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1.
目的制备抗人肝癌抗体与索拉非尼偶联免疫毫微球,观察其特性及抗肝癌效果。方法通过异型双功能交联剂SPDP,将抗人肝癌单克隆抗体HAb18与索拉非尼(sorafenib,SAF)人血清白蛋白毫微球[HSA(SAF)-NS]偶联,制成抗人肝癌抗体与索拉非尼偶联免疫毫微球HAb18-HSA(SAF)-NS,使用凝集试验检测其活性,光镜和电镜下观察其与人肝癌细胞株SMMC-7721特异性结合。MTT法检测该免疫毫微球的体外杀伤性。于人肝癌裸鼠模型上分别使用HAb18-HSA(SAF)-NS、HSA(SAF)-NS及SAF,检测三者的肿瘤抑制率。结果 HAb18-HSA(SAF)-NS具有单抗活性,能与肝癌细胞特异结合;其体外杀伤SMMC-7721细胞IC 50值为42.4μg/mL,与HSA(SAF)-NS(368.9μg/mL)及SAF(377.5μg/mL)相比,明显降低;体内肿瘤抑制率比HSA(SAF)-NS及SAF显著增强(P0.001)。结论 HAb18-HSA(SAF)-NS具有免疫活性,对肝癌细胞有主动靶向性,体内外均具有比HSA(SAF)-NS及SAF更强的抗癌效果。  相似文献   

2.
抗体介导的阿霉素白蛋白免疫毫微粒的抗人肝癌作用研究   总被引:1,自引:0,他引:1  
本研究将人肝癌特异性抗体HAb18同载阿霉素 (ADR)人血清白蛋白毫微粒 (ADR HSA NP)交联构建了阿霉素白蛋白免疫毫微粒 (HAb18 ADR HSA NP) ,本文报道了该免疫毫微粒对培养细胞的特异性结合 ,杀伤作用及在裸鼠体内的分布 ,抗人肝癌作用。一、材料和方法1.主要材料 :ADR HSA NP ,本室自制 ;HAb18单抗 ,第四军医大学陈志南教授提供 ;HAb18 ADR HSA NP ,采用异型双功能交联剂SPDP将HAb18抗体同ADR HSA NP交联制备[1] ;人肝癌细胞株SMMC 772 1为本室保种传代 ;BALB/C裸…  相似文献   

3.
将抗人肝癌单克隆抗体MD的重链可变区VH和轻链可变区VL基因重组,并使其表达。采用PT-PCR技术扩增VH及VL基因,通过重叠延伸拼接PCR在VH和VL基因间引入连接短肽,体外构建MDscFV基因,经过常规转化与筛选,诱导表达蛋白。MDscFV基因全长为732bp,VH354bp位于上游VL330bp位于下游。重组蛋白相对分子量36kDa。scFV保留了与亲本抗体MD相似的免疫活性。成功地构建了抗人单链抗体MDscFV,并获得了较高水平的功能性表达。  相似文献   

4.
目的 制备长效紫杉醇聚乳酸-羟基乙酸共聚物(PLGA)微球,对微球的常规理化特性、体外释放特性进行考察并对该微球的抗肝癌疗效进行鼠体内评估.方法 采用单乳溶剂挥发法制备紫杉醇PLGA微球成功后利用激光粒度分析仪测定其平均粒径,利用扫描电镜观测微球表面形貌,对3批微球样品进行载药量及体外释放检测,构建小鼠H22肝癌模型,以瘤内方式给药,给药15 d后观测肿瘤病理切片,评估疗效.结果 微球表观平整,形态圆滑,平均粒径为36.4 μm,3批样品平均载药量为7.42%,可维持30 d左右的体外释放,体内实验显示微球具备良好抗H22型肝癌疗效.结论 所制备的紫杉醇PLGA缓释微球具备良好的理化特性、体外释放特点并具备良好的抗肿瘤疗效.  相似文献   

5.
6.
目的 研究粉尘螨变应原明胶微球经口服免疫小白鼠后的脱敏疗效。 方法 以粉尘螨变应原明胶微球 (含粉尘螨变应原 2× 10 -5mg )口服免疫小白鼠 ,以ELISA法检测 3 5d内血清特异性IgG水平变化。并以腹腔注射相同剂量的粉尘螨变应原浸液的小白鼠为对照实验 ,以口服不含粉尘螨变应原的空白明胶微球的小白鼠为空白实验。 结果口服粉尘螨变应原微球的小白鼠实验组可产生高水平的血清抗体 ,在给药后第 14d抗体最高值为 2 .45× 10 5Au/ml(Ar bitraryunitspermilliliter) ,高于腹腔注射相同剂量的粉尘螨变应原浸液小白鼠的最高抗体水平 (4 .2 7× 10 4Au/ml)。结论 在给予相同剂量粉尘螨变应原的前提下 ,明胶微球口服制剂的免疫效果优于变应原浸液腹腔注射剂。  相似文献   

7.
据Medscape.com5月17日报道(原载J Med Virol 2005:76:7—15),在老鼠中的一项新研究显示,通过树突细胞介导,毫微球表面携带HIV抗原的鼻内给药能够激活抗体和细胞免疫应答。  相似文献   

8.
聚乳酸羟基乙酸(poly D,L-lactic-co-glycolic acid, PLGA)是一种无毒可生物降解的聚合物,可用作医用手术缝合线和注射用微胶囊、微球及埋植剂等制剂的材料。最近国内外学者先后报道有机砷化合物——氧化酚砷(phenylarsine oxide,PAO)对于肿瘤具有明显的抑制作用,其效果为无机砷的数倍而毒性更小。本实验以氧化酚砷为靶向药物,将PLGA作为载体材料,以Fe3O4为导向磁流体,制备了磁性聚乳酸羟基乙酸氧化酚砷纳米微球(M-PLGA-PAO-NP),并  相似文献   

9.
葡聚糖微球肝栓塞治疗肝癌疗效的病理学评估   总被引:5,自引:0,他引:5  
病理组织学评估葡聚糖微球栓塞治疗肝癌的疗效。11例原发性肝癌行葡聚糖微球肝栓塞治疗,栓塞后择期作有切除术。切除后的肝瘤标本作组织病理研究以观察肿瘤的坏死程度及葡聚糖微球在人体内的状况。7例肝癌病灶为完全坏死,未见存活癌细胞;另4例为不完全坏死。两者相比,完全坏死组肿瘤较为远离膈面、肝裂、及胆囊窝等动脉侧支吻合丰富的区域。葡聚糖微球能产生均一的末梢性动脉栓塞。微球在体内191天仍未被吸收。门脉系统内未见栓子微球。部分远离肝侧支循环的肝癌可通过葡聚糖微球肝栓塞得到临床治愈。  相似文献   

10.
目的:制备抗肝癌单链抗体二聚体高分子免疫纳米颗粒,观察其对肝癌细胞增殖的影响.方法:采用离子交联的方法,以壳聚糖水溶性衍生物多糖为基材,将已获得的抗肝癌单链抗体二聚体BDM制备成免疫纳米颗粒,检测纳米颗粒的表征、包封率及载药量,并通过MTT法观察免疫纳米颗粒对肝癌细胞株增殖的影响.结果:制备粒径为100-200nm的抗肝癌单链抗体二聚体高分子纳米颗粒,最佳包封率为53%,栽药量为75μg/mg抗体二聚体,抗肝癌单链抗体二聚体高分子纳米颗粒显示较好的抗肿瘤作用,其对肝癌细胞的抑制率为34%左右,且有浓度依赖性.结论:成功制备了抗肝癌单链抗体二聚体高分子纳米颗粒,初步应用具有抑瘤性,为下一步开展体内肝癌的放射免疫诊断和靶向治疗奠定了基础.  相似文献   

11.
Summary SCK-29 is a tumor cell line derived from human gastric adenocarcinoma with the feature of producing lung metastases when xenografted in nude mice. Monoclonal antibodies were produced against SCK-29 tumor cells or their glycoproteins prepared by affinity chromatography on a lectin-agarose column. Five antigens defined by the monoclonal antibodies MG-1 to MG-5 were expressed in a large number of gastric or colonic adenocarcinomas. Among the antigens, MG-1 and MG-3 proved to be tumor-associated, since they were detected only occasionally in normal tissues. MG-5 antigen was often detected in normal gastric mucosa but not in other tissues. The degree of expression of MG-1, MG-3 and MG-5 antigens differed considerably in metastatic lesions. In metastatic liver lesions of gastric adenocarcinoma, expression of these MG antigens was less marked than in primary tumors. MG-1 and MG-3 antigens were abolished by neuraminidase digestion and periodate oxidation. MG-5 antigen was likely to be a protein antigen, since it was resistant to neuraminidase digestion and to periodate oxidation but was sensitive to protease digestion.Abbreviations NP-40 Nonidet-P40 - RCA-1 Recinis communis agglutinin-1 - WGA wheat germ agglutinin This study was supported in part by a grant-in-aid for scientific research (B. no. 63480309) and for cancer research from the Ministry of Education, Science and Culture, Japan  相似文献   

12.
目的制备和鉴定抗T-2毒素单克隆抗体。方法将T-2毒素与牛血清白蛋白(BSA)交联,制备T-2毒素与BSA交联物(T-2-BSA),以T-2-BSA免疫BALB/c小鼠,取其脾脏细胞与小鼠骨髓瘤细胞Sp2/0融合,以HAT培养液筛选杂交瘤细胞,用有限稀释法进行克隆化。用筛选的阳性单克隆细胞株,按常规方法制备腹水,腹水用饱和硫酸铵沉淀后,用阴离子交换法纯化,获得纯化的单克隆抗体。采用ELISA鉴定抗体的亚类,并测定血清和腹水中抗体的效价。结果制备出T-2毒素与BSA交联物T-2-BSA,免疫小鼠血清的效价在1×10-6以上。获得1株能稳定分泌抗T-2毒素抗体的杂交瘤细胞系,该抗体(T2mAb)属于IgG1亚类,轻链为κ链。腹水效价为1×10-6。ELISA法证明T2mAb可与T-2毒素发生特异性反应。结论成功制备出抗T-2毒素单克隆抗体,为建立测定食品、饲料和组织液中T-2毒素的免疫学方法打下了坚实的基础。  相似文献   

13.
14.
Background: Until recently there has been no effective therapy for patients with relapsed ovarian carcinoma following standard platinum based chemotherapy. Paclitaxel has recently been approved for clinical use in this malignancy. Aims: To evaluate the objective response rate and toxicity of paclitaxel in patients with relapsed ovarian cancer. Methods: Paclitaxel was given on an outpatient basis as a three hour infusion every 21 days for a maximum often cycles to 72 patients with advanced ovarian cancer previously treated with at least one platinum containing regimen. The starting dose was either 175 mg/m2 (patients with one or two prior chemotherapy regimens) or 135 mg/m2 (three previous regimens). Premedication was given because of the documented risk of hypersensitivity reactions to paclitaxel. Results: The overall response rate was 22% (95% confidence interval [CI] 13% to 34%) in the 72 patients enrolled in the study: four patients had a complete response. Three patients (4%) ceased treatment due to hypersensitivity reactions. Other significant (WHO grade 3 or 4) toxicities included neutropenia (51%), myalgia (14%), neurological (3%), alopecia (93%) and nausea and vomiting (3%). The estimated median survival of all patients was 9.8 months (95% CI: 9.1–13.0 months) with 44% alive at one year (standard error [SE] 7%). Conclusions: This study confirms that paclitaxel given as a three hour infusion has significant activity and acceptable toxicity in advanced ovarian carcinoma previously treated with platinum regimens.  相似文献   

15.
AIM: To explore the molecular mechanisms of action of paclitaxel and NM-3 on human gastric cancer in severe combined immune deficiency (SCID) mice.
METHODS: Human gastric cancer cells SGC-7901 were implanted into SCID mice and mice were treated with paclitaxel and NM-3. The effects of paclitaxel and NM-3 on apoptosis of human gastric cancer cells were analyzed using flow cytometry, TUNEL assays, and DNA fragment analyses.
RESULTS: Apoptosis of SGC-7901 cells was successfully induced by paclitaxel, NM-3, and the combination of paclitaxel and NM-3 24 h after injection as shown by the presence of apoptotic hypodiploid peaks on the flow cytometer before G1-S and a characteristic apoptotic band pattern in the DNA electrophoresis. The apoptotic rate detected by TUNEL assay was found to be significantly higher in the paclitaxel/NM-3 compared to the control group (38.5% ± 5.14% vs 13.2%± 1.75%, P 〈 0.01).
CONCLUSION: Paclitaxel in combination with NM-3 is able to induce apoptosis of the human gastric cancer cells in SCID mice effectively and synergistically.  相似文献   

16.
肝癌特异性谷氨酰转肽酶单克隆抗体的制备与初步应用   总被引:1,自引:0,他引:1  
目的 制备抗肝癌特异性谷氨酰转肽酶(GGT)单克隆抗体及研究此单克隆抗体的临床应用。 方法 以纯品GGT-Ⅱ免疫BALB/C小鼠,取免疫鼠脾细胞与SP2/0骨髓瘤细胞融合以制备能产生抗GGT-Ⅱ单克隆抗体的杂交瘤细胞株;以此抗GGT-Ⅱ单克隆抗体采用竞争抑制性ELISA检测人血清GGT-Ⅱ。 结果对融合细胞阳性孔反复克隆后获得1株稳定分泌抗GGT-Ⅱ单克隆抗体的小鼠杂交瘤细胞系:2G4F6B2,此单克降抗体为IgG1类,与GGT-I无交叉反应。以此单克隆抗体测定人血清GGT-II的结果与聚丙酰胺梯度电泳法相符。 结论 研究制备的抗GGT-Ⅱ单克隆抗体特异性高,可应用于临床检测人血清中GGT-Ⅱ。  相似文献   

17.
We report for the first time the possibility of weekly paclitaxel chemotherapy for a patient with advanced, nonresectable gastric cancer undergoing hemodialysis. A 50-year-old man with chronic renal failure due to bilateral polycystic kidneys, who had undergone hemodialysis three times a week for 5 years, presented with hematemesis in December 2004. Based on the diagnosis of gastric cancer with lymph node metastases, surgery was performed. On the 15th postoperative day, the patient was treated with chemotherapy using paclitaxel. Paclitaxel was administered at a dose of 60 mg/m2 as a 1 h iv infusion in 250 mL of saline. Hemodialysis was started 1 h after the completion of the paclitaxel infusion and was performed for 3 h. Paclitaxel was administered weekly on d 1, 8, and 15 on a 28-d cycle. The maximum plasma concentration of paclitaxel was 1390μg/L. The area under the curve of paclitaxel was 4398.6μg·h/L Grade 2 leukopenia was encountered during the first cycle. The plasma concentrations of paclitaxel from 6 to over 24 h after the infusion were 0.01 to 0.1μmol/L in our patient, and these concentrations have been shown to be effective on inhibiting the growth of gastric cancer cells without producing adverse side effects in the patient. The plasma concentration of paclitaxel was not influenced by hemodialysis. We conclude that the pharmacokinetics of paclitaxel is not altered in a patient with renal failure, and that weekly paclitaxel is a suitable treatment regimen for hemodialysis patients with advanced gastric cancer.  相似文献   

18.
Purpose The aim of this study was to evaluate the possibility of using a monoclonal antibody against exon 9 deleted E-cadherin (E-cad delta 9-1) for immunotherapy of gastric cancer. Methods Among nine human diffuse-type gastric cancer cell lines, we selected a cell line expressing exon 9 deleted E-cadherin (HSC-45M2) by direct sequencing. Tumor specificity and tumor specific in vivo targeting of E-cad delta 9-1 were evaluated in nude mouse bearing a tumor derived from HSC-45M2 cell line by immunohistochemical staining. The expression rate of E-cad delta 9-1 was evaluated in 299 gastric cancer patients, and in positive cases, the mutational status of E-cadherin exon 9 was examined. Results Immunohistochemical staining of various tissues from nude mice showed that only tumor tissue reacted with E-cad delta 9-1. However, immunohistochemical staining of the same tissues after systemic injection of E-cad delta 9-1 showed that reticuloendothelial and hypervascular organs reacted with E-cad delta 9-1, but tumor tissue showed only a slight reaction. Evaluation of the reactivity of 299 gastric cancer patients to E-cad delta 9-1 showed that 4.8% (9/187) of patients, who all had diffuse- or mixed-type gastric cancers, reacted positively, but none of the 112 intestinal-type gastric cancer patients reacted positively. Two of 9 patients (22%) with positive staining to E-cad delta 9-1 were confirmed to have mutant forms of E-cadherin exon 9. Conclusion Considering that E-cad delta 9-1 showed good tumor specificity and that some diffuse-type gastric cancers were immunopositive to it, this antibody could be a candidate therapeutic antibody against gastric cancers that express mutant E-cadherin.  相似文献   

19.
Objective:To explore inhibition effects of veliparib as PARP inhibitor combined doxorubicin for BEL-7404 proliferation of human liver cancer cell line.Methods:BEL-7404 was taken as the object of study and conventional culture was performed.It waslreated by doxorubicin and(or) veliparib after 24 h.Cell proliferation rate was detected by four methyl thiazolyl tetrazolium(MTT) assay,cell apoptosis was measured with annexin V-F1TC/PI double staining method by flow cytometry,DNA damage degree evaluation by single cell gel electrophoresis assay,and cytosolic C levels of the mitochondrial and cytosol by polyacrylamide gel electrophoresis(Western blotting).Results:Cell proliferation rate of doxorubicin combined veliparib group was lower than that of the control group and doxorubicin alone treated group significantly(P0.01),the apoptosis rate was significantly higher than that of the control group and doxorubicin alone treated group(P0.05).At the same time,DNA damage level of doxorubicin combined with veliparib group was significantly higher than doxorubicin alone treatment group and the control group(P0.01),and cytochrome C in the cytosol was significantly higher than that of control group and doxorubicin alone treated group(P0.01).Conclusions:Veliparib,PARP inhibitor could inhibit PARP activity,block tumor cell DNA repair,and have significant sensitizing effect for hepatocellular carcinoma cell line BEL-7404 treated with doxorubicin.This might provide a new target for clinical treatment of hepatic carcinoma.  相似文献   

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