Combretastatin A-4 Prodrug in the Treatment of a Murine Model of Retinoblastoma

Escalona-Benz, Erika; Jockovich, Maria Elena; Murray, Timothy G.; Hayden, Brandy C.; Hernandez, E.; Feuer, William J.; Windle, Jolene J.

doi:10.1167/iovs.04-0751

Cited by 38 publications

(21 citation statements)

References 26 publications

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“…21,36,37 It is possible, however, that vessel targeting may lead to increased selection of hypoxic cells within the tumor. Thus, the addition of glycolytic inhibitors as adjuvants to vessel targeting therapy has the potential to eliminate hypoxic regions while enhancing vascular targeting.…”

Section: Discussionmentioning

confidence: 99%

Targeting Hypoxia, a Novel Treatment for Advanced Retinoblastoma

Boutrid

Jockovich

Murray

et al. 2008

Invest. Ophthalmol. Vis. Sci.

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Section: Discussionmentioning

confidence: 99%

Targeting Hypoxia, a Novel Treatment for Advanced Retinoblastoma

Boutrid

Jockovich

Murray

et al. 2008

Invest. Ophthalmol. Vis. Sci.

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“…Subconjunctival injection has previously been shown to be an effective method to deliver substances to the retina. 33,34 Mice were killed at p17, and eyes were processed for retinal fluorescein angiography quantification of preretinal neovascular nuclei, and immunohistochemistry, as described. 9,31,32 To quantify retinal neovascularization, 6-m paraffin-embedded sections were stained with periodic acid-Schiff (PAS) and hematoxylin, and 10 intact sections of equal length, each 18 m apart, were evaluated.…”

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confidence: 99%

Inhibition of pathologic retinal neovascularization by -defensins

Economopoulou

Bdeir

Cines

et al. 2005

Blood

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Proliferative retinopathies, such as those complicating prematurity and diabetes, are major causes of blindness. A prominent feature of these retinopathies is excessive neovascularization, which is orchestrated by the hypoxia-induced vascular endothelial growth factor (VEGF) stimulating endothelial cells and the integrin-mediated adhesive interactions of endothelial cells with extracellular matrix components such as fibronectin (FN). Recently, we demonstrated that ␣-defensins interfere with ␣5␤1-FN interactions and dependent endothelial cell functions. Here, ␣-defensins were studied in hypoxia-induced proliferative retinopathy. In vitro, ␣-defensins specifically inhibited ␣5␤1-integrin-dependent migration of bovine retinal endothelial cells (BRECs) to FN, attenuated the VEGF-stimulated increase in endothelial permeability, and blocked BREC proliferation and capillary sprout formation in 3-dimensional fibrinmatrices. An up-regulation of ␤1-integrin and FN was observed in the retinal vessels in the mouse model of hypoxiainduced retinal angiogenesis. Systemic and local administration of ␣-defensins reduced retinal neovascularization by 45% and 60%, respectively, and this effect was comparable to the inhibitory effect of ␣5␤1-blocking antibody. ␣-Defensins were detected in human diabetic retinas associated with normal retinal vessels but were absent from proliferative lesions. Together, these data show that ␣-defensins inhibit pathologic retinal neovascularization in vivo and may provide a clinically efficient strategy against proliferative retinopathies. IntroductionRetinopathy of prematurity and proliferative diabetic retinopathy are the major causes of neonatal and adult blindness, respectively. 1 Pathologic retinal neovascularization is ectopic-that is, the new vessels invade the vitreous cavity, resulting in vision-threatening complications, such as vitreous hemorrhage and retinal detachment. During proliferative retinopathy, neovascularization is regulated by several growth factors, especially the hypoxia-induced vascular endothelial growth factor (VEGF) that regulates endothelial cell proliferation, migration, and permeability and by the adhesive contacts of endothelial cells with the extracellular matrix. [2][3][4] Proteins of the extracellular matrix, such as fibronectin (FN), vitronectin (VN), and fibrinogen (FBG), are deposited into an adhesive fibrillar network and control endothelial growth, differentiation, and migration by transmitting signals to the cells through specific integrins. 5-8 Accordingly, we and others 9,10 have previously shown that interference with integrin-extracellular matrix interactions and blockade of VEGF are effective in inhibiting retinal neovascularization in a mouse model of hypoxia-induced retinal angiogenesis.Emerging evidence indicates that inflammatory cells may regulate endothelial cell functions related to angiogenesis in proliferative retinopathies. In retinopathy of prematurity and in diabetic retinopathy, leukocyte adhesion to retinal structures may lead to blood-ret...

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“…3 Vincristine is not mutagenic; however, secondary tumors have been reported in patients taking vincristine in a standard chemotherapy regimen. 30 Therefore, newer modalities, such as antiangiogenic treatments, 7,8 are under investigation. In previous studies, paclitaxel has been used to treat experimental proliferative vitreoretinopathy 16 and has also been used successfully to treat choroidal metastasis of breast cancer 10 ; however, it has never been tested as a treatment for primary ocular malignancy.…”

Section: Discussionmentioning

confidence: 99%

“…4 -6 Therefore, treatments that function through alternative mechanism are under investigation. 7,8 Paclitaxel is an antimitotic therapeutic agent that stabilizes microtubules and disrupts normal spindle formation during metaphase. 9 It is as an effective treatment for a wide range of cancers 10 -13 but has been used primarily for breast, ovarian, lung, cervical, and endometrial cancer.…”

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confidence: 99%