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Screening of Chemopreventive Agents in Animal Models: Results on Reproducibility, Agents of a Given Class, and Agents Tested During Tumor Progression.
Lubet, Ronald A; Steele, Vernon E; Shoemaker, Robert H; Grubbs, Clinton J.
Afiliación
  • Lubet RA; Division of Cancer Prevention, National Cancer Institute, Bethesda, Maryland.
  • Steele VE; Division of Cancer Prevention, National Cancer Institute, Bethesda, Maryland.
  • Shoemaker RH; Division of Cancer Prevention, National Cancer Institute, Bethesda, Maryland.
  • Grubbs CJ; Department of Surgery, University of Alabama at Birmingham, Birmingham, Alabama. Clintongrubbs@uabmc.edu.
Cancer Prev Res (Phila) ; 11(10): 595-606, 2018 10.
Article en En | MEDLINE | ID: mdl-30045934
Because of the importance of testing reproducibility of results, we present our findings regarding screening agents in preclinical chemoprevention studies in rodent models performed by the Chemopreventive Agent Development Research Group (CADRG) of the Division of Cancer Prevention of the NCI. These studies were performed via contracts to various commercial and academic laboratories. Primarily, results with positive agents are reported because positive agents may progress to the clinics. In testing reproducibility, a limited number of direct repeats of our standard screening assays were performed; which entailed initiating treatment shortly after carcinogen administration or in young transgenic mice and continuing treatment until the end of the study. However, three additional protocols were employed relating to reproducibility: (i) testing agents at lower doses to determine efficacy and reduced toxicity; (ii) testing agents later in tumor progression when microscopic lesions existed and, (iii) testing multiple agents of the same mechanistic class. Data with six models that were routinely employed are presented: MNU-induced ER-positive mammary cancer in rats; MMTV-Neu ER-negative mammary cancers in transgenic mice; AOM-induced colon tumors in rats; intestinal adenomas in Min mice; OH-BBN-induced invasive rat urinary bladder cancers in rats; and UV-induced skin squamous carcinomas in mice. It was found that strongly positive results were highly reproducible in the preclinical models evaluated. Cancer Prev Res; 11(10); 595-606. ©2018 AACR.
Asunto(s)

Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Ensayos de Selección de Medicamentos Antitumorales / Transformación Celular Neoplásica / Anticarcinógenos / Neoplasias / Neoplasias Experimentales Tipo de estudio: Diagnostic_studies / Etiology_studies / Guideline / Prognostic_studies / Screening_studies Límite: Animals Idioma: En Revista: Cancer Prev Res (Phila) Asunto de la revista: NEOPLASIAS Año: 2018 Tipo del documento: Article Pais de publicación: Estados Unidos

Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Ensayos de Selección de Medicamentos Antitumorales / Transformación Celular Neoplásica / Anticarcinógenos / Neoplasias / Neoplasias Experimentales Tipo de estudio: Diagnostic_studies / Etiology_studies / Guideline / Prognostic_studies / Screening_studies Límite: Animals Idioma: En Revista: Cancer Prev Res (Phila) Asunto de la revista: NEOPLASIAS Año: 2018 Tipo del documento: Article Pais de publicación: Estados Unidos