中药安迪粉针剂的放射增敏作用

目的 探讨安迪粉针剂(Andi)增强电离辐射生物学效应的作用机理。方法 以人食管癌细胞株(ECA l09)为观察对象，采用电镜、流式细胞仪分析、台盼兰染色等方法，分别观察对照、Andi、^60Co—γ线照射和Andi 照射4个组对ECA 109细胞的形态、细胞周期、细胞凋亡和坏死等的影响；并采用改良硫代巴比妥酸荧光法测定丙二醛(MDA)；羟胺法测定超氧化物歧化酶(SOD)。结果 在乏氧条件下，Andi能引起ECA 109细胞坏死(P＜0．05)，并增加MDA含量(P＜0．05)；而Andi 照射组的作用比单用Andi和单纯照射明显增强(F＝6．53，P＜0．01)；从Andi、照射、Andi照射3个组的光镜和电镜结果发现，ECA l09癌细胞明显变性、坏死、凋亡，但以Andi 照射组的改变更显著；电镜显示Andi组有较多ECA l09细胞存在糖原颗粒堆积。结论Andi可以引起乏氧ECA 109细胞的糖代谢障碍，增加细胞内自由基的产生，引起细胞坏死；Andi与^60Co—γ线合用能进一步促进乏氧细胞坏死，具有协同作用；Andi放射增敏作用的机理可能与其促进癌细胞内自由基产生或影响癌细胞糖代谢有关。     

四磺酸卟啉镁对小鼠Lewis肺癌的放射增敏效应

探讨四磺酸卟啉镁的放射增敏效应。材料与方法将荷Ｌｅｗｉｓ肺癌的Ｃ５７ＢＬ／６小鼠随机分为４组：对照组、单药组、单放组及用药加放射组。其中单药组和用药加放射组小鼠腹腔单次注射四磺酸卟啉镁１３．７５ｍｇ／ｋｇ体重，单放组和用药加放射组各分１０、１５、２０Ｇｙ３个剂量小组进行单次放射，每组各８只鼠，结果（１）当肿瘤体积达原照射体积４倍时，测得四磺酸卟啉镁的增敏比为１．４５～１．７０，平均１．５８。（２）各组小鼠生存时间无显著差异。结论四磺酸卟啉镁对Ｌｅｗｉｓ肺癌具有放射增敏效应。     

Allosteric effectors of hemoglobin as modulators of chemotherapy and radiation therapy in vitro and in vivo

Introduction: A series of molecules designed to be allosteric effectors of hemoglobin were examined for their potential as radiation sensitizers in vitro and in vivo and for their potential as chemosensitizers in vivo as well as for their antimetastatic effect. Results: At a concentration of 100 μM for 1 h prior to, during and for 1.5 h after radiation exposure, the allosteric effectors decreased the shoulder of the radiation survival curve of normally oxygenated EMT-6 cells and increased the slope of the radiation survival curves of hypoxic EMT-6 cells resulting in dose-modifying factors of 1.8 to 2.1. In vivo the allosteric effectors had antitumor activity against the Lewis lung carcinoma and produced primarily additive tumor growth delay when administered along with fractionated radiation therapy. When administered on days 4 through 18 after tumor implantation, the allosteric effectors, especially JP-7, RSR-13 and RSR-4, were highly effective antimetastatic agents in animals bearing Lewis lung carcinoma. In cell culture, simultaneous exposure to the allosteric effectors (at 100 μM ) effectively sensitized EMT-6 cells to the effects of 4-hydroperoxycyclophosphamide, thiotepa and carboplatin. The allosteric effectors were not very cytotoxic toward EMT-6 tumor cells from tumors treated in vivo with single doses of each molecule nor were these agents very cytotoxic toward bone marrow CFU-GM taken from the same animals. Conclusions: It is likely that the allosteric effectors have a molecular target in addition to hemoglobin. Other possible targets include hydroxymethyl-glutaryl-CoA reductase or microsomal cytochrome b₅. Received: 27 June 1997 / Accepted: 8 October 1997     

铈纳米颗粒在辐射领域的研究进展

随着核技术在工业，医学领域等方面应用的迅速发展，人们遭受辐射损伤的可能性也随之增加。辐射损伤防治药物是救治与防护辐射损伤最为有效和直接的手段，但目前的辐射损伤防治药物作用效果有限。铈纳米材料因独特的价态结构，使其具有多种酶学模拟活性和可再生性，体现出优越的抗氧化性，强大的清除自由基功能，可以保护细胞免受辐射损伤，可作为理想的辐射防护剂，并应用于多种生物学领域。对相关文献进行查阅可知，铈纳米颗粒的抗氧化性、高SOD模拟活性、清除自由基能力以及抗辐射能力均源自于Ce³⁺/Ce⁴+相互间的转化、氧空位的形成。本文主要介绍铈纳米颗粒的抗辐射活性基础、辐射防护效应及放疗增敏方面的研究进展，为铈纳米颗粒在辐射方向领域提供理论依据与参考。     

Hyperthermic Enhancement of Tumor Radiosensitization Strategies

Local hyperthermia of living tissue can cause significant increases in blood flow and oxygenation depending on time-temperature history. Increases in perfusion of the abnormal and insufficient vasculature found in solid tumors may increase tumor oxygenation, thereby increasing the radiation sensitivity of the tumor. We hypothesized that local heating of tumor would increase the oxygenation of the tumor tissue and allow other oxygenating agents to further modify tumor oxygenation and radiation response. In the present study the effect of moderate temperature hyperthermia (MTH) at 41.5–42.5°C for 30–60 min, 250 mg/kg nicotinamide, or carbogen breathing (95% O₂/5% CO₂) on the radiation sensitivity of FSaII murine fibrosarcomas or R3230 AC rat adenocarcinomas was studied. Individually, these treatments increased the tumor cell sensitivity to single dose 10–15 Gy X-irradiation by 1–5 fold on average, as measured by the in vivo/in vitro tumor excision assay. The combination of tumor MTH with nicotinamide or carbogen breathing increased the radiation sensitivity by 3–5 fold in FSaII tumors and 10–30 fold in R3230 tumors with varying levels of statistical significance. Finally, the triple combination of adjuvant MTH, nicotinamide and carbogen breathing increased the radiation-induced cell death in FSaII tumors to a similar extent as the dual combinations of MTH, nicotinamide or heat, carbogen breathing. However, in R3230 AC tumors the triple adjuvant combination significantly increased radiation-induced cell killing compared to all other dual adjuvant treatments (p < 0.04). To interrogate the mechanism by which heating alters tumor physiology, nitric oxide production in tumor and endothelial cells in culture and tumor tissue after heating was studied. Heating caused an increase in nitric oxide production over a 24 h period after treatment. Subsequently, inhibiting the enzymatic production of NO with L-NAME was found to increase heat-induced growth delay of FSaII tumors. The cause and effect of increased nitric oxide production and the response of the tumor vasculature to heat are discussed in the context of the tumor radiosensitization achieved by heating, carbogen breathing and nicotinamide.     

缓释渗透增敏化疗加放疗综合治疗食管癌50例

目的:探讨缓释渗透增敏化疗加放疗综合治疗食管癌的疗效.方法:采取食管缓释渗疗器局部缓释渗疗同时配合X线常规放疗50例食管癌,另50例行单纯常规分割X线外照射作为同期对照研究;观察近期疗效及1,3,5a生存率.结果:缓释渗透治疗组与单纯放疗组的完全缓解(CR),部分缓解(PR),CR PR,无变化(NC),肿瘤进展(PD)分别为:55.1%,10%;40.8%,60%;95.9%,70%;0,20%;4.8%,10%.缓释渗透治疗组的CR,CR PR,PR与单纯放疗组相比有显著性差异(P<0.01或P<0.05).生存情况:缓释渗透治疗组与单纯放疗组1a生存率为73.46%,52%(P<0.05);3a生存率为40.8%,28%(P>0.05);5a生存率为16.3%,0(P<0.005).结论:食管缓释渗疗器局部缓释渗疗配合常规分割放疗综合治疗食管癌,有显著的近期疗效;同时改善了患者的生存率.     

埃克替尼对人鼻咽癌 CNE -1细胞的放射增敏作用

目的：探讨埃克替尼对人鼻咽癌离体细胞系 CNE -1的放射增敏作用及机制。方法通过实验室对人鼻咽癌 CNE -1进行细胞培养,对不同浓度埃克替尼及不同剂量放疗治疗进行实验分组。利用多靶单击数学模型拟合放射剂量-细胞存活曲线,用 MTT 法观察药物对体外培养的鼻咽癌 CNE -1细胞凋亡的影响,用荧光染色法检测凋亡细胞。采用流式细胞术分析药物对 CNE -1细胞周期的影响,高倍光镜下观察细胞形态。结果埃克替尼作用后,0.094μmol/ L,0.188μmol/ L,0.376μmol/ L 的放射增敏比分别为1.095,1.433,1.639,呈药物浓度依赖性。通过流式细胞仪检测,在药物浓度增加情况下,在4 Gy 照射下可使周期中 G0/ G1有所增高（ P <0.05）,S 期所占比率降低（ P <0.05）。药物与放射联合的情况下,细胞凋亡比率增加明显,差异具有统计学意义（ P <0.05）。凋亡指数与药物剂量及放射剂量具有明显相关性（ P <0.05）,并且在两者联合的情况下,凋亡的程度有叠加（ P <0.05）。结论埃克替尼对鼻咽癌离体细胞系 CNE -1有明显的放射增敏效益,放射增敏机制与埃克替尼抑制肿瘤细胞的再修复能力,改变细胞分裂周期中分布,从而增加细胞凋亡率有关。     

DNA-PK基因沉默对卵巢癌细胞细胞凋亡的影响

目的 探讨DNA-PK基因对沉默卵巢癌细胞凋亡的影响及机制.方法 DNA-PK shRNA以脂质体介导转染卵巢癌细胞株Skov3,24h后接受2Gy X射线照射,继续培养48 h.收集细胞,标记Annexin Ⅴ/PI,流式细胞术分析细胞凋亡情况,同时,RT-PCR检测p53和p21 mRNA的表达量.结果 2Gy辐射引起2.40％±1.53％ Skov3细胞凋亡,高于对照组（t=2.618,P=0.026）,而转染DNA-PK shRNA的Skov3细胞经2Gy照射,凋亡细胞为18.74％±4.15％,明显高于单纯2Gy照射组（t=9.052,P＜0.001）及DNA-PK shRNA转染组（2.77％±1.73％）（t=8.869,P＜0.001）.RT-PCR检测结果显示,2Gy照射组,Skov3细胞p53 mRNA表达量高于对照组,而DNA-PKshRNA转染的Skov3细胞接受2Gy照射,其p53 mRNA表达量降低,接近正常水平,单独转染DNA-PK shRNA组p53 mRNA表达量无明显变化.转染DNA-PK shRNA的Skov3细胞经2Gy照射,其p21 mRNA表达量低于2Gy照射组接近正常组水平,单独转染DNA-PK shRNA组Skov3细胞p21 mRNA表达水平与正常对照组相当.结论 DNA-PK shRNA可增加辐射后巢癌细胞株的细胞凋亡,其可能机制是通过下调p53和p21 mRNA表达,而启动细胞凋亡.     

hape反义核酸的构建及其对细胞辐射效应的影响

目的克隆人ＡＰ内切核酸酶基因（ｈａｐｅ）ｃＤＮＡ全长编码序列,研究ｈａｐｅ反义核酸对细胞辐射敏感性和Ｈ２Ｏ２细胞毒的影响。方法反转录ＰＣＲ克隆人ｈａｐｅｃＤＮＡ,应用基因重组技术构建真核反义表达载体,用Ｌｉｐｏｆｅｃｔａｍｉｎｅ介导基因转染,细胞克隆形成法分析细胞存活。结果从人胚肺（ＨＥＬ）细胞中克隆出ｈａｐｅｃＤＮＡ全长编码序列,构建了ｈａｐｅ的真核反义表达质粒ｐＣＩＮ／ＡＳｈａｐｅ并转染ＨＯＣ８细胞,研究表明ｈａｐｅ反义核酸,提高了ＨＯＣ８细胞对γ射线和Ｈ２Ｏ２损伤的敏感性。结论利用分子生物学技术手段,阻断细胞ＤＮＡ修复过程中的某一环节,是细胞辐射或化疗药物增敏的一种有效途径。     

Tat-SmacN7对人乳腺癌细胞系的放射增敏作用

目的 观察Tat-SmacN7对人乳腺癌SK-BR-3细胞放射敏感性的影响并探讨其机制。方法 取对数生长期乳腺癌SK-BR-3细胞,分为对照组、γ射线照射组、Tat-SmacN7组和Tat-SmacN7联合γ射线照射组（联合组）。MTT法检测Tat-SmacN7对SK-BR-3细胞的毒性;克隆形成实验检测Tat-SmacN7的存活分数;单击多靶模型拟合细胞存活曲线并计算放射增敏比（SER）;流式细胞术检测Tat-SmacN7联合γ射线照射对细胞凋亡的影响;Western blot法检测细胞凋亡抑制蛋白XIAP和cIAP-1蛋白表达水平。结果 Tat-SmacN7随浓度升高对SK-BR-3细胞的增殖抑制率增大,药物浓度与细胞增殖率呈正相关（r=0.924,P<0.05）,IC₅₀为（62.62±1.19）μmol/L,IC₂₀为（5.66±0.67）μmol/L;5 μmol/L Tat-SmacN7能增加SK-BR-3细胞的放射敏感性,联合组与照射组放射增敏比为1.48;6 Gy γ射线照射后48 h,联合组凋亡率显著高于照射组（t=7.01,P<0.05）;与对照组相比,Tat-SmacN7组XIAP表达水平降低,联合组XIAP和cIAP-1蛋白表达水平均降低。结论 Tat-SmacN7通过促进人乳腺癌细胞SK-BR-3细胞的凋亡,增加其辐射敏感性,这一特性与XIAP的表达有关。