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Titolo:
COMPARATIVE DISPOSITION OF THE ANTINEOPLASTIC AGENT 9-NITIROCAMPTOTHECIN AND THE INACTIVE ISOMER 12-NITRO CAMPTOTHECIN IN CASE-BEARING NUDE-MICE - EFFECT OF ROUTE OF ADMINISTRATION ON TISSUE DISTRIBUTION
Autore:
AHMED AE; JACOB S; GIOVANELLA BC; KOZIELSKI AJ; LIEHR JG; STEHLIN JS;
Indirizzi:
UNIV TEXAS,MED BRANCH,DEPT PATHOL GALVESTON TX 77555 UNIV TEXAS,MED BRANCH,DEPT PHARMACOL & TOXICOL GALVESTON TX 77555 STEHLIN FDN CANC RES HOUSTON TX 77002
Titolo Testata:
Cancer chemotherapy and pharmacology
fascicolo: 1, volume: 41, anno: 1997,
pagine: 29 - 36
SICI:
0344-5704(1997)41:1<29:CDOTAA>2.0.ZU;2-T
Fonte:
ISI
Lingua:
ENG
Soggetto:
XENOGRAFTS; CANCER; CHEMOTHERAPY; INHIBITION; MECHANISM; TUMORS; CELLS;
Keywords:
CAMPTOTHECIN ANALOGS; WHOLE-BODY AUTORADIOGRAPHY; TUMOR UPTAKE; ROUTE OF ADMINISTRATION; CASE; DISPOSITION;
Tipo documento:
Article
Natura:
Periodico
Settore Disciplinare:
Science Citation Index Expanded
Science Citation Index Expanded
Citazioni:
24
Recensione:
Indirizzi per estratti:
Citazione:
A.E. Ahmed et al., "COMPARATIVE DISPOSITION OF THE ANTINEOPLASTIC AGENT 9-NITIROCAMPTOTHECIN AND THE INACTIVE ISOMER 12-NITRO CAMPTOTHECIN IN CASE-BEARING NUDE-MICE - EFFECT OF ROUTE OF ADMINISTRATION ON TISSUE DISTRIBUTION", Cancer chemotherapy and pharmacology, 41(1), 1997, pp. 29-36

Abstract

Purpose: 9-Nitrocamptothecin (9-NC) and 12-nitrocamptothecin (12-NC) are synthetic structural analogues of camptothecin (CPT) which have been prepared to explore the structure/activity relationship of this group of compounds against a wide variety of experimental tumors. As partof our investigation of the pharmacology and the mechanism of tumor inhibition of these compounds, we examined the effect of route of administration on the distribution of tritium-labeled 9-NC and 12-NC, an active and a poor chemotherapeutic agent, respectively. Methods: Quantitative whole-body autoradiography was used and our results were compared with previous results obtained with the parent compound CPT. Results: These studies revealed that, independent of the route of administration, both CPT derivatives were rapidly distributed to gall bladder, gastrointestinal tract and kidney. The excretion from these organs was indicated by the high levels of radioactivity in urine (urinary bladder) and feces (large intestines). The studies also indicated that the distributions of 9-NC and 12-NC were qualitatively similar, but quantitatively higher uptake of radioactivity was observed in animals treated with 12-NC than in those treated with 9-NC at 30 min following treatment. With the exception of the late sampling time (12 h after administration), the accumulation of radioactivity in the lungs (bronchioles) of animals that received an intravenous (i.v.) dose of 9-NC or 12-NC was higher than those treated with an intramuscular (i.m.) dose. However, the retention of drug-derived radioactivity in the tumors of mice treated with an i.m. dose of 9-NC was higher than that in the tumors of i.v.-treated animals and was also higher than that in tumors of animals treated with 12-NC, Conclusions: These results suggest that higher accumulation of 9-NC in tumor tissues than of 12-NC may contribute to the more potent chemotherapeutic activity of the former agent. Our results also suggest that i.m. injection is a more effective route of administration than i.v. administration.

ASDD Area Sistemi Dipartimentali e Documentali, Università di Bologna, Catalogo delle riviste ed altri periodici
Documento generato il 25/01/21 alle ore 15:24:37