Effects of mesenchymal stem cell therapy, in association with pharmacologically active microcarriers releasing VEGF, in an ischaemic stroke model in the rat.

Few effective therapeutic interventions are available to limit brain damage and functional deficits after ischaemic stroke. Within this context, mesenchymal stem cell (MSC) therapy carries minimal risks while remaining efficacious through the secretion of trophic, protective, neurogenic and angiogenic factors. The limited survival rate of MSCs restricts their beneficial effects.

Noninvasive assessment of hypoxia with 3-[18F]-fluoro-1-(2-nitro-1-imidazolyl)-2-propanol ([18F]-FMISO): a PET study in two experimental models of human glioma.

Despite multiple advances in cancer therapies, patients with glioblastoma (GBM) still have a poor prognosis. Numerous glioma models are used not only for the development of innovative therapies but also to optimize conventional ones. Given the significance of hypoxia in drug and radiation resistance and that hypoxia is widely observed among GBM, the establishment of a reliable method to map hypoxia in preclinical human models may contribute to the discovery and translation of future and more targeted therapies.

Angiopoietin-2 is vasoprotective in the acute phase of cerebral ischemia.

Most forms of cerebral ischemia are characterized by damage to the entire neurovascular unit, which leads to an increase in the permeability of the blood-brain barrier (BBB). In response to permanent focal cerebral ischemia in mice, we detected an early concomitant increase in the expression of the vascular endothelial growth factor (VEGF), a key inducer of vascular leakage and pathological blood vessel growth, and of angiopoietin-2 (Ang2), which is closely associated with VEGF in vascular remodeling. Thus, the aim of this study was to evaluate the role of Ang2 alone, or in combination with VEGF, in the acute phase of cerebral ischemia.

Complementary information from magnetic resonance imaging and (18)F-fluoromisonidazole positron emission tomography in the assessment of the response to an antiangiogenic treatment in a rat brain tumor model.

Introduction: No direct proof has been brought to light in a link between hypoxic changes in glioma models and the effects of antiangiogenic treatments. Here, we assessed the sensitivity of the detection of hypoxia through the use of (18)F-fluoromisonidazole positron emission tomography ([(18)F]-FMISO PET) in response to the evolution of the tumor and its vasculature.

Methods: Orthotopic glioma tumors were induced in rats after implantation of C6 or 9L cells.

Targeting the erythropoietin receptor on glioma cells reduces tumour growth.

Hypoxia has been shown to be one of the major events involved in EPO expression. Accordingly, EPO might be expressed by cerebral neoplastic cells, especially in glioblastoma, known to be highly hypoxic tumours. The expression of EPOR has been described in glioma cells.

Angiopoietin-2 regulates cortical neurogenesis in the developing telencephalon.

Vascular-specific growth factor angiopoietin-2 (Ang2) is mainly involved during vascular network setup. Recently, Ang2 was suggested to play a role in adult neurogenesis, affecting migration and differentiation of adult neuroblasts in vitro. However, to date, no data have reported an effect of Ang2 on neurogenesis during embryonic development.

Molecular mechanisms underlying effects of epidermal growth factor receptor inhibition on invasion, proliferation, and angiogenesis in experimental glioma.

Purpose: Epidermal growth factor receptor (EGFR) signal transduction pathways are implicated in malignant glioma aggressiveness and promote tumor cell invasion, proliferation, and angiogenesis. Nevertheless, response to EGFR tyrosine kinase inhibitor gefitinib (Iressa, ZD1839) has been disappointing in clinical trials. One potential explanation may come from the diversity of molecular alterations seen in gliomas.