P53突变蛋白表达与胃癌远处器官转移有关

 应用ABC免疫组化染色法，研究P₅₃突变蛋白表达与胃癌周围淋巴结及远处器官转移的关系。结果表明：P₅₃在胃癌中表达率为54.8%（34/62）。P₅₃表达在未发生转移的胃癌中为50%（7/14），在已发生癌周淋巴结转移的胃癌中为56%（27/48），两组无显著性差异（P＞0.05），但在已发生远处器官转移的胃癌中P₅₃表达率为72.7%（8/11），显著高于前两组（P＜0.01）。提示该基因表达与胃癌远处器官转移及不良的预后有关。     

EFFECTS OF SeO2 ON REGULATORY REGIONS p250 OF c—fos GENE

Objective: This study was designed to determine whether regulatory regions p250 of c-fos gene were responsive to SeO₂ and to seek the possible mechanisms of regulation. Methods: HeLa cells were transfected with plasmids p250-tk CAT containing upstream regulating regions of c-fos gene. Cells were treated by SeO₂ for 20 min. CAT expression in transfected cells was observed by thin layered chromatography. Results: In transfected HeLa cells CAT expression showed obvious increase after exposure to SeO₂, especially in 10 μmol/L and 30 μmol/L group (P<0.05). Conclusion: Through affecting regulatory regions p250 of c-fos gene, SeO₂ exerted biological effect on tumor cells. SeO₂ possibly had anti-tumor effects. Biography: YU Hai-jian (1963–), male, doctor of medicine, associate professor, Peking Union Medical College Hospital, majors in research on the respiratory diseases.     

亚硒酸钠对体外培养的人食管癌上皮细胞和人胚肺二倍体细胞的生物效应

 “亚硒酸钠对体外培养的人食管癌上皮细胞和人胚肺二倍体细胞的生物效应”的研究表明: 1μg/ml Na₂SeO₃对于食管癌细胞的分裂、增殖有抑制作用,对周期中各期的进程普遍有阻滞作用。1μg/mlNa₂SeO₃对人胚肺细胞的分裂、增殖无抑制作用,对周期中各期的进程亦无明显阻滞作用。3μg/ml,Na₂SeO₃对原代培养的食管上皮细胞作用24小时后形态无改变,对食管癌细胞则产生明显的中毒形态改变。     

早期乳腺癌的围手术辅助化疗

 1977～1980年,我院采用Cu联合化疗辅助手术治疗病检腋淋巴结阴性T₁N₀M₀和T₂N₀M₀早期乳腺癌42例,并以同期相同病例49例做对照。用药组5年治愈率100%,对照组85.7%（P<0.05）,10年两组分别为92.2%及81.6%（P>0.05）,当T₁N₀M₀时,两组预后相似,T₂N₀M₀时,5年健在率分别为100%及82.8%（P<0.05）,10年为95.7%及75.9%（P<0.05）,指出固手术辅助化疗能改善早期乳腺癌,特别是T₂N₀M₀的预后。     

NDPK/nm23-H1在膀胱癌、肺癌、大肠癌中的表达及意义

 收集石腊包埋组织标本膀胱癌80例、肺癌69例、大肠癌37例,对有转移者同时收集其转移灶标本,应用免疫组织化学法检测NDPK/nm23-H₁的表达情况。结果显示：NDPK/nm23-H₁在膀胱癌、肺癌和大肠癌中表达的阳性率分别为64%、80%和94%;其表达水平在膀胱癌、大肠癌与分化程度有关,随分化程度降低而显著降低（P＜0.05）;在肺癌与组织学类型有关,以肺鳞癌中最高,其次为腺癌和小细胞癌（P＜0.05）;在大肠癌与淋巴结转移有关,伴淋巴结转移者其原发灶中显著降低（P＜0.01）;对原发灶和转移灶的配对分析,未发现相关性。提示NDPK/nm23-H₁表达水平是一个与肿瘤恶性行为相关的因素,但其临床意义存在组织学差异。     

影响Ⅰ期子宫内膜腺癌预后的因素

 一、肿瘤分级Ⅰ期子宫内膜腺癌通常按癌细胞的分化程度分为三级。Ⅰ级（G₁）一高分化癌：Ⅱ级（G₂）一中分化腺癌：部分区域呈实性癌：Ⅲ级（G₃）一实性癌为主，或全部为未分化癌。肿瘤分级对预后的重要意义，在于肿瘤分级愈高，淋巴结转移与宫体浸润的机会愈大，预后愈差。Disaia报告淋巴结转移与深肌层浸润G₁分别是2%与4%。     

含A蛋白葡萄球菌对小鼠肝癌、恶性淋巴瘤及白血病免疫预防效果的进一步观察

 615系和昆明种小鼠经含A蛋白葡萄球菌腹腔免疫后两周，分别用小鼠腹水肝癌(H₂₂)、恶性淋巴瘤（ARS）及白血病（L7712）细胞（1×10⁵）腹腔攻击，观察二个月。结果表明，SPA菌免疫动物对H₂₂肝癌细胞攻击的保护率为30%，抑制率为143.6%，对SRS恶性淋巴瘤细胞攻击的保护率为15%，抑制率达207.8%；对L7712白血病细胞攻击的抑制率为216.0%。SPA菌诱导的免疫保护效应强度不低子厌氧棒状杆菌免疫组。这些结果进一步证明，SPA菌腹腔免疫能诱导非特导性抗肿瘤免疫效应。     

亚硒酸钠和维甲酸联合对HL-60细胞c-myc和c-fos基因表达的影响

 以HL-60细胞为实验对象，利用Slot-blot技术，观察了亚硒酸钠和维甲酸（RA）联合对其原癌基因c-myc和c-fos表达的影响。结果表明：硒和RA在第一和第二天都可使c-myc基因表达下降，以后逐渐上升到对照组或稍高水平。联合可使c-myc表达显著下降，强于两单独作用。硒和pA在第三至第四天均可使c-fos表达明显升高，第四天5.8ｕmol/L Na₂SeO₃ 和0.1ｕmol/LRA以及联合组c-fos表达水平分别为对照组的2.8，3.7和5.4倍。     

三氧化二砷诱导骨髓瘤细胞SOCS-1基因-去甲基化及其对P-STAT3蛋白表达的影响

 目的 探讨三氧化二砷（AS₂O₃) 对多发性骨髓瘤 (MM) 细胞内细胞因子信号转导抑制因子-1（SOCS-1）基因甲基化状态的影响及其对磷酸化的信号转导与转录激活因子-3（P-STAT3）表达的影响。方法 采用甲基特异性PCR法检测AS₂O₃作用前后MM细胞株U266和CZ-1细胞内 SOCS-1基因的甲基化状态,应用蛋白免疫印迹法检测AS₂O₃处理前后细胞内P-STAT3蛋白的表达变化,并采用流式细胞技术检测AS₂O₃作用前后MM细胞增殖和凋亡的变化。结果 MM细胞株内SOCS-1基因存在程度不同的甲基化状态,与对照组相比,AS₂O₃作用后MM细胞内SOCS-1基因甲基化程度明显减弱或消失,P-STAT3蛋白的表达也明显减弱,同时细胞生长受抑,凋亡比率升高。AS₂O₃浓度分别为0、0.5、1.0、2.0 μmol/L时,U266细胞株的总凋亡率分别为0.06%、0.56%、48.96%、61.07%（χ²=9.19,P<0.05）;而CZ-1细胞株的总凋亡率分别为4.20%、40.30%、47.72%、68.49%（χ²=8.96,P<0.05）。结论 AS₂O₃可能通过诱导MM细胞内SOCS-1基因去甲基化作用,进一步抑制细胞增殖信号Janus激酶（JAK）-STAT通路的活化,从而诱导MM细胞的凋亡。     

香菇多糖对肺癌患者免疫功能的调节作用

 应用香菇多糖治疗化疗后休疗期肺癌患者30例，观察治疗前后细胞免疫和体液免疫变化，结果显示治疗前后各项体液免疫指标均无明显改变。NK细胞，CD₃⁺细胞，CD₄⁺细胞的百分率显著增加（P＜0．05），淋巴细胞转化率增加，CD₈⁺细胞百分率下降，CD₄⁺/CD₈⁺细胞比值上升。提示香菇多糖对肺癌患者免疫功能有正向调节作用。     

Effect of Na2SeO3 on the damages of genetic materials induced by MNNG in children's foreskin fibroblasts in vitro

In order to study the effect of selenium on anticarcinogenesis, micronuclei (MN) and chromosome aberrations (CA) were used as the indexes to reflect the damages on the genetic materials induced by MNNG in children's foreskin fibroblasts in vitro. In the MN test, the final concentrations of Na2SeO3 were 10(-7), 10(-6), 10(-5) and 10(-4) M and MNNG, 10(-5)M. In the CA test, Na2SeO3 were used in 10(-7), 10(-6) and 10(-5)M and MNNG, 10(-6)M as the final concentrations. Relative to the time of MNNG treatment, the cells were exposed to Na2SeO3 4 hours before and at the same time as with the carcinogen. The results showed that the MN% (number of cells out of one thousand MN) was reduced from 4.31 +/- 0.91% to 1.55 +/- 0.54% and 1.54 +/- 0.54% (P less than 0.05), respectively. The CA% (the percentage of the cell with CA) was reduced from 86 +/- 7% to 34 +/- 9% and 33 +/- 9% (P less than 0.05), respectively. However there was no like results when the cells were treated with Na2SeO3 and MNNG simultaneously. Na2SeO3 had no significant protective effects on the cells when the concentration was 10(-7)M. If the dose was 10(-4)M or more, Na2SeO3 became toxic to the cells. The results suggested that the protection of Na2SeO3 on the damages of genetic materials induced by MNNG be time and dose dependent.     

The effect of sodium selenite on cell proliferation and transformation of primary rat tracheal epithelial cells.

The effects of sodium selenite (Na2SeO3) on cell proliferation and the development of preneoplastic transformed variants were studied in primary cultures of rat tracheal epithelial cells. Results revealed a biphasic effect of Na2SeO3 on cell proliferation: at concentrations between 6 x 10(-8) and 6 x 10(-6) M, it stimulated and at concentrations of approximately 2 x 10(-5) and above it inhibited cell proliferation (presumably due to toxicity). Nontoxic concentrations of Na2SeO3 (6 x 10(-8) -6 x 10(-7) M) significantly reduced the spontaneous transformation frequency. Transformation induced by the tobacco-specific nitrosamine 4-(methyl-nitrosamino)-1-(3-pyridyl)-1-butanone (NNK) was effectively inhibited by nontoxic as well as toxic concentrations of Na2SeO3. Treatment of cultures with Na2SeO3 after cessation of NNK exposure, i.e. during the selection period, also significantly reduced the transformation frequency. These experiments show that the inhibition of transformation by Na2SeO3 is not the result of an antiproliferative effect. They further indicate that the inhibitory effect occurs even when the chemical treatment occurs during the 'postinitiation' phase. Thus the inhibition of transformation by Na2SeO3 cannot solely be explained by its effects on drug metabolism.     

Possible role of glutathione in mitochondrial apoptosis of human oral squamous cell carcinoma caused by inorganic selenium compounds

Selenium (Se) is a very effective anti-cancer agent. We studied the effects of inorganic Se compounds on induction of apoptosis by which Se compounds exert cancer chemopreventive activity. With the use of HSC-3 human oral squamous cell carcinoma cells, the present study showed that treatment with Se for 72 h, in the form of SeO2 and Na2SeO3, but not Na2SeO4, markedly induced apoptosis in a dose-dependent manner. Treatment of HSC-3 cells with 100 microM SeO2 resulted in the caspase-3-like and -9-like activation. Se compounds induced a loss of mitochondrial membrane potential (DeltaPsim), but did not induce the generation of reactive oxygen species. Treatment with SeO2 for 18 h resulted in 80% loss of reduced glutathione (GSH), which is known to be involved in the metabolism of Se. Treatment with N-acetyl-L-cysteine, or exogenous GSH, prevented the SeO2-induced apoptosis. Treatment with GSH led to the partial reverse in reduction of DeltaPsim caused by SeO2, while buthionine sulfoximine augmented the SeO2- or Na2SeO3-induced apoptosis.These results suggest that modulation of the mitochondrial redox equilibrium by Se contributes to the mitochondrial pathway, regulating caspase-9-mediated apoptosis without a concurrent increase in ROS.     

富硒大蒜对体内外人胃癌细胞生长的影响

目的 比较富硒大蒜、普通大蒜、亚硒酸钠以及普通大蒜与亚硒酸钠混合（蒜硒联合）处理影响人胃癌细胞生长的能力。方法 利用细胞计数、流式细胞术、Western blot和裸鼠瘤体积测定等方法,观察富硒大蒜水溶物对离体培养的MGC803胃癌细胞系及其在裸鼠皮下生长的影响。结果 （1）在离体条件下,富硒大蒜对MGC803细胞增殖有明显抑制作用,与等蒜量普通大蒜作用强度相似;等硒量亚硒酸钠抑制作用最弱,蒜硒联合抑制作用最强。（2）富硒大蒜、普通大蒜和亚硒酸钠处理24h后,未同步化的细胞G1期增多,已同步化的细胞S期增多;蒜硒联合处理则使未同步化和已同步化细胞G2＋M期增多。（3）4种处理24h后,同步化细胞的Cdk2-CyclinE和Cdk4-CyclinD1复合物蛋白含量均降低。（4）饲喂Balb/C裸小鼠含1．67％富硒大蒜粉（含硒2μg/g)的饲料,对移植瘤生长的抑制率达29．92％;0．83％富硒大蒜、1．67％普通大蒜和4．38μg/g亚硒酸钠（含硒2μg/g)处理组未见明显抑制作用。（5）0．83％富硒大蒜处理可诱发裸鼠单核细胞包裹肿瘤。结论 富硒大蒜能够抑制MGC803细胞在体外的生长,主要作用在于蒜。富硒大蒜对裸鼠移植胃癌有抑制作用,作用比普通大蒜和亚硒酸钠强。     

INDUCTION OF APOPTOSIS BY SeO_2 IN HUMAN LUNG CARCINOMA CELL LINE GLC-82

Thetraceelementselenium(Se)hasbeenshowntobecytotoxicinvitroinmultiplecellmodelsincludingbreastcancercelllineMCF-7[1],coloniccarcinomacellsHT29[2]andimmortalhumanhepaticcelllineHL-7702[3].Seleniumisanessentialcomponentofanumberofenzymespresentintheaminoacidselenocysteine(Se-Cys)andinhibittumorigenesisinbothanimalmodelsandhumans[3].SupplementingwithSeindietmayreducethehumancancerrisk[3].Clarketal.[4]foundthattheincidentoflungcancerwaslowerinSe-supplementedpatients.Apoptosisinducedbyselenium…     

二氧化硒对GLC-82肺癌细胞株C-FOS蛋白表达的影响

目的:本研究通过观察不同浓度的二氧化硒(SeO2)对GLC-82肺癌细胞株C-FOS蛋白表达的影响,初步探讨SeO2致肺癌细胞损伤的机制。方法:把GLC-82细胞分别接种于3个6孔板中,同时在每个孔中放置4片盖玻片后;于37℃、5% C02下培养爬片24h,分别加SeO2,使每个板5个孔SeO2的浓度分别为3,10,30礛,而每板保留1个孔作为空白对照。分别在1h、6h、12h和24h捞片。100%丙酮固定后,进行SP法的C-FOS蛋白免疫组化染色。在光镜10×40倍视野下,应用CMIAS-H图像分析仪对阳性细胞的图像学参数进行分析,最后结果经Spss8.0统计软件统计分析。 结果:Se02在早期(1h)即可引起 C-FOS蛋白表达增强,随后逐渐增强,在6～12h时GLC-82细胞C-FOS均呈明显的高表达(P<0.05和P相似文献   

DETOXIFYING EFFECT OF LISHENG－SE ON CDDP AND ITS RELATION TO METALLOTHIONEIN INDUCTION

徐卓立，郭军华，宋三泰，卢淑娟，吴德政ＤＥＴＯＸＩＦＹＩＮＧＥＦＦＥＣＴＯＦＬＩＳＨＥＮＧ－ＳＥＯＮＣＤＤＰＡＮＤＩＴＳＲＥＬＡＴＩＯＮＴＯＭＥＴＡＬＬＯＴＨＩＯＮＥＩＮＩＮＤＵＣＴＩＯＮ￥ＸｕＺｈｕｏｌｉ；ＧｕｏＪｕｎｈｕａ；ＳｏｎｇＳａｎｔａｉ；...     

Chemoprevention of experimental mammary carcinogenesis by the synthetic organoselenium compound, benzylselenocyanate, in rats

The effect of the dietary organoselenium compound, benzylselenocyanate (BSC) along with its sulphur analogue, benzylthiocynanate (BTC) and sodium selenite (Na2SeO3), on 7,12-dimethylbenz[a]anthracene (DMBA)-induced mammary carcinogenesis was examined in female Sprague-Dawley rats during the initiation phase of carcinogenesis. Semipurified diets containing 25 p.p.m. of BSC and 25 p.p.m. BTC, and 4 p.p.m. Selenium as Na2SeO3 in drinking water were given to 5-week-old rats for 3 weeks starting 2 weeks before, during and until 1 week after carcinogen treatment. At 7 weeks of age animals were given a single dose of DMBA (10 mg) in 1 ml olive oil by oral intubation. One week after DMBA treatment, the groups receiving BSC- and BTC-supplemented diets were transferred to the unsupplemented standard diets and the group of rats receiving Na2SeO3 in drinking water was transferred to regular tap water for the duration of the experiment. The results indicate that the rats receiving BSC in their diet showed a highly significant inhibition of tumor incidence and tumor multiplicity as well as a prolonged latency period when compared to the group fed the control diet. Neither BTC nor Na2SeO3 had any effect on the subsequent development of mammary tumors. These results indicate that dietary BSC inhibits mammary tumor incidence during the initiation phase of carcinogenesis and is a considerably more potent inhibitor than its sulphur analogue BTC and inorganic selenium. This is the first report that demonstrates the inhibition of mammary carcinogenesis by a synthetic organoselenium compound.     

Effect of SeO<Subscript>2</Subscript> on telomerase activity in human lung carcinoma cell line GLC-82

Objective: To observe the effect of inhibition of telomerase activity by selenium dioxide (SeO2) on lung carcinoma cell line GLC-82. Methods: TRAP-PCR-ELISA was used to study the changes of telomerase activity in human pulmonary adenocarcinoma cell line GLC-82 treated by SeO2 at the different concentrations (3, 10, 30 μmol/L) and for different times (24, 48, and 72 h). Results: SeO2 inhibited the telomerase activity of GLC-82 at the different concentrations after treatment of 24, 48 and 72 h. Conclusion: SeO2 inhibits from telomerase activity of human lung carcinoma line GLC-82. The effect of inhibition is dose-dependant and time-dependant.     

Modulation of genotoxic activity of tobacco smoke

Tobacco smoke (TS) caused a three- to nine-fold increase in the frequency of his+ revertants in Salmonella typhimurium TA98 but not in TA97a, TA100 or TA102. Activation by a post-mitochondrial fraction obtained from the liver of rats pretreated with Aroclor-1254 or methylcholanthrene was required; fractions from phenobarbital-pretreated or untreated rats had no effect. Vitamins A and E, but not ascorbic acid, inhibited the TS-induced mutagenesis by up to 63%, whereas glutathione and cysteine increased it slightly. Na2SeO3, but neither CoCl2 nor caffeine, inhibited the mutagenic effect of TS by 46-56%. In Chinese hamster ovary cells, both Na2SeO3 and caffeine strongly potentiated the number of chromosomal aberrations induced by TS, while theophilline slightly reduced its clastogenic effect. Treatment of mice with TS for 60 min/day increased the frequency of micronuclei in polychromatic erythrocytes in bone marrow and in fetal liver and the number of NCE micronuclei in peripheral blood by four to five fold. Simultaneous treatment of mice with TS and Na2SeO3 reduced the clastogenic effect of TS. Ascorbic acid had no effect on clastogenicity but reduced toxicity as measured by body weight loss. Both Na2SeO3 and ascorbic acid suppressed the induction of TS-induced hyperplastic and metaplastic changes in bronchial mucosa but had no effect on the number of urethane-induced lung adenomas. Vitamins A and E and ascorbic acid may have a protective effect against the toxic and genotoxic activities of TS.