Role of Acid Ceramidase In Xenografted Zebrafish Glioblastoma Model.

Mentor 1

Shama P. Mirza

Location

Union Wisconsin Room

Start Date

5-4-2019 1:30 PM

End Date

5-4-2019 3:30 PM

Description

Glioblastoma is considered as the most aggressive form of brain tumor with overall survival less than fifteen months after diagnosis, even with multimodal therapy. It constitutes a major percentage of malignant brain tumors, with over 10,000 new cases reported every year in the USA. Comprehensive proteomic study of the disease in our lab has revealed that acid ceramidase is a novel target for possible drug development. Previous in Vitro study has found that acid ceramidase inhibitors (e.g. carmofur) have better efficacy than the standard chemotherapeutic drug available. This study aims to identify the role of acid ceramidase in glioblastoma and the efficacy of acid ceramidase inhibitors in suppressing the tumor, which may potentially lead to the development of a new chemotherapeutic agent for treating glioblastoma. Herein, we have worked towards the development of xenografted zebrafish (Danio rerio) glioblastoma model. For which, we have developed a zebrafish experimental microinjection protocol, where zebrafish embryos were dechorionated and mounted on agarose gel with a goal of microinjecting glioblastoma cell lines. Development of the protocol consisted of optimizing quality and quantity of embryos, as well as injection site and dosage. We have continued to optimize the microinjection protocol in order to provide the most accurate injection site while performing the less intrusive injection possible. Further work is to develop zebrafish xenografts by injecting GFP transfected glioblastoma cell lines to EK zebrafish strain. This model system will be used to study if acid ceramidase inhibitors can cross the blood-brain barrier, and their role in tumor suppression using imaging microscopy and mass spectrometric techniques.

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Apr 5th, 1:30 PM Apr 5th, 3:30 PM

Role of Acid Ceramidase In Xenografted Zebrafish Glioblastoma Model.

Union Wisconsin Room

Glioblastoma is considered as the most aggressive form of brain tumor with overall survival less than fifteen months after diagnosis, even with multimodal therapy. It constitutes a major percentage of malignant brain tumors, with over 10,000 new cases reported every year in the USA. Comprehensive proteomic study of the disease in our lab has revealed that acid ceramidase is a novel target for possible drug development. Previous in Vitro study has found that acid ceramidase inhibitors (e.g. carmofur) have better efficacy than the standard chemotherapeutic drug available. This study aims to identify the role of acid ceramidase in glioblastoma and the efficacy of acid ceramidase inhibitors in suppressing the tumor, which may potentially lead to the development of a new chemotherapeutic agent for treating glioblastoma. Herein, we have worked towards the development of xenografted zebrafish (Danio rerio) glioblastoma model. For which, we have developed a zebrafish experimental microinjection protocol, where zebrafish embryos were dechorionated and mounted on agarose gel with a goal of microinjecting glioblastoma cell lines. Development of the protocol consisted of optimizing quality and quantity of embryos, as well as injection site and dosage. We have continued to optimize the microinjection protocol in order to provide the most accurate injection site while performing the less intrusive injection possible. Further work is to develop zebrafish xenografts by injecting GFP transfected glioblastoma cell lines to EK zebrafish strain. This model system will be used to study if acid ceramidase inhibitors can cross the blood-brain barrier, and their role in tumor suppression using imaging microscopy and mass spectrometric techniques.