Linked Life Data

1830248

Source:http://linkedlifedata.com/resource/pubmed/id/1830248

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
3
pubmed:dateCreated
1991-8-27
pubmed:abstractText
In an effort to improve the therapeutic efficacy and selectivity of cyclophosphamide (CTX), cis-diamminedichloroplatinum(II) (CDDP), and carboplatin (Carbo), these antitumor alkylating agents were combined with the 2-nitroimidazole drug etanidazole (ETA). As revealed by tumor-cell survival assay in the FSaIIC murine fibrosarcoma, the addition of ETA (1 g/kg, i.p.) just prior to the i.p. injection of various doses of the alkylating agents resulted in increases in the tumor-cell kill produced by each drug (CTX, 10-fold; CDDP, 20-fold; and Carbo, 5- to 15-fold), whereas toxicity to bone marrow granulocyte-macrophage colony-forming units (CFU-GM) increased only about 0- to 3-fold. When CTX was combined with either CDDP or Carbo, striking increases in tumor-cell killing were observed (20- to 100-fold across the CDDP dose range and 5- to 20-fold across the dose range of Carbo), which were supra-additive for CDDP and additive for Carbo as revealed by isobologram analysis. The addition of ETA to these alkylating-agent combinations produced a further approx. 20-fold increase in tumor-cell kill for both CTX/CDDP and CTX/Carbo. This effect was greatest at the lowest dose of the platinum drug tested and was supra-additive in the case of CDDP and additive for Carbo. Following treatment with ETA/CTX/CDDP, bone marrow CFU-GM toxicity increased only about 5-fold over that of CTX/CDDP alone, but the injection of ETA/CTX/Carbo resulted in a 10- to 20-fold increase in bone marrow toxicity as compared with that obtained using CTX/Carbo alone. Tumor growth-delay studies revealed significant increases in the antitumor effect of the alkylating agents when these were given in combination with ETA. Both the ETA/CTX/CDDP and the ETA/CTX/Carbo combinations produced tumor growth delays of 23 days, which represented approx. 1.6-fold increases over those obtained using the alkylating-agent combinations alone. These results suggest that ETA could significantly improve the therapeutic efficacy of these alkylating agents, whether they are given individually or in combination.
pubmed:grant
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:issn
0344-5704
pubmed:author
pubmed:issnType
Print
pubmed:volume
28
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
153-8
pubmed:dateRevised
2007-11-14
pubmed:meshHeading
pubmed-meshheading:1830248-Animals, pubmed-meshheading:1830248-Antineoplastic Combined Chemotherapy Protocols, pubmed-meshheading:1830248-Bone Marrow, pubmed-meshheading:1830248-Bone Marrow Cells, pubmed-meshheading:1830248-Carboplatin, pubmed-meshheading:1830248-Cell Survival, pubmed-meshheading:1830248-Cisplatin, pubmed-meshheading:1830248-Cyclophosphamide, pubmed-meshheading:1830248-Dose-Response Relationship, Drug, pubmed-meshheading:1830248-Drug Screening Assays, Antitumor, pubmed-meshheading:1830248-Drug Synergism, pubmed-meshheading:1830248-Etanidazole, pubmed-meshheading:1830248-Fibrosarcoma, pubmed-meshheading:1830248-Hematopoietic Stem Cells, pubmed-meshheading:1830248-Male, pubmed-meshheading:1830248-Mice, pubmed-meshheading:1830248-Mice, Inbred C3H, pubmed-meshheading:1830248-Neoplasm Transplantation, pubmed-meshheading:1830248-Nitroimidazoles, pubmed-meshheading:1830248-Time Factors
pubmed:year
1991
pubmed:articleTitle
Combination of etanidazole with cyclophosphamide and platinum complexes.
pubmed:affiliation
Dana-Farber Cancer Institute, Boston, MA 02115.
pubmed:publicationType
Journal Article, Comparative Study, Research Support, U.S. Gov't, P.H.S., Research Support, Non-U.S. Gov't