Purpose: To examine the effect of an intravitreal injection of angiostatin on vascular leakage in retina and iris of the diabetes and study its possible mechanism. Methods: Experimental diabetes was induced in 24 rats...Purpose: To examine the effect of an intravitreal injection of angiostatin on vascular leakage in retina and iris of the diabetes and study its possible mechanism. Methods: Experimental diabetes was induced in 24 rats by an intravenous injection of streptozotocin (STZ) during 48 adult rats. Three groups were randomization distributed of them. There were 8 of both normal and diabetic rats in each group. STZ-diabetic rats and age-matched normal rats received an intravitreal injection of 5 μl of sterile PBS (Phosphate Buffered Saline) into the right eye, and the left eye was non-injected in the group A; Angiostatin was injected into the vitreous of the right eye (7.5 μg / 5 μl / eye), and the left eye received the same volume of sterile PBS as the control in the group B and C. The vascular permeability of retina and iris was measured using the Evans blue method at 2 days following the injection in the group A and B. Expression of VEGF in retina was evaluated using western blot analysis 24 hours following the injection in the group C. Results: Diabetic rats showed significant increases of vascular permeability in the retina ( P < 0.01) and iris ( P < 0.05). Angiostatin-injected eyes showed significant decreases in vascular permeability in the retina ( P < 0.01) and iris ( P < 0.05) comparing with the PBS-injected eyes in STZ-diabetic rats. In contrast, intravitreal injection of the same dose of angiostatin into the age-matched normal rats did not result in any significant reduction in vascular permeability in the retina and iris, when compared with the contralateral eye with PBS injection ( P > 0.05). Angiostatin injection significantly reduced VEGF level in the retinas of STZ-diabetic rats but did not affect retinal VEGF level in normal rats. Conclusions: Angiostatin significantly reduce pathological vascular permeability in the retina and iris of STZ-diabetic rats but not in normal rats. Angiostatin down-regulates VEGF expression and thus, blocks the major cause of vascular leakage in the diabetic retina. Therefore, angiostatin may have a therapeutic potential in the treatment of diabetic macular edema, cystoid macular edema, uvietis and other diseases with vascular leakage.展开更多
Cancer is a group of diseases with significant morbidity and mortality.In cancer cells,where energy requirements are exceptionally high,angiogenesis,which is the sprouting of new blood vessels from pre-existing ones,i...Cancer is a group of diseases with significant morbidity and mortality.In cancer cells,where energy requirements are exceptionally high,angiogenesis,which is the sprouting of new blood vessels from pre-existing ones,is an important process for tumour survival and progression.Hence,extensive research in recent years focuses on the discovery of new anticancer drugs that target angiogenesis.Several methodologies have been developed preclinically,including the inhibition of pro-angiogenic factors and their receptors via micromolecular agents or monoclonal antibodies and the inhibition of other compensatory pathways beyond the traditional angiogenic ones.The purpose of the literature review is to present new anticancer drugs that target the process of angiogenesis and have been under preclinical or clinical investigation during the last five years.Many new anticancer drugs targeting angiogenesis are identified in the literature.The results of the in vitro and in vivo evaluation of these drugs show that,apart from inhibiting angiogenesis,they also affect cancer cell proliferation and tumour growth.Recent clinical studies show that these drugs increase the overall or disease-free survival of patients,even those with persistent,chemotherapy-resistant and metastatic types of cancer,although treatment-related side effects are not uncommon.Drugs that target the process of angiogenesis are likely to be the future of anticancer therapy,especially in cases where more traditional treatments do not produce the desired results and where combination regimens of anti-angiogenic agents with standard chemotherapeutics increase patient survival.展开更多
基金Supported by a grant from 2004 Shenzhen Technological Plan( code:200405097)
文摘Purpose: To examine the effect of an intravitreal injection of angiostatin on vascular leakage in retina and iris of the diabetes and study its possible mechanism. Methods: Experimental diabetes was induced in 24 rats by an intravenous injection of streptozotocin (STZ) during 48 adult rats. Three groups were randomization distributed of them. There were 8 of both normal and diabetic rats in each group. STZ-diabetic rats and age-matched normal rats received an intravitreal injection of 5 μl of sterile PBS (Phosphate Buffered Saline) into the right eye, and the left eye was non-injected in the group A; Angiostatin was injected into the vitreous of the right eye (7.5 μg / 5 μl / eye), and the left eye received the same volume of sterile PBS as the control in the group B and C. The vascular permeability of retina and iris was measured using the Evans blue method at 2 days following the injection in the group A and B. Expression of VEGF in retina was evaluated using western blot analysis 24 hours following the injection in the group C. Results: Diabetic rats showed significant increases of vascular permeability in the retina ( P < 0.01) and iris ( P < 0.05). Angiostatin-injected eyes showed significant decreases in vascular permeability in the retina ( P < 0.01) and iris ( P < 0.05) comparing with the PBS-injected eyes in STZ-diabetic rats. In contrast, intravitreal injection of the same dose of angiostatin into the age-matched normal rats did not result in any significant reduction in vascular permeability in the retina and iris, when compared with the contralateral eye with PBS injection ( P > 0.05). Angiostatin injection significantly reduced VEGF level in the retinas of STZ-diabetic rats but did not affect retinal VEGF level in normal rats. Conclusions: Angiostatin significantly reduce pathological vascular permeability in the retina and iris of STZ-diabetic rats but not in normal rats. Angiostatin down-regulates VEGF expression and thus, blocks the major cause of vascular leakage in the diabetic retina. Therefore, angiostatin may have a therapeutic potential in the treatment of diabetic macular edema, cystoid macular edema, uvietis and other diseases with vascular leakage.
文摘Cancer is a group of diseases with significant morbidity and mortality.In cancer cells,where energy requirements are exceptionally high,angiogenesis,which is the sprouting of new blood vessels from pre-existing ones,is an important process for tumour survival and progression.Hence,extensive research in recent years focuses on the discovery of new anticancer drugs that target angiogenesis.Several methodologies have been developed preclinically,including the inhibition of pro-angiogenic factors and their receptors via micromolecular agents or monoclonal antibodies and the inhibition of other compensatory pathways beyond the traditional angiogenic ones.The purpose of the literature review is to present new anticancer drugs that target the process of angiogenesis and have been under preclinical or clinical investigation during the last five years.Many new anticancer drugs targeting angiogenesis are identified in the literature.The results of the in vitro and in vivo evaluation of these drugs show that,apart from inhibiting angiogenesis,they also affect cancer cell proliferation and tumour growth.Recent clinical studies show that these drugs increase the overall or disease-free survival of patients,even those with persistent,chemotherapy-resistant and metastatic types of cancer,although treatment-related side effects are not uncommon.Drugs that target the process of angiogenesis are likely to be the future of anticancer therapy,especially in cases where more traditional treatments do not produce the desired results and where combination regimens of anti-angiogenic agents with standard chemotherapeutics increase patient survival.
