Study progression of recombinant human endostatin (Endostar) for the treatment of malignant serous effusion

Since recombinant human endostatin (rh-endostatin;Endostar) has been listed 5 years,clinicians have combined it with chemotherapy for the treatment of lung cancers and other malignant tumors,and proved its effect and safety.A number of scholars have explored the application of Endostar alone or in combination with chemotherapy for treatment of malignant serous effusion,finding its high efficiency and low toxicity;and that hydrops controlling is stronger,and that it can significantly improve patients' quality of life.It is worthy of conducting prospective,randomized and multi-center clinical studies and basic researches to clarify the mechanism.

Antitumor effect of recombinant human endostatin combined with cisplatin on rats with 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.

Effect of recombinant human endostatin onradiotherapy for esophagus cancer

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.

Epidermal growth factor receptor antibody plus recombinant human endostatin in treatment of hepatic metastases after remnant gastric cancer resection

We report a 55-year-old male who developed advanced hepatic metastasis and peritoneal carcinomatosis after resection of remnant gastric cancer resection 3 mo ago. The patient only received epidermal growth factor (EGF) receptor antibody (Cetuximab) plus recombinant human endostatin (Endostar). Anti-tumor activity was assessed by 18F-fluorodeoxyglucose (18F-FDG) positron emission tomography/computer tomography (PET/CT) at baseline and then every 4 wk. The case illustrates that 18FDG-PET/CT could make an early prediction of the response to Cetuximab plus Endostar in such clinical situations. 18FDG-PET/CT is a useful molecular imaging modality to evaluate the biological response advanced hepatic metastasis and peritoneal carcinomatosis to Cetuximab plus Endostar in patients after remnant gastric cancer resection.

117 cases of advanced malignancies treated with recombinant human endostatin plus chemotherapy

Objective: The aim of this study was to evaluate the recent efficacy and adverse reactions of recombinant human endostatin (Endostar) plus chemotherapy in the treatment of advanced malignancies. Methods: One hundred and seventeen cases of advanced malignancies were diagnosed and confirmed by histopathological examination, patients were treated with Endostar combined with chemotherapeutic drugs with no cross-resistance. Evaluate the efficacy and adverse reactions after finished two cycles of combination therapy. Results: All the 117 cases of patients were evaluated according to relevant standards, and there were 12 cases of complete remission (CR), 30 cases of partial remission (PR), 58 cases of stable disease (SD), 17 cases of progressive disease (PD). The response rate (RR) was 35.8%, disease control rate (DCR) was 85.4%. Conclusion: The protocol of Endostar combined with chemotherapy could improve the quality of life of patients with malignances, it also has the advantage of low toxicity. Considering the time span of the study, the long-term efficacy remains to be observed.

Continuous intravenous infusion of recombinant human endostatin using infusion pump plus chemotherapy in non-small cell lung cancer

BACKGROUND Lung cancer is one of the deadliest cancers in the world with the highest incidence and mortality rate among all cancers.Non-small cell lung cancer(NSCLC)accounts for approximately 80%of primary lung cancer.However,efficacy and safety of the current regimens for NSCLC is unsatisfactory.Therefore,there has been an increasing urgency for development of potential therapeutic therapies for NSCLC.AIM To investigate the therapeutic outcomes and safety of continuous intravenous infusion of recombinant human endostatin(Rh-endostain)using an infusion pump in retreated advanced NSCLC.METHODS Patients with retreated advanced NSCLC who were admitted to Zhejiang Provincial People's Hospital from October 2017 to April 2019 were recruited.These patients received continuous intravenous infusion of Rh-endostain using an infusion pump.Objective response rate(ORR),clinical benefit rate(CBR),median progression-free survival(mPFS),and incidences of adverse events(AEs)were analyzed after treatment.RESULTS A total of 45 patients with retreated advanced NSCLC were included,and all of them were evaluated.In these patients,ORR was 22.2%,CBR was 84.4%,and mPFS was 5.3 mo.The following AEs were observed,decreased hemoglobin(34 cases,75.6%),nausea/vomiting(32 cases,71.1%),elevated transaminase(24 cases,53.3%),leukopenia(16 cases,35.6%),thrombocytopenia(14 cases,31.1%),and constipation(1 case,3.4%).None of the patients had leukopenia,nausea/vomiting,and constipation of grade III and above.CONCLUSION The patients showed improved adherence to 5-d continuous intravenous infusion of Rh-endostain using an infusion pump.Favorable efficacy and safety of this treatment regimen were achieved in retreated advanced NSCLC.

Clinical Study of Recombinant Human Endostatin Combined with Iressa in Targeted Treatment of Patients with Lung Adenocarcinoma with Pleural Metastasis

Objective:To evaluate and comprehensively analyze the clinical efficacy of recombinant human endostatin combined with Iressa targeted therapy in patients with pleural metastasis of lung adenocarcinoma.Methods:The interval of the selected study period span was from January 2017 to April 2021.The sample source of the study was 42 patients with lung adenocarcinoma admitted to hospital.The random number table method was used for study grouping,and they were further divided into study groups(n=21,14 cases with pleural metastasis)and control group(n=21,13 cases with pleural metastasis),all patients received systemic chemotherapy with pemetrexed and cisplatin.Patients with pleural metastases in the control group were injected with 60 mg cisplatin into the thoracic cavity.Patients in the study group were treated with Iressa(gefitinib)targeted therapy if genetic testing showed epidermal growth factor receptor(EGRF)mutations,and patients with pleural metastases were treated with pleural metastasis with Endo(recombinant human endostatin YH-16)to control pleural effusion.Two sets of related indicators were compared and analyzed.Results:Comparing the short-term disease control rate,treatment effectiveness and long-term survival rate between the two groups shows that the study group has more advantages(P<0.05).In the comparison between the two groups of serum markers and related indicators,the study group has more advantages(P<0.05),whereas in the comparison between the two groups in the incidence of adverse reactions,there is no significant difference(P>0.05).Based on statistics of the recurrence rate of pleural fluid in the two groups,the study group is significantly lower than the control group(P<0.05).Conclusion:Recombinant human endostatin combined with Iressa targeted therapy for patients with lung adenocarcinoma with pleural metastasis has significant short-term and long-term effects without serious adverse reactions.It can be fully promoted in medical institutions at all levels.

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. Methods： Lung adenocarcinoma cell line A549 and its DDP-resistant cell line A549/DDP were treated with DDP and/or recombinant human Endostatin. Difference in drug resistance was analyzed between different regi- mens and between different cell lines after a 72 h-treatment in vitro. And below the non-cytotoxic concentration of rh-End- ostatin, the possibility of rh-Endostatin in reversing DDP-resistance in A549/DDP was evaluated. The resistance protein which was detected in the study included P glycoprotein （P-gp） and topoisomerase II （Topo-II）. Results： Rh-Endostatin below 400 IJg/mL showed no cytotoxicity in either A549 or A549/DDP after 72 h-treatment with it. The inhibited concentration of 50% （IC50） observed for DDP was （0.79 _＋ 0.05） IJg/mL in A549 and （13.2 ＋ 1.1） in A549/DDP respectively. IC50 was reduced to 2.57 ＋ 0.05 #g/mL in A549/DDP treated by rh-Endostatin below the non-cytotoxic concentrations in combination with DDP, with a reversal fold （RF） of 5.14 and a relative reversal rate of 85.6%. Apoptotic rates were 2.01%, 13.47% and 29.26% re- spectively for cells treated with rh-Endostain, DDP, and the combination. The rate of the A549/DDP control group was 0.99%. The expression level of P-gp or Topo-II was higher in A549/DDP cells than in A549 cells. Rh-Endostatin may partially reverse DDP-resistance in A549/DDP cells in vitro, with a probable mechanism related to lowering expression of P-gp and Topo-II. Conclusien： Rh-Endostatin of non-cytotoxic dose partially reversed cisptatin resistance in cisplatin-resistant human lung adenocarcinoma cell line A549/DDP. Rh-Endostatin reversed the resistance of A549/DDP cells to DDP, which may be related to decreased protein expression of P-gp and Topo-II in A549/DDP cells.

Recombinant human vascular endostatin injection to synchronize craniospinal radiotherapy for the treatment of recurrent medulloblastoma in children:A retrospective clinical study

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.

Effect of continuous recombinant human endostatin pumping combined with TP chemotherapy on serum malignant molecules and angiogenesis molecules in patients with advanced ovarian cancer

Objective:To study the effect of continuous recombinant human endostatin pumping combined with TP chemotherapy on serum malignant molecules and angiogenesis molecules in patients with advanced ovarian cancer.Methods:78 patients with advanced ovarian cancer who were treated in our hospital between July 2011 and December 2015 were selected and divided into observation group and control group (n=39) according to the single-blind randomized control method. Before treatment and after 4 cycles of treatment, electrochemical luminescence immunity analyzer was used to detect serum tumor marker levels;RIA method was used to determine serum apoptosis molecule levels;enzyme-linked immunosorbent assay (ELISA) was used to detect the serum angiogenesis molecule levels.Results:Before treatment, differences in serum levels of tumor markers, apoptosis molecules and angiogenesis molecules were not statistically significant between two groups of patients (P>0.05). After 4 cycles of treatment, serum carbohydrate antigen 125 (CA125), carbohydrate antigen 153 (CA153), human epididymis protein 4 (HE4), carcinoembryonic antigen (CEA), human chorionic gonadotropin (β-HCG), Bcl-2, Survivin, Bag-1, angiogenin-2 (Ang-2), vascular endothelial growth factor (VEGF) and basic fibroblast growth factor (bFGF) levels of observation group were significantly lower than those of control group (P<0.05) while Bax level was significantly higher than that of control group (P<0.05).Conclusions:Continuous recombinant human endostatin pumping combined with TP chemotherapy can decrease the malignant degree of advanced ovarian cancer and inhibit angiogenesis.

Inhibitory effect of endostatin expressed by human liver carcinoma SMMC7721 on endothelial cell proliferation in vitro

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.

重组人血管内皮抑制素联合脑部放疗与单纯脑部放疗治疗实体肿瘤脑转移的疗效及预后

目的探究重组人血管内皮抑制素(rh-Endostatin)联合脑部放疗(WBRT)与单纯WBRT治疗实体肿瘤脑转移的疗效及预后。方法回顾性分析2020-03—2022-11于资阳市人民医院肿瘤科治疗的94例患者的临床资料,根据治疗方式分为试验组和对照组,采用WBRT治疗的46例患者纳入对照组,采用rh-Endostatin联合WBRT治疗的48例患者纳入试验组,治疗结束1个月后比较临床疗效及肿瘤标志物指标[癌胚抗原(CEA)、癌抗原(CA125)、糖类抗原(CA19-9)、血管内皮生长因子(VEGFA、VEGFB、VEGFC)]、免疫功能(CD3^(+)、CD4^(+)、CD8^(+)、CD4^(+)/CD8^(+))、脑水肿体积和脑血流动力学参数(大脑前动脉平均血流速度和搏动指数)、生存质量[欧洲癌症研究治疗组织生命质量测定量表(EORTCQLQ)]、神经认知水平[简易精神状态量表(MMSE)],比较2组患者治疗期间放射性损伤,通过制作生存曲线分析患者预后情况。结果试验组患者治疗结束1个月时临床总有效率高于对照组(47.92%比26.09%),差异有统计学意义(P<0.05);2组患者治疗结束1个月时肿瘤标志物CEA、CA125、CA19-9、VEGFA、VEGFB、VEGFC水平,CD3^(+)、CD4^(+)、CD4^(+)/CD8^(+)水平,脑水肿体积、搏动指数均较治疗前显著降低(P<0.05),试验组患者肿瘤标志物水平和脑水肿体积显著低于对照组患者(18.76±2.54比20.78±3.12,26.78±4.98比33.12±5.19,31.34±3.12比37.24±3.98,90.76±16.97比121.78±18.12,83.78±11.02比105.23±12.19,65.34±9.12比83.23±10.98,144.58±71.55比203.87±70.59),CD3^(+)、CD4^(+)、CD4^(+)/CD8^(+)水平显著升高(59.67±4.33比55.41±4.02,31.22±3.34比27.74±3.79,1.17±0.22比0.96±0.15),差异均有统计学意义(P<0.05);2组患者CD8^(+)水平、大脑前动脉平均血流速度、EORTC各维度评分和MMSE评分相较治疗前均明显升高(P<0.05),试验组患者CD8^(+)水平明显低于对照组(27.02±3.08比28.92±3.31),大脑前动脉平均血流速度(56.67±3.33比55.01±2.06)、EORTC各维度评分和MMSE评分(26.58±1.11比25.87±1.17)明显高于对照组,差异均有统计学意义(P<0.05);2组患者治疗期间均发生轻微放射性损伤,差异无统计学意义(P>0.05);治疗后试验组患者中位总生存期(OS)和颅内疾病无进展期(iPFS)均明显长于对照组患者(9.5比7.5,8.0比6.0),差异有统计学意义(P<0.05)。结论rh-Endostatin联合WBRT治疗实体肿瘤脑转移患者可有效改善近期疗效,抑制肿瘤进展,改善脑血流,维持认知功能及生存质量,保护免疫功能。该方案安全性良好,可一定程度上延长患者的OS和iPFS。

重组人血管内皮抑制素联合奥希替尼治疗晚期非小细胞肺癌的疗效及预后分析

目的:分析重组人血管内皮抑制素联合奥希替尼对晚期非小细胞肺癌(non-small cell lung cancer, NSCLC)患者疗效及预后的影响。方法:选择2020年06月至2022年02月医院就诊的晚期NSCLC患者92例,采用随机数字表法将其分成对照组与研究组,各46例。对照组接受奥希替尼治疗,研究组在对照组的基础上接受重组人血管内皮抑制素治疗。21 d为1个周期,2组均治疗3个周期评估效果。对比2组临床疗效、健康状况、生活质量、肿瘤标志物、肿瘤相关蛋白因子及不良反应,随访1年,记录2组无进展生存期(PFS)。结果:研究组客观缓解率(50.00%)高于对照组(26.09%)(P<0.05),研究组疾病控制率(76.09%)高于对照组(54.35%)(P<0.05)。治疗3个周期后,2组卡氏功能状态(KPS)评分、癌症治疗功能性量表(FACT-L)评分均升高(P<0.05),且研究组更高(P<0.05)。治疗3个周期后,2组血清细胞角蛋白19片段(CYFRA21-1)、鳞状细胞癌抗原(SCC)、糖类抗原50(CA50)水平均降低(P<0.05),且研究组更低(P<0.05)。治疗3个周期后,2组磷酸酶张力蛋白同源物(PTEN)相对表达量均升高(P<0.05),且研究组更高(P<0.05);治疗3个周期后,2组血黏蛋白(MUC1)相对表达量均降低(P<0.05),且研究组更低(P<0.05)。2组Ⅰ-Ⅳ级消化道反应、血小板下降、肝肾功能损伤、中性粒细胞减少不良反应总发生率比较差异无统计学意义(P>0.05)。随访1年,2组均失访1例,随访率为97.83%,研究组中位PFS为8.97(95%CI:6.13~11.35)个月,对照组中位PFS为6.53(95%CI:3.85~9.61)个月,研究组PFS曲线优于对照组(P<0.05)。结论:重组人血管内皮抑制素联合奥希替尼治疗晚期NSCLC患者疗效确切,可降低肿瘤标志物水平,改善患者生活质量,调节肿瘤相关蛋白因子表达,安全可靠,且可延长患者PFS。

腹腔热灌注联合XELOX化疗方案治疗胃癌腹腔积液的效果

目的观察腹腔热灌注重组人血管内皮抑制素注射液联合XELOX化疗方案(奥沙利铂+卡培他滨)治疗胃癌腹腔积液的临床效果。方法将2020年1月至2021年12月于医院接受XELOX化疗方案治疗的48例胃癌腹腔积液患者纳入对照组,将2022年1月至2022年12月接受腹腔热灌注重组人血管内皮抑制素注射液联合XELOX化疗方案治疗的48例胃癌腹腔积液患者纳入观察组。比较两组疗效、患者生命质量[采用卡氏功能状态量表(KPS)评估]。比较治疗前、治疗4个周期时患者免疫功能[T淋巴细胞亚群(CD3^(+)、CD4^(+)、CD4^(+)/CD8^(+))]。统计治疗期间不良反应发生情况。结果治疗4个周期时,观察组整体疗效优于对照组,治疗总有效率高于对照组(P<0.05)。治疗4个周期时,观察组生命质量改善率高于对照组(P<0.05)。治疗4个周期时,两组CD3^(+)、CD4^(+)、CD4^(+)/CD8^(+)水平均较治疗前降低,但观察组各指标水平均高于对照组(P<0.05)。治疗期间,两组不良反应发生率比较,差异无统计学意义(P>0.05)。结论在XELOX化疗方案基础上加用腹腔热灌注重组人血管内皮抑制素注射液治疗胃癌腹腔积液效果良好,可改善患者生命质量,减轻因化疗药物使用引起的免疫抑制,且不增加不良反应风险。

重组人血管内皮抑制素注射液联合GP化疗方案治疗晚期NSCLC的可行性

目的观察重组人血管内皮抑制素注射液联合GP化疗方案治疗晚期非小细胞肺癌(NSCLC)的可行性。方法回顾性选取2020年5月—2022年12月皖北煤电集团总医院肿瘤内科收治的晚期NSCLC患者80例,将采用GP化疗方案治疗者纳入GP化疗组(n=40),重组人血管内皮抑制素注射液联合GP化疗方案治疗者纳入联合用药组(n=40),2组均以3周为1个治疗周期,共治疗2个周期。比较2组患者近期疗效,用药前后实验室指标、生活质量评分,不良反应及1年存活率。结果联合用药组客观缓解率为85.00%,高于GP化疗组的52.50%(χ^(2)=9.833,P=0.002)。用药2个周期后,2组血清癌胚抗原、糖类抗原125水平低于用药前,凝血酶时间、活化部分凝血活酶时间短于用药前,凝血酶原时间长于用药前,血浆纤维蛋白原、D-二聚体水平高于用药前,且联合用药组各指标优于对照组(P<0.05或P<0.01);2组生理功能、躯体功能、精神状态、社会关系评分高于用药前,且联合用药组高于GP化疗组(P<0.01)。联合用药组与GP化疗组不良反应总发生率分别为22.50%、15.00%,组间比较差异无统计学意义(χ^(2)=0.738,P=0.390)。联合用药组1年存活率为65.00%,高于GP化疗组的42.50%(χ^(2)=4.073,P=0.044)。结论晚期NSCLC治疗中采用重组人血管内皮抑制素注射液联合化疗药物的可行性较高,可有效降低肿瘤标志物水平,延缓病情进展,提高患者生活质量及1年存活率,且具有一定安全性。

持续静脉泵注重组人血管内皮抑制素联合化疗一线治疗晚期非小细胞肺癌的随机、对照临床试验

目的探讨持续静脉泵注重组人血管内皮抑制素联合化疗一线治疗晚期非小细胞肺癌(Non-Small Cell Lung Cancer,NSCLC)的随机、对照临床试验。方法选取2019年3月—2022年9月期间雅安市人民医院接受治疗的150例晚期NSCLC患者为研究对象,根据随机数表法划分成两组,每组75例,化疗组给予常规一线化疗方案治疗,联合组在化疗组基础上加以持续静脉泵注重组人血管内皮抑制素治疗,分析两组治疗效果。结果治疗结束后,联合组的总有效率72.00高于化疗组的56.00%,差异有统计学意义(χ^(2)=4.167,P<0.05);联合组血清细胞角蛋白19片段、糖类抗原125、癌胚抗原均低于化疗组,差异有统计学意义(P均<0.05);联合组缺氧诱导因子-1α、血管内皮生长因子及血管生成素2、CD8^(+)均低于化疗组(P均<0.05);联合组CD3^(+)、CD4^(+)、CD4^(+)/CD8^(+)高于化疗组,CD8^(+)低于化疗组,差异有统计学意义(P均<0.05);两组不良反应发生率对比,差异无统计学意义(P>0.05)。结论持续静脉泵注重组人血管内皮抑制素联合化疗一线对晚期NSCLC治疗效果显著,可明显降低患者血清肿瘤标志物和血管内皮因子水平,改善机体免疫功能,以增强对体内肿瘤细胞活性的控制,进而提高临床疗效,且不增加不良反应。

放疗联合重组人血管内皮抑素治疗肺癌脑转移瘤合并脑水肿的疗效评估

目的探讨放疗联合重组人血管内皮抑素(rh-Endostatin)治疗肺癌脑转移瘤合并脑水肿的疗效。方法选取2020-05—2023-03阜阳市肿瘤医院收治的肺癌脑转移瘤合并脑水肿患者74例为研究对象,按随机数排序法分为研究组37例与对照组37例,对照组予以放疗联合传统治疗(激素、甘露醇),研究组予以放疗联合rh-Endostatin治疗,均治疗2周,比较2组患者疗效、水肿程度、癌胚抗原(CEA)水平与不良反应。结果2组患者总有效率比较差异无统计学意义(χ^(2)=1.770,P>0.05),2组患者治疗2周后脑水肿程度均较治疗前改善(Z=17.704、6.211,P<0.05),且研究组优于对照组(Z=5.681,P<0.05)。重复测量方差分析结果显示,2组患者治疗后CEA水平与治疗前相比均降低,且治疗2周后CEA水平低于治疗1周后(P<0.05),研究组治疗1周后、治疗2周后CEA水平均低于对照组(6.12±2.01比7.45±2.03,4.31±1.14比5.52±1.77,P<0.05)。2组患者均未发生贫血、出血倾向、心功能不良反应,心律失常不良反应分级、血小板减少不良反应分级、粒细胞减少不良反应分级比较差异无统计学意义(P>0.05)。结论放疗联合rh-Endostatin治疗肺癌脑转移瘤合并脑水肿具有较好疗效,可有效改善脑水肿指数,降低CEA水平,且无明显不良反应,安全性较好。

重组人血管内皮抑制素(rh-Endostatin)大肠杆菌表达体系发酵条件的优化

优化了重组人血管内皮抑制素的E.coli表达体系的发酵条件。利用E.coli表达体系得到了较高的产量,在9h左右的发酵周期内达到OD600值140,包涵体蛋白产量为3g/L。主要优化了异丙基-β-D-硫代半乳糖苷(Isopropyl-β-D-thiogalactopyranoside,IPTG)的终浓度、诱导时间、培养温度、补料控制方法等条件,并且在诱导后提高培养温度到40℃,在非常短的培养周期内达到了高密度培养的目的。利用E.coli表达,继而通过复性获得有活性的重组人血管内皮抑制素,成本低、生产过程稳定可控、得到的蛋白性质稳定,符合工业生产的需要。

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。