Medicine and Health Sciences Commons^™

Effect Of Selenof Loss In Combination With A Western Diet On Tumorigenesis, Brenna Joy Flowers

Master's Theses

SELENOF is an understudied selenium-containing protein that has previously been postulated to behave as a tumor suppressor in the breast. Examination of patient databases showed that SELENOF levels were lowest in tumors from patients with aggressive late-stage breast cancers. Whether loss of SELENOF drives breast tumorigenesis remains to be determined. To address this question, we used juvenile female wild type or systemic Selenof knockout mice and exposed them to 7,12-Dimethylbenz[a]anthracene (DMBA), a carcinogen that replicates the multistep process of breast tumorigenesis. Previous reports have shown that loss of Selenof led to glucose and metabolic dysregulation in mice suggesting a link …

Murine Tbk1 Is Required By Flt3+ Leukemia Stem Cells Yet Dispensable In Homeostatic Hematopoiesis, Austin Patrick Runde

Master's Theses

The TANK-binding kinase 1 (TBK1) is a cytoplasmic, serine/threonine kinase and a critical activator of the innate immune system. Reports have implicated TBK1 as a promoter of multiple cancer types. Acute myeloid leukemia (AML) is a cancer arising from the hematopoietic stem/progenitor cells (HSPCs). Although ~70% of AML patients achieve complete remission with chemotherapy, at least half will relapse due to the failure to eradicate leukemia stem cells (LSCs). As our previous data indicate the TLR-TAK1/TICAM-1 axes regulate LSCs, we suspect TBK1 also regulates LSCs. To study TBK1 in AML, we generated tamoxifen-inducible, Tbk1-knockout (Tbk1NULL) mice and Tbk1NULL MLL-AF9+ mouse …

Tumor Immunology: Understanding The Immune System And Cancer To Enhance The Efficacy Of Cancer Immunotherapies, Natasha Malibu Lenart

Master's Theses

Tumor cells are notorious for their ability to escape immune surveillance, but developments in the understanding of the tumor microenvironment and how the immune system can be re-activated in tumors have had significant clinical impact. Commercially available and experimental methods such as adoptive cellular therapy, cytokine stimulation, and immune checkpoint blockade are promising immunotherapies for a variety of cancers, including solid tumors and hematological malignancies. However, induction of persistent, long-term anti-tumor immunity after initial treatment is infamously difficult. as a result, scientists are searching for new approaches to improve established immunotherapies. by employing combination treatments or enhancing the functionality of …

Using Tcr Transgenic, Gp100 Reactive T Cells And Checkpoint Inhibition To Target Lymphangioleimyomatosis, Christian Ankney

Master's Theses

Lymphangioleiomyomatosis (LAM) is a low-grade neoplastic disease affecting primarily women. It is characterized by cystic lung disease as well as renal and retroperitoneal tumors called angiomyolipomas and lymphangiomas. Tumor cells have smooth muscle features as well as neuroendocrine cell surface markers, and the disease can be diagnosed by HMB45 staining of tumor cells. We questioned whether expression of melanocytic antigens, specifically gp100, creates an opportunity to treat LAM by adoptive T cell transfer. LAM lung lesions demonstrate poor immune surveillance, therefore adoptive T cell transfer could offer benefits in this disease.

A link was made between melanoma and depigmenting vitiligo …

Separating Autoimmune And Anti-Tumor Responses With Hsp70iq435a, James Mahon

Master's Theses

Vitiligo and melanoma are both melanocyte-derived diseases; vitiligo progresses through the autoimmune-targeted destruction of healthy melanocytes while melanoma results from uncontrolled proliferation of cancerous melanocytes. Treatment of vitiligo with HSP70iQ435A inhibits the DC-mediated auto-immune response against melanocytes in vitiligo mouse models; this raises the concern that treatment with this modified HSP may also inhibit natural anti-tumor responses against melanocyte-derived melanoma tumor cells.

We hypothesized that HSP70iQ435A prevents migration of melanocyte-antigen reactive T cells to the skin in a way that is mechanistically different from anti-tumor responses to melanoma and therefore would not have a negative effect on anti-tumor responses. We …