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Naumann, Max [Author]; Czempiel, Tabea [Author]; Lößner, Anna Jana [Author]; Pape, Kristin [Author]; Beyreuther, Elke [Author]; Löck, Steffen [Author]; Drukewitz, Stephan [Author]; Hennig, Alexander [Author]; von Neubeck, Cläre [Author]; Klink, Barbara [Author]; Krause, Mechthild [Author]; William, Doreen [Author]; E. Stange, Daniel [Author]; Bütof, Rebecca [Author]; Dietrich, Antje [Author]

Combined Systemic Drug Treatment with Proton Therapy: Investigations on Patient-Derived Organoids

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  • Media type: E-Article
  • Title: Combined Systemic Drug Treatment with Proton Therapy: Investigations on Patient-Derived Organoids
  • Contributor: Naumann, Max [Author]; Czempiel, Tabea [Author]; Lößner, Anna Jana [Author]; Pape, Kristin [Author]; Beyreuther, Elke [Author]; Löck, Steffen [Author]; Drukewitz, Stephan [Author]; Hennig, Alexander [Author]; von Neubeck, Cläre [Author]; Klink, Barbara [Author]; Krause, Mechthild [Author]; William, Doreen [Author]; E. Stange, Daniel [Author]; Bütof, Rebecca [Author]; Dietrich, Antje [Author]
  • Published: Basel: MDPI, [2023]
  • Published in: Cancers ; 14,3781 (2022), Seite 1-15
  • Language: English
  • DOI: 10.3390/cancers14153781
  • Keywords: 3D cell culture ; PDAC ; pancreatic cancer ; proton irradiation ; patient-derived organoid ; translational radiooncology ; radiochemotherapy
  • Origination:
  • University thesis:
  • Footnote:
  • Description: To optimize neoadjuvant radiochemotherapy of pancreatic ductal adenocarcinoma (PDAC),the value of new irradiation modalities such as proton therapy needs to be investigated in relevantpreclinical models. We studied individual treatment responses to RCT using patient-derived PDACorganoids (PDO). Four PDO lines were treated with gemcitabine, 5-fluorouracile (5FU), photon andproton irradiation and combined RCT. Therapy response was subsequently measured via viabilityassays. In addition, treatment-naive PDOs were characterized via whole exome sequencing andtumorigenicity was investigated in NMRI Foxn1nu/nu mice. We found a mutational pattern containing common mutations associated with PDAC within the PDOs. Although we could unravelpotential complications of the viability assay for PDOs in radiobiology, distinct synergistic effectsof gemcitabine and 5FU with proton irradiation were observed in two PDO lines that may lead to further mechanistical studies. We could demonstrate that PDOs are a powerful tool for translationalproton radiation research.
  • Access State: Open Access
  • Rights information: Attribution (CC BY)