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.
Highlights
Gastric cancer (GC) and adenocarcinomas of the esophagogastric junction (AEG) are aggressive and highly heterogeneous tumors [1]
To the best of our knowledge, this is the first description of the successful establishment of ex vivo organotypic slice cultures of human gastric and esophagogastric junction cancers
We can show that cytotoxic drug effects like changes in tumor cellularity, proliferation, and apoptosis can be assessed in this model making this new technique an interesting platform for the assessment of individual drug response
Summary
Gastric cancer (GC) and adenocarcinomas of the esophagogastric junction (AEG) are aggressive and highly heterogeneous tumors [1]. Due to their critical prognosis following curative resection (R0), adjuvant treatment is the standard of care in most parts of the world. Western world studies advise perioperative chemotherapy or Gastric Cancer Slice Cultures chemoradiation [2,3,4,5], whereas postoperative chemotherapy is the standard of care in East Asia [6,7,8]. GC and AEG have unpredictable responses to cytotoxic treatment and the majority of patients are nonresponders [9, 10]. New methods are needed to overcome the limitations of established models in predicting treatment response [15]
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