甲状腺激素及其受体与乳腺癌关系研究进展

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。     

肥胖与乳腺癌关系的研究进展

乳腺癌是世界女性最常见的恶性肿瘤之一,每年新确诊的癌症病例中有1/10是女性乳腺癌,每年约有120万女性罹患乳腺癌,约50万人死于该病[1]。资料显示,全世界有9.8%的男性和13.8%的女性被认为是肥胖者[2]。肥胖已经成为全球的重大公共卫生问题,同时,流行病学资料显示肥胖能增加乳腺癌风险[3],因而肥胖与乳腺癌的关系日益受到学者们的重视。本文从肥胖人群中乳腺癌患者的临床及生物学机制等方面对肥胖与乳腺癌的研究进展作一综述。     

2型糖尿病与乳腺癌关系的研究进展

目的:总结国内外关于2型糖尿病与乳腺癌关系方面的研究进展。方法:应用PubMed和CNKI期刊全文数据库检索系统,以"2型糖尿病、乳腺癌"为关键词,检索2006-01-2012-10的有关文献。纳入标准:1)关于2型糖尿病和乳腺癌的流行病学文献;2)关于2型糖尿病和乳腺癌相关的基础研究和临床研究文献。根据纳入标准,符合分析的文献51篇。结果:2型糖尿病增加乳腺癌的发病和总死亡风险,在绝经后期女性中尤为显著。2型糖尿病与乳腺癌通过高血糖、高胰岛素血症、胰岛素样生长因子、脂肪细胞因子及内源性性激素等机制发生联系。这些机制在分子水平上相互联系,针对这些机制中某些靶点的抑制剂或单克隆抗体在基础实验和(或)临床试验中取得一定程度的进展。结论:2型糖尿病和乳腺癌相关的具体机制需要更多的基础研究和大型前瞻性临床试验来揭示,这些抑制剂或单克隆抗体有望为难治性乳腺癌提供新的选择,更有利于乳腺癌的个体化治疗。     

乳腺癌的流行病学研究进展

简要回顾近20年来乳腺癌流行病学研究的进展,主要内容包括乳腺癌的流行特点、乳腺癌的危险因素、乳腺疾病的普查和自我检查、乳腺癌的遗传流行病学研究和乳腺癌的预防性研究.     

中药植物雌激素效应与乳腺癌关系的研究进展

植物雌激素是一类天然存在于植物中与雌激素结构相似的非甾体类化合物。现代研究显示,植物雌激素不仅可以天然存在,而且其前体物质经胃肠道吸收代谢以后形成。植物雌激素大多数具有雌二醇的结构,可以与雌激素受体结合,从而产生雌激素样作用或者抗雌激素样作用。全文就近年来植物雌激素效应以及与乳腺癌关系的研究作一综述。     

乳腺癌循环肿瘤细胞研究进展与展望

目的:总结国内外乳腺癌循环肿瘤细胞(CTC)在检测手段及相关临床意义方面的研究进展,以及CTC检测项目在研究肿瘤转移过程中的地位、必要性及未来的发展方向.方法:应用Medline、PubMed及CNKI期刊全文数据库系统,以“乳腺癌、循环肿瘤细胞、转移、上皮间质转化”等为关键词,检索2006-06-2011-06的相关文献,共选择文献48篇加以分析总结.文献纳入标准:1)乳腺癌CTC的起源及其特点;2)乳腺癌CTC的检测方法;3)检测乳腺癌CTC的临床意义;4)乳腺癌CTC的特性.结果:CTC的检测在预测乳腺癌患者无病生存期和总生存期方面有重要价值;同时,它在预测和判断疗效方面优于一些传统方法.除此之外,CTC的分子学和生物学特性,如ER、PR、HER-2表达和上皮间质转化等,以及这些特性与乳腺癌转移的关系已成为新的研究热点.结论:对CTC的深入研究能够使我们进一步了解它,使其成为乳腺癌患者监测转移和预后的常规的检测指标,并有助于了解血行转移的机制,更有望发现乳腺癌治疗的新靶点.     

乳腺癌干细胞的研究进展

目的:总结国内外关于乳腺癌干细胞在乳腺癌中的作用及对其进行靶向调控的研究进展.方法:应用Medline及CNKI期刊全文数据库系统,以"乳腺癌干细胞、信号通路、表皮生长因子受体(EGFR)"为关键词,检索1997-01-2008-12的相关文献,共检索到英文文献4 191篇和中文文献25篇.纳入标准:1)乳腺癌干细胞的起源及其特点;2)乳腺癌干细胞的分选及富集方法;3)调控乳腺癌干细胞自我更新的信号通路;4)EGFR信号通路在乳腺癌干细胞中的作用.根据纳入标准,精选60篇文献,最后纳入分析29篇文献.结果:乳腺癌干细胞在乳腺癌的发生发展以及复发转移中发挥重要作用.因其具有较高的耐药性,故传统的化疗药物很难对其杀伤,通过阻断癌干细胞中激活的信号通路,如EGFR信号通路可以有效抑制干细胞的生长.结论:根据乳腺癌干细胞的自身特点,靶向于其中激活的信号通路对其进行抑制为乳腺癌的治疗提供了一个新的思路.     

乳腺癌诊断学研究进展

介绍几十年来对乳腺癌诊断方法研究的进展,分析当前临床常用的诊断方法的特点及不足,其中X线摄影及超声检查是发展最快和诊断正确率较高的技术,也是早期发现的重要手段.另外强调,临床医师对疾病的认识和多种诊断方法的联合应用,是提高诊断效果不可或缺的两个因素.     

乳腺癌骨转移机制的研究进展

目的:总结近年来国内外对乳腺癌骨转移机制研究进展.方法:应用计算机检索CHKD期刊全文数据库及PubMed检索系统,以乳腺癌和骨转移为关键词检索2003-01-2008-08相关乳腺癌骨转移机制研究的文献.纳入标准:1)乳腺癌骨转移机制的分子生物学及物理、化学因素的研究; 2)成骨细胞与破骨细胞微环境的研究;3)乳腺癌骨转移的药物靶向治疗.粗选近百篇关于乳腺癌骨转移方面的文章,根据纳入标准,精选62篇文献,最后纳入分析26篇文献.结果:乳腺癌骨转移大部分呈现溶骨性特征,骨转移涉及复杂的步骤和机制,其中癌细胞、破骨细胞、成骨细胞和骨基质中产生和释放的大量细胞因子之间复杂的相互作用促进了骨转移的形成和发展.另外一些理化因子与骨肿瘤转移也有很大关系.结论:乳腺癌骨转移涉及的因素复杂,靶向抑制其启动和进展中任何一个环节均可能阻止骨转移的恶性循环.研究乳腺癌骨转移的发生机制,可为骨转移的预防和治疗提供新的药物靶点.     

ERα磷酸化与乳腺癌内分泌疗效关系的研究进展

激素依赖性乳腺癌的内分泌治疗在乳腺癌的综合治疗中占有不可替代的地位。它以确切的疗效，相对较轻的毒副作用，加之低廉的费用，促使其被广泛应用于各期乳腺癌的治疗及乳腺癌高危人群的预防。然而，并不是所有的激素依赖性乳腺癌对内分泌治疗均敏感。以往的研究发现，雌孕激素受体状况不明者的内分泌治疗有效率为20％～30％，ER阳性者为50％～60％，ER、PR均阳性者为75％以上。     

Milk, milk products and lactose intake and ovarian cancer risk: a meta-analysis of epidemiological studies

It has been proposed, on the basis of animal models and ecological studies, that consumption or metabolism of dairy sugar may increase the risk of ovarian cancer. Case-control and cohort studies of the association between lactose and dairy food consumption and ovarian cancer risk, however, have yielded varied findings. We summarized the available literature on this topic using a meta-analytic approach. Random-effects models were used to estimate the summary relative risks (RR(summary)). A linear regression analysis of the natural logarithm of the RR was carried out to assess a possible dose-response relationship between lactose intake and ovarian cancer risk. Eighteen case-control and 3 prospective cohort studies were eligible for inclusion in the meta-analysis. The findings of case-control studies were heterogeneous, and, except for whole milk (RR(summary) for highest vs. lowest category = 1.27, 95% confidence interval [CI] = 0.97-1.68), do not provide evidence of positive associations between dairy food and lactose intakes with risk of ovarian cancer. In contrast, the 3 cohort studies are consistent and show significant positive associations between intakes of total dairy foods, low-fat milk, and lactose and risk of ovarian cancer. The RR(summary) for a daily increase of 10 g in lactose intake (the approximate amount in 1 glass of milk) was 1.13 (95% CI = 1.05-1.22) for cohort studies. In conclusion, prospective cohort studies, but not case-control studies, support the hypothesis that high intakes of dairy foods and lactose may increase the risk of ovarian cancer.     

Milk, dairy intake and risk of endometrial cancer: a 26-year follow-up

Estrogens have a central role in the etiology of endometrial cancer. Milk and dairy products are a source of steroid hormones and growth factors that might have physiological effects in humans. We hypothesized that high intakes of milk and dairy products are associated with an increased risk of endometrial cancer, particularly among postmenopausal women not using hormone therapy. This was a prospective cohort study with 68,019 female participants in the Nurses' Health Study aged 34-59 in 1980. Milk and dairy consumption were assessed in 1980, 1984, 1986, 1990, 1994, 1998 and 2002 as servings per day and the follow-up continued through 2006. The multivariate relative risks (RRs) of adenocarcinoma of the endometrium across categories of cumulatively averaged total dairy consumption compared with < 1 svg/day were: 0.94 (95% CI = 0.71-1.25) for 1-1.4 svg/day, 1.14 (0.87-1.49) for 1.5-1.9 svg/day, 1.10 (0.84-1.44) for 2-2.9 svg/day, 1.26 (0.94-1.70) for ≥ 3 svg/day (p for trend = 0.06). The association between total dairy intake and endometrial cancer was significant only among the postmenopausal women (for ≥ 3 svg/day RR = 1.41, 95% CI = 1.01-1.98, p for trend = 0.02) and was evident only among those who were not currently using hormone therapy (RR = 1.58, 95% CI = 1.05-2.36, p for trend = 0.003). Total dairy intake was not significantly associated with risk of preinvasive endometrial cancer. In conclusion, we observed a marginally significant overall association between dairy intake and endometrial cancer and a stronger association among postmenopausal women who were not using estrogen-containing hormones.     

Endoglin与乳腺癌

Endoglin是内皮细胞表面与细胞增殖相关的膜抗原,也是转化生长因子β超家族受体复合物成分之一。其具有调节内皮细胞对TGF的反应、促内皮细胞增殖和促血管形成等功能,与肿瘤血管的发生密切相关。近年来,Endoglin在肿瘤诊断、判断预后和疗效及抗肿瘤血管靶向治疗等方面的作用得到重视。     

Tamoxifen and risk of large bowel cancer in women with breast cancer

Background: The increasingly consistent association between estrogen replacement therapy and colorectal cancer suggests that the anti-estrogen tamoxifen may also be associated with large bowel cancer incidence.Methods: Women with new diagnoses of breast cancer were identified from the Surveillance Epidemiology and End Results (SEER) Program, a set of geographically defined, population based cancer registries representing approximately ten percent of the U.S. population. Of 85,411 women with local or regional breast cancer diagnosed from 1983–90, 14,984 women were reported to have received hormonal therapy and 70,427 were not known to have received hormonal therapy. Subsequent cancer diagnoses were identified in this cohort beginning 6 months after initial breast cancer diagnosis until death, or December 31, 1994. Multivariate Cox proportional hazards models were used to estimate the risk of developing colorectal cancer and other second cancers according to hormonal therapy use.Results: Over the follow-up period 793 colorectal, 2,648 contralateral breast, 506 endometrial, 250 ovarian, 98 gastric, and 1,765 other cancers were identified in the study cohort. While overall there was no association between hormonal therapy use and colorectal cancer (relative risk (RR) 1.09, 95% confidence interval (CI) 0.88–1.35), in the period five or more years after diagnosis, risk was increased significantly by about 50% (95% CI 1.00–2.15). As expected, based upon clinical trials data, cancers of the contralateral breast were significantly decreased, and cancers of the uterine endometrium were significantly increased. No other meaningful associations were observed. When women were excluded for whom hormonal therapy might represent therapy other than tamoxifen (premenopausal women and those who received chemotherapy), this did not meaningfully alter these estimates.Conclusions: The results of this large population based cohort study suggest that tamoxifen therapy may modestly increase risk of large bowel cancer in women, but only after 5 years following initiation of breast cancer therapy.     

Dairy consumption and ovarian cancer risk in the Netherlands Cohort Study on Diet and Cancer

Ovary cancer risk in relation to consumption of dairy products was investigated using a self-administered questionnaire on dietary habits and other risk factors for cancer, which was completed in 1986 by 62 573 postmenopausal women participating in the Netherlands Cohort Study. Follow-up for cancer was implemented by annual record linkage with the Netherlands Cancer Registry and a nationwide pathology registry. After 11.3 years of follow-up, data of 252 incident epithelial ovarian cancer cases and 2216 subcohort members were available for analysis. No association was seen between consumption of milk, yoghurt, cheese or fermented dairy products and ovarian cancer risk. The multivariable adjusted relative risk of epithelial ovarian cancer for women in the highest compared to the lowest quintile of intake of lactose or dairy fat was 0.93 (95% confidence interval (CI)=0.60-1.45; P(trend)=0.32) and 1.53 (95% CI=1.00-2.36; P(trend)=0.11), respectively. Lactose or dairy fat intakes were not associated with serous ovarian cancer risk. Our results do not support an association between consumption of dairy products or lactose intake and ovarian cancer.     

IGFs系统与乳腺癌

乳腺癌的高发病率及发病年龄的年轻化已引起人们越来越多的关注，在众多发病因素方面，目前胰岛素样生长因子这个庞大复杂的系统引起了人们的高度关注。该类调节因子主要由肝脏产生，存在于血液中，参与调节细胞的生长增殖。胰岛素样生长因子（IGF）可以抑制细胞凋亡的速度，刺激细胞增殖活性，血清高浓度的IGF是乳腺癌高发的重要因素；IGF受体与胰岛素有70％的同源性，与IGF结合后可引起细胞的分裂分化，具有潜在的有丝分裂原作用；胰岛素样生长因子结合蛋白（IGFBP）主要是起运输作用，通过与IGF相结合而产生生物效应，血浆高浓度的IGFBP可以降低IGF的生物作用。     

乳腺癌化疗耐药中肿瘤干细胞的作用及其机制

目的:了解肿瘤干细胞在乳腺癌化疗耐药中的作用及其相关机制的研究进展。方法:应用检索Pubmed及CNKI数据库检索系统,以肿瘤、干细胞、乳腺癌、化疗和耐药等为关键词,检索1999-01-2011-05的相关文献,纳入标准:肿瘤干细胞与乳腺癌化疗耐药。根据纳入标准分析42篇文献。结果:肿瘤干细胞是导致乳腺癌化疗耐药和治疗失败的主要细胞,其耐药的机制包括ATP结合盒转运子的过度表达、细胞解毒酶的过度活化、细胞存活和凋亡相关信号转导通路的异常激活、肿瘤壁龛对肿瘤干细胞的保护作用以及大部分肿瘤干细胞处于静止期。通过对这些耐药机制的干预,可以逆转肿瘤干细胞的耐药性。结论:肿瘤干细胞是导致乳腺癌化疗耐药的关键细胞,对其耐药机制的研究有助于展开针对肿瘤干细胞的靶向治疗,改善患者的预后。     

IGFs系统与乳腺癌

乳腺癌的高发病率及发病年龄的年轻化已引起人们越来越多的关注,在众多发病因素方面,目前胰岛素样生长因子这个庞大复杂的系统引起了人们的高度关注。该类调节因子主要由肝脏产生,存在于血液中,参与调节细胞的生长增殖。胰岛素样生长因子(IGF)可以抑制细胞凋亡的速度,刺激细胞增殖活性,血清高浓度的IGF是乳腺癌高发的重要因素;IGF受体与胰岛素有70%的同源性,与IGF结合后可引起细胞的分裂分化,具有潜在的有丝分裂原作用;胰岛素样生长因子结合蛋白(IGFBP)主要是起运输作用,通过与IGF相结合而产生生物效应,血浆高浓度的IGFBP可以降低IGF的生物作用。     

市场牛奶和传统牛奶对乳腺癌发生影响的研究

目的:评价市场牛奶和传统牛奶对二甲基苯并蒽(DMBA)诱导的大鼠乳腺肿瘤发生的影响。方法:120只雌性大鼠采用致癌剂DMBA诱发乳腺癌后,将大鼠分为市场牛奶组(C)、内蒙古黄牛奶组(T)和自来水组(W),比较3组大鼠的乳腺肿瘤发生率、发生时间和数量。结果:C组大鼠乳腺首发肿瘤出现最早(DMBA干预后的第5周),T和W组分别比C组晚1和2周;C组大鼠肿瘤发生的潜伏期〔(9.1±3.8)周〕短于T组〔(11.7±4.0)周〕;C、T和W组肿瘤发生率分别为80.0%(32/40)、80.0%(32/40)和52.5%(21/40);C组肿瘤发生的数量(142个)高于T组(92个)和W组(65个)。结论:目前,我国市场上销售的牛奶对DMBA诱导的大鼠乳腺肿瘤的发生具有促进作用,牛奶中的雌孕激素,特别是雌激素在促癌实验中发挥了关键作用。     

细胞紧密连接蛋白与乳腺癌侵袭转移相关性研究的现状分析

目的:总结国内外关于细胞间紧密连接的破坏在乳腺癌浸润与转移中的作用.方法:应用Medline及CNKI期刊全文数据库系统以"乳腺癌、转移和紧密连接"为关键词检索1997-2010年的相关文献,分析文献30篇.纳入标准:1)乳腺癌的转移机制;2)紧密连接的结构及功能;3)紧密连接的破坏与乳腺癌转移的相关性.结果:紧密连接...