Effect Of Rh-endostatin Research Articles

Efficacy and safety of recombinant human endostatin combined with whole-brain radiotherapy in patients with brain metastases from NSCLC.

e21158 Background: Brain metastasis (BM) is the first cause of poor prognosis in non-small cell lung cancer (NSCLC) patients. To date, localized whole-brain radiotherapy (WBRT) is still the therapeutic option for patients with extensive BM. However, effectiveness is currently unsatisfactory. This study aimed to investigate the effects of Rh-endostatin combined with WBRT on NSCLC patients with BMs. Methods: 43 NSCLC patients with BMs were divided into two groups randomly. Rh-endostatin combination group (n = 19) received WBRT combined with Rh-endostatin, and radiation group (n = 24) received WBRT alone. The primary endpoint of the study was progression free survival (PFS). The secondary endpoints were intracranial progression free survival (iPFS), overall survival (OS), objective response rate (ORR) and the change of cerebral blood volume (CBV), cerebral blood flow (CBF) of the contrast medium pre- and one month post-radiation. Results: Median progression-free survival (PFS) was 8.1 months in the Rh-endostatin combination group versus 4.9 months in the radiation group (95%CI: 0.2612-0.9583, p= 0·0428). Besides, median iPFS was 11.6 months in Rh-endostatin combination group versus 4.8 months in the radiation group (95%CI：0.2530-0.9504, p= 0·0437). Overall survival (OS) was 14.2 months in the Rh-endostatin combination group versus 6.4 months in the radiation group (95%CI：0.2508-1.026, p= 0·0688). Compared with radiotherapy alone, CBV and CBF in the Rh-endostatin combination group increased more significantly than before radiotherapy, indicating that Rh-endostatin may improve local blood supply and microcirculation. Conclusions: Rh-endostatin showed better survival and a safety profile, improved cerebral perfusion and increased the quality of life of NSCLC patients with BMs. Clinical trial information: NCT03614065.

Recombinant Human Endostatin Suppresses Mouse Osteoclast Formation by Inhibiting the NF-κB and MAPKs Signaling Pathways.

Rheumatoid arthritis is an autoimmune disease characterized by synovial hyperplasia and progressive joint destruction. As reported previously, recombinant human endostatin (rhEndostatin) is associated with inhibition of joint bone destruction present in rat adjuvant-induced arthritis; however, the effect of rhEndostatin on bone destruction is not known. This study was designed to assess the inhibitory effect and mechanisms of rhEndostatin on formation and function of osteoclasts in vitro, and to gain insight into the mechanism underlying the inhibitory effect of bone destruction. Bone marrow-derived macrophages isolated from BALB/c mice were stimulated with receptor activator of NF-κB ligand (RANKL) and macrophage colony-stimulating factor to establish osteoclast formation. Osteoclast formation was determined by TRAP staining. Cell viability of BMMs affected by rhEndostatin was determined using a MTT assay. Bone resorption was examined with a bone resorption pits assay. The expression of osteoclast-specific markers was analyzed using quantitative real-time PCR. The related signaling pathways were examined using a Luciferase reporter assay and western blot analysis. Indeed, rhEndostatin showed a significant reduction in the number of osteoclast-like cells and early-stage bone resorption. Moreover, molecular analysis demonstrated that rhEndostatin attenuated RANKL-induced NF-κB signaling by inhibiting the phosphorylation of IκBα and NF-κB p65 nuclear translocation. Furthermore, rhEndostatin significantly inhibited the activation of RANKL-dependent mitogen-activated protein kinases, such as ERK1/2, JNK, and p38. Hence, we demonstrated for the first time that preventing the formation and function of osteoclasts is an important anti-bone destruction mechanism of rhEndostatin, which might be useful in the prevention and treatment of bone destruction in RA.

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

Objective Recombinant human Endostatin (rh-Endostatin, YH-16) can reverse cisplatin resistance in A549/DDP cells. However, the possible effect of rh-Endostatin in reversing DDP-resistance in A549/DDP cells and the mechanism are needed to be investigated.

Effect of rh-endostatin on factors associated with vascular xanocraft tumor and normal tissue

Effect of rh-endostatin on factors associated with vascular xanocraft tumor and normal tissue

Effects of recombinant human endostatin and its synergy with cisplatin on circulating endothelial cells and tumor vascular normalization in A549 xenograft murine model

Endostatin can normalize the tumor vasculature to some extent. However, exact length of its time window and corresponding markers for tumor vascular normalization are needed to be explored. The A549 lung adenocarcinoma xenograft murine model was treated with recombinant human endostatin (rh-endostatin) for 14days. Cisplatin was combined in different schedules. The effects of rh-endostatin on circulating endothelial cells (CECs) by flow cytometry, tumor vasculature and angiogenesis-related factors by confocal microscope and immunohistochemistry, and anti-tumor efficacy of cytotoxic drugs were observed. The activated CECs (aCECs) were increased on day 7 and decreased on day 10, and apoptotic CECs were increased on day 10. Tumor vasculature was transiently normalized with increased collagen coverage, decreased vessel permeability, intratumoral hypoxia, and microvascular density from day 7 to 10 after rh-endostatin administration. Extracellular matrix metalloproteinase inducer, vascular endothelial growth factor, matrix metalloproteinase (MMP)-2, and MMP-9 were transiently decreased by rh-endostatin from day 4 to 10, whereas the opposite effects were observed with tissue inhibitors of matrix metalloproteinase (TIMP)-1 and TIMP-2. The maximal anti-tumor effects of cisplatin were observed on administration from day 5 to 9 after rh-endostatin initial administration. Rh-endostatin could transiently normalize tumor vasculature, probably via regulation of both pro- and anti-angiogenesis factors. The synergistic efficacy of anti-angiogenesis and chemotherapy was found during "the normalization window". CEC could be a feasible blood biomarker for defining "vascular normalization window" and providing the evidence to make an optimizing combination therapeutic schedule in human tumor.

The effect of rh-endostatin on micrangium and angiogenic factors in tumor and myocardium tissue

Objective The aim of this study was to compare effect of rh-endostatin on microvasculature in tumor and myocardium tissue.

Observation of Short-Term Effects of Rh-endostatin Combined with Chemotherapy for Medium and Advanced Nonsmall Cell Lung Cancer

Objective To investigate and compare the short-term effect and safety of rh-endostatin(endostar) combined with chemotherapy and conventional chemotherapy for NSCLC.Methods One hundred and four 104 patients with advanced non-small cell lung cancer confirmed by histopathology or cytopathology,were divided into two groups.Forty-one patients were given rh-endostatin plus chemotherapy(trial group),and 63 patients were given chemotherapy only(control group).The efficacy and toxicity were evaluated after 2 cycles according to RECIST criteria and NCI CTC 3.0 respectively.Results Totally,data from the 104 patients were evaluable.The total response rate(RR) in two groups were 34.15% and 30.16%,and the total clinical benefit rate(CBR) were 73.17% and 71.43%,respectively.The RR of untreated patients was 34.78% and 39.02%,CBR was 73.91% and 80.49%.The RR of retreated patients was 33.33% and 13.64%,CBR was 72.22% and 54.55%.The RR of squamous cell carcinoma was 27.27% and 28.00%,CBR was 81.82% and 72.00%.The RR of adenocarcinoma was 36.67% and 31.58%,CBR was 70.00% and 71.05%.There was no significant difference in patients' quality of life in two groups,and the incidence rates of side effect showed no statistical difference between two groups(P0.05).Conclusion The chemotherapy combined with rh-endostatin tended to show a better efficacy than chemotherapy alone and was well-tolerated in patients with non-small cell lung cancer,especially for the retreated patients.

The effect of rh-endostatin in combination with radiotherapy on the HIF-1α and VEGF expression in mice with lung cancer

Objective To study the effect of rh-endostatin on the hypoxia-inducible factor 1α （HIF-1α） and vascular endothelial growth factor （VEGF） expression in mice with lung cancer treated with radiotherapy. Methods Sixty rats were randomly divided into five groups： control group, the large dose single-γ-ray irradiation group, the small dose fraction irradiation group, the large dose irradiation ＋ YH-16 group and the low dose irradiation ＋ YH-16 group. Inhibition rate and the tumor growth curve were observed. Immunohistochemisty was adopted to detect the expression of HIF-1α and VEGF. The correlation between the expression of HIF-1α, VEGF and inhibilion rate was analyzed. Results The expression of HIF-1α or VEGF and inhibition was correlated negatively （r=-7.823,-8.314, respectively ,P〈0.05）. There was no significant correlation between the expression of HIF-1α and VEGF. Conclusion Adminis-tration of YH-16 before radiotherapy can inhibit the HIF-1α and VEGF expression in mice with lung canc-er, and effectively increase the radiosensitivity of lung cancer,. Key words: Pulmonary carcinoma; HIF-1α; VEGF; Radiotherapy; Endostatin

The inhibitory effects of rh-endostatin (YH-16) in combination with radiotherapy on lung adenocarcinoma A549 in mice and the underlying mechanisms

In order to investigate the inhibitory effects of Endostar (rh-endostatin, YH-16) in combination with radiotherapy on lung adenocarcinoma A549 in mice and the interaction mechanisms of combined therapy, the transplantation tumor models of A549 lung adenocarcinoma were established. When the largest diameter of tumor reached 1.0 cm, all nude mice were randomly divided into 4 groups: Endostar group, radiotherapy group, radiotherapy plus Endostar (combined treatment) group, and control group (n=6 in each group). The largest diameter and the vertical diameter of tumor were measured at different time points. At the 16th day, mice were executed, and the tumors were applied to analysis of rate of tumor cell apoptosis, and the expression levels of basic fibroblast growth factor (bFGF) mRNA were detected by reverse transcription-polymerase chain reaction (RT-PCR) and those of vascular endothelial growth factor (VEGF) by immunohistochemistry. The results demonstrated that the rate of tumor inhibition in combined treatment group was higher than that in other groups. And the rate of tumor cell apoptosis in combined treatment group was also higher than that in other groups. Meanwhile, the levels of bFGF mRNA and VEGF expression in combined treatment group were lower than those in other groups. It was concluded that Endostar obviously enhanced the curative effectiveness of radiotherapy on lung adenocarcinoma A549 in mice. The underlying mechanisms may involve the down-regulation of bFGF mRNA and VEGF expression to inhibit angiogenesis by Endostar and the cooperative effect of Endostar and radiotherapy to synergistically promote tumor cell apoptosis. And Endostar inhibits angiogenesis by down-regulating the expression of bFGF mRNA and VEGF.

The effect of rh-endostatin on phenotype of HUVECs at different activating levels

The effect of rh-endostatin on phenotype of HUVECs at different activating levels