OBJECTIVES: To observe the efficacy and adverse reactions of the combination of endostar with chemotherapy in the treatment of advanced (IVb) and recurrent metastatic cervical cancer. METHODS: Forty-four patients with recurrent and metastatic cervical cancer, who were admitted to the Second Xiangya Hospital, Central South University from December 2016 to December 2018 were randomly divided into an experimental group and a control group (22 cases in each group). The control group was given gemcitabine plus cisplatin (GP) or docetaxel plus cisplatin (DP) treatment, the experimental group was treated with endostar on the basis of the control group. RESULTS: The objective response rate (ORR) was 42.9% in the experimental group and 22.7% in the control group. There was no significant difference between the 2 groups ( CONCLUSIONS Compared with chemotherapy alone, endostar combined with chemotherapy can prolong the median progression-free survival, with higher ORR and similar adverse reactions.
Antineoplastic Combined Chemotherapy Protocols/adverse effects* ; Cisplatin/therapeutic use* ; Endostatins ; Female ; Humans ; Lung Neoplasms/pathology* ; Neoplasm Recurrence, Local/pathology* ; Neoplasm Staging ; Recombinant Proteins ; Uterine Cervical Neoplasms

Gastric cancer (GC) has high mortality owing to its aggressive nature. Tumor angiogenesis plays an essential role in the growth, invasion, and metastatic spread of GC. The aim of this work was to review the angiogenic biomarkers related to the behavior of GC, documented in the literature. A search of the PubMed database was conducted with the MeSH terms: “Stomach neoplasms/blood [MeSH] or stomach neoplasms/blood supply [MeSH] and angiogenic proteins/blood [Major]”. A total of 30 articles were initially collected, and 4 were subsequently excluded. Among the 26 articles collected, 16 examined the role of vascular endothelial growth factor (VEGF), 4 studied endostatin, 3 investigated angiopoietin (Ang)-2, 2 studied the Ang-like protein 2 (ANGTPL2), and 1 each examined interleukin (IL)-12, IL-8, and hypoxia inducible factor. Regarding VEGF, 6 articles concluded that the protein was related to lymph node metastasis or distant metastases. Five articles concluded that VEGF levels were elevated in the presence of GC and decreased following tumor regression, suggesting that VEGF levels could be a predictor of recurrence. Four articles concluded that high VEGF levels were correlated with poor prognosis and lower survival rates. Ang-2 and ANGTPL2 were elevated in GC and associated with more aggressive disease. Endostatin was associated with intestinal GC. VEGF is the most extensively studied angiogenic factor. It is associated with the presence of neoplastic disease and lymph node metastasis. It appears to be a good biomarker for disease progression and remission, but not for diagnosis. The data regarding other biomarkers are inconclusive.
Angiogenesis Inducing Agents ; Angiogenic Proteins ; Anoxia ; Biomarkers ; Diagnosis ; Disease Progression ; Endostatins ; Interleukin-8 ; Interleukins ; Lymph Nodes ; Mortality ; Neoplasm Metastasis ; Prognosis ; Recurrence ; Stomach ; Stomach Neoplasms* ; Survival Rate ; Vascular Endothelial Growth Factor A*

To obtain sufficient purified and active fusion protein-hepatocyte-targeting peptide-human endostatin (HTP-rES), we studied the growth curve and the optimal induction timing of BL21/pET21b-HTP-rES. Different conditions of pH value, induction time, induction concentration and induction temperature were optimized by univariate analysis. After washing, refolding and purifying, the activity of fusion protein was identified by flow cytometry and 3-(4,5)-dimethylthiahiazo (-z-y1)-3,5-di-phenytetrazoliumromide (MTT). Results show that the logarithmic growth phase of BL21/pET21b-HTP-rES was from 1.5 h to 3.5 h, the optimum expression conditions were pH 8.0, 0.06 mmol/L IPTG, at 42 ℃ for 5 h. The purity of inclusion bodies was up to 60% after washing. The purity of target protein was more than 95% after refolding and purification. Our findings provide the foundation for further biological activity and drug development.
Drug Delivery Systems ; Endostatins ; pharmacology ; Escherichia coli ; Hepatocytes ; drug effects ; Humans ; Inclusion Bodies ; Peptides ; pharmacology ; Recombinant Fusion Proteins

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.
Endostatins* ; Enzyme-Linked Immunosorbent Assay ; Follow-Up Studies ; Healthy Volunteers ; Humans ; Pituitary Neoplasms* ; Plasma ; Radiosurgery* ; Vascular Endothelial Growth Factor A*

OBJECTIVETo investigate the ability of invasion and migration of breast cancer MDA-MB-231 cells under serum starvation and hypoxia, and the effect of antiangiogenic drugs, rh-endostatin and bevacizumab, on the ability of invasion and migration of breast cancer cells under serum starvation and/or hypoxia, in order to explore the potential risk of antiangiogenic therapy in clinics.

METHODSThe cells were randomized into 4 groups, i.e., group A: 10% fetal bovine serum (FBS) group; group B: hypoxia + 10% FBS group; group C: serum starvation group; group D: hypoxia + serum starvation group; each group was further divided into three subgroups as blank control, treated with rh-endostatin and bevacizumab, respectively. Cell counting kit-8 (CCK-8) was used to assess the inhibition rate of cell growth induced by endostatin and bevacizumab, in order to determine the proper working concentration and time of the two drugs. Transwell assay was conducted to detect the cell invasion and migration in vitro. The expressions of c-Met and MMP-9 were detected by Western blot. The cells treated with rh-endostatin or bevacizumab under serum starvation were tested by hybridization using Exiqon miBase 18.0 microarray. The miRNAs which exibited significant differences (P < 0.05) in miRNA hybridization were verified by real-time PCR assay.

RESULTSCCK-8 assay showed that the inhibition rates of MDA-MB-231 cells cultured with 800 mg/L rh-endostatin for 48 h and 24 h were (32.2 ± 2.5)% and (27.0 ± 1.3)%, respectively, showing a significant difference (P = 0.023). The inhibition rates of MDA-MB-231 cells cultured with 80 mg/L bevacizumab for 48 h and 24 h were (30.5 ± 1.4) % and (26.1 ± 2.4) %, respectively, showing also a significant difference (P = 0.015). The Transwell assay showed that in the starvation blank group, the number of invaded and penetrated cells were 28.8 ± 2.2 and 31.4 ± 1.5, respectively, significantly different from that in the rh-endostatin and bevacizumab groups (P < 0.05). The relative expressions of c-Met and MMP-9 were 0.213 ± 0.017 and 0.542 ± 0.048, respectively, with a significant difference from those of the groups treated with each drug (P < 0.05 for both). The numbers of penetrated cells in the Transwell assay treated with rh-endostatin in hypoxia were 17.5 ± 2.1 and 16.5 ± 2.8, respectively, and the numbers of penetrated cells in the Transwell assay treated with bevacizumab were 16.3 ± 3.5 and 17.5 ± 2.4, respectively, showing no significant difference among them (P > 0.05 for both). The ability of migration and invasion of MDA-MB-231 cells and the expression of c-Met and MMP-9 were not impacted by hypoxia (P > 0.05). Real-time PCR assay showed that only the levels of miR-2355 and miR375 were significantly and stably decreased in the cells which had increased ability of invasion and migration. The relative expression levels of miR375 and miR-2355 in the serum starvation blank group were 0.550 ± 0.036 and 0.852 ± 0.121, respectively, significantly lower than that in the groups treated with rh-endostatin or bevacizumab (P<0.05). In the serum starvation group, the expression levels of miR375 and miR-2355 of cells treated with rh-endostatin were 0.295 ± 0.012 and 0.253 ± 0.011, and the expression levels of cells treated with bevacizumab were 0.234 ± 0.020 and 0.309 ± 0.022, respectively, (P > 0.05 for all). Compared with the serum starvation blank group, the expression levels of miR2355 and miR375 were significantly decreased when cells were treated with rh-endostatin/bevacizumab under serum starvation, but no significant difference was found between the two drugs (P > 0.05). However, hypoxia did not affect the expressions of miR2355 and miR375 (P > 0.05).

CONCLUSIONSThe results of this study suggest that serum starvation can increase the ability of invasion and migration of breast cancer cells. Furthermore, both rh-endostatin and bevacizumab may enhance their invasion and penetration ability under serum starvation condition.

Angiogenesis Inhibitors ; adverse effects ; Bevacizumab ; adverse effects ; Breast Neoplasms ; pathology ; Cell Hypoxia ; Cell Line, Tumor ; Cell Movement ; drug effects ; Cell Proliferation ; drug effects ; Culture Media, Serum-Free ; Endostatins ; adverse effects ; Female ; Humans ; Matrix Metalloproteinase 9 ; metabolism ; MicroRNAs ; analysis ; Neoplasm Invasiveness ; Proto-Oncogene Proteins c-met ; metabolism ; Random Allocation ; Real-Time Polymerase Chain Reaction ; Time Factors

OBJECTIVETo compare the short-term efficacy and observe the tolerability and safety of recombinant human endostatin combined with induction chemotherapy followed by chemoradiotherapy for locally advanced nasopharyngeal carcinoma.

METHODSFifty-three patients with locally advanced nasopharyngeal carcinoma, who received recombinant human endostatin combined with induction chemotherapy followed by chemoradiotherapy, treated in our department from December 2011 to March 2013 were included in the study group of this study. Another 48 patients, who received induction chemotherapy followed by chemoradiotherapy alone in the same period, were chosen as a control group. The short-term outcome, overall survival (OS), progression-free survival (PFS), and acute side effects of the two groups were compared.

RESULTSThe complete remission rates of nasopharyngeal tumor in the study and control groups were 77.4% and 72.9%, respectively (P=0.154). The complete remission rates of patients with and without cervical lymph node metastasis were 75.5% and 62.6%, respectively, showing a significant difference (P=0.037). The 2-year OS, PFS, and DMFS rates for the study group were 82.3%, 77.2%, and 82.2%, respectively, versus 87.2%, 84.3% and 84.2% for the control group, showing a non-significant differences between the two groups (P=0.938, P=0.551, and P=0.725).

CONCLUSIONSThe short-term results of recombinant human endostatin (Endostar) combined with induction chemotherapy followed by concurrent chemoradiotherapy in the treatment of locally advanced nasopharyngeal carcinoma are slightly better than that of induction chemotherapy followed by concurrent chemoradiotherapy alone, with tolerable treatment-related toxicity and no more side effects.

Antineoplastic Combined Chemotherapy Protocols ; therapeutic use ; Carcinoma ; Chemoradiotherapy ; Cisplatin ; Disease-Free Survival ; Endostatins ; therapeutic use ; Humans ; Induction Chemotherapy ; Lymphatic Metastasis ; Nasopharyngeal Neoplasms ; drug therapy ; radiotherapy ; Remission Induction

Adult ; Aged ; Antineoplastic Agents ; therapeutic use ; Antineoplastic Combined Chemotherapy Protocols ; therapeutic use ; Bone Neoplasms ; drug therapy ; secondary ; Endostatins ; therapeutic use ; Epirubicin ; administration & dosage ; Feasibility Studies ; Female ; Follow-Up Studies ; Hemangiosarcoma ; drug therapy ; pathology ; Humans ; Liver Neoplasms ; drug therapy ; secondary ; Male ; Middle Aged ; Pubic Bone ; pathology ; Taxoids ; administration & dosage

OBJECTIVETo evaluate the safety and efficacy of Endostar combined with chemotherapy in the treatment of end-stage colorectal cancer.

METHODSs The relevant randomized controlled trials were retrieved from the electronic databases of Cochrane library, PubMed, EMbase, CNKI, CBM, VIP and Chinese Medical Association. The retrieval time limit was from the database construction to January 2013. The data were extracted from eligible studies assessed for methodological quality according to Cochrane handbook for systematic reviews and analyzed using RevMan 5.2 software.

RESULTSFive randomized controlled trials involving 220 cases were included for meta-analysis. The results showed that Endostar combined with chemotherapy had an overall advantage over chemotherapy alone in terms of complete response rate (10.91% vs 2.73% RR=4.08, 95% CI: 1.19-13.95, P=0.02), partial response rate (48.18% vs 30.91% RR=2.18, 95% CI: 1.23-3.87, P=0.007), progressive disease (15.45% vs 41.82% RR=0.25, 95% CI: 0.13-0.47, P<0.0001), and the response rate (60.00% vs 33.64% RR=3.23, 95% CI: 1.79-5.81, P<0.0001). Clinical benefit response(82.73% vs 55.45% RR=4.30,95% CI:1.19-13.95, P<0.0001). The main adverse reactions included nausea, vomiting, constipation, palpitation, and electrocardiogram changes.

CONCLUSIONEndostar combined with chemotherapy is effective for advanced colorectal cancer and can be used as a routine treatment.

Antineoplastic Agents ; administration & dosage ; Antineoplastic Combined Chemotherapy Protocols ; therapeutic use ; Colorectal Neoplasms ; drug therapy ; Endostatins ; administration & dosage ; Humans ; Randomized Controlled Trials as Topic

OBJECTIVETo analyze the efficacy and safety of combination of rh-endostatin (Endostar) with docetaxel treatment on patients of non-small cell lung cancer (NSCLC) who presented PD or intolerable toxicity in/after first-line chemotherapy.

METHODSA randomized, double-blind, placebo-controlled and multi-center clinical trial was conducted. Patients with stage IIIB/IV of NSCLC experienced previous chemotherapy of one-regimen were screened for this trial. A total of 68 cases were included in this study. Single docetaxel and that combined with endostar were conducted in two arms. The response, time to progression (TTP) and adverse effects were observed in both arms.

RESULTSThe objective response rate (ORR) and clinical benefit rate (CBR) were 0 and 62.5% in the combined arm, along with 0 and 53.3% in the single docetaxel arm, with a non-significant difference between the two groups (all P > 0.05), respectively. The median TTPs in the combined and single docetaxel arms were 2.63 and 2.07 months, respectively (P = 0.079). The median TTPs of the participants with progressive disease (PD) after first-line chemotherapy were 1.33 and 1.67 months in the combined and single docetaxel arms, respectively (P = 0.946). The median TTPs of the participants with intolerant adverse effects in first-line chemotherapy were 4.70 months and 3.17 months in the combined and single docetaxel arms, respectively (P = 0.070). The median TTPs of the patients with SD after 2 therapeutic cycles in the combined and single docetaxel arms were 6.23 months and 3.27 months, respectively (P = 0.040). The differences between two arms were non-significant in adverse, serious adverse and cardiovascular adverse effects (all P > 0.05).

CONCLUSIONSEndostar may prolong TTP in patients with advanced NSCLC benefited from docetaxel treatment without increased toxicities.

Adult ; Aged ; Antineoplastic Combined Chemotherapy Protocols ; adverse effects ; therapeutic use ; Carcinoma, Non-Small-Cell Lung ; drug therapy ; pathology ; Disease Progression ; Double-Blind Method ; Endostatins ; administration & dosage ; adverse effects ; Female ; Humans ; Leukopenia ; chemically induced ; Lung Neoplasms ; drug therapy ; pathology ; Male ; Middle Aged ; Neoplasm Staging ; Neutropenia ; chemically induced ; Prospective Studies ; Remission Induction ; Taxoids ; administration & dosage ; adverse effects

OBJECTIVETo explore the feasibility of volume perfusion CT imaging to dynamically monitor and evaluate the response of rabbit VX2 soft-tissue tumor to antiangiogenic treatment.

METHODSTo establish an experimental animal model of VX2 soft tissue tumor on 20 New Zealand white rabbits. Twenty rabbits were randomly divided into 2 groups. The therapy group was treated with recombinant human endostatin (3 mg·kg⁻¹·d⁻¹) for 7 days, and the control group received saline in the same dose only. Four times of CT volume perfusion scan were performed before treatment and on the second, forth, seventh days of treatment, respectively. The value of blood flow (BF), blood volume (BV), mean transit time (MTT), and permeability (PMB) in the VX2 tumors were measured after scanning. The microvessel density (MVD) and expression of vascular endothelial growth factor (VEGF) in the tumors were determined using immunohistochemical staining.

RESULTSThe tumor volume of the therapy group was (1.36 ± 0.73) cm³ on the forth day of treatment and (1.69 ± 0.68) cm³ on the seventh day of the treatment. The tumor volume of the control group was (2.35 ± 0.62) cm³ on the fourth day of treatment and (3.87 ± 0.93) cm³ on the seventh day of the treatment (P < 0.05). On the seventh day of treatment, tumor necrosis ratio of the therapy group and the control group was (25.58 ± 5.51)% and (42.93 ± 4.34)%, respectively (P < 0.05). Comparing the perfusion parameters between the two groups on the same day, and the second, forth, seventh days of treatment, the value of PMB of the therapy group was (70.36 ± 23.46) ml·100 ml⁻¹·min⁻¹, (79.64 ± 13.68) ml·100 ml⁻¹·min⁻¹ and (84.76 ± 3.55) ml·100 ml⁻¹·min⁻¹, respectively, and that in the control group was (26.61 ± 6.47) ml·100 ml⁻¹·min⁻¹, (33.74 ± 16.47) ml·100 ml⁻¹·min⁻¹ and (30.47 ± 10.64) ml·100 ml⁻¹·min⁻¹, respectively (P < 0.05). The value of BF in the therapy group and control group was (71.19 ± 12.21) ml·100 ml⁻¹·min⁻¹ and (43.56 ± 12.21) ml·100 ml⁻¹·min⁻¹, respectively, on the seventh day of treatment (P < 0.05). The parameters on different days in the same group were compared. In the control group, the value of BF on the seventh day of treatment was significantly lower than that before and on the second and forth days of treatment (P < 0.05). However, in the therapy group, the value of PMB on the second, forth, and seventh days of treatment was significantly higher than that before treatment (P < 0.05). MVD of tumor in the control group was increased gradually, whereas increased on the first day and then decreased more in the therapy group. The VEGF expressions did not differ significantly between the experimental and control groups.

CONCLUSIONSVolume perfusion CT is helpful to quantify the tumor perfusion and evaluate the functional changes of tumor vasculature, and then evaluate the early therapeutic effect of antiangiogenic treatment.

Angiogenesis Inhibitors ; therapeutic use ; Animals ; Antineoplastic Agents ; therapeutic use ; Blood Volume ; Capillary Permeability ; Cone-Beam Computed Tomography ; methods ; Endostatins ; therapeutic use ; Female ; Male ; Microvessels ; pathology ; Neovascularization, Pathologic ; diagnostic imaging ; Perfusion Imaging ; Rabbits ; Random Allocation ; Regional Blood Flow ; Soft Tissue Neoplasms ; blood supply ; diagnostic imaging ; drug therapy ; pathology ; Tumor Burden ; Vascular Endothelial Growth Factor A ; metabolism