Endothelial cell implantation and survival within experimental gliomas.

Lal, Bachchu; Indurti, Ravi R.; Couraud, Pierre Olivier; Goldstein, Gary W.; Laterra, John

doi:10.1073/pnas.91.21.9695

Cited by 44 publications

(19 citation statements)

References 39 publications

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“…By virtue of their residing at the gateway to the CNS parenchyma, they might serve as prime sites for drug delivery and gene therapy. Advancing this possibility, Lal et al (1994) recently demonstrated that genetically modified brain endothelial cells could be stably grafted into growing gliomas. Success in this endeavor highlights the prospect of employing endothelial transplantation to deliver therapeutic genes or toxins to brain tumors.…”

Section: Endothelial Cells As Therapeutic Targets and Effectors In Cnmentioning

confidence: 98%

Central nervous system endothelium in neuroinflammatory, neuroinfectious, and neurodegenerative disease

Andjelkovic

Pachter

1998

J. Neurosci. Res.

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Section: Endothelial Cells As Therapeutic Targets and Effectors In Cnmentioning

confidence: 98%

Central nervous system endothelium in neuroinflammatory, neuroinfectious, and neurodegenerative disease

Andjelkovic

Pachter

1998

J. Neurosci. Res.

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“…An additional interesting aspect is highlighted by a study in which endothelial cells carrying a reporter gene were injected into experimental gliomas in rats. The transfected cells stably engrafted into the growing gliomas [82], suggesting that endothelial cell implantation provides the means of delivering therapeutic genes to neoplasms. Such techniques may also prove useful in defining the molecular processes necessary for angiogenesis on the endothelial side [82].…”

Section: Cancermentioning

confidence: 99%

Angiogenesis: mechanistic insights, neovascular diseases, and therapeutic prospects

1995

J Mol Med

498

284

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This review of angiogenesis aims to describe (a) stimuli that either elicit or antagonize angiogenesis, (b) the response of the vasculature to angiogenic or anti-angiogenic stimuli, i.e., processes required for the formation of new vessels, (c) aspects of angiogenesis relating to tissue remodeling and disease, and (d) the potential of angiogenic or antiangiogenic therapeutic measures. Angiogenesis, the formation of new vessels from existing microvessels, is important in embryogenesis, wound healing, diabetic retinopathy, tumor growth, and other diseases. Hypoxia and other as yet ill-defined stimuli drive tumor, inflammatory, and connective tissue cells to generate angiogenic molecules such as vascular endothelial growth factor (VEGF), fibroblast growth factor (FGF), transforming growth factor-beta (TGF-beta), platelet-derived growth factor (PDGF), and others. Natural and synthetic angiogenesis inhibitors such as angiostatin and thalidomide can repress angiogenesis. Angiogenic and antiangiogenic molecules control the formation of new vessels via different mechanisms. VEGF and FGF elicit their effects mainly via direct action on relevant endothelial cells. TGF-beta and PDGF can attract inflammatory or connective tissue cells which in turn control angiogenesis. Additionally, PDGF may act differently on specific phenotypes of endothelial cells that are engaged in angiogenesis or that are of microvascular origin. Thus phenotypic traits of endothelial cells committed to angiogenesis may determine their cellular responses to given stimuli. Processes necessary for new vessel formation and regulated by angiogenic/antiangiogenic molecules include the migration and proliferation of endothelial cells from the microvasculature, the controlled expression of proteolytic enzymes, the breakdown and reassembly of extracellular matrix, and the morphogenic process of endothelial tube formation. In animal models some angiogenesis-dependent diseases can be controlled via induction or inhibition of new vessel formation. Life-threatening infantile hemangiomas are a first established indication for antiangiogenic therapy in humans. Treatment of other diseases by modulation of angiogenesis are currently tested in clinical trials. Thus the manipulation of new vessel formation in angiogenesis-dependent conditions such as wound healing, inflammatory diseases, ischemic heart and peripheral vascular disease, myocardial infarction, diabetic retinopathy, and cancer is likely to create new therapeutic options.

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“…By this route the Gene Therapy vector, or other form of DNA, is taken up by cells only in the immediate vicinity of the injection site, as diffusion is limited, with slower injection rates allowing somewhat wider dispersion. Spread of vectors to many other brain regions can be mediated by anterograde or retrograde transport of vectors within neurons projecting to the injection site (Figure 2 122,123 or endothelial cells, 124 to increase the range of gene delivery in the brain.…”

Section: Lentivirus Vectorsmentioning

confidence: 99%

Gene therapy in the CNS

et al. 2000

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Endothelial cell implantation and survival within experimental gliomas.

Abstract: The delivery of therapeutic genes to primary brain neoplasms opens new opportunities for treating these frequently fatal tumors. Efcint gene delivery to tissues remains an important obstacle to therapy, and this problem has unique characteristics in brain tumors due to the blood-brain

Cited by 44 publications

References 39 publications

Central nervous system endothelium in neuroinflammatory, neuroinfectious, and neurodegenerative disease

Central nervous system endothelium in neuroinflammatory, neuroinfectious, and neurodegenerative disease

Angiogenesis: mechanistic insights, neovascular diseases, and therapeutic prospects

Gene therapy in the CNS

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