Treatment Effects of TF on Chronic Hepatitis B and

胸腺肽(ThymosinFractionTF)是一组从胸腺组织提取的小分子生物多肽, 对机体免疫功能的调节T细胞的分化成熟以及自身免疫稳定性的维持均具有 重要作用TF在临床上已被广泛用于肿瘤病毒感染和自身免疫性疾病等治疗 近年来国内外报道大剂量TF治疗慢性乙肝有较好的疗效与IFN联用治疗慢性 乙肝有协同作用但其确切的治疗机理尚不清楚最佳治疗方案也待于进一步探 讨本文应用现代免疫学和分子生物学方法体内外探讨大剂量TF对T细胞免疫 功能的影响及其抗HBV活性与作用机制并对其与干扰素联合应用治疗慢性乙肝 的疗效做较系统的评价为探索新的乙型肝炎治疗方案和最佳参数提供科学依据 与理论指导...TF (thymosin fraction ) is a group of small bio-peptides isolated from thymus tissue. Recently, many published reports showed that large dose of TF remarkably showed a significant effect on chronic hepatitis B (CHB), and there was a co-operate effect of TF combined IFN in chronic hepatitis B therapy. But its treatment mechanisms are remained unclear. The effects of TF on T cell immune activiti...学位：理学博士院系专业：生命科学学院生物学系_动物学学号：B19962600

Radioimmunoimaging of 131 I Labeled Monoclonal Antibody JHⅢFab′ in Nude Mice Bearing Human Hepatocellular Carcinoma

用蛋白酶切技术制备MCAbJHⅢfAb′片段，回收率约10%。片段活性相当于完整MCAb的1102稀释浓度。用氯胺T法标记MCAbJHⅢfAb′，对荷人肝细胞癌bEl-7402裸鼠体内的放射免疫显像进行了研究。腹腔注射131I-MCAbJHⅢfAb′后24~96H，肿瘤部位有放射性浓聚，以48~72H影像最为清晰；而注射131I-MCAbJHⅢ肿瘤部位也有积聚现象，但本底消除更慢。131I-MCAbJHⅢfAb′注射后72H，13种器官的肿瘤组织与非瘤组织的放射性比值均大于3，肿瘤的定位指数为2.56。这表明MCAbJHⅢfAb′在肝细胞癌的诊断和指导治疗方面有更好的应用前景McAb JHⅢFab′ Fragment was prepared with pepsin digestion It′s receiving percentage was about 10% Its titer was 1∶10 2 of McAb JHⅢ McAb JHⅢFab′ Fragment was radiolabeled with 131 I by Ch T method Its distribution and radioimmunoimaging in the nude mice bearing human hepatoma BEL 7402 were studied Between 24-96 h aFter intraperitoneal administration, the image of the concentrating radioacitivity in tumor was obtained by the γ camera and it was the clearest during 48-72 h; whereas the injection of 131 I McAb JHⅢ into the nude mice resulted in an equal radioactivity in tumor, but it′s background was more slowly cleared. At 72 h aFter the injection of 131 I McAb JHⅢFab′, the radioactivity ratioes of tumor/normal tissue(T/NT) For 13 kinds of organ/tissue were all over 3, and the localization index of tumor was 2 56 These results showed that McAb JHⅢFab′ may be useFul in the localization and targeting treatment of human hepatocellular carcinom

MTT法检测平阳霉素对肿瘤细胞的药物活性研究

本文选用两种细胞株:人肝癌bEl-7402和肺腺癌l-342细胞,利用MTT法检测平阳霉素对两株细胞药物敏感性的探讨。将每毫升含10--6个细胞的培养液按(1/2)--n(n=0~7)梯度稀释,种于96孔板(100μl/孔),5%CO_2,37℃,培养34H,加MTT20μl(母液2Mg/Ml);再37%培养4H,加dMSO100μl溶解,测570nMOd值,结果贴壁生长的bEl-7402细胞的平均Od值为0.31(0.43~0.24),悬浮生长的l-342细胞的平均Od值为0.27(0.29~0.24),两者无显著性差别(P>0.05)。MTT甲月赞产物最大吸收波长为550~570nM,细胞浓度在一定范围内与甲月赞量近似成正比,MTT浓度以每孔4μg,孵育时间4小时为宜。将平阳霉素(母液1Mg/Ml)按(n=0~5)梯度稀释,加到每孔含有10000个细胞的培养板中,同上法测570nMOd值,结果显

NRP- 1 monoclonal antibody in combination with metronomic chemotherapy (MCT) inhibits the growth of gastric cancer xenografts in nude mice

目的:探讨NRP-1单抗联合多西他赛节律化疗对胃癌裸鼠移植瘤的抗肿瘤疗效。方法:BALB/c裸鼠皮下接种胃癌BGC-823细胞制备移植瘤模型,将; 荷瘤裸鼠以数字随机表法随机分为对照组、NRP-1单抗组、节律化疗组(MCT)、联合组(NRP-; 1mAb+MCT),每组6只。除对照组,其余各组于造模第8天开始分别给予相应治疗,给药2周,观察裸鼠一般状况,隔天测量裸鼠体重及肿瘤体积。裸鼠处; 死后称瘤质量,H-E染色观察瘤组织形态,免疫组化检测裸鼠瘤组织中NRP-1蛋白、VEGF、MVD表达。结果:联合组移植瘤的体积和质量显著低于其他; 各组[ (0.3940.128)vs(0.7480.152)、(0.8670.361)、(1.2470.494) g;(0.6130.223); vs (0.8660.115)、(1.0980.343)、(1.4740.644); cm~3。均P<0.05],抑瘤率较其他治疗组差异有统计学意义(P<0.05)。对照组癌组织细胞生长良好,血管丰富,给药组癌组织出现不同程度的片; 状坏死,血管成分减少。免疫组化染色显示,对照组NRP-1表达明显高于治疗各组(P<0.05),联合组的NRP-1、VEGF、MVD表达均显著低于; 其余各组(P<0.05)。结论:NRP-1单抗联合多西他赛节律化疗可能通过下调NRP-1表达而显著抑制BGC-823胃癌移植瘤的生长及血管生成。Objective: To investigate the antitumor effect of NRP-1 monoclonal; antibody combined with docetaxel metronomic chemotherapy in nude mice; bearing gastric cancer xenografts. Methods: BALB / c mice were; inoculated subcutaneously with BGC-823 cells to establish xenograft; model; the tumor bearing rats were randomly divided into control group,; NRP-1 monoclonal antibody group (NRP-1mAb), rhythm chemotherapy group; (MCT) and combined group (NRP-1mAb+MCT). Except the control group, the; other three groups were given the corresponding treatment on the 8th day; after the model establishment. After 2 weeks of administration, the; general condition of nude mice was observed and the body weight and; tumor volume were measured the next day. The mice were sacrificed and; the mass of tumor was calculated; HE staining was used to observe the; morphology of the tumor tissue. The expression of NRP-1 protein, VEGF; and MVD were detected by immunohistochemistry. Results: The tumor volume; (0.6130.223 vs 0.8660.115, 1.0980.343, 1.4740.644 V/cm~3; P<0.05) and; weight (0.3940.128 vs 0.748 0.152, 0.8670.361, 1.2470.494 m/g; P<0.05); of the combined group were significantly lower than those of the other; groups, and the tumor inhibition rate was statistically higher compared; with the other treatment groups (P< 0.05). Under microscope, the cancer; cells in the control group were well grown and the blood vessels were; rich; the cancerous tissues of each treatment group showed different; degree of sheet necrosis and the blood vessel composition decreased.; Immunohistochemistry results showed that the expression of NRP-1 in the; control group was significantly higher than that in each treatment group; (P<0.05); and the expression of NRP-1, VEGF and MVD in combined; treatment group was significantly lower than the other groups.; Conclusion: NRP-1 monoclonal antibody combined with docetaxel rhythmic; chemotherapy may significantly inhibit the growth and angiogenesis of; BGC-823 gastric cancer by down-regulating the expression of NRP-1.厦门市科技计划创新项目资

自杀基因治疗恶性肿瘤的研究现状及展望

肿瘤的自杀基因疗法是近年来肿瘤基因治疗的研究热点,是一种具有潜在临床应用前景的新的肿瘤基因治疗策略。本文就近年来自杀基因疗法在肿瘤治疗中取得的研究进展,分别从作用机制、自杀基因系统、旁观者效应、自杀基因的转导以及联合基因治疗等几个方面进行综述

抗肺癌免疫光敏剂的制备及其杀伤作用

以碳二亚胺(EDCI)为连接剂将抗肺癌单克隆抗体(McAb 3D3与血卟啉衍生物(HpD)共价连接,制备成免疫光敏剂,经ELISA法测定及溶血试验,结果表明偶联物保留了 McAb的反应性及HpD的光敏活性,偶联物经紫外光谱及荧光光谱扫描分析表明,偶联HpD与非偶联HpD的光谱特性有所差别,体外杀伤试验表明,偶联物的杀伤效率提高了10.5倍,且对非靶细胞的杀伤作用微弱,证明HpD与McAb偶联后,对靶细胞具有特异杀伤作用,可为肿瘤的治疗提供一种新的药物

单克隆抗体3D3重链可变区基因结构分析

单克隆抗体（MCAb）在科研及影像诊断等领域应用十分广泛，鼠源性单克隆抗体，由于其抗原性，在人体疾病治疗应用受到限制，利用dnA重组技术，构建各种重组抗体基因，表达制备重组抗体，可降低其抗原性，前提是必须获得其可变区基因，我们利用设计合成的一对鼠抗体...国家自然科学基

欧鳗“狂游症”病调查报告

欧鳗“狂游症”病调查报告黄印尧陈信忠颜江华（厦门动植物检疫局361012）（厦门大学抗癌研究中心361021）近年来，我国从欧美引进了大量的鳗苗，但欧鳗的病害，尤其是以狂游衰竭而死亡为主要特征的“狂游症“病常常造成全场鳗鱼发病死亡，死亡率达90%以上..

Inhibitory effect of NRP-1mAb on the growth of gastric cancer cell BGC-823

目的观察自主研发的抗NRP-1b1/b2IgG单克隆抗体（NRP-1mAb）对胃癌BGC-823细胞生长的影响,并初步探讨可能的作用机制。方法实验室制备NRP-1mAb,采用SDS-PAGE检测纯度。采用0、25、100、200、400μg/ml NRP-1mAb培养胃癌BGC-823细胞,光学显微镜下观察细胞形态学变化;采用MTT法、集落形成实验、流式细胞术观察胃癌细胞BGC-823的增殖、集落形成和凋亡的情况;Western blotting法检测NRP-1mAb作用后Akt、p38、ERK、JNK信号蛋白磷酸化情况。结果SDS-PAGE检测显示,NRP-1mAb的纯度在95%以上。光学显微镜观察显示,NRP-1mAb作用后,BGC-823细胞形态呈凋亡改变。MTT实验显示,NRP-1mAb抑制BGC-823细胞的增殖作用呈浓度和时间依赖性（P〈0.01）。集落形成实验显示,不同浓度NRP-1mAb均能显著抑制BGC-823细胞的集落形成,其抑制率呈浓度依赖性（P〈0.01）。流式细胞术检测显示,不同浓度NRP-1mAb均明显促进BGC-823细胞凋亡,且大部分集中在早期凋亡。Western blotting检测显示,BGC-823细胞的Akt磷酸化受到抑制,ERK、p38、JNK的磷酸化水平无明显变化。结论NRP-1mAb能抑制胃癌细胞BGC-823的生长、促进凋亡,可能与抑制Akt磷酸化有关。Objective To observe the effect of NRP-1b1/b2 IgG monoclonal antibody（ NRP-1） on the growth of gastric cancer cell BGC-823,and to explore the possible mechanism of the antibody. Methods NRP-1mAb was prepared in laboratory,and the purity of antibody was detected by SDS-PAGE. Gastric cancer BGC-823 cells were cultured by 0,25,100,200,400 μg/ml NRP-1 mAb. The morphological changes of BGC-823 cells were observed by microscope. The proliferation,colony formation and apoptosis of gastric cancer BGC-823 cells were observed by MTT assay,colony forming assay and flow cytometry. The phosphorylation of related signal proteins was detected by Western blotting analysis. Results SDS-PAGE test showed that the purity of NRP-1mAb was above95%. Microscopy showed apoptotic changes of BGC-823 cells treated by NRP-1mAb. MTT assay showed that NRP-1mAb could inhibit the proliferation of BGC-823 cells in a time and dose dependent manner（ P〈0. 01）. Colony forming assay showed that different doses of NRP-1mAb could inhibit the colony formation of BGC-823 cells in a dose dependent manner（ P〈0. 01）. Flow cytometry showed that different doses of NRP-1mAb could promote the apoptosis of BGC-823 cells mainly at early apoptosis stage. It was found that the level of Akt phosphorylation was decreased after treated by NRP-1mAb,and there was no significant phosphorylation of ERK,p38 and JNK protein. Conclusion NRP-1mAb can inhibit the growth of gastric cancer cell BGC-823 and promote apoptosis,which may be related to the inhibition of Akt phosphorylation.厦门市科技计划创新资助项目（3502z20134026,3502z20144034