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  11. Comprehensive Clinical Imaging, Histopathological Analysis And Liquid Biopsy-based Surveillance Of Human Uveal Melanoma In A Prolonged Rabbit Xenograft Model

Comprehensive clinical imaging, histopathological analysis and liquid biopsy-based surveillance of human uveal melanoma in a prolonged rabbit xenograft model

Prisca Bustamante1,2,3, Jacqueline Coblentz1,2, Christina Mastromonaco2

  • 1Cancer Research Program, Research Institute of the McGill University Health Centre.

Melanoma Research
|June 7, 2024

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View abstract on PubMed

Summary
This summary is machine-generated.

This study optimized a human uveal melanoma rabbit model by adjusting cyclosporine A doses, enabling longer observation and early detection of tumors using liquid biopsy and advanced imaging techniques.

Area of Science:

  • Ophthalmology
  • Oncology
  • Animal Models

Background:

  • Uveal melanoma is the most common adult intraocular tumor.
  • Previous animal models were limited by short survival (12 weeks) due to cyclosporine A side effects.

Purpose of the Study:

  • To optimize a human uveal melanoma rabbit xenograft model for extended observation up to 20 weeks.
  • To evaluate the efficacy of different cyclosporine A doses on tumor progression and animal survival.
  • To assess the utility of multimodal imaging and liquid biopsy for monitoring tumor development.

Main Methods:

  • Twenty rabbits were inoculated with human uveal melanoma cell lines (92.1 or MP41) and assigned to four groups with varying cyclosporine A doses (0-10 mg/kg).
  • Tumor progression was monitored using fundoscopy, ultrasound, and optical coherence tomography.

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  • Histopathological analysis and liquid biopsy (plasma and aqueous humor ctDNA) were performed.

    • Main Results:

    • Intraocular tumors were detected in all animals, with size and growth correlating to cyclosporine A dose; tumors regressed upon cyclosporine A withdrawal.
    • Tumor markers HMB-45 and MelanA were expressed in all tumors, with variations in size, pigmentation, and morphology between cell lines.
    • Circulating tumor DNA (ctDNA) was detected earlier than imaging and correlated with tumor growth.

    Conclusions:

    • Adjusting cyclosporine A dosage successfully extended the observation period in a human uveal melanoma rabbit model.
    • Multimodal imaging combined with liquid biopsy provides effective monitoring of tumor progression.
    • This optimized model facilitates further research into uveal melanoma treatment and biomarker discovery.