Detection and significance of angiogenic factors and vascular endothelial function in patients with hypertensive retinopathy of pregnancy / 国际眼科杂志(Guoji Yanke Zazhi)

@#AIM: To investigate the changes of angiogenic factors and vascular endothelial function in patients with hypertensive retinopathy complicating pregnancy, and to analyze the relationship between the relevant factors and the degree of retinopathy. <p>METHODS: Totally 82 cases of patients with hypertensive retinopathy in pregnancy were selected as the research subjects. According to the Duker-Elder fundus staging criteria, they were divided into stage Ⅰ group(<i>n</i>=42), patients with stage Ⅱ group(<i>n</i>=25)and stage Ⅲ group(<i>n</i>=15), in addition, pregnancy hypertension patients without retinopathy were selected as control group. We compared the levels of angiogenic factors and vascular endothelial function among groups, and analyzed the relationship between the levels of relevant factors and retinopathy. <p>RESULTS:The levels of vascular endothelial growth factor(VEGF), insulin like growth factors(IGF-1)and endothelin(ET)-1 in the observation group were significantly higher than those in the control group(<i>P</i><0.01), and the levels were significantly increased with the increase of fundus staging, the difference was statistically significant. The level of NO in the observation group was significantly lower than that of the control group, with the increase of the fundus staging, the level of NO decreased significantly, and the difference was statistically significant(<i>P</i><0.01). Spearman correlation analysis showed that the degree of pregnancy induced hypertension retinopathy was positively correlated with VEGF, IGF-1 and ET-1, and negatively correlated with NO(<i>P</i><0.05). <p>CONCLUSION: There are obvious angiogenic factors disorder and vascular endotheial dysfunction in patients with hypertensive retinopathy of pregnancy, and its level is correlated with the degree of retinopathy.

Effect of recombinant human endostatin combined with chemotherapy on chemotherapy response and VEGF expression in patients with advanced malignant tumor / 中国生化药物杂志

Objective To investigate the effect of recombinant human endostatin combined with chemotherapy on the expression of vascular endothelial growth factor (VEGF) in patients with advanced cancer.Methods250 patients with advanced malignant tumors were randomly selected from February 2012 to February 2016 the Third Hospital of Jiaxing, with unit control method experiment principle divided into two groups: experimental group (125 cases) and control group (125 cases).The experimental group treated by recombinant human endostatin combined chemotherapy, control group received routine chemotherapy for a week during the period of 21 days, after two cycles of treatment, clinical efficacy and adverse reactions of the two groups of patients were compared, and the expression of VEGF in tumor blood vessels weredetected.ResultsAfter two cycles of treatment, objective response rate, disease control rate in the experimental group patients was significantly higher than that in control group (P<0.05);after treatment, the expression level of VEGF in serum of the experimental group and the control groupwere decreased significantly, but the experimental group was lower than that of control group was more obvious (P<0.05).ConclusionRecombinant human endostatin combined with chemotherapy in the treatment of advanced malignant tumors can enhance the effect of chemotherapy, regulate the level of VEGF.

The changes of aqueous humor vascular endothelial growth factor and pigment epithelium-derived factor levels before and after intravitreal injection of ranibizumab in proliferative diabetic retinopathy / 中华实验眼科杂志

Background Intraocular neovascularization is a primary cause of visual reduce in proliferative diabetic retinopathy (PDR) , and intravitreal injection of ranibizumab is one of treating approachs.Researching the mechanism of intravitreal injection of ranibizumab for PDR is a new target for the prevention and management of PDR.Objective This study was to determine the levels of vascular endothelial growth factor (VEGF) and pigment epithelium-derived factor (PEDF) in aqueous humor of PDR eyes before and after intravitreai injection of ranibizumab.Methods Self-controlled observational study was designed.Fifteen eyes of 15 PDR patients with type 2 diabetes mellitus were included in Fuzhou General Hospital of Nanjing Military Command from January to August 2014, and 1 eye combined with neovascular glaucoma and iris rubeosis.Aqueous samples of 0.1 ml at each time were collected before and 7 days after the injection of ranibizumab from all patients under the informed consent.The changes of aqueous VEGF and PEDF concentrations were detected and analyzed by enzyme-linked immunosorbent assay.This study complied with Declaration of Helsinki and the protocol was approved by this hospital.Results The freeVEGF concentrations before and 7 days after intravitreal injection were (179.4±136.5) pg/ml and (27.1 ±23.5) pg/ml, respectively, showing a significant reduce after intravitreal injection of ranibizumab (t =4.172, P =0.001).PEDF concentrations before and 7 days after intravitreal injection were (394.0-±237.2) pg/ml and (267.7±199.6) pg/ml, respectively, showing a significant reduce after intravitreal injection of ranibizumab (t =5.443, P =0.000).Intraocular neovascularization vanished after intravitreal injection of ranibizumab and vitrectomy was carried out at the seventh day after intravitreal injection.Conclusions Free VEGF and PEDF levels in aqueous humor appear to be significantly decreased after intravitreal injection of ranibizumab, and ocular neovascularization disappears at same time,which avoids intraoperative bleeding during vitrectomy.

Morphological and immunohistochemical characterization of angiogenic and apoptotic factors and the expression of thyroid receptors in the ovary of tilapia Oreochromis niloticus in captivity / Caracterização morfológica e imuno-histoquímica de fatores angiogênicos e apoptóticos e da expressão de receptores tireoidianos no ovário de tilápia Oreochromis niloticus em cativeiro

Morphological and immunohistochemical characterization of angiogenic and apoptotic factors and the expression of thyroid receptors in the ovary of tilapia Oreochromis niloticus in captivity were studied. The morphological evaluation of the ovaries was performed by histological paraffin embedded and stained with HE. The immunohistochemical expressions of CDC47, VEGF, Flk-1, angiopoietin, Tie-2 and thyroid receptor (TRα) were performed by the technique of streptavidein-biotin-peroxidase. Apoptosis was assessed using the TUNEL kit. The relative expression of thyroid hormone receptors (TRα and TRß) was assessed by RT-PCR real time. The nuclear expression of CDC47 increased with the stage of maturation of the oocyte and was observed in the follicle cells. Apoptotic bodies were observed in the follicular cells of atretic follicles and postovulatory follicles from the ovaries of 150g and 350g fish. Expression of VEGF and its receptor Flk-1 was also observed in the follicular cells, and the expression of both increased with the maturity of the oocyte, with a higher intensity observed in the full-grown follicle. The expression of angiopoietin and of its receptor (Tie 2) was discrete and moderate respectively. TRα expression was independent of follicular development. However, the 350 g tilapia exhibited higher expression of TRß compared with the 50 g tilapia. We conclude that the proliferative activity and the expression of VEGF and its receptor increase with follicular maturation and that the TRs expression increases with ovarian maturity in tilapia (Oreochromis niloticus).(AU)

Foram estudadas as caracterizações morfológica e imuno-histoquímica de fatores angiogênicos e apoptóticos e a expressão de receptores tireoidianos no ovário de tilápia Oreochromis niloticus de cativeiro. A avaliação morfológica dos ovários foi realizada por cortes histológicos incluídos em parafina e corados por HE. As expressões imuno-histoquímicas de CDC47, VEGF e seu receptor Flk-1, angiopoetina e seu receptor Tie-2 e recertor tireoidiano (TRα) foram realizadas pela técnica de estreptavideina-biotina-peroxidade. A apoptose foi avaliada utilizando-se kit de TUNEL. A expressão relativa dos receptores de hormônios tireoidianos (TRα e TRß) foi avaliada pela técnica de RT-PCR tempo real. A expressão nuclear de CDC47 aumentou com a fase de maturação do oócito e foi observada nas células foliculares. Corpos apoptóticos foram observados nas células foliculares de folículos atrésicos e folículos pós-ovulatórios de ovários de peixes com 150g e 350g. A expressão de VEGF e do seu receptor Flk-1 foi também observada nas células foliculares , e a expressão de ambos aumentou com a maturidade do oócito , com uma maior intensidade no folículo maduro. A expressão de angiopoietina e do seu receptor (Tie 2) foi discreta e moderada, respectivamente. A expressão de TRα foi independente do desenvolvimento folicular. No entanto, a tilápia de 350g apresentou maior expressão de TRß em comparação com a tilápia de 50g. Conclui-se que a atividade proliferativa e a expressão de VEGF e de seu receptor aumenta com a maturação folicular e que a expressão dos TRs aumenta com a maturidade do ovário em tilápia (Oreochromis niloticus).(AU)

The effect of angiogenic factors with HA/PCL scaffold containing matrigel in a rat calvarial defect model / 동물의과학연구지

The current study was conducted in order to investigate bone formation using matrigel and angiogenic factors with HA and poly epsilon-caprolactone (HA/PCL) in a rat calvarial defect model. Calvarial defect formation was surgically created in Sprague Dawley rats (n=36). Rats in the control group (CD group, n=6) did not receive a graft. The HA/PCL scaffold was grafted with matrigel (M-HA/PCL group, n=6) or without matrigel (HA/PCL group, n=6); and 100 ng of vascular endothelial growth factor with HA/PCL scaffold containing matrigel (VEGF100 group, n=6), 100 ng (PDGF100 group, n=6) and 300 ng (PDGF300 group, n=6) of PDGF with HA/PCL scaffold containing matrigel were grafted in calvarial defects, respectively. Four weeks after surgery, bone formation was evaluated with micro computed tomography (micro CT) scanning, and histologically. According to the results, bone mineral density was significantly increased in the VEGF100, PDGF100, and PDGF300 groups compared to the HA/PCL group, in which angiogenic factors were not applied. In histological evaluation, more new bone formation around scaffolds was observed in the PDGF100 and the PDGF300 groups, compared with the VEGF100 group. Thus, the results indicate that HA/PCL containing matrigel with VEGF and PDGF is an effective grafting material for enhancement of bone formation in critical-sized bone defects. Especially, due to its price and capacity for bone formation, PDGF may be more effective than VEGF.

The possible dual role of neuronal guidance factor netrin-1 during angiogenesis and vascularization / 第二军医大学学报

The netrin family is known as classical axon guidance factors. Recent studies suggested the wide existence of netrins in non-nerve tissues, indicating a more complicated role for netrin family than previously known. The dual role of netrin-1 in promoting and inhibiting vasculariztion is undoubtedly the most attractive research area. Though the specific role of netrin-1 in vascularization is not determined, it casts new lights on the close link between the nervous system and vascular system, and it also provides new thoughts on the treatment of cardiac and cerebral ischemia disorders, diabetes-induced vascular and nervous disorders, and on inhibition of tumor angiogenesis. This paper reviews the possible dual role of netrin-1 in vascularization and its potential significance.

Expressão gênica de fatores angiogênicos na placenta de ratas submetidas ao estresse / Expression of the angiogenic factors in the placenta of stressed rats

Objetivos: Avaliar a influencia do estresse sobre os pesos maternos, placentários e fetais, as alterações histológicas placentárias e a expressão gênica dos fatores angiogênicos em ratas prenhes. Métodos: De setembro de 2007 a julho de 2008, foi realizado um estudo experimental do tipo casocontrole, em que 6 ratas prenhes foram submetidas a estímulos estressantes crônicos e agudos enquanto que 6 animais constituíram o grupo controle. No 20º dia de prenhez, todas as ratas foram sacrificadas. Os seguintes dados foram analisados e comparados entre os grupos: a. pesos maternos, placentários e fetais; b. alterações histológicas placentárias; e, c. expressão gênica dos fatores angiogênicos (VEGF-A e PlGF), dos seus receptores (VEGFR-1 e VEGFR-2) e do fator induzido por hipoxia (HIF-1). Resultados: Os pesos maternos, placentários e fetais foram significativamente menores no grupo de ratas prenhes-estressadas em relação ao controle. Histologicamente foram encontradas a presença de núcleos picnóticos no grupo prenhe-estressado. Observou-se expressão gênica significativamente maior de VEGF-A no grupo rata prenhe-estressada assim como redução significante da expressão gênica de PlGF, VEGFR-1, VEGFR-2, quando comparadas ao controle. Não houve alterações entre os grupos para o gene HIF-1. Conclusões: No modelo animal de estresse estudado, observou-se alterações significativas no peso placentário e da expressão gênica dos fatores angiogênicos placentários em ratas submetidas ao estresse.

Objectives: to evaluate the influence of the stress on the maternal, placental and fetal weights, on the histological findings and on the genetic expression of the angiogenic factors in pregnant rats. Methods: From September 2007 to Julie 2008, an experimental case-control study was conduced in which 6 pregnant rats were submitted to chronic and acute stress while six other were considered as controls. In the 20th day of gestation, all animals were sacrified. The following data were evaluated and compared between both groups: a. maternal, placental and fetal weights; b. histological findings; and c. genetic expression of angiogenic factors (VEGF-A and PIGF), receptors (VEGFR-1 and VEGFR-2) and hypoxic-induced factor (HIF- 1). Results: Maternal, placental and fetal weights were statistically smaller in the stressed animals comparing to controls. Histological analysis revealed picnotic nuclei in the placentas of stressed rats. A statistically significant increase in the genetic expression of VEGF-A as well as a reduction of the expression of the PlGF, VEGFR-1, VEGFR-2 were observed in the placentas of the stressed group in comparison to controls. There was no difference of expression of the gene HIF-1 between both groups. Conclusions: In the present animal model of stress, significant alterations in the placental weights, histology and genetic expression of the angiogenic factors among pregnant rats under stress.

Comparative immunohistochemical assays for the expression of angiogenic factors in tumors of human salivary glands

Local Angiogenesis and Neurological Functional Recovery After Cerebral Ischemia / 国际脑血管病杂志

Cerebral ischemia activates endogenous angiogenic factors,and increase microvessel density and form new capillaries in ischemic brain tissues.Exogenous angiogenic factors can more effectively promote angiogenesis and the establishment of collateral circulation in ischemic regions and peripherial tissues,improving local blood supply and reducing infarct size.The further study of the mechanisms and methods in promoting regional angiogenesis after cerebral ischemia will contribute to improve neurologic deficit.

The Effect of Cyclooxygenase-2 Inhibitor on the Gene Expression Profile of N-butyl-N-(4-hydroxybutyl) nitrosamine-induced Rat Urinary Bladder Cancer / 대한비뇨기과학회지

PURPOSE: Cyclooxygenase (COX)-2 plays an important role in promoting cancer cell proliferation and angiogenesis in human bladder cancer. In this study, we investigated the antitumor or antiangiogenic effects of selective COX-2 inhibitor on N-butyl-N-(4-hydroxybutyl)nitrosamine (BBN)-induced rat bladder tumorigenesis. MATERIALS AND METHODS: Forty male Fischer 344 rats (control) were given only 0.05% BBN, while 40 rats (experimental) were administered 1,500mg/ kg celecoxib once daily and this treatment started from 1 week before their BBN treatment. Ten rats from the control groups and the experimental groups were then sacrificed at 4, 12, 16 and 24 weeks after BBN treatment. We observed all the bladders macroscopically as well as microscopically, and we measured the COX-2 expression in the bladder tissues. Utilizing a cDNA microarray, we analyzed the significant differences of gene expression between the 12 week-control group and the 12 week-experimental group. RESULTS: The incidence of tumor was lower in the experimental group than in the control group from week 12 to week 24. The COX-2 expressions were more significantly decreased via the BBN induction (p<0.05) in the experimental groups than in the control groups after 4 weeks. For the 12 week-experimental group, there were 15 genes altered by the administration of selective COX-2 inhibitor, and the selective COX-2 inhibitor especially regulated transgelin, membrane metallo endopeptidase and apolipoprotein E of these 15 genes to prevent the incidence of bladder tumor. CONCLUSIONS: Selective COX-2 inhibitor has an inhibitory effect on BBN-induced rat bladder tumorigenesis. In the pre-neoplastic phase, selective COX-2 inhibitor regulates transgelin, membrane metallo endopeptidase and apolipoprotein E to prevent the incidence of bladder tumor.

Cyclooxygenase-2 Inhibitor Delayed the Tumorigenesis of N-Butyl-N-(4-hydroxybutyl)nitrosamine-induced Rat Urinary Bladder Cancer Model / 대한비뇨기과학회지

PURPOSE: Cyclooxygenase-2 (COX-2) plays an important role in promoting cancer cell proliferation and angiogenesis in human bladder cancer. The selective COX-2 inhibitor has antitumor activities in vivo and in vitro in a variety of tumor types. In this study, the antitumor or antiangiogenic effects of selective COX-2 inhibitor on N-butyl-N-(4-hydroxybutyl)nitrosamine-induced rat bladder tumorigenesis were investigated. MATERIALS AND METHODS: Forty male Fischer 344 rats (Control group) were given only 0.05% BBN in water ad libitum, while 40 others (Experimental group) were administered 1,500mug/kg celecoxib once daily through the gavage tube, which started 1 week before the BBN treatment. Ten rats were used as the normal bladder. Ten rats from the control and experimental group were sacrificed 4, 12, 16, and 24 weeks after the start of the BBN treatment. All bladders were evaluated both macroscopically and microscopically. We also measured COX-2 expression, microvessel density (MVD), and vascular endothelial growth factor (VEGF) protein concentrations in the bladder tissues. RESULTS: Macroscopically and microscopically, the incidence of tumor was lower in the experimental group than in the control group from the 12th week to the 24th week. Each incidence of tumor in week 12, week 16, and week 24 was 20%, 50%, and 80% in the control group and 0%, 20%, and 40% in the experimental group, respectively. In both the control and experimental groups, COX-2 expression had a tendency to be concentrated in the cytoplasm of the epithelial cells of the papillary tumor and the endothelial cells adjacent to the vessel the basal layer of bladder. COX-2 and VEGF expression were significantly more decreased in the experimental groups than in the control groups after 4 weeks from the BBN induction (p<0.05). MVD was significantly decreased in the experimental group at week 16 (p<0.05). CONCLUSIONS: The selective COX-2 inhibitor has an inhibitory effect on BBN-induced rat bladder tumorigenesis because of its partially antiangiogenic properties. In the future, the selective COX-2 inhibitor could be expected to play an important role as a chemo-preventive agent and as therapeutic aids in bladder cancer if these inhibitory effects can be reproduced in human bladder tumorigenesis.

Expression of chemokine CXCR4 and formyl peptide receptor FPR in rat C6 glioma cell line / 第三军医大学学报

Objective To detect the expression of chemoattractant receptors, CXCR4 and formyl peptide receptor (FPR), in rat glioma cell line C6 and to explore their relation to tumor differentiation and angiogenesis. Methods The expression of CXCR4 and FPR by C6 cells were detected with immunocytochemistry. The differentiatial degrees were also detected to analyze the relationship of chemoattractant receptors with angiogenesis and malignancy of glioma. Results C6 cells were of a long spindle shape, expressing high level of vimentin but relatively low level of glial fibrillary acidic protein (GFAP). C6 cells were positive for CXCR4 and FPR in the cytoplasm and strongly positive for vascular endothelial growth factor (VEGF). Conclusion C6 cell line is poorly differentiated and highly expresses chemoattractant receptors CXCR4 and FPR, both of which might be related to the angiogenic potentials.

Expression of VEGF and bFGF in xenografts of human osteosarcoma OS-732 on chick embryo chorioallantoic membrane and its significance / 中国癌症杂志

Purpose:To study the characterics of angiogenesis induced by osteosarcoma OS-732 cell line. Methods:With a tumor model of the chick embryo chorioallantoic membrane(CAM),the angiogenesis induced by OS-732 cell line was observed by a stereo-microscope and transmission electron microscope, and the expression of angiogenic factors vascular endothelial growth factor(VEGF) and basic fibroblast growth factor(bFGF) in xenografts of OS-732 cell line on CAM was detected by immunohistochemical technique. Results:This cell line was strongly angiogenic, which probably is associated with production of many factors.The new capillaries converging upon the tumor can be observed by a stereo-microscope. Furthermore,under transmission electron microscope, it also can be noted that the new blood vessel consisted of a monolayer of vascular endothelial cells with enlarged fissures,and the basal membrane was not intact. The expression of VEGF and bFGF was positive in xenografts on CAM, and VEGF was expressed at high levels constantly. Conclusions:The new blood vessels induced by tumors have pathologic and physiopathologic characteristics and many angiogenic factors are alm involved in the angiogenic process of OS-732. Furthermore, the application of angiogenic factors as a target in antiangiogenic therapy of osteosarcoma may be useful to improve the prognosis of patients with this disease.