Details

Autor(en) / Beteiligte

• Koerfer, Justus
• Kallendrusch, Sonja
• Merz, Felicitas
• Kubick, Christoph
• Kassahun, Woubet
• Schumacher, Guido
• Moebius, Christian
• Gassler, Nikolaus
• Eckmann, Christian
• Koerfer, Alfred
• Weimann, Arved
• Wiechmann, Volker
• Geister, Daniela
• Aigner, Achim
• Bechmann, Ingo
• Lordick, Florian

Titel

Organotypic slice cultures of human gastric cancer (GC) and esophagogastric junction adenocarcinoma (AEG): A new technology to study treatment response, resistance, and tumor heterogeneity

Ist Teil von

• Journal of clinical oncology, 2015-01, Vol.33 (3_suppl), p.76-76

Erscheinungsjahr

2015

Link zum Volltext

Quelle

EZB Free E-Journals

Beschreibungen/Notizen

• Abstract only 76 Background: GC and AEG have an unpredictable response to cytotoxic treatment and a poor prognosis. There is an urgent need for new research methods allowing for the determination of chemotherapy sensitivities, the analysis of resistance mechanisms and tumor heterogeneity. Here, we describe a novel technique extending our recent findings in other tumors (Gerlach et al. 2014; Merz et al. 2013), by which cancer specimens can be cultured in vitro and maintained in their natural micro-environment. Methods: Using a tissue chopper, fresh surgical and endoscopic tissue samples from GC and AEG were cut in 400 µm thick slices and cultivated in 6-well plates for up to 6 days. The slices were then fixed, embedded in paraffin and cut for routine histopathology and immunohistochemistry. Cytokeratin stains (CK8 and AE1/3) were used for determining tumor cellularity, ki-67 for proliferation, and cleaved caspase 3 staining for apoptosis. The slices were examined under naïve condition and following in-vitro exposure to 5-FU, cisplatin or docetaxel over a period of 2-4 days. Results: GC and AEG slice cultures from resection specimens (n=14) and endoscopic biopsies (n=17) revealed a good preservation of tissue morphology and tumor cell integrity during the culture period in most cases. The stroma and the tumor cellularity remained stable over at least 4 days, proving the viability of cancer in slice cultures. The amount of sampled tissue from endoscopic biopsies was identified as a critical determinant for the feasibility of slice cultures. During treatment of cultures with chemotherapy, a significant loss of tumor cellularity and an increase of apoptotic cells were observed, although a systematic and reproducible read-out still needs to be established. Conclusions: Slice cultures of GC and AEG were successfully established. They can be expected to provide a unique and powerful in vitro platform for the determination of sensitivities of a given tumor towards chemotherapy, to examine mechanisms of drug-resistance and to analyze tumor heterogeneity in patient samples.