumor cells was determined based on a comparison with non-BrdU-treated tumors. Without MTH, HMTA and TPZ had a nearly equal radiosensitizing and cisplatin sensitivity-enhancing effect on both total and Q cells. With MTH, radio- and cisplatin-sensitizing effects by HMTA were reduced, particularly in the Q cells. In contrast, the enhancing effects of TPZ were increased, particularly in the Q cells. Continuous administration of HMTA and TPZ resulted in higher radio- and cisplatin-sensitizing effects than intraperitoneal single administration. In terms of tumor cytotoxicity as a whole, including Q cells, the administration of γ-ray irradiation or cisplatin treatment combined with continuous HMTA administration is promising, taking into account the clinical use of HMTA. However, MTH should not be combined with HMTA administration.

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Journals

International Journal of Molecular Medicine

International Journal of Oncology

Molecular Medicine Reports

Oncology Reports

Experimental and Therapeutic Medicine

Oncology Letters

Biomedical Reports

Molecular and Clinical Oncology

World Academy of Sciences Journal

International Journal of Functional Nutrition

International Journal of Epigenetics

Medicine International

Adverse effect of mild temperature hyperthermia combined with hexamethylenetetramine compared to its effect combined with tirapazamine in the treatment of solid tumors

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