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  • El-Heliebi, Amin (author)

In Situ Detection and Quantification of AR-V7, AR-FL, PSA, and KRAS Point Mutations in Circulating Tumor Cells

  • Article/chapterEnglish2018

Publisher, publication year, extent ...

  • 2018-03-01
  • Oxford University Press (OUP),2018
  • printrdacarrier

Numbers

  • LIBRIS-ID:oai:DiVA.org:su-154822
  • https://urn.kb.se/resolve?urn=urn:nbn:se:su:diva-154822URI
  • https://doi.org/10.1373/clinchem.2017.281295DOI
  • http://kipublications.ki.se/Default.aspx?queryparsed=id:137735715URI

Supplementary language notes

  • Language:English
  • Summary in:English

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  • Subject category:ref swepub-contenttype
  • Subject category:art swepub-publicationtype

Notes

  • BACKGROUND: Liquid biopsies can be used in castration-resistant prostate cancer (CRPC) to detect androgen receptor splice variant 7 (AR-V7), a splicing product of the androgen receptor. Patients with AR-V7-positive circulating tumor cells (CTCs) have greater benefit of taxane chemotherapy compared with novel hormonal therapies, indicating a treatment-selection biomarker. Likewise, in those with pancreatic cancer (PaCa), KRAS mutations act as prognostic biomarkers. Thus, there is an urgent need for technology investigating the expression and mutation status of CTCs. Here, we report an approach that adds AR-V7 or KRAS status to CTC enumeration, compatible with multiple CTC-isolation platforms.METHODS: We studied 3 independent CTC-isolation devices (CellCollector, Parsortix, CellSearch) for the evaluation of AR-V7 or KRAS status of CTCs with in situ padlock probe technology. Padlock probes allow highly specific detection and visualization of transcripts on a cellular level. We applied padlock probes for detecting AR-V7, androgen receptor full length (AR-FL), and prostate-specific antigen (PSA) in CRPC and KRAS wildtype (wt) and mutant (mut) transcripts in PaCa in CTCs from 46 patients.RESULTS: In situ analysis showed that 71% (22 of 31) of CRPC patients had detectable AR-V7 expression ranging from low to high expression [1-76 rolling circle products (RCPs)/CTC]. In PaCa patients, 40% (6 of 15) had KRAS mut expressing CTCs with 1 to 8 RCPs/CTC. In situ padlock probe analysis revealed CTCs with no detectable cytokeratin expression but positivity for AR-V7 or KRAS mut transcripts.CONCLUSIONS: Padlock probe technology enables quantification of AR-V7, AR-FL, PSA, and KRAS mut/wt transcripts in CTCs. The technology is easily applicable in routine laboratories and compatible with multiple CTC-isolation devices.

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  • Hille, Claudia (author)
  • Laxman, NavyaStockholms universitet,Institutionen för biokemi och biofysik,Science for Life Laboratory (SciLifeLab)(Swepub:su)nlaxm (author)
  • Svedlund, JessicaStockholms universitet,Institutionen för biokemi och biofysik,Science for Life Laboratory (SciLifeLab) (author)
  • Haudum, Christoph (author)
  • Ercan, Erkan (author)
  • Kroneis, Thomas (author)
  • Chen, Shukun (author)
  • Smolle, Maria (author)
  • Rossmann, Christopher (author)
  • Krzywkowski, TomaszStockholms universitet,Institutionen för biokemi och biofysik,Science for Life Laboratory (SciLifeLab)(Swepub:su)maku5421 (author)
  • Ahlford, AnnikaStockholms universitet,Institutionen för biokemi och biofysik,Science for Life Laboratory (SciLifeLab),Devyser AB, Sweden(Swepub:su)anah7164 (author)
  • Darai, EvangeliaStockholms universitet,Institutionen för biokemi och biofysik,Science for Life Laboratory (SciLifeLab)(Swepub:su)evda1426 (author)
  • von Amsberg, Gunhild (author)
  • Alsdorf, Winfried (author)
  • König, Frank (author)
  • Löhr, MatthiasKarolinska Institutet (author)
  • de Kruijff, Inge (author)
  • Riethdorf, Sabine (author)
  • Gorges, Tobias M. (author)
  • Pantel, Klaus (author)
  • Bauernhofer, Thomas (author)
  • Nilsson, MatsStockholms universitet,Institutionen för biokemi och biofysik,Science for Life Laboratory (SciLifeLab)(Swepub:su)matsn (author)
  • Sedlmayr, Peter (author)
  • Stockholms universitetInstitutionen för biokemi och biofysik (creator_code:org_t)

Related titles

  • In:Clinical Chemistry: Oxford University Press (OUP)64:3, s. 536-5460009-91471530-8561

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