Glioblastoma multiforme: Pathogenesis and treatment

Alifieris, Constantinos; Trafalis, Dimitrios T.

doi:10.1016/j.pharmthera.2015.05.005

Cited by 665 publications

(602 citation statements)

References 283 publications

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“…[8] The most common malignant brain tumor is glioblastoma multiforme (GBM, 81% of malignant CNS tumors), which is usually associated with poor prognosis. [9][10][11] GBM is classified as a subtype of astrocytoma. GBM is classified as grade IV/V according to the WHO.…”

Section: Types Of Brain Tumorsmentioning

confidence: 99%

“…GBM is classified as grade IV/V according to the WHO. [11] With regard to treatment, GBM and grade III brain tumors are managed similarly.…”

Section: Types Of Brain Tumorsmentioning

confidence: 99%

“…[12] The most common complications are seizures, peritumoral edema, venous thromboembolism, fatigue, and cognitive dysfunction. [11][12][13] GBM, is usually described in two different clinical forms, primary and secondary. [14] Primary GBM is the most common form (about 95%); it typically arises de novo, within 3-6 months, in older patients.…”

Section: Types Of Brain Tumorsmentioning

confidence: 99%

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Tailored nanocarriers and bioconjugates for combating glioblastoma and other brain tumors

ElAmrawy¹,

Othman²,

Adkins³

et al. 2016

JCMT

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Worldwide, the incidence of primary brain tumors is on the rise. Unfortunately, noninvasive drug therapy is hampered by poor access of most drugs to the brain due to the insurmountable blood-brain barrier (BBB). Nanotechnology holds great promise for noninvasive therapy of severe brain diseases. Furthermore, recent bioconjugation strategies have enabled the invasion of the BBB via tailored-designed bioconjugates either with targeting moieties or alterations in the physicochemical and/or the pharmacokinetic parameters of central nervous system (CNS) active pharmaceutical ingredients. Multifunctional systems and new entities are being developed to target brain cells and tumor cells to resist the progression of brain tumors. Direct conjugation of an FDA-approved drug with a targeting moiety, diagnostic moiety, or pharmacokinetic-modifying moiety represents another current approach in combating brain tumors and metastases. Finally, genetic engineering, stem cells, and vaccinations are innovative nontraditional approaches described in different patents for the management of brain tumors and metastases. This review summarizes the recent technologies and patent applications in the past five years for the noninvasive treatment of glioblastoma and other brain tumors. Till now, there has been no optimal strategy to deliver therapeutic agents to the CNS for the treatment of brain tumors and metastases. Intensive research efforts are ongoing to bring novel CNS delivery systems to potential clinical application.

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Section: Types Of Brain Tumorsmentioning

confidence: 99%

“…GBM is classified as grade IV/V according to the WHO. [11] With regard to treatment, GBM and grade III brain tumors are managed similarly.…”

Section: Types Of Brain Tumorsmentioning

confidence: 99%

Section: Types Of Brain Tumorsmentioning

confidence: 99%

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Tailored nanocarriers and bioconjugates for combating glioblastoma and other brain tumors

ElAmrawy¹,

Othman²,

Adkins³

et al. 2016

JCMT

View full text Add to dashboard Cite

show abstract

“…Despite current multimodality treatments including maximal surgical resection, followed by a combination of radiotherapy and chemotherapy, the median survival is typically limited to 14 months after diagnosis [1,2]. The extent of resection in patients with high-grade Abstract The extent of 5-aminolevulinic acid (5-ALA) guided tumor resection has a determining impact in highgrade glioma and glioblastoma surgery.…”

Section: Introductionmentioning

confidence: 99%

Epithelial Growth Factor Receptor Expression influences 5-ALA Induced Glioblastoma Fluorescence

Reinert¹,

Fontana²

2017

Journal of Neurological Surgery Part A: Central European Neurosurgery

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overexpression) compared to BS153 (EGFR overexpression/EGFRvIII+). Treatment of U87MG and LN229EGFR cells with EGF significantly reduced cellular fluorescence, by promoting HO-1 transcription and expression in a concentration-dependent manner. This effect could be reversed by EGFR-specific siRNA treatment, which reduced protein expression of about 80% in U87MG. Remarkably, inhibition of HO-1 activity by SnPP or reduction of HO-1 protein levels by siHO-1 treatment restored fluorescence in all cell lines, independently of EGFR quantitative and qualitative expression. Gefitinib treatment was able to restore fluorescence after EGF stimulation in U87MG cells but not in BS153 cells, overexpressing EGFR/EGFRvIII. In GBM cell lines, 5-ALA induced fluorescence is variable and influenced by EGF-induced downstream activation of HO-1. HO-1 protein expression was identified as a negative regulator of 5-ALA induced fluorescence in GBM cells. We further propose that co-expression of EGFRvIII but not quantitative EGFR expression influence HO-1 activity and therefore cellular fluorescence.

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“…Genetic and histopathological studies have thoroughly described the important receptors and pathways involved in this disease. The importance and recurrence of some of these molecules have made them attractive biomarkers in understanding the tumor, as well as in choosing a more adequate and effective treatment [10][11][12][13] . One of the most studied markers is the epidermal growth factor receptor (EGFR), which plays a crucial role in the biology of GBM; in this regard, there is a lot of information about the EGFR signaling network, which has been significantly implicated in the initiation and progression of these kinds of tumors [14][15][16] .…”

Section: Introductionmentioning

confidence: 99%

Growth factors and kinases in glioblastoma growth

Peña-Ortiz¹,

Germán-Castelán²,

González-Arenas³

2016

Adv Mod Oncol Res

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Glioblastoma multiforme (GBM) is the most aggressive type of brain cancer, having the highest invasion, migration, proliferation, and angiogenesis rates. Several signaling pathways are involved in the regulation of these processes including growth factors and their tyrosine kinase receptors, such as vascular endothelial growth factor (VEGF), transforming growth factor beta (TGFβ), fibroblast growth factor (FGF), platelet-derived growth factor (PDGF), and insulin-like growth factor-I (IGF-I). Different kinases and regulators also participate in signaling pathways initiated by growth factors, such as mitogen-activated kinases (MAPK), protein kinases C (PKC), phosphatidylinositol-3 kinases (PI3K), protein kinase B (PKB or Akt), glycogen synthase kinase 3β (GSK3β), the mTOR complex, and Bcl-2. In this review, we will focus on the role of these proteins as possible therapeutic targets in GBM.

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Glioblastoma multiforme: Pathogenesis and treatment

Cited by 665 publications

References 283 publications

Tailored nanocarriers and bioconjugates for combating glioblastoma and other brain tumors

Tailored nanocarriers and bioconjugates for combating glioblastoma and other brain tumors

Epithelial Growth Factor Receptor Expression influences 5-ALA Induced Glioblastoma Fluorescence

Growth factors and kinases in glioblastoma growth

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