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1.
Int J Mol Sci ; 25(4)2024 Feb 15.
Artigo em Inglês | MEDLINE | ID: mdl-38396993

RESUMO

Glioblastoma, a grade 4 glioma as per the World Health Organization, poses a challenge in adult primary brain tumor management despite advanced surgical techniques and multimodal therapies. This review delves into the potential of targeting epidermal growth factor receptor (EGFR) with small-molecule inhibitors and antibodies as a treatment strategy. EGFR, a mutationally active receptor tyrosine kinase in over 50% of glioblastoma cases, features variants like EGFRvIII, EGFRvII and missense mutations, necessitating a deep understanding of their structures and signaling pathways. Although EGFR inhibitors have demonstrated efficacy in other cancers, their application in glioblastoma is hindered by blood-brain barrier penetration and intrinsic resistance. The evolving realm of nanodrugs and convection-enhanced delivery offers promise in ensuring precise drug delivery to the brain. Critical to success is the identification of glioblastoma patient populations that benefit from EGFR inhibitors. Tools like radiolabeled anti-EGFR antibody 806i facilitate the visualization of EGFR conformations, aiding in tailored treatment selection. Recognizing the synergistic potential of combination therapies with downstream targets like mTOR, PI3k, and HDACs is pivotal for enhancing EGFR inhibitor efficacy. In conclusion, the era of precision oncology holds promise for targeting EGFR in glioblastoma, contingent on tailored treatments, effective blood-brain barrier navigation, and the exploration of synergistic therapies.


Assuntos
Neoplasias Encefálicas , Receptores ErbB , Glioblastoma , Inibidores de Proteínas Quinases , Adulto , Humanos , Neoplasias Encefálicas/tratamento farmacológico , Receptores ErbB/antagonistas & inibidores , Glioblastoma/tratamento farmacológico , Medicina de Precisão , Inibidores de Proteínas Quinases/farmacologia , Inibidores de Proteínas Quinases/uso terapêutico , Transdução de Sinais
2.
J Vis Exp ; (196)2023 06 16.
Artigo em Inglês | MEDLINE | ID: mdl-37395572

RESUMO

Human mesenchymal stem cells (hMSCs) offer a patient-derived cell source for conducting mechanistic studies of diseases or for several therapeutic applications. Understanding hMSC properties, such as their electrical behavior at various maturation stages, has become more important in recent years. Dielectrophoresis (DEP) is a method that can manipulate cells in a nonuniform electric field, through which information can be obtained about the electrical properties of the cells, such as the cell membrane capacitance and permittivity. Traditional modes of DEP use metal electrodes, such as three-dimensional electrodes, to characterize the response of cells to DEP. In this paper, we present a microfluidic device built with a photoconductive layer capable of manipulating cells through light projections that act as in situ virtual electrodes with readily conformable geometries. A protocol is presented here that demonstrates this phenomenon, called light-induced DEP (LiDEP), for characterizing hMSCs. We show that LiDEP-induced cell responses, measured as cell velocities, can be optimized by varying parameters such as the input voltage, the wavelength ranges of the light projections, and the intensity of the light source. In the future, we envision that this platform could pave the way for technologies that are label-free and perform real-time characterization of heterogeneous populations of hMSCs or other stem cell lines.


Assuntos
Células-Tronco Mesenquimais , Técnicas Analíticas Microfluídicas , Humanos , Eletroforese/métodos , Linhagem Celular , Eletricidade , Eletrodos , Técnicas Analíticas Microfluídicas/métodos
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