Analysis of drug sensitivity of human high-grade osteosarcoma in a chick chorioallantoic membrane (CAM) model: a proof o
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RESEARCH NOTE
Analysis of drug sensitivity of human high‑grade osteosarcoma in a chick chorioallantoic membrane (CAM) model: a proof of principle study Wiebke K. Guder1,2* , Wolfgang Hartmann3, Marcel Trautmann3, Jendrik Hardes1,2, Eva Wardelmann3, Maurice Balke4 and Arne Streitbürger1,2
Abstract Objective: Multi-agent chemotherapy is an important pillar in treatment of high-grade osteosarcoma. In an effort to improve patient survival, it is imperative to determine the effectiveness of new substances. The objective of this study was to investigate whether the chick chorioallantoic membrane (CAM) model can be used to analyze drug sensitivity in high-grade osteosarcoma. Results: Spare biopsy tissue from five patients diagnosed with high-grade osteosarcoma was transferred into nonimmortalized primary cell culture. After a pre-incubation period of 10 days, fertilized chick eggs were inoculated with primary tumor cells suspended in extracellular matrix gel. On day 16, treatment with 20 µmol/l doxorubicin (n = 4) or 25 µl of culture medium (n = 6) was performed for 24 h. CAM membranes were documented macroscopically, harvested and examined histologically. Transfer of biopsy specimens into primary cell culture was successful in all cases. 50% (n = 10) of eggs died after inoculation with tumor cells and before application of doxorubicin. No deaths occurred after application of doxorubicin. Histological examination found a response to doxorubicin in all four specimens. Based upon these results, the CAM model represents a promising preclinical alternative to animal experiments to determine drug sensitivity of osteosarcoma cells. Further research with regard to other substances and dosages appear justified. Keywords: Chorioallantoic membrane model, CAM, Osteosarcoma, Primary cell culture Background High-grade osteosarcoma is a rare disease, mostly affecting children, adolescents and young adults. A combination of chemotherapy and wide tumor resection are the main pillars for successful treatment of these patients. The significance of chemotherapy
*Correspondence: wiebke.guder@uk‑essen.de 1 Department of General and Tumor Orthopedics, University Hospital Muenster, Albert‑Schweitzer‑Campus 1, Building A1, 48149 Münster, Germany Full list of author information is available at the end of the article
becomes clear when considering how overall survival rates improved from 20% to more than 60% with the introduction of multi-agent chemotherapy [1]. Standard chemotherapeutic agents include doxorubicin, cisplatin, ifosfamide and methotrexate [2]. Patients are usually enrolled in multimodal clinical trials in an effort to improve treatment outcomes by comparing new approaches to a standard regimen. Current protocols intend patients to undergo neoadjuvant chemotherapy to evaluate response to chemotherapy as the percentage of tumor regression found in the resection specimen of the primary tumor. As a result, good
© The Author(s) 2020. This article is licensed under a Creative Commons Attribution 4.0
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