肝动脉灌注化疗联合Endostar-碘油栓塞治疗原发性肝癌的研究

目的探索Endostar用于肝癌介入栓塞的疗效。方法 48例患者分为Endostar组合对照组。所有病例行TACE治疗1～2次,行化疗药物肝动脉灌注,然后对照组用丝裂霉素同碘化油混合物做肝动脉栓塞,在Endostar组使用Endostar同碘化油混合物做动脉栓塞。结果两组患者有不同程度的发热及右上腹疼痛,治疗后两组患者AFP水平、谷丙转氨酶、谷草转氨酶、总胆红素水平、肿瘤体积等指标均明显好于治疗前;且上诉指标在Endostar组能观察到更好的疗效。结论Endostar介入栓塞治疗肝癌未见明显不良反应,而且在肿瘤体积、甲胎蛋白水平、肝功等方面改善更为明显,值得推广应用。

DCE-MRI评价Endostar对兔VX2骨肿瘤模型抗血管生成的疗效

目的:探讨基于Reference-Region模型的DCE-MRI评价恩度对兔VX2骨肿瘤抗血管生成疗效的可行性。方法:将成功建立胫骨VX2肿瘤模型(软组织肿块直径>1.0cm)的20只兔子随机分成对照组(n=10)和实验组(n=10),分别于给药前、连续给药14天后(对照组药物为生理盐水;实验组药物为恩度,药物浓度为1.5mg/8mL)行DCE-MRI扫描,使用Referrence Region模型获得肿瘤组织的对比剂容积转移常量Ktrans和反流速率常数Kep。于第14天扫描结束后处死动物,取肿瘤外周及中心区域的组织进行免疫组化染色检测,得到肿瘤不同区域的微血管密度(MVD)及血管内皮生长因子(VEGF)的表达情况,将DCE-MRI各参数与免疫组化结果进行相关分析。结果:对照组中肿瘤外周区域和中心区域的Ktrans值在治疗前分别为(32.58±3.10)和(28.50±3.54)min-1,治疗后分别为(37.66±2.78)和(34.20±3.39)min-1;实验组中肿瘤组织的外周区域和中心区域的Ktrans值在治疗前分别为(27.70±4.75)和(23.90±4.40)min-1,在治疗后分别为(22.20±4.29)和(18.30±4.23)min-1。实验组VX2骨肿瘤外周区域与中心区域的Ktrans值、MVD值及VEGF表达情况间的差异均有统计学意义(P<0.05),Kep值的差异无统计学意义(P>0.05)。实验组治疗后肿瘤外周和中心区域的VEGF表达、MVD值与Ktrans值间均呈正相关关系(r值分别为0.924、0.945、0.848和0.909,P<0.01);与Kep值间均无显著相关性(r值分别为0.022、0.162、0.219和0.042,P>0.01)。结论:兔VX2骨肿瘤模型的血流灌注空间分布具有异质性;基于Reference模型的DCE-MRI定量参数Ktrans可以评价恩度对兔VX2骨肿瘤抗血管生成的疗效。

重组人血管内皮抑制素胸腔灌注治疗对非小细胞肺癌恶性胸腔积液患者的效果

目的分析不同剂量重组人血管内皮抑制素(恩度)胸腔灌注治疗对非小细胞肺癌(non-small cell lung cancer,NSCLC)恶性胸腔积液患者的疗效与安全性。方法选取150例NSCLC恶性胸腔积液患者作为研究对象,分为3组,各50例。3组均给予恩度胸腔灌注治疗:低剂量组30 mg,中剂量组60 mg,高剂量组90 mg。对比3组的疗效、肿瘤标志物[细胞角蛋白片段21-1(cytokeratin fragment 21-1,CYFRA21-1)、癌胚抗原(carcinoembryonic antige,CEA)、癌抗原125(cancer antigen 125,CA125)、癌抗原19-9(cancer antigen 19-9,CA19-9)]变化以及安全性。结果治疗后,中、高剂量组的总有效率高于低剂量组(P<0.05),中、高剂量组总有效率比较差异无统计学意义(P>0.05);3组CYFRA21-1、CEA、CA19-9水平均降低(P<0.05),低剂量组CEA、CA125、CA19-9水平高于中、高剂量组(P<0.05);3组并发症总发生率比较差异无统计学意义(P>0.05)。结论恩度60 mg与90 mg进行胸腔灌注治疗均可提高NSCLC恶性胸腔积液患者的疗效,还有助于积极控制肿瘤标志物水平,且随恩度用药剂量的增加其用药风险并未升高。

重组人血管内皮抑制素联合顺铂心包灌注治疗非小细胞肺癌恶性心包积液疗效观察

目的研究重组人血管内皮抑制素联合顺铂行心包内灌注治疗非小细胞肺癌的疗效。方法选取非小细胞肺癌伴恶性心包积液患者77例,随机分为3组重组人血管内皮抑制素(恩度)组(n=26)、顺铂组(n=24)、恩度+顺铂组(n=27),3组患者均行心包穿刺并留置中心静脉导管于心包腔内,按分组分别向心包内灌注重组人血管内皮抑制素(恩度)单药、顺铂单药及重组人血管内皮抑制素(恩度)+顺铂。观察3组疗效及不良反应发生情况。结果恩度组、顺铂组、恩度+顺铂组治疗非小细胞肺癌引起的恶性心包积液,组间差异均有统计学意义(P<0.05);有效率依次升高,且恩度组、恩度+顺铂组不良反应发生率均低于顺铂组(P<0.05),而恩度组与恩度+顺铂组比较,差异无统计学意义(P>0.05)。结论恩度联合顺铂心包灌注非小细胞肺癌恶性心包积液疗效好,且不良反应发生率低。

Endostar对肿瘤血管内皮细胞生长及功能的抑制作用

目的探讨Endostar对肿瘤血管内皮细胞生长和功能的抑制作用及其相关的抗血管形成机制。方法采用A549细胞上清诱导人脐静脉内皮细胞(human umbilical vein endothelial cells,HUVEC)成为肿瘤血管内皮细胞(tumor-derived endothelial cells,Td-EC),通过MTT法、细胞迁徙试验、流式细胞术、TUNEL法等检测Endostar对Td-EC细胞生物学特性的影响。结果Endostar在体外对于Td-EC有显著的生长抑制作用,并具有时间和浓度依赖性,但对于HUVEC的生长抑制作用并不显著;一定浓度的Endostar能显著降低Td-EC细胞迁徙活性,促使细胞凋亡数目增加、细胞形态学发生改变,并能显著增加Td-ECS期细胞比例(P<0.01),而同样条件下,Endostar影响细胞迁徙活性及促进细胞凋亡的作用对于HUVEC并不显著(P>0.05)。结论Endostar可以特异性地抑制肿瘤血管内皮细胞的生长及功能。

Endostar体外稳定性研究

目的:比较重组人内皮抑素恩度TM(EndostarTM)和毕赤酵母表达的内皮抑素(endostatin)在不同温度及不同pH条件下的稳定性,通过检测对内皮细胞的增殖抑制比较Endostar在4℃和37℃下的生物活性。方法:将Endostar和endostatin于4℃保存或37℃放置96 h后进行不同条件的聚丙烯酰胺凝胶电泳,比较Endostar和endostatin之间以及它们在不同温度放置后的电泳行为,采用兔源多克隆抗体进行Western blot验证。同时检测在两种温度下的Endostar对于人脐静脉内皮细胞HUVEC细胞增殖的抑制作用。结果:在还原性电泳中Endostar和endostatin在20 kD左右处均只出现一条带。在3种酸性非还原电泳条件下,endostatin出现明显的"smear"现象,无法观察到主要条带,Endostar在酸性不连续非还原电泳条件下只出现一条带,而在两种连续非还原电泳中虽然也出现"smear"现象,但是主要条带仍然存在,Endostar和en-dostatin在37℃放置96 h后与它们保存在4℃的样品相比,在各种电泳条件下有相似的电泳行为,Western blot验证了相应电泳的结果。在两种温度下的Endostar对于HUVEC的增殖抑制作用基本相同。结论:Endostar和endostatin具有相似的热稳定性,但在酸性条件下Endostar较endostatin更为稳定。

Effect of endostar combined with cisplatin on expression of VEGF and Sema3A of Lewis lung cancer rats

Objective:To evaluate the therapeutic effect of endostar(ED) combined with cisplatin(DDP) on model of C57BL/6 rats,and to further investigate the inhibiting mechanism of endostar from tumor angiogenesis.Methods:Lewis lung cancer cells were inoculated in C57BL/6 mouse,then the mouse were randomized into control group(group A),ED(group B),DDP(group C) and ED/DDP (group D).They were treated according to the plan.And the expressions of VEGF and Sema3A were evaluated by immunhistochemisty.Results:The weight of tumor increased in group A and B.It was decreased in group C and D.The tumor volume was increased in all the 4 groups. The VEGF expression of group D was obviously lower than the other group 3,but the Sema3A expressed of group D was significantly strengthener than the other group 3.The VEGF expression of group B and group D were obviously low especially in the 4th-8th days.Pearson correlated analysis showed that the expression VEGF and Sema3A were negatively correlated(r=-0.72, P【0.05).Conclusions:ED combined with DDP could control the tumor growth effectively,and avoid weight loss.ED could reduce VEGF expression,and enhance Sema3A expression.Tumor vessel presents transient normalization.It is easy for DDP perfusion,and to kill tumor cells.

Inhibitory Effect of Endostar in Combination with Radiotherapy in a Mouse Model of Human CNE2 Nasopharyngeal Carcinoma

The inhibitory effects of Endostar in combination with radiotherapy in BALB/c nude mice model of human CNE2 nasopharyngeal carcinoma and the mechanism were investigated.In nude mice model of CNE2 nasopharyngeal carcinoma,the inhibitory rate and the sensitizing enhancement ratio（E/O） were calculated according to the tumor volumes in different groups.The expression of microvascular density（MVD） in tumor tissues was examined by using immunohistochemistry staining.The transcription of VEGF gene was detected by using RT-PCR.The inhibitory rate in Endostar＋radiotherapy group was higher than in other groups.In Endostar＋radiotherapy group,the tumor volume was significantly decreased and the E/O ratio was 2.335,suggesting that Endostar could be a radiosensitizer.The expression of MVD of tumor tissues in Endostar＋radiotherapy group was reduced significantly.The expression of the MVD in treatment groups was significantly different from that in control group（P〈0.05）.Compared to other groups,VEGF mRNA expression in Endostar＋radiotherapy group was decreased remarkably.Endostar in combination with radiotherapy significantly inhibited the growth of CNE2 tumor.The combination therapy decreased the expression of VEGF,and inhibited tumor angiogenesis and proliferation.When combined with radiotherapy,Endostar acted as a radiosensitizer.

Perioperative rh-endostatin with chemotherapy improves the survival of conventional osteosarcoma patients: a prospective non-randomized controlled study

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 osteosarcoma.Methods: 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 years.The 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 months.Results: 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 groups.Conclusions: The addition of perioperative rh-endostatin to chemotherapy could significantly improve the DMFS and OS of patients with non-metastatic osteosarcoma.

小剂量VCR联合Endostar抑制PLA-802细胞系VEGF表达

目的探讨小剂量长春新碱(VCR)联合恩度(Endostar,Endo)对横纹肌肉瘤细胞生长的影响及其机制。方法体外培养PLA-802细胞系,用小剂量Endo、VCR单独或联合处理细胞。用MTT和流式细胞仪检测细胞的生长和细胞周期;用RT-PCR和Western blot检测药物处理后细胞内VEGFmRNA和蛋白水平;用ELISA检测上清液中VEGF水平。结果单独应用VCR(0.5和2.0μg/mL)和单独应用Endo(2.0μg/mL)均能够抑制PLA-802细胞的增殖,并促进细胞的凋亡,抑制细胞内VEGF的表达和生成。而两者联合应用时,上述作用得到明显增强。结论小剂量VCR与Endo联合应用协同抑制PLA-802细胞中VEGF的生成和表达,诱导细胞凋亡。

Comparison of intra-pleural injection efficacy between Endostar and Bevacizumab combined with pemetrexed/cisplatin for the treatment of malignant pleural effusion in patients with epidermal growth factor receptor-/anaplastic lymphoma kinase-lung adenocarci

Objective To compare intra-pleural injection efficacy and safety between Endostar and bevacizumab combined with pemetrexed/cisplatin for the treatment of malignant pleural effusion in patients with epidermal growth factor receptor(EGFR)-/anaplastic lymphoma kinase(ALK)-lung adenocarcinoma. Methods Sixty-four pCVatients with EGFR-/ALK-lung adenocarcinoma with malignant pleural effusion(MPE) were admitted to the authors' hospital between January 2016 and June 2017. Patients were randomly divided into two groups: Endostar combined with pemetrexed/cisplatin(Endostar group); and bevacizumab plus pemetrexed/cisplatin(Bevacizumab group). They underwent thoracic puncture and catheterization, and MPE was drained as much as possible. Both groups were treated with pemetrexed 500 mg/m^2, intravenous drip(d1), cisplatin 37.5 mg/m^2 per time, intra-pleural injection(d1, d3). Patients in the Endostar group were treated with Endostar 30 mg per time, intra-pleural injection(d1, 3), and patients in the Bevacizumab group were treated with bevacizumab 5 mg/kg per time, intra-pleural injection(d1). Only one cycle of treatment was applied. MPE was extracted before treatment and on day 7 after treatment. The levels of vascular endothelial growth factor(VEGF) were determined using ELISA. Efficacy and side effects were evaluated according to the Response Evaluation Criteria in Solid Tumors(RECIST) version 1.1, and National Cancer Institute Common Terminology Criteria for Adverse Events(CTCAE) version 3.0 criteria. Results The objective response rates in the Endostar and Bevacizumab groups were 50.0% and 56.3%, respectively; there was no statistical difference between the groups(P > 0.05). After one cycle of treatment, the mean VEGF levels in MPE in both groups decreased significantly, and there was no significant difference in the degree of decline between the two groups(P > 0.05). In both groups, pre-treatment VEGF levels for patients achieving complete response were significantly higher than those for patients achieving stable disease + progressive disease(P < 0.05). No specific side effects were recorded. Conclusion Endostar and Bevacizumab demonstrated similar efficacy in controlling MPE in patients with EGFR-/ALK-lung adenocarcinoma through an anti-angiogenesis pathway, with tolerable side effects. The levels of VEGF in MPE could predict the efficacy of intra-pleural injection of anti-angiogenesis drugs.

Effect of Endostar combined with Paclitaxel on the proliferation and migration of metalloproteinases and tumor cells in NSCLC patients

Objective: To explore the effect of endostar combined with taxol on tumor markers, vascular endothelial growth factor, neuron-specific enolase, metalloproteinase and tumor cell proliferation and migration in NSCLC patients. Methods Patients with advanced NSCLC were studied. The patients in the control group received chemotherapy with paclitaxel combined with cisplatin. Patients in the combination group received intravenous infusion of endostar on the basis of treatment of patients in the control group. 21 days was a cycle, and all patients were treated for 2 cycles. Fasting venous blood 3mL of all patients before and after treatment was collected, and CEA and saccharide antigen (CA50) were detected by radioimmunoassay. Vascular endothelial growth factor (VEGF), neuron-specific enolase (NSE), serum matrix metalloproteinase (MMP-2, MMP-9), high-mobility family protein at-hook 2 (HMGA 2) and high-mobility family protein B 1 (HMGB 1) were detected by ELISA. Results There were no significant differences in serum CA50, CEA, VEGF, NSE, mmp-2, mmp-9, HMGB 1, and HMGA 2 between the two groups before treatment (P>0.05). After two courses of chemotherapy, CA50, CEA, VEGF, NSE, MMP-2, MMP-9, HMGB 1, and HMGA 2 in the combination group and control group were significantly lower than before treatment (P<0.05), and the combination group was significantly lower than the control group (P<0.05). Conclusion Endostar combined with paclitaxel can enhance the chemotherapy effect of NSCLC patients, reduce the level of serum tumor markers, neuronal specific enolase and vascular endothelial growth factor, and inhibit the proliferation and migration of tumor cells.

Safety and efficacy of multi-kinase inhibitor plus endostar treatment in patients with metastatic renal cell carcinoma and pleural effusion

Objective The aim of this study was to evaluate the safety and efficacy of multi-kinase inhibitor plus endostar treatment in patients with metastatic renal cell carcinoma(m RCC) and pleural effusion. Methods A total of 10 patients with m RCC(8 clear-cell RCCs, 1 papillary RCC, 1 chromophobe RCC) with pleural effusion from January 2014 to October 2015 were recruited. Four patients received sorafenib(400 mg, twice daily), while six received sunitinib(50 mg, once daily; 2 weeks on and 1 week off). All patients received multi-kinase inhibitor plus pleural cavity perfusion of endostar(15 mg on days 1–4 for 1 or 2 weeks). Results The response rate of pleural effusion was 70%. Adverse reactions were limited and mild.Conclusion The regimen of multi-kinase inhibitor plus pleural cavity perfusion of endostar was both effective and safe for the treatment of patients with m RCC with pleural effusion, and may control local symptoms.

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

Objective To analyze the efficacy and safety of Rh-endostatin combined with chemotherapy in the treatment of metastatic colorectal cancer.Methods 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 scheme.Results The response rates were 53.3% in test group and 36.7% in control group respectively(P < 0.05), the disease control rate were 83.3% and 73.3%(P < 0.05). The median progression-free survival in test group and control group were 7.3 months versus 5.3 months(P < 0.05) and median overall survival were 11.6 months versus 9.3 months(P < 0.05). Among 27 cases of liver metastases were sub group analysis, difference on the test group and the control group response rate(RR) and disease control rate(DCR) had statistical significance(P < 0.05), but difference on progression free survival(PFS) and overall survival(OS) had no statistical significance(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.

Study on the Clinical Efficacy and Safety of Endostar Combined with Pemetrexed and Cisplatin in the Treatment of Lung Adenocarcinoma

Objective:To analyze and study the efficacy and safety of Endu combined with pemetrexed and cisplatin in the clinical treatment of lung adenocarcinoma.Methods:From August 2016 to September 2020,32 patients with lung adenocarcinoma who were treated in our hospital were selected for group trials.According to their specific treatment plan,the patients were divided into control group and experimental group,with 16 cases in each group.The control group was treated with pemetrexed and cisplatin,and the experimental group was treated with Endostar combined with the treatment received by the control group.The clinical efficacy and safety of the two regimens were assessed by comparing the changes in symptoms and the incidence of adverse reactions between the two groups of patients after treatment.Results:The disease control rate of the experimental group was significantly higher than that of the control group,and there was no significant difference in the incidence of adverse reactions between the two groups.Conclusions:From the experimental results,we found that the treatment of patients with lung adenocarcinoma by Endostar combined with pemetrexed and cisplatin can effectively improve the treatment efficacy without increasing adverse reactions and therefore relevant chemotherapy regimens can be considered for wider clinical applications.

局部晚期宫颈癌患者采用恩度配合同步放化疗治疗的效果及对血清指标的影响

目的探析恩度配合同步放化疗治疗局部晚期宫颈癌的价值。方法选取2017年2月至2018年2月河北省人民医院收治的局部晚期宫颈癌患者58例为研究对象,依据随机数表法分为对照组和观察组,每组各29例。对照组仅采用同步放化疗治疗,观察组加用恩度配合治疗。比较两组治疗有效率、血清指标水平、生存率、不良反应及生活质量评分。结果观察组患者的治疗有效率高于对照组,差异有统计学意义(P<0.05);观察组患者的血清血管内皮生长因子(VEGF)、鳞状细胞癌相关抗原(SCCA)、血清细胞角蛋白19片段抗原21-1(CYFRA21-1)水平低于对照组,差异有统计学意义(P<0.05);观察组患者的生存率高于对照组,差异有统计学意义(P<0.05);两组患者不良反应发生率比较,差异无统计学意义(P>0.05);观察组治疗后患者癌症治疗功能总体评价量表(FACT-G)评分高于对照组,差异有统计学意义(P<0.05)。结论局部晚期宫颈癌患者采用恩度配合同步放化疗效果较好,患者血清指标趋于正常水平,治疗后3、5年生存率较高,其生活质量显著提升,患者的整体预后结局得到改善,临床上可借鉴及推广。

恩度联合顺铂胸腔灌注治疗肺癌合并恶性胸腔积液疗效的meta分析

目的系统评价恩度联合顺铂胸腔灌注治疗肺癌合并恶性胸腔积液的有效性和安全性。方法计算机检索中国知网、万方数据库、维普数据库、中国生物医学文献数据库、Pubmed、The Cochrane Library、Web of Science、Proquest和Embase,筛选出有关恩度联合顺铂胸腔内灌注治疗肺癌合并恶性胸腔积液随机对照试验,通过RevMan 5.3软件进行meta分析,计算相对危险度(RR)及95%可信区间(CI),采用Stata 15.0软件进行Egger检验。结果共纳入12项随机对照研究,共728例患者。对照组为单顺铂药物治疗共363例,试验组为恩度联合顺铂治疗共365例。Meta分析显示,与对照组相比,试验组的总有效率[RR=1.62,95%CI(1.45~1.81);Z=8.48,P<0.05]和生活质量改善率[RR=1.68,95%CI(1.44~1.96);Z=6.60,P<0.05]均高于对照组,但两组在主要不良反应如:白细胞减少、血小板减少、恶性呕吐方面比较,差异无统计学意义(P>0.05)。结论恩度联合顺铂胸腔内灌注治疗肺癌合并恶性胸腔积液的效果优于顺铂单药组,联合治疗对比顺铂单药治疗能提高总有效率,患者的生活质量有所改善,且总体不增加不良反应发生率。

恩度联合同步放化治疗宫颈癌疗效的Meta分析

目的对恩度联合同步放化疗治疗宫颈癌的临床疗效及安全性进行系统评价。方法对中文数据库中国知网(CNKI)、万方(Wanfang)、维普(VIP)、中国生物医学文献数据库(CBM)及英文数据库PubMed、Cochrane图书馆、Embase进行检索,收集并筛选2005年1月1日~2021年10月19日期间关于恩度联合同步放化疗治疗宫颈癌的随机对照试验的相关临床研究进行Meta分析。采用RevMan 5.4软件分析患者的完全缓解(complete response,CR)、客观缓解率(objective response rate,ORR)、疾病控制率(disease control rate,DCR)以及不良反应发生率。结果最终纳入7篇研究,共498例患者。Meta分析结果显示,恩度联合同步放化疗可以提高宫颈癌患者的CR(OR=2.45,95%CI:1.59~3.77,P<0.0001)、ORR(OR=3.29,95%CI:1.90~5.70,P<0.0001)和DCR(OR=3.04,95%CI:1.51~6.15,P=0.002),且在各不良反应如白细胞计数减少(OR=0.77,95%CI:0.42~1.40,P=0.39)、血小板计数下降(OR=0.76,95%CI:0.40~1.46,P=0.42)、腹泻(OR=0.71,95%CI:0.42~1.20,P=0.20)、泌尿生殖系统不良反应(OR=0.72,95%CI:0.34~1.49,P=0.37)等的发生率与单纯同步放化疗比较,差异均无统计学意义。结论与单纯同步放化疗比较,恩度联合同步放化疗可显著改善宫颈癌患者的CR、ORR和DCR,且两种方法的主要不良反应事件发生率相似。

恩度抑制大鼠肝纤维化与肝癌的机制研究

目的探究恩度抑制大鼠肝纤维化与肝癌的机制。方法将90只SD雄性大鼠随机分为正常组(注射9 g/L生理盐水)、模型组[10 mg/kg腹腔注射0.2%二乙基亚硝胺(DEN),5次/周,16周]和恩度组[模型组+20 mg/(kg·d)恩度,4周],每组均30只。每隔4周处死5只,至20周时应用苏木精-伊红染色观察肝组织病理变化,酶联免疫吸附法与比色法测定血清肝功能、肝纤维化水平,聚合酶链式反应及蛋白印迹法测定肝组织转化生长因子-β(TGF-β)/转化生长因子-β受体(TβR)/Smad2/3信号通路m RNA及蛋白。结果恩度组大鼠的肝脏纤维化分级、肝脏指数、结节数、瘤重分别为2.60±0.55、(3.97±0.5)%、(7.43±1.82)个、(1.52±0.39)g,明显低于模型组的4.00±0.71、(5.19±0.72)%、(10.82±2.67)个、(2.95±0.33)g,差异均有统计学意义(P<0.05);恩度组大鼠抑瘤率为(18.26±3.86)%;恩度组与模型组大鼠肝脏指数分别为(3.97±0.5)%、(5.19±0.72)%,明显高于正常组的(1.56±0.29)%,差异均有统计学意义(P<0.05);恩度组大鼠的ALT、AST、TBI分别为(64.85±7.12)U/L、(109.58±11.36)U/L、(7.59±1.39)μmol/g,明显低于模型组的(88.54±9.87)U/L、(176.24±18.6)U/L、(11.14±1.26)μmol/g,ALB为(38.52±4.06)g/L,明显高于模型组的(22.74±2.39)g/L,差异均有统计学意义(P<0.05);恩度组大鼠羟脯氨酸、碱性磷酸酶分别为(4.26±0.51)μg/g、(5.32±0.61)k U/L,明显低于模型组的(6.85±0.74)μg/g、(6.76±0.68)k U/L,差异均有统计学意义(P<0.05);恩度组大鼠的TGF-β1、TβRⅠ、TβRⅡ、Smad2/3分别为2.32±0.31、1.74±0.19、1.71±0.20、1.76±0.18,明显低于模型组的3.35±0.42、2.86±0.47、2.92±0.36、2.24±0.34,差异均有统计学意义(P<0.05)。结论恩度可以有效抑制DEN导致大鼠“肝纤维化-肝癌”进程,这一抑制作用可能与TGF-β/TβR/Smad2/3信号通路激活有关。

恩度与化疗联合治疗多种晚期恶性肿瘤的临床观察

目的:前瞻性观察抗肿瘤新药重组人血管内皮抑素注射液(YH-16,恩度)联合化疗治疗多种晚期恶性肿瘤的有效性和安全性。方法:经病理组织学或细胞学检查确诊的Ⅳ期恶性肿瘤患者36例,其中非小细胞肺癌(NSCLC)9例,其他肿瘤27例(大肠癌7例,头颈部鳞癌5例,小细胞肺癌、食管癌、肾癌、胰腺癌和胆管癌各2例,肾盂癌、原发性肝癌、卵巢癌、纵隔卵黄囊瘤和腹膜转移性腺癌各1例),接受恩度联合化疗的方案治疗。其中恩度15mg,加入生理盐水500ml中匀速缓慢静脉滴注,第1～14天连续给药,间歇7天重复;同时联合既往未使用的或与既往治疗无交叉耐药的化疗药物。每21天为1个周期。按照RECIST标准评价近期疗效,参照Karnofsky评分(KPS)变化评价生活质量(QOL),按照NCICTC3.0版标准评价毒性反应。用药1周期即可评价毒性,2周期后方可评价疗效。结果:全组36例患者中,有30例患者可以评价客观疗效,36例均可进行安全性评价。总共完成的周期数为83个周期,平均2.3个周期。30例可评价病例中,获得PR4例,SD17例,PD9例,即客观有效率(RR)为13.3%(4/30),疾病控制率(DCR)为70.0%(21/30);而生活质量改善者有11例(36.7%),稳定者13例(43.3%),仅6例(20.0%)下降。G3/4级毒性主要与化疗药物有关,包括1例(2.7%)白细胞下降、3例(8.3%)血小板下降、1例(2.7%)恶心/呕吐以及1例(2.7%)腹泻。结论:恩度与化疗药物联合使用可以改善和稳定多种晚期恶性肿瘤患者的生活质量,与部分化疗药物具有协同作用,其毒性低,安全性好,值得临床上推广应用和进一步深入观察。