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1.
电子垃圾拆解区新生儿脐带血铬水平 总被引:5,自引:0,他引:5
背景与目的:探讨电子垃圾拆解区--贵屿镇新生儿铬污染状况及其影响因素.材料与方法:选择2006年5~9月足月健康新生儿152例,其中来自贵屿镇的100例(暴露组),来自周边乡镇的52例(对照组).采用石墨炉原子吸收光谱法检测新生儿脐带血铬水平,通过调查表对产妇进行问卷调查,分析相关影响因素.结果:贵屿组新生儿脐带血铬几何均值为303.38 μg/L,与对照组20.30 μg/L相比,差别有统计学意义(P<0.01).孕妇从事电子垃圾处理相关工作等因素与新生儿脐带血铬水平呈正相关.结论:电子垃圾拆解区部分新生儿铬负荷处于较高的水平,新生儿的铬负荷水平与当地的电子垃圾拆解业及所造成的铬污染有关,铬污染可能对当地新生儿的健康构成威胁. 相似文献
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目的:运用Meta分析的方法探讨中国人群胃癌发病的影响因素,为我国胃癌的预防控制提供参考依据。方法:计算机检索PubMed、Embase、Cochrane Library、Web of Science、中国生物医学文献数据库(CBM)、中国学术期刊全文数据库(CNKI)、万方数据库(WANFANG)及维普数据库(VIP),收集2000年1月至2020年12月公开发表的关于中国人群胃癌发病影响因素的相关文献,并利用Stata16.0软件对纳入的文献进行分析。结果:共纳入45篇文献,均为病例对照研究,累计病例10 643例,对照14 073例。各影响因素的合并OR值及95%CI如下:吸烟(2.34,2.04~2.67)、慢性胃病史(4.40,3.68~5.24)、肿瘤家族史(2.98,2.49~3.56)、常吃蔬菜(0.29,0.24~0.36)、不良情绪(1.85,1.62~2.11)、常吃腌制食品(3.09,2.58~3.71)、进食不规律(3.06,2.32~4.05)、常吃烫食(1.87,1.61~2.16)、常饮茶(0.38,0.32~0.45)、常饮(1.76,1.51~2.05)、高盐饮食(2.53,2.14~2.99)、常吃葱姜蒜(0.56,0.48~ 0.65)、幽门螺杆菌感染(3.30,2.67~4.10)、常吃水果(0.49,0.40~0.60)、进食速度快(3.36,2.83~3.99)、常吃烤制食品(2.64,2.02~3.44)、常吃豆类食品(0.66,0.56~0.78)、常吃油炸食品(2.82,1.94~4.09)、常吃干硬食物(1.98,1.40~2.78)、常吃霉变食品(4.94,3.24~7.54)。结论:吸烟、慢性胃病史、肿瘤家族史、不良情绪、常吃腌制食品、进食不规律、常吃烫食、常饮酒、高盐饮食、幽门螺杆菌感染、进食速度快、常吃烤制食品、常吃油炸食品、常吃干硬食物、常吃霉变食品为中国人群胃癌发病的危险因素。常吃蔬菜、常饮茶、常吃葱姜蒜、常吃水果、常吃豆类食品为胃癌发病的保护因素。 相似文献
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目的 运用系统评价方式探讨乳腺癌内乳区淋巴结转移的危险因素,为内乳区放疗的决策提供循证依据。方法 在Medline、Embase以及Cochrane library数据库中检索截至2021年1月29日发表的与内乳区淋巴结转移相关文献。采用Review Manager 5.3软件进行统计分析。结果 涉及5 484例乳腺癌患者的13项研究纳入Meta分析。与内乳区淋巴结转移相关的因素为:年龄≤35岁(OR=1.83,95%CI=1.33~2.51)、年龄≤40岁(OR=2.93,95%CI=1.16~7.41)、内侧或中央肿瘤(OR=1.32,95%CI=1.11~1.57)、肿瘤>2 cm(OR=1.65,95%CI=1.14~2.41)、肿瘤>5 cm(OR=1.58,95%CI=1.25~2.00)、腋窝淋巴结转移(OR=5.27,95%CI=3.72~7.47)、≥4枚阳性腋窝淋巴结(OR=6.49,95%CI=5.12~8.23)、PR阴性(OR=1.35,95%CI=1.00~1.84)。结论 年轻女性、内侧或中央区肿瘤、较大肿瘤、腋窝淋巴结转移和PR阴性是乳腺癌内... 相似文献
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目的 探讨吸烟、饮酒与中国人群食管癌p53基因改变的关系。方法 在Medline和CNKI数据库中系统检索相关文献,应用Meta分析的方法进行定量综合分析。结果 共纳入14篇文献,累积食管癌2 108例,p53基因改变1 142例,平均阳性率为54.2%。在中国人群中,吸烟与食管癌p53基因改变的合并OR值为1.61(95% CI:1.09-2.38),P=0.003;饮酒与食管癌p53基因改变的合并OR值为1.91(95% CI:1.44-2.53),P<0.001。结论 中国人群中,吸烟、饮酒均与食管癌p53基因改变有显著联系。 相似文献
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中国人群饮食因素与食管癌Meta分析 总被引:4,自引:1,他引:4
[目的]研究中国人群饮食因素与食管癌的关联。[方法]对国内2000~2005年发表的21项关于食管癌饮食因素的病例对照研究文献中的饮食因素进行Meta分析。累计病例5759例,对照8795例。[结果]腌制食品、饮食不规律、霉变食品、喜烫食、高盐饮食、进餐速度快、酸菜的合并OR值及其95%CI均大于1,分别为2.79(1.85~4.20)、2.76(2.42~3.14)、2.53(2.16~2.95)、2.51(1.75~3.60)、2.27(1.35~3.82)、2.17(1.61~2.92)、1.71(1.16~2.54);饮茶、水果、豆及豆制品的合并OR值及其95%CI均小于1,分别为0.25(0.21~0.30)、0.46(0.44~0.48)、0.50(0.31~0.79);而葱蒜、动物肉类、禽蛋、辛辣食品、蔬菜、油炸食品与食管癌之间的关联无统计学意义。[结论]在中国人群的饮食因素中,腌制食品、饮食不规律、霉变食品、喜烫食、高盐饮食、进餐速度快、酸菜是食管癌的危险因素,饮茶、水果、豆及豆制品是食管癌的保护因素。 相似文献
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目的:系统评价中国人群儿荼酚氧位甲基转移酶(catechol-O-methyltransferase,COMT)Vall58Met基因多态性与乳腺癌易感性的关系。方法:在PubMed、MEDLINE、webofScience、Embase、中国期刊全文数据库(CJFD)及万方数据库中检索1999-10-01-2012-01-01发表的所有有关中国人群COMTVall58Met基因多态性与乳腺癌易感性关系的相关文献,并按STREGA原则对文献进行筛选、评价。纳入文献均为病例对照研究,对照群体基因型分布均符合H-W遗传平衡定律。应用Stata 12.0软件进行Meta分析,计算合并0R值及95%CI,并进行敏感性分析和发表偏倚的估计。结果:按照入选标准,有11项病例对照研究纳入,包括乳腺癌患者3184例,健康对照4065例。Meta分析结果显示,与基因型Val/Val(GG)、Val/Met(GA)比较,基因型Met/Met(AA)均增加中国人群罹患乳腺癌的风险[OR=1.55,95%CI:1.03~2.33,P=0.035;OR-1.63,95%CI:1.10~2.42,P=0.015];在隐性效应模型(Met/Met/vs Val/Val+Val/Met)中,基因型Met/Met(AA)增加中国人群罹患乳腺癌的风险,0R-1.59,95%CI:1.07~2.36,P=0.021。与等位基因Val(G)比较,等位基因Met(A)不增加中国人群罹患乳腺癌的风险,OR=1.12,95%CI:0.96~1.32,P=0.157。结论:COMTVall58Met基因多态性与中国人群乳腺癌易感性相关,基因型Met/Met(AA)增加中国人群罹患乳腺癌的风险。 相似文献
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目的:检测贵屿电子垃圾污染区新生儿胎盘镉含量及胎盘金属硫蛋白(metallothionein,MT)表达量,评估贵屿地区新生儿镉暴露情况及对新生儿的可能影响。方法:选取贵屿当地医院妇产科2006年7~9月出生的足月健康新生儿胎盘100例为实验组,纳入研究的产妇为贵屿镇当地居民,妊娠期间在贵屿居住。取汕头市潮南民生医院妇产科2006年5~6月出生的足月健康新生儿胎盘52例为对照组,产妇来自贵屿周边乡镇。石墨炉原子吸收法检测胎盘镉含量。链霉菌素_生物素(S_P)免疫组化技术检测胎盘组织MT的表达水平。问卷调查收集可能影响镉负荷的产妇年龄、家庭、环境、健康、饮食等因素。结果:实验组新生儿胎盘镉水平的平均值为(0.17±0.48)μg/g,明显高于对照组(0.10±0.11)μg/g,差异具有统计学意义(P〈0.01)。相关分析表明产妇在贵屿居住时间、产妇妊娠期间在贵屿居住时间、产妇怀孕期间在公路附近活动时间是影响胎盘镉水平的主要因素。S_P免疫组织化学检测显示胎盘组织中蜕膜细胞、合体滋养层细胞、绒毛间质细胞均有MT的表达。实验组胎盘组织MT阳性表达率(67.00%)高于对照组(32.69%)(P〈0.01)。新生儿胎盘MT表达量与胎盘镉水平呈显著正相关(r=0.761,P〈0.05)。结论:贵屿部分新生儿处于高镉负荷状态,贵屿当地环境和从事电子垃圾作业是影响当地新生儿高镉负荷的危险因素。贵屿地区新生儿胎盘可能通过增加MT的表达拮抗镉的毒性。 相似文献
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目的系统评价中国人群肿瘤家族史及与鼻咽癌之间的关系及相关强度,为我国鼻咽癌的防治策略提供依据。方法系统检索CNKI、万方和维普3个中文数据库及PudMed、ScienceDirect和SpringerLink 3个英文数据库2013-03之前发表的鼻咽癌病例对照研究及队列研究。文献检索、选取、信息提取及质量评价(NOS评分)均由2人独立进行。采用基于方差倒数加权的随机效应模型合并研究结果。结果纳入合格研究文献16篇,鼻咽癌患者7 478例,对照8 456例。肿瘤家族史与鼻咽癌患病的合并OR=2.63,95%CI为1.56~4.01;I2=49.2%,P=0.023;N=13;鼻咽癌家族史与鼻咽癌患病的合并OR=3.12,95%CI为2.47~3.78;I2=0,P=0.700;N=8。结合漏斗图及发表偏倚检验的结果,尚不能排除潜在的发表偏倚对结果的影响。结论在中国,肿瘤家族史,尤其是鼻咽癌家族史,会显著增加鼻咽癌的患病风险。 相似文献
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[目的]系统评价中国大肠癌筛查人群的依从性,为开展相关预防与控制工作提供基础数据.[方法]计算机检索中国生物医学文献数据库(光盘版)、中文期刊全文数据库(光盘版)、万方电子期刊、PubMed、EBSCO等数据库,并辅以参考文献追溯和手工检索方法,查找大肠癌初筛人群数量在5000~300 000人的研究文献,且采用的筛查方法为问卷调查与大便潜血检测(FOBT)进行初筛,发现高危人群再接受肠镜检查.检索时限为建库时间至2016年6月.由2位评价员按照纳入与排除标准独立筛选文献、提取资料和评价纳入研究的方法学质量后,采用R3.3.1软件进行Meta分析.[结果]最终纳入25篇文献,共827 904人接受初筛.Meta分析结果显示,问卷调查、FOBT、肠镜的依从率分别为56% (95%CI:40%~72%,P<0.0001)、50% (95%CI:33%~67%,P<0.0001)、44% (95%CI:33%~56%,P<0.0001).对肠镜依从率分层分析发现,农村地区肠镜依从率为64%(95%CI:52%~75%,P<0.0001),高于城市地区33% (95%CI:22%~45%,P<0.0001);北方为44%(95%CI:27%~70%,P<0.0001),略高于南方42%(95%CI:29%~55%,P<0.0001);初筛人数≥10 000人的大样本研究依从率为49%(95%CI:34%~64%,P<0.0001),高于小样本研究的35%(95%CI:16%~57%,P<0.0001);与职工体检结合的大肠癌伺机性筛查的肠镜依从率为83%(95%CI:32%~98%,P<0.0001),高于一般社区人群筛查的40% (95%CI:29%~52%,P<0.0001).[结论]中国大肠癌筛查人群依从性较低,因此需从筛查方式的选择、筛查流程设计、筛查过程的质量控制、健康宣传等多方面入手提高依从性. 相似文献
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《中国肿瘤临床与康复》2017,(2)
目的探讨血清促甲状腺激素(TSH)水平对甲状腺乳头状癌(PTC)颈侧区淋巴结转移的诊断价值。方法选取2013年2月至2016年4月间新疆医科大学附属肿瘤医院收治的110例PTC患者,同时选取40例甲状腺良性结节患者作为对照,分析患者术前血清TSH与颈侧区淋巴结转移的关系。结果 PTC组患者血清TSH为(2.32±0.61)IU/ml,明显高于甲状腺结节组的(1.42±0.73)IU/ml,差异有统计学意义(P<0.05)。不同性别、年龄和单双侧PTC患者血清TSH比较,差异均无统计学意义(均P>0.05)。肿瘤直径>1cm、Ⅲ~Ⅳ期、有钙化和伴颈侧区淋巴结转移的患者比肿瘤直径≤1cm、Ⅰ~Ⅱ期、无钙化和不伴颈侧区淋巴结转移患者的血清TSH均较高,差异均有统计学意义(均P<0.05)。血清TSH诊断PTC颈侧区淋巴结转移的ROC曲线下面积为0.865,截断值为2.86IU/ml时,灵敏度为75.9%,特异度为81.1%。结论 PTC患者血清TSH水平可作为预测颈侧区淋巴结转移的指标之一。 相似文献
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目的探讨乳腺癌患者三碘甲腺原氨酸(3,5,3’triiodothyronine,T3)、四碘甲腺原氨酸(3,5,3’,5’tetraiodothyronine,T4)、促甲状腺激素(thyroidstimulatinghormone,TSH)水平变化和甲状腺过氧化物酶抗体(TPO—Ab)的表达情况,分析其与乳腺癌临床病理因素的关系。方法收集2008年9月至2009年10月本院治疗的乳腺癌患者87例(乳腺癌组),良性乳腺腺瘤患者79例(良性组),应用放射免疫方法检测两组患者术前甲状腺激素(T3,T4andTSH)水平及TPO—Ab表达,并分析它们与乳腺癌临床病理因素的关系。统计学分析采用t检验和卡方检验。结果乳腺癌患者的血清T3水平较良性对照组降低(P=0.044),TPO-Ab的表达阳性率较良性对照组高(P=0.040),T4、TSH在两组间差异无统计学意义(P〉0.050)。乳腺癌患者T3降低与肿块大小、肿瘤分期、淋巴结转移有关(P〈0.050),与年龄、病理类型、ER、PR表达情况无关(P〉0.050)。乳腺癌患者TPO—Ab高表达与肿块大小、肿瘤分期、淋巴结转移、ER、PR表达情况有关(P〈0.050),与年龄、病理类型无关(P〉0.050)。结论乳腺癌患者血清甲状腺激素T3降低及TPO-Ab高表达可能反映乳腺癌的严重程度。 相似文献
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《International journal of hyperthermia》2013,29(5):560-567
AbstractPurpose: Microwave ablation (MWA) is a new minimally invasive method for thermal ablation of benign thyroid nodules with promising results. The aim of this study was to investigate whether MWA has an impact on thyroid function. Materials and methods: Thirty patients with a total of 34 benign thyroid nodules underwent MWA between January 2013 and July 2014. Serum levels of triiodothyronine (T3), thyroxine (T4), thyrotropin (TSH), thyroglobuline (Tg) and additionally antibodies against Tg (anti-Tg), thyrotropin receptors (TRAb) and thyroid peroxidase (anti-TPO) were measured at enrolment, 24?h after MWA, as well as at the 3-month and 6-month follow-up. Moreover, the nodule volume was evaluated to determine effectiveness. Results: Serum TSH, T4, T3 and Tg levels did not change significantly at the 3-month or 6-month follow-up (p?>?0.05); thyroid function was not affected by MWA. Antibody levels did not change significantly either; however, two patients developed antibodies after treatment. A volume reduction of 51.4% or 7.85?mL could be demonstrated after 3 months and a reduction of 55.8% or 14.0?mL after 6 months. Slight complications such as mild pain during the ablation or superficial haematomas emerged. The development of Graves’ disease and mild Horner’s syndrome were observed as more severe side effects. Conclusions: The data suggest MWA as an alternative for the treatment of benign thyroid nodules. While first results for preservation of thyroid function are positive, further measurements of laboratory data and especially antibodies are necessary. 相似文献
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目的:探讨邻苯二甲酸二(2-乙基)己酯(DEHP)长期暴露对成年雄性大鼠甲状腺激素水平产生的影响。方法:将36只健康的成年雄性Wistar大鼠按体质量随机分为4组,分别为对照组以及150、300、600 mg/kg DEHP暴露组。对照组大鼠正常饮食和饮水,暴露组大鼠连续灌胃给予DEHP 3个月。处死大鼠前称取大鼠体质量并计算各组织脏体比,检测尿碘含量,血清甲状腺激素含量及血清TTR、TRH、TSAb水平。采用单因素方差分析法分析各指标的组间差异,进一步的多重比较采用SNK检验。结果:经过3个月的DEHP暴露,大鼠体质量无明显变化。与对照组相比,各剂量组大鼠甲状腺湿重和脏体比无显著性差异。150、300、600 mg/kg剂量组大鼠肝脏脏体比增加并呈剂量-效应关系(P < 0.05)。600 mg/kg剂量组大鼠尿碘水平显著降低(P < 0.05)。600 mg/kg剂量组血清FT4(血清游离甲状腺素)水平降低(P < 0.05)。结论:DEHP 3个月的暴露期对大鼠体质量未产生明显影响,对甲状腺、肝脏脏器系统功能产生一定的影响。DEHP的暴露可抑制大鼠体内TSH的合成、分泌及转运,扰乱甲状腺激素水平。 相似文献
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Ido Didi Fabian Mordechai Rosner Ina Fabian Vicktoria Vishnevskia-Dai Ofira Zloto Elena Shinderman Maman Keren Cohen Martin Ellis Hung-Yun Lin Aleck Hercbergs Paul J. Davis Osnat Ashur-Fabian 《Oncotarget》2015,6(13):11038-11046
Uveal melanoma is highly metastatic, prognosis is poor and there are no effective treatments to extend survival. Accumulating evidence suggests that thyroid hormones have a mitogenic effect via binding to αvβ3 integrin. We aimed to examine the impact of thyroid status on survival in a murine B16F10 model for ocular melanoma, highly expressing the integrin. In two independent experiments oral propylthiouracil (PTU) was used to induce hypothyroidism (n=9), thyroxine to induce hyperthyroidism (n=11) and mice given plain water served as control (n=8). At day 21, the subretinal space was inoculated with 102 B16F10 cells. In non-inoculated mice (n=6 of each group) serum free T4 (FT4) levels were measured and additional non-inoculated mice (3 given PTU and 4 given thyroxine or water) served as internal control to demonstrate the impact of the dissolved substance. The PTU-inoculated mice showed clinical evidence of intraocular tumor growth significantly later than the thyroxine mice (P=0.003) and survival time was significantly longer (P<0.001). FT4 levels differed significantly between groups (P<0.001) and with no signs of illness in the internal control group. Our findings suggest that hyperthyroidism shortens survival, whereas relative hypothyroidism may have a protective role in metastatic ocular melanoma. 相似文献
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Hüdayi Korkusuz Michael Sennert Niklas Fehre Christian Happel Frank Grünwald 《International journal of hyperthermia》2014,30(7):480-485
Objective: The aim of this study was to assess whether high-intensity focused ultrasound (HIFU), a new and promising method for the treatment of benign hot and cold thyroid nodules using thermal ablation, has an impact on thyroid function, and to evaluate its feasibility in outpatient settings. Additionally, a possible difference in the treatment of solid and complex thyroid nodules was evaluated. Method: Ten patients with one thyroid nodule each (six cold and four hot nodules) underwent HIFU in January 2014. Four nodules were solid and six nodules were complex. Serum levels of triiodothyronine (T3), thyroxine (T4), thyrotropin (TSH), thyroglobulin (hTg) and additionally antibodies against hTg (TAK), TSH receptors (TRAK) and thyroid peroxidase (TPO) were measured at enrolment and 24?h after the HIFU treatment. The pre- and post-thyroglobulin reduction was measured to evaluate the scale of ablation. In addition, patients’ pain was recorded on a numeric rating scale from 0 to 10. Results: The HIFU treatment did not affect thyroid function, since hormone levels stayed stable (p?0.05). No serious immune reaction was induced. Thyroglobulin serum levels increased significantly (p?0.05) and were correlated to the total energy emitted by HIFU (p?0.1). The results of complex thyroid nodules did not differ from solid thyroid nodules. Similarly, the results of hot thyroid nodules did not differ from cold thyroid nodules. All patients tolerated the whole treatment and no severe complications were observed. Conclusion: HIFU is a safe and effective method to treat benign, solid, complex, hot and cold thyroid nodules preserving thyroid function. Further developments of the system are needed to gain suitability for daily use. 相似文献
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Relationship between Breast Cancer and Levels of Serum Thyroid Hormones and Antibodies: a Meta-analysis
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《Asian Pacific journal of cancer prevention》2014,15(16):6643-6647
The breast and the thyroid are hormone responsive organs that are closely related with changes of endocrine function and glandular disease. An association between thyroid disorders and breast cancer (BC) risk has been suggested, although the results are inconclusive. The purpose of the present study was to summarize evidence supporting a relationship between BC and the level of thyroid hormones and antibodies. The MEDLINE and EMBASE electronic databases were searched for studies published between 2000 and 2014. The pooled effects were presented as weighted mean differences (WMD) with 95% confidence intervals (CI) using fixed or random effect models. We summarized the results of 8 cross-sectional studies with 4, 189 participants. The overall pooledresults showed that the levels of FT3 and FT4 were significantly increased in patients with BC (WMD=1.592 pmol/l; 95% CI: 0.15-3.033 and WMD=0.461 ng/dl; 95% CI: 0.015-0.906; p=0.043). The TPOAb level in patients with BC was higher than that in the control group (WMD=81.4 IU/ml; 95% CI: 78.7-84.0; p=0.000). The overall pooled results of the TgAb with random effects analyses showed that the TgAb level was significantly increased in patients with BC (WMD=101.3 IU/ml; 95% CI: 48.7-153.9; p=0.000). The present results indicated that the serum levels of FT3, TPOAb and TgAb are significantly higher in patients with breast cancer than in healthy controls. 相似文献
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18.
Comparison of effective I‐131 half‐life between thyroid hormone withdrawal and recombinant human thyroid‐stimulating hormone for thyroid cancer: A retrospective study
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Solveig Grenfell Daniel Roos James Rijken Braden Higgs Ian Kirkwood 《Journal of Medical Imaging and Radiation Oncology》2015,59(2):248-254
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甲状腺激素及其受体与乳腺癌关系研究进展 总被引:3,自引:0,他引:3
目的:对甲状腺激素及其受体与乳腺癌发生发展的关系及其作用机制。方法:应用PubMed期刊全文数据库检索系统,以“乳腺癌、甲状腺激素和甲状腺激素受体”为关键词,检索1896—07—2012—11的相关文献。纳入标准:1)甲状腺激素水平与乳腺癌的关系;2)甲状腺激素受体与乳腺癌的关系;3)甲状腺激素、甲状腺激素受体影响乳腺癌发生发展的作用机制。根据纳入标准符合分析的文献23篇。结果:流行病学研究显示,甲状腺激素水平升高促进乳腺癌发生发展,甲状腺激素水平降低与乳腺癌关系尚无定论。实验研究显示,高甲状腺激素水平可以促进乳腺癌细胞生长,低甲状腺激素水平减缓乳腺癌细胞生长的同时促使其发生上皮~间质转化(epithelial—mesenchymal transition,EMT)现象。另外,细胞内甲状腺激素受体缺失促进乳腺癌发生进展。有研究表明,甲状腺激素及其受体可能通过细胞核、细胞膜、肿瘤微环境及细胞凋亡等各个层面对乳腺癌的发生发展起促进或抑制作用。结论:甲状腺激素及其受体影响乳腺癌发生发展,但其具体作用方式、作用机制尚不完全明确,对其相互作用的研究可能为未来乳腺癌治疗提供新的策略。 相似文献
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The C-terminal frame-shift mutant of the thyroid hormone receptor TRβ1, PV, functions as an oncogene. An important question is whether the oncogenic activity of mutated TRβ1 is uniquely dependent on the PV mutated sequence. Using four C-terminal frame-shift mutants—PV, Mkar, Mdbs, and AM—we examined that region in the oncogenic actions of TRβ1 mutants. Remarkably, these C-terminal mutants induced similar growth of tumors in mouse xenograft models. Molecular analyses showed that they physically interacted with the p85α regulatory subunit of PI3K similarly in cells. In vitro GST-binding assay showed that they bound to the C-terminal Src-homology 2 (CSH2) of p85α with markedly higher avidity. The sustained association of mutants with p85α led to activation of the common PI3K-AKT-ERK/STAT3 signaling to promote cell proliferation and invasion and to inhibit apoptosis. Thus, these results argue against the oncogenic activity of PV being uniquely dependent on the PV mutated sequence. Rather, these four mutants could favor a C-terminal conformation that interacted with the CSH2 domain of p85α to initiate activation of PI3K to relay downstream signaling to promote tumorigenesis. Thus, we propose that the mutated C-terminal region of TRβ1 could function as an “onco-domain” and TRβ1 is a potential therapeutic target. 相似文献