Simple, Sensitive and Accurate Multiplex Detection of Clinically Important Melanoma DNA Mutations in Circulating Tumour DNA with SERS Nanotags

Wee, Eugene J. H.; Wang, Yuling; Tsao, Simon Chang-Hao; Trau, Matt

doi:10.7150/thno.15871

Cited by 115 publications

(111 citation statements)

References 38 publications

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“…The RAF dimers are subsequently disrupted by ERK-mediated feedback phosphorylation, which also disrupts the RAS-RAF interaction and attenuates RAF signaling. However, dimerization is not needed for the function of BRAF V600E which alone has a high catalytic activity 42, 43. In the current study, we observed that Vemurafenib could promote BRAF/CRAF dimerization causing paradoxical ERK activation in Vemurafenib-resistant DTC cells.…”

Section: Discussionsupporting

confidence: 44%

Obatoclax and LY3009120 Efficiently Overcome Vemurafenib Resistance in Differentiated Thyroid Cancer

Wei¹,

Sun²,

Shen³

et al. 2017

Theranostics

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Although the prognosis of differentiated thyroid cancer (DTC) is relatively good, 30-40% of patients with distant metastases develop resistance to radioactive iodine therapy due to tumor dedifferentiation. For DTC patients harboring BRAFV600E mutation, Vemurafenib, a BRAF kinase inhibitor, has dramatically changed the therapeutic landscape, but side effects and drug resistance often lead to termination of the single agent treatment. In the present study, we showed that either LY3009120 or Obatoclax (GX15-070) efficiently inhibited cell cycle progression and induced massive death of DTC cells. We established that BRAF/CRAF dimerization was an underlying mechanism for Vemurafenib resistance. LY3009120, the newly discovered pan-RAF inhibitor, successfully overcame Vemurafenib resistance and suppressed the growth of DTC cells in vitro and in vivo. We also observed that expression of anti-apoptotic Bcl-2 increased substantially following BRAF inhibitor treatment in Vemurafenib-resistant K1 cells, and both Obatoclax and LY3009120 efficiently induced apoptosis of these resistant cells. Specifically, Obatoclax exerted its anti-cancer activity by inducing loss of mitochondrial membrane potential (ΔΨm), dysfunction of mitochondrial respiration, reduction of cellular glycolysis, autophagy, neutralization of lysosomes, and caspase-related apoptosis. Furthermore, the cancer killing effects of LY3009120 and Obatoclax extended to two more Vemurafenib-resistant DTC cell lines, KTC-1 and BCPAP. Taken together, our results highlighted the potential value of LY3009120 for both Vemurafenib-sensitive and -resistant DTC and provided evidence for the combination therapy using Vemurafenib and Obatoclax for radioiodine-refractory DTC.

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Section: Discussionsupporting

confidence: 44%

Obatoclax and LY3009120 Efficiently Overcome Vemurafenib Resistance in Differentiated Thyroid Cancer

Wei¹,

Sun²,

Shen³

et al. 2017

Theranostics

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“…Compared to real-time PCR, ddPCR is much more accurate and easier to perform; accordingly, it requires much more costly equipment and consumables [33]. …”

Section: Resultsmentioning

confidence: 99%

A digital PCR method for identifying and quantifying adulteration of meat species in raw and processed food

et al. 2017

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Meat adulteration is a worldwide concern. In this paper, a new droplet digital PCR (ddPCR) method was developed for the quantitative determination of the presence of chicken in sheep and goat meat products. Meanwhile, a constant (multiplication factor) was introduced to transform the ratio of copy numbers to the proportion of meats. The presented ddPCR method was also proved to be more accurate (showing bias of less than 9% in the range from 5% to 80%) than real-time PCR, which has been widely used in this determination. The method exhibited good repeatability and stability in different thermal treatments and at ultra-high pressure. The relative standard deviation (RSD) values of 5% chicken content was less than 5.4% for ultra-high pressure or heat treatment. Moreover, we confirmed that different parts of meat had no effect on quantification accuracy of the ddPCR method. In contrast to real-time PCR, we examined the performance of ddPCR as a more precise, sensitive and stable analytical strategy to overcome potential problems of discrepancies in amplification efficiency discrepancy and to obtain the copy numbers directly without standard curves. The method and strategy developed in this study can be applied to quantify the presence and to confirm the absence of adulterants not only to sheep but also to other kinds of meat and meat products.

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“…[129] Basically, generated PCR amplicons were tagged with biotin molecules and target-specific overhang hybridization sequences. For example, Wee et al incorporated the standard PCR assay with a multiplex SERS barcoding system for ultrasensitive detection of cancer DNA mutations (BRAF V600E, c-Kit L576P, and NRAS Q61K) in ctDNA from serum samples of melanoma patients.…”

Section: Nanotag-based Detectionmentioning

confidence: 99%

Engineering State‐of‐the‐Art Plasmonic Nanomaterials for SERS‐Based Clinical Liquid Biopsy Applications

et al. 2019

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Precision oncology, defined as the use of the molecular understanding of cancer to implement personalized patient treatment, is currently at the heart of revolutionizing oncology practice. Due to the need for repeated molecular tumor analyses in facilitating precision oncology, liquid biopsies, which involve the detection of noninvasive cancer biomarkers in circulation, may be a critical key. Yet, existing liquid biopsy analysis technologies are still undergoing an evolution to address the challenges of analyzing trace quantities of circulating tumor biomarkers reliably and cost effectively. Consequently, the recent emergence of cutting-edge plasmonic nanomaterials represents a paradigm shift in harnessing the unique merits of surface-enhanced Raman scattering (SERS) biosensing platforms for clinical liquid biopsy applications. Herein, an expansive review on the design/synthesis of a new generation of diverse plasmonic nanomaterials, and an updated evaluation of their demonstrated SERS-based uses in liquid biopsies, such as circulating tumor cells, tumor-derived extracellular vesicles, as well as circulating cancer proteins, and tumor nucleic acids is presented. Existing challenges impeding the clinical translation of plasmonic nanomaterials for SERS-based liquid biopsy applications are also identified, and outlooks and insights into advancing this rapidly growing field for practical patient use are provided.

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Simple, Sensitive and Accurate Multiplex Detection of Clinically Important Melanoma DNA Mutations in Circulating Tumour DNA with SERS Nanotags

Cited by 115 publications

References 38 publications

Obatoclax and LY3009120 Efficiently Overcome Vemurafenib Resistance in Differentiated Thyroid Cancer

Obatoclax and LY3009120 Efficiently Overcome Vemurafenib Resistance in Differentiated Thyroid Cancer

A digital PCR method for identifying and quantifying adulteration of meat species in raw and processed food

Engineering State‐of‐the‐Art Plasmonic Nanomaterials for SERS‐Based Clinical Liquid Biopsy Applications

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