Pharmacy and Pharmaceutical Sciences Commons^™

A Small Peptide Increases Drug Delivery In Human Melanoma Cells, Shirley Tong, Shaban Darwish, Hanieh Hossein Nejad Ariani, Kate Alison Lozada, David Salehi, Maris A. Cinelli, Richard B. Silverman, Kamaljit Kaur, Sun Yang

Pharmacy Faculty Articles and Research

Melanoma is the most fatal type of skin cancer and is notoriously resistant to chemotherapies. The response of melanoma to current treatments is difficult to predict. To combat these challenges, in this study, we utilize a small peptide to increase drug delivery to melanoma cells. A peptide library array was designed and screened using a peptide array-whole cell binding assay, which identified KK-11 as a novel human melanoma-targeting peptide. The peptide and its D-amino acid substituted analogue (VPWxEPAYQrFL or D-aa KK-11) were synthesized via a solid-phase strategy. Further studies using FITC-labeled KK-11 demonstrated dose-dependent uptake in human melanoma cells. D-aa …

Short-Term Treatment With Multi-Drug Regimens Combining Braf/Mek-Targeted Therapy And Immunotherapy Results In Durable Responses In Braf-Mutated Melanoma, Michael G. White, Robert Szczepaniak Sloane, Russell G. Witt, Alexandre Reuben, Pierre Olivier Gaudreau, Miles C. Andrews, Ningping Feng, Sarah Johnson, Caleb Class, Christopher Bristow, Khalida Wani, Courtney Hudgens, Luigi Nezi, Teresa Manzo, Mariana Pettaccia De Macedo, Jianhua Hu, Richard Davis, Hong Jiang, Peter Prieto, Elizabeth Burton, Patrick Hwu, Hussein Tawbi, Jeffrey Gershenwald, Alexander J. Lazar, Michael T. Tetzlaff, Willem Overwijk, Scott E. Woodman, Zachary A. Cooper, Joseph R. Marszalek, Michael A. Davies, Timothy P. Heffernan, Jennifer A. Wargo

Scholarship and Professional Work – COPHS

Targeted and immunotherapy regimens have revolutionized the treatment of advanced melanoma patients. Despite this, only a subset of patients respond durably. Recently, combination strategies of BRAF/MEK inhibitors with immune checkpoint inhibitor monotherapy (α-CTLA-4 or α-PD-1) have increased the rate of durable responses. Based on evidence from our group and others, these therapies appear synergistic, but at the cost of significant toxicity. We know from other treatment paradigms (e.g. hematologic malignancies) that combination strategies with multi-drug regimens (>4 drugs) are associated with more durable disease control. To better understand the mechanism of these improved outcomes, and to identify and prioritize …

Genomic Data From Nsclc Tumors Reveals Correlation Between Shp-2 Activity And Pd-L1 Expression And Suggests Synergy In Combining Shp-2 And Pd-1/Pd-L1 Inhibitors, Keller J. Toral, Mark A. Wuenschel, Esther P. Black

Pharmaceutical Sciences Faculty Publications

The identification of novel therapies, new strategies for combination of therapies, and repurposing of drugs approved for other indications are all important for continued progress in the fight against lung cancers. Antibodies that target immune checkpoints can unmask an immunologically hot tumor from the immune system of a patient. However, despite accounts of significant tumor regression resulting from these medications, most patients do not respond. In this study, we sought to use protein expression and RNA sequencing data from The Cancer Genome Atlas and two smaller studies deposited onto the Gene Expression Omnibus (GEO) to advance our hypothesis that inhibition …

Multiple Sclerosis Outcomes After Cancer Immunotherapy, Catherine R. Garcia, Rani Jayswal, Val R. Adams, Lowell B. Anthony, John L. Villano

Markey Cancer Center Faculty Publications

INTRODUCTION: Neurological immune-related adverse events are a rare but potentially deadly complication after immune checkpoint inhibitor (ICI) treatment. As multiple sclerosis (MS) is an immune-mediated disease, it is unknown how ICI treatment may affect outcomes.

METHODS: We analyzed the United States Food and Drug Administration (FDA) Adverse Event Reporting System (FAERS) database for pembrolizumab, atezolizumab, nivolumab, ipilimumab, avelumab, and durvalumab 2 years prior their FDA approval until December 31, 2017, to include all cases with confirmed diagnosis/relapse of MS. We also included cases reported in the literature and a patient from our institution.

RESULTS: We identified 14 cases of MS …

Components In Aqueous Hibiscus Rosa-Sinensis Flower Extract Inhibit In Vitro Melanoma Cell Growth, Karina H. Goldberg, Ariel C. Yin, Archana Mupparapu, Edward P. Retzbach, Gary S. Goldberg, Catherine F. Yang

Faculty Scholarship for the College of Science & Mathematics

Skin cancer is extremely common, and melanoma causes about 80% of skin cancer deaths. In fact, melanoma kills over 50 thousand people around the world each year, and these numbers are rising. Clearly, standard treatments are not effectively treating melanoma, and alternative therapies are needed to address this problem. Hibiscus tea has been noted to have medicinal properties, including anticancer effects. Extracts from Hibiscus have been shown to inhibit the growth of a variety of cancer cells. In particular, recent studies found that polyphenols extracted from Hibiscus sabdariffa by organic solvents can inhibit melanoma cell growth. However, effects of aqueous …

Tumor Growth Suppressive Effect Of Il-4 Through P21-Mediated Activation Of Stat6 In Il-4rα Overexpressed Melanoma Models, Hye Lim Lee, Mi Hee Park, Ju Kyoung Song, Yu Yeon Jung, Youngsoo Kim, Kyung Bo Kim, Dae Yeon Hwang, Do Young Yoon, Min Jong Song, Sang Bae Han, Jin Tae Hong

Pharmaceutical Sciences Faculty Publications

To evaluate the significance of interleukin 4 (IL-4) in tumor development, we compared B16F10 melanoma growth in IL-4-overespressing transgenic mice (IL-4 mice) and non-transgenic mice. In IL-4 mice, reduced tumor volume and weight were observed when compared with those of non-transgenic mice. Significant activation of DNA binding activity of STAT6, phosphorylation of STAT6 as well as IL-4, IL-4Rα and p21 expression were found in the tumor tissues of IL-4 mice compared to non-transgenic mice. Higher expression of IL-4, STAT6 and p21 in human melanoma tissue compared to normal human skin tissue was also found. Higher expression of apoptotic protein such …

Patent No. Us 9,090,589 B2: Specific Nnos Inhibitors For The Therapy And Prevention Of Human Melanoma, Richard B. Silverman, Frank L. Meyskens Jr., Sun Yang, Haitao Ji, Fengtian Xue, Thomas L. Poulos

Pharmacy Faculty Articles and Research

Methods for melanoma treatment and prevention with selective nitric oxide synthase inhibitor compounds and related pharmaceutical compositions, alone or in conjunction with one or more other melanoma therapies.

An Update On Braf Inhibitors And Other New Molecular Targets For The Treatment Of Malignant Melanoma Of The Skin, M. O. Faruk Khan, Carroll L. Ramos

Pharmaceutical Science and Research

Malignant melanoma of the skin originates from mutations in melanocytes and can be lethal if unrecognized or untreated in its earlier stages. Deaths from melanoma are increasing in the United States and around the world every year. The available treatments produce low rates of response with modest survival impact. Among potential molecular targets under investigation, which are mostly in the tyrosine kinase pathway, the BRAF (V-raf murine sarcoma viral oncogene homolog B1) gene is the best studied and most frequently reported mutation in melanoma. The molecular targets for melanoma treatment, promising drugs for future melanoma treatment as well as the …

The Value Proposition Of Molecular Medicine., Scott A. Waldman, Andre Terzic

Department of Pharmacology and Experimental Therapeutics Faculty Papers

Individualized patient management is rapidly evolving, driven by the emergence of insights in discovery, development, regulatory, and comparative effectiveness sciences.^1-4 The pace of discovery is accelerating, enabled by platforms, including “omics”, stem cell biology, network medicine, and medical and biological informatics that provide unanticipated insights into pathophysiology.^{2, 4-6} The integration of these paradigms has established a model for identifying the mechanistic underpinnings of disease, offering novel opportunities to individualize diagnostics that shape how modern therapies are deployed, including markers of disease prognosis, clinical predictors of therapeutic responses, and molecular determinants that optimize clinical management.^7-10 Importantly, deconvolution of …