Search

Simple Summary: Subependymal giant cell astrocytoma is a slow-growing brain tumor affecting children and young adults. Despite the characteristic molecular and clinical features, the severity of the disease varies from patient to patient, and, in addition, tumors in their early stages can be asymptomatic for a long time. Morbidity and mortality are due to the location of the tumor, which can obstruct the flow of cerebrospinal fluid, leading to progressive hydrocephalus and even death. The etiology and the response to treatment are still poorly understood due to the diversity of the background and the course of the disease. Therefore, this review aims to present and discuss the latest research on SEGA, its diagnosis, and treatment. Subependymal giant cell astrocytoma (SEGA) is most often found in patients with TSC (Tuberous Sclerosis Complex). Although it has been classified as a benign tumor, it may create a serious medical problem leading to grave consequences, including young patient demise. Surgery and chemotherapy belong to the gold standard of treatment. A broader pharmacological approach involves the ever-growing number of rapalogs and ATP-competitive inhibitors, as well as compounds targeting other kinases, such as dual PI3K/mTOR inhibitors and CK2 kinase inhibitors. Novel approaches may utilize noncoding RNA-based therapeutics and are extensively investigated to this end. The purpose of our review was to characterize SEGA and discuss the latest trends in the diagnosis and therapy of this disease. [ABSTRACT FROM AUTHOR]

Treatment options for glioblastoma remain limited and unfortunately even with maximal resection and postoperative adjuvant treatments, the median overall survival of patients remains approximately 15 months. In the present study we investigated the effect of HBO (2ATA - atmospheres absolute) prolonged to 2 hours on antitumor efficacy of selected CK2 kinase inhibitors in two distinct human malignant glioma cell lines, T98G and U87MG. Tested compounds were administered in increasing concentrations within the range of 5-100µM either under normoxia or with the addition of HBO at the beginning of experiments. After 24 hour incubation, 2 hour HBO decreased the viability of T98G cells in response to CK2 kinase inhibitors 2-aminoetylo-amino-4,5,6,7-tetrabromo-1H-benzimidazol (TBIAEA), 2/ 4,5,6,7-tetrabromoN²metylo-N²hydroksyetylo 2 ami-nobenzimidazol (TMHA), and 3/ 1-(β-D-2'-deoxy-ribofuranosyl)-4,5,6,7-tetrabromo-1H-benzimidazol(TDB), as compared to treatments with these inhibitors under normoxia. The 2 hour HBO-induced reductions of viability amounted up to 36% over pharmaceutics alone and occurred at 5-100µM of their concentration range. Notably, as compared with 1 hour HBO sessions combined with CK2 kinase inhibitors, 2 hour HBO sessions combined with these pharmaceuticals produced greater reductions of viability of T98G cells, resulting in the lowest numbers of surviving tumor cells in the whole experiment. In T98G cells, as compared with U87MG cells, 2 hour HBO caused more potent reductions over pharmaceuticals alone. Thus, the prolonged dosing of HBO may increase tumoricidal effect of antiglioma agents and hence deserves further study. Investigating even more prolonged HBO exposures and other kinase inhibitors combined with HBO against glioblastoma cells would be worth a while. This work was supported by the Foundation for Development of Diagnostic and Therapy Warsaw. [ABSTRACT FROM AUTHOR]

Background/aim: Tumours of astroglial origin are the most common primary brain malignancy characterized by infiltrative growth and resistance to standard antitumour therapy. Glioma progression is thought to be related to various intracellular signal transduction pathways that involve the activation of protein kinases. Protein kinases play important roles in cell differentiation, proliferation, and survival. Recently, novel, specific inhibitors of constitutively active serine/threonine kinases and structurally similar isothiourea derivatives were suggested to induce apoptosis and inhibit proliferation in several types of human cancer cells., Materials and Methods: In this study, we examined the cytotoxic and proapoptotic activities of selected modified pentabromobenzyl isothioureas (ZKKs) in an adult human glioblastoma (T98G) and a subependymal giant cell astrocytoma cell (SEGA) line. We evaluated cell proliferation, viability, and apoptosis., Results: Two pentabromobenzyl isothiourea bromide derivatives, ZKK-13 and N,N,N'-trimethyl-ZKK1 (TRIM), exhibited the most potent cytotoxic and proapoptotic efficacies against human glioma-derived cells, even at a very low concentration (1 μM). ZKK-13 (25-50 μM) inhibited cell growth by approximately 80-90% in 24 and 48 h of treatment. We showed that selected ZKKs exerted antiproliferative activity against astroglial neoplastic cells of both low- and high-grade tumour malignancy classes. No synergistic effects were detected when ZKKs were combined with serine/threonine kinase inhibitors., Conclusion: Our findings indicated that modified ZKKs show promise for the treatment of glioma-derived brain tumours., (Copyright© 2018, International Institute of Anticancer Research (Dr. George J. Delinasios), All rights reserved.)