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Full-Text Articles in Medicine and Health Sciences
Targeting Neuronal Nitric Oxide Synthase (Nnos) For Melanoma Treatment, Shirley Tong
Targeting Neuronal Nitric Oxide Synthase (Nnos) For Melanoma Treatment, Shirley Tong
Pharmaceutical Sciences (PhD) Dissertations
Human cutaneous melanoma is the most aggressive form of skin cancer and the incidence rates have continued to increase over the years. Neuronal nitric oxide synthase (nNOS) produces nitric oxide (NO) has been found to be overexpressed in human melanoma and the expression of nNOS is induced by interferon-gamma (IFN-γ). In our studies, nNOS has been implicated in IFN-γ-stimulated melanoma progression and the inhibition of nNOS using novel inhibitors effectively inhibited IFN-γ-stimulated tumor growth in a xenograft mouse model. Programmed death-ligand 1 (PD-L1) is overexpressed in melanoma and plays an important role in suppressing the immune system 12-14. Our …
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. …
Impact Of Intratumor Heterogeneity And The Tumor Microenvironment In Shaping Tumor Evolution And Response To Therapy, Akash Mitra
Impact Of Intratumor Heterogeneity And The Tumor Microenvironment In Shaping Tumor Evolution And Response To Therapy, Akash Mitra
Dissertations & Theses (Open Access)
Intratumor heterogeneity (ITH) is a crucial challenge in cancer treatment. The genotypic and phenotypic heterogeneity underlying diverse cancer types leads to subclonal variation, which may result in mixed or failed response to therapy. The heterogeneity at the tumor level, along with the tumor microenvironment (TME), often shapes tumor evolution and ultimately clinical outcome. Given that modern treatment paradigms increasingly expose patients with metastatic disease to multiple treatment modalities through the course of their disease, there exists a need to characterize robust and predictive biomarkers of response to therapy. In order to accurately characterize tumor evolution, we need to account for …
Elucidating The Roles Of Il-15 In The Tumor Microenvironment, Rosa Maria Santana Carrero
Elucidating The Roles Of Il-15 In The Tumor Microenvironment, Rosa Maria Santana Carrero
Dissertations & Theses (Open Access)
ELUCIDATING THE ROLES OF IL-15 IN THE TUMOR MICROENVIRONMENT
Rosa M. Santana Carrero, B.S.
Advisory Professors: Shao-Cong Sun, Ph.D. & Kimberly S. Schluns, Ph.D.
Interleukin-15 (IL-15) is a factor that promotes activation, proliferation, cytotoxicity, and survival of CD8 T cells and NK cells, and has been shown to have anti-tumor effects. Moreover, loss of IL-15 expression in human colorectal tumors correlates with increased risk of relapse, diminished survival, decreased density and proliferation of T cells. All together these findings suggest that IL-15 expressed locally in the tumor microenvironment (TME) is an important mediator of anti-tumor responses by tumor infiltrating lymphocytes …
Il-1Α Blockade Reduces Immune Suppression In The Early Tumor Micro-Environment, Brenda Melendez
Il-1Α Blockade Reduces Immune Suppression In The Early Tumor Micro-Environment, Brenda Melendez
Dissertations & Theses (Open Access)
IL-1α Blockade Reduces Immune Suppression in the Early Tumor Micro-Environment
Brenda Melendez, B.S.
Advisory Professor: Gregory Lizee, PhD.
Immunotherapy against melanoma has shown great promise in the clinic for treating advanced-stage patients. However, a major barrier against effective T cell mediated cytotoxicity is immunosuppression in the tumor micro-environment. It has been described that tumors secrete pro-inflammatory cytokines capable of modulating immune responses that favors the growth of tumor cells. Specifically, IL-1 plays a critical role in myeloid cell recruitment and activation, which can in turn inhibit T cell activity in vivo. Moreover, IL-1 is also known to up-regulate immune inhibitory …
Evaluation Of Oncolytic And Immunomodulatory Potential Of The Hsv-1 Live-Attenuated Vaccine Strain Vc2 In An Immunocompetent Murine Melanoma Model, Natalie Wall Fowlkes
Evaluation Of Oncolytic And Immunomodulatory Potential Of The Hsv-1 Live-Attenuated Vaccine Strain Vc2 In An Immunocompetent Murine Melanoma Model, Natalie Wall Fowlkes
LSU Doctoral Dissertations
Melanoma accounts for 90% of skin cancer-related deaths in humans. Treatment options for metastatic melanoma in people is very limited. Melanoma is considered to be an immunogenic tumor, spurring interest in development of immunotherapies for the treatment of metastatic melanoma. Oncolytic virotherapy has been widely investigated. The first ever oncolytic virotherapy to receive FDA-approval is an HSV-1-based virus (Talimogene Laherperavec (T-Vec) or Imlygic) containing a transgene for human GM-CSF to enhance anti-tumor immune responses after injection. Durable response rate in human patients was only 16% despite impressive efficacy in anti-tumor effects in vitro and in murine tumor models. Novel viruses …
Characterization Of Differentiation And Prognostic Biomarkers On Cd8+ Tumor-Infiltrating Lymphocytes In Metastatic Melanoma, Richard C. Wu
Characterization Of Differentiation And Prognostic Biomarkers On Cd8+ Tumor-Infiltrating Lymphocytes In Metastatic Melanoma, Richard C. Wu
Dissertations & Theses (Open Access)
CD8+ cytotoxic T lymphocytes (CTL) frequently infiltrate tumors, yet most melanoma patients fail to undergo tumor regression. We studied the differentiation of the CD8+ tumor-infiltrating lymphocytes (TIL) from 44 metastatic melanoma patients using known T-cell differentiation markers. We also compared CD8+ TIL against the T cells from matched melanoma patients’ peripheral blood. We discovered a novel subset of CD8+ TIL co-expressing early-differentiation markers, CD27, CD28, and a late/senescent CTL differentiation marker, CD57. This CD8+CD57+ TIL expressed a cytolytic enzyme, granzyme B (GB), yet did not express another cytolytic pore-forming molecule, perforin (Perf). In …
Histone Deacetylases As Targets For Melanoma Immunotherapy, David Michael Woods
Histone Deacetylases As Targets For Melanoma Immunotherapy, David Michael Woods
USF Tampa Graduate Theses and Dissertations
Cancer represents the second leading cause of death in the United States. For many malignancies, currently available treatment options offer little long-lasting survival benefits to patients. However, recent studies have shown immunotherapeutic approaches to be an attractive strategy to cancer treatment. While many current immunotherapeutic strategies convey durable responses, such responses are only seen in a minority of patients. An increased understanding of the mechanisms governing tumor immunogenicity and the biology of immune responses is crucial to improving upon the efficacy of current and future cancer immunotherapies. Histone deacetylases (HDACs), enzymes classically associated with regulation of gene expression, have been …