Management of Gliomas: Overview of the Latest Technological Advancements and Related Behavioral Drawbacks

Ganau, Laura; Paris, Marco; Ligarotti, Gianfranco K.I.; Ganau, Mario

doi:10.1155/2015/862634

Cited by 38 publications

(34 citation statements)

References 52 publications

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“…Gliomas represent the most common type of malignant tumors of the central nervous system (Ganau et al, 2015), and they are the most aggressive and lethal (Robins et al, 2009;Van Meir et al, 2010;Wei et al, 2010) among the primary brain tumors (Noch and Khalili, 2009). Despite recent therapeutic advances in multimodality therapies, including surgery and radio/chemotherapy, the treatment of these malignant gliomas remains palliative, with an average survival of about 1 year (Omuro and DeAngelis, 2013).…”

Section: Introductionmentioning

confidence: 99%

Calcium Channels and Associated Receptors in Malignant Brain Tumor Therapy

Morrone¹,

Gehring²,

Nicoletti³

2016

Mol Pharmacol

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Malignant brain tumors are highly lethal and aggressive. Despite recent advances in the current therapies, which include the combination of surgery and radio/chemotherapy, the average survival rate remains poor. Altered regulation of ion channels is part of the neoplastic transformation, which suggests that ion channels are involved in cancer. Distinct classes of calciumpermeable channels are abnormally expressed in cancer and are likely involved in the alterations underlying malignant growth. Specifically, cytosolic Ca 21 activity plays an important role in the regulation of cell proliferation, and Ca 21 signaling is altered in proliferating tumor cells. A series of previous studies emphasized the importance of the T-type low-voltage-gated calcium channels (VGCC) in different cancer types, including gliomas, and remarkably, pharmacologic inhibition of T-type VGCC caused antiproliferative effects and triggered apoptosis of human glioma cells. Other calcium permeable channels, such as transient receptor potential (TRP) channels, contribute to changes in Ca 21 by modulating the driving force for Ca 21 entry, and some TRP channels are required for proliferation and migration in gliomas. Furthermore, recent evidence shows that TRP channels contribute to the progression and survival of the glioblastoma patients. Likewise, the purinergic P2X7 receptor acts as a direct conduit for Ca 21 -influx and an indirect activator of voltage-gated Ca 21 -channel. Evidence also shows that P2X7 receptor activation is linked to elevated expression of inflammation promoting factors, tumor cell migration, an increase in intracellular mobilization of Ca 21 , and membrane depolarization in gliomas. Therefore, this review summarizes the recent findings on calcium channels and associated receptors as potential targets to treat malignant gliomas.

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Section: Introductionmentioning

confidence: 99%

Calcium Channels and Associated Receptors in Malignant Brain Tumor Therapy

Morrone¹,

Gehring²,

Nicoletti³

2016

Mol Pharmacol

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“…As mentioned previously, glioma is a common brain tumor which is hard to cure at present due to high rate of relapse [1,2]. Hypoxia is an important feature of glioma microenvironment leading to intratumoral necrosis and angiogenesis [3].…”

Section: Discussionmentioning

confidence: 99%

“…Glioblastoma has strong activity of migration and invasion [2], which is associated to low oxygen condition of tumor microenvironment [4][5][6]. Thus it's essential to find a way to block hypoxia-induced migration and invasion.…”

Section: Discussionmentioning

confidence: 99%

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Resveratrol inhibits hypoxia-induced glioma cell migration and invasion by the p-STAT3/miR-34a axis

Wang¹,

Han²,

Zhang³

2016

neo

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Hypoxia promotes aggressiveness, angiogenesis and resistance in glioma. It has been reported that resveratrol has strong anti-tumor ability and can inhibit migration and invasion of varieties of tumor including glioma. However, whether resveratrol inhibits hypoxia-induced migration and invasion of glioma cells is still unknown. In this study, we found glioma U87 and U251 cells migration and invasion was reduced by resveratrol under hypoxia condition and higher doses led to stronger block, while proliferation of U87 and U251 cells was hardly effected. Mechanically, hypoxia-induced upregulation of phosphorylated signal transducer and activator of transcription 3(p-STAT3) was blocked by resveratrol. MicroRNA-34a (miR-34a) is a tumor suppressor whose promoter region has a conserved STAT3-binding site and can be negatively regulated by STAT3. Interestingly, miR-34a was downregulated under hypoxia but upregulated by resveratrol which was perhaps relevant to changes in level of p-STAT3. The effect of resveratrol on p-STAT3 and miR-34a was both time-and dose-dependent. Summarizing, resveratrol inhibits hypoxia-induced migration and invasion possibly via p-STAT3/miR-34a axis and this effect is both time-and dose-dependent.

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“…Glioblastoma multiforme (GBM) is the highest grade and most malignant type of glioma (Blume et al, 2013;Lee et al, 2015). Current treatment includes surgical resection of cancerous tissues, where possible, as well as radiotherapy followed by chemotherapy with the DNA alkylating agent temozolomide (Yin et al, 2007;Ganau et al, 2015). However, the median survival time is approximately 16 months with current treatment and there is a 5-year survival time of 5% (Ganau et al, 2015).…”

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confidence: 99%

The mechanism of action of the scorpion toxin, chlorotoxin, a bioinformatics approach

Sheikh¹

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Glioblastoma is a very invasive and metastatic cancer with low patient survival-rate and high resistance to current treatment. Matrix metalloproteinase 2 (MMP2) is upregulated in glioblastoma multiforme (GBM) and its high expression is directly correlated with invasion and metastasis of GBM cells. Annexin A2 is involved in angiogenesis, and it is overexpressed in GBM. MMP2 and annexin A2 are potential targets for effective glioma therapy. Chlorotoxin is a promising toxin peptide for glioma targeted therapy. Chlorotoxin decreased migration and metastasis of GBM cells, although mechanism of action of the toxin is unclear due to the complicated nature of GBM, slow and costly experiments and challenging techniques. The relationship of chlorotoxin binding to both MMP2 and annexin A2 is controversial and further work is needed to clarify a complex situation. Chlorotoxin-like short toxins are homologous peptides that may also have potential therapeutic effects for glioma.In this study homology modelling was used to predict 3D models of chlorotoxin-like short toxins. Stereochemical quality estimation of 3D models was performed with QMEAN, Z-Score and Procheck server. ClusPro docking programme was used to dock 3D structures of chlorotoxin and chlorotoxin homologues with their putative binding partners MMP2 and annexin A2 to provide a first step to understand the mechanism of action of the toxin. Chlorotoxin shows binding interaction with both MMP2 and annexin A2. Chlorotoxin-like short toxins also showed stronger binding interaction with activated MMP2 than annexin A2. The positively charged surface of chlorotoxin is mainly involved in interaction with MMP2. All three chlorotoxin-like short toxins bind to a similar site on MMP2 but on separate sites on annexin A2hence suggesting the significance of observed interaction between chlorotoxin and MMP2.

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Management of Gliomas: Overview of the Latest Technological Advancements and Related Behavioral Drawbacks

Cited by 38 publications

References 52 publications

Calcium Channels and Associated Receptors in Malignant Brain Tumor Therapy

Calcium Channels and Associated Receptors in Malignant Brain Tumor Therapy

Resveratrol inhibits hypoxia-induced glioma cell migration and invasion by the p-STAT3/miR-34a axis

The mechanism of action of the scorpion toxin, chlorotoxin, a bioinformatics approach

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