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

作者：Masunaga Shin Ichiro^*; Tano Keizo; Nakamura Jun; Watanabe Masami; Kashino Genro; Suzuki Minoru; Kinashi Yuko; Ono Koji

来源：Experimental and Therapeutic Medicine, 2010, 1(1): 169-174.

DOI：10.3892/etm_00000027

• mild temperature hyperthermia
• hexamethylenete tramine
• tirapazamine quiescent cell
• hypoxia

This study aimed to assess the effect on solid tumors of mild temperature hyperthermia (MTH) combined with hexamethylenetetramme (HMTA) or tirapazamme (TPZ) Squamous cell carcinoma (SCC VII) tumor-beanng mice were continuously administered 5-bromo-2'-deoxyundme (BrdU) to label intratumor proliferating (P) cells Mice received HMTA or TPZ through intrapentoneal single or subcutaneous continuous aaministration, with or without MTH (40 degrees C, 60 min), followed or not by y-ray irradiation or cisplatin treatment After HMTA or TPZ administration without y-ray irradiation or cisplatin treatment, immediately after y-ray irradiation, or 1 h ifter 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 neatly equal radisensitizing and cisplatin sensitivity-enhancing ffect on both Vital 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 cisplatm-sens Wing effects than intrapentoneal single administration In terms of tumor cytotoxicity as a whole, including Q cells, the administration of gamma-ray irradiation or cisplatin treatment combined with continuous HMTA administration is promising, taking into aecount the clinical use of HMTA However, MTH should not be combined with HMTA administration

• 出版日期2010-2