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Full-Text Articles in Pharmacy and Pharmaceutical Sciences

Effects Of Nnos Inhibitors On Melanoma-Induced Immunosuppression, Kate Alison Lozada Aug 2022

Effects Of Nnos Inhibitors On Melanoma-Induced Immunosuppression, Kate Alison Lozada

Pharmaceutical Sciences (MS) Theses

The incidence of cutaneous melanoma (CM) rises despite advances in immunotherapy and targeted therapy. Studies have shown that interferon-gamma (IFN-γ), a pro-tumorigenic cytokine in CM, induces the expression of programmed death-ligand 1 (PD-L1), leading to the escape of melanoma cells from immunosurveillance. Our previous study suggests that neuronal nitric oxide synthase (nNOS)-mediated nitric oxide (NO) signaling is crucial for melanoma progression and forms a mechanistic rationale behind nNOS inhibition as a novel treatment strategy for CM. An additional study demonstrated that IFN-γ interacts with nNOS signaling in melanoma and novel nNOS inhibitors (nNOSi) effectively diminished the induction of PD-L1 post …


Targeting Neuronal Nitric Oxide Synthase (Nnos) For Melanoma Treatment, Shirley Tong May 2022

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 Development Of A Cancer-Targeting Peptide-Drug Conjugate For The Treatment Of Melanoma, Cassandra Dill Jan 2021

The Development Of A Cancer-Targeting Peptide-Drug Conjugate For The Treatment Of Melanoma, Cassandra Dill

Pharmaceutical Sciences (MS) Theses

Cancer is an ongoing global pandemic which has caused a dramatic shift in research priorities. One of the most aggressive and difficult to treat has invariably remained metastatic melanoma. Although encompassing only 4% of overall skin cancer diagnoses, chances for recovery were slim until recent revolutionary development of immunotherapy adding to its regimen spectrum. This is due to its resistance to many standard-of-care treatment methods, along with its relatively high-metastatic potential. Within the past decade, eight new targeted and immune checkpoint inhibitors have gained FDA approval. The median life survival has increased significantly from 9 months to over 2 years …