# Patient-specific 3D-tissue slices from peritoneal metastases – An in vitro model for individual susceptibility analysis

**Authors:** Christian Etzold, Orestis Lyros, Matthias Mehdorn, Robert Nowotny, Stefan Niebisch, Boris Jansen-Winkeln, Katrin Schierle, Ines Gockel, René Thieme

PMC · DOI: 10.1515/pp-2024-0012 · 2025-02-26

## TL;DR

Researchers developed a lab model using patient-specific 3D tissue slices from peritoneal metastases to study individual responses to chemotherapy drugs.

## Contribution

The study introduces a novel in vitro model using 3D-tissue slices from peritoneal metastases to assess patient-specific chemosensitivity.

## Key findings

- 3D-tissue slices from peritoneal metastases retained tumor cell morphology and Ki-67 expression after in vitro culture.
- Doxorubicin treatment reduced cytokeratin-positive tumor cells and proliferative cells in the slices.
- The model successfully cultured patient-specific slices for up to 4 days, preserving tumor characteristics.

## Abstract

The prognosis of patients with peritoneal metastases (PM) is poor, and these patients have a brief overall survival. Most patients with advanced PM receive palliative therapy to maintain their quality of life. In our current study, we investigated whether patient-specific 3D-tissue slices from patients with PM subjected to pressurized intraperitoneal aerosol chemotherapy could be cultured in vitro.

Biopsies from gastric cancer patients with PM were characterized for cytokeratin-positive tumor cells and the proliferation marker Ki-67. Biopsies from seven patients were cut to 350 µM thick slices in a standardized manner, cultured with 10 µM 5-fluorouracil, doxorubicin, cisplatin, oxaliplatin, or irinotecan for 96 h, and then examined histopathologically and via immunohistochemistry for persistent cytokeratin and Ki-67 expression.

In vitro cultured slices revealed a similar morphology to un-cultured specimens, and Ki-67-positive tumor cell areas were present after 96 h. The total amount of tumor cells per slice was determined by pan-cytokeratin staining. In the doxorubicin-treated slices, the cytokeratin-positive tumor cell fraction and proliferative (Ki-67pos) cells were decreased. Patient-specific 3D-tissue-slice cultures from peritoneal biopsies were cultured in vitro for up to 4 days.

Potentially, these cultures are a reliable model to evaluate the chemosensitivity of patients with PM. Further investigation is needed to match the chemosensitivity with the clinical course of these patients.

## Linked entities

- **Proteins:** krt12.4.S (Keratin 12, gene 4 S homeolog), Mki67 (antigen identified by monoclonal antibody Ki 67)
- **Chemicals:** 5-fluorouracil (PubChem CID 3385), doxorubicin (PubChem CID 31703), cisplatin (PubChem CID 5460033), oxaliplatin (PubChem CID 9887053), irinotecan (PubChem CID 60838)
- **Diseases:** gastric cancer (MONDO:0001056)

## Full-text entities

- **Diseases:** PM (MESH:D010538), tumor (MESH:D009369), gastric cancer (MESH:D013274)
- **Species:** Homo sapiens (human, species) [taxon 9606]

## Figures

6 figures with captions in the complete paper: https://tomesphere.com/paper/PMC12016018/full.md

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Source: https://tomesphere.com/paper/PMC12016018