The objective of this Phase I project is the development of novel assays for gelatinase - i.e., matrix metalloprotease 2 and 9 - activity using a proprietary enhanced Fluorescence Resonance Energy Transfer (FRET) probe with a formulation that enables highly sensitive and specific measurements with a simple workflow and a 10 minute incubation time. The assay will be formulated for use with complex biological matrices and evaluated for melanoma prognostics. Melanoma is a type of cancer that is generated by abnormal growth of melanocytes, dendritic cells in the epidermis that synthesize melanin. Early stages of melanoma may be effectively treated by surgical resection, but its metastatic stage is very aggressive and generally unresponsive to treatment. The American Cancer Society estimates a US incidence rate of 76,100 melanomas for 2014 with 9,710 deaths.
Public Health Relevance Statement:
Public Health Relevance: Differences in protease assay methodology and the lack of standard analytical validation methods have made it difficult to draw consistent conclusions from gelatinase measurements done in different laboratory settings. Therefore, we believe the development of sample processing protocols and a carefully validated assay for gelatinase activity will resolve inconsistencies in the understanding of the role of gelatinases in melanoma invasiveness and will provide a robust and convenient tool for melanoma prognostics, research, and pharmacological evaluation of melanoma therapies.
Project Terms:
advanced disease; American Cancer Society; assay development; Binding (Molecular Function); Biological; Biological Assay; Biopsy; Biopsy Specimen; Blood Vessels; Buffers; cancer type; Cessation of life; Cleaved cell; Clinical; Clinical Research; Collagen; Complex; Connective Tissue; Cutaneous Melanoma; Data; Dendritic Cells; Dermis; Development; Drug Formulations; Elastin; Epidermis; Evaluation; Excision; Fibronectins; fibrous protein; Fluorescence Resonance Energy Transfer; Freezing; Gelatinase A; Gelatinase B; Gelatinases; Goals; Government; Growth; Guidelines; Human; Incidence; Laboratories; Lactate Dehydrogenase; Lesion; Link; lymph nodes; Lymphatic; Matrix Metalloproteinases; Measurement; Melanins; melanocyte; melanoma; Melanoma Cell; Membrane; Metalloproteases; Metastatic Neoplasm to the Liver; Metastatic to; Methodology; Methods; migration; Mitotic; Mohs Surgery; Molecular Profiling; Neoplasm Metastasis; novel; Operative Surgical Procedures; Peptide Hydrolases; Persons; Phase; phase 1 study; Primary Neoplasm; Probability; Process; prognostic; Proteins; Proteolysis; Protocols documentation; public health relevance; Research; Role; Sampling; Serum; Skin Tissue; Specificity; Staging; Thick; Time; Tissues; tool; tumor; Ulcer; Validation; Zinc
