Translational Research

Presentation Title (IN ALL CAPS)

FLUORESCENCE BASED DETECTION OF HYALURONIDASE ACTIVITY AS A BIOMARKER FOR SKIN CANCER.

Departmental Affiliation and City, State, Zip for All Authors

Rahul Chib1, Sunil Shah1, Mark Mummert2, Sangram Raut1,3, Ilkay Bora4, Robert Pendry3, Ignacy Gryczynski 1, Zygmunt Gryczynski1,3, Rafal Fudala 1. 1Department of Cell Biology and Immunology, Center for Fluorescence Technologies and Nanomedicine, University of North Texas Health Science Center, Fort Worth, TX, 76107, USA. 2Department of Psychiatry and Behavioral Health, University of North Texas Health Science Center, Fort Worth, TX 76107, USA. 3Department of Physics and Astronomy, Texas Christian University, Fort Worth, TX, 76129, USA. 4 Nano-Science Center and Department of Chemistry, University of Copenhagen, Universitetsparken 5, DK2100 København Ø, Denmark.

Classification

GSBS Student (For Competition)

Research Presentation Category

Translational Research

Brief Narrative or Summary

A fluorescent probe was synthesized to measure hyaluronidase activity which is a biomarker for cancer. Hyaluronic acid was heavily labelled with ADOTA fluorophore to make this probe. The change in fluorescence intensity as a function of the change in hyaluronidase concentration was used to estimate the enzymatic concentration and hence the stage of cancer.

Scientific Abstract

Malignant melanoma (MM) is a type of skin cancer that has a high potential to metastasize to distant organs and cause death. MM is the third most common skin cancer in the United States and has an incidence of 18 new cases per 100,000. It is more lethal compared to other types of skin cancers due to its higher rate of metastasis and has a 5 years survival rate of 7-18%. In MM, the levels of hyaluronidase are overexpressed. Hyaluronidase is an endoglycosidase that degrades glycosaminoglycan and the hyaluronan (HA). Therefore, monitoring the hyaluronidase activity can be used as a contrasting mechanism for its detection. A novel fluorescence-based detection of enzyme activity using a fluorophore with long fluorescence lifetime can enable a simple wide field molecular analysis of the cancer activities at the cellular and tissue level. HA is a large biopolymer (over 1MDa) that is cleaved by the hyaluronidase enzyme to smaller elements. Monitoring kinetics of HA degradation by fluorescence intensity will be a simple and precise tool reflecting hyaluronidase activity and can be used for detecting/diagnosing/monitoring of MM. An intact HA will be highly quenched and will have less fluorescence intensity; on the other hand, the cleaved HA will have higher fluorescence intensity. The change in the fluorescence intensity directly reflects hyaluronidase activity. In future, this probe can be used in actual clinical settings.

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FLUORESCENCE BASED DETECTION OF HYALURONIDASE ACTIVITY AS A BIOMARKER FOR SKIN CANCER.

Malignant melanoma (MM) is a type of skin cancer that has a high potential to metastasize to distant organs and cause death. MM is the third most common skin cancer in the United States and has an incidence of 18 new cases per 100,000. It is more lethal compared to other types of skin cancers due to its higher rate of metastasis and has a 5 years survival rate of 7-18%. In MM, the levels of hyaluronidase are overexpressed. Hyaluronidase is an endoglycosidase that degrades glycosaminoglycan and the hyaluronan (HA). Therefore, monitoring the hyaluronidase activity can be used as a contrasting mechanism for its detection. A novel fluorescence-based detection of enzyme activity using a fluorophore with long fluorescence lifetime can enable a simple wide field molecular analysis of the cancer activities at the cellular and tissue level. HA is a large biopolymer (over 1MDa) that is cleaved by the hyaluronidase enzyme to smaller elements. Monitoring kinetics of HA degradation by fluorescence intensity will be a simple and precise tool reflecting hyaluronidase activity and can be used for detecting/diagnosing/monitoring of MM. An intact HA will be highly quenched and will have less fluorescence intensity; on the other hand, the cleaved HA will have higher fluorescence intensity. The change in the fluorescence intensity directly reflects hyaluronidase activity. In future, this probe can be used in actual clinical settings.