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.     

紫杉醇联合放射线照射对肺腺癌细胞放射增敏作用的研究

目的 探讨化疗药紫杉醇是否对肺腺癌A973细胞有放射增敏作用.方法 取指数生长期的人肺腺癌细胞A973,采用成克隆分析法检测紫杉醇毒性,确定IC10、IC50和IC90剂量作为药物浓度.分析照射前后紫杉醇IC10、IC50和IC90浓度下作用24 h,照射剂最分别为0、1、2、4、6、8、10 Gy时的细胞存活分数,并用多靶单击模型拟合细胞存活曲线.采用流式细胞术分析不同浓度紫杉醇作用0、2、4、6、10、18、24 h,A973细胞周期分布变化.结果 紫杉醇对A973细胞的IC10、IC50和IC90剂量分别为0.5、2.6和8.7 nmol/L.IC10剂量紫杉醇照前给药增敏比为0.97(D0值比)、1.01(D0值比)、1.00(SF2值比),照后给药为0.97、1.02、1.02;IC50剂量照前给药为1.06、129.00、2.61,照后给药为0.94、129.00、2.14;IC90剂量照前给药为1.00、120.00、2.09,照后给药为0.98、120.00、2.09.IC10剂量紫杉醇对A973细胞无明显的G2+M期阻滞作用,而IC50和IC90剂量紫杉醇分别于2和18 h将A973细胞阻滞在G2+M期.结论 紫杉醇对肺腺癌细胞A973产生明显的放射增敏作用,且照射前后给药均有相似的增敏作用,中高浓度剂量联合小剂量X线照射增敏效果最好.     

地龙、复方丹参、野木瓜对鼻咽癌放射增敏的前瞻性研究（附557例近期疗效分析）

收集５５７例鼻咽癌以随机分组联合应用地龙、复方丹参、野木瓜进行放射增敏的前瞻性研究。近期疗效结果显示，不管放疗结束时原发灶的全消中还是放疗后３个月鼻咽ＣＴ扫描复查原发灶的全消率，中药放疗组均优于对照组，Ｐ＜０．００５。但颈淋巴结转移灶的全消率两组之间无明显差异，Ｐ＞０．５。同时还讨论了以上３种中药放射增敏的机理。     

甘氨双唑钠对肺鳞癌放射增敏的临床前瞻性研究

目的 通过对肺鳞癌放射增敏的临床研究，探讨甘氨双唑钠（CMNa)放射增敏的治疗效果。方法 402例肺鳞癌患者随机分为放射增敏组和对照观察组，放射增敏组病人在放疗过程中，分别给予CMNa 1200mg/m^2静脉滴注0.5h，同步给予对照组病人生理盐水250ml静脉滴注，观察两组患者不同的近期疗效。结果 肿瘤原发病灶CR率与CR PR率在两组之间差异有显著性，原发病灶达CR时吸收剂量明显低于对照组。两组患者治疗前后血常规和肝肾功能的检查结果，治疗中和治疗后不良反应及严重程度的比较无统计学意义。结论 CMNa可提高肺鳞癌的CR率和总有效率，并可降低肿瘤达到CR和PR时所需的吸收剂量。     

Combination therapy with misonidazole and mitomycin C: lack of chemosensitization of EMT6 tumor cells in vivo or in vitro

The effect of the nitroimidazole misonidazole on the cytotoxicity of mitomycin C was examined using EMT6 Rw tumors in mice and EMT6 cells in culture. In contrast to reports by others using a different tumor system, we were unable to detect any significant increase of mitomycin cytotoxicity by misonidazole in vivo using tumor cell survival or host toxicity endpoints. Studies with cells in vitro provided no evidence for marked chemosensitization of either hypoxic or aerobic cells.