Endostatins Research Articles

Effect of Selfheal soup combined benzene sulfonic acid amlodipine on elderly patients with hypertension and its effect on plasma endothelin-1

Objective To study the clinical curative effect of Chinese traditional medicine Prunella vulgaris Decoction for elderly hypertensive patients, and its influence on endothelin-1(ET-1). Methods From January 2016 to January 2018, 76 senile patients with hypertension in Wenling Hospital of Traditional Chinese Medicine were selected.According to different therapeutic methods, the patients were divided into two groups, with 38 cases in each group.The control group was given calcium antagonists benzene sulfonic acid amlodipine therapy, the observation group was given the combined therapy of Chinese and western medicine (Prunella vulgaris Decoction combined with benzene sulfonic acid amlodipine). All the patients were treated for 2 months, the therapeutic effect was evaluated.The 24-hour average diastolic blood pressure (24hDBP), 24-hour average systolic blood pressure (24hSBP), and diastolic pressure (dDBP), the day systolic blood pressure (dSBP), diastolic blood pressure at night (nDBP) and nocturnal systolic blood pressure (nSBP) were used to evaluate the clinical curative effect.Before and after treatment, the plasma ET-1 level was used to evaluate the influence on endothelial function.The clinical curative effect and its influence on ET-1 were compared between the two groups. Results After treatment, the 24hDBP, 24hSBP, dDBP, dSBP, nDBP and nSBP in the observation group were significantly lower than those in the control group[24hDBP (72.26±4.62)mmHg vs.(86.63±5.18)mmHg, 24hSBP (133.26±6.71)mmHg vs.(143.29±7.22)mmHg, dDBP (76.08±5.26)mmHg vs.(87.32±5.73)mmHg, dSBP (136.51±8.63)mmHg vs.(153.67±9.51)mmHg, nDBP (72.34±3.96)mmHg vs.(80.75±4.27)mmHg, nSBP (133.64±5.21)mmHg vs.(148.27±6.32)mmHg, t=12.637, 11.268, 11.762, 12.406, 10.625, 11.738, all P<0.05]. The plasma ET-1 level of the observation group was (59.37±7.82)μg/L, which was significantly lower than (67.58±7.72)μg/L of the control group (t=10.653, P<0.05). Conclusion Prunella vulgaris Decoction in the treatment of elderly hypertensive patients can effectively improve therapeutic effect, lower the blood pressure levels, and can improve endothelial function, it is worthy of popularization and application. Key words: Hypertension; Drugs, Chinese herbal; Selfheal soup; Endostatins; Aged

Endostatins combined radiotherapy and chemotherapy in the treatment of advanced non-small cell lung cancer

Objective To preliminary study clinical efficacy and toxicity of endostatin （ES） combined radiotherapy and chemotherapy in advanced non-small cell lung cancer （NSCLC）,and evaluate its effectiveness and safety.Methods We retrospectively reviewed 64 patients with Ⅲ B-Ⅳ stage NSCLC of Harbin Medical University Cancer Hospital from February 2009 to February 2012.The patients were divided into two groups：chemoradiotherapy group,39 patients and ES add chemoradiotherapy group,25 patients.The short-term effect,the total efficiency,median survival time,progression-free survival time and disease-free survival time were compared.Results The total effective rate of chemoradiotherapy group was 76.9%,while the total effective rate of ES add chemotherapy group was 84.0% （χ^2 =0.47,P =0.492）.Chemoradiotherapy group,compared to ES add chemotherapy group,the median survival time,median progression-free survival time,median disease-free survival time were 11.52 months vs 16.51 months （χ^2 =3.74,P =0.042）,7.32 months vs 10.37 months （χ^2 =5.32,P =0.025） and 5.21 months vs 7.57 months （χ^2 =4.56,P =0.035） respectively.The mainly adverse drug reactions were hematologic toxicity and gastrointestinal reactions,but there were no significant differences between the two groups; radiotherapy side effects mainly showed the grade 1 to 2 radiationinduced lung injury and radiation esophagitis （chemotherapy group had one case of grade 3 radiation-induced lung injury）,but also had no significant differences between the two groups.Conclusion ES combined chemoradiotherapy can achieve a better short-term clinical efficacy without increasing adverse effects of radiotherapy or chemotherapy in advanced non-small cell lung cancer. Key words: Carcinoma, non-small cell lung; Radiotherapy ; Chemotherapy, adjuvant; Endostatins

Expressions of angiostatin and endostatin in vascular proliferative skin diseases and their clinical implications

Objective To investigate the expressions of angiostatin and endostatin in different vascular proliferative skin diseases.Methods This study included 43 paraffin-embedded and 19 fresh skin tissue specimens from the lesions of patients with vascular proliferative skin diseases (such as capillary hemangioma,cavernous hemangioma,hemangioma racemosum,and pyogenic granuloma) as well as 6 fresh skin tissue specimens from the foreskin of infants.Immunohistochemistry and real-time qPCR were used to determine the expression pattern and levels of angiostatin and endostatin in these specimens.Results Both angiostatin and endostatin were expressed to a certain extent in the membrane and cytoplasm of vascular endothelial cells in these specimens of vascular proliferative skin diseases.The expression rates of angiostatin and endostatin in capillary hemangioma tissue specimens were 15.77％ ± 5.92％ and 19.35％ ± 7.81％ respectively,with their relative expression levels being 2.4 and 2.7 times those in the normal control skin specimens.No significant differences were observed in the expression level of angiostatin or endostatin between the normal control skin and lesions of the other vascular proliferative skin diseases (all P ＞ 0.05).Conclusions Angiostatin and endostatin are highly expressed in capillary hemangioma tissue,suggesting that they play biological roles in the pathogenesis of hemangioma via specifically acting against actively proliferating vascular endothelial cells. Key words: Angiostatins; Endostatins; Hemangioma, capillary; Hemangioma, cavernous; Granuloma,pyogenic

Effect of induction chemotherapy and three-dimensional conformal radiation (3D-CRT) combined with endostar in the treatment of locally advanced non-small cell lung cancer

Objective To evaluate the efficacy and safety of induction chemotherapy and three-dimensional conformal radiation (3D-CRT) combined with endostar in the treatment of locally advanced non-small cell lung cancer (NSCLC).Methods Thirty patients with locally advanced NSCLC were enrolled and divided into observation group (15 cases) and control group (15 cases).In the observation group,the patients received induction chemotherapy and 3D-CRT combined with endostar.Chemotherapy:Vinorelbine 25mg/m2 on day 1 and 8,DDP 30mg/m2 on day 2 to 4.Endostar 7.5mg/m2 on day 1 to 14,which was used again after 7 days for 2 to 4 cycles.In the control group,the patients received induction chemotherapy and 3D-CRT at the same dosage.All patients were treated with 3D-CRT and the prescription dose was 60 ～ 68Gy per fraction.The responses were evaluated according to WHO criteria.The shortterm efficacy between the 2 groups was compared.Results The overall effective rate of the two groups were 66.7％ and 60.0％,respectively (P ＞ 0.05).The median progression-free survival time was 12 months in the observation group and 10 months in the control group.The median survival time was 20 months in the observation group and 18 months in the control group.The 1 year overall survival rate was 80.0％ in the observation group and 73.3％ in the control group(P ＞ 0.05).The main toxicities in the two groups were marrow suppression,gastrointestinal symptoms,acute radiation pneumonitis and acute radiation esophagitis.There was no significant difference between the two groups (P ＞ 0.05).Conclusions The combination of endostar with induction chemotherapy and 3D-CRT can improve the short-term efficacy rate of locally advanced NSCLC,the adverse events of which are tolerable,but the improvement is not significant in both groups.The result pending further randomized multi-center phase Ⅲ clinical study. Key words: Carcinoma, non-small-cell lung; Endostatins ; Vinorelbine ; Radiotherapy, conformal

Endostatin in the treatment of non-small cell lung cancer

Endostatin is a novel anti-angiogenic drug which through multiple pathway inhibits vascular endothelial growth factor expression,to achieve the purpose of the inhibition of tumor angiogenesis.The drug in the treatment of non-small cell lung cancer in pre-clinical study and clinical application show that:used alone have anti-tumor effect; combined with radiotherapy and chemotherapy can obtain short-term curative effect,and does not increase treatment related toxicity.The adverse effect of the drug is mild and can be well tolerated. Key words: Endostatins; Carcinoma, non-small-cell lung; Radiotherapy; Drug therapy

Efficacy of genetically engineered oncolytic virus on glioma stem cells in vitro

Objective Exploring the effect of endostatin and angiostatin(Endo-Angio) fusion genemodified herpes simplex virus ( VAE ) on glioma stem cells ( GSCs ) in vitro. Method Surgical specimens of human high grade glioma ( WHO Ⅲ, Ⅵ) were collected, and GSCs were isolated under the culture conditionsoriginally designed for selective expansion of neural stem cells. In order to identify GSCs,the number of CD133 positive cells in GSCs were detected by flow cytometry; self - renewal capacity and the expression of Nestin, GFAP, NF, and MAG of GSCs were detected by monoclonal forming and immunofluorescence assay respectively. After that, GSCs viability was detected by MTS assay. Expression of Endo - Angio fusion gene at mRNA and protein level was detected by RT - PCR and Western blot. At last,the efficacy of fusion protein to human brain microvascular endothelial cells (HBMEC) and the biological properties of GSCs were detect after infected by VAE. Results ( 1 )4 GSCs isolated from 20 surgical specimens could suspend growth and had the ability of self-renewal and multipotential differentiation,and could express neural stem cells marker,CD133 and Nestin. (2)VAE could infect GSCs and significantly inhibit the viability of GSCs( P ＜0.05). (3) Significant expression of Endo-Angio fusion gene was observed and it could inhibit HBMEC proliferation( P ＜0.05). (4) Residual viable cells lost the ability of self - renewal and adherent differentiation. Conclusions In vitro, VAE can inhibit the activity of GSCs and the expression of exogenous Endo - Angio fusion gene can inhibit HBMEC proliferation. VAE can be used as a novd virus -gene therapy strategy for glioma. Key words: Glioma; Neoplastic stem cells; Endostatins; Angiogenesis inhibitors; Virus - gene therapy

Advance in research on anti-tumor of endostatin

Endostatin is an antitumor molecular targeting angiogenesis of tumor and plays an inhibitory role in tumorigenesis through inhibiting pathological angiogenesis, proliferation and metastasis of tumor. As increasing drugs for targeting therapy aim in clinic, endostatin has become one of hot spots of research on combined treatment of cancer in recent years. Key words: Endostatins; Neoplasms; Targeted therapy

Experimental research on inhibition of carotid artery atherosclerosis induced by endostatin gene mediated by ultrasound targeted microbubble destruction in rabbits

Objective To explore the inhibition effect on angiogenesis and plaque growth of carotid atherosclerosis by transfection of endostatin gene using microbubbles combined with ultrasound exposure.Methods Twenty rabbit models of carotid atherosclerosis were randomly divided into 3 groups:group A,microbubble+ ultrasound; group B, control plasmid + microbubble + ultrsound; group C, ES plasmid +microbubble+ ultrasound. Two weeks after surgery, ultrasound/microbubble mediated gene transfer was performed,and it was performed once again three weeks after the first transfection. Ultrasonography and digital subtraction angiography(DSA) were performed at the time of 14 weeks. The carotid arteries were taken to detect the neointima and angiogenesis, and the expression of endostatin was detected using pathological means. Results The imagings of ultrasound showed that the intima in group A and B were thick significantly with larger plaques, and the lumen became stenosis with the peak systolic velocity increasing,however,in group C,the parameters mentioned above were significantly less than those of group A and B ( P＜0.05). Pathological results displayed that intima-media thickness (IMT), intima thickness (IT), intima thickness/media thickness (IT/MT), intima area (IA), intima area/media area (IA/MA) and neointimal stenosis rates were greater in group A and B, however, they were less in group C ( P＜0.05).The number of neovascularization and vascular endothelial growth factor(VEGF) expression in group A and B were more than those of group C. There was more endostatin positive expression in carotid arteries and anterior tibial muscles of group C, while there was nearly no expression in group A and B. Conclusions Under the conditioned ultrasonic irradiation, ultrasound/microbubble mediated endostatin gene transfection can inhibit the development of carotid atherosclerosis in rabbits, which might provide a safe and effective strategy for gene therapy of atherosclerotic disease in future. Key words: Ultrasonography; Microbubbls ; Atherosclerosis ; Gene therapy; Endostatins

Reversal effect of recombinant human Endostatin on cisplatin resistance line A549/DDP human lung adenocarcinoma cells

Objective To evaluate reverse effect of recombinant human Endostatin on drug-resistance of A549/DDP cells to cisplatin (DDP). Methods Lung adenocarcinoma cell line A549 and its DDP-resistant cell line A549/DDP were treated with DDP and recombinant human Endostatin. Difference in drug resistance was analyzed between different regimens ( DDP, Endostatin and combination) and between different cell lines ( human lung adenocarcinoma A549 and drug resistant A549/DDP), after a 72h-treatment in vitro. Reverse effect of recombinant human Endostatin on drug-resistance of A549/DDP to DDP was tested by MTT assay. Results The observed 50% inhibitory concentration ( IC50 ) was (0.72 ± 0.05 ) ug/ml against A549 and ( 11.54 ± 0.64)against A549/DDP in DDP, and (2.0 ± 0.1 ) μg/ml against A549/DDP in rh-Endostatin- DDP combination respectively, with a reversal fold (RF) of 5.77 and a relative reversal rate of 88. 2%. Conclusion rh-Endostatin may reverse drug-resistance of A549/DDP cells to DDP. Key words: Endostatins; Lung neoplasms; Drug resistance,neoplasms; A549/DDP cell line

Adenovirus-mediated human endostatin gene delivery in the treatment of mouse melanoma

Objective To observe the bioactivity of adenovirus-mediated human endostatin gene in vivo and in vitro.Methods B16F10 melanoma cells and human endothelial cells(ECV 304)were both transfected with recombinant adenovirus containing green fluorescent protein(Ad-GFP)or human endostatin gene (Ad-mES) at various multiplicity of infection(MOI).Then,the expression of endostatin gene was detected by RT-PCR,and the growth of cells by MTT assay.B16F10 cells were inoculated into the back of mice to establish melanoma models,which were classified into treated groups intratumorally injected with Ad-mES once (single Ad-mES group) or repeatedly(repetitive Ad-mES group)with an interval of 7 days,and control groups intratumorally injected with Ad-GFP (Ad-GFP group)or phosphate buffred solution (PBS group).Subsequently,the growth of tumors was observed at an interval of 4 days;tumor tissue samples were obtained from killed mice and subjected to the detection of endostatin expression with immunohistochemistry on day 7 after the first intratumoral injection;transmission electron microscopy was used to observe the apoptosis of tumor cells and endothelial cells on day 14.Results Adenovirus could efficiently infect targeted cells.When the MOI of Ad-GFP was 10,20,50,100,200 and 500,B16F10 cells were infected at a rate of 15.6%,35%,73%,88%,95.2%and 97%,respectively,and ECV304 cells at a rate of 19%,35%,80%,90%,97%and 98.5%,respectively.The endosmtin gene was proved to be expressed in targeted cells.Ad-mES had no obvious effect on B16F10 cells,but inhibited the growth of ECV 304 ceils,and the inhibitive effect was enhanced with the concentration of Ad-mES.The rate of tumor formation was 100% on day 8 after injection of B16F10 cells,and the earliest death of mice was observed on dav 16 in PBS group,day 18 in Ad-GFP group,day 20 in single Ad-mES group and repetive Ad-mES group.Conclusions The recombinant Ad-mES could affect the bioactivity of targeted cells in vivo and in vitro.Intratumoral injection of Ad-mES prolonged the survival of mice bearing melanoma and deccelarated the growth of melanoma. Key words: Melanoma; Endostatins; Gene therapy

Changes in vascular endothelial growth factor and endostatin in rat brain tissues following cerebral ischemia-reperfusion injury

Objective To investigate the changes in vascular endothelial growth factor (VECF) and endostatin (ES) in rat brain tissues following cerebral ischemia-reperfusion (IR) injury. Methods Forty-eight male Wistar rats weighing 270-330 g were randomly divided into 2 groups: sham operation group (group S, n = 8) and IR group ( n = 40). The animals were anesthetized with intraperitoneal chloral hydrate 3 ml/kg. Left common, internal and external carotid arteries (CCA, ICA, ECA) were exposed. Middle cerebral artery occlusion (MCAO) was produced by inserting a nylon thread 17-19 mm in length into ICA and advancing it cranially until resistance was felt using Zea Longa's method. At 90 min of MCAO, the nylon thread was withdrawn to allow reperfusion. In group S, the nylon thread was inserted 10 mm in length into ICA but no MCAO was performed. The neurological deficit was scored at 1 d after operation in group S, and at 6h, 1 d, 2 d, 4 d and 7 d of reperfusion in group IR (8 animals at each time point) . The rats were then killed and the brains were removed and sliced. Brain tissue slices from 2 out of the 8 rats were stained with triphenyl tetrazolium chloride to estimate the infarct size, while those from the other 6 rats were used to determine the expression of VEGF mRNA and ES mRNA using RT-PCR. ES/VEGF ratio was calculated. Results Compared with group S, neurological deficit score was significantly increased and VEGF mRNA expression in brain tissues was up-regulated at each time point following reperfusion, ES mRNA expression in brain tissues was up-regulated at 1, 2, 4 and 7 d of reperfusion, and ES/VEGF ratio in brain tissues was significantly decreased at 2, 4 and 7 d of reperfusion in group IR ( P < 0.01). The neurological deficit score was the highest, expression of VEGF mRNA and ES/VEGF ratio reached the valley value ES mRNA, expression reached the peak value, and infarct size was the largest at 2 d of reperfusion. Conclusion The expression of VEGF mRNA and ES mRNA is up-regulated during cerebral IR in rats and the degree of brain injury may be related to the balance of ES and VEGF in brain tissues. Key words: Reperfusion injury; Brain; Endostatins; Vascular endothelial growth factors

Experimental study of recombinant human vascular endostatin for breast cancer in nude mice model

Objective To explore the effect of recombinant human vascular endostatin(Endostar,YH-16) on MCF-7 human breast cancer cells in nude mice. Methods Forty nude mice were randomized into four groups and received injection with MCF-7 cells. When gross tumor volume reached 1.0 cm3 ,mice were injected subcutaneously once every two days as following for 20 days: (1) O. 9% NS(0. 2 mg/kg) in negative control group;(2) YH-16(20 mg/kg) in YH-16 group; (3) DDP (1 mg/kg) in positive control group; (4) DDP (1 mg/kg) plus YH-16(20 mg/kg) in DDP plus YH-16 group. Mice were killed by cervical spine disloca-tion. And the body weight, tumor volume, rate of tumor inhibited, VEGF, apoptosis rate of tumor cells and pul-monary metastasis rate were detected. Results The means (SD) of tumor volume in DDP plus YH-16 group,positive control group, YH- 16 group and negative control group were 0. 686 (0. 229), 1. 258 (0. 101), 1. 888 (0. 215), 3. 366 (0. 284) cm3, respectively (P <0. 05) ; the rates of tumor inhibited in the four groups were 92. 1% ,57.3 %, 36. 5 % and 0, respectively (P < 0. 05) ; pulmonary metastasis rates were 0, 10%, 20% and 90% ,respectively(P <0. 05) ;the mean (SD) of apoptosis rates of tumor ceils were 31.6% (2. 7%) ,28. 1%(2. 7%), 19. 4% (2. 9%), 15.7% (3.2%), respectively (P < 0. 05). The mean of absorbance of VEGF in the four groups were 0. 530 ± 0. 164,0. 759 ± 0. 210,1. 063 ± 0. 295,1. 268 ±0. 145 (RT-PCR) and O. 260 ±0. 082,0. 348 ±0. 085,0. 461 ±0. 099,0. 556 ± 0. 113(Western blot) ,respectively(P < 0. 05). Conclusion YH-16 can inhibit MCF-7 breast cancer cell growth and distant metastasis in nude mice with little adverse reac-tion. YH-16 has synergistic effect combined with DDP. Key words: Endostatins; Breast neoplasms; Angiogenesis inhibitors; Vascular endothelial growth factors