Therapeutic synergism of hyperthermia-cis-platinum in a mouse tumor model

David S Alberts, Y. M. Peng, H. S G Chen, T. E. Moon, T. C. Cetas, J. D. Hoeschele

Research output: Contribution to journalArticle

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Abstract

A small-animal model was developed as a guide to whole-body hyperthermia in cancer patients. Anesthetized DBA/2 mice were secured to a platform, and their hindlimbs were immersed in a 42.3°C water bath for 30-60 min. Hindlimb hyperthermia resulted in steady-state rectal and femoral bone marrow and muscle temperatures of 42°C and upper extremity muscle and esophagus temperatures of 41°C. With this hyperthermia technique, the mouse spleen colony assay could be used to quantitate the lethality of hyperthermia and/or cis-dichloro-diammineplatinum(II) (cis-platinum) on clonogenic bone marrow and leukemia cells. Hyperthermia prior to cis-platinum administration increased cis-platinum inhibition of leukemia colony formation as much as 2 logs; however, antileukemia synergism was greatest when cis-platinum administration immediately preceded hyperthermia and no evidence existed of synergism against normal bone marrow colonies. Correlative in vivo drug uptake studies showed a marked increase in leukemia cell uptake of 195mPt-cis-platinum at elevated temperatures, which suggested a potential mechnism for the apparent antileukemia synergism of cis-platinum and heat.

Original languageEnglish (US)
Pages (from-to)455-461
Number of pages7
JournalJournal of the National Cancer Institute
Volume65
Issue number2
StatePublished - 1980

Fingerprint

Induced Hyperthermia
Fever
Neoplasms
Leukemia
Hindlimb
Temperature
Bone Marrow
Muscles
Inbred DBA Mouse
Thigh
Baths
Upper Extremity
Bone Marrow Cells
Esophagus
Spleen
Animal Models
Hot Temperature
Water
Pharmaceutical Preparations

ASJC Scopus subject areas

  • Cancer Research
  • Oncology

Cite this

Alberts, D. S., Peng, Y. M., Chen, H. S. G., Moon, T. E., Cetas, T. C., & Hoeschele, J. D. (1980). Therapeutic synergism of hyperthermia-cis-platinum in a mouse tumor model. Journal of the National Cancer Institute, 65(2), 455-461.

Therapeutic synergism of hyperthermia-cis-platinum in a mouse tumor model. / Alberts, David S; Peng, Y. M.; Chen, H. S G; Moon, T. E.; Cetas, T. C.; Hoeschele, J. D.

In: Journal of the National Cancer Institute, Vol. 65, No. 2, 1980, p. 455-461.

Research output: Contribution to journalArticle

Alberts, DS, Peng, YM, Chen, HSG, Moon, TE, Cetas, TC & Hoeschele, JD 1980, 'Therapeutic synergism of hyperthermia-cis-platinum in a mouse tumor model', Journal of the National Cancer Institute, vol. 65, no. 2, pp. 455-461.
Alberts, David S ; Peng, Y. M. ; Chen, H. S G ; Moon, T. E. ; Cetas, T. C. ; Hoeschele, J. D. / Therapeutic synergism of hyperthermia-cis-platinum in a mouse tumor model. In: Journal of the National Cancer Institute. 1980 ; Vol. 65, No. 2. pp. 455-461.
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