ObjectiveTo study the effects of angiogenesis inhibitor SU5416 on the microvessel density(MVD) of pancreatic cancer and to evaluate its influence on the growth and metastasis of pancreatic cancer. Methods A rat model of pancreatic cancer was established with dimethylbenzanthracine(DMBA). 60 rats with pancreatic cancer were randomly divided into 4 groups: saline group, 5-Fu group, SU5416 group, 5-Fu and SU5416 group. Thirteen weeks after injection, the microvascular density (MVD) of pancreatic cancer was detected.Results The microvascular densities (MVD) were (12.3±3.2)%, (11.4±3.8)%, (2.1±1.5)% and (1.8±1.1)% in the saline group, 5-Fu group, SU5416 group and 5-Fu+SU5416 group respectively. The MVDs in the SU5416 group and 5Fu+SU5416 group were statistically lower than those in the saline group and 5-Fu group(P＜0.05). There was no significant difference between the 5-Fu group and saline group(Pgt;0.05). ConclusionSU5416 can inhibit the microvascular growth in pancreatic cancer. And the inhibition can be enhanced when combined with chemotheraputic drugs.
【Abstract】Objective To introduce the progress on clinic trial of antiangiogenic breast cancer therapy. Methods The current literatures on progress on clinic trial of antiangiogenic breast cancer therapy were reviewed. ResultsPathological angiogenesis is a hallmark of cancer. Concentrated efforts in this area of research are leading to the discovery of a growing number of antiangiogenic molecules, more than 30 of which are already on clinical trial. About 10 of angiogenic inhibitors are already on clinical trial of antiangiogenic breast cancer therapy. Most of them are in clinical phase Ⅰ or Ⅱ studies and a few, however, have progressed to phase III evaluation. Some results show that angiogenic inhibitors can reduce the toxicity and be less likely to generate drug resistance than conventional cytotoxic drugs. Conclusion Pathological angiogenesis is indeed essential for breast cancer metastasis and recurrence. Antiangiogenesis can cause regression of the breast cancer and provide a optimum stragy to treat the breast cancer.
Objective To observe the inhibitory effects and characteristics of intravitreal injection with bevacizumab on laser induced choroidal neovascularization (CNV).Methods Twelve male brown norway（BN）rats were divided into the bevacizumab group and control group with six rats in each group. One eye of rats were received a series of 8 diode laser esions around optic disc to induce CNV,then the rats in bevacizumab group and control group underwent intravitreal injection with 2 mu;l bevacizumab and ringer's lactate.On days 7,14,and 21，the morphology and leakage of CNV were observed by fundus fluorescein angiography (FFA) and indocyanine green angiography (ICGA).On day 21 after photocoagulation,the photocoagulated eyes were enucleated and processed for histopathologic examination, including hematoxylin and eosin (Hamp;E) staining and immunohistochemistry staining for vascular endothelial growth factor（VEGF）.Results On day 7 after photocoagulation,ICGA showed that CNV developed in the bevacizumab group and the control group. FFA showed that leakage intensity in the bevacizumab group was significantly lower than that in the control group，but the bevacizumab group gradually increased over time. The mean thickness of CNV significantly decreased in the bevacizumab group.The CNV in the bevacizumab group were negative for VEGF according to the result of immmuohistochemistry staining.Conclusions Early intravitreal injection with 2 mu;l bevacizumab can reduce the thickness of CNV and inhibit the leakage of CNV. However, bevacizumab could neither block the formation of CNV, nor suppress the permeability permanently. Combined other therapies with bevacizumab may be more potential to treat CNV effectively.
ObjectiveTo observe the inhibitory effect of endostatin (ES) on oxygen-induced retinal neovascularization.MethodsThirtyfour 7-day-old C57BL/6J mice were randomly divided into 3 groups: oxygen-exposed group (12 mice), ES group (12 mice) and the control group (8 mice). The mice in oxygen-exposed and ES group were exposed to (75±5)％ oxygen for 5 days and then back to the normal air. In ES group, 1 μg ES endostatin were injected into vitreous in one eye, while PBS was injected into the other eye as the control 12 and 36 hours after being exposed to oxygen. The mice in the control group were fed in normal circumstance. The changes of retinal neovascularization was examined by fluorescence angiography with fluorescein isothiocyanatedextran. The number of endothelial cells breaking through the internal limiting membrane (ILM) was counted and the inhibitory effects of ES on retinal neovascularization was observed.ResultsCompared with the oxygen-exposed group, the branches of retinal vessels went normal without any un-perfused area in ES group. The number of nuclei of endothelial cells breaking through ILM on each retinal crosssection decreased to (5.39±1.52), which differed much from that in the oxygen-exposed group (22.56±2.13) (plt;0.001).ConclusionES can effectively inhibit the formation of retinal neovascularization in rats and might be a new path of the treatment for proliferative retinopathy.(Chin J Ocul Fundus Dis, 2005,21:314-317)
ObjectiveTo observe the effects of angiostatin on the activity of extra-cellular signal-regulated protein kinase (ERK) of retinal microvascular endothelial cells of mice.MethodsAngiostatin was separated and purified by l-lysine sepharose 4B from human plasma. The primary retinal microvascular endothelial cells were divided into 4 groups: the control group, vascular endothelial growth factor (VEGF) 10 ng/ml group, angiostatin 130 μg/ml group, and VEGF (10 ng/ml) + angiostatin (130 μg/ml) group. The expression of ERK1 was assayed by Westernblotting method 1, 2, 5, 10, 15, and 30 minutes after the treatment of angiostatin.ResultsCompared with the control group, the expression of ERK-1 reduced 1 minute after treatment, reduced markedly after 10 minutes. After 30 minutes, no differences of the expression of ERK were seen between the control group and angiostatin group. The activation of ERK-1 of retinal microvascular endothelial cells occurred after stimulated by VEGF, and at the pitch at the peak after 5 minutes. The level of ERK in VEGF group increased 210% than that in the control (P＜0.05). After 30 minutes, no significant difference of the level of ERK between VEGF and the control group. And because of angiostatin, the expression of ERK-1 decreased 11.9%(1 minute)、17.9%(2 minutes)、38.7%(5 minutes)、49.3%(10 minutes) （P＜0.05）、27.9%(15 minutes)、1.12%(30 minutes) respectively.ConclusionsAngiostatin can effectively block the signal path through which VEGF transmits from outside of the cell to cellular nuclei. (Chin J Ocul Fundus Dis, 2005,21:170-173)
Objective To explore the inhibitory effects of r-k4k5 on retinal neovascularization. Methods Eighty-eight one-week-old C57BL/6J mice were put into the environment with 75% oxygen for 5 days to establish models of vascular proliferation retinopathy. One eye of each mouse received an intravitreal injection of 500 ng of r-k4k5 (large-dosage group) and of 250 ng of r-k4k5(small-dosage group), and the same volume of BSS was injected into the other eye of the mice both in these two groups as a control. The ADPase histochemical staining was used for retinal flatmount to observe changes of retinal vessels. The inhibitory effects of r-k4k5 on retinal neovascularization were evaluated by counting the endotheliocyte nuclei of new vessels extending from retina to vitreous in the tissue-slice. Results Regular distributions and reduced density of retinal blood vessels in eyes in the treatment group were found in retinal flatmount. The number of the endotheliocyte nuclei of new vessels extending from retina to vitreous was less in the eyes in the treatment group than which in control group (Plt;0.001). The nuclei of new blood vessels in the large-dosage group were less than which in small-dosage group (Plt;0.001). No histologic evidence of retinal toxicity or inflammatory response was found in the tissue-slice after the injection of r-k4k5. Conclusions Retinal neovascularization can be inhibited by intravitreal injection of r-k4k5,which suggests that intravitreal injection of r-k4k5 may have potential therapeutic benifits in retinal vascular disease. (Chin J Ocul Fundus Dis，2003，19：121-124)
Objective To determine whether kringle 4-5 could inhibit choroidal neovascularization (CNV) in mice induced by argon laser photocoagulat ion. Methods Fundus laser photocoagulation was performed on C57BL/6J mice to induce CNV. In treatment group, 20 μg (low dosage group) and 50 μg (high dosage group) kringle 4-5 were injected retrobulbarly after photocoagulation. In control group, equilibrium liquid was injected retrobulbarly. Choroidal neovascularization was evaluated on the 7th and 14th day after photocoagulation by fundus fluorescein ang iography. The mice were killed on the 14th day after photocoagulation, the lesions were evaluated histologically and immunohistochemically, and the expression of CD105 was detected. The Expression of VEGF and bFGF was detected by immunohist ochemistry on the 4th day after photocoagulation.Results The incidence of CNV was 64.3% in control group, 51.2%（P＜0.05）in low dosage group, and 44. 1% (P＜0.01) in high dosage group. The CNV lesions were smaller in kringle 4-5 injected eyes in a dose-dependent manner and the number of proliferative vascular endothelial cells in the subretinal membrane of the treated eyes was smaller than that of the control eyes. There was no significant difference of the expression of VEGF and bFGF between the mice in control and treatment group.Conclus ions Kringle 4-5 could inhibit the development of choroidal neovascularization in the experimental mice model.(Chin J Ocul Fundus Dis，2003，19：201-268)
ObjectiveTo observe the efficacy of intravitreal injection of ranibizumab (IVR) and combined treatment for severe Coats disease. MethodsNineteen Coats disease patients (24 eyes) were enrolled in this retrospective non-comparative interventional clinical study. The patients included 17 males and 2 females. The age was ranged from 1 to 42 years old, with an average of (13.05±6.78) years. The patients included 15 children (age ≤14 years old) and 4 adults (age ≥18 years old). There were 13 patients with 3a stage and 6 patients with 3b stage. The treatment methods including IVR only, IVR combined with cryotherapy, IVR combined with cryotherapy and sclerotomy to drain subretinal fluid, IVR combined with vitrectomy. Treatments were repeated if it was necessary at the first day, the first week and the first month after injection. The interval between treatments was ≥1 month. Eleven patients (57.9%) underwent one treatment, 3 patients (15.8%) underwent 2 treatments, 3 patients (15.8%) underwent 3 treatments, 2 patients (10.5%) underwent 4 treatments. The treatment frequency including 22 times of IVR only, 6 times of IVR combined with cryotherapy, 5 times of IVR combined with cryotherapy and sclerotomy to drain subretinal fluid, 1 time of IVR combined with vitrectomy. The follow-up period was ranged from 6 to 36 months, with an average of (19.11±7.05) months. Visual acuity, retinal reattachment and ocular adverse events were observed. ResultsThree children (15.8%) were failing to test the visual acuity. Visual acuity was improved in 2 patients (10.5%), stable in 13 patients (68.4%) and decreased in 1 patient (5.3%). Three patients (15.8%) achieved totally retinal reattachment after treatment, while 16 patients (84.2%) achieved partially retinal reattachment. One patient had vitreous hemorrhage. One patient had neovascular glaucoma. ConclusionIVR and combined treatment were effective for severe Coats disease.