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Targeting the Nf-Kb and Mgmt Pathways in Newly Diagnosed Glioblastoma

AJAS · 2020 Biomedical and Health Sciences (inferred)

Albert Ting · Kepa Oyarbide and Leya Joykutty, Florida Academy of Sciences

Overview

Grade IV glioblastoma is the most lethal and aggressive brain tumor in adults. Despite treatment advances combining maximal surgical resection with radiotherapy and concurrent adjuvant chemotherapy (temozolomide), a patient prognosis remains marginal and survival is limited to 14.6 months. Furthermore, higher end therapticual treatments such as gene therapy are financially crippling, with costs starting at around $500,000 and rising to 1.5 million dollars. As repositioned drugs inflict minimal harm on the human body and, compared to newly developed drugs, are 170 million times less expensive to bring into market and keep it in market, researchers are becoming increasingly more interested in this area of treatment. With this problem in mind, various combinations of zinc, disulfiram (Antabuse), and temozolomide were tested to treat glioblastoma. A combinatorial matrix of the three drugs was created and alamar blue, proteasome-glo, and cell proliferation assays were conducted on newly diagnosed glioblastoma cell line (ATCC 73M). The alamar blue test demonstrated a time dependent statistically significant cytotoxic effect of various drug combinations. When analyzing both the proteasome-glo and cell proliferation data, temozolomide and disulfiram alone were the least effective in inducing apoptosis. However, when these drugs were combined with zinc, their activity showed a synergistic cytotoxic effect, thus resulting in a sharp decline in proliferation and proteasome activity in the glioblastoma cells. If the most effective drug combinations are able to succeed in clinical trials, a viable treatment would be introduced to glioblastoma patients, thus potentially increasing patient prognosis.

Competition history

  • AJAS 2020 Category not listed

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Source: AAAS Annual Meeting (Confex) / American Junior Academy of Science

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