1530P Gemcitabine/nab-paclitaxel versus (modified) FOLFIRINOX for palliative first-line treatment of advanced pancreatic cancer: A propensity score analysis

Riedl, Jakob M.; Posch, Florian; Horvath, Lena; Gantschnigg, Antonia; Renneberg, Felix; Schwarzenbacher, E.; Moik, Florian; Barth, Dominik A.; Stotz, Michael; Schaberl-Moser, Renate; Pichler, Martin; Stöger, Herbert; Greil, Richard; Djanani, Angela; Schlick, Konstantin; Gerger, Armin

doi:10.1016/j.annonc.2020.08.2013

Cited by 1 publication

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“…Since 1997, gemcitabine has been a primary monotherapy option for the palliative treatment of PDAC. 47 However, resistance to gemcitabine frequently develops, potentially due to mechanisms such as epithelial-mesenchymal transition, presence of cancer stem cells, dysregulation of the epigenetic factor, overexpression of anti-apoptotic proteins and survival genes, metabolic adaptation complicating treatment and limiting effectiveness. 48,49 Our results show that sub-IC50 concentrations of gemcitabine induce the formation of TNTs between cancer cells.…”

Section: Tnts and Chemoresistancementioning

confidence: 99%

Pancreatic cancer cells exchange ribosomes through tunneling nanotubes

Martínková,

Jansová,

Vorel

et al. 2024

Preprint

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SUMMARYPancreatic ductal adenocarcinoma (PDAC) is recognized as one of the most lethal types of cancer. Tunneling nanotubes (TNTs) are thin membranous intercellular communications, which allow cells to exchange intracellular material and promote cell fitness. We show here that PDAC cells increase the formation of TNTs upon exposure to gemcitabine and that these TNTs contain ribosomal components. In the PANC-1 cell line and in PDAC explants obtained from patient biopsies, we observe polyadenylated RNA and assembled 80S ribosomes within the TNTs, indicating the possibility of an intercellular transfer of translationally active ribosomes. Using cells with labelled small ribosomal subunits (40S), we demonstrate active transport of the ribosomal subunit via TNTs to recipient cells. Our results show that PDAC cells can exchange components of the translational machinery, including mRNA, which may contribute to the resistance to therapy, highlighting the potential of targeting TNT dynamics as a therapeutic approach for PDAC.HighlightsPDAC cells derived from tumor biopsy samples form tunneling nanotubes in 2D cultureFormation of tunneling nanotubes is stimulated by gemcitabine5.8S ribosomal RNA is transferred in PDAC via activated tunneling nanotubesPolyadenylated RNA is present in tunneling nanotubesRibosomal components are detected in activated tunneling nanotubesPDAC cells exchange assembled ribosomes via tunneling nanotubesRibosomes are transferred via TNTs to recipient cells, incorporated into ribosomes

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Section: Tnts and Chemoresistancementioning

confidence: 99%