KMID : 0362919950130020121
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Journal of the Korean Society for Therapeutic Radiology and Oncology 1995 Volume.13 No. 2 p.121 ~ p.128
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Effect of Increased Intracellular pH by HMA on the Cytotoxicity of Combined Treatment of Hyperthermia and Chemotherapy
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Hur Won-Joo
Song Chang-Won
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Abstract
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Purpose: The enhanced cytotoxic effect of combined treatement of hyperthermia and chemotherapy by increasing intracellular acidify with HMA was investigated.
Materials and Methods: Fsall tumor cells were injected on the hindlegs of female C3H mice. When the tumor volume reached about 200mm3 , experiments were performed on the groups classified as follows :
Group I : Control
Group II : Melphalan alone (2.5 mg/kg, 5 mg/kg, 10 mg/kg, 15 mg/kg).
Group III : Heat alone (42.5¡ÆC for 1 hour)
Group IV : Melphalan + Heat (42.5¡ÆC for 1 hour)
Group V : HMA(10 mg/kg) + Melphalan (5.0 mg/kg) + Heat (42.5¡ÆC for 1 hour)
Each group included 8-12 mice on each experiment. HMA (3-amino-6-chloro-5(1-homopiperidyl)-N-(diaminomethylene)-c-pyrazinecarboxamide), an analog of amiloride which increases intracellular pH(pHi) was dissolved in dimethyl sulfoxide(DMS) and injected into the tumor-bearing mice through the tail vein. 10mg/kg of HMA and each dose of melphalan were injected into peritoneum of the tumor-bearing mice 30 minutes before heating. Tumor growth delay was calculated when the tumor vlme reached at 1500mm3 . Excision assay was performed on each group and repeated 2-4 times.
Results: Tumor growth delay of each experimental groups at 1500 mm3 were 9, 10, 13 and 19 days respectively. In vivo-in vitro excision assay using Fsall tumor cells, the cytotoxicity of each experimental groups was 1.2 X 107 , 1 X 107 , 6 X 106 , 1.7 X 106 and 1 X 105 clonogenic cells/gm respectively. When HMA was added to the combined treatment of heat and chemotherapy, the tumor growth ws delayed more than combined treatment without HMA i.e., 6 days tumor growth delay at 1500 mm3 of tumor volume.
Conclusion: he combined effect of cytotoxicity by heat and chemotherapy can be much more enhanced by HMA.
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KEYWORD
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Intracellular pH, HMA, Chemotherapy and Hyperthermia
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