Suppressive effect of iodine on DMBA-induced breast tumor growth in the rat

Concerning the suppressive effect of inorganic iodine on the growth of 7,12-dimethyl-benz(a)anthracene (DMBA)-induced breast tumor in female Sprague-Dawley (SD) rats, we previously reported that although iodine itself had a suppressive effect on the tumor growth, its effect was not as strong as that of MPA (medroxy-progesterone acetate). However, the combined medication of iodine at a low concentration + MPA showed a stronger effect than MPA alone. The purpose of the present study is to elucidate this mechanism of action by determining the uptake of the administered iodine into breast tumor tissue. Breast tumors were induced with DMBA in female SD rats, and these animals were treated with MPA + inorganic iodine at various concentrations for 4 weeks to determine tumor growth and tumor iodine content. In the comparison of tissue iodine content in growth-suppressive tumors with that in nonsuppressive tumors, the former showed a much higher iodine content. This suggests that direct uptake of inorganic iodine by breast tumors led to the suppression of tumor growth. © 1996 Wiley-Liss, Inc.     

The combination of methyl-CCNU and irradiation: cell survival studies on a human tumor xenograft

Cell survival studies on a human tumor xenograft grown in mice have demonstrated that the chemotherapeutic drug methyl-CCNU can increase the cytotoxic effect of γ-irradiation. Injection of 25 mg/kg of methyl-CCNU three hours before irradiation was the most effective time schedule of those tested. This pre-treatment reduced the D_o of the radiation survival curve from 231 rad to 135 rad without showing any evidence of a reduced shoulder.     

己烯雌酚对Wistar大鼠乳腺癌发生的干预作用

背景与目的:作为一类人工合成雌激素药物,二乙基己烯雌酚(diethyl-stilbestrol,DES)被广泛应用于治疗雌激素不足所致的更年期综合征及骨质疏松症等,但其对乳腺上皮细胞作用的研究有待进一步探讨。本研究通过建立与人相似的Wistar大鼠乳腺癌发生的模型,并用DES进行干预,观察DES在Wistar大鼠乳腺癌发生过程中的作用。方法:利用不同剂量的DES干预二甲基苯蒽[7,12-dimethylben(a)anthracene,DMBA]诱导Wistar大鼠乳腺癌模型,研究其对乳腺上皮细胞的作用。实验分为6个组:对照组、DES1组、DMBA组、DES1+DMBA组、DES2+DMBA组和DES3+DMBA组,其中DES1、DES2和DES3中DES剂量分别为:0.1mg·kg-1·d-1、0.2mg·kg-1·d-1和0.4mg·kg-1·d-1喂养大鼠,观察44周处死大鼠,取乳腺组织作常规病理分析以及核仁组成区相关嗜银蛋白(silver-binding nucleolar organizer regions,AgNOR)计数、PCNA染色强度指数(proliferating cell nuclear antigen staining intensity index,PCNA SII)、Bcl-2和C-erbB-2蛋白表达测定。结果:DMBA组和DES1+DMBA组分别有13只和2只Wistar大鼠发生癌变;单纯DES1组大鼠乳腺上皮细胞AgNOR计数及PCNASII水平上升,Bcl-2及C-erbB-2的表达提高,但未导致癌变;与其他组相比,DES2+DMBA组大鼠乳腺上皮细胞的AgNOR计数和PCNASII水平下降,Bcl-2及C-erbB-2的表达降低(P<0.05);DES3+DMBA组上述指标与DES1+DMBA组差异无统计学意义(P>0.05)。结论:单纯小剂量DES可导致大鼠乳腺上皮细胞增生,但不导致乳腺组织癌变;在DMBA诱发大鼠乳腺上皮细胞癌变过程中,小剂量DES可以促使乳腺导管上皮细胞增生、乃至癌变;而中等剂量DES可以明显抑制大鼠乳腺上皮细胞增生,加大DES剂量,抑制作用不增强。     

Chemopreventive potential of Annona muricata L leaves on chemically-induced skin papillomagenesis in mice

Annona muricata L (Annonaceae), commonly known as soursop has a long, rich history in herbal medicine with a lengthy recorded indigenous use. It had also been found to be a promising new anti-tumor agent in numerous in vitro studies. The present investigation concerns chemopreventive effects in a two-stage model of skin papillomagenesis. Chemopreventive effects of an ethanolic extract of A. muricata leaves (AMLE) was evaluated in 6-7 week old ICR mice given a single topical application of 7,12-dimethylbenza(α)anthracene (DMBA 100 μg/100 μl acetone) and promotion by repeated application of croton oil (1% in acetone/ twice a week) for 10 weeks. Morphological tumor incidence, burden and volume were measured, with histological evaluation of skin tissue. Topical application of AMLE at 30, 100 and 300 mg/kg significantly reduced DMBA/croton oil induced mice skin papillomagenesis in (i) peri-initiation protocol (AMLE from 7 days prior to 7 days after DMBA), (ii) promotion protocol (AMLE 30 minutes after croton oil), or (iii) both peri-initiation and promotion protocol (AMLE 7 days prior to 7 day after DMBA and AMLE 30 minutes after croton oil throughout the experimental period), in a dose dependent manner (p<0.05) as compared to carcinogen-treated control. Furthermore, the average latent period was significantly increased in the AMLE-treated group. Interestingly, At 100 and 300 mg/ kg, AMLE completely inhibited the tumor development in all stages. Histopathological study revealed that tumor growth from the AMLE-treated groups showed only slight hyperplasia and absence of keratin pearls and rete ridges. The results, thus suggest that the A.muricata leaves extract was able to suppress tumor initiation as well as tumor promotion even at lower dosage.     

Optimization of 7,12-dimethylbenz(a)anthracene-induced rat epithelial ovarian tumors

Ovarian carcinoma is the second most common malignant tumor of the female reproductive system and an notable cause of cancer death. The detection and diagnosis of early ovarian carcinomas are still clinical challenges, which calls for imaging studies using early ovarian carcinoma animal models. The present study aimed to optimize the 7,12-dimethylbenz(a)anthracene (DMBA)-induced model of rat ovarian tumors by investigating the delivery methods, induction dose and time of DMBA exposure, and explored the morphological features of tumors using MRI. Three schemes were performed. In scheme one the ovary was covered with absorbable hemostatic gauze loaded with a high concentration of liquid DMBA. For this scheme, 150 Sprague-Dawley rats were divided into three groups depending on the DMBA dose (1.0, 2.0 and 3.0 mg). In scheme two DMBA solution was injected under the ovarian capsule. For this scheme, 159 rats were divided into 0.5, 1.0 and 1.5 mg DMBA groups. In scheme three the ovary was covered with absorbable gauze loaded with a high concentration of solid DMBA. For this scheme 161 rats were divided into 1.0, 2.0 and 3.0 mg DMBA groups. Each group of the three schemes was further subdivided into 60-, 90-, 120-, 150- and 180-day groups. In scheme two, the tumor formation rate was 75.6% (99/131), which was the highest in the 1.5 mg group (86.4%, 38/44) and reached 100% (10/10) on day 120. The induced tumors were serous in 93.9% (93/99) of tumors. Borderline ovarian tumors accounted for 19.2% (19/99) of all tumors, and ovarian cancer accounted for 46.5% (46/99). The mean maximum diameter (MMD) of borderline ovarian tumors was 10.29±3.41 mm, and that of ovarian cancer was 15.19±7.10 mm. MMD of the solid components increased with increasing malignancy. Cystic, cystic-solid and solid tumors were observed. The ovarian subcapsular injection of 1.5 mg DMBA was the best scheme for the rat ovarian tumor model. The present model is ideal for investigating the occurrence, development and imaging of ovarian tumors.     

二甲基苯蒽诱发家兔卵巢肿瘤及其生物学特性的初步观察

目的以二甲基苯蒽(DMBA)原位埋线法诱发家兔卵巢肿瘤,并初步观察其生物学特性.方法棉线浸入加热熔化的DMBA中,取雌性家兔5只,分别在其双侧卵巢埋入含有DMBA的棉线,连续观察8个月,处死荷瘤家兔,通过大体、光镜、电镜以及流式细胞技术等方面进行肿瘤生物学特性的初步观察.结果 1只家兔因术后感染而死亡,2只观察8个月无肿瘤发生.2只分别发生未分化癌及腺癌,组织学特点与相应的人卵巢肿瘤很相似;流式细胞分析S期细胞含量分别为40.72%和29.87%.结论二甲基苯蒽能原位诱发较大型动物家兔的卵巢肿瘤,可用于人卵巢癌的相关实验研究.     

扶正抗癌胶囊1号对实验肿瘤细胞体内外生长的抑制作用

目的 :研究扶正抗癌胶囊 1号(扶抗 1号 )对移植性肉瘤 180 (S180 )和移植性肝癌 (HepA)细胞体内外生长的抑制作用。方法 :将实验荷瘤小鼠随机分成 4组 ,分别进行扶抗 1号在体内外的抑瘤实验 ,并观察该药对小鼠HepA腹水型生长期的影响。结果 :扶抗 1号在 3 0、60g/(kg·d)体内抗癌实验时 ,对小鼠S180的抑瘤率分别为 5 3 2 2 %及60 78% ,对小鼠HepA的抑瘤率分别为3 6 84%及 45 2 9% ;在体外实验显示 ,扶抗 1号对S180及HepA有直接杀灭作用 ,并能延长HepA腹水型小鼠存活期。结论 :扶抗 1号能明显抑制S180和HepA细胞的体内外生长 ,并能延长移植性HepA腹水型小鼠的存活期。     

Elimination of Deleterious Effects of Free Radicals in Murine Skin Carcinogenesis byBlack Tea Infusion,Theaflavins & Epigallocatechin Gallate

In recent years, numerous reports have been published on the identification of novel, naturally occurring ‍antioxidants from plants, animals, microbial sources and processed food products. Most natural antioxidants are ‍phenolic compounds, which have a modulatory role on physiological functions and biotransformation reactions ‍involved in the detoxification process, thereby affording protection from cytotoxic, genotoxic and metabolic actions ‍of environmental toxicants. As part of our program on evaluation of food, beverage and traditional medicinal plants ‍for their anticarcinogenic activity, the present report deals with the evaluation of aqueous infusion of Black tea ‍(Camellia sinensis), Black tea extract (80% Theaflavins) & EGCG on mice exposed to the chemical carcinogen ‍DMBA. All the four detoxification enzymes studied viz, GST, GPx, SOD and CAT were found to be activated to ‍different degrees following treatment with black tea and two of its active compounds. The activation of the enzymes ‍was accompanied by significant reduction in lipid peroxidation. The effect on apoptosis and cell proliferation was ‍also studied in mice skin following administration of DMBA. Theaflavins, and EGCG significantly inhibited cell ‍proliferation and induced apoptosis. The observation suggests chemopreventive potential of black tea infusion, ‍black tea extract Theaflavins and the compound EGCG.‍     

Chemopreventive efficacy of Moringa oleifera pods against 7, 12-dimethylbenz[a]anthracene induced hepatic carcinogenesis in mice

Oxidative stress is a common mechanism contributing to initiation and progression of hepatic damage in a variety of liver disorders. Hence there is a great demand for the development of agents with potent antioxidant effect. The aim of the present investigation is to evaluate the efficacy of Moringa oleifera as a hepatoprotective and an antioxidant against 7, 12-dimethylbenz[a]anthracene induced hepatocellular damage. Single oral administration of DMBA (15 mg/kg) to mice resulted in significantly (p<0.001) depleted levels of xenobiotic enzymes like, cytochrome P450 and b5. DMBA induced oxidative stress was confirmed by decreased levels of reduced glutathione (GSH) and glutathione-S-transferase (GST) in the liver tissue. The status of hepatic aspartate transaminase (AST), alanine transaminase (ALT), and alkaline phosphatase (ALP) which is indicative of hepatocellular damage were also found to be decreased in DMBA administered mice. Pretreatment with the Moringa oleifera (200 and 400 mg/kg) orally for 14 days significantly reversed the DMBA induced alterations in the liver tissue and offered almost complete protection. The results from the present study indicate that Moringa oleifera exhibits good hepatoprotective and antioxidant potential against DMBA induced hepatocellular damage in mice that might be due to decreased free radical generation.     

和厚朴酚抗血管生成作用的实验研究

目的：本研究通过检测和厚朴酚在体内对鸡胚尿囊膜（chicken chorilallantoic membranes，CAM）血管生成的抑制作用及体外对肿瘤血管生成的影响，探讨和厚朴酚的抗血管生成作用及其初步机制。方法：（1）用四甲基偶氮唑盐（MTT）法检测和厚朴酚对人脐静脉内皮细胞（human umbilical vein endothelial cell，HUVEC）、人成纤维细胞及人结肠癌RKO细胞增殖的抑制作用；（2）采用鸡胚绒毛尿囊膜模型，观测和厚朴酚对CAM新生血管生成的抑制作用；（3）逆转录聚合酶链反应（RT-RCR）方法检测和厚朴酚对RKO细胞血管内皮生长因子A（VEGF-A）mRNA表达及细胞培养上清液VEGF蛋白分泌的影响。结果：和厚朴酚对血管内皮细胞具有优先抑制作用，对HUVEC的半数抑制剂量（inhibitory concentration 50％，IC50）为14．5μmol/L，而对原代培养的人成纤维细胞的IC50高达150μmol/L，对人结肠癌RKO细胞的IC50为42μmol/L；和厚朴酚0．1μg／只和0．2μg／只剂量时显著抑制CAM新生血管形成，抑制率分别为58％和86％；和厚朴酚在10μmol/L和20μmol/L剂量时显著抑制RKO细胞的VEGF-A mRNA表达及细胞培养上清液中VEGF蛋白的分泌，具有显著性差异。结论：和厚朴酚在非凋亡剂量时具有抗血管形成作用，其机制与抑制血管内皮细胞增殖以及抑制肿瘤细胞表达VEGF有关。     

放化疗对恶性肿瘤患者T细胞亚群的影响

目的探讨放疗、化疗、同步放化疗对恶性肿瘤患者T细胞亚群的影响。方法 65例恶性肿瘤患者中,有40例接受单纯化疗,有12例接受单纯放疗;有13例接受同步放化疗。治疗前后采用流式细胞技术检测患者外周血T细胞亚群情况,包括CD+3、CD+4、CD+8和CD+4/CD+8比值。结果单纯化疗组患者治疗后CD+3、CD+4、CD+8均下降,CD+4/CD+8比值升高,但均无统计学意义。单纯放疗组患者治疗后CD+3、CD+4、CD+8和CD+4/CD+8比值均降低,且差异有统计学意义(P<0.05)。同步放化疗组患者治疗后CD+3、CD+4和CD+4/CD+8比值均降低,且差异有统计学意义(P<0.05)。结论放疗、同步放化疗患者免疫功能显著下降。     

The effect of childbirth on carcinogenesis of DMBA-induced breast cancer in female SD rats

Many epidemiologic and clinical studies have indicated that the frequency of breast cancer was lower in parous women than in nulliparous women. Moreover, the incidence of breast cancer has been reported to be lower in women with early childbirth than in women with late childbirth. To verify the effect of childbirth and the age at first childbirth on carcinogenesis and progression of breast cancer, we induced breast cancer by 7,12-dimethylbenanthracene (DMBA) in 120 female Sprague-Dawley (SD) rats, and divid...     

99mTc-PPM应用于肺肿瘤的显像和导向手术的研究

背景与目的:肉眼判断和冰冻切片病理检查是我们在术中判断肿瘤的良恶性及其侵袭范围的常规方法,但肉眼判断缺乏准确性,术中冰冻检查需要等待一段时间;而术中用手持式γ探测仪( gamma detecting probe, GDP)判断肿瘤的浸润范围及转移程度,可以帮助术者快速准确地决定手术切除范围及治疗方案,使手术更加合理化及个体化.本研究以 99mTc 培普利欧霉素( peplomycin,PPM)为肿瘤示踪剂,进行肺癌显像和放射性核素导向手术的初步临床研究.方法:对 37例肺肿瘤患者注射 99mTc PPM,术前进行肺肿瘤的显像,以 ROI(region of interest)法处理并计算 T/NT;术中以手持式γ探测仪 (GDP)对手术标本进行放射性探测,以正常肺组织为本底组织( NT)计算 T/NT比值,以比值的高低来确定探测标本的性质.结果:良、恶性肿瘤对 99mTc PPM的摄取值 (良性病变 N/NT 1.04± 0.08,肺癌 N/NT 1.41±0.16)的差异有统计学意义( P< 0.01) ;以良性病变 T/NT的 x± 2s为判断良恶性病变的阈值, 99mTc PPM显像对肺癌诊断灵敏度为 90%,特异性为 87.5%,准确度为 89.3%;应用 GDP能够准确地探测出肿瘤的侵袭范围,并可以判定肿瘤的淋巴结转移情况,其灵敏度、特异性和准确率分别达到 91.0%、 88.0%和 90.0%.结论:可以将 99mTc PPM作为肿瘤示踪剂对肿瘤进行术前诊断和术中 GDP探测.术中应用 GDP探测,可以有效地判断肺癌的浸润范围及淋巴结转移,对肺癌手术的实施有一定的指导意义.     

The effect of systemic arterial hypertension on blood-to-tissue transport in experimental gliomas

Systemic arterial hypertension was induced with epinephrine in 15 rats with 39 transplanted RG-2 brain tumors in an attempt to increase blood-to-tissue transport of a water-soluble compound. In 4 rats, hypertension was induced acutely (< 5 sec), and in 11 hypertension was induced more slowly (over 5 min). Regional values of the unidirectional blood-to-tissue transfer constant (K) of alpha aminoisobutyric acid were measured with quantitative autoradiography. Mean arterial blood pressure (BP) over the experimental period increased from 117 ± 17 mmHg (SD) to 168 ± 18 mmHg in the rats with slowly induced hypertension, and from 124 ± 4 to 142 ± 5 mmHg in the acute hypertension group. Peak BP was 208 ± 16 in the first group and 216 ± 13 mmHg in the second. Intracerebral hemorrhage occurred in 10/15 animals, and there was disruption of BBB in tumor-free brain in 10/15 animals. Averaged mean whole tumor K of AIB in all hypertensive rats was 0.052 ± 0.022 ml/g/min, compared to 0.037 ± 0.015 ml/g/min in normotensive controls; there was no difference in mean tumor K between the two hypertensive groups. However, in intraparenchymal tumors without hemorrhage, K was only 0.039 ± 0.013 ml/g/min. Although the mean K of AIB was higher in brain tumors of the hypertensive rats, the increase is unlikely to be meaningful in terms of augmented delivery of watersoluble drugs to brain tumors, and the high incidence of intracerebral hemorrhage countermands any clinical use of this approach.     

B7-H3对小鼠Lewis肺癌细胞生长的影响

目的观察B7-H3对Lewis肺癌(LLC)细胞生长的影响并探讨其作用机制。方法采用40只C57BL/6小鼠,右腋下接种Lewis肺癌细胞悬液,建立皮下种植瘤模型,随机分为4组,在瘤体附近皮下围绕瘤体分别注射多西他赛、B7-H3及多西他赛+B7-H3,以注射空质粒作为对照。注射后第1、3、7、14天测量肿瘤的大小,计算肿瘤的体积;采用免疫组织化学及Western blot检测瘤组织中B7-H3的表达;采用ELISA检测小鼠血清IL-12的水平。结果多西他赛和B7-H3均能分别抑制肿瘤的生长,两者联合则抑制作用增强,多西他赛组、B7-H3组及多西他赛+B7-H3组的抑瘤率分别为32.98%、28.59%和4595%,上述处理后肿瘤细胞凋亡率均比对照组明显提高(P<0.01);B7-H3组及多西他赛+B7-H3组肿瘤组织中B7-H3的表达下调,但差异无统计学意义(P>0.05);小鼠血清中IL-12的表达在B7-H3组及多西他赛+B7-H3组均较对照组水平升高(P<0.05)。结论 B7-H3能抑制小鼠Lewis肺癌细胞的生长,其机制可能与通过IL-12诱导激活细胞毒性T细胞而产生抗肿瘤免疫应答有关。     

呫吨酮并吡啶衍生物XP-15抗人胃癌MGC-803细胞作用及其机制研究

目的 研究呫吨酮并吡啶衍生物9-(2-吗啡啉乙酰胺基)-7H-吡啶并(4,3-c)呫吨-7-酮(XP-15)抗人胃癌MGC-803细胞的作用及其可能的机制.方法 实验包括5个组,分别为空白对照组、5-氟尿嘧啶(5-FU)组、10 μmol/LXP-15组、50 μmol/L XP-15组和100μmol/L XP-15组.通过MTT法、细胞形态学和克隆实验观察XP-15对MGC-803细胞增殖的影响;应用Hoechest33258和PI双染法观察给药前后MGC-803细胞凋亡情况;用荧光分光光度计检测XP-15对细胞内钙Ca2+i及线粒体膜电位的影响;用RT-PCR检测Bad和金属硫蛋白1A (metallothionein 1A,MT-1A)mRNA的表达,比较给药前后的变化.结果 XP-15能明显抑制MGC-803细胞增殖,x2=19.40,P＜0.01;对MGC-803细胞克隆的抑制作用,呈剂量和时间依赖性,x2=16.58,P＜0.01.XP-15作用MGC-803细胞24 h后,100 μmol/LXP-15引起MGC-803细胞凋亡率为25.1％,明显高于空白对照组的9.4％,x2=29.76,P＜0.01.XP-15作用后,MGC-803细胞的Ca2+ i(x2=165.81,P＜0.01)和线粒体膜电位(x2=830.77,P＜0.01)降低,Bad和MT-1A mRNA表达增加明显.结论 XP-15能诱导MGC-803细胞凋亡,其机制可能是通过降低MGC-803细胞Ca2+i和线粒体膜电位以及上调MT-1A表达来实现的.     

关节内注射BMP-7影响骨关节炎进展的实验研究

目的拟应用骨形态发生蛋白-7（BMP-7）进行关节内注射干预骨关节炎的动物模型,观察和判断BMP-7关节内注射对于家兔骨关节炎进展的影响,为临床对于骨关节炎的防治提供新的方法和思路。方法拟选用雄性新西兰大白兔15只,体重2．8～3．2kg,平均3kg,双侧后腿膝关节采用ALCT方法联合内侧半月板前1／3切除建立骨关节炎模型后,取右膝关节作为实验组进行每周关节内定量注射BMP-7,左膝关节作为空白对照组不予处置,分别于4、8、12周各取5只实验兔双侧后腿膝关节进行观察对比,对骨关节炎关节软骨组织形态学观察和评分,通过对于病变明显部位进行病理切片、甲苯胺蓝染色观察关节软骨的退变情况,所得结果采用国际骨关节炎研究协会（OARSI）骨关节炎软骨组织病理分级制度进行评分及对比,通过免疫组化检测Ⅱ型胶原的表达情况。结果进行BMP-7关节内注射4、8、12周后实验组组织形态学评分以及病理切片苯胺蓝染色国际骨关节炎研究协会（OARSI）骨关节炎软骨组织病理分级制度评分均优于对照组,Ⅱ型胶原持续表达情况实验组明显高于对照组。结论关节内注射BMP-7可以减缓骨关节炎的病情进展。     

蜂蛇胶囊对荷瘤小鼠的抗肿瘤作用

目的 :验证蜂蛇胶囊对小鼠H2 2 肝癌和小鼠肉瘤 180 (S180 )的抑制作用及小鼠艾氏腹水癌的生命延长作用。方法 :荷瘤小鼠灌胃给药 14d后处死称瘤重 ,计算抑瘤率 ,艾氏腹水癌计算生存期延长率。结果 :蜂蛇胶囊对小鼠H2 2肝癌和小鼠S180有较强的抑制作用 ,对艾氏腹水癌有生命延长作用 ,抑瘤率 >3 0 % ,生命延长率 >5 0 % ,3次实验重现性较好。结论 :该药对实体瘤和腹水癌疗效稳定 ,抑瘤作用较强 ,有延长生命的作用。