穿心莲内酯对食管癌细胞的放射增敏作用

目的研究穿心莲内酯对食管癌细胞的放射增敏作用。方法培养食管癌 ECA?109细胞,通过四甲基偶氮唑盐微量酶反应比色法(MTT法)检测穿心莲内酯对细胞生长的抑制;克隆集落形成实验观察穿心莲内酯的放射增敏作用;通过免疫荧光实验观察促凋亡蛋白 Bax的表达情况;流式细胞仪检测细胞的凋亡和周期情况;蛋白质印迹法(Western Blot)检测细胞内核因子 κB(NF?κB)半胱氨酸天冬氨酸蛋白酶 3(caspase3)Bax,B淋巴细胞瘤 ?2基因(Bcl?2)的表达;磷酸化组蛋白 H2AX(γ? H2AX)焦点形成检,测 DNA分钟损伤情况。细胞划痕实验,检测细胞增殖、迁移的情况。结果穿心莲内酯抑制食管癌 ECA? 109细胞的生长,并且有明显的时间和剂量依赖性;通过单击靶模型拟合曲线,可见低浓度穿心莲内酯预处理 6h,相对比单纯照射组可以增加 ECA?109细胞的放射敏感性(t＝4.59,P＝0.02)放射增敏比为 1.28;与单纯照射组(26.5±2.2)%相比,加入穿心莲内酯联合 X射线照射组中的细胞凋亡率(32.5±0.9)%明显增加,(P＜0.05);穿心莲内酯作用于食管癌细胞,可以使凋亡相关蛋白 caspase3,Bax的表达升高,并且呈明显的量效关系, NF?κB表达趋势与 Bcl?2一致;相对于单纯照射组,穿心莲内酯与 X射线联合作用,能够增加双链 DNA断裂(DSB)数目;药物联合放射可以明显影响食管癌细胞的增殖迁移能力。结论穿心莲内酯能够提高食管癌细胞的放射敏感性,机制可能与其增加食管癌细胞的凋亡率和调节细胞内的 NF?κB的表达有关。     

DL型丁胱亚磺酰亚胺对大鼠C_6神经胶质瘤细胞放射增敏效应研究

目的　研究有氧及乏氧状态下DL型丁胱亚磺酰亚胺(DL BSO)对大鼠C6神经胶质瘤细胞的放射增敏效应。方法　以60 Coγ射线为放射源 ,分有氧和乏氧状态下单纯照射组、加药照射组。采用细胞克隆形成方法观察DL BSO对神经胶质瘤细胞的放射增敏效应。结果　有氧状态下 ,DL BSO的放射增敏作用和药物作用时间有关。 0 1mmol·L-1DL BSO用药 2、6、12h ,未能观察到放射增敏作用 ,放射增敏作用仅在用药后 2 4、4 8h出现。乏氧状态下 ,0 1mmol·L-1DL BSO用药后 ,各时间点 (2～ 4 8h)均可见放射增敏效应。有氧、乏氧状态下不同浓度DL BSO的放射增敏作用和药物浓度有关。结论　DL BSO对有氧及乏氧状态下的大鼠C6神经胶质瘤细胞均有放射增敏作用。离体状态下 ,DL BSO主要表现出乏氧增敏作用 ,并呈现一定的时间、浓度依赖关系。     

五麦党黄口服液对辐射损伤小鼠脏器中自由基清除能力的影响

目的观察五麦党黄口服液（wMDH）对^60Coγ射线照射所致小鼠主要脏器中超氧化物歧化酶（SOD）活力、丙二醛（MDA）含量、抑制羟自由基能力的影响。方法将小鼠随机分成正常对照组,辐照模型组及WMDH低、中、高剂量组。辐照模型组及WMDH低、中、高剂量组各接受1次γ射线照射,同时WMDH各剂量组用WMDH灌胃,连续7d。处死后取肝、脾、肾和肺组织,测定SOD活力、MDA含量、抑制羟自由基能力。结果WMDH能提高受照小鼠脏器中SOD活力,降低脏器中MDA含量,增加肝脏、肾脏和肺组织中抑制羟自由基的能力（P〈0．05或P〈0．01）。结论WMDH能提高辐射损伤小鼠脏器组织的自由基清除能力,具有一定的抗辐射损伤作用。     

一氧化氮合酶对丝裂霉素C衍生物629细胞毒性的影响

目的评价一氧化氮合酶对丝裂霉素C(MMC)衍生物——5-氮丙啶基-3-羟基-1-甲基吲哚-4，7-二酮(629)的细胞毒性和乏氧选择性的影响。方法以人纤维肉瘤细胞株HT1080和其诱导型一氧化氮合酶(iNOS)基因转染的细胞克隆(iNOS9，iNOS12)为实验对象。四噻唑蓝(MTT)法检测MMC与其衍生物629的细胞毒性，比较乏氧和有氧条件下两种化合物半数抑制率(IC₅₀)的差异；琼脂糖凝胶电泳和流式细胞术观察629作用后肿瘤细胞脱氧核糖核酸(DNA)的损伤情况，分析不同iNOS活性的肿瘤细胞对629敏感性的差异及原因。结果629的IC₅₀较MMC低数百倍，是高细胞毒性的化合物；随着细胞中iNOS活性的增加，629对乏氧细胞的选择性损伤作用显著增强，DNA电泳显示629引起细胞坏死，造成细胞周期G₂/M阻滞。结论MMC衍生物629是具有更高乏氧选择性的增敏化合物。     

冬虫夏草水提液体外对缺氧再给氧时心肌细胞脂质过氧化作用的影响

目的：在细胞水平研究冬虫夏草水提液对心肌细胞缺氧再给氧时细胞内丙二醛（MDA）含量、超氧化物歧化酶（SOD）活性及细胞膜脂质流动性的影响，探讨冬虫夏草抗脂质过氧化作用及其可能机制。结果：缺氧再给氧组心肌细胞MDA含量增加，SOD活性降低，细胞膜脂质流动性下降，与对照组比较，P均＜0．01；缺氧再给氧＋冬虫夏草组上述改变减轻，其中100μg／ml、1000μg／ml组上述指标与缺氧再给氧组及10μg／ml组比较，P均＜0．01。结论：缺氧再给氧时细胞内脂质过氧化作用增强；冬虫夏草明显减轻缺氧再给氧时细胞内脂质过氧化作用，且呈良好量效关系。     

锌对γ射线致小鼠骨髓造血细胞损伤的影响

目的 探讨锌对γ射线诱导的体外培养小鼠骨髓细胞辐射损伤的影响及可能机制，为进一步开发和利用锌体的辐射损伤的防护物质提供依据。方法 分离小鼠骨髓细胞并悬浮于RPMI 1640培养基中，分别将锌按20、200、400、800μmol／L终浓度加入细胞培养液中，5Gy^60Coγ射线照射骨髓细胞后置于37℃，5％CO2细胞培养箱中培养，16h后终止培养，分别测定有核细胞数、细胞DNA含量、细胞培养液及细胞内超氧化物歧化酶(SOD)活力、丙二醛(MDA)含量和细胞培养液活性氧(ROS)含量。结果5Gy^60Coγ射线照射体外培养的小鼠骨髓细胞后，骨髓有核细胞数、DNA含量均明显下降；细胞培养液和细胞内SOD活力均明显下降，而MDA含量显著增加，培养液ROS含量明显升高。照射前在培养液中加入一定浓度的锌，DNA含量升高，有核细胞数增加；培养液ROS含量下降、细胞内SOD活力升高、MDA含量下降，并在200—800μmol／L的剂量范围内，存在剂量-反应关系。结论 锌在一定剂量范围内对经。Coγ射线照射的体外培养，小鼠骨髓细胞的辐射损伤具有较好的防护作用，其作用机制可能与锌的抗脂质过氧化作用有关。     

用CB微核法研究离体血辐射剂量与微核的量效关系

本实验应用外周微量血培养加细胞松弛素B观察微核(CB法)探讨了X射线与不同剂量率的*铆射线诱发馓校率的量散关系。结果表明．剂量率相同．辐射剂量相同，^60Coγ射线辐照所得微核频率明显高于X射线照射所得微核频率；不同剂量率的^60Coγ射线照射，高剂量率所得微核产率高．因而在辐射事故时，应选用同一性质及相应剂量率的效应曲线．来评估诱发微核的辐射剂量．     

肉苁蓉总苷对~(60)Coγ射线照射小鼠造血系统损伤保护作用的研究

目的　研究肉苁蓉总苷 (GCs )对60 Coγ射线照射小鼠造血系统损伤的辐射防护作用 ,探讨其作用机制。方法　连续动态观察GCs对小鼠经60 Coγ射线照射后d 3,d 7,d14,d 2 1外周血血红蛋白、白细胞、网织红细胞、骨髓有核细胞数、脾集落数 (CFU S)以及骨髓细胞硒 谷胱甘肽过氧化物酶 (Se GSH Px)活性和丙二醛 (MDA)含量的影响。结果　辐射损伤后小鼠外周血白细胞、网织红细胞、骨髓有核细胞数、CFU S明显减少 ,骨髓细胞及脾Se GSH Px活性降低 ,MDA含量明显增加。GCs可促进上述各造血指标的恢复 ,提高Se GSH Px活性 ,降低MDA含量。结论　GCs对受照小鼠造血系统具有保护作用 ,其机制可能与抗氧化作用有关。     

姜黄素调控乳腺癌细胞增殖与转移机制研究

目的研究姜黄素对人乳腺癌细胞MDA MB 453中缺氧诱导因子 1α（HIF 1α）的影响及其对肿瘤细胞增殖和转移的作用。方法采用噻唑蓝（MTT）法和细胞计数观察姜黄素抑制MDA MB 453细胞增生作用；采用transwell侵袭小室测定姜黄素对MDA MB 453转移的影响；采用Real time PCR和Western blot印迹法检测常氧和乏氧状态下姜黄素对MDA MB 453细胞系中HIF 1α的mRNA和蛋白表达水平的影响，同时采用Real time PCR和ELISA法检测姜黄素对HIF 1α下游靶基因血管内皮生长因子（VEGF）mRNA水平和蛋白表达水平的影响。结果姜黄素对MDA MB 453细胞体外生长和转移具有抑制作用；常氧、乏氧状态下加入姜黄素后，MDA MB 453细胞系中HIF 1α的mRNA水平无变化，但蛋白水平明显降低，VEGF mRNA水平和蛋白水平均明显降低。结论姜黄素通过HIF 1α调控MDA MB 453细胞系增殖和转移。     

大黄素对乏氧鼻咽癌细胞的放射增敏性与DNA修复基因的关系

目的研究广西何首乌中大黄素(emodin)对乏氧状态鼻咽癌CNE-1细胞KU70/80表达的影响,探讨其放射增敏作用与DNA修复基因的关系。方法通氮乏氧条件下,应用实时荧光定量PCR技术检测放射增敏实验组和对照组鼻咽癌细胞中乏氧诱导因子(HIF-1α)和DNA双链断裂修复基因(KU70/KU80)mRNA的表达水平。结果乏氧作用不同时间后HIF-1αmRNA表达都明显升高,而单独药物组HIF-1α表达无明显变化;单纯放疗组能诱导KU70/KU80 mRNA表达上调,放疗联合乏氧组对KU70/KU80的上调作用比单纯放疗组更明显;而在乏氧情况下进行加药和照射处理后KU70/KU80 mRNA表达明显降低。结论在乏氧环境下,大黄素联合放疗能有效下调HIF-1α和DNA双链断裂修复基因(KU70/KU80)mRNA的表达水平,这可能是其增敏作用的分子机制。     

安迪粉针剂抗肿瘤作用的实验研究

目的　探讨安迪粉针剂 (简称安迪 )对小鼠移植性肿瘤的抑制作用 ,以及对其免疫功能的影响。方法　采用小鼠移植性肿瘤即艾氏腹水癌 (ECA)、肉瘤180 (S180 )、肝癌 (HCA)、Lewis肺癌模型 ,以 5 - FU为阳性对照组 ,观察 2 5 ,1 2 ,6 mg·kg-1安迪的抗肿瘤作用 ,并采用小鼠溶血素实验和小鼠迟发性变态反应实验观察安迪对荷瘤小鼠免疫功能的影响。结果　不同浓度安迪对体外 ECA肿瘤细胞的蓝染率分别为 1 0 0 % ,96 % ,89% ,6 5 %和 49% (P <0 .0 1 ) ;安迪对 S180 、HCA和 Lewis移植瘤的抑制率分别达 42 .1 %～ 5 4 .8% ,3 8.2 %～ 5 3 .5 %和42 .1 %～ 5 5 .3 % (P <0 .0 1 ) ;对小鼠腹水型 HCA的生命延长率为 1 1 0 .4%～ 1 3 6 .1 % (P <0 .0 1 ) ;与阳性对照组比较 ,安迪对荷瘤小鼠免疫功能无抑制作用。结论　安迪具有较强的抗肿瘤作用 ,且对荷瘤小鼠免疫功能无影响     

Silencing Prx1 and/or Prx5 sensitizes human esophageal cancer cells to ionizing radiation and increases apoptosis via intracellular ROS accumulation

Aim:

To investigate whether down-regulation of peroxiredoxin 1 (Prx1) and/or peroxiredoxin 5 (Prx5) sensitizes human esophageal cancer cells to ionizing radiation (IR).

Methods:

Human esophageal carcinoma cell lines Eca-109 and TE-1 were used. Prx mRNA expression profiles in Eca-109 and TE-1 cells were determined using RT-PCR. Two highly expressed isoforms of Prxs, Prx1 and Prx5, were silenced by RNA interference (RNAi). Following IR, intracellular reactive oxygen species (ROS) and apoptosis were measured using flow cytometry, the activities of catalase, superoxide dismutase and glutathione peroxidase were measured, and the radiosensitizing effect of RNAi was observed. Tumor xenograft model was also used to examine the radiosensitizing effect of RNAi in vivo.

Results:

Down-regulation of Prx1 and/or Prx5 by RNAi does not alter the activities of catalase, superoxide dismutase and glutathione peroxidase, but made human tumor cells more sensitive to IR-induced apoptosis both in vitro and in vivo. When the two isoforms were decreased simultaneously, intracellular ROS and apoptosis significantly increased after IR.

Conclusion:

Silencing Prx1 and/or Prx5 by RNAi sensitizes human Eca-109 and TE-1 cells to IR, and the intracellular ROS accumulation may contribute to the radiosensitizing effect of the RNAi.     

塞来西布对食管癌ECA-109细胞系放射增敏效应的研究

目的：了解环氧化物酶-2（COX-2）选择性抑制剂——塞来西布对食管癌ECA-109细胞系的放射增敏作用。方法：选择ECA-109细胞系作为试验对象,检测ECA-109细胞系的COX-2表达水平,设塞来西布0.25、50、100μmol/L4个实验组,分别予6MV-X线照射0、2、4、6Gy后,再分别行MTT比色试验、克隆形成实验、流式细胞仪计数,检测细胞的增殖能力、克隆形成能力及凋亡3项指标。结果：不同辐射剂量与不同浓度的塞来西布对ECA-109细胞的增殖、凋亡率作用有统计学差异（P〈0.05）,塞来西布与放射对ECA-109细胞的增殖抑制和诱导凋亡作用随塞来西布的浓度和照射剂量的增加而增强;塞来西布联合放射对ECA-109细胞的存活率、D0值和Dq值作用均小于单纯放射组,Dq变小;塞来西布和4Gy（6MV-X）联合用于ECA-109细胞其凋亡率有统计学差异（P〈0.05）。结论：塞来西布能抑制ECA-109细胞增殖,诱导其凋亡。塞来西布与放射联合应用对ECA-109细胞的增殖抑制、诱导凋亡有协同增强的作用。     

Cytotoxicity and radiosensitising activity of synthesized dinitrophenyl derivatives of 5-fluorouracil

Background and the purpose of the study

Dual functional agents in which nitroaromatic or nitroheterocyclic compounds are attached through a linker unit to mustards and aziridines have shown higher cytotoxicities than the corresponding counterparts to both aerobic and hypoxic cells and enhanced radiosensitizing activity. In the present investigation cytotoxicity and radiosensitizing activity of 2,4-dinitrobenzyl, 2,4-dinitrobenzoyl, and 2,4-dinitrophenacetyl derivatives of 5-fluorouracil which was assumed to release cytotoxic active quinone methidide and 5-fluorouracil under hypoxic conditions on HT-29 cell line under both aerobic and hypoxic conditions was investigated.

Methods

5-fluorouracil derivative X-XIII were prepared by the reaction of the corresponding di-nitro substituted benzyl, benzoyl and phenacetyl halides with 5-fluorouracil protected at N-1 with di-t-butoxydicarbonate (BOC) in dimethyl formamide (DMF) in the presence of the potassium carbonate followed by hydrolysis of the blocking group by potassium carbonate in methanol. Cytotoxicity of fluorouracil VIII and tested compounds X-XIII against HT-29 cell line under both aerobic and hypoxic conditions after 48 hrs incubation were measured by determination of the percent of the survival cells using 3-(4,5-Dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay and percent of the dead cells using propidium iodide(PI)-digitonine assay and results were used to calculate the corresponding IC₅₀ values. Radiosensitization experiments were carried out by irradiation of the incubations with a ⁶⁰Co source and clonogenic assay was performed to determine the cell viabilities following treatment with the tested compounds and/or radiation. Sensitization Enhancement Ratio (SER) of each tested compound was obtained from the radiation survival curves in the absence and presence of each sensitizer for 37% survival respectively.

Results and major conclusion

Findings of the present study showed that alkylation or acylation of 5-fluorouracil result in compounds which have little or no cytotoxicity and radiosensitizing activity under aerobic conditions, but have high cytotoxicity and radiosensitizing effects under hypoxic conditions. Furthermore radiosensitizing activities of compounds under hypoxic conditions increased by increase in their concentrations and SER of the tested 5-FU derivatives at concentrations higher than 50 μmol were equal or higher than 1.6 which is the minimum effective SER of a radiosensitizer in an in vitro assay.     

Synthesis and evaluation of some nitrobenzenesulfonamides containing nitroisopropyl and (ureidooxy)methyl groups as novel hypoxic cell selective cytotoxic agents

Basic nitrobenzenesulfonamides containing nitroisopropyl and (ureidooxy)methyl groups were prepared and evaluated as novel hypoxic cell selective cytotoxic agents. In vitro, N-(2-aminoethyl)-N-methyl-3-nitro-4-(1-methyl-1-nitroethyl)benzene sulfonamide hydrochloride (11) proved to be preferentially toxic to hypoxic EMT6 mammary carcinoma cells. At 1 mM concentration in vitro, 11 reduced the surviving fraction of these hypoxic cells to 3 x 10(-3) with no effect on aerobic cells. In radiation experiments, 11 appeared to function as a hypoxic cell radiosensitizer as well as a selective cytotoxic agent. However, administration of 11 at 200 mg/kg ip or 100 mg/kg iv to BALB/c mice implanted with solid EMT6 tumors produced no evidence of significant in vivo cytotoxic or radiosensitizing activity. N-Methyl-N-[2-(methylamino)ethyl]-3-nitro-4- [(ureidooxy)methyl]benzenesulfonamide hydrochloride (20) showed slight differential toxicity toward EMT6 cells at 3 mM concentration and radiosensitizing activity comparable to misonidazole at 1 mM concentration.     

槟榔醇提物对H9C2心肌细胞的抗缺氧保护作用

目的 研究槟榔无水醇提物对低氧H9C2心肌细胞的作用及其保护机制。方法 建立H9C2心肌细胞低氧模型,CCK-8法检测槟榔无水醇提物对H9C2细胞存活率的影响;通过检测细胞内丙二醛（MDA）含量,过氧化物歧化酶（SOD）、还原型谷胱甘肽（GSH）活力,研究槟榔无水醇提物对H9C2细胞的保护作用;RT-PCR法检测细胞内Nrf2、Caspase-3 mRNA水平的表达,从分子水平研究槟榔无水醇提物对低氧H9C2细胞的保护机制。结果 与常氧对照组相比,低氧24 h时细胞存活为28.46%（P<0.01）,细胞内MDA含量升高44.33%（P<0.05）,SOD、GSH活力分别下降16.18%、30.64%（P<0.05或P<0.01）。RT-PCR实验结果表明,Nrf2被激活,其mRNA表达上升1.74倍（P<0.05）。与低氧模型组相比,槟榔无水醇提物处理组H9C2细胞存活率明显升高（P<0.01）,且呈现剂量依赖性,槟榔无水醇提物处理组细胞内SOD、GSH活力分别增加14.90%、28.94%（P<0.05）,Nrf2基因mRNA相对表达下降66%（P<0.05）。结论 槟榔无水醇提物对低氧H9C2细胞有显著的保护作用,其保护机制可能与提高细胞内抗氧化物酶活力,减轻细胞氧化应激损伤,提高细胞耐低氧能力有关。     

The Application of Photofrin II as a sensitizing agent for ionizing radiation--a new approach in tumor therapy?

Radiosensitizers represent an enticing concept in tumor therapy. As ionizing radiation affects both neoplastic and normal tissues, its effects are generally non-specific. The aim of applying a radiosensitizing agent is to achieve a maximum effect on tumor tissue, while minimizing the damage to normal tissues. A variety of parameters such as the oxygen supply and the state in the cell cycle, need to be taken into account when evaluating a potential radiosensitizer. Most of the previously known radiosensitizers are neither selective nor tumor specific. In this article, we review the properties and radiosensitizing potential of Photofrin II. Photofrin II is well-known as a photosensitizing agent in photodynamic therapy. In recent years, a radiosensitizing potential of the substance has been demonstrated, specifically increasing the sensitivity of solid tumor tissues, especially of radio-resistant, hypoxic tumor cells, to radiation. This radiosensitizing effect has been demonstrated both by in vitro studies and by animal experiments. Several studies with tissue cultures have demonstrated a radiosensitizing effect of Photofrin II in glioblastoma (U-373MG) and bladder cancer cell lines (RT-4). No effect was noted in colon carcinoma cell lines (HT-29). Unpublished data of additional cell lines will be mentioned in the review. Animal experiments with Lewis sarcoma and with bladder cancer have moreover demonstrated an in vivo effect of Photofrin II as a radiosensitizer. The mechanism of this radiosensitizing effect is not completely understood. In vitro data, however, support the hypothesis that the radiosensitizing action involves OH-radicals in addition to a potential impairment of repair mechanisms after sublethal damage of ionizing radiation. Moreover, early results of a phase I trial are available and document the potential feasibility of the application of Phototofrin II as a radiosensitizing agent in clinical practice.     

两种PARP-1抑制剂对羟基喜树碱诱导ECA-109细胞增殖及凋亡的影响

目的研究两种PARP-1抑制剂NU1025和AG14361在羟基喜树碱诱导的ECA-109细胞增殖及凋亡中的作用。方法常规培养ECA-109细胞,经HCPT、HCPT和NU1025、HCPT和AG14361处理24h后,采用四甲基偶氮唑蓝比色法观察细胞的增殖情况,通过流式细胞术AnnexinV-FITC/PI双染法分析细胞凋亡情况,通过彗星实验评价DNA损伤程度变化。结果相比于对照组和HCPT组,HCPT和NU1025、HCPT和AG14361联用均显著抑制了细胞的增殖、促进了细胞凋亡、加重了DNA损伤,差异有统计学意义(P<0.05);且HCPT和NU1025联用组较HCPT和AG14361联用组作用更强,两者比较差异有统计学意义(P<0.05)。结论 PARP-1抑制剂NU1025和AG1436均可通过抑制PARP-1活性,进而阻碍细胞DNA损伤修复,增强ECA-109细胞对于抗癌药物HCPT的药敏性,且NU1025具有更低细胞毒性和更强增敏作用的优势,可为食管癌的临床治疗提供一个新的靶点。     

Immune modulation by ionizing radiation and its implications for cancer immunotherapy

Ionizing radiation exhibits immunomodulatory properties, which could portend a future collaboration of cancer immunotherapy with radiation therapy. The danger model of immunity describes antigen-specific cellular immunity engendered by an inflammatory milieu. Dendritic cells (DCs) are attracted to this microenvironment, undergoing maturation after internalizing apoptotic and necrotic cellular debris. Mature DCs mediate antigen-specific cellular immunity via presentation of processed antigen to T cells. Administration of radiation has been utilized in vitro and in vivo to create an inflammatory setting, via induction of apoptosis, necrosis, cell surface molecules, and secretory molecules. Caspase-mediated cellular apoptosis is induced by radiation thro ugh multiple signaling pathways. Radiation upregulates expression of immunomodulatory surface molecules (MHC, costimulatory molecules, adhesion molecules, death receptors, heat shock proteins) and secretory molecules (cytokines, inflammatory mediators) in tumor, stromal, and vascular endothelial cells. Results of animal studies indicate possible radiation-mediated modulation of tumor antigen-specific immunity. Experimental data could indicate that the radiation-induced danger microenvironment engenders a DC-mediated antigen-specific immune response. Further enhancement of radiation-mediated inflammation and cell death can be achieved via administration of radiosensitizing pharmaceuticals. Radiation-mediated immune modulation currently remains unquantified and poorly understood. A major research effort will be required to elucidate mechanisms of action. With a thorough understanding of this phenomenon, we believe that ionizing radiation could be optimized for use with cancer vaccines and generate tumor antigen-specific cellular immunity.     

Synthesis and evaluation of novel electrophilic nitrofuran carboxamides and carboxylates as radiosensitizers and bioreductively activated cytotoxins

A series of 5-nitrofuran-2- and 3-carboxamides bearing alkylating side-chains has been synthesized and tested for their ability to radiosensitize selectively hypoxic Chinese hamster cells (V79) to the lethal effects of ionizing radiation and also for their ability to act directly and selectively as cytotoxic drugs on hypoxic V79 cells. The compounds were extremely efficient radiosensitizers of such cells in vitro and were more efficient than known nitroimidazoles of similar type. Their efficiencies as radiosensitizers correlated with their high electron affinity (E7(1] as measured by pulse-radiolysis. However the compounds showed little radiosensitizing activity towards KHT sarcomas in C3H mice. The compounds in this series of nitrofurans were generally more toxic towards hypoxic cells than towards oxic cells in vitro but were less effective upon the basis of a differential effect than were similar nitroimidazoles reported previously.