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Selective drug-induced reduction of blood flow in tumor transplants.

Abstract
The effect of a calcium antagonist and a physiologic amine on tumor and muscle perfusion was investigated with the aim of improving the preconditions for external hyperthermia treatment of cancer. Nisoldipine (0.04-4.0 mg/kg) and 5-hydroxy tryptamine (5-HT) (0.2-8.0 mg/kg) were administered i.p. in Sprague-Dawley rats bearing Walker 256 carcinoma, Yoshida sarcoma, or a homologous tumor transplant derived from a spontaneous leiomyosarcoma of the uterus. At the maximum dosage used, nisoldipine injection caused a decrease of the regional washout rate of Xenon-133 of 63 +/- 8% (SEM) in the Walker carcinoma and an increase of 80 +/- 41% in the muscle of the hind leg. 5-HT (8 mg/kg) caused a drop of 79 +/- 29% in the Walker carcinoma and only a slight fall of the washout rate in muscle of 14 +/- 4.8%. Tumor-to-muscle uptake ratios of 11C-butanol fell from 5.63 +/- 1.98 to 3.32 +/- 1.21, and from 5.3 +/- 0.56 to 2.98 +/- 0.30, after injection of 0.2 mg/kg nisoldipine and 4 mg/kg 5-HT, respectively. Similar reaction patterns and percentage changes were observed in different tumor lines at constant doses of 0.2 mg/kg nisoldipine and 4 mg/kg 5-HT. Both drugs representing two different rationales of vasomotor action were able to reduce blood flow specifically in transplanted tumors; nisoldipine increased muscle blood flow and decreased arterial blood pressure, whereas 5-HT acted without substantial systemic effects.
AuthorsW H Knapp, J Debatin, K Layer, F Helus, A Altmann, H J Sinn, H Ostertag
JournalInternational journal of radiation oncology, biology, physics (Int J Radiat Oncol Biol Phys) Vol. 11 Issue 7 Pg. 1357-66 (Jul 1985) ISSN: 0360-3016 [Print] United States
PMID4008292 (Publication Type: Journal Article)
Chemical References
  • Calcium Channel Blockers
  • Serotonin
  • Nisoldipine
  • Nifedipine
Topics
  • Animals
  • Calcium Channel Blockers (therapeutic use)
  • Hyperthermia, Induced
  • Neoplasm Transplantation
  • Neoplasms, Experimental (blood supply, therapy)
  • Nifedipine (analogs & derivatives, therapeutic use)
  • Nisoldipine
  • Rats
  • Rats, Inbred Strains
  • Regional Blood Flow (drug effects)
  • Serotonin (therapeutic use)

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