亲和素-生物素系统预定位放免治疗白血病的研究

1预定位技术概述单克隆抗体在肿瘤学中已成为将放射性核素传递至肿瘤细胞的载体用于肿瘤的诊断及治疗。放免治疗（RIT）成为最令人期待的治疗形式之一,特别是在血液系统恶性肿瘤。例如,抗CD20介导的RIT即可单独或联合化疗或造血细胞移植（HCT）可明显提高惰性B-细胞非霍奇金淋巴瘤病人的预后,为侵袭性淋巴瘤的预后带来希望。

驱动基因阴性的晚期非小细胞肺癌放免联合治疗研究进展

非小细胞肺癌(NSCLC)患者中有很大比例在发现时被诊断为转移性和不可治愈的晚期肺癌,以致于失去了手术的机会,5年生存率较低。免疫治疗时代,众多种类的免疫检查点抑制剂被批准用于驱动基因阴性的晚期NSCLC患者的一/二线治疗,同时与放疗联合作为晚期NSCLC患者的重要治疗策略。放射治疗与免疫治疗相结合的创新策略在临床研究中获得了大量的可行性证据。在分子和细胞水平上观察免疫机制的临床前实验初步揭示了肿瘤、辐射和免疫系统之间的相互作用。本文对放免联合治疗在驱动基因阴性晚期NSCLC治疗中的进展进行简要综述。

CD20阳性B细胞NHL^(131)I-美罗华放射免疫治疗剂量个体化的临床初步研究

本研究旨在观察不同个体间131I-美罗华全身清除速率的差异,并拟定131I-美罗华放射免疫治疗个体化治疗剂量。选取CD20阳性B细胞NHL患者13例,于不同时相行全身平面显像,监测131I-美罗华的全身分布和清除情况,绘制时间-放射性曲线得到全身清除速率常数(λ),计算全身有效半清除时间Teff,采用医用内照射吸收剂量(Medical Internal Radiation Dosimetry,MIRD)法求得示踪剂量水平的全身辐射吸收剂量,并参照体重为70 kg的标准人体模型131I-美罗华全身最大耐受剂量为75 cGy,求得个体化的最大允许注射活度。结果显示:13例患者Teff为58.73~177.69 h(96.87±30.58 h),似呈正态分布;最大允许注射活度为1.14~2.95 GBq,其分布无明显规律。根据求得的最大允许注射活度试行治疗其中1例病人,其病情获得了部分缓解。

^(131)I标记抗Peroxiredoxin I肺腺癌噬菌体抗体在荷瘤裸鼠体内的分布及其对肿瘤生长的抑制作用

目的研究抗Peroxiredoxin I(PrxI)肺腺癌相关单链抗体体外对肺腺癌细胞的增殖抑制;观察131I标记抗体在肺腺癌裸鼠模型体内分布、靶向显像及体内抑瘤作用。方法放射性核素计数法测定单链抗体细胞内摄水平;MTT法及流式细胞仪检测单链抗体抑制肺腺癌A549细胞生长情况;免疫印迹法检测单链抗体作用于A549细胞后对细胞内PrxI表达水平的影响。放射性核素131I标记纯化抗体,进行荷瘤裸鼠体内分布、SPECT放免显像及病理切片观察抑瘤作用。结果单链抗体干预后细胞PrxI蛋白表达水平较对照组下降(P<0.05)。体内分布研究表明单链抗体与肺腺癌组织有效结合。荷瘤裸鼠尾静脉注射131I标记抗体48h后,瘤/血和瘤/肌肉放射性比值均达到最大值4.06±0.13和5.17±0.97。SPECT示抗体注射后48hT/NT值明显高于12h、24h和72h(F均>86,P均<0.01)。治疗4周后,131I标记抗体治疗组肿瘤体积为(0.68±0.17)cm3,质量为(1.58±0.21)g,抑瘤率56.8%,与对照组比较有统计学差异。结论抗PrxI肺腺癌单链抗体能有效抑制肺腺癌细胞生长,131I标记单链抗体在体内能抑制肿瘤生长。

130例肝癌手术中应用皮下埋入式输药装置的体会

目的 :提高肝癌的诊治水平。方法 :对 130例肝癌手术中放置皮下埋入式输药装置 (DDS)进行回顾性分析。结果 :一期肝切除后 1、3、5a生存率为 86 5 %、5 2 6 %、31 2 % ;无法一期切除而行化疗或放免治疗后 1、3、5a生存率为 5 2 3%、18 7%、0 ,其中 4例获二期切除。结论 :肝癌手术中应常规放置DDS ,术后经DDS进行化疗或放免治疗 。

The effects of low-dose splenic irradiation and radiotherapy on immune system of patients with locally advanced non-small cell lung cancer

Objective： The aim of the research was to study the effects of low-dose splenic irradiation and radiotherapy on immune system of patients with locally advanced non-small cell lung cancer （NSCLC）. Methods： Twelve cases of stage III NSCLC in Tumor Radiotherapy Center of our hospital （the Affiliated Hospital of Medical College Qingdao University, China） were collected from July 2011 to July 2012; all patients were under 75 years old with clear pathology, measurable lesions and good personal statement. They were randomly divided into combined treatment group （D1 ＋ D2） and control group （D1）. The control group （D1） only received radiotherapy to the chest; combined treatment group （D1 ＋ D2） received low-dose splenic irradiation plus conventional dose irradiation. Flow cytometry was used to detect the peripheral blood T lymphocyte immune indexes of patients before, during and after the treatment, classification by five blood cell analyzer was used to determine white blood cells, neutrophils, hemoglobin and platelet count. The radiation induced toxicity including esophagitis, pneumonia and gastrointestinal reaction was observed, as well as the dose when it happened. Results： There was no significant difference in the ratio between two groups in cells CD4＋, CD8＋ and CD4＋/CD8＋ after radiotherapy （P 〉 0.05）. There was no change in these indicators in combined treatment group after treatment （P 〉 0.05）, but it decreased in control group （P 〈 0.05）. There was no significant difference in the incidences of radiation esophagitis, pneumonia, gastrointestinal reactions and bone marrow suppression between two groups （P 〉 0.05）, but the patients in combined treatment group seemed to tolerate high dose well （P 〈 0.05）. Conclusion： Low-dose splenic irradiation combined with radiotherapy to the chest can alleviate the injury degree of acute radiation induced the toxicity of locally advanced NSCLC patients, through affect the patient＇s immune function.

放射性碘标记热休克蛋白90α单克隆抗体用于肿瘤放射免疫治疗的研究

[目的]用放射性碘Na^(131)I标记热休克蛋白90α单克隆抗体,研究其在胶质瘤荷瘤小鼠模型的生物分布以及放射免疫治疗效果。[方法]热休克蛋白90α单克隆抗体的放射性^(131)I标记采用氯胺T法进行。标记抗体经尾静脉注射到U87细胞荷瘤小鼠模型体内,在注射体内后6、12、24h处死小鼠,测量其在各组织器官内的分布。放免实验分为实验组、对照组和未标记组,每组6只小鼠,注射药物后每5天测量肿瘤体积,连续40天。并记录全部小鼠注射后的生存时间。[结果]热休克蛋白90α单克隆抗体标记效率达到56%,纯化后放射化学纯度超过95%。分布数据表明^(131)I-Hsp90α单克隆抗体主要累积在肝脏、脾脏和肿瘤。治疗组肿瘤体积明显小于其他两组,抑瘤率高于其余两组且生存时间更长。[结论]热休克蛋白90α单克隆抗体可以用氯胺T法成功标记^(131)I。^(131)I标记热休克蛋白90α单克隆抗体可以被U87荷瘤小鼠的肿瘤组织特异性摄取,其用于放免治疗有一定的研究价值和临床应用前景。

Assistant radiotherapeutic effect of Jiaqi Mixture on tumor-bearing mice

Objective:The aim was to study the assistant radiotherapeutic effect of Jiaqi Mixture (JQM) on Ehrlich's ascites carcinoma (EAC) mice.Methods:The EAC-cancer model was made up with Kunming mice.The tumor-bearing mice were treated with whole body exposure (8 Gy) and intragastric administration of JQM,and the changes of tumor weight,the total number of white blood cells (WBC) and immune system were observed.Results:The average tumor weight,WBC,spleen coefficient,the stimulation index (SI) of Con A and LPS and the natural killing (NK) cell activity of mice decreased in some degree after radiotherapy,but the average tumor weight decreased more obviously in radiotherapy + medicine groups (compared with tumor control group,P < 0.05);and the other above indexes were much higher in radiotherapy + medicine groups than those in radiotherapy groups (P < 0.05-0.01).Conclusion:It was suggested that JQM can enhance the effect of radiation therapy and protect the normal immune system caused by radiation therapy.