Assessment of GRB2 Dynamics vs. Bioimpedance Measurements as a Function of Systemic Infusion of "Magnetic Nanoparticle - Anti-HER2" in an Experimental Breast Cancer Model

Carla P Cedillo Alvarez, Guadalupe C VillanuevaLópez, Valeria Quintanar Jurado, M. Zayas
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Abstract

Breast cancer (BC) is the most common malignancy among the female population. Ablation Radiofrequency (RF) assisted with magnetic nanoparticles (MNPs) coupled to a monoclonal antibody anti-HER2 (Human epidermal growth factor receptor 2) has been proposed as an alternative therapeutic technique, the concept behind the technical proposal is to change the tissue electrical conductivity by the use of MNPs, however, the local biochemical and bioimpedance effects of MNPs in cancerous tissue remain unknown, as a first approach to explore such effects caused by MNPs, the present work was focused on to assess biochemically the bioconjugated “MNPs - anti-HER2” systemic infusion effect on tumor tissue through studying the protein dynamics of the Growth Factor Receptor-Bound Protein 2 (GRB2) and its implication on the HER2 signaling pathway as well as its correlation with changes in bioimpedance measurement. A breast cancer model in rats in three specific conditions was evaluated by tissue immunostaining and bioimpedance measurements. Normal breast tissue (Healthy), Breast Cancer tissue (BC) and Breast Cancer tissue with MNPs (BC+MNPs). The results show that GRB2 protein expression in BC+MNPs is null or similar to Healthy, both compared with respect to BC. In addition, bioimpedance measurements are similar in BC+MNPs and Healthy conditions, and different values are evident in BC, those findings are in agreement with GRB2 expression. It seems that systemic bioconjugate infusion inhibits HER-2 signaling pathway and changes in the electrical conductivity of the tumor tissue.
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在实验性乳腺癌模型中,系统输注“磁性纳米颗粒-抗her2”对GRB2动力学和生物阻抗测量的影响
乳腺癌(BC)是女性中最常见的恶性肿瘤。射频(RF)辅助磁性纳米颗粒(MNPs)偶联单克隆抗体抗her2(人表皮生长因子受体2)已被提出作为一种替代治疗技术,该技术提案背后的概念是通过使用MNPs改变组织电导率,然而,MNPs在癌组织中的局部生化和生物阻抗效应尚不清楚,作为探索MNPs引起的此类效应的第一种方法。本研究主要通过研究生长因子受体结合蛋白2 (Growth Factor Receptor-Bound protein 2, GRB2)的蛋白动力学及其对HER2信号通路的影响及其与生物阻抗测量变化的相关性,从生化角度评估生物偶联的“MNPs - anti-HER2”对肿瘤组织的全身输注作用。采用组织免疫染色法和生物阻抗法对三种特定条件下的大鼠乳腺癌模型进行了评价。正常乳腺组织(健康),乳腺癌组织(BC)和乳腺癌组织与MNPs (BC+MNPs)。结果显示,与BC相比,GRB2蛋白在BC+MNPs中的表达为零或与Healthy相似。此外,在BC+MNPs和健康状态下,生物阻抗测量值相似,而在BC中,生物阻抗值明显不同,这些发现与GRB2表达一致。系统输注生物偶联物似乎抑制HER-2信号通路和肿瘤组织电导率的改变。
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