Date of Award

12-1-2018

Degree Type

Dissertation

Degree Name

Doctor of Philosophy

Field of Study

Biomedical Sciences

Department

Graduate School of Biomedical Sciences

First Advisor

Dong-Ming Su

Second Advisor

Rance E. Berg

Third Advisor

Alakananda Basu

Abstract

Tumor metastatic relapse is the major cause of cancer-associated mortality. Metastatic relapse is believed to arise from quantities of tumor cells that are below detectable thresholds, which are able to resist radio/chemotherapy by obtaining a dormant state and hiding in certain organs, i.e., tumor reservoirs. The thymus, the central T-cell immune organ, has been suggested to be a pre-metastatic tumor reservoir for B-lymphoma cells. However, it remains unknown whether the thymus is able to harbor nonlymphoid solid tumor cells, and whether chemotherapy can thoroughly eliminate cancer cells in the thymus. If chemotherapy is not able to eliminate these cells in the thymus, then what processes allow for this? Melanoma cell–inoculated and genotoxic doxorubicin-treated mouse model systems were used to determine that the thymus, particularly the atrophied thymus, was able to harbor bloodstream–circulating melanoma cells. In addition, chemotherapy-induced DNA-damage response triggered p53 activation in nonmalignant thymic cells, which in turn resulted in thymocyte death and thymic epithelial cell senescence to develop an inflammatory thymic microenvironment. This inflammatory condition induced thymic-harbored minimal tumor cells to acquire a chemo-resistant state.

Comments

Sizova, Olga, Atrophied thymus, a tumor reservoir for harboring melanoma cells. Doctor of Philosophy (Biomedical Sciences), November, 2018, 106pp., 25 illustrations, references:153

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