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Reference: https://app.jove.com/t/2558/orthotopi... The process of orthotopic xenografting involves the implantation of human luciferase-tagged malignant peripheral nerve sheath tumor cells, which serves as a model for in vivo evaluation of potential therapeutic agents. This innovative approach allows researchers to study the behavior of these tumor cells in a living organism, closely mimicking the natural environment of the tumor. By utilizing luciferase tagging, the growth and response of the tumor cells to various treatments can be monitored in real-time, providing valuable insights into the efficacy of candidate therapies. In this experimental framework, the malignant peripheral nerve sheath tumor cells are carefully selected and modified to express luciferase, a bioluminescent enzyme that facilitates the tracking of tumor progression and response to treatment. The orthotopic placement of these cells ensures that they are situated in their original anatomical location, which is crucial for accurately assessing the interactions between the tumor and the surrounding tissues. This method not only enhances the relevance of the findings but also allows for a more comprehensive understanding of the tumor microenvironment and its influence on therapeutic outcomes. Ultimately, the use of orthotopic xenografting with luciferase-tagged cells represents a significant advancement in preclinical research, enabling the identification and optimization of new therapeutic strategies for treating malignant peripheral nerve sheath tumors. By providing a robust platform for in vivo testing, this approach holds the potential to accelerate the development of effective treatments, ultimately improving patient outcomes in the clinical setting.