통합 검색 | Korea Science

Elucidating molecular mechanisms of acquired resistance to BRAF inhibitors in melanoma using a microfluidic device and deep sequencing

Han, Jiyeon;Jung, Yeonjoo;Jun, Yukyung;Park, Sungsu;Lee, Sanghyuk
- Genomics & Informatics
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- 제19권1호
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- pp.2.1-2.10
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- 2021
BRAF inhibitors (e.g., vemurafenib) are widely used to treat metastatic melanoma with the BRAF V600E mutation. The initial response is often dramatic, but treatment resistance leads to disease progression in the majority of cases. Although secondary mutations in the mitogen-activated protein kinase signaling pathway are known to be responsible for this phenomenon, the molecular mechanisms governing acquired resistance are not known in more than half of patients. Here we report a genome- and transcriptome-wide study investigating the molecular mechanisms of acquired resistance to BRAF inhibitors. A microfluidic chip with a concentration gradient of vemurafenib was utilized to rapidly obtain therapy-resistant clones from two melanoma cell lines with the BRAF V600E mutation (A375 and SK-MEL-28). Exome and transcriptome data were produced from 13 resistant clones and analyzed to identify secondary mutations and gene expression changes. Various mechanisms, including phenotype switching and metabolic reprogramming, have been determined to contribute to resistance development differently for each clone. The roles of microphthalmia-associated transcription factor, the master transcription factor in melanocyte differentiation/dedifferentiation, were highlighted in terms of phenotype switching. Our study provides an omics-based comprehensive overview of the molecular mechanisms governing acquired resistance to BRAF inhibitor therapy.
https://doi.org/10.5808/gi.20074 인용 PDF KSCI

An Investigation of the Terahertz Absorption Characteristics of a Graphene Oxide Aqueous Solution Using Microfluidic Technology

Ningyi Cai;Boyan Zhang;Qinghao Meng;Siyu Qian;Bo Su;Hailin Cui;Shengbo Zhang;Cunlin Zhang
- Current Optics and Photonics
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- 제7권2호
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- pp.119-126
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- 2023
The vibratory and rotational levels of many biological macromolecules lie in the terahertz (THz) band, which means that THz techniques can be used to identify and detect them. Moreover, since the biological activity of most biomolecules only becomes apparent in aqueous solution, we use microfluidic technology to study the biological properties of these biomolecules. THz time-domain spectroscopy was used to study the THz absorption characteristics of graphene oxide (GO) aqueous solution at different concentrations and different exposure times in fixed electric or magnetic fields. The results show that the spectral characteristics of the GO solution varied with the concentration: as the concentration increased, the THz absorption decreased. The results also show that after placing the solution in an external electric field, the absorption of THz first increased and then decreased. When the solution was placed in a magnetic field, the THz absorption increased with the increase in standing time. In this paper, these results are explained based on considerations of what is occurring at the molecular scale. The results of this study provide technical support for the further study of GO and will assist with its improved application in various fields.
https://doi.org/10.3807/COPP.2023.7.2.119 인용 PDF