两种甲胎蛋白抗体标记物导向治疗肝癌的疗效比较

目的比较以甲胎蛋白单抗隆抗体(抗AFP McAb)和多克隆抗体(抗AFP PcAb)为载体的两种双弹头标记物131I-抗AFP McAb-MMC和131I-抗AFP PcAb-MMC的疗效.方法通过直接偶联和改良氯胺T法制备两种双弹头标记物131I-抗AFP McAb-MMC和131I-抗AFP PcAb-MMC,用于治疗荷肝癌裸鼠和31例不能手术的中晚期肝癌患者.结果在荷肝癌裸鼠,腹腔给药后第13天,单抗标记物的抑瘤率为81.5%,显著高于多抗标记物(为50.0%),P＜0.05.在临床上,多抗标记物的肿瘤缩小率及1、2年生存率分别为63.2%,52.6%和36.8%,较单抗标记物的高(分别为45.5%,45.5%和33.3%),但差异无显著性(P＞0.05).结论两种双弹头标记物的动物实验结果有差别,但临床应用结果无差别.     

导向内照射化疗栓塞治疗56例肝癌随访报告

目的　为提高肝癌治疗效果 ,以超液态碘化油 (LUF)及体毛颗粒 (H)作为载体 ,12 5I及细胞周期非特异性抗癌药 (CCNSA)为弹头 ,制成能经导管灌注的导向抗癌物ILCH ,并随访其疗效。方法　对 5 6例肝癌患者经股动脉插管至肿瘤供血动脉内灌注ILCH。治疗前后分别做CT、B超、DSA、AFP及血尿中12 5I放射性测定。结果　12 5I与L标记率为 6 0 %～ 90 % ,能与H一起在 10 0 μm直径以下的末梢动脉中长期滞留 ,不通过毛细血管进入全身循环 ,并将抗癌药限制在癌区共同发挥接触性内照射和化疗栓塞作用。术后副作用小 ,无排异反应 ,DSA证实发丝样肿瘤血管和肿瘤染色消失 ,肿瘤直径缩小 5 0 %～ 70 %者 ,占 6 4.3% ;肿瘤无变化或缩小 5 0 %以下者 ,占 35 .7%。临床症状、肝功能及AFP均有改善。 6个月、1,2 ,3年生存率分别为 10 0 %、82 .1%、6 3.1%和 5 5 .6 %。结论　ILCH作为一种新的导向抗癌物治疗肝癌 ,简便易行 ,导向性强 ,可显著提高患者生存质量和生存率。     

125I-抗AFP抗体介入灌注联合化疗栓塞治疗肝癌的临床观察

目的　观察12 5I 抗AFP抗体经肝动脉灌注后在癌灶内的定位导向能力及与化疗栓塞(TACE)联合治疗肝癌的近期疗效和毒副作用。方法　肝动脉内介入灌注12 5I 抗AFP抗体联合行TACE ,综合治疗肝癌 36例。结果　导向组瘤 肝放射比值平均为 1 86± 0 72 ,有效率、AFP显著下降率及中位缓解期与TACE组相比 ,各为 55 6 %比 4 1 2 % (P >0 0 5)、77 8%比 52 9% (P <0 0 5)、8 5M比 5 6M(P <0 0 5)。两组的毒性反应相似。结论　经肝动脉灌注并与TACE联合可显著增强12 5I 抗AFP抗体在肝癌灶中的导向定位能力和滞留能力及内照射作用 ,提高综合疗效。     

载131I和阿霉素"双弹头" F(ab′)2片段免疫毫微粒的抗人肝癌作用

目的研究载131I和阿霉素“双弹头”F(ab′)2片段免疫毫微粒的抗肿瘤效应及其在荷瘤裸鼠体内的分布。方法采用氯胺T法,将核素131I结合到抗人肝癌HAb18抗体的F(ab′)2片段靶向的载阿霉素毫微粒上,构建“双弹头”F(ab′)2片段免疫毫微粒;采用花环形成实验、MTT比色分析法等分别研究该免疫毫微粒对人肝癌细胞株(SMMC-7721)的特异性结合及体外细胞毒作用;应用皮下荷人肝癌裸鼠模型,评价该免疫毫微粒的体内分布及其抗肝癌作用。结果“双弹头”F(ab′)2片段免疫毫微粒能特异性结合于SMMC-7721细胞周围形成花环,其IC50明显低于“单弹头”F(ab′)2片段免疫毫微粒;该免疫毫微粒经尾静脉给药后,主要分布于肝、脾等处,而经瘤体注射主要滞留于瘤体内,其抑瘤率显著高于对照“单弹头”毫微粒。结论载131I和阿霉素“双弹头”F(ab′)2片段免疫毫微粒,具有较“单弹头”F(ab′)2片段免疫毫微粒更佳的抗肿瘤效应。     

^125I—抗AFP抗体介入导向治疗肝癌的药物体内代谢和疗效观察

目的研究 125I-抗AFP抗体经肝动脉介入灌注后的体内代谢特点,并探讨导向综合治疗中晚期原发性肝癌的疗效.方法经肝动脉灌注 125I-抗AFP结合化疗栓塞(TACE)和静脉滴注CD3AK细胞综合治疗原发性肝癌患者21例,检测 125I-抗AFP抗体在病人体内的药代动力学各项参数及体内生物学分布特点,并对比观察导向治疗组与对照组临床疗效.结果 125I-抗AFP抗体血中放射性 T1/2α、 T1/2β分别为1.85±1.79及156.46±65.11小时,尿放射活性半排时间为94小时,器官体表外辐射强度测定提示肝脏相对其他器官有强度较强及时间较长的放射性积蓄,肝脏SPECT检查瘤/肝比平均值为2.1±0.6,.导向组和对照组的有效率为 61.9%(13/21)与25.0%(5/20),1年累计生存率比较亦为61.9%与25.0%,差异均有显著性(P<0.05).结论125I-抗AFP抗体经肝动脉给药后可选择性滞留在肝肿瘤内较长时间而起持续内照射作用,与TACE和免疫治疗应用是肝癌综合治疗的有效方案.     

THP和ADM在肝癌导向综合治疗中的作用对比研究

 为对比观察THP和ADM在肝癌导向综合治疗中的作用,分别对24例中晚期原发性肝癌患者进行了125I—AFPAb肝动脉灌注联合栓塞化疗的导向综合治疗。结果显示;THP组和ADM组的有效率分别为66.7％和58.2％(P>0.05)。THP组的脱发率和心脏毒性反应明显低于ADM组(P<0.05),其它的毒副反应两组相近。提示:肝动脉灌注125I—AFPAb与葱环类抗癌药为主的栓塞化疗联合治疗中晚期原发性肝癌具有较高的疗效,THP的疗效与ADd相近,但脱发和对心脏的毒副作用较小。     

~(125)I-抗AFP抗体介入导向治疗肝癌的药物体内代谢和疗效观察

目的 :研究 1 2 5I 抗AFP抗体经肝动脉介入灌注后的体内代谢特点 ,并探讨导向综合治疗中晚期原发性肝癌的疗效。方法 :经肝动脉灌注 1 2 5I 抗AFP结合化疗栓塞 (TACE)和静脉滴注CD3 AK细胞综合治疗原发性肝癌患者 2 1例 ,检测 1 2 5I 抗AFP抗体在病人体内的药代动力学各项参数及体内生物学分布特点 ,并对比观察导向治疗组与对照组临床疗效。结果 :1 2 5I 抗AFP抗体血中放射性T1 2 α、T1 2 β分别为 1.85± 1.79及 15 6 .46± 6 5 .11小时 ,尿放射活性半排时间为 94小时 ,器官体表外辐射强度测定提示肝脏相对其他器官有强度较强及时间较长的放射性积蓄 ,肝脏SPECT检查瘤 肝比平均值为 2 .1± 0 .6 ,。导向组和对照组的有效率为 6 1.9%(13 2 1)与 2 5 .0 %(5 2 0 ) ,1年累计生存率比较亦为 6 1.9%与 2 5 .0 %,差异均有显著性 (P <0 .0 5 )。结论 :1 2 5I 抗AFP抗体经肝动脉给药后可选择性滞留在肝肿瘤内较长时间而起持续内照射作用 ,与TACE和免疫治疗应用是肝癌综合治疗的有效方案。     

“双弹头”抗AFP抗体对肝癌导向综合治疗的实验和临床研究

为增强导向治疗的“弹头”杀伤力，提高肝癌导向综合治疗的疗效，对马抗人ＡＦＰ抗体进行了１３１Ⅰ和丝裂霉素（ＭＭＣ）双标记，制备同时携带１３１Ⅰ和ＭＭＣ的“双弹头”马抗人ＡＦＰ抗体（１３１Ⅰ－ＡＦＰＡｂ－ＭＭＣ）。荷人肝癌裸鼠的定位显像和抑癌率实验显示１３１Ⅰ－ＡＦＰＡｂ－ＭＭＣ具有良好的定位显像作用，抑癌率达７３．５％，明显高于对照组（Ｐ＜０．０５）。２２例配对的中晚期原发性肝癌患者的“双弹头”导向综合治疗结果：治疗组的有效率（ＣＲ＋ＰＲ＋ＭＲ）为６３．２％明显高于对照组（３１．８％），Ｐ＜０．０５；治疗组的１年生存率（５２．６％）亦明显高于对照组（２２．７％）Ｐ＜０．０５，且无严重毒副作用。表明：１３１Ⅰ－ＡＦＰＡｂ－ＭＭＣ的“双弹头”导向综合治疗可提高中晚期原发性肝癌的疗效     

肝癌^131I—抗AFP抗体—MMC“双弹头”免疫导向治疗的研究

目的 观察一种集化疗和内照射于一体的新型“双弹头”免疫导向治疗肝癌的效果。方法 以大鼠抗人甲胎蛋白（ＡＦＰ）单克隆抗体（抗ＡＦＰＭｃＡｂ）和马抗人ＡＦＰ多克隆抗体（抗ＡＦＰＡｂ）为载体，＾１３１碘（＾１３１Ｉ）或＾１２５碘（＾１２５Ｉ）和丝裂霉素（ＭＭＣ）为“双弹头”用改良氯胺Ｔ法制备＾１３１Ｉ－抗ＡＦＰＭｃＡｂ－ＭＭＣ（双弹头Ｉ）和＾１３１Ｉ（或＾１２５Ｉ）－抗ＡＦＰＡｂ－ＭＭＣ（双弹头Ⅱ）治疗     

定量放射自显影法测定人类肿瘤抗原浓度及分布

作者用~(125)Ⅰ标记 McAb,在体外做定量放射自显影,测定人类肿瘤组织切片中抗原浓度。用2株核素标记 McAb 研究恶性黑色素瘤,即~(125)Ⅰ-96.5为抗 P_(97)人类黑色素瘤抗原的 MeAb,~(125)Ⅰ-9.2.27是抗黑色瘤相关抗原 P_(250)的McAb。另外2株与黑色素瘤不相关的 MeAbBL-3或2-135反应做阴性对照。简要程序如下:连续冰冻切片,厚81μm,戊二醛固定。用核素标记的特异性McAb(96.5或9(?)2.27)22℃孵育1h,抗体浓度1.4～126nmo1/L;非特异性结合组加入过量的非标记抗体,总结合组     

AFP、CA125和TSGF联合检测在原发性肝癌诊治中的应用

目的通过联合检测血清中AFP、CA125和肿瘤相关物质群(TSGF)的含量,观察其对原发性肝癌(PLC)的临床诊断及疗效观察的价值。方法75例原发性肝癌患者、38例肝良性疾病患者血清样品,分别用电化学发光免疫测定法和生物化学比色定量法测定AFP、CA125和TSGF含量。结果与良性肝病组相比,原发性肝癌患者血清AFP、CA125和TSGF的含量明显升高(P<0.01),3项标志物的阳性检出率分别是80.0%、44.0%和69.3%,三者联合检测阳性率为93.3%。原发性肝癌患者血清AFP、CA125、TSGF含量在治疗后与治疗前相比,有显著性差异(P<0.05)结论3项肿瘤标志物对肝肿瘤的良恶性辅助诊断及鉴别诊断具有一定应用价值,联合检测不仅可以提高原发性肝癌的阳性诊断率,对原发性肝癌的疗效观察和术后监测也具有重要价值。     

Combination Therapy with Vascular Endothelial Growth Factor Neutralizing Antibody and Mitomycin C on Human Gastric Cancer Xenograft

Antiangiogenic therapy has been proposed as a new strategy for the treatment of solid tumors. To enhance the therapeutic effect of antiangiogenic agents, combination with conventional anticancer therapy should be investigated. In the present study, we investigated the therapeutic effect of the combination of vascular endothelial growth factor neutralizing antibody (VEGF Ab) and mitomycin C (MMC) on MT-2, a human gastric cancer xenograft. When small pieces of MT-2 were transplanted orthotopically into 62 nude mice, liver metastasis developed 6 weeks after transplantation. The VEGF Ab (100 μg/mouse) was administered i.p. in the VEGF Ab group ( n =14) and the combination group ( n =16) twice a week from day 10 after transplantation. MMC (2 mg/kg) was administered in the MMC group ( n =16) and the combination group ( n =16) on days 10, 17 and 24 after transplantation. Compared with the control group, in which saline solution was administered i.p., all three treatments inhibited tumor growth significantly and the effects of MMC and combination therapy were potent. Liver metastases were also inhibited significantly by the administration of VEGF Ab alone, MMC alone or combination therapy. Liver metastasis developed in 9 mice of the control group, 3 of the VEGF Ab group, and 4 of the MMC group, but no mice had liver metastasis in the combination therapy group. However a significant body weight loss and a decrease in spleen weight were observed in the MMC and combination groups, with no significant difference between the two groups. These results suggest that combination therapy with VEGF Ab and MMC may be a potent therapy for human gastric cancer.     

^131I—Hepama—1单克隆抗体导向治疗肝癌的初步观察

采用１３１Ｉ－Ｈｅｐａｍａ－１单克隆抗体，经股动脉插管至肝动脉或皮下药盒注入肝动脉，治疗２２例不能手术之晚期肝癌患者。结果显示９０％患者卡氏评分上升，多数患者癌性症状减轻，生活质量提高，ＣＲ＋ＰＲ＋ＭＲ率为７２．７％（１６／２２），１年生存率３６．４％（８／２２）。并使部分不能切除之巨大肝癌变为可手术的小肝癌，二期切除率３１．８％（７／２２），经二期切除的患者，１年生存率提高到７１％。认为本方法作为肝癌综合治疗方法之一，疗效肯定，安全，副作用轻，值得进一步应用观察     

抗人肝癌单克隆抗体的人体放射免疫定位及治疗

研究单抗Ｈｅｐａｍａ－Ⅰ在原发性肝癌患者中的导向定位及治疗效果。方法本研究包括３０个失去手术指征的原发性肝癌患者,其中１８例行放射免疫显像（ＲＩ）研究,１２例行放射免疫治疗（ＲＩＴ）研究,分别从肝动脉投与１３１Ｉ－ＨｅｐａｍａＩ９．２５ＧＢｑ（ＲＩ）及１８．５ＧＢｑ（ＲＩＴ）。结果接受该制剂后未见明显毒性反应,显像率为１４／１８,最佳显像时间在注射后９６小时,ＡＦＰ下降率为７５．０％,肿瘤部分缩小率６６．６％,与对照组比较,生存时间明显延长。结论单抗ＨｅｐａｍａＩ能在人体内认识原发性肝癌细胞,并能与之特异结合。核素碘标记的ＨｅｐａｍａＩ可作为治疗晚期肝癌的综合疗法之一。     

GP73、AFP、CA －199联合检测在原发性肝癌诊断中的应用价值

目的：探讨高尔基体蛋白73（GP73）、甲胎蛋白（AFP）和糖类抗原199（CA －199）联合检测对原发性肝癌（PLC）诊断的意义。方法：54例原发性肝癌患者均为邯郸市人民医院住院患者,采用酶偶联吸附法（ELISA 法）检测 GP73、化学发光免疫分析法检测 AFP、CA －199,并与55名健康对照者进行比较。结果：原发性肝癌组血清 GP73、AFP 及 CA －199水平较对照组均明显升高,差异均有统计学意义（P 均＜0．01）。PLC组 GP73、AFP 及 CA －199水平呈显著正相关（r ＝0．729、0．651、0．627,P 均＜0．05）。三项肿瘤标记物联合测定的阳性率为87．0％,明显高于单项分别测定 GP73、AFP、CA －199阳性率,其阳性率分别为48．1％、77．8％和33．3％,差异有统计学意义（P ＜0．05）。结论：血清 GP73、AFP、CA －199联合检测可明显提高原发性肝癌的阳性检出率,对原发性肝癌的早期诊断具有重要的临床意义。     

Clinical study on preoperative chemotherapy of primary breast cancer. 2--A comparative study of CPA + FT-207 (5-FUDS) and CPA + FT-207 (5-FUDS) + MMC

In 41 cases of primary breast cancer preoperative treatment was performed using 2 methods consisting CPA + FT-207 (5-FUDS) (for Group I) and CPA + FT-207 (5-FUDS) + MMC (for Group II) to determine clinical and histological efficacies. A daily dose of each anticancer drug was: CPA 50-200 mg, FT-207 200-600 mg, and 5-FUDS 200 mg orally, and MMC 4-20 mg intravenously. The mean total doses were 1.8 g, 6.3 g, 3.4 g and 26.3 mg, respectively. Reduction in tumor size was obtained in 11 cases (37.9%) in Group I and 6 cases (50.0%) in Group II. According to Ohboshi's criteria, histological efficacy as defined over Grade II a was seen in 5 cases (17.2%) in Group I and 6 cases (50.0%) in Group II, while the efficacy classified as Grade III was not seen in any of the cases. Although the clinical effect was not always consistent with the histological effect, there was a tendency of agreement between them in Group II. As to the dosages of anticancer drugs, more effective cases were seen when dosages of more than 25 mg/kg of CPA, 80 mg/kg of FT-207 (5-FUDS) or 0.5 mg/kg of MMC were used. Reduction in tumor size began to appear at 2 to 3 weeks after the initiation of treatment.     

Combination therapy with vascular endothelial growth factor neutralizing antibody and mitomycin C on human gastric cancer xenograft.

Antiangiogenic therapy has been proposed as a new strategy for the treatment of solid tumors. To enhance the therapeutic effect of antiangiogenic agents, combination with conventional anticancer therapy should be investigated. In the present study, we investigated the therapeutic effect of the combination of vascular endothelial growth factor neutralizing antibody (VEGF Ab) and mitomycin C (MMC) on MT-2, a human gastric cancer xenograft. When small pieces of MT-2 were transplanted orthotopically into 62 nude mice, liver metastasis developed 6 weeks after transplantation. The VEGF Ab (100 micro g / mouse) was administered i.p. in the VEGF Ab group (n = 14) and the combination group (n = 16) twice a week from day 10 after transplantation. MMC (2 mg / kg) was administered in the MMC group (n = 16) and the combination group (n = 16) on days 10, 17 and 24 after transplantation. Compared with the control group, in which saline solution was administered i.p., all three treatments inhibited tumor growth significantly and the effects of MMC and combination therapy were potent. Liver metastases were also inhibited significantly by the administration of VEGF Ab alone, MMC alone or combination therapy. Liver metastasis developed in 9 mice of the control group, 3 of the VEGF Ab group, and 4 of the MMC group, but no mice had liver metastasis in the combination therapy group. However a significant body weight loss and a decrease in spleen weight were observed in the MMC and combination groups, with no significant difference between the two groups. These results suggest that combination therapy with VEGF Ab and MMC may be a potent therapy for human gastric cancer.