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NF-Kb inhibition in glioblastoma: in vitro and in vivo effects of DHMEQ in tumor chemoresistence, invasion and progression


Glioblastoma (GBM) is the most biologically aggressive primary brain tumor that accounts for about 50% of gliomas. Despite the improvements in neurosurgery, radiation treatment techniques, and the advent of temozolomide, GBM remains the most common and least curable brain cancer with a median survival of only 14 months. The major contributors to malignancy are the ability of glioma cells to infiltrate surrounding brain tissue, and to escape current therapeutic modalities. The transcription factor NF-kB (nuclear factor kappa B) is constitutively activated in most cancers, including GBM. By virtue of its ability to regulate the expression of genes involved in cell apoptosis, differentiation, migration and survival, NF-kB constitutes the point of convergence of many oncogenic pathways. Aside from its criticaI role in cancer, this factor is intimately involved in the regulation of resistance to radiation and chemotherapy. Thus, the inhibition of this pathway could result in sensibilization to cytotoxic insults along with an increase in patient's survival. Recently, DHMEQ (dehydroxymethylepoxyquinomicin), a new NF-kB inhibitor that prevents the factor from translocating into the nucleus, has shown to be a potent chemo-sensitizing agent. In view of this, we propose to study the effects of NF-kB inhibition by DHMEQ (alone or in combination with standard treatments) in pediatric and adult glioblastoma cell lines and in GBM CD133+ stem cells isolated from the formers. In addition, we aim the implementation of an in vivo model with athymic mice in order to validate the effects of this drug in GBM chemoresistance, invasion and progression as well as to facilitate future studies. (AU)

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(References retrieved automatically from Web of Science and SciELO through information on FAPESP grants and their corresponding numbers as mentioned in the publications by the authors)
MEDEIROS, MARIANA; CANDIDO, MARINA FERREIRA; VALERA, ELVIS TERCI; BRASSESCO, MARIA SOL. The multifaceted NF-kB: are there still prospects of its inhibition for clinical intervention in pediatric central nervous system tumors?. CELLULAR AND MOLECULAR LIFE SCIENCES, v. 78, n. 17-18, . (10/16652-9, 10/50635-4)
CANDIDO, M. F.; BALDISSERA, G. C.; MEDEIROS, M.; UMEZAWA, K.; BRASSESCO, MARIA SOL. NF-kB inhibition by DHMEQ: in vitro antiproliferative effects on pilocytic astrocytoma and concise review of the current literature. CHILD'S NERVOUS SYSTEM, v. 36, n. 11, . (10/16652-9, 10/50635-4)

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