Thesis
Understanding the role of the circadian clock in radiation and immunotherapy efficacy in melanoma mouse model
Washington State University
Master of Science (MS), Washington State University
12/2019
DOI:
https://doi.org/10.7273/000000089
Handle:
https://hdl.handle.net/2376/123758
Abstract
Skin cancer is among the most commonly diagnosed cancers in the US. Melanoma is one of the
most fatal and belligerent forms of cutaneous skin cancer, resulting from the malignant
transformation of melanocytes. Conventionally, radiation therapy (RT) has been used in the
palliative treatment of melanoma, but due to the increased incidence of tumor cells resistance
and healthy tissue toxicities associated with radiation, melanoma treatment has been challenging.
Several studies have demonstrated that radiation can induce immunogenic tumor cell death,
hence the tumor gaining the role of in situ vaccine. For more effective treatment of melanoma,
the combination of radiation and immunotherapy has shown to have promising outcomes in
several cancer types including melanoma. The connection between the circadian clock, the DNA
damage response pathway, and the immune system has been demonstrated by various studies,
but further delineated mechanistic regulation of these pathways by the circadian clock remains to
be explored. This study focused on understanding the circadian clock influence in enhancing
ionizing radiation (IR) induced DNA damage response (DDR) signalling and immune response.
We observed that B16F10-Luc2 melanoma cells displayed a rhythmic expression of BMAL1 post serum shock synchronization. Maximum DNA damage in these cells was observed post IR
treatment when BMAL1 levels were low (CT 26) which indicates the probable role of clock in
the DDR signalling pathway. In our mouse model, we observed a decreased in tumor volume
during the evening hours compared to untreated mice which may be due to increased infiltration
of CD8+ T cells to the tumor site during the evening hours (ZT 9). Further studies using a
combination of radiation and immunotherapy, we expect to see a difference in tumor volume
reduction with reduced healthy tissue toxicities.
Metrics
Details
- Title
- Understanding the role of the circadian clock in radiation and immunotherapy efficacy in melanoma mouse model
- Creators
- Jinita Bhupendra Modasia
- Contributors
- Shobhan Gaddameedhi (Degree Supervisor) - Washington State University, Pharmaceutical Sciences, Department ofKATHRYN MEIER (Committee Member) - Washington State University, Pharmaceutical Sciences, Department ofHUI H ZHANG (Committee Member) - Washington State University, Pharmaceutical Sciences, Department ofJONATHAN WISOR (Committee Member) - Washington State University, Biomedical Sciences, Department ofBOYANG WU (Committee Member) - Washington State University, Pharmaceutical Sciences, Department of
- Awarding Institution
- Washington State University
- Academic Unit
- Pharmacy and Pharmaceutical Sciences, College of
- Theses and Dissertations
- Master of Science (MS), Washington State University
- Publisher
- Washington State University
- Format
- pdf
- Number of pages
- 59
- Identifiers
- 99900591863401842
- Language
- English
- Resource Type
- Thesis