Efficacy and safety of three days continuous intravenous pumping of recombinant human endostatin combined with platium-contained chemotherapeutic agents in patients with advanced non-small cell lung cancer aged 60 years or older / 中华老年医学杂志

Objective:To investigate the efficacy and safety of recombinant human endostatin(Endostar)combined with platium-contained chemotherapeutic agents in advanced non-small cell lung cancer(NSCLC)patients over 60 years old.Methods:93 advanced NSCLC patients from January 2019 to June 2021 were selected as the research objects.The patients received three days of continuous intravenous infusion of Endostar(210 mg for 72 hours)combined with platinum-containing chemotherapy.The efficacy and toxicities were evaluated according to Response Evaluation Criteria in Solid Tumors(RECIST)version1.1 and National Cancer Institute Common Terminology Criteria for Adverse Events(NCI-CTCAE version 4.0), respectively.Follow-up data were obtained to perform the Kaplan-Meier survival analysis.Results:In our study, the objective remission rate(ORR)and disease control rate(DCR)were 38.7% and 78.5%, respectively.The median progression-free survival(PFS)and overall survival(OS)were 6.8 months and 16.5 months, respectively.A Multivariate analysis showed that tumor staging and TP53 mutation were independent prognostic factors related to PFS and OS in advanced NSCLC patients.Adverse reactions related to Endostar during treatment included arrhythmia in 2 cases(2.2%), myocardial ischemia in 1 case(1.07%)and bloody sputum in 1 case(1.07%), all of which were Grade 1 or Grade 2.Conclusions:The application of three days continuous intravenous infusion of Endostar combined with platium-contained chemotherapeutic agents is worthy to be recommended for clinical application in elderly patients with advanced NSCLC due to its high effective rate and survival advantage, as well as good safety.

Efficacy observation of deep hyperthermia combined with recombinant human vascular endothelial inhibitor injection and AP regimen in treatment of advanced non-small cell lung cancer / 肿瘤研究与临床

Objective:To investigate the efficacy of deep hyperthermia combined with recombinant human vascular endothelial inhibitor injection and AP (pemetrexed + cisplatin) regimen in the treatment of advanced non-small cell lung cancer (NSCLC) and its effects on serum tumor marker levels and immune function of patients.Methods:In this prospective randomized controlled study, 106 patients with advanced NSCLC who were admitted to the Seventh People's Hospital of Hebei Province from January 2016 to January 2022 were included, and were divided into two groups according to the random number table method, with 53 cases in each group. The control group was treated with recombinant human vascular endothelial inhibitor injection combined with AP regimen. The observation group was given recombinant human vascular endothelial inhibitor injection combined with AP regimen and deep hyperthermia. After 4 consecutive cycles of treatment, the short-term efficacy of the two groups was observed. Chemiluminescence assay was used to detect the serum levels of carcinoembryonic antigen (CEA), carbohydrate antigen 125 (CA125) and cytokeratin fragment 19 CYFR21-1 before and after treatment. T lymphocyte subsets in peripheral blood were detected by flow cytometry. The occurrence of adverse reactions was compared between the two groups.Results:The objective response rates in observation group and control group were 58.49% (31/53) and 37.74% (20/53), the disease control rates in observation group and control group were 92.45% (49/53) and 75.47% (40/53), the observation group was higher than the control group ( χ2 = 4.53, P = 0.033; χ2 = 5.62, P = 0.018). The differences in serum carcinoembryonic antigen (CEA), glycoantigen 125 (CA125) and CYFR21-1 levels between the two groups before treatment were not statistically significant (all P > 0.05), they were lower in both groups after treatment than before treatment (all P < 0.05), and they were lower in the observation group after treatment than in the control group after treatment (all P < 0.05). The differences in peripheral blood CD3 +, CD4 + and CD8 + T-cell levels and CD4 + to CD8 + T-cell ratio (CD4 +/CD8 +) between the two groups before treatment and in the observation group before and after treatment were not statistically significant (all P > 0.05). Peripheral blood CD3 + and CD4 + T-cell levels and CD4 +/CD8 + in the control group after treatment were lower than before treatment (all P < 0.05), and the peripheral blood CD8 + T-cell level was higher than before treatment ( P < 0.05). CD3 + and CD4 + cell levels and CD4 +/CD8 + in the observation group after treatment were higher than those in the control group after treatment, CD8 + T-cell level was lower than the control group after treatment, and the differences were statistically significant (all P < 0.001). There were different degree of gastrointestinal reactions, bone marrow suppression, liver and kidney damage and cardiotoxicity in both groups during treatment, but the differences in the incidence of each adverse reaction between the two groups were not statistically significant (all P > 0.05). Conclusions:Deep hyperthermia combined with recombinant human vascular endothelial inhibitor injection and AP regimen in the treatment of advanced NSCLC can effectively reduce the serum tumor marker levels, improve the immunosuppression status of the body and enhance the recent efficacy, and the overall adverse reactions are controllable and well tolerated by patients.

Application value of recombinant human endostatin in the treatment of cardiac carcinoma / 中国基层医药

Recombinant human endostatin is an antiangiogenic drug,which limits the progression of tumor through normalize the tumor vessels and inhibits the proliferation of tumor cells in combination with chemotherapeutic drugs;and directly inhibits the formation of neovascularization endothelium.Gastric cardia carcinoma is a common digestive tumor in China,which is mainly treated by surgical resection,radiotherapy and chemotherapy.Based on the principle of recombinant human vascular endostatin and its good effect in the treatment of various kinds of malignant tumors,especially in the radiochemotherapy of digestive tract malignant tumors.In order to inhibit the development of tumor,improve patients' postoperative survival rate,and prolong the survival time of disease free progression,this article will discuss the application value of recombinant human vascular endostatin in the comprehensive therapy of cardiac carcinoma.

Application value of recombinant human endostatin in the treatment of cardiac carcinoma / 中国基层医药

Recombinant human endostatin is an antiangiogenic drug, which limits the progression of tumor through normalize the tumor vessels and inhibits the proliferation of tumor cells in combination with chemotherapeutic drugs; and directly inhibits the formation of neovascularization endothelium.Gastric cardia carcinoma is a common digestive tumor in China, which is mainly treated by surgical resection, radiotherapy and chemotherapy.Based on the principle of recombinant human vascular endostatin and its good effect in the treatment of various kinds of malignant tumors, especially in the radiochemotherapy of digestive tract malignant tumors.In order to inhibit the development of tumor, improve patients′ postoperative survival rate, and prolong the survival time of disease free progression, this article will discuss the application value of recombinant human vascular endostatin in the comprehensive therapy of cardiac carcinoma.

Efficacy and safety of recombinant human endostatin combined with gemcitabine and carboplatin as first-line treatment of advanced NSCLC with liver metastases / 肿瘤

Objective: To compare the efficacy and safety of GC (gemcitabine plus carboplatin) regimen combined with recombinant human endostatin (rh-endostatin) and GC regimen alone in the first-line treatment of advanced non-small cell lung cancer (NSCLC) with liver metastases. Methods: The clinical and pathological data of patients with advanced NSCLC and liver metastases, who were diagnosed from October 2013 to July 2017 in Hunan Cancer Hospital and treated with rh-endostatin combined with GC regimen or GC regimen alone as the firstline treatment, were retrospectively analyzed. A total of 94 patients were enrolled, including 46 cases in combination group and 48 cases in chemotherapy group. All patients received at least 2 cycles of treatment (21 days per cycle). Objective response rate (ORR), progressionfree survival (PFS), overall survival (OS), and adverse events were observed and compared between the two groups. Results: After 2 cycles of treatment, the ORR in the combination group and the chemotherapy group were 27.1% and 10.9%, respectively; while the ORR in the combination group was significantly higher than that in the chemotherapy group (P = 0.046). Subgroup analysis showed that the patients in adenocarcinoma subgroup could benefit more from the combination treatment (combination group vs chemotherapy group: 35.0% vs 11.1%, P = 0.048). The median PFS time was 4.5 months and 3.4 months in the combination group and the chemotherapy group, respectively; while the median OS time was 7 months and 6 months in the two groups, respectively; so the PFS and OS in the combination group were significantly prolonged (both P < 0.001). In the patients receiving 4 or more cycles of treatment, the survival benefit of combination therapy was more significant as compared with the chemotherapy group (PFS: 7 months vs 4 months, P < 0.001; OS: 10 months vs 6 months, P < 0.001). The main adverse reactions in the two groups were nausea, vomiting and myelosuppression, in which myelosuppression was mainly caused by leukopenia and neutropenia. Conclusion: Compared with the chemotherapy alone, rh-endostatin combined with GC regiment as the first-line treatment can significantly improve the median PFS, median OS and ORR in the patients with advanced NSCLC and liver metastases, and has good safety and clinical application prospects.

Vascular endothelial growth factor, endostatin levels and clinical features among patients with ulcerative colitis and irritable bowel syndrome and among healthy controls: a cross-sectional analytical study

ABSTRACT BACKGROUND: Increased angiogenetic activity in inflammatory bowel disease (IBD) has been shown in previous studies. The aim of this study was to evaluate the relationship of serum vascular endothelial growth factor (VEGF) and endostatin levels with clinical features and mucosal expression in patients with ulcerative colitis (UC). DESIGN AND SETTING: Cross-sectional analytical study conducted in a tertiary-level public hospital. METHODS: Serum VEGF and endostatin levels were determined in 82 individuals: 39 with UC, 28 with irritable bowel syndrome (IBS) and 15 healthy controls (HCs), using enzyme-linked immunosorbent assays (ELISA). VEGF and endostatin expressions were studied using immunohistochemistry (IHC). RESULTS: Mean serum VEGF and endostatin levels were significantly higher in patients with UC than in patients with IBS and in HCs (511.9 ± 377.5 pg/ml, 305.0 ± 121.42 pg/ml and 36.1 ± 40.6 pg/ml; P = 0.001 for VEGF; and 155.50 ± 59.8 ng/ml, 116.9 ± 23.8 ng/ml and 102.2 ± 22.4 ng/ml; P < 0.001 for endostatin, respectively). There was a positive correlation between serum VEGF and endostatin levels (r = 0.422; P < 0.01). Mean H-scores for VEGF expression were higher in the active UC group than in the inactive UC and IBS groups, in the stroma, endothelium and epithelium. Mean H-scores for endostatin expression were higher in the active UC group than in the inactive UC and IBS groups, in the stroma and endothelium. There was no endostatin expression in the epithelium. CONCLUSION: Increased endostatin appears to be a defensive reaction to increased VEGF in patients with UC.

Expression differences and analysis of Endostatin and VEGF in different efficacy NSCLC patients treated with rh-endostatin combined chemotherapy / 中国医师杂志

Objective To investigate the clinical significance and difference in the expression of endostatin and vascular endothelial growth factor (VEGF) in non-small cell lung cancer (NSCLC) patients with different response to recombinant human endostatin (rh-endostatin) combined with chemotherapy.Methods Serum levels of endostatin and VEGF in peripheral blood of 30 patients with stage Ⅳ NSCLC (NSCLC group) and 30 healthy controls (control group) were determined by enzyme-linked immunosorbent assay.Two cycles of chemotherapy combined with rh-endostatin were provided to NSCLC patients to evaluate the efficacy of the regimen.Simultaneously,serum levels of endostatin and VEGF were measured before and after treatment.Results The level of serum endostatin was (37.96 ± 9.01) ng/ml and (40.12 ± 12.11)ng/ml in NSCLC patients and healthy controls,respectively,which was lower in the former than that of the latter,without statistical difference (P ＞ 0.05).Furthermore,the level of serum VEGF was (127.98 ± 33.88) pg/ml and (36.33 ± 15.43) pg/ml in NSCLC patients and healthy controls,respectively,which was higher in the former than that of the latter,with statistical difference (t =13.48,P ＜ 0.05).Besides,levels of endostatin and VEGF in serum were not correlated with the sex,age,tumor pathological type and differentiation of NSCLC patients (P ＞ 0.05).After two cycles of chemotherapy combined with rh-endostatin treatment,the level of serum endostatin in partial response (PR) or stable disease (SD) patients was (76.22 ± 20.41) ng/ml,higher than that of progressive disease (PD) patients,which was (31.24 ± 13.09) ng/ml (t =7.143,P ＜ 0.05).In addition,the level of serum VEGF in PR or SD patients was (93.28 ± 21.33) pg/ml,which was lower than (155.81 ± 48.38) pg/ml of the PD patients (t =3.503,P ＜ 0.05).Conclusions The levels of endostatin and VEGF are associated with the efficacy of anti-angiogenesis combined with chemotherapy in NSCLC patients.

Effect of Selfheal soup combined benzene sulfonic acid amlodipine on elderly patients with hypertension and its effect on plasma endothelin-1 / 中国基层医药

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 .

Endostatin a Potential Biomarker for Heart Failure with Preserved Ejection Fraction / Endostatina é um Potencial Biomarcador para a Insuficiência Cardíaca com Fração de Ejeção Preservada

Abstract Background: Endostatin is a circulating endogenous angiogenesis inhibitor preventing neovascularization. Previous studies demonstrated the prognostic value of Endostatin among patients with heart failure with reduced ejection fraction (HFrEF). However, the role of Endostatin among patients with heart failure with preserved ejection fraction (HFpEF) remains unclear. Objective: This study aimed to investigate the association between serum Endostatin levels, natriuretic peptide levels and the severity of left ventricular diastolic dysfunction and the diagnosis of HFpEF. Methods: Endostatin serum concentrations were measured in 301 patients comprising 77 HFpEF patients, 169 patients with asymptomatic left ventricular diastolic dysfunction (ALVDD), and 55 controls with normal cardiac function. Results: Endostatin serum levels were significantly elevated in patients with HFpEF (median/interquartile range 179.0 [159-220]) and ALVDD (163.8 [145.4-191.3]) compared to controls (149.1 [130.6-176.9]), p < 0.001 and p = 0.004, respectively) and significant correlated with N-terminal pro B-type natriuretic peptide (NT-proBNP). Conclusions: This hypothesis-generating pilot study gives first evidence that Endostatin correlates with the severity of diastolic dysfunction and may become a novel biomarker for HFpEF. We hypothesize a rise in Endostatin levels may reflect inhibition of adaptive angiogenesis and adverse cardiac remodeling.

Resumo Fundamentos: A Endostatina é um inibidor circulante endógeno da angiogênese que previne a neovascularização. Estudos anteriores demonstraram o valor prognóstico da Endostatina em pacientes com insuficiência cardíaca com fracção de ejeção reduzida (ICFEr). No entanto, o papel da Endostatina entre os pacientes com insuficiência cardíaca com fração de ejeção preservada (ICFEp) permanece incerto. Objetivo: Investigar a associação entre os níveis séricos de Endostatina, níveis de peptídeos natriuréticos e a gravidade de disfunção ventricular esquerda e diastólica e o diagnóstico de ICFEp. Métodos: Mediu-se a concentração sérica de Endostatina em 301 pacientes, compreendendo 77 pacientes com ICFEp, 169 pacientes com disfunção ventricular esquerda assintomática diastólica (DVEAD) e 55 controles com a função cardíaca normal. Resultados: Os níveis de Endostatina no soro foram significativamente elevados em pacientes com ICFEp (mediana / intervalo interquartil 179,0 [159-220]) e DVEAD (163,8 [145,4-191,3]) em comparação com os controles (149,1 [130,6-176,9]), p < 0,001 e p = 0,004, respectivamente) e correlação significativa com o terminal do pro-peptídeo natriurético tipo B (NT-proBNP). Conclusões: Este estudo piloto gerador de hipótese fornece a primeira evidência de que a Endostatina se correlaciona com a gravidade da disfunção diastólica e pode tornar-se um novo biomarcador para ICFEp. Nossa hipótese é de que um aumento nos níveis de Endostatina pode refletir inibição da angiogênese adaptativa e remodelação cardíaca adversa.

Efficacy and safety of injecting endostar combined with platinum complexes into pleural cavity for treatment of malignant pleural effusion: a meta-analysis review / 中国医师杂志

Objective To investigate the efficacy and safety of patients with malignant pleural effusion treated with injecting endostar combined with platinum complexes into pleural cavity.Methods Cochrane systematic review methods were used in the data selection,and data were selected from the PubMed,Embase,Cochrane Library,China National Knowledge Infrastructure (CNKI),WanFang,and VIP database to get all clinical controlled trials.The retrieval time was August 2014.The objects of these randomized controlled trials were malignant pleural effusion patients.Endostar combination with platinum complexes was used for the experimental group.Platinum complexes alone were used for the control group.The efficacy and adverse effects of two groups were compared.The quality of included trials was evaluated by two reviewers independently.The software RevMan 5.3 was used for meta-analyses.Results Nine trials with 488 patients were included according to the including criterion.All trials were randomized controlled trials,one of them had B level in quality and eight had C level.Meta analysis results were as follows:there was significant difference in overall effective rate (OR =3.52,95％ CI =2.37 ～ 5.22),Karnofsky (KPS) score changes rate (OR =2.64,95％ CI =1.67 ～ 4.19),between endostar combination with platinum complexes and platinum complexes alone group.The incidences of severe leucopenia (OR =1.0,95％ CI =0.62 ～ 1.61) and nausea and vomiting (OR =0.77,95％ CI =0.43 ～ 1.38) were similar in the endostar combination with platinum complexes group compared to those in the platinum complexes alone group.Conclusions In the treatment of malignant pleural effusion,injecting endostar in combination with platinum complexes into pleural cavity improves the effective rate without obviously raised side effects.Owing to the small sample size and poor quality of included trials,more well-designed double-blinded randomized controlled trials should be performed.

Effects of endostatin pretreatment on fibrosis of human skin fibroblasts and the mechanisms / 中华烧伤杂志

Objective@#To explore the effects of endostatin pretreatment on fibrosis of human skin fibroblasts and the mechanisms.@*Methods@#Human skin fibroblasts were routinely cultured in vitro, and then the cells of passage 3 to 5 were used in the following experiments. The cells were divided into blank control, endostatin, platelet-derived growth factor-BB (PDGF-BB), endostatin+ PDGF-BB, transforming growth factor-β1 (TGF-β1), and endostatin+ TGF-β1 groups according to the random number table, with 3 wells in each group. Cells in blank control group were cultured with DMEM medium for 24 h. Cells in endostatin group were cultured with DMEM medium containing 5 μg/mL endostatin for 24 h. Cells in PDGF-BB group and TGF-β1 group were cultured with DMEM medium containing 200 ng/mL PDGF-BB and 10 ng/mL TGF-β1 for 24 h, respectively. Cells in endostatin+ PDGF-BB group were pretreated with DMEM medium containing 5 μg/mL endostatin for 48 h and then cultured with DMEM medium containing 200 ng/mL PDGF-BB for 24 h. Cells in endostatin+ TGF-β1 group were pretreated with DMEM medium containing 5 μg/mL endostatin for 48 h and then cultured with DMEM medium containing 10 ng/mL TGF-β1 for 24 h. The content of type Ⅰ collagen in the cell culture supernatant of three wells in each group was determined by enzyme-linked immunosorbent assay. The protein expression levels of α-smooth muscle actin (α-SMA), PDGF receptor β (PDGFRβ), phosphorylated PDGFRβ (p-PDGFRβ), and phosphorylated extracellular signal-regulated protein kinases 1/2 (p-ERK1/2) of three wells in each group were detected by Western blotting. Data were processed with one-way analysis of variance and SNK test.@*Results@#(1) Compared with (5.05±0.29) pg/mL in blank control group, content of type Ⅰ collagen in the cell culture supernatant of endostatin group [(4.72±0.37) pg/mL] was close to it (P>0.05), content of type Ⅰ collagen in the cell culture supernatant of PDGF-BB group and TGF-β1 group [(8.60±0.57) and (9.20±0.64) pg/mL, respectively] was higher (with P values below 0.05). Content of type Ⅰ collagen in the cell culture supernatant of endostatin+ PDGF-BB group [(5.32±0.17) pg/mL] was lower than that of PDGF-BB group (P<0.05), and content of type Ⅰ collagen in the cell culture supernatant of endostatin+ TGF-β1 group [(5.41±0.20) pg/mL] was lower than that of TGF-β1 group (P<0.05). (2) Compared with those in blank control group, protein expression levels of α-SMA, PDGFRβ, p-PDGFRβ, and p-ERK1/2 of cells in endostatin group showed no obvious differences (with P values above 0.05), while those in PDGF-BB and TGF-β1 group were significantly higher (with P values below 0.01). Protein expression levels of α-SMA, PDGFRβ, p-PDGFRβ, and p-ERK1/2 of cells in endostatin+ PDGF-BB group and endostatin+ TGF-β1 group were significantly lower than those in PDGF-BB group and TGF-β1 group, respectively (with P values below 0.05).@*Conclusions@#Pretreatment of endostatin can inhibit the fibrosis of human skin fibroblast and its transformation into myofibroblast, which may be related to the down-regulation of protein expression of p-PDGFRβ, PDGFRβ, and p-ERK.

Clinical observation of body-gamma knife combined with recombinant human endostatin injection (Endostar) as the therapy in the elderly patients with advanced non-small cell lung cancers / 中国医师杂志

Objective To explore the efficacy and safety of human recombinant vascular endothelial inhibition (en) combined with gamma knife in the treatment of elderly advanced non-small cell lung cancer patents.Methods Totally 38 cases of senile non-small cell lung cancer patients were divided into two groups:A group was treatment group with 17 cases of recombinant human endostatin combined with gamma knife,group B was control group with 21 cases of patients receiving body gamma knife alone.Recombinant human endostatin was given intravenously 15 mg per day in 500 ml of saline for 3 ～ 4 hours for 14 days a cycle,and the total dose of body gamma knife therapy was 36 ～ 48 Gy/10 ～ 12f.Results The response rate (RR) of groups A and B were 58.82％ and 57.14％ without statistical difference.One-year survival rate of groups A and B were 47.06％ and 38.09％,respectively;and there was no statistical significance.The main side-effects of both groups were bone marrow suppression and gastrointestinal reactions,but no statistical difference was observed.Two groups of patients'quality of life were improved without statistical difference (P ＞ 0.05).Conclusions Body-gamma knife therapy combined with recombinant human endostatin in elderly advanced non-small cell lung cancer patients has better efficacy such as CR rate and long-term survival,and similar side-effects.

Effect of Intravenous Infusion of Vasostatin-2 on Hemodynamics in Experimental Rats With Spontaneous Hypertension / 中国循环杂志

Objective: To observe the effect of the intravenous infusion of vasostatin-2 (VS-2) on hemodynamics in experimental rats with spontaneous hypertension (SH). Methods: A total of 36 (14-16) weeks male SH rats with the mean body weight at (160-250) g were randomly divided into 6 groups:①Control group, the rats received normal saline (100μl/kg),②Catestatin (20μg/kg) group,③VS-2 (5μg/kg) group,④VS-2 (10μg/kg) group,⑤VS-2 (20μg/kg) group and⑥VS-2 (40μg/kg) group. n=6 in each group. The average blood pressure (BP), heart rate (HR) and barorelfex sensitivity (BRS) were monitored and compared upon VS-2 treatment and between VS-2 and catestatin treatments in conscious and freelance rats. Results: Compared with prior treatment, VS-2 (20μg/kg) and VS-2 (40μg/kg) could obviously decrease the HR, BP and BRS in SH rats. In VS-2 (20μg/kg) group, HR by bpm was (341.3 ± 19.3) vs (365.5 ± 25.5), BP by mmHg was (133.0 ± 8.9) vs (147.5 ± 11.2) and BRS by ms/mmHg was (0.52 ± 0.18) vs (0.37 ± 0.12);in VS-2 (40μg/kg) group, HR was (348.8 ± 30.8) vs (374.5 ± 34.8), BP was (131.5 ± 9.3) vs (151.7 ± 10.8) and BRS was (0.53 ± 0.05) vs (0.38 ± 0.03), all P0.05. Conclusion: Intravenous infusion of VS-2 may obviously affect HR, BP and BRS in experimental SH rats;compared with the same dosage of catestatin, VS-2 had the weaker reduction of HR, BP and BRS.

Analysis of Circulating Endostatin and Vascular Endothelial Growth Factor in Patients with Pituitary Adenoma Treated by Stereotactic Radiosurgery: A Preliminary Study

BACKGROUND: The purpose of this study was to investigate plasma levels of endostatin and vascular endothelial growth factor (VEGF) in normal subjects and in patients with pituitary adenoma and to evaluate change in these levels following stereotactic radiosurgery (SRS) for pituitary adenoma. METHODS: Peripheral venous blood was collected from five patients with pituitary adenoma before SRS using Gamma Knife and at the 1 week and 1 month follow-up visits. Plasma endostatin and VEGF levels were measured using commercially available enzyme-linked immunosorbent assay kits. Peripheral blood samples were obtained from 10 healthy volunteers as controls. RESULTS: Mean baseline plasma endostatin level (105.3 ng/mL, range, 97.0-120.2 ng/mL) in patients with pituitary adenoma was higher than that of the healthy controls (86.6 ng/mL, range, 71.3-98.2 ng/mL) (p=0.001). Mean plasma VEGF level was 89.5 pg/mL (range, 24.1-171.8 pg/mL) in patients with pituitary adenoma at baseline and 29.3 pg/mL (range, 9.2-64.3 pg/mL) in the control group (p=0.050). Plasma endostatin level changed to 106.6 ng/mL 1 week after SRS and decreased to 95.9 ng/mL after 1 month. Plasma VEGF level following SRS decreased to 74.1 pg/mL after 1 week and 79.0 pg/mL after 1 month. There was a trend toward decreased plasma endostatin and VEGF concentrations 1 month after SRS compared to baseline levels (p=0.195, p=0.812, respectively). CONCLUSION: Plasma endostatin and VEGF levels in patients with pituitary adenoma were significantly elevated over controls at baseline, which decreased from baseline to 1 month after SRS for pituitary adenomas.

The effect of iguratimod on the cytokines of human synovial fibroblast cell line MH7A stimulated with interleukin-1β / 中华风湿病学杂志

Objective To observe the possible anti-inflammatory and anti-angiogenesis effects of iguratimodon human synovial fibroblast cell line MH7A derived from patients with rheumatoid arthritis (RA).Methods MH7A cells were stimulated with interleukin (IL)-1β and treated simult aneously or sequenti-ally with different concentrations of iguratimod and methotrexate (MTX).Release of vascular endothelial growth factor (VEGF), endostatin (ES) and tumour necrosis factor-α (TNF-α) was quantified by enzyme linked immunosorbent assay (ELISA).The statistics software SPSS 13.0 was used for statistical analyses.The experimental data were analyzed in terms of variance analysis and LSD test.In all cases, a P value lower than 0.05 was considered significant.Results The concentrations of VEGF, ES and TNF-α of the control group were (57±98) pg/ml, (924±39) pg/ml, (16.40±6.08) pg/ml respectively, while those of the experimental group were (1 155±177) pg/ml, (295±35) pg/ml and (36.90±3.54) pg/ml respectively.The differences of VEGF (t=9.092, P＜0.01) and ES (t=19.685, P＜0.01) between the control group and the experimental group was statistically significant.There was significant difference in the levels of TNF-α between the two groups (t=2.495, P＜0.05).VEGF of the iguratimod groups was (640±127) pg/ml in the iguratimod group (100 μmol/L), (787±172) pg/ml in the iguratimod group (25 μmol/L), and (776±99) pg/ml in the iguratimod group (6.25 μmol/L).VEGF of the MTX groups was (1 322±264) pg/ml in the MTX group (100 μmol/L), (1 071±63) pg/ml in the MTX group (25 μmol/L), and (863±70) pg/ml in the MTX group (6.25 μmol/L).All concentration of the iguratimod groups could effectively reduce the expression of VEGF in MH7A cells.Compared with the experimental group, the difference was statistically significant (100 μmol/L group: t=4.264, P＜0.01;25 μmol/L group: t=3.045, P＜0.01;6.25 μmol/L group: t =3.132, P ＜0.01).MTX (6.25 μ mol/L) could reduce the expression of VEGF in MH7A cells.Compared with the experimental group, the difference was statistically significant (t=2.415,P＜0.05).ES of the iguratimod groups was (979±30) pg/ml in the iguratimod group (100 μmol/L), (842±14)pg/ml in the iguratimod group (25 μmol/L), and (485 ±72) pg/ml in the iguratimod group (6.25 μmol/L).ES of the MTX group was (934±23) pg/ml in the MTX (100 μmol/L) group, (825±28) pg/ml in the MTX group (25 μmol/L), and (772 ±44) pg/ml in the MTX group (6.25 μmol/L).Both iguratimod and MTX groups effectively increased the expression of ES in MH7A cells.Compared with the experimental group, the difference was statistically significant (100 μmol/L group: t=21.387, P＜0.01;25 μmol/L group: t=17.122,P＜0.01;6.25 μmol/L group: t=5.929, P＜0.01).The expression of ES of the iguratimod group (100 μmol/L)and iguratimod group(25 μmol/L) was higher than that of the iguratimod group (6.25 μmol/L).The difference was statistical significant(100 μmol/L group: 6.25 μmol/L group was t=15.458,P＜0.01;100 μmol/L group: 6.25 μ mol/L group was t=11.193, P＜0.01).The expression of ES of the iguratimod group(6.25 μmol/L) was lower than that of the MTX group (6.25 μmol/L).The difference was statistically significant (t=9.001, P＜0.01).TNF-α was (4.73 ±1.15) pg/ml in the iguratimod group (100 μmol/L), (4.40±2.65) pg/ml in the iguratimod group (25 μmol/L), and (4.40±0.10) pg/ml in the iguratimod group (6.25 μmol/L).TNF-α of the MTX groups were (4.40±3.61) pg/ml in the MTX group (100 μ mol/L), (13.40±16.46) pg/ml in the MTX group (25 μmol/L),and (21.73±16.50) pg/ml of the MTX group (6.25 μmol/L).Both the iguratimod groups and the MTX group (100 μmol/L) effectively reduced the expression of TNF-α in MH7A cells.Compared with the experimental group, the difference was statistically significant(100 μmol/L group: t=3.914, P＜0.01;25 μ mol/Lgroup: t=3.955,P＜0.01;6.25 μ mol/L group: t=3.955, P＜0.01).Theexpression of TNF-α of the MTX groups (100 μ mol/L and 25 μmol/L) reduced significantly.Compared with the experimental group, the difference was statistically significant (100 μmol/L group: t=3.955, P＜0.01;25 μmol/L group: t=2.859, P＜0.05).The expression of TNF-αof the iguratimod group (6.25 μmol/L) was lower than that of the MTX group (6.25 μmol/L).The difference was statistical significant (t=2.359, P＜0.05).Conclusion Iguratimod presents strong anti-inflammatory and antiangiogenesis properties.This study provides insight into the possible molecular mechanisms of iguratimod and suggests that it can be a medication for the treatment of chronic inflammatory diseases like RA.

Construction of pcDNA3-Endo eukaryon expression plasmid and angiogenesis inhibition in vitro / 中国组织工程研究

BACKGROUND:The eradication therapy of glioma is the major problem, and anti-angiogenesis therapy is a potential treatment of glioma. OBJECTIVE:To confirm the inhibiting effect of endostatin on angiogenesis in vitro, and to lay the foundation in inhibiting the growth of tumor by endostatin in the future. METHODS:Endostatin mRNA was extracted from the liver of Wistar rats by Trizol and endostatin cDNA was synthesized by RT-PCR. Endostatin cDNA and pcDNA3 were connected and pcDNA3-Endo recombined plasmid was constructed successful y. The recombinant pcDNA3-Endo was transfected into bone marrow mesenchymal stem cells by Lipofectamine. The expression of endostatin was identified by RT-PCR and western blot analysis. Endostatin proteinum activity was detected by ECV-304 cellproliferation inhibition experiment using MTT assay. The in vitro experiments were divided into four groups:recombinant plasmid group, vector plasmid group, liposome control group and blank control group. RESULTS AND CONCLUSION:PcDNA3-Endo eukaryon expression plasmid was constructed successful y. Endostatin gene can be transcribed and expressed effectively in vitro by pcDNA3-Endo plasmid. The growth of ECV-304 cellwas inhibited obviously by pcDNA3-Endo. The growth of vascular endothelial cells can be inhibited obviously by endostatin gene.

Endostatins combined radiotherapy and chemotherapy in the treatment of advanced non-small cell lung cancer / 国际肿瘤学杂志

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％ (x2 =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 (x2 =3.74,P =0.042),7.32 months vs 10.37 months (x2 =5.32,P =0.025) and 5.21 months vs 7.57 months (x2 =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.

The curative effect of targeted siRNA of vascular endothelial growth factor combined endostatin on collagen-induced arthritis rat / 中华风湿病学杂志

Objective To investigate the effect of treatment with endostatin combined with siRNA targeting VEGF on rats with collagen-induced arthritis (CIA).Methods Two mg/ml bovinetype Ⅱ collagen was injected into the rat footpad to build up the animal model of CIA.The experimental animal models were treated with endostatin combined with siRNA targeting VEGF 18 days later after immunization and the treatment ended 32 day later.The efficacy was evaluated by the weight,foot and ankle volume of rats.The levels of VEGF in plasma were detected by enzyme-linked immunosorbent assay (ELISA).The VEGF distribution within synovial tissue was detected and examined by immunohistochemical technique.The pathological changes of CIA were evaluated by the pathological changes of the biopsied ankle joints.Student's t test was used to evaluate the experimental data.Results The ELISA test showed that comparing with the model group (17.5±0.3),the endostatin group (15.7±0.3) ng/L and the endostatin combined siRNA targeting VEGF group (14.7±0.5) ng/L showed a significant efficacy in the treatment of CIA in rats (P＜0.05).The endostatin group (135±27) and the endostatin combined siRNA targeting VEGF group (126±71) were different in the number of VEGF in plasma and the VEGF distribution within synovial tissue (P＜0.05),the symptoms of arthritis in these rats were reduced than the model group.Conclusion Endostatin combined siRNA targeting VEGF has good therapeutic effect on rats with CIA.

Primary tumorectomy promotes angiogenesis and pulmonary metastasis in osteosarcoma-bearing nude mice

PURPOSE: To investigate the effect of primary tumorectomy on angiogenesis and pulmonary metastasis in osteosarcoma-bearing nude mice. METHODS: Osteosarcoma was introduced to nude mice via subcutaneous injection of MG-63 cells. One hundred and eighty osteosarcoma-bearing mice were used equally in 3 parallel experiments. The effect of tumorectomy (TR) on the expression of vascular endothelial growth factor (VEGF) and endostatin was investigated by ELISA. Meanwhile, the effect on angiogenesis was evaluated by Matrigel plug assay, and pulmonary metastasis assessed by calculating the metastatic foci. Sham-operation (SO) and untreated (UT) groups served as controls. RESULTS: The VEGF (TR: 79.55 ± 7.82 pg/mL vs. SO: 110.01 ± 5.69 pg/mL, UT: 123.50 ± 10.41 pg/mL; p < 0.01) and endostatin (TR: 47.09 ± 6.22 ng/mL vs. SO: 117.64 ± 7.39 ng/mL, UT: 126.73 ± 6.55 ng/mL; p<0.01) were down-regulated significantly after tumorectomy, and angiogenesis was significantly promoted simultaneously. The incidence of pulmonary metastatic foci was 80.0% in the TR group, 40.0% in the SO group and 35.0% in the UT group. CONCLUSION: Primary tumorectomy can down-regulate the expression of VEGF and endostatin and promote angiogenesis which leads to the acceleration of pulmonary metastasis. These findings imply that anti-angiogenic treatment can be considered after primary tumorectomy.

Endostatin in the treatment of non-small cell lung cancer / 国际肿瘤学杂志

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.