New perspectives in glioblastoma antiangiogenic therapy

Popescu, A; Purcaru, Ștefana Oana; Alexandru, Oana; Dricu, Anica

doi:10.5114/wo.2015.56122

Cited by 24 publications

(30 citation statements)

References 109 publications

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“…Additional evidence linking MAPK/ERK to the expression of ATP synthase subunits was reported in studies using glioblstomas that highly expressed ATP5α1 and ATP5β (Xu and Li, 2016) along with increased levels of activated MAPK/ERK (Popescu et al, 2016). Furthermore, ketamine reduced substance P-induced MAPK/ERK activity in human glioblastoma cells (Yamaguchi et al, 2017).…”

Section: Discussionmentioning

confidence: 83%

Mechanistic studies on ketamine-induced mitochondrial toxicity in zebrafish embryos

Robinson

Dumas

Ali

et al. 2018

Neurotoxicology and Teratology

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Ketamine, a phencyclidine derivative, is an antagonist of the Ca2+-permeable N-methyl-D-aspartate (NMDA)-type glutamate receptors. It is a pediatric anesthetic and has been implicated in developmental neurotoxicity. Ketamine has also been shown to deplete ATP in mammalian cells. Our previous studies showed that acetyl L-carnitine (ALCAR) prevented ketamine-induced cardiotoxicity and neurotoxicity in zebrafish embryos. Based on our finding that ALCAR’s protective effect was blunted by oligomycin A, an inhibitor of ATP synthase, we further investigated the effects of ketamine and ALCAR on ATP levels, mitochondria and ATP synthase in zebrafish embryos. The results demonstrated that ketamine reduced ATP levels in the embryos but not in the presence of ALCAR. Ketamine reduced total mitochondrial protein levels and mitochondrial potential, which were prevented with ALCAR co-treatment. To determine the cause of ketamine-induced ATP deficiency, we explored the status of ATP synthase. The results showed that a subunit of ATP synthase, atp5α1, was transcriptionally down-regulated by ketamine, but not in the presence of ALCAR, although ketamine caused a significant upregulation in another ATP synthase subunit, atp5β and total ATP synthase protein levels. Most of the ATP generated by heart mitochondria are utilized for its contraction and relaxation. Ketamine-treated embryos showed abnormal heart structure, which was abolished with ALCAR co-treatment. This study offers evidence for a potential mechanism by which ketamine could cause ATP deficiency mediated by mitochondrial dysfunction.

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Section: Discussionmentioning

confidence: 83%

Mechanistic studies on ketamine-induced mitochondrial toxicity in zebrafish embryos

Robinson

Dumas

Ali

et al. 2018

Neurotoxicology and Teratology

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“…The processes of pathological angiogenesis and possible Polivka Jr. et al: Targeted Therapy and Immunotherapy in Patients with GBM (Review) 23 mechanisms for their therapeutic inhibition have been extensively studied in GBM (19,71,72). The major role in tumor angiogenesis is played by vascular growth factors, especially vascular endothelial growth factor (VEGF) and its variant VEGF-A, primarily through its interactions with the VEGFR1 and VEGFR2 receptors found on endothelial as well as cancer cells.…”

Section: Inhibition Of Angiogenesis In Gbmmentioning

confidence: 99%

“…The GBM microenvironment and its involvement in cancer development and progression was also extensively studied, especially tumor angiogenesis and aberrations in anticancer immune responses (19,20). Together these findings allow the possibility of developing innovative and better personalized treatment strategies for clinical patient management in the future.…”

mentioning

confidence: 99%

“…The mutations in IDH1/2 serve also as an independent and important GBM prognostic factor (13-15). Their routine assessment is now highly recommended in the clinical management of patients with glioma (including GBM) according to the recently updated World Health Organization (WHO) 2016 classification of CNS tumors (16-18).The GBM microenvironment and its involvement in cancer development and progression was also extensively studied, especially tumor angiogenesis and aberrations in anticancer immune responses (19,20). Together these findings allow the possibility of developing innovative and better personalized treatment strategies for clinical patient management in the future.…”

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confidence: 99%

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Advances in Experimental Targeted Therapy and Immunotherapy for Patients with Glioblastoma Multiforme

et al. 2017

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Abstract. Glioblastoma multiforme (GBM) represents the most malignant primary brain tumor in adults with generally dismal prognosis, early clinical deterioration and high mortality. GBM is extremely invasive, characterized by intense and aberrant vascularization and high resistance to multimodal treatment. Standard therapy (surgery, radiotherapy and chemotherapy with temozolomide) has very limited effectiveness, with median overall survival of patients no longer than 15 months. Progress in genetics and epigenetics of GBM over the past decade has revealed various aberrations in cellular signaling pathways, the tumor microenvironment, and pathological angiogenesis. A number of targeted anticancer drugs, such as small-molecule kinase inhibitors and monoclonal antibodies, have been evaluated in clinical trials with newly-diagnosed, as well as recurrent GBM. Unfortunately, to date, only a single antiangiogenic agent, bevacizumab, has been approved for the treatment of recurrent GBM in the USA and Canada. The novel possibilities of cancer immunotherapy, especially immune checkpoint inhibitors, are being evaluated in clinical trials of patients with GBM. The most recent clinical experiences with targeted therapy as well as immunotherapy of GBM are given in this review. The relative lack of success of some of these approaches recently revealed in well-designed randomized clinical trials is also discussed.Glioblastoma multiforme (GBM) belongs to the largest group of primary central nervous system (CNS) tumors, so-called gliomas, which are formed from supporting glial cells in the brain parenchyma (1, 2). GBM represents the most common and most malignant tumor in this class, with an incidence of 3-4/100,000/year (3, 4). GBM is an extremely invasive and difficult to treat tumor, characterized by intense and aberrant vascularization and high resistance to radiotherapy (RT) and chemotherapy (CHT). The current standard of care for patients with newly-diagnosed GBM comprises of neurosurgery and subsequent concomitant chemoradiotherapy by fractionated external-beam RT and systemic temozolomide followed by systemic temozolomide in the adjuvant setting (5). There are only very limited possibilities for the treatment of subsequent recurrences, generally with minimal clinical efficacy (6). Despite intensive multimodal treatment strategies, the median survival of patients with GBM is still 12.1-14.6 months and only 3-5% of patients survive longer than 3 years (7).Enormous progress has been made in the genetics and epigenetics of GBM during the past decade. The Cancer 21Τhis article is freely accessible online.Correspondence to: Jiri Polivka, Department of Neurology, Faculty Hospital Plzen, alej Svobody 80, 304 60, Plzen, Czech Republic. E-mail: polivka@fnplzen.cz Key Words: Glioblastoma multiforme, GBM, targeted therapy, immunotherapy, immune checkpoint inhibitors, PD1 inhibition, CTLA4 inhibition, clinical trials, personalized medicine, review. ANTICANCER RESEARCH 37: 21-34 (2017) [8][9][10][11][12]. The most important genetic...

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“…Availability of drugs to cross the blood-brain-barrier (BBB), or more accurately termed blood-CNS barrier, have limited the number, type, and doses of effective therapies against GBM. Various agents, including chemotherapeutics 4 , antiangiogenic drugs 5,6 , immunotoxins 7,8 , viral vectors and gene therapy 9 , among others, have been tried, all with suboptimal results.…”

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confidence: 99%

Commentary: Current status of intratumoral therapy for glioblastoma

Mehta¹

2016

J Neurol Neuromedicine

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New perspectives in glioblastoma antiangiogenic therapy

Cited by 24 publications

References 109 publications

Mechanistic studies on ketamine-induced mitochondrial toxicity in zebrafish embryos

Mechanistic studies on ketamine-induced mitochondrial toxicity in zebrafish embryos

Advances in Experimental Targeted Therapy and Immunotherapy for Patients with Glioblastoma Multiforme

Commentary: Current status of intratumoral therapy for glioblastoma

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