2021.4.30 Praga_MS.pdf (2.13 MB)

ELECTROCHEMOTHERAPY WITH GALLOFLAVIN FOR EFFECTIVE TRIPLE NEGATIVE BREAST CANCER TREATMENT: AN IN VITRO MODEL STUDY

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posted on 05.05.2021, 16:37 by Pragatheiswar GiriPragatheiswar Giri

One in eight woman develop breast cancer in the United States of America and is the most common type of cancer in the world. Breast cancer has the highest rate of death compared to any other form of cancer. Triple Negative Breast Cancer (TNBC) is the most lethal type of breast cancer, which is the most fatal of all breast cancer types. TNBC is onerous to treat since it lacks all the three most commonly targeted hormones and receptors. Current patients afflicted with TNBC are treated with platinum core chemotherapeutics, namely Cisplatin. Despite the anticancer effects shown by Cisplatin, TNBC attenuates its effect and develops a resistance eventually, which results in reoccurrence of TNBC after few years. Hence there is a demand for effective and alternative ways to treat TNBC. To inhibit the TNBC cell proliferation, blocking the key glycolytic enzyme Lactase Dehydrogenase B (LDHB) is studied and validated. Galloflavin (GF), a proven LDHB inhibitor is utilized in this series of studies and analysis. In addition, Electrochemotherapy, which involves the application of electrical pulses (EP) were utilized to enhance the uptake of GF. The combination of Electrochemotherapy (ECT) with LDHB is a novel way to treat TNBC to produce an alternative to traditional chemotherapy. EP+GF will be subjected onto TNBC cells at various concentrations and pulse parameters. The purpose of this study is to test the effect of alternative chemotherapeutic drug delivery methods for TNBC patients for decrease in mortality rate and improve quality of life. Results indicate TNBC cell viability is the least for EP+GF treatments and the maximum Reactive Oxygen Species (ROS) levels and a maximum decrease in Glucose and Lactate uptake for EP+GF treatments relative to control. Immunoblotting studies indicate the inhibition of LDHB is the most on EP+GF treatments, indicating that this could be a novel modality to treat TNBC.

History

Degree Type

Master of Science

Department

Engineering Technology

Campus location

West Lafayette

Advisor/Supervisor/Committee Chair

Dr. Raji Sundararajan

Additional Committee Member 2

Dr. Ken Burbank

Additional Committee Member 3

Dr. Ignacio Camarillo