RESUMO
Grazing steers from Angus and Hereford breeds, their cross-breeds and a three-way cross-breed (Limousin × Angus-Hereford) were measured for growth, carcass and meat quality traits. Breed effects were studied, and the association of SNPs with fat deposition and fatty acid (FA) composition (leptin, melanocortin-4 receptor, stearoyl-CoA desaturase, FA synthase and thyroglobulin) was tested. Limousin cross-breed showed the greatest final body weight, ultrasound rib eye area, dressing percentage, carcass and leg length, and the lowest backfat thickness and intramuscular fat content. Genetic groups had similar pH, shear force, cooking loss, L* and b* and n-6:n-3 ratio. Meat from 1/2-Angus presented greater a* than Limousin cross-breed. Whereas Angus had the highest total SFA content, Hereford had the lowest total SFA and the highest total MUFA. Limousin cross-breed had greater content of several individual PUFAs, total PUFA, n-6 and n-3 FA than Angus and 1/2-Angus. Leptin and FA synthase were associated with some FAs, supporting their influence over fat metabolism for grazing animals.
Assuntos
Composição Corporal , Peso Corporal , Cruzamento , Ácidos Graxos/análise , Metabolismo dos Lipídeos/genética , Carne/análise , Polimorfismo de Nucleotídeo Único , Tecido Adiposo/metabolismo , Animais , Bovinos , Cor , Culinária , Cruzamentos Genéticos , Gorduras na Dieta/análise , Genótipo , Crescimento , Humanos , Concentração de Íons de Hidrogênio , Masculino , Carne/normas , Músculos/metabolismo , Fenótipo , Especificidade da Espécie , Estresse MecânicoRESUMO
PURPOSE: Immune-based therapies, such as the immunocytokine huKS-IL2, exert potent antitumor responses in some animal models by targeting cytokine activity to the tumor microenvironment. We found that certain chemotherapy agents in the appropriate dose and schedule can augment the antitumor activity of huKS-IL2. EXPERIMENTAL DESIGN: Chemotherapy agents were given in a single dose followed 1 day (paclitaxel) or 3 days (cyclophosphamide) later with five daily doses of huKS-IL2 in mice bearing established s.c. tumors, liver metastases, or lung metastases. Tumor models used were CT26/KSA colon, 4T1/KSA mammary, or LLCKSA Lewis lung carcinomas. To measure huKS-IL2 distribution, radiolabeled protein was given to CT26/KSA tumor-bearing mice 1 or 24 h after paclitaxel. huKS-IL2 levels in the tumors were evaluated. RESULTS: Both paclitaxel and cyclophosphamide followed by huKS-IL2 resulted in enhanced antitumor responses compared with either of the treatments alone in the three different tumor models. Results from studies to determine whether the role of the cytotoxic agents in antitumor activity enhancement was related to tumor uptake indicated that a larger fraction of the radiolabeled huKS-IL2 penetrated the tumors when it was administered 24 h after cytotoxic drug "sensitization." CONCLUSION: These data support the idea that prior drug therapy serves to decompress the tumor and lower the diffusion barrier for macromolecules, thus allowing for increased uptake of the huKS-IL2 immunocytokine into the tumor microenvironment. Because the toxicity of the immunocytokine is relatively low at optimal doses, the therapeutic index would likely be greater with the combination treatments.
Assuntos
Anticorpos Monoclonais/administração & dosagem , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Interleucina-2/imunologia , Neoplasias Experimentais/tratamento farmacológico , Animais , Anticorpos Monoclonais/farmacologia , Sobrevivência Celular/efeitos dos fármacos , Ciclofosfamida/administração & dosagem , Relação Dose-Resposta a Droga , Sinergismo Farmacológico , Humanos , Concentração Inibidora 50 , Camundongos , Camundongos Endogâmicos C57BL , Transplante de Neoplasias , Neoplasias Experimentais/metabolismo , Neoplasias Experimentais/patologia , Paclitaxel/administração & dosagem , Fatores de Tempo , Células Tumorais CultivadasRESUMO
Abstract 3.1. A regional approach often reveals features of population trends not evident in national data. We have already pointed out that the 1768 census followed the ecclesiastical sub-divisions of the country; therefore its territorial data are not comparable with those derived from later enumerations. The 1787 and 1797 censuses, on the other hand, were based on civil sub-divisions, which can be compared, when aggregated, with later censuses of the modern statistical era.