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Cancer Biology & Medicine 2019年第1期16卷 166-172页

作者： Hairong Xu Zhen Huang Yuan Li Qing Zhang Lin Hao Xiaohui Niu Department of Orthopedic Oncology Surgery Beijing Ji Shui Tan Hospital Peking University

Objective: Anti-angiogenic drugs are an emerging treatment option against malignant tumors. The aim of this study was to determine whether the addition of perioperative rh-endostatin to chemotherapy could improve the probability of distant metastasis-free survival(DMFS) and overall survival(OS) in patients newly diagnosed with non-metastatic conventional ***: This was a controlled non-randomized clinical study that included 388 patients without clinically detectable metastatic disease enrolled from January 2008 to April 2012. The control treatment group had 272 patients; 180 were male and 92, female,with a median age of 17 years. The treatment group had 58 patients; 36 were male and 22, female, with a median age of 16 *** control group received preoperative chemotherapy followed by surgery and postoperative chemotherapy. The treatment group received 4 cycles of rh-endostatin perioperatively in addition to chemotherapy as per the control group. Patients were followed up from 6-101 months with a median follow-up period of 50.2 ***: The 5-year DMFS of the control group(61%) was significantly lower than that of the rh-endostatin group(79%)(P = 0.013). The 5-year OS of the control group(74%) was significantly lower than that of the rh-endostatin treatment group(87%)(P = 0.029). No difference in adverse drug reactions was found between these 2 ***: The addition of perioperative rh-endostatin to chemotherapy could significantly improve the DMFS and OS of patients with non-metastatic osteosarcoma.

关键词： Osteosarcoma rh-endostatin perioperative distant metastasis overall survival

Clinical observation of rh-endostatin combined with chemotherapy as first line treatment for metastatic colorectal cancer

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Oncology and Translational Medicine 2016年第6期2卷 279-284页

作者： Wenwu Wang Shanshan Huang Xiaoyan Huang Yan Zhang Xiaoyan Qi Department of Oncology Nanjing Military Command Fuzhou General Hospital Department of Oncology Central Hospital of Zibo

Objective To analyze the efficacy and safety of rh-endostatin combined with chemotherapy in the treatment of metastatic colorectal *** All 60 metastatic colorectal cancer patients were divided into the test group(n = 30) and the control group(n = 30). The control group was treated with chemotherapy regime FOLFOX4(Oxaliplatin + Fluorouracil + Calcium Levofolinate), the test group was treated by Endostar combined with FOLFOX4 *** The response rates were 53.3% in test group and 36.7% in control group respectively(P 0.05). The major toxicities were myelosuppression, gastrointestinal symptoms, neurotoxicity, most in grade I-II. After chemotherapy, quality of life(QOL) of patients were more improved than before treatment. After treatment the carcino embryonie antigen(CEA) and caner antigent 199(CA199) levels decreased obviously, furthermore, the test group decreased more obviously than the control group. Conclusion rh-endostatin combined with chemotherapy in the treatment of metastatic colorectal cancer is safer and effective, and also improves PFS.

关键词： rh-endostatin FOLFOX4 regimen metastatic colorectal cancer

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

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The Chinese-German Journal of Clinical Oncology 2012年第1期11卷 43-48页

作者： Cuicui Zhang Kai Li Jing Wang Department of Thoracic Oncology Tianjin Medical University Cancer Institute and HospitalTianjin Key Laboratory of Cancer Prevention and TherapyLung Cancer Center of TianjinTianjin 300060China

Objective： The aim of this study was to compare effect of rh-endostatin on microvasculature in tumor and myocardium tissue. Methods： Nude mice were randomized into 4 groups, blank control group [did not burden tumor, normalsaline （NS） 100 μL/d], drug control group （did not burden tumor, rh-endostatin 400 μg/d）, model group （mice burdened tumor, NS 100 μL/d） and treatment group （mice burdened tumor, rh-endostatin 400 μg/d）, administration was given during d1-d28. The volume of tumor and the weight of mouse were measured before and after administration. The expression of CD34, MMP-2, MMP-9, HIF-la and VEGF in myocardium and tumor were detected by immunohistochemistry. The structure of vasculature was observed by immunoenzymatic double staining with CD34 and Masson. Results： The tumor volume increase of treatment group （48.18 mm3） was less than the model group （113.80 mm3）, the change of weight was not significant among the four groups. After treated with endotar, the expression of MMP-9 and VEGF in tumor were obviously down-regulated, but the same results was not found in MMP-2, HIF-la of tumor. MVD in tumor of treatment group decreased significantly compared with model group. Proportion of tumor vessels covered by collagen in treatment group increased compared with model group. However, MVD and microvasculature in myocardium did not change significantly. Conclusion： rh-endostatin can decrease the expression of MMP-9, VEGF and MVD to inhibit growth of tumor and normalize micrangium in tumor but cannot weaken MMPs and MVD of mature micrangium in myocardium.

关键词： rh-endostatin xenografted tumor myocardium tissue micrangium

The anti-cancer effect of Huaier aqueous extract with rh-endostatin and DDP

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The Chinese-German Journal of Clinical Oncology 2014年第8期13卷 349-354页

作者： Yuxuan Che Meixiang Zhou Peng Zhan Tiantian Zou Xiuhua Sun Medical Onoclogy The Second Affiliated Hospital of Dalian Medical University

Objective: The aim of our study was to explore the inhibition and apoptosis-inducing effect of the combination of Huaier aqueous extract with recombinant human endostatin and DDP in human lung adenocarcinoma A549 cells. We also investigated the reversal effect of Huaier aqueous extract in reversing cisplatin resistance in human lung adenocarcinoma A549/DDP cells. Methods: We treated A549 cells with Huaier aqueous extract and the combination of Huaier aqueous extract and DDP or rh-endostatin for 24 h, 36 h and 48 h. And then we calculated the inhibition rate through MTT approach and detected the apoptosis rate by flow cytometry. We also treated A549 and A549/DDP cells with DDP, Huaier aqueous extract, DDP and Huaier aqueous extract for 72 h, respectively. Results: Huaier aqueous extract can inhibit the growth of A549 cells and the inhibition rate improved with the increase of the concentration. The inhibition rate of the combination of rh-endostatin and 4 mg/mL of Huaier aqueous extract in three time points and the combination of rh-endostatin and 2 mg/mL of Huaier aqueous extract in the time point of 48 h on the growth of A549 cells all improved(P rh-endostatin and DDP can improve the inhibition on the growth of A549 cells(P rh-endostatin or DDP has the synergistic effects on the inhibition of A549 cells. The combination of Huaier aqueous extract with rh-endostatin and DDP has the synergistic effects on the inhibition of A549 cells. Huaier aqueous extract can reverse the cisplatin resistance in human lung adenocarcinoma A549/DDP

关键词： Huaier aqueous extract rh-endostatin anti-cancer effects A549 cells A549/DDP cells

放疗联合周剂量重组人血管内皮抑素对A549肺腺癌裸鼠移植瘤生长抑制作用的研究

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肿瘤 2010年第11期30卷 917-923页

作者：蒋晓东戴鹏吴瑾宋大安于金明天津医科大学研究生院天津300021 连云港市第一人民医院肿瘤科连云港222002 山东省肿瘤医院放射治疗科济南250117

目的:研究放疗联合周剂量重组人血管内皮抑素(recombinant human endostatin,rh-endostatin)对肺腺癌A549裸鼠移植瘤生长的抑制作用。方法:40只裸鼠A549细胞移植瘤模型随机分成4组:空白对照组、rh-endostatin治疗组、放射治疗组和放疗联... 详细信息

目的:研究放疗联合周剂量重组人血管内皮抑素(recombinant human endostatin,rh-endostatin)对肺腺癌A549裸鼠移植瘤生长的抑制作用。方法:40只裸鼠A549细胞移植瘤模型随机分成4组:空白对照组、rh-endostatin治疗组、放射治疗组和放疗联合rh-endostatin治疗组,观察并绘制肿瘤生长曲线图,计算肿瘤体积抑制率;肿瘤组织行常规HE病理学检查,免疫组织化学法检测肿瘤组织中微血管内皮CD31的表达及肿瘤微血管密度(microvessel density,MVD)的变化;采用免疫组织化学及Western印迹法检测血管内皮生长因子(vascular endothelial growth factor,VEGF)的表达;TUNEL法检测肿瘤细胞的凋亡。结果:治疗第8天起,放疗联合rh-endostatin治疗组的肿瘤体积与对照组相比,差异有统计学意义(Prh-endostatin治疗组、放射治疗组和放疗联合rh-endostatin治疗组小鼠的肿瘤体积的抑制率依次为68.35%、90.78%和106.56%;rh-endostatin治疗组小鼠的MVD较放射治疗组下降明显(Prh-endostatin治疗组与对照组、放疗联合rh-Endostati治疗组及放射治疗组相比,VEGF的改变差异均无统计学意义;放疗联合rh-endostatin治疗组细胞凋亡明显。结论:放疗联合周剂量rh-endostatin能抑制肿瘤的生长,较早诱导肿瘤退缩,可能与减少放射治疗后肿瘤血管再生及增加肿瘤细胞和内皮细胞的凋亡相关;各治疗组小鼠均未出现急性不良反应,因此该方法具有短疗程的优势,可用于临床推广。

关键词：放疗周剂量重组人血管内皮抑素 A549肺腺癌裸鼠移植瘤生长抑制作用 nude mice pulmonary adenocarcinoma human endostatin rh-endostatin 治疗组肿瘤体积放射治疗 endothelial growth factor 免疫组织化学法统计学意义对照组肿瘤组织肿瘤细胞

重组人endostatin在甲醇酵母Pichia Pastoris中的分泌表达

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四川大学学报（自然科学版） 2002年第S1期39卷 -页

作者：吴纬陈静娴宋宁焦丽华中国协和医科大学.中国医学科学院输血研究所生物技术室成都610081

为了获得高效表达分泌型重组人endostatin菌株 ,利用基因工程技术 ,将目的基因连接到Pichia表达载体 pPIC9K中 ,将该重组质粒转入GS115菌株后筛选His阳性菌株 ,并用G4 18筛选高拷贝阳性克隆菌 .重组表达的endostatin经SDS PAGE电泳 ,可... 详细信息

为了获得高效表达分泌型重组人endostatin菌株 ,利用基因工程技术 ,将目的基因连接到Pichia表达载体 pPIC9K中 ,将该重组质粒转入GS115菌株后筛选His阳性菌株 ,并用G4 18筛选高拷贝阳性克隆菌 .重组表达的endostatin经SDS PAGE电泳 ,可在分子量 2 2kD处见到单一目标带 .经体外生物学活性检测 ,Pichia菌株表达的endostatin能有效地抑制培养的ECV30 4细胞及P6 1细胞的生长 .

关键词： Pichia Pastoris rh-endostatin 分泌表达