title: Organotypic slice cultures of human gastric and esophagogastric junction cancer.
abstract: Gastric and esophagogastric junction cancers are heterogeneous and aggressive tumors with an unpredictable response to cytotoxic treatment. New methods allowing for the analysis of drug resistance are needed. Here, we describe a novel technique by which human tumor specimens can be cultured ex vivo, preserving parts of the natural cancer microenvironment. Using a tissue chopper, fresh surgical tissue samples were cut in 400 μm slices and cultivated in 6-well plates for up to 6 days. The slices were processed for routine histopathology and immunohistochemistry. Cytokeratin stains (CK8, AE1/3) were applied for determining tumor cellularity, Ki-67 for proliferation, and cleaved caspase-3 staining for apoptosis. The slices were analyzed under naive conditions and following 2-4 days in vitro exposure to 5-FU and cisplatin. The slice culture technology allowed for a good preservation of tissue morphology and tumor cell integrity during the culture period. After chemotherapy exposure, a loss of tumor cellularity and an increase in apoptosis were observed. Drug sensitivity of the tumors could be assessed. Organotypic slice cultures of gastric and esophagogastric junction cancers were successfully established. Cytotoxic drug effects could be monitored. They may be used to examine mechanisms of drug resistance in human tissue and may provide a unique and powerful ex vivo platform for the prediction of treatment response.
authors.affiliation: Institute for Anatomy, University Medicine Leipzig, Liebigstraße 13, 04103, Leipzig, Germany.|University Cancer Center Leipzig (UCCL), University Medicine Leipzig, Liebigstraße 20, 04103, Leipzig, Germany.
authors.forename: Justus
authors.initials: J
authors.lastname: Koerfer
authors.affiliation: Institute for Anatomy, University Medicine Leipzig, Liebigstraße 13, 04103, Leipzig, Germany.
authors.forename: Sonja
authors.initials: S
authors.lastname: Kallendrusch
authors.affiliation: Institute for Anatomy, University Medicine Leipzig, Liebigstraße 13, 04103, Leipzig, Germany.
authors.forename: Felicitas
authors.initials: F
authors.lastname: Merz
authors.affiliation: Institute of Pathology, University Medicine Leipzig, Liebigstraße 24, 04103, Leipzig, Germany.
authors.forename: Christian
authors.initials: C
authors.lastname: Wittekind
authors.affiliation: Institute of Pathology, University Medicine Leipzig, Liebigstraße 24, 04103, Leipzig, Germany.
authors.forename: Christoph
authors.initials: C
authors.lastname: Kubick
authors.affiliation: Department for Visceral, Transplantation Thoracic and Vascular Surgery, University Medicine Leipzig, Liebigstraße 20, 04103, Leipzig, Germany.
authors.forename: Woubet T
authors.initials: WT
authors.lastname: Kassahun
authors.affiliation: Department for General and Visceral Surgery, Klinikum Braunschweig, Salzdahlumer Straße 90, 38126, Braunschweig, Germany.
authors.forename: Guido
authors.initials: G
authors.lastname: Schumacher
authors.affiliation: Department for General and Visceral Surgery, Klinikum Braunschweig, Salzdahlumer Straße 90, 38126, Braunschweig, Germany.
authors.forename: Christian
authors.initials: C
authors.lastname: Moebius
authors.affiliation: Institute of Pathology, Klinikum Braunschweig, Celler Straße 38, 38114, Braunschweig, Germany.
authors.forename: Nikolaus
authors.initials: N
authors.lastname: Gaßler
authors.affiliation: Institute for Anatomy, University Medicine Leipzig, Liebigstraße 13, 04103, Leipzig, Germany.
authors.forename: Nikolas
authors.initials: N
authors.lastname: Schopow
authors.affiliation: Institute of Pathology, Klinikum St. Georg, Delitzscher Str. 141, 04129, Leipzig, Germany.
authors.forename: Daniela
authors.initials: D
authors.lastname: Geister
authors.affiliation: Institute of Pathology, Klinikum St. Georg, Delitzscher Str. 141, 04129, Leipzig, Germany.
authors.forename: Volker
authors.initials: V
authors.lastname: Wiechmann
authors.affiliation: Department for General and Visceral Surgery, Klinikum St. Georg, Delitzscher Str. 141, 04129, Leipzig, Germany.
authors.forename: Arved
authors.initials: A
authors.lastname: Weimann
authors.affiliation: Department for General, Visceral and Thoracic Surgery, Klinikum Peine, Virchowstraße 8, 31226, Peine, Germany.
authors.forename: Christian
authors.initials: C
authors.lastname: Eckmann
authors.affiliation: Rudolf-Boehm-Institute for Pharmacology and Toxicology, Clinical Pharmacology, University Medicine Leipzig, Härtelstraße 16-18, 04107, Leipzig, Germany.
authors.forename: Achim
authors.initials: A
authors.lastname: Aigner
authors.affiliation: Institute for Anatomy, University Medicine Leipzig, Liebigstraße 13, 04103, Leipzig, Germany.
authors.forename: Ingo
authors.initials: I
authors.lastname: Bechmann
authors.affiliation: University Cancer Center Leipzig (UCCL), University Medicine Leipzig, Liebigstraße 20, 04103, Leipzig, Germany.
authors.forename: Florian
authors.initials: F
authors.lastname: Lordick
mesh_terms: D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use; D001706:Biopsy; D003131:Combined Modality Therapy; D019008:Drug Resistance, Neoplasm; D004938:Esophageal Neoplasms / Q000188:drug therapy / Q000473:pathology* / Q000601:surgery; D004943:Esophagogastric Junction / Q000473:pathology*; D006801:Humans; D009924:Organ Culture Techniques; D057285:Precision Medicine / Q000379:methods; D013274:Stomach Neoplasms / Q000188:drug therapy / Q000473:pathology* / Q000601:surgery; D046509:Tissue Culture Techniques
keywords: Chemosensitivity; esophagogastric junction cancer; gastric cancer; organotypic slice cultures; personalized treatment