Objective Medulloblastoma(MB)is the most common primary central nervous system malignancy in children.Nonetheless,there is no standard treatment for recurrent MB.The purpose of this study was to investigate the clinic...Objective Medulloblastoma(MB)is the most common primary central nervous system malignancy in children.Nonetheless,there is no standard treatment for recurrent MB.The purpose of this study was to investigate the clinical value and toxicity of recombinant human endostatin injection(Endostar~?)combined with craniospinal radiotherapy for the treatment of recurrent MB in children.Methods This study retrospectively analyzed 13 patients with recurrent MB aged 5–18 years.Endostar?7.5 mg/m~2/d was synchronized during craniospinal radiotherapy for 7 children with a portable micro uniform speed infusion pump.Endostar~?was applied 3 days prior to the initiation of radiotherapy.The drug was in continuous use for 7 days.Similarly,the withdrawal of the drug took place over 7 days.This represented a cycle.During radiotherapy,the application was repeated until the end of radiotherapy(experimental group).In the other 6 cases,only craniospinal radiotherapy was used(control group).Results The complete remission rate was 71.4%in the experimental group and 16.7%in the control group.The median progression-free survival(PFS)was 14 months(95%CI:0.0–29.60)and 19 months(95%CI:0.0–39.53)in the experimental and control groups,respectively.The median overall survival(OS)was 19 months(95%CI:0.0–38.20)and 23 months(95%CI:2.47–43.53)in the experimental and control groups,respectively.The most common adverse events included grade 1 thrombocytopenia(7.7%),grade 3 neutropenia(38.5%),and grade 1 anemia(30.8%).Conclusion Endostar~?synchronizing craniospinal radiotherapy significantly improved the complete response rate of children with recurrent MB.It did not increase the side effects of radiation therapy.However,it did not improve the PFS or OS.展开更多
Objective: To observe the antitumor effect and mechanism of recombinant human endostatin(Endostar) injection in tumor combined with intraperitoneal injection of cisplatin on subcutaneous transplanted Lewis lung cancer...Objective: To observe the antitumor effect and mechanism of recombinant human endostatin(Endostar) injection in tumor combined with intraperitoneal injection of cisplatin on subcutaneous transplanted Lewis lung cancer in rats. Methods: A total of 30 C57 rats were selected, and the monoplast suspension of Lewis lung cancer was injected into the left axilla to prepare the subcutaneous transplanted tumor models in the axilla of right upper limb. The models were randomly divided into Groups A, B, and C. Medication was conducted when the tumor grew to 400 mm3. Group A was the control group without any interventional treatment. Group B was injected with Endostar 5 mg.kg-1.d for 10 d. Group C was given the injection of Endostar 5 mg.kg-1.d combined with intraperitoneal injection of cisplatin 5 mg.kg-1.d for 10 d. All the rats in three groups were executed the day after the 10-d medication and the tumor was taken off for measurement of volume and mass changes and calculation of antitumor rate, after which the vascular endothelial growth factor(VEGF) concentration in rats' plasma was determined by ELISA. The tumor tissues were cut for the preparation of conventional biopsies. After hematoxylin-eosin staining, the pathologic histology was examined to observe the structures of tumor tissues, VEGF score and microvessel density(MVD) in each group. Results: The volume and mass of tumor in Groups B and C were significantly lower than Group A(P < 0.05) while the tumor volume and mass in Group C were significantly lower than Group B(P < 0.05). The antitumor rate in Group C was significantly higher than Group B(P < 0.05), but the tumor VEGF score, MVD and plasma VEGF level in Group C were significantly lower than Groups A and B(P < 0.05). In Group B, the tumor VEGF score, MVD and plasma VEGF level were significantly lower than Group A(P < 0.05). The microscopic image of Group C showed that its number of active tumor cells and the blood capillary around tumor was significantly smaller than that of Groups A and B, and meanwhile atrophy and liquefactive necrosis were seen in local tumor. Conclusions: Endostar injection combined with intraperitoneal injection of cisplatin is effective in reducing tumor VEGF score and MVD of transplanted tumor tissues in rats with Lewis lung cancer to obstruct the nutrient supply of tumor cells and kill tumor cells, so that the inhibition of tumor cell proliferation and metastasis can be achieved with a remarkable effect.展开更多
Objective:To investigate the effect of radiotherapy plus recombinant human endostatin（RHendostatin） on esophageal cancer and its mechanism.Methods:A total of SO nudemice were equally randomized into control group,ra...Objective:To investigate the effect of radiotherapy plus recombinant human endostatin（RHendostatin） on esophageal cancer and its mechanism.Methods:A total of SO nudemice were equally randomized into control group,radiotherapy group,and combined therapy group Ⅰ,Ⅱ,and Ⅲ after inoculating with Ecal09 cell suspension（1×107 cells/mL）.On the day of grouping,control group and radiotherapy group were injected normal saline,while radiotherapy group and 3 combined therapy groups received radiotherapy;besides,combined therapy group Ⅰ,Ⅱ,and Ⅲ was injected RH-endostatin of 2.5,5,10 mg/kg respectively.After 3-week therapy,the tumors of each group were collected and microvessel density and VEGF expression in tumors were determined.In vitro,Eca109 cells were divided into control group,radiotherapy group,and combined therapy group.Forty-eight hours after treatment cell cycle distribution and apoptosis rate were detected,and the activity of VEGF signal paths was semiquantitatively analyzed.Results:Since the 6th day of treatment,the relative tumor proliferation rate of combined therapy group Ⅱ was lower than radiotherapy group（P<0.05） and 40%since the 15 th day.Average microvessel density and EGFR expression in combined therapy group Ⅱ were lower than radiotherapy group（P<0.05）.In vitro,the cell percentage in S and G2/M phase of combined therapy group cells was lower than that in radiotherapy group cells,while the apoptosis rate and the expression of VEGF,AKT,p-AKT,ERK1/2 and p-ERKl/2 in combined group were higher than that in radiotherapy group（P<0.05）.Conclusions:RH-endostatin promotes the efficacy of radiotherapy on esophageal cancer,which may be partly realized by inhibiting the activity of VEGF related signal paths.展开更多
AIM: To construct a stable transfectant of human liver carcinoma cell line SMMC7721 that could secret human endostatin and to explore the effect of human endostatin expressed by the transfectant on endothelial cell pr...AIM: To construct a stable transfectant of human liver carcinoma cell line SMMC7721 that could secret human endostatin and to explore the effect of human endostatin expressed by the transfectant on endothelial cell proliferation. METHODS: Recombinant retroviral plasmid pLncx-Endo containing the cDNA for human endostatin gene together with rat albumin signal peptide was engineered and transferred into SMMC7721 cell by lipofectamine. After selection with G418, endostatin-transfected SMMC7721 cells were chosen and expanded. Immunohistochemical staining and Western blot were used to detect the expression of human endostatin in transfected SMMC7721 cells and its medium. The conditioned medium of endostatin-transfected and control SMMC7721 cells were collected to cultivate with human umbilical vein endothelial cells for 72 hours. The inhibitory effect of endostatin, expressed by transfected SMMC7721 cells, on endothelial proliferation in vitro was observed by using MTT assay. RESULTS: A 550 bp specific fragment of endostatin gene was detected from the PCR product of endostatin-transfected SMMC7721 cells. Immunohistochemistry and Western blot analysis confirmed the expression and secretion of foreign human endostatin protein by endostatin-transfected SMMC7721 cells. In vitro endothelial proliferation assay showed that 72 hours after cultivation with human umbilical vein endothelial cells, the optical density (OD) in group using the medium from endostatin-transfected SMMC7721 cells was 0.51 +/- 0.06, lower than that from RPMI 1640 group (0.98 +/- 0.09) or that from control plasmid pLncx-transfected SMMC7721 cells (0.88 +/- 0.11). The inhibitory rate for medium from endostatin-transfected SMMC7721 cells was 48%, significantly higher than that from empty plasmid pLncx-transfected SMMC7721 cells (10.2%, P【0.01). CONCLUSION: Human endostatin can be stably expressed by SMMC7721 cell transferred with human endostatin gene and its product can significantly inhibit the proliferation of human umbilical vein endothelial cell in vitro.展开更多
Objectives: To observe the curative effects and adverse reactions of recombinant human (rh)-endostatin injection combined with a TP regimen for treating patients with advanced ovarian cancer.Methods: Fifty-four patien...Objectives: To observe the curative effects and adverse reactions of recombinant human (rh)-endostatin injection combined with a TP regimen for treating patients with advanced ovarian cancer.Methods: Fifty-four patients with pathologically confirmed ovarian cancer were randomly divided into a combined treatment (intravenous pump of rh-endostatin + TP regimen) group and a control (single chemotherapy) group, twenty-seven patients in each group.All patients were given a conventional CT examination.The level of vascular endothelial growth factor (VEGF), the size of tumor before treatment, after 2 cycles and after 4 cycles of treatment were determined for the comparison of curative effects and adverse reactions.Results: The effective rate was 37.0％ (10/27) and disease control rate was 63.0％ (17/27) in the combined treatment group after 2 cycles of treatment.The effective rate was 25.9％ (7/27) and disease control rate was 63.0％ (17/27) in the control group.The comparison between these two groups showed no significant differences (P ＞ 0.05).The effective rate was 63.0％ (17/27) and disease control rate was 92.6％ (25/27) in the combined treatment group after 4 cycles of treatment.The effective rate was 29.6％ (8/27) and disease control rate was 63.0％ (17/27) in the control group.The effective rate and disease control rate between these two groups after 4 cycles of treatment showed significant differences (P ＜ 0.05).The incidences of cardiovascular toxicity, myelosuppression, sore muscles and joints, alopecia and gastrointestinal reaction was not significantly different between two groups (P ＞ 0.05).Conclusion: The pump delivery of rh-endostatin can down-regulate the expression of VEGF in ovarian cancer and has the better curative effect and slighter adverse reactions.Copyright 2015, Chinese Medical Association Production.Production and hosting by Elsevier B.V.on behalf of KeAi Communications Co., Ltd.This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/ by-nc-nd/4.0/).展开更多
基金Supported by a grant from the Chongqing Science and Health Joint Medical Research Foundation of China(No.2019MSXM079)。
文摘Objective Medulloblastoma(MB)is the most common primary central nervous system malignancy in children.Nonetheless,there is no standard treatment for recurrent MB.The purpose of this study was to investigate the clinical value and toxicity of recombinant human endostatin injection(Endostar~?)combined with craniospinal radiotherapy for the treatment of recurrent MB in children.Methods This study retrospectively analyzed 13 patients with recurrent MB aged 5–18 years.Endostar?7.5 mg/m~2/d was synchronized during craniospinal radiotherapy for 7 children with a portable micro uniform speed infusion pump.Endostar~?was applied 3 days prior to the initiation of radiotherapy.The drug was in continuous use for 7 days.Similarly,the withdrawal of the drug took place over 7 days.This represented a cycle.During radiotherapy,the application was repeated until the end of radiotherapy(experimental group).In the other 6 cases,only craniospinal radiotherapy was used(control group).Results The complete remission rate was 71.4%in the experimental group and 16.7%in the control group.The median progression-free survival(PFS)was 14 months(95%CI:0.0–29.60)and 19 months(95%CI:0.0–39.53)in the experimental and control groups,respectively.The median overall survival(OS)was 19 months(95%CI:0.0–38.20)and 23 months(95%CI:2.47–43.53)in the experimental and control groups,respectively.The most common adverse events included grade 1 thrombocytopenia(7.7%),grade 3 neutropenia(38.5%),and grade 1 anemia(30.8%).Conclusion Endostar~?synchronizing craniospinal radiotherapy significantly improved the complete response rate of children with recurrent MB.It did not increase the side effects of radiation therapy.However,it did not improve the PFS or OS.
基金supported by Liaoning BaiQianWan Talents Program(No.2012921017)
文摘Objective: To observe the antitumor effect and mechanism of recombinant human endostatin(Endostar) injection in tumor combined with intraperitoneal injection of cisplatin on subcutaneous transplanted Lewis lung cancer in rats. Methods: A total of 30 C57 rats were selected, and the monoplast suspension of Lewis lung cancer was injected into the left axilla to prepare the subcutaneous transplanted tumor models in the axilla of right upper limb. The models were randomly divided into Groups A, B, and C. Medication was conducted when the tumor grew to 400 mm3. Group A was the control group without any interventional treatment. Group B was injected with Endostar 5 mg.kg-1.d for 10 d. Group C was given the injection of Endostar 5 mg.kg-1.d combined with intraperitoneal injection of cisplatin 5 mg.kg-1.d for 10 d. All the rats in three groups were executed the day after the 10-d medication and the tumor was taken off for measurement of volume and mass changes and calculation of antitumor rate, after which the vascular endothelial growth factor(VEGF) concentration in rats' plasma was determined by ELISA. The tumor tissues were cut for the preparation of conventional biopsies. After hematoxylin-eosin staining, the pathologic histology was examined to observe the structures of tumor tissues, VEGF score and microvessel density(MVD) in each group. Results: The volume and mass of tumor in Groups B and C were significantly lower than Group A(P < 0.05) while the tumor volume and mass in Group C were significantly lower than Group B(P < 0.05). The antitumor rate in Group C was significantly higher than Group B(P < 0.05), but the tumor VEGF score, MVD and plasma VEGF level in Group C were significantly lower than Groups A and B(P < 0.05). In Group B, the tumor VEGF score, MVD and plasma VEGF level were significantly lower than Group A(P < 0.05). The microscopic image of Group C showed that its number of active tumor cells and the blood capillary around tumor was significantly smaller than that of Groups A and B, and meanwhile atrophy and liquefactive necrosis were seen in local tumor. Conclusions: Endostar injection combined with intraperitoneal injection of cisplatin is effective in reducing tumor VEGF score and MVD of transplanted tumor tissues in rats with Lewis lung cancer to obstruct the nutrient supply of tumor cells and kill tumor cells, so that the inhibition of tumor cell proliferation and metastasis can be achieved with a remarkable effect.
基金supported by the Science and Technology Development Plan of Henan province(No.122102310245)
文摘Objective:To investigate the effect of radiotherapy plus recombinant human endostatin（RHendostatin） on esophageal cancer and its mechanism.Methods:A total of SO nudemice were equally randomized into control group,radiotherapy group,and combined therapy group Ⅰ,Ⅱ,and Ⅲ after inoculating with Ecal09 cell suspension（1×107 cells/mL）.On the day of grouping,control group and radiotherapy group were injected normal saline,while radiotherapy group and 3 combined therapy groups received radiotherapy;besides,combined therapy group Ⅰ,Ⅱ,and Ⅲ was injected RH-endostatin of 2.5,5,10 mg/kg respectively.After 3-week therapy,the tumors of each group were collected and microvessel density and VEGF expression in tumors were determined.In vitro,Eca109 cells were divided into control group,radiotherapy group,and combined therapy group.Forty-eight hours after treatment cell cycle distribution and apoptosis rate were detected,and the activity of VEGF signal paths was semiquantitatively analyzed.Results:Since the 6th day of treatment,the relative tumor proliferation rate of combined therapy group Ⅱ was lower than radiotherapy group（P<0.05） and 40%since the 15 th day.Average microvessel density and EGFR expression in combined therapy group Ⅱ were lower than radiotherapy group（P<0.05）.In vitro,the cell percentage in S and G2/M phase of combined therapy group cells was lower than that in radiotherapy group cells,while the apoptosis rate and the expression of VEGF,AKT,p-AKT,ERK1/2 and p-ERKl/2 in combined group were higher than that in radiotherapy group（P<0.05）.Conclusions:RH-endostatin promotes the efficacy of radiotherapy on esophageal cancer,which may be partly realized by inhibiting the activity of VEGF related signal paths.
文摘AIM: To construct a stable transfectant of human liver carcinoma cell line SMMC7721 that could secret human endostatin and to explore the effect of human endostatin expressed by the transfectant on endothelial cell proliferation. METHODS: Recombinant retroviral plasmid pLncx-Endo containing the cDNA for human endostatin gene together with rat albumin signal peptide was engineered and transferred into SMMC7721 cell by lipofectamine. After selection with G418, endostatin-transfected SMMC7721 cells were chosen and expanded. Immunohistochemical staining and Western blot were used to detect the expression of human endostatin in transfected SMMC7721 cells and its medium. The conditioned medium of endostatin-transfected and control SMMC7721 cells were collected to cultivate with human umbilical vein endothelial cells for 72 hours. The inhibitory effect of endostatin, expressed by transfected SMMC7721 cells, on endothelial proliferation in vitro was observed by using MTT assay. RESULTS: A 550 bp specific fragment of endostatin gene was detected from the PCR product of endostatin-transfected SMMC7721 cells. Immunohistochemistry and Western blot analysis confirmed the expression and secretion of foreign human endostatin protein by endostatin-transfected SMMC7721 cells. In vitro endothelial proliferation assay showed that 72 hours after cultivation with human umbilical vein endothelial cells, the optical density (OD) in group using the medium from endostatin-transfected SMMC7721 cells was 0.51 +/- 0.06, lower than that from RPMI 1640 group (0.98 +/- 0.09) or that from control plasmid pLncx-transfected SMMC7721 cells (0.88 +/- 0.11). The inhibitory rate for medium from endostatin-transfected SMMC7721 cells was 48%, significantly higher than that from empty plasmid pLncx-transfected SMMC7721 cells (10.2%, P【0.01). CONCLUSION: Human endostatin can be stably expressed by SMMC7721 cell transferred with human endostatin gene and its product can significantly inhibit the proliferation of human umbilical vein endothelial cell in vitro.
文摘Objectives: To observe the curative effects and adverse reactions of recombinant human (rh)-endostatin injection combined with a TP regimen for treating patients with advanced ovarian cancer.Methods: Fifty-four patients with pathologically confirmed ovarian cancer were randomly divided into a combined treatment (intravenous pump of rh-endostatin + TP regimen) group and a control (single chemotherapy) group, twenty-seven patients in each group.All patients were given a conventional CT examination.The level of vascular endothelial growth factor (VEGF), the size of tumor before treatment, after 2 cycles and after 4 cycles of treatment were determined for the comparison of curative effects and adverse reactions.Results: The effective rate was 37.0％ (10/27) and disease control rate was 63.0％ (17/27) in the combined treatment group after 2 cycles of treatment.The effective rate was 25.9％ (7/27) and disease control rate was 63.0％ (17/27) in the control group.The comparison between these two groups showed no significant differences (P ＞ 0.05).The effective rate was 63.0％ (17/27) and disease control rate was 92.6％ (25/27) in the combined treatment group after 4 cycles of treatment.The effective rate was 29.6％ (8/27) and disease control rate was 63.0％ (17/27) in the control group.The effective rate and disease control rate between these two groups after 4 cycles of treatment showed significant differences (P ＜ 0.05).The incidences of cardiovascular toxicity, myelosuppression, sore muscles and joints, alopecia and gastrointestinal reaction was not significantly different between two groups (P ＞ 0.05).Conclusion: The pump delivery of rh-endostatin can down-regulate the expression of VEGF in ovarian cancer and has the better curative effect and slighter adverse reactions.Copyright 2015, Chinese Medical Association Production.Production and hosting by Elsevier B.V.on behalf of KeAi Communications Co., Ltd.This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/ by-nc-nd/4.0/).
