**2.3 Antiepileptic drugs**

A common symptom of GBM is epilepsy, which occurs in half of all cases; thus, patients are often treated with antiepileptic drugs, such as valproic acid (VPA) and levetiracetam (LEV) (**Figure 2**). Enzymatic modifications of histone proteins that regulate gene expression have been investigated as therapeutic drug targets. Histones are modified by histone acetyltransferase (HAT) and histone deacetylase (HDAC). A HDAC inhibitor (HDACi) enhances the acetylation by HAT and causes a hyperacetylated state, which exerts multiple antitumor effects such as cell differentiation, apoptosis, cell cycle arrest, sensitivity to chemotherapy, and inhibition of migration and angiogenesis [30].

**2.4 Pesticides**

**Figure 2.**

*2.4.1 Chloroquine (CHQ)*

*phosphoinositide 3-kinase; TMZ, temozolomide.*

*DOI: http://dx.doi.org/10.5772/intechopen.92803*

and NCT02378532).

**141**

CHQ is a therapeutic drug for the treatment of malaria [42]. This agent has antitumor effects for some cancer cells, including glioma cells [43]. However, the mechanism of the antitumor effect of CHQ in glioma is not well known. Some studies have suggested that CHQ leads to cancer cell death by controlling autophagy [44], and recent research has revealed more effects of CHQ treatment. CHQ adjusts the metabolism of amino acids and inhibits glycogenesis [42]. CHQ administration also induces the alteration of mitochondrial membrane potential in glioma cells and causes apoptosis [45]. Some studies have investigated the molecular signaling associated with CHQ treatment. The molecular signaling changes in glioma cells caused by CHQ include the inhibition of the signaling pathway of transforming growth factor-β (TGF-β) and nuclear factor-kappaB (NF-κB), which play a role in tumorigenesis [42, 45]. CHQ treatment also suppresses glioma cell invasion by the inhibition of matrix metalloproteinase-2 (MMP-2) and improved radiosensitivity by the accumulation of glioma cells in the G2/M phase [45]. Based on the results of these in vitro studies, clinical trials that investigated the therapeutic effects of CHQ in patients with glioma have been conducted [43]. In a randomized trial (doubleblind, placebo-controlled) of patients with primary GBM, there were no statistically significant differences between the CHQ treatment group and the placebo group; however, the death rate in the CHQ group was half as large as that in the placebo group [46]. Further clinical trials are in progress (NCT03243461, NCT02432417,

*Antitumor mechanisms of VPA and LEV in glioma. VPA: hyperacetylation of histones via the inhibition of HDAC suppresses cell proliferation and increases radiosensitivity. The activation of Akt/extracellular signal-regulated kinase (ERK) inhibits glycogen synthase kinase-3β (GSK3β) and induces apoptosis. LEV: recruitment of the mSin3A/HDAC1 corepressor complex and direct binding to the MGMT promoter via p53. Abbreviations: HAT, histone acetyltransferase; MEK, mitogen-activated protein kinase/ERK kinase; PI3K,*

*Drug Repositioning for the Treatment of Glioma: Current State and Future Perspective*


*Edited by Aamir Shahzad*

This book is intended to provide a deep understanding on the advanced treatments of thermal properties of materials through experimental, theoretical, and computational techniques. This area of interest is being taught in most universities and institutions at the graduate and postgraduate levels. Moreover, the increasing modern technical and social interest in energy has made the study of thermal properties more significant and exciting in the recent years. This book shares with the international community a sense of global motivation and collaboration on the subject of thermal conductivity and its wide spread applications in modern technologies. This book presents new results from leading laboratories and researchers on topics including materials, thermal insulation, modeling, steady and transient measurements, and thermal expansion. The materials of interest range from nanometers to meters, bringing together ideas and results from across the research field.

ISBN 978-1-78923-672-9

Impact of Thermal Conductivity on Energy Technologies

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