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Combination and individual antitumor effects of hyperthermia, cisplatin, and selected dithiocarbamates.

Abstract
The antitumor effects produced by combinations of cisplatin (Pt), substituted dithiocarbamates (dimethyldithiocarbamate [DmDTC] and sodium N-methyl-D-glucamine dithiocarbamate [NMGDTC]) and hyperthermia (H) were measured and compared to those produced by single agents alone in C3H/HeN mice bearing the transplantable radiation-induced fibrosarcoma, RIF-1, in one or both hind feet. The average tumor volumes of control and treatment groups were compared periodically after treatment with H. Combinations of H and Pt completely resolved established foot tumors in 10/13 mice. However, evidence of long-term nephrotoxicity and gastrointestinal (GI) toxicity became evident causing death of these mice within 120 to 122 days after tumor inoculation. Hyperthermia plus DmDTC resolved tumors in heated and non-heated feet in 3/8 mice, thus demonstrating both ipsilateral and contralateral anti-tumor activity. Furthermore, H-Pt-NMGDTC produced complete tumor resolution in 7/13 mice; these mice survived and were tumor-free 180 days post inoculation and autopsies revealed no appreciable nephro- or GI toxicity. In addition, 4/8 mice underwent complete tumor resolution in heated left feet plus dramatic retarding of tumor growth in unheated right feet (ipsilateral and contralateral anti-tumor effects). Five heat-treated left foot tumors resolved in the H-Pt-DmDTC group with one mouse demonstrating resolution of tumor in both feet. Advanced foot tumors were treated with H-DmDTC and H-Pt-DmDTC. Hyperthermia and Pt were administered on day 0 of the experiment and DmDTC on days 0 through 3; dramatic tumor shrinkage continued through day 6 for a total of 75 to 80 percent reduction of tumor volume in both groups. The concurrent administration of DmDTC or NMGDTC with H and Pt prevented or greatly reduced nephrotoxicity and GI toxicity in all experiments without retarding anti-tumor efficacy.
AuthorsE M Walker Jr, R F Schaefer, K J Henle, B J Schmidt, G R Gale, D J Cannon, M M Jones, A J Moss Jr
JournalAnnals of clinical and laboratory science (Ann Clin Lab Sci) 1989 Jul-Aug Vol. 19 Issue 4 Pg. 242-54 ISSN: 0091-7370 [Print] United States
PMID2757352 (Publication Type: Journal Article, Research Support, U.S. Gov't, Non-P.H.S.)
Chemical References
  • Antineoplastic Agents
  • Thiocarbamates
  • Cisplatin
Topics
  • Animals
  • Antineoplastic Agents (administration & dosage, therapeutic use)
  • Antineoplastic Combined Chemotherapy Protocols (therapeutic use)
  • Cisplatin (administration & dosage, therapeutic use)
  • Combined Modality Therapy
  • Female
  • Fibrosarcoma (drug therapy, pathology, therapy)
  • Hyperthermia, Induced
  • Mice
  • Mice, Inbred C3H
  • Thiocarbamates (administration & dosage, therapeutic use)

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