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Articles 1 - 5 of 5
Full-Text Articles in Medicine and Health Sciences
The Regulation Of Pannexin1 And Pannexin2 In The Skin In Health And Disease, Rafael E. Sanchez Pupo
The Regulation Of Pannexin1 And Pannexin2 In The Skin In Health And Disease, Rafael E. Sanchez Pupo
Electronic Thesis and Dissertation Repository
Pannexins (PANX1, 2, 3) are a family of channel-forming glycoproteins that mediate intracellular and paracrine signaling. In contrast to PANX2, PANX1 has been extensively investigated in the skin, modulating cell differentiation, wound healing, and melanoma development. PANX1 and PANX2 can co-exist in the same cell and form mixed channels where their glycosylation seems to regulate their intermixing. N-glycosylation and caspase cleavage have been proposed as modulators of the function of PANX1, but their effects on PANX2 are unknown. We explored the PANX2 expression in mouse skin and showed that a Panx2 splice variant (PANX2-202) is continuously expressed throughout aging skin. …
Mirna Regulation Of Programmed Cell Death-1 In T Cells: Potential Prognostic And Therapeutic Markers In Melanoma, Nathan J. Johnston
Mirna Regulation Of Programmed Cell Death-1 In T Cells: Potential Prognostic And Therapeutic Markers In Melanoma, Nathan J. Johnston
Electronic Thesis and Dissertation Repository
Immunoinhibitory cell receptors that can induce a state of T cell exhaustion upon exposure to tumor antigen include Programmed Cell Death-1 (PD1). Although much research has been conducted on PD1, global miRNA regulation of PD1 in a cancer model has not been investigated. We hypothesized that miRNAs exist that can silence PD1 in vitro and revert symptoms of T cell exhaustion. Eleven miRNAs were discovered with altered expression between PD1+ and PD1- CD4+ T cells from melanoma-bearing mice. miR-28 and miR-107 mimics were shown to bind to and silence the 3’UTR of PD1, and miR-28, miR-150 and …
Targeted Sirna Delivery Methods For Rnai-Based Therapies, Di Chen
Targeted Sirna Delivery Methods For Rnai-Based Therapies, Di Chen
Electronic Thesis and Dissertation Repository
RNAi has great potential in future therapeutics as it has the ability to regulating many disease-related genes. However, many barriers prevent practical applications. To overcome the barriers, the specific targeting, efficient delivery system, the validated gene and the potent siRNA sequence are all vital important. The studies throughout this thesis have been focued on examining the validation of three RNAi therapies for two different disease models: allergic contact dermatitis and melanoma. For allergic contact dermatitis, I developed and tested a novel topical delivery system for siRNAs targeting TNFα (siTNFα) and MyD88 siRNA (siMyD88). While siRNAs applied without the transdermal enhancer …
In Vivo Magnetic Resonance Imaging For Assessing The Integrity Of The Blood-Tumour Barrier In A Mouse Model Of Melanoma Brain Metastasis, Mariama Henry
Electronic Thesis and Dissertation Repository
Melanoma is the deadliest form of skin cancer. Metastasis to the brain is a life-threatening complication of melanoma in which the clinical incidence is 6-43%. Few animal models exist for melanoma brain metastases, and many are not clinically relevant. MRI was implemented to examine the development of tumors in a clinically relevant model of melanoma brain metastases. Balanced steady-state free precession (b-SSFP) sequence was used to assess total metastasis burden, T1wSE MRI using Gd-DTPA was used to assess blood-tumour barrier (BTB) integrity in vivo and dextran perfusion was used to assess BTB leakiness in situ. This model produced low tumour …
Metastatic Disease: Interactions Between Tumor Cells And Host Environment During Cancer Cell Spread, Jennifer M. Maclean
Metastatic Disease: Interactions Between Tumor Cells And Host Environment During Cancer Cell Spread, Jennifer M. Maclean
Electronic Thesis and Dissertation Repository
Tumor and metastasis formation are not cell autonomous phenomena, but rather an evolution of disease within and responding to the host environment. Metastatic spread from a primary tumor occurs as a result of a complex interplay between tumor cells and the host, wherein tumor cells must escape the primary tumor, enter the host vasculature, travel to and arrest in a distant tissue and survive and grow in that new organ. It is known that cells that progress through these stages must both escape and exploit host systems, yet the mechanisms used are not fully understood. Therefore, the goal of this …