放射线联合p53基因及内皮抑素治疗小鼠前列腺癌皮下移植瘤

Objective To test the hypothesis that p53 gene therapy combined with endostatin can enhance tumor response to radiation therapy of RM-1 mouse xenograft prostate cancer and to investigate its mechanism. Methods A mouse prostate cancer model was established. Then mice with xenograft tumor were randomly divided into group A (control), B (radiation), C (radiation and rAdp53), D (radiation and rh-endostatin) and E (radiation and rAdp53 and rh-endostatin). On day 1, rAdp53 was injected intra-tumorously with 1 × 1010 vp per animal to group C and E. From day 1 to 14, rh-endostatin was given 15 mg/kg intraperitoneally daily to group D and E. On day 4 single fraction of 15 Gy was given to tumors in groups B, C, D and E. Normal saline was injected intra-tumorously or intraperitoneaUy accordingly as control. No treatment was done to group A. Tumor volume was measured daily. Samples were collected on Days 5, 10 and 15. Ki67, CD31, p53 and VEGF were detected by means of immunohistochemistry. Results (1) Radiation alone, radiation combined with intra-tumorous injection of Adp53 and/or intraperitoneal injection of rh-endostatin resulted in tumor growth arrest of RM-1 cells in vivo (P = 0.000). Radiation combined with both rAdp53 and rh-endostatin was the most effective treatment (P < 0.05). (2) All the four treatment groups had a decreased expression of mutant type P53 (P = 0.000). The expression of Ki67 in groups B and C were equal (P 0.05) and increasing (P = 0.000), respectively. Group D had a up-down-up curve (P < 0.05), but group E had a up-down one. On day 5 the expresion of VEGF in group E was the lowest (P < 0.05). An increased expression of MVD compared with the control was shown, and MVD in groups C, D and E were always higher than that in the control (P < 0.05). Conclusions The limitation of radiotherapy could be overcome by combination with beth p53 gene therapy and endostatin on the growth of mouse prostate cancer cell. Radiation, rAdp53 and endostatin have their own role but they can be interacted with each other.     

BOPPPS模式在放射生物学线上教学活动中的效果分析

目的 利用BOPPPS模式,包括导入（bridge-in）、学习目标（outcome）、前测（pre-test）、参与式学习（participation）、后测（post-test）、总结（summary）,探讨肿瘤放疗从业人员线上学习放射生物学相关知识的效果。方法 选取细胞存活曲线、细胞周期和放射敏感性为例,以多个大学附属医院放疗从业人员为研究对象,开展了一项多中心前瞻随机对照研究。所有学员采用分类随机分组的方式,分为BOPPPS组和对照组。BOPPPS组是将课程设计为网上课堂,分为课前准备、网络授课以及课后阶段3个环节。网络授课阶段包含视频观看、基础知识学习、文献探讨及分组讨论等多种形式。对照组即为传统的教学模式。采用χ²检验比较两组一般情况的一致性,采用非参检验比较两组或者多组间成绩的差异。结果 课前摸底测试为（58.56±0.99）分。课后BOPPPS组平均分为（85.48±0.85）分,对照组为（77.79±1.10）分,与对照组相比,BOPPPS组平均分升高7.69分（Z=5.31,P < 0.001）。BOPPPS组和对照组的平均答题时间分别为（296.62±15.40）和（386.41±21.27） s,BOPPPS组缩短了89.79 s （Z=3.34,P=0.001）。亚组分析发现,学员不论是否学过放射生物学课程,BOPPPS组的成绩均有显著性提高,且在未学过的学员中,成绩提升幅度更大。从不同岗位情况分析,发现BOPPPS组和对照组相比均有提高,特别是对于医师、副主任医师和技师成绩的提高差异有统计学意义（Z=3.98、3.53、2.32,P<0.05）;不同学位之间成绩也有差异,本科和博士学员的成绩有显著提高（Z=3.64、4.18,P< 0.001）。结论 将BOPPPS教学模式灵活应用于放射生物学等枯燥的学科的线上教育中,对于提高放疗科医技人员的理论基础具有重要意义。     

低氧对小鼠小肠的放射防护作用

为探讨放射治疗中氧效应,在低氧状态下对小鼠一次性照射,计数小肠纵断面隐窝数,观察低氧对小鼠的防护作用。结果为:未受照射的低氧组与空气组的组织学表现或隐窝计数无显著差异,表明短时间单纯吸入低氧(11％)72小时后不会对小肠产生明显影响。5Gy照射后72小时后78％隐窝明显再生,与对照组无明显差异。8Gy,10Gy,12Gy,15Gy,18Gy组与空气对照组都有显著性统计差异。     

前列腺癌的放射免疫治疗

放射免疫治疗(radioimmunotherapy,RIT)以单克隆抗体为载体,通过特异性结合于表达相关抗原的肿瘤细胞,实现对肿瘤细胞的近距离内照射.与传统放疗相比,RIT较长时间内持续低剂量照射细胞,将细胞周期阻滞在对辐射最敏感的G2/M期,且通过抑制DNA的损伤修复而增强杀伤作用[1].     

白桦脂酸抑制食管鳞状细胞癌增殖及相关机制的实验研究

 目的研究抗肿瘤药物白桦脂酸（BA）对人食管鳞癌KYSE170细胞的抑制作用及抗肿瘤作用机制。方法采用不同质量浓度(0、5、10、20、40、60、80、100 μg·mL-1)白桦脂酸处理KYSE170细胞,作用不同时间 (24、48、72 h)后 ,噻唑蓝（MTT）法检测KYSE170 细胞生长的短期抑制作用;不同质量浓度（0、5、20、40 μg·mL-1）白桦脂酸作用于细胞24 h后以克隆形成实验检测药物对细胞生长的长期抑制作用;不同质量浓度白桦脂酸 (10、60、100 μg·mL-1)作用KYSE170细胞 24、48 h后以流式细胞仪FITC Annexin V/PI双染法检测细胞凋亡变化,不同质量浓度白桦脂酸（0、10、40 μg·mL-1）作用细胞24 h后以流式细胞仪检测细胞周期的改变。结果噻唑蓝实验显示,不同质量浓度白桦脂酸对KYSE170细胞均有抑制作用,抑制效果呈时间和剂量依赖性,24、48、72 h的IC50分别为(5681±256)、(3973±277)和(2928±305)  μg·mL-1;克隆形成结果显示,0、5、20、40 μg·mL-1药物作用细胞后,克隆形成率分别为（8956+500）%、（6100+203）%、（3133+351）%和（1533+233）%,随白桦脂酸质量浓度增大而明显降低（P< 001）。凋亡结果显示, 各实验组KYSE170细胞凋亡率随白桦脂酸质量浓度加大和药物作用时间的延长明显增高（P＜ 005或001）。细胞周期结果显示,0、1、10 μg·mL-1白桦脂酸作用细胞24 h后,随药物质量浓度增大,G1期细胞比例减少,S期细胞比例不断增加,实验组与空白组对比均有统计学差异（P<001）。结论白桦脂酸能抑制人食管鳞癌KYSE170细胞的生长,这一作用可能是通过诱导细胞凋亡、阻滞细胞停留在S期来实现的。