New molecular targets in angiogenic vessels of glioblastoma tumours

Anderson, Joshua C.; McFarland, Braden C.; Gladson, Candece L.

doi:10.1017/s1462399408000768

Cited by 67 publications

(54 citation statements)

References 189 publications

(392 reference statements)

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“…In addition, elevated interstitial pressure decreases the net transport of medication to tumor cells 9 and increases access of tumor cells to the vasculature, which is one possible mechanism for the wide dissemination seen in glioblastoma. 10 Thus strategies that serve to decrease permeability of tumor blood vessels or halt angiogenesis hold the promise of decreasing brain edema and enhancing chemotherapy delivery.…”

Section: The Blood Brain Barrier In Gliomamentioning

confidence: 99%

“…12,33 The final product of glioma angiogenesis is a vasculature with highly tortuous dilated vessels, decreased density of astrocytic foot processes, alterations in endothelial cell adhesion molecule expression, disrupted basement membrane, and an increased ratio of small diameter vessels. 10,34,35 …”

Section: Migration Of Endothelial Cells and Formation Of New Blood Vementioning

confidence: 99%

“…50 VEGF-C and VEGF-D, ligands for VEGF-R3, are expressed in cells in close proximity to tumor endothelial cells, suggesting that a signaling pathway may exist in the glioma neovascular niche. 10,50 Also, multiple growth factors implicated in angiogenesis, such as bFGF, epidermal growth factor (EGF), and PDGF have been shown to increase VEGF expression. 38 The end result of VEGF signaling in tumors is production of immature, highly permeable blood vessels with subsequent poor maintenance of the BBB and parenchymal edema.…”

Section: Pro-angiogenic Factorsmentioning

confidence: 99%

“…Perhaps the best understood endogenous anti-angiogenic protein is angiostatin. 10 Angiostatin is derived from degradation of plasminogen by proteases such as cathepsin D and MMPs, resulting in a molecule comprised of kringle domains 1 through 4. 81,82 Studies in mice indicate that angiostatin inhibits glioma angiogenesis and growth 83,84 through binding of ␣ v ␤ 3 on proliferating endothelial cells, result in apoptosis.…”

Section: Anti-angiogenic Factorsmentioning

confidence: 99%

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Biology of Angiogenesis and Invasion in Glioma

2009

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Summary: Treatment of adult brain tumors, in particular glioblastoma, remains a significant clinical challenge, despite modest advances in surgical technique, radiation, and chemotherapeutics. The formation of abnormal, dysfunctional tumor vasculature and glioma cell invasion along white matter tracts are believed to be major components of the inability to treat these tumors effectively. Recent insight into the fundamental processes governing glioma angiogenesis and invasion provide a renewed hope for development of novel strategies aimed at reducing the morbidity of this uniformly fatal disease. In this review, we discuss background biology of the blood brain barrier and its pertinence to blood vessel formation and tumor invasion. We will then focus our attention on the biology of glioma angiogenesis and invasion, and the key mediators of these processes. Last, we will briefly discuss recent and ongoing clinical trials targeting mediators of angiogenesis or invasion in glioma patients. The findings provide a renewed hope for those endeavoring to improve treatment of patients with glioma by providing a novel set of rational targets for translational drug discovery.

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Section: The Blood Brain Barrier In Gliomamentioning

confidence: 99%

Section: Migration Of Endothelial Cells and Formation Of New Blood Vementioning

confidence: 99%

Section: Pro-angiogenic Factorsmentioning

confidence: 99%

Section: Anti-angiogenic Factorsmentioning

confidence: 99%

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Biology of Angiogenesis and Invasion in Glioma

2009

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“…High grade gliomas are particularly aggressive tumors characterized by their high angiogenic levels (3,4). The vascular endothelial growth pathway appears particularly important and has been a prominent therapeutic target in cancer treatment of gliomas.…”

Section: Introductionmentioning

confidence: 99%

Histogram analysis of the microvasculature of intracerebral human and murine glioma xenografts

Just

2010

Magnetic Resonance in Med

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The purpose of this study is to examine the usefulness of histogram analysis combined with vessel size index (VSI) magnetic resonance imaging for the specific characterization of brain tumor microvasculature in a panel of six volume-matched glioma xenografts. Using a simple descriptive histogram analysis, significant differences of the mean tumoral VSI (P 5 0.0035 for 9L, P 5 0.008 for glioma mix, P 5 0.05 for C6), the 75th VSI percentile (P 5 0.003-0.075) as well as the 25th and median blood volume (BV) percentiles were found in murine gliomas compared to their contralateral healthy brain. Using a segmented histogram analysis, dilatation of already existing vessels in murine gliomas and development of new small caliber vessels in human glioblastomas were suggested. Most gliomas showed a higher proportion of pixels with BV below 1% (glioma mix [21% vs 1%], Glioblastoma 2 (GBM2) [9% vs 3.7%]) and a smaller proportion of pixels with BV in the range 1.7-6.3% (65 vs 90% for glioma mix, 80 vs 85% in GBM2) relative to their contralateral part. In glioblastomas, VSI and BV distributions were similar to normal brain distributions and in agreement with immunohistochemical findings. The histogram analysis of VSI and BV heterogeneity in experimental brain tumors allowed detection of microregional differences in gliomas from different origins. Magn Reson Med 65:778-789,

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CNSCancers

Graeme

2010

Burger's Medicinal Chemistry and Drug Discovery

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CNS tumors represent a diverse collection of tumor types driven by a range of signaling inputs that often generate highly aggressive and at the same time heterogeneous tumor types. The effect of these tumors is particularly dramatic and impacts on children as well as adults. Malignant CNS tumors are characterized by being highly heterogeneous, aggressive, and frequently invasive, leading to poor overall patient survival times. As CNS tumors present within the nervous system, there are particular challenges in the development of effective molecular‐targeted therapies in dealing not only with the aggressive nature of these tumors and their ability to evade treatment but also, particularly, with maintaining normal neuronal and brain functions. Compounding this is the need to deliver systemically small molecules or other agents such as vaccines and for immunotherapy approaches to confront the complexity of the relationship between the nervous system and the immune system. Research to find effective treatments for CNS tumors is being facilitated by two key inputs both of which are reviewed in this chapter; first, a much greater understanding of tumor pathobiology and the potential role of developmental signaling pathways and tumor stem‐like cells, and by the development of animal models that more adequately represent endpoints measurable in the clinic. Together, these advances should assist in the selection of better targets and the optimization of better compounds to progress into clinical trials.

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New molecular targets in angiogenic vessels of glioblastoma tumours

Cited by 67 publications

References 189 publications

Biology of Angiogenesis and Invasion in Glioma

Biology of Angiogenesis and Invasion in Glioma

Histogram analysis of the microvasculature of intracerebral human and murine glioma xenografts

CNSCancers

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