常见肿瘤患者血清维生素A,E,C水平

本文报告２６０例恶性肿瘤患者血清维生素Ａ、Ｅ、Ｃ水平的测定结果。发现除慢性白血病外，蓁７种恶性肿瘤患者血清维生素Ａ水平平均显著低于健康人（Ｐ＜０．０１）；急性白血，肝癌、食管癌患者血清维生素Ｅ水平显著低于健康人（Ｐ＜０．０５）；急性粒细胞白血病、急性单核细胞白血病、肝癌患者血维生素Ｃ水平显著低于健康人（Ｐ＜０．０１）。本研究工作为维生素Ａ、Ｅ、Ｃ药物在肿瘤临床上的应用提供了参考。     

维生素E的防癌抗癌作用

六十年代以前维生素E(VE)一直作为妇科药物应用,六十年代中期后,发现VE是一种“多功能”药物,被临床用来治疗许多疾病。本文旨在阐述VE在防癌抗癌方面的进展。 一、维生素E对正常组织的保护作用 大量研究表明,人类约 90％的癌症与饮食、环境和生活习惯有关,其中约30％～40％的男性及60％的     

维生素E与硫辛酸对光气损伤的抗氧化作用探讨

背景与目的:观察维生素E或/和硫辛酸对光气损伤小鼠的抗氧化作用,为临床救治光气中毒提供实验资料.材料与方法:确定小鼠在光气中毒后体内发生了一定程度的氧化损伤,然后分组给予维生素E或/和硫辛酸,应用全自动血球分析仪进行血液学分析,采用荧光法测定动物肝脏与肺脏MDA.结果:维生素E(6 mg/kg)或/和硫辛酸(0.8 mg/kg)对光气引起的全血WBC、PLT降低有促进恢复作用,对肝脏与肺脏MDA的升高有一定的抑制作用,维生素E单用组效果显著,维生素E与硫辛酸复合组效果最差.结论:维生素E对光气导致的脂质过氧化的抗氧化作用优于硫辛酸,维生素E与硫辛酸复合组效果不及单用.     

白血病患者红细胞超氧化物歧化酶活性,血清过氧化脂质,维生素E…

本文观察了４４例白血病患者红细胞中铜、锌超氧化物歧化酶（ＲＢＣ·ＣｕＺｎ－ＳＯＤ）的活性、血清过氧化脂质（ＬＰＯ）和维生素Ｅ（ＶＥ）的水平，结果表明ＲＢＣ·ＣｕＺｎ－ＳＯＤ活性和ＬＰＯ水平在白血病患者中显著增高（Ｐ值均小于０．０１），而ＶＥ水平则明显降低（Ｐ〈０．０１）。对其中１５例急性白血病（ＡＬ）患者进行动态观察，在治疗获完全缓解后，其三者水平恢复到基本正常。反应了白血病患者体内存在着自由基产     

维生素C和维生素E对镉诱发精子畸形影响的实验研究

采用小鼠精子畸形实验，证实了给氯化镉０．６ｍｇ／ｋｇ．ｉｐＱｄＸ５。能诱发小鼠精子畸形，并且亦证实了在给氯化镉前五天分别给与维生素Ｃ１ｇ／ｋｇ．ｉｇ．Ｑｄ×１０或维生素Ｅ０５ｇ／ｋｇ．ｉｇＱｄ×１０，均能够对抗氯化镉致精子畸形的作用     

桑牛强生胶囊保护小鼠抗辐射损伤作用的观察

目的:研究桑牛(SN)强生胶囊对γ射线辐射的防护作用,为研制防治辐射损伤的药食两用制品提供理论依据.方法:雄性昆明健康小鼠随机分为正常对照组、辐射模型组与SN强生胶囊制品大中小3个剂量组,共5组.灌胃21 d,于给药18 d后,分别以4.0和7.0 Gy60Coγ射线全身照射小鼠造成辐射损伤后,分别测定各组小鼠脾脏及胸腺重量指数、外周血W B C数量及SOD活力与MDA含量.结果:照射后第3天和第14天,SN强生胶囊大剂量组小鼠白细胞总数与辐射模型组比较差异均有统计学意义,P<0.05.SN强生胶囊大、中剂量组与辐射模型组比较,SN强生胶囊能显著提高辐射小鼠的胸腺、脾脏免疫脏器重量指数,P<0.05.辐射后使小鼠胸腺、脾脏的MDA水平明显升高,SOD活力明显下降(P<0.05),补充SN强生胶囊后,SN强生胶囊大、中剂量组脾脏和胸腺MDA水平分别降低,与辐射模型组比较差异有统计学意义,P<0.05;使脾脏和胸腺SOD活性较辐射模型组分别提高,变化均具有统计学意义,P<0.05.结论:SN强生胶囊在一定程度上可减缓由辐射引起的小鼠外周血白细胞细胞数下降,可明显提高电离辐射机体的抗氧化能力,进而提高机体抗辐射能力.     

大剂量维生素E和C抗氧化活性及对DNA损伤影响的研究

背景与目的:观察大剂量维生素E(VitaminE,VE)和C(VitaminC,VC)的抗氧化活性及对大鼠DNA氧化损伤、烷化损伤的影响。材料与方法:将72只Wistar大鼠(雌雄各半)随机分为6组,每组12只,即对照组(基础饲料,VE、VC摄入量分别为5、0mg/kg·d),VC组(VE5mg/kg·d、VC1000mg/kg·d),VE1组(VE33mg/kg·d、VC0mg/kg·d),VE2组(VE500mg/kg·d、VC0mg/kg·d),VE1 VC组(VE33mg/kg·d、VC1000mg/kg·d)和VE2 VC组(VE500mg/kg·d、VC1000mg/kg·d),实验期为8周。实验结束前收集动物24h尿液,实验结束后处死动物,留取血液,分离血浆并收集淋巴细胞,测定超氧化物歧化酶(Superoxidedismutase,SOD)、谷胱甘肽过氧化物酶(Glutathioneperoxidase,GSH-Px)活性、丙二醛(Malondialdehyde,MDA)含量,分析DNA损伤。结果:VE1组的抗氧化活性显著提高:血浆SOD、GSH-Px活力明显高于对照组(P<0.05)、MDA含量低于对照组;而VE1 VC组SOD、GSH-Px则较VE1组显著下降(P<0.05)。VE1组10μmol/LH2O2诱导的淋巴细胞DNA氧化损伤为150.42AU,显著低于其它组(P<0.05);该组DNA烷化损伤产物尿O6-甲基鸟嘌呤(O6-methylguanine,O-6meG)含量为0.89mg/g肌酐,比对照组、VE2组分别下降了50.28%、50.00%(P<0.05)。结论:较大剂量VE能提高大鼠抗氧化活性,降低DNA氧化损伤及烷化损伤,但联合补充大剂量VC时可能对其影响产生拮抗作用;过大剂量VE和VC补充时均未观察到有利作用,并且可能降低机体的遗传稳定性。     

超氧化物歧化酶,维生素A对顺铂所致的肾及骨髓损伤的保护作用

一次极量注射顺铂后，检测超氧化物歧化酶（ＳＯＤ）、维生素Ａ（ＶＡ）保护兔及对照兔血尿素氮（ＢＵＮ）、肌酐（Ｃｒ）、２４小时尿蛋白（ＵＰ）、耳血粒细胞计数。结果发现ＳＯＤ保护组及ＶＡ保护组兔ＢＵＮ、Ｃｒ、ＵＰ检测值明显低于对照组（Ｐ＜０．０１）．而粒细胞计数高于对照组（Ｐ＜０．０５）．说明ＳＯＤ及ＶＡ能保护肾及骨髓，免受顺铂所致的损伤。实验结果为临床大剂量应用氧自由基抗癌药，减少毒性，提高疗效，提供了新的方法。     

酒精对大鼠睾丸的亚慢性氧化损伤及维生素A的保护作用

背景与目的:观察亚慢性摄入酒精对大鼠睾丸结构和功能的损害及维生素A(VitaminA,VA)的保护作用。材料与方法:30只健康雄性成年SD大鼠随机分为对照组、酒精组、酒精 VA组,各组每日分别灌胃给予酒精0、7.5g/kg、酒精7.5g/kg VA50μg/kg,连续13周后对各组大鼠的精子计数、精子活动率、精子畸形率、血清睾酮(Serumtestosterone,T)进行检测,光、电镜观察睾丸生精上皮的组织学改变。同时测定睾丸线粒体中丙二醛(MalonaldehydeMDA)的产生量。结果:与对照组相比,酒精组大鼠精子计数减少,精子活动率下降,精子畸形率升高,血清T水平明显降低,睾丸生精上皮结构破坏,支持细胞和各级生精细胞均有退化变性,睾丸线粒体丙二醛含量明显升高;酒精 VA组较单纯酒精组精子计数、精子活动率有所上升,生精细胞退化变性程度减轻,睾丸线粒体MDA减少,但血清T仍低于对照组。结论:亚慢性摄入酒精抑制精子生成和睾酮合成,补充VA可以限制酒精引起的睾丸过氧化损伤,保护睾丸的生精功能,但是仍有间质细胞合成睾酮障碍。     

The effect of vitamin E acetate on ultraviolet-induced mouse skin carcinogenesis

Despite the benefits of sunscreens, ultraviolet (UV) exposure can still lead to skin cancer. In this study we investigated the effect of topical application of the antioxidant vitamin E acetate (VEA) on the inhibition of UV-induced carcinogenesis. Hairless SKH-1 mice received 5.2 mg of VEA 30 min before (VEA/UV) or after (UV/VEA) a single minimal erythemic dose of UV light. Vehicle-control animals received acetone 30 min before UV exposure (Ace/UV). After 24 h, cyclobutane dimer repair was twofold and 1.5-fold greater in the UV/VEA and VEA/UV groups, respectively. Expression of p53 protein in the UV/VEA group was maximum at 12 h after UV exposure, whereas in the Ace/UV- and VEA/UV-treated mice, maximum p53 immunostaining was statistically higher at 15 h (P = 0.03). DNA synthesis as determined by 5-bromo-2′-deoxyuridine incorporation was twofold higher after 15 h in all groups but was not statistically different among treatment groups. Protein levels of cyclin D1 and p21 were increased in both VEA groups by 6 h. In addition, VEA treatments delayed tumor formation and yield for the first 20 wk, although this difference was lost by 30 wk. The telomerase activity of carcinomas from the UV/VEA-treated mice was statistically lower than that of the Ace/UV-treated mice (P = 0.05). This study showed that although VEA may mitigate some of the initial events associated with UV irradiation such as DNA damage and p53 expression, it has limited potential in preventing UV-induced proliferation and tumor formation. Mol. Carcinog. 23:175–184, 1998. © 1998 Wiley-Liss, Inc.     

Intakes of vitamins A, C and E and folate and multivitamins and lung cancer: a pooled analysis of 8 prospective studies

Intakes of vitamins A, C and E and folate have been hypothesized to reduce lung cancer risk. We examined these associations in a pooled analysis of the primary data from 8 prospective studies from North America and Europe. Baseline vitamin intake was assessed using a validated food-frequency questionnaire, in each study. We calculated study-specific associations and pooled them using a random-effects model. During follow-up of 430,281 persons over a maximum of 6-16 years in the studies, 3,206 incident lung cancer cases were documented. Vitamin intakes were inversely associated with lung cancer risk in age-adjusted analyses; the associations were greatly attenuated after adjusting for smoking and other risk factors for lung cancer. The pooled multivariate relative risks, comparing the highest vs. lowest quintile of intake from food-only, were 0.96 (95% confidence interval (CI) 0.83-1.11) for vitamin A, 0.80 (95% CI 0.71-0.91) for vitamin C, 0.86 (95% CI 0.76-0.99) for vitamin E and 0.88 (95% CI 0.74-1.04) for folate. The association with vitamin C was not independent of our previously reported inverse association with beta-cryptoxanthin. Further, vitamin intakes from foods plus supplements were not associated with a reduced risk of lung cancer in multivariate analyses, and use of multivitamins and specific vitamin supplements was not significantly associated with lung cancer risk. The results generally did not differ across studies or by sex, smoking habits and lung cancer cell type. In conclusion, these data do not support the hypothesis that intakes of vitamins A, C and E and folate reduce lung cancer risk.     

线粒体复合物在维生素E琥珀酸酯诱导人胃癌细胞凋亡中的作用

目的： 探讨维生素E琥珀酸酯(vitamin E succinate,VES)诱导人胃癌细胞凋亡过程中线粒体4种复合物的作用,并寻找对肿瘤细胞有抑制作用的关键酶。方法：体外常规培养SGC-7901细胞,分别加入线粒体复合物Ⅰ、Ⅱ、Ⅲ和Ⅳ (complexⅠ~Ⅳ, CⅠ~Ⅳ)的抑制剂鱼藤酮(rotenone,ROT)、噻吩甲酰三氟丙酮 (thenoyltri?uoroacetone,TTFA)、抗霉素A (antimycin A,AA)和叠氮钠 (sodium azide,SA)2 h后以20 μg/ml VES诱导处理,并设阴性对照组(含0.1%乙醇的培养液),20 μg/ml VES单独处理组;MTT法测定细胞增殖情况,共聚焦显微镜观察活性氧(reactive oxygen species,ROS)水平,流式细胞术检测细胞凋亡情况,Western blot法检测细胞中细胞色素C和Caspase-3表达情况。结果：与VES对照组比较,在VES诱导SGC-7901细胞凋亡的过程中,添加5 μg/ml TTFA抑制线粒体复合物Ⅱ酶活性后,细胞增殖抑制率水平显著降低 (P<0.05)。4个线粒体复合物抑制剂处理组ROS水平均显著降低 (P<0.05),而细胞凋亡率显著升高 (P<0.05);但5 μg/ml TTFA处理组ROS及凋亡率的升高均显著低于其他3个处理组 (P均<0.05)。分别抑制CⅠ~Ⅳ酶活后,VES上调细胞中细胞色素C和Caspase-3的能力均受到抑制,其中VES+TTFA组抑制程度明显高于另外3组 (P均<0.05)。结论：VES处理SGC-7901细胞,可影响线粒体复合物Ⅱ中琥珀酸脱氢酶活性,致使线粒体中ROS堆积,这可能是VES诱导人胃癌细胞凋亡的机制之一。     

依达拉奉对原代培养大鼠海马神经元放射性损伤的保护作用

目的:研究依迭拉奉对原代培养大鼠海马神经元放射性损伤的保护作用.方法:30 Gy的X射线单次照射培养至12 d的海马神经元,用DAPI染核方法检测海马神经元凋亡情况,用MDA含量及SOD活性试剂盒测定细胞培养液MDA含量及SOD活性.结果:各组之间核固缩分数差异有统计学意义(P＜0.01),30 Gy组在照射后24 h核固缩百分数为(25.2±4.02)%,较0 Gy组差异有统计学意义,P＜0.01;30 Gy+依达拉奉100 mol/L组在照射后24 h核固缩百分数为(7.68±2.31)%,较30 Gy组及0 Gy组差异均有统计学意义(P＜0.01).各组之间MDA含量及SOD活性差异有统计学意义(P＜0.01).结论:依达拉奉通过降低自由基水平而对放射损伤的大鼠海马神经元起到保护作用.     

MDA和SOD在VC、VE对60Co照射家兔作用中的变化意义

背景与目的:研究维生素C(VC)、维生素E(VE)对辐射损伤家兔的保护作用以及SOD和MDA在这一作用中的意义.材料与方法:健康家兔30只,按体质量和性别均衡随机分为5组,每组6只.阴性对照组和阳性对照组,均iv生理盐水1 ml/kg和ig处理过的花生油1 ml/kg,其余3组分别为复合实验1、2、3组:分别iv剂量为10、20、30 mg/kg的VC,同时ig剂量分别为20、40、60mg/kg的VE.喂养第3 d阳性组及各实验组给予剂量为4.5Gy的60Co γ线全身照射.照射后继续给药至第5 d后,宰杀家兔取肝脏和腹腔静脉血后检测SOD和MDA的变化.结果:家兔经照射后,血清照射组SOD活性较正常组增加,而给予VC、VE复合干预之后,随干预剂量增加,活性稍有降低,但均高于正常组;而肝脏照射组SOD的活性较正常组低,给于不同剂量的干预因素后,各组SOD值较照射组均增高.照射后血清MDA较照射有明显下降趋势,高剂量时最低.而给于干预因素后,肝脏MDA较照射组均明显降低.且中、高剂量组较低剂量组均低.结论:照射后,肝脏即应激性地释放SOD入血液,使血液中SOD增高,执行抗氧化功能,给予干预因素后,血液中MDA即降低,因此肝脏SOD向血中释放减少.     

维生素E琥珀酸酯的抗肿瘤机制

维生素E琥珀酸酯（vitamin E succinate,RRR-α-tocopheryl succinate．VES）是维生素E的一种酯化衍生物。对维生素E家族在肿瘤预防和治疗中作用的研究始于20世纪60年代。实验证据显示,VES是维生素E家族中抗肿瘤效果最好的化合物之一,能有效抑制多种肿瘤,但对正常的细胞和组织没有明显的不良反应。近年来大量的研究对VES抗肿瘤的作用机制也作了进一步的探讨。本文从4个方面阐述VES抗肿瘤机理的研究进展：①VES的分子结构、化学性质和运送载体;②VES抑制肿瘤细胞增殖的机制;③VES诱导肿瘤细胞凋亡的机制;④VES抑制肿瘤转移的机制。全面了解VES抗肿瘤的机理,将有助于发现新的抗癌药物靶点,促进研发安全有效的肿瘤预防和治疗性药物。     

Vitamin E amides, a new class of vitamin E analogues with enhanced proapoptotic activity

Vitamin E (VE) analogues, epitomized by alpha-tocopheryl succinate (alpha-TOS), are proapoptotic agents with selective antineoplastic activity. The molecule of alpha-TOS comprises several structurally and functionally distinct moieties that can be modified in order to yield analogues with higher activity. In order to find analogues with higher apoptogenic efficacy, we prepared novel compounds where the ester bond was replaced by an amide bond. All of these analogues were significantly more proapoptotic than their ester counterparts, with alpha-tocopheryl maleyl amide being the most effective. Importantly, methylation of the free carboxylic group completely obliterated apoptogenic activity of the compounds. Similarly as shown for the ester analogues, the amides induced apoptosis by mitochondrial destabilization. Superiority of amides over the ester analogues may be due to their higher partitioning into the lipid phase, as suggested by the log p-values that were lower for the amides than the corresponding esters. In conclusion, we present evidence that modification of the ester bond of agents such as alpha-TOS can be used as a basis for generating novel analogues with higher efficacy of killing malignant cells, an activity that suggests anticancer effect of the agents.     

p16~(INK4A)和HPV16 E7/HPV18 E6在ASCUS中的表达及临床意义

目的:探讨p16 INK4A和HPV16 E7/HPV18 E6在宫颈细胞学诊断为非典型性鳞状细胞不明确意义型(ASCUS)中的表达及筛查潜在宫颈病变的价值。方法:对150例ASCUS患者行阴道镜检查并取活检,同时对该150例患者的TCT标本进行免疫细胞化学染色检测p16INK4A的表达和RT-PCR法检测其中HPV16型E7蛋白和18型E6蛋白(HPV16 E7/HPV18 E6)mRNA的表达。结果:p16INK4A和HPV16 E7/HPV18 E6 mRNA在ASCUS中表达的阳性率分别为37.33%和46.67%,随着病理级别的增加,p16INK4A和HPV16E7/HPV18 E6 mRNA表达的阳性率也随之增加;p16INK4A和HPV16 E7/HPV18 E6 mRNA筛查ASCUS中宫颈病变的灵敏度、特异度、阳性预测值和阴性预测值分别为0.88、0.95、0.91、0.93和0.81、0.75、0.67、0.86,在p16INK4A和HPV16 E7/HPV18 E6 mRNA阳性的样本中,宫颈病变发生率分别为91.07%和67.14%,均明显高于阴性样本中的发病率7.45%和13.75%(P<0.001);ASCUS中宫颈病变样本中p16INK4A和HPV16 E7/HPV18 E6 mRNA呈高表达,且具有较高的一致性(κ=0.6475)。结论:p16INK4A和HPV16 E7/HPV18 E6 mRNA在ASCUS中病理诊断为宫颈病变的样本中均呈高表达,对筛查潜在的宫颈病变具有重要意义,其中p16INK4A的筛查效能优于HPV16E7/HPV18E6mRNA;p16INK4A能间接反映HPV的转录活性,在ASCUS的分流中有重要意义,且可视性的p16INK4A免疫染色比HPV检测更直观。     

Estimated intake of vitamin D and its interaction with vitamin A on lung cancer risk among smokers

Data are very limited on vitamin D and lung cancer prevention in high‐risk populations. The authors investigated whether estimated vitamin D intake was associated with lung cancer risk and whether effect modification by vitamin A existed among current/former heavy smokers and workers with occupational exposure to asbestos. A case–cohort study selected 749 incident lung cancers and 679 noncases from the Carotene and Retinol Efficacy Trial (CARET), 1988–2005. The active intervention was supplementation of 30 mg β‐carotene + 25,000 IU retinyl palmitate/day. Baseline total intake including both diet (from food frequency questionnaire) and personal supplements (from brand names linked to the labeled potencies) was assessed. Hazard ratios (HRs) were estimated by Cox proportional hazard models. No significant association of total vitamin D intake with lung cancer was observed overall. However, total vitamin D intake ≥600 versus <200 IU/day was associated with a lower risk of non‐small cell lung cancer among former smokers [HR = 0.36, 95% confidence interval (CI) = 0.13–0.96]. Total vitamin D intake ≥400 versus <400 IU/day was associated with a lower risk of total lung cancer among participants who received the CARET active intervention (HR = 0.56, 95% CI = 0.32–0.99) and among those who had total vitamin A intake ≥1,500 µg/day retinol activity equivalent (RAE; HR = 0.46, 95% CI = 0.23–0.91). The beneficial associations were attenuated among those who did not receive the CARET active intervention or who had total vitamin A intake <1,500 µg/day RAE (p‐interaction = 0.02 for current smokers). Our observation suggests that vitamin A may assist vitamin D in preventing lung cancer among smokers.     

Vitamins and carotenoids intake and the risk of basal cell carcinoma of the skin in women (United States)

Objective: We examined prospectively intakes of vitamins A, C, and E, folate, and specific carotenoids in relation to the risk of basal cell carcinoma of the skin (BCC) in women. Methods: Dietary intake was assessed by food-frequency questionnaires every two–four years and the first diagnosis of BCC was ascertained by self-report every two years. We used logistic regression to model the association between dietary intake and the risk of BCC adjusting for various health, sun exposure, and sun sensitivity factors. Results: During 12 years of follow-up we recorded 5392 cases. We did not find any significant inverse associations between these dietary factors and BCC. On the contrary, weak positive trends were seen with vitamins A, C, and E, and folate. The multivariate relative risks (RRs) comparing the top to bottom quintile were 1.20 (95% CI = 1.10–1.31) for folate, 1.16 (95% CI = 1.06–1.26) for vitamin A, 1.13 (95% CI = 1.03–1.23) for vitamin C, and 1.15 (95% CI = 1.06–1.26) for vitamin E. Exploration of latency periods did not suggest different associations with a particular duration. Conclusions: We did not find evidence that vitamins A, C, and E, and folate, or specific carotenoids play an important protective role against the incidence of BCC.