Keke Chen1, Zhijun Huang1, Xianbo Shen2, Xin Tian1, Chengguang Zhu1, Qin Shi1, Minhui Zen1, Zexi Yin1, Xiangling He1
1Department of Pediatric Hematology and Oncology, Hunan Provincial People’s Hospital, the First Affiliated Hospital of Hunan Normal University, Changsha, China.
2Department of Hepatology, Hunan Provincial People’s Hospital, the First Affiliated Hospital of Hunan Normal University, Changsha, China.
Summary
Purpose: To establish a neuroblastoma patient derived xenograft (PDX) mouse model to select antitumor drug and guide individualized therapy.
Methods: The tumor tissues from a child with neuroblastoma were transplanted into NSG mice to establish neuroblastoma PDX. The mice were divided into different groups treated with different anti-tumor drugs for 1 week. The physical condition, weight of mice, the pathological changes and protein expressions were observed to select the best clinical treatment. After individualized therapy, the therapeutic effect was evaluated by glioblastoma specific indicators and imaging examination. The feasibility and effectiveness of the individualized therapy were also verified in another 3 patients.
Results: The PDX mouse model was successfully established with the same pathologic characteristics as the child’s neuroblastoma. The chemotherapy regimens in group B and D showed toxicity with the larger decrease of weight in mice. The chemotherapy regimen in group G had strong killing ability on tumor with neuroblastoma cell rate of 0%, and negative expression of CD56, CGA, SYN, which was recommended as the optimal regimen. The child completed chemotherapy successfully, and is currently disease-free. During 23-month follow-up, neuron specific enolase was in normal range and no obvious sign of recurrence was found. The individualized therapy based on PDX in another 3 children also obtained good therapeutic effect and prognosis.
Conclusion: The neuroblastoma PDX mouse model has been successfully established for drug efficacy evaluation, and the screened regimen can be applied to individualized treatment with favourable prognosis.
Key words: neuroblastoma, patient derived xenograft model, individualized therapy, preclinical model.
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