TY - JOUR
T1 - The effect of various chemotherapeutic agents given with mild hyperthermia on different types of tumours
AU - Takemoto, M.
AU - Kuroda, M.
AU - Urano, M.
AU - Nishimura, Y.
AU - Kawasaki, S.
AU - Kato, H.
AU - Okumura, Y.
AU - Akaki, S.
AU - Kanazawa, Susumu
AU - Asaumi, J.
AU - Joja, Ikuo
AU - Hiraki, Y.
N1 - Funding Information:
This study was partially supported by a Grant-in-Aid for International Scientific Research [Joint Research (08044290)], a Grant-in-Aid for Scientific Research on Priority Areas [A (09042002)], and a Grant-in-Aid for Scientific Research [B (10470196)] from the Ministry of Education, Science, Sports and Culture of Japan.
PY - 2003/3
Y1 - 2003/3
N2 - It has been shown that hyperthermia can enhance the cytotoxicity of some chemotherapeutics. However, the most effective agent(s) at elevated temperatures have yet to be determined. A previous study suggests that the drug of choice at elevated temperatures may be different from that at the physiological temperature, and that the alkylating agents may be most effective at elevated temperatures. To further investigate these possibilities, the effect of chemotherapeutic agents were compared. These agents were cyclophosphamide, ifosfamide, melphalan, cisdiamminedichloroplatinum (II), 5-fluorouracil, mitomycin C and bleomycin. Three tumours (mammary carcinoma, osteosarcoma and squamous cell carcinoma) were used. They were transplanted into the feet of C3H/He mice. When tumours reached 65 mm3, a test agent was injected intraperitoneally. Tumours were immediately heated at 41.5°C for 30 min, and the tumour growth (TG) time was studied for each tumour. Using the TG times, the TG-50 (the time required for one-half of the total number of the treated tumours to reach the volume of 800 mm3 from 65 mm3) was calculated. Subsequently, the tumour growth delay time (GDT) and the thermal enhancement ratio (TER) were obtained. The GDT was the difference between the TG-50 of treated tumours and that of non-treated control tumours. The TER was the ratio of the GDT of a group treated with an agent at 41.5°C to that of a group treated with the agent at room temperature. Results showed that the top three effective agents tested at 41.5°C were solely alkylating agents - CY, IFO and L-PAM - for each kind of tumour. A GDT of cisplatin was smaller than those of the alkylating agents. The smallest TER, 1.1, was observed for 5-fluorouracil, which was given for mammary carcinoma, and for mitomycin C, which was given for squamous cell carcinoma. It could be concluded that the alkylating agents at elevated temperatures might be the drugs of choice for many types of tumours. The possible mechanisms of thermal enhancement associated with these agents are discussed.
AB - It has been shown that hyperthermia can enhance the cytotoxicity of some chemotherapeutics. However, the most effective agent(s) at elevated temperatures have yet to be determined. A previous study suggests that the drug of choice at elevated temperatures may be different from that at the physiological temperature, and that the alkylating agents may be most effective at elevated temperatures. To further investigate these possibilities, the effect of chemotherapeutic agents were compared. These agents were cyclophosphamide, ifosfamide, melphalan, cisdiamminedichloroplatinum (II), 5-fluorouracil, mitomycin C and bleomycin. Three tumours (mammary carcinoma, osteosarcoma and squamous cell carcinoma) were used. They were transplanted into the feet of C3H/He mice. When tumours reached 65 mm3, a test agent was injected intraperitoneally. Tumours were immediately heated at 41.5°C for 30 min, and the tumour growth (TG) time was studied for each tumour. Using the TG times, the TG-50 (the time required for one-half of the total number of the treated tumours to reach the volume of 800 mm3 from 65 mm3) was calculated. Subsequently, the tumour growth delay time (GDT) and the thermal enhancement ratio (TER) were obtained. The GDT was the difference between the TG-50 of treated tumours and that of non-treated control tumours. The TER was the ratio of the GDT of a group treated with an agent at 41.5°C to that of a group treated with the agent at room temperature. Results showed that the top three effective agents tested at 41.5°C were solely alkylating agents - CY, IFO and L-PAM - for each kind of tumour. A GDT of cisplatin was smaller than those of the alkylating agents. The smallest TER, 1.1, was observed for 5-fluorouracil, which was given for mammary carcinoma, and for mitomycin C, which was given for squamous cell carcinoma. It could be concluded that the alkylating agents at elevated temperatures might be the drugs of choice for many types of tumours. The possible mechanisms of thermal enhancement associated with these agents are discussed.
KW - Animal tumours
KW - Chemotherapy
KW - Mild hyperthermia
KW - Thermal enhancement
KW - Thermochemotherapy
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U2 - 10.1080/0265673021000035235
DO - 10.1080/0265673021000035235
M3 - Article
C2 - 12623641
AN - SCOPUS:0037335525
SN - 0265-6736
VL - 19
SP - 193
EP - 203
JO - International Journal of Hyperthermia
JF - International Journal of Hyperthermia
IS - 2
ER -
