AIM: To compare the effect of transarterial chemoembolization(TACE) plus GRGDSP(Gly-Arg-Gly-Asp-SerPro, integrin-inhibitor) loaded nanoparticles with TACE alone or TACE + GRGDSP in a rat model of liver tumor. METHODS:...AIM: To compare the effect of transarterial chemoembolization(TACE) plus GRGDSP(Gly-Arg-Gly-Asp-SerPro, integrin-inhibitor) loaded nanoparticles with TACE alone or TACE + GRGDSP in a rat model of liver tumor. METHODS: Morris hepatoma 3924 A tumors were implanted in the livers of 30 ACI rats. The ACI rats were divided randomly into three groups(10 animals each). Tumor volume before treatment(V1) was examined by magnetic resonance imaging(MRI), and then, after laparotomy and placement of a PE-10 catheter into the hepatic artery, the following interventional protocols were performed: TACE(mitomycin C + lipiodol + degradable starch microspheres) + GRGDSP loaded nanoparticles for group A; TACE + GRGDSP for group B(control group 1); TACE alone for group C(control group 2). Tumor volume(V2) was assessed by MRI and the mean ratio of the post-treatment to pretreatment tumor volumes(V2/V1) was calculated. Immunohistochemical analysis was performed to assess the quantification of matrix metalloprotein 9(MMP-9) and vascular endothelial growth factor(VEGF) positive tumor cells in each treatment group.RESULTS: The mean tumor growth ratios(V2/V1) were 1.3649 ± 0.1194 in group A, 2.0770 ± 0.1595 in group B, and 3.2148 ± 0.1075 in group C. Compared with groups B and C, group A showed a significant reduction in tumor volume. Lower expression of MMP-9 and VEGF in hepatocellular carcinoma was observed in group A than in groups B and C. The angiogenesis of tumor was evaluated using anti-VEGF antibodies, and the metastasis of tumor was assessed using antiMMP-9 antibody. MMP-9 and VEGF were expressed in all specimens. The immunoexpression of these proteins was confirmed by the presence of red cytoplasmic staining in tumor cells. Lower expression of MMP-9 and VEGF in hepatocellular carcinoma was observed in group A than in groups B and C.CONCLUSION: Transarterial administration of integrin inhibitor loaded nanoparticles combined with TACE evidently retards tumor growth and intrahepatic metastases compared with TACE alone or TACE plus integrin inhibitor in an animal model of hepatocellular carcinoma.展开更多
Diabetic retinopathy(DR),a leading cause of visual loss,is the result of microvascular damage induced by prolonged hyperglycemia.Numerous studies have revealed the pivotal role of integrins in the pathogenesis of DR,p...Diabetic retinopathy(DR),a leading cause of visual loss,is the result of microvascular damage induced by prolonged hyperglycemia.Numerous studies have revealed the pivotal role of integrins in the pathogenesis of DR,particularly in key processes such as inflammation,vascular leakage,microthrombus formation,and angiogenesis.Consequently,targeting integrins is considered a promising strategy for the treatment of DR.This review focuses on the function of integrins in DR and their potential as therapeutic targets.It describes the molecular mechanisms through which integrins influence DR progression and summarizes the latest outcomes of integrin antagonist-based therapeutic strategies in clinical studies,evaluating their efficacy and potential challenges,which offer promise as novel treatment options for DR.展开更多
Age-related macular degeneration(AMD)is a leading cause of blindness worldwide.AMD most commonly affects older individuals and is characterized by irreversible degeneration of the retinal pigment epithelium and neuros...Age-related macular degeneration(AMD)is a leading cause of blindness worldwide.AMD most commonly affects older individuals and is characterized by irreversible degeneration of the retinal pigment epithelium and neurosensory retina.Currently,there are limited treatment options for dry AMD outside of lifestyle modification and nutrient supplementation.Risuteganib[Luminate(ALG-1001),Allegro Ophthalmics,CA,USA]is an intravitreally administered inhibitor of integrin heterodimersαVβ3,αVβ5,α5β1,andαMβ2.It is currently undergoing clinical trials for the treatment of dry AMD and diabetic macular edema(DME).Preclinical studies have shown that risuteganib has an effect on the pathways for angiogenesis,inflammation,and vascular permeability.Ongoing clinical trials have had promising results showing improvements in patient best corrected visual acuity(BCVA)and reduced central macular thickness measured by optical coherence tomography(OCT).There is a pressing need for treatments for dry AMD and while risuteganib appears to have a potential benefit for patients,more data are needed before one can truly evaluate its efficacy.This narrative review provides a concise summary of the most up to date data regarding the proposed mechanism of action of risuteganib in the treatment of nonexudative AMD and DME as well as the results from recent phase 1 and phase 2 clinical trials.展开更多
基金Supported by the National Natural Science Foundation of China,No.81071241
文摘AIM: To compare the effect of transarterial chemoembolization(TACE) plus GRGDSP(Gly-Arg-Gly-Asp-SerPro, integrin-inhibitor) loaded nanoparticles with TACE alone or TACE + GRGDSP in a rat model of liver tumor. METHODS: Morris hepatoma 3924 A tumors were implanted in the livers of 30 ACI rats. The ACI rats were divided randomly into three groups(10 animals each). Tumor volume before treatment(V1) was examined by magnetic resonance imaging(MRI), and then, after laparotomy and placement of a PE-10 catheter into the hepatic artery, the following interventional protocols were performed: TACE(mitomycin C + lipiodol + degradable starch microspheres) + GRGDSP loaded nanoparticles for group A; TACE + GRGDSP for group B(control group 1); TACE alone for group C(control group 2). Tumor volume(V2) was assessed by MRI and the mean ratio of the post-treatment to pretreatment tumor volumes(V2/V1) was calculated. Immunohistochemical analysis was performed to assess the quantification of matrix metalloprotein 9(MMP-9) and vascular endothelial growth factor(VEGF) positive tumor cells in each treatment group.RESULTS: The mean tumor growth ratios(V2/V1) were 1.3649 ± 0.1194 in group A, 2.0770 ± 0.1595 in group B, and 3.2148 ± 0.1075 in group C. Compared with groups B and C, group A showed a significant reduction in tumor volume. Lower expression of MMP-9 and VEGF in hepatocellular carcinoma was observed in group A than in groups B and C. The angiogenesis of tumor was evaluated using anti-VEGF antibodies, and the metastasis of tumor was assessed using antiMMP-9 antibody. MMP-9 and VEGF were expressed in all specimens. The immunoexpression of these proteins was confirmed by the presence of red cytoplasmic staining in tumor cells. Lower expression of MMP-9 and VEGF in hepatocellular carcinoma was observed in group A than in groups B and C.CONCLUSION: Transarterial administration of integrin inhibitor loaded nanoparticles combined with TACE evidently retards tumor growth and intrahepatic metastases compared with TACE alone or TACE plus integrin inhibitor in an animal model of hepatocellular carcinoma.
基金Supported by the Natural Science Foundation of Inner Mongolia,No.2022MS080572022 Autonomous Region Medical and Health Science and Technology Plan Projects,No.202202190.
文摘Diabetic retinopathy(DR),a leading cause of visual loss,is the result of microvascular damage induced by prolonged hyperglycemia.Numerous studies have revealed the pivotal role of integrins in the pathogenesis of DR,particularly in key processes such as inflammation,vascular leakage,microthrombus formation,and angiogenesis.Consequently,targeting integrins is considered a promising strategy for the treatment of DR.This review focuses on the function of integrins in DR and their potential as therapeutic targets.It describes the molecular mechanisms through which integrins influence DR progression and summarizes the latest outcomes of integrin antagonist-based therapeutic strategies in clinical studies,evaluating their efficacy and potential challenges,which offer promise as novel treatment options for DR.
文摘Age-related macular degeneration(AMD)is a leading cause of blindness worldwide.AMD most commonly affects older individuals and is characterized by irreversible degeneration of the retinal pigment epithelium and neurosensory retina.Currently,there are limited treatment options for dry AMD outside of lifestyle modification and nutrient supplementation.Risuteganib[Luminate(ALG-1001),Allegro Ophthalmics,CA,USA]is an intravitreally administered inhibitor of integrin heterodimersαVβ3,αVβ5,α5β1,andαMβ2.It is currently undergoing clinical trials for the treatment of dry AMD and diabetic macular edema(DME).Preclinical studies have shown that risuteganib has an effect on the pathways for angiogenesis,inflammation,and vascular permeability.Ongoing clinical trials have had promising results showing improvements in patient best corrected visual acuity(BCVA)and reduced central macular thickness measured by optical coherence tomography(OCT).There is a pressing need for treatments for dry AMD and while risuteganib appears to have a potential benefit for patients,more data are needed before one can truly evaluate its efficacy.This narrative review provides a concise summary of the most up to date data regarding the proposed mechanism of action of risuteganib in the treatment of nonexudative AMD and DME as well as the results from recent phase 1 and phase 2 clinical trials.
