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Vom Gewebe über die Primärzellkultur zum Xenograftmodell

Patientennahe und funktionelle Prostatakarzinomforschung

From tumor tissue via primary cultures to xenograft models

A functional approach in prostate cancer research

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Zusammenfassung

Der klinische Verlauf eines Prostatakarzinoms, der häufigsten Krebserkrankung des Mannes, ist sehr variabel. Trotz intensiver Forschung fehlen bis heute – abgesehen von den klassischen histopathologischen Kriterien – prognostische Marker, die den Verlauf der Tumorerkrankung valide vorhersagen und eine gute Einschätzung der Therapiebedürftigkeit erlauben. Ein Grund hierfür liegt wahrscheinlich in dem Fehlen guter, patientennaher Tumormodellsysteme. Diese sind nicht nur von elementarer Bedeutung für ein besseres Verständnis der Pathogenese des Prostatakarzinoms, sondern spielen auch in der Entwicklung neuer therapeutischer Strategien eine wichtige Rolle. Da die an permanenten Zelllinien gewonnenen Ergebnisse nur bedingt auf die Klinik übertragbar sind und Primärkulturen aus Patientenproben nicht beliebig gezüchtet werden können, müssen neue Lösungsansätze geschaffen werden, die eine nachhaltige, patientennahe Prostatakarzinomforschung ermöglichen.

In der vorliegenden Arbeit wird die Entwicklung unterschiedlicher Strategien der Zellkultivierung aus Prostatakarzinomgewebe und die Kombination mit einem Mausxenograftmodell dargestellt und damit ein Ausblick auf zukünftige Forschungsziele gegeben.

Abstract

The clinical course of prostate cancer, the most common cancer in men, is very variable. Despite intense research activities over the years and besides histopathological criteria, prognostic markers that reliably predict tumor behavior and the necessity for treatment are still missing. A likely explanation for this fact is the lack of good tumor models, mimicking the in vivo situation. These models are not only essential for a better understanding of the pathogenesis of prostate cancer but also play an important role in the development of new therapeutic strategies. Since results of permanent cell culture experiments reflect only in part real tumor behavior and primary cultures from patient material cannot be grown indefinitely, novel approaches need to be developed to achieve reliable and clinically relevant prostate cancer research.

In this work the development of several approaches for culturing primary prostate cancer tissue is illustrated and a forecast of future research plans utilizing xenograft models in mice is made.

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Abb. 1

Abbreviations

CGH:

Comparative genomic hybridization = komparative genomische Hybridisierung

ECM:

Extracellular matrix = extrazelluläre Matrix

EMT:

Epithelial-mesenchymal transition = epitheliale mesenchymale Transition

FISH:

Fluorescence in situ hybridization = Fluoreszenz-in-situ-Hybridisierung

hTERT:

Human telomerase reverse transcriptase = humane telomerase-reverse Transkriptase

RNA:

Ribonucleic acid = Ribonukleinsäure

SKY:

Spectral karyotyping = spektrale Karyotypisierung

SOP:

Standard operating procedure = Standardvorgehensweise

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Correspondence to G. Unteregger.

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Saar, M., Kamradt, J., Jung, V. et al. Vom Gewebe über die Primärzellkultur zum Xenograftmodell. Urologe 50, 961–967 (2011). https://doi.org/10.1007/s00120-011-2630-7

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