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1.
Bioorg Med Chem ; 33: 115996, 2021 03 01.
Artigo em Inglês | MEDLINE | ID: mdl-33494011

RESUMO

In the present work, the radioimmunoconjugates 111In-DTPA-trastuzumab and 177Lu-DOTA-trastuzumab were evaluated regarding the influence of the chelating agents on the physical-chemical parameters and human epidermal growth factor receptor 2 (HER2) tumor cell binding. Data showed that both chelating agents, at predetermined molar ratios (antibody:chelator - 1:10 and 1:20), did not influence the immunoconjugates integrity, the radiolabeling process and the radiolabeled antibodies stability. However, differences were observed in the lipophilic feature between DOTA and DTPA radioimmunoconjugates and in the specific binding to SK-BR-3 tumor cells (HER2 positive). Therefore, this study showed the importance of assessing the influence of chelating agents and their molar ratios in the development process of radioimmunoconjugates.


Assuntos
Anticorpos Monoclonais/farmacologia , Quelantes/farmacologia , Imunoconjugados/farmacologia , Receptor ErbB-2/antagonistas & inibidores , Anticorpos Monoclonais/química , Quelantes/síntese química , Quelantes/química , Relação Dose-Resposta a Droga , Humanos , Imunoconjugados/química , Estrutura Molecular , Receptor ErbB-2/metabolismo , Relação Estrutura-Atividade , Células Tumorais Cultivadas
2.
Biochim Biophys Acta ; 1820(7): 1009-19, 2012 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-22542782

RESUMO

BACKGROUND: Fibroadenoma is the most common breast tumor in young women, and its growth and metabolism may be under hormonal control. In the present paper we described the proteoglycan (PG) composition and synthesis rate of normal breast and fibroadenoma during the menstrual cycle. METHODS: Samples of fibroadenoma and adjacent normal breast tissue were obtained at surgery. PGs were characterized by agarose gel electrophoresis and enzymatic degradation with glycosaminoglycan (GAG) lyases, and immunolocalized by confocal microscopy. To assess the synthesis rate, PGs were metabolic labeled by 35S-sulfate. RESULTS: The concentration of PGs in normal breast was higher during the secretory phase. Fibroadenoma contained and synthesized more PGs than their paired controls, but the PG concentrations varied less with the menstrual cycle and, in contrast to normal tissue, peaked in the proliferative phase. The main mammary GAGs are heparan sulfate (HS, 71%-74%) and dermatan sulfate (DS, 26%-29%). The concentrations of both increased in fibroadenoma, but DS increased more, becoming 35%-37% of total. The DS chains contained more ß-d-glucuronic acid (IdoUA/GlcUA ratios were >10 in normal breast and 2-7 in fibroadenoma). The 35S-sulfate incorporation rate revealed that the in vitro synthesis rate of DS was higher than HS. Decorin was present in both tissues, while versican was found only in fibroadenoma. CONCLUSIONS: In normal breast, the PG concentration varied with the menstrual cycle. It was increased in fibroadenoma, especially DS. GENERAL SIGNIFICANCE: PGs are increased in fibroadenoma, but their concentrations may be less sensitive to hormonal control.


Assuntos
Mama/metabolismo , Fibroadenoma/metabolismo , Glicosaminoglicanos/metabolismo , Ciclo Menstrual/metabolismo , Proteoglicanas/metabolismo , Adolescente , Adulto , Estudos de Casos e Controles , Feminino , Humanos , Immunoblotting , Adulto Jovem
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