<> "The repository administrator has not yet configured an RDF license."^^ . <> . . "MYCN, proliferative heterogeneity and treatment response\r\nin neuroblastoma"^^ . "The amplification of the MYCN oncogene, occurring in 20% of neuroblastomas, a tumor of early childhood, is associated with drug-resistant relapse and poor prognosis. High MYCN expression has paradoxical effects in most cells: it promotes cell cycle progression and sensitizes to cell death. This work aims to characterize, at population and single-cell level, the mechanisms through which amplified MYCN allows tumor regrowth after chemotherapy in neuroblastoma.\r\nIn MYCN-regulatable neuroblastoma cell line models, MYCN shortens the lengths of cell cycle phases, preferentially in G1, and increases the proportion of cycling cells under exponential growth. Upon DNA-damage induced by the chemotherapeutic agent, doxorubicin (DOX), MYCN delays activation of cell cycle checkpoints and boosts the proportion of transiting cells. During and after chemotherapy MYCN favors cell death and suppresses cellular senescence, shifting p53 downstream effects from cell cycle arrest to apoptosis. However, MYCN also drives clonal regrowth of a small fraction of surviving resister cells after DNA-damage. These resister cells exhibit nearly identical molecular and phenotypic profiles as cells before treatment. Live-cell imaging reveals that resister cells arise exclusively from the G1-phase-arrested subpopulation and rapidly repair DNA-damage-induced double-strand breaks (DSBs). The suppression of DNA repair via ATM inhibition during chemotherapy results in reduction of G1 phase arrest and prevents DNA DSB repair, completely eradicating resister cells.\r\nTaken together, these data show that non-genetic tumor heterogeneity and a key oncogenic lesion, MYCN, synergize to resume cellular proliferation after DNA damage and probably cause chemotherapy resistance. This work indicates that improved first-line therapies could specifically target resister cells and help avoid cellular regrowth."^^ . "2017" . . . . . . . "Tatsiana"^^ . "Ryl"^^ . "Tatsiana Ryl"^^ . . . . . . "MYCN, proliferative heterogeneity and treatment response\r\nin neuroblastoma (Other)"^^ . . . . . . "preview.jpg"^^ . . . "MYCN, proliferative heterogeneity and treatment response\r\nin neuroblastoma (Other)"^^ . . . . . . "medium.jpg"^^ . . . "MYCN, proliferative heterogeneity and treatment response\r\nin neuroblastoma (Other)"^^ . . . . . . "small.jpg"^^ . . . "MYCN, proliferative heterogeneity and treatment response\r\nin neuroblastoma (Other)"^^ . . . . . . "indexcodes.txt"^^ . . . "MYCN, proliferative heterogeneity and treatment response\r\nin neuroblastoma (PDF)"^^ . . . "PhD Thesis_Tatjana Ryl_Bib.pdf"^^ . . . "MYCN, proliferative heterogeneity and treatment response\r\nin neuroblastoma (Other)"^^ . . . . . . "lightbox.jpg"^^ . . "HTML Summary of #20738 \n\nMYCN, proliferative heterogeneity and treatment response \nin neuroblastoma\n\n" . "text/html" . . . "500 Naturwissenschaften und Mathematik"@de . "500 Natural sciences and mathematics"@en . . . "570 Biowissenschaften, Biologie"@de . "570 Life sciences"@en . .