RESUMO
Hormone receptor (HR)+ breast cancer (BC) causes most BC-related deaths, calling for improved therapeutic approaches. Despite expectations, immune checkpoint blockers (ICBs) are poorly active in patients with HR+ BC, in part reflecting the lack of preclinical models that recapitulate disease progression in immunocompetent hosts. We demonstrate that mammary tumors driven by medroxyprogesterone acetate (M) and 7,12-dimethylbenz[a]anthracene (D) recapitulate several key features of human luminal B HR+HER2- BC, including limited immune infiltration and poor sensitivity to ICBs. M/D-driven oncogenesis is accelerated by immune defects, demonstrating that M/D-driven tumors are under immunosurveillance. Safe nutritional measures including nicotinamide (NAM) supplementation efficiently delay M/D-driven oncogenesis by reactivating immunosurveillance. NAM also mediates immunotherapeutic effects against established M/D-driven and transplantable BC, largely reflecting increased type I interferon secretion by malignant cells and direct stimulation of immune effector cells. Our findings identify NAM as a potential strategy for the prevention and treatment of HR+ BC.
Assuntos
Neoplasias da Mama/terapia , Imunoterapia/métodos , Niacinamida/administração & dosagem , Receptor ErbB-2/imunologia , 9,10-Dimetil-1,2-benzantraceno , Animais , Neoplasias da Mama/imunologia , Neoplasias da Mama/metabolismo , Carcinogênese/efeitos dos fármacos , Carcinogênese/imunologia , Progressão da Doença , Feminino , Humanos , Interferon Tipo I/imunologia , Interferon Tipo I/metabolismo , Neoplasias Mamárias Experimentais/induzido quimicamente , Neoplasias Mamárias Experimentais/imunologia , Neoplasias Mamárias Experimentais/prevenção & controle , Acetato de Medroxiprogesterona , Camundongos Endogâmicos BALB C , Camundongos Endogâmicos C57BL , Camundongos Knockout , Receptor ErbB-2/metabolismo , Análise de SobrevidaRESUMO
Sweetpotato French fries (SPFF) are growing in popularity, however limited information is available on SPFF textural properties in relation to chemical composition. This study investigated the relationship between chemical components of different sweetpotato varieties and textural characteristics of SPFF. Sixteen sweetpotato genotypes were evaluated for (1) chemical constituents; (2) instrumental and sensory textural properties of SPFF; and (3) the relationship between chemical components, instrumental measurements, and sensory attributes. Dry matter (DM), alcohol-insoluble solids (AIS), starch, sugar, and oil content, and also α- and ß-amylase activities were quantified in raw sweetpotatoes and SPFF. Peak force and overall hardness describing instrumental textural properties of SPFF were measured using a texture analyzer. Descriptive sensory analysis was conducted and 10 attributes were evaluated by a trained panel. Results showed that DM, AIS, and starch content in raw sweetpotatoes were significantly correlated (P < 0.05) with instrumental peak force and overall hardness (r = 0.41 to 0.68), and with sensory surface roughness, hardness, fracturability, and crispness (r = 0.63 to 0.90). Total sugar content in raw sweetpotatoes was positively correlated with sensory smoothness and moistness (r = 0.77), and negatively correlated with instrumental peak force and overall hardness (r = -0.62 to -0.69). Instrumental measurements were positively correlated with sensory attributes of hardness, fracturability, and crispness (r = 0.68 to 0.96) and negatively correlated with oiliness, smoothness, moistness, and cohesiveness (r = -0.61 to -0.91). Therefore, DM, AIS, starch, and total sugar contents and instrumental measurements could be used as indicators to evaluate sweetpotato genotypes for SPFF processing. PRACTICAL APPLICATION: In recent years, sweetpotato French fries (SPFF) have grown in popularity, but limited information is available on SPFF textural properties in relation to the differences in chemical constituents among sweetpotato varieties. This study demonstrated that sensory texture attributes of SPFF varied widely and were significantly correlated with chemical components such as dry matter, starch, and total sugar contents of raw sweetpotatoes and instrumental texture measurements of SPFF. The knowledge generated from this study will benefit the food industry and breeding programs with the selection of sweetpotato varieties for improved SPFF quality.