P2X7 receptor as predictor gene for glioma radiosensitivity and median survival.

Glioblastoma multiforme (GBM) is considered the most lethal intracranial tumor and the median survival time is approximately 14 months. Although some glioma cells present radioresistance, radiotherapy has been the mainstay of therapy for patients with malignant glioma. The activation of P2X7 receptor (P2X7R) is responsible for ATP-induced death in various cell types.

Extracellular ATP reduces tumor sphere growth and cancer stem cell population in glioblastoma cells.

Glioblastoma is the most aggressive tumor in the CNS and is characterized by having a cancer stem cell (CSC) subpopulation essential for tumor survival. The purinergic system plays an important role in glioma growth, since adenosine triphosphate (ATP) can induce proliferation of glioma cells, and alteration in extracellular ATP degradation by the use of exogenous nucleotidases dramatically alters the size of gliomas in rats. The aim of this work was to characterize the effect of the purinergic system on glioma CSCs.

Gastrin-releasing peptide receptor content in human glioma and normal brain.

The gastrin-releasing peptide receptor (GRPR) has been put forward as a therapeutic target in brain tumors. Here we evaluated GRPR presence in glioma specimens from patients as well as in normal human brain samples. Sections of paraffin-embedded brain tumors and non-neoplastic control brain tissue were analyzed with immunohistochemistry for GRPR content.

Cancer stem cells and the biology of brain tumors.

There is now compelling evidence that brain tumors harbor a small population of cells characterized by their ability to undergo self-renewal and initiate tumors, termed cancer stem cells (CSCs). The development of therapeutic strategies targeted towards CSC signaling may improve the treatment of brain tumors such as malignant gliomas and medulloblastomas. Here we review the role of cancer stem cells in glioma and medulloblastoma and some of the signaling mechanisms involved in brain tumor stem cell (BTSC) biology, and discuss how these signaling pathways may represent new stem cell targets for the treatment of brain tumors.

Stimulation of proliferation of U138-MG glioblastoma cells by gastrin-releasing peptide in combination with agents that enhance cAMP signaling.

Increasing evidence indicates that gastrin-releasing peptide (GRP) acts as an autocrine growth factor for brain tumors. However, it remains unclear whether the cAMP/protein kinase A (PKA) signaling pathway plays a role in mediating the mitogenic effects of GRP. We show here that GRP combined with agents that stimulate the cAMP/PKA pathway promotes proliferation of human gliobastoma cells.

Gastrin-releasing peptide receptors regulate proliferation of C6 Glioma cells through a phosphatidylinositol 3-kinase-dependent mechanism.

Gastrin-releasing peptide (GRP) has been proposed as a major growth factor in brain tumors, and GRP receptor (GRPR) antagonists show antiproliferative effects in experimental gliomas. However, the underlying molecular events downstream of GRPR activation remain poorly understood. In the present study, we examined the role of the GRPR in regulating proliferation of glioma cells in vitro and its possible interaction with the phosphatidylinositol 3-kinase (PI3K) signaling pathway.

A role for hippocampal gastrin-releasing peptide receptors in extinction of aversive memory.

Although the gastrin-releasing peptide receptor has been implicated in memory consolidation, previous studies have not examined whether it is involved in extinction. Here we show that gastrin-releasing peptide receptor blockade in the hippocampus disrupts extinction of aversive memory. Male rats were trained in inhibitory avoidance conditioning and then returned repeatedly to the training context without shock on a daily basis for 3 days.

Oxidative damage in brains of mice treated with apomorphine and its oxidized derivative.

Increasing evidence suggests that some of the neurobiological and neurotoxic actions of apomorphine and other dopamine receptor agonists might be mediated by their oxidation derivatives. The aim of the present study was to evaluate the effects of apomorphine and its oxidation derivative, 8-oxo-apomorphine-semiquinone (8-OASQ), on oxidative stress parameters and antioxidant enzyme activity. Adult male CF-1 mice were treated with a systemic injection of apomorphine (0.

DNA damage in brain cells of mice treated with an oxidized form of apomorphine.

We investigated whether systemic injection of apomorphine and its oxidation derivative 8-oxo-apomorphine-semiquinone (8-OASQ) could induce DNA damage in mice brain, using the single-cell gel assay. 8-OASQ induced DNA damage in the brains at 1 and 3 h, but not at 24 h after treatment whereas apomorphine induced a slight increase in brain DNA damage frequency at 3 h after treatment, suggesting that both drugs display genotoxic activity in brain tissue.

Facilitation of long-term object recognition memory by pretraining administration of diphenyl diselenide in mice.

Selenium compounds display antioxidant and neuroprotective properties. Diphenyl diselenide (PhSe)(2) is an organic selenium compound that affects a number of neuronal processes. The aim of the present study was to evaluate the effects of the systemic administration of (PhSe)(2) on novel object recognition memory in mice.