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Prostate cancer patient‐derived organoids: detailed outcome from a prospective cohort of 81 clinical specimens
The Journal of pathology, 2021-08, Vol.254 (5), p.543-555
Servant, Raphaëlle
Garioni, Michele
Vlajnic, Tatjana
Blind, Melanie
Pueschel, Heike
Müller, David C
Zellweger, Tobias
Templeton, Arnoud J
Garofoli, Andrea
Maletti, Sina
Piscuoglio, Salvatore
Rubin, Mark A
Seifert, Helge
Rentsch, Cyrill A
Bubendorf, Lukas
Le Magnen, Clémentine
2021
Details
Autor(en) / Beteiligte
Servant, Raphaëlle
Garioni, Michele
Vlajnic, Tatjana
Blind, Melanie
Pueschel, Heike
Müller, David C
Zellweger, Tobias
Templeton, Arnoud J
Garofoli, Andrea
Maletti, Sina
Piscuoglio, Salvatore
Rubin, Mark A
Seifert, Helge
Rentsch, Cyrill A
Bubendorf, Lukas
Le Magnen, Clémentine
Titel
Prostate cancer patient‐derived organoids: detailed outcome from a prospective cohort of 81 clinical specimens
Ist Teil von
The Journal of pathology, 2021-08, Vol.254 (5), p.543-555
Ort / Verlag
Chichester, UK: John Wiley & Sons, Ltd
Erscheinungsjahr
2021
Link zum Volltext
Quelle
Wiley Blackwell Single Titles
Beschreibungen/Notizen
Patient‐derived organoids (PDOs) represent promising preclinical models in various tumor types. In the context of prostate cancer (PCa), however, their establishment has been hampered by poor success rates, which impedes their broad use for translational research applications. Along with the necessity to improve culture conditions, there is a need to identify factors influencing outcomes and to determine how to assess success versus failure in organoid generation. In the present study, we report our unbiased efforts to generate PDOs from a cohort of 81 PCa specimens with diverse pathological and clinical features. We comprehensively analyzed histological features of each enrolled sample (Gleason score, tumor content, proliferation index) and correlated them with organoid growth patterns. We identified improved culture conditions favoring the generation of PCa organoids, yet no specific intrinsic tumor feature was broadly associated with sustained organoid growth. In addition, we performed phenotypic and molecular characterization of tumor–organoid pairs using immunohistochemistry, immunofluorescence, fluorescence in situ hybridization, and targeted sequencing. Morphological and immunohistochemical profiles of whole organoids altogether provided a fast readout to identify the most promising ones. Notably, primary samples were associated with an initial take‐rate of 83% (n = 60/72) in culture, with maintenance of cancer cells displaying common PCa alterations, such as PTEN loss and ERG overexpression. These cancer organoids were, however, progressively overgrown by organoids with a benign‐like phenotype. Finally, out of nine metastasis samples, we generated a novel organoid model derived from a hormone‐naïve lung metastasis, which displays alterations in the PI3K/Akt and Wnt/β‐catenin pathways and responds to androgen deprivation. Taken together, our comprehensive study explores determinants of outcome and highlights the opportunities and challenges associated with the establishment of stable tumor organoid lines derived from PCa patients. © 2021 The Authors. The Journal of Pathology published by John Wiley & Sons, Ltd. on behalf of The Pathological Society of Great Britain and Ireland.
Sprache
Englisch
Identifikatoren
ISSN: 0022-3417
eISSN: 1096-9896
DOI: 10.1002/path.5698
Titel-ID: cdi_pubmedcentral_primary_oai_pubmedcentral_nih_gov_8361965
Format
–
Schlagworte
1-Phosphatidylinositol 3-kinase
,
Aged
,
AKT protein
,
Cell culture
,
Cell Culture Techniques - methods
,
Cohort Studies
,
disease modeling
,
Fluorescence in situ hybridization
,
Growth patterns
,
Humans
,
Immunofluorescence
,
Immunohistochemistry
,
Male
,
Metastases
,
Metastasis
,
Middle Aged
,
Organoids
,
Original Paper
,
Original Papers
,
patient‐derived organoids
,
personalized medicine
,
Phenotypes
,
phenotypic and molecular features
,
Prostate cancer
,
Prostatic Neoplasms
,
PTEN protein
,
Wnt protein
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