HER-2／neu基因与肿瘤

肿瘤的发生发展是多阶段性、多基因参与、多种转录因子调控的过程。人类表皮生长因子受体2（humanepidermalre-eeptor2，HER-2），又名e-erbB-2基因，是一种原癌基因，编码跨膜蛋白P185HER2。HER_2／neu在调节肿瘤细胞生长、分化及存活起着重要的作用。与肿瘤的发生、转移、预后、治疗等密切相关。研究显示在乳腺癌、卵巢癌、胃癌、大肠癌、肺癌、前列腺癌中均存在不同程度的HER-2过表达。HER一2／neu基因与肿瘤的发生、发展、预后及靶点治疗成为研究的热门课题。文章针对HER-2／neu基因的结构、功能、导致肿瘤发生机制、与各种肿瘤的相关性、检测方法及靶向治疗等内容作综述。     

脂多糖对小鼠巨噬细胞ABCA1表达和胆固醇流出的影响

目的观察脂多糖(LPS)对小鼠腹腔巨噬细胞ATP结合盒转运体A1(ABCA1)表达和胆固醇流出的影响,探讨肝X受体α(LXRα)信号途径的作用。方法 60只C57小鼠分成两组,分别注射LPS(1.0 mg/kg)和等量生理盐水。12 h后取腹腔巨噬细胞,实时荧光定量PCR和Western-blot印迹法检测ABCA1和LXRαmRNA和蛋白质表达水平,液体闪烁计数器检测细胞内胆固醇流出。LXRα激动剂22(R)-羟基胆固醇(22(R)-Hch)预处理小鼠,观察对LPS调节ABCA1表达和胆固醇流出的影响。结果 LPS抑制LXRα和ABCA1的mRNA和蛋白质表达;22(R)-Hch预处理抑制LPS对ABCA1表达和胆固醇流出的下调作用。结论通过抑制TLR4/LXRα信号途径的激活,可以减轻LPS诱导的急性时相反应中的炎症程度,上调ABCA1的表达,促进细胞内胆固醇的流出。     

酸敏感离子通道1在肿瘤中的研究进展

酸敏感离子通道(acid-sensing ion channels,ASICs)是细胞外酸性p H值的关键受体,在生物体内广泛表达,在疼痛、炎症、记忆、脑缺血等多项涉及酸中毒的病理和生理过程中起着重要作用。它能介导肿瘤细胞的迁移和侵袭,参与肿瘤的发展。ASIC1在肺癌、胰腺癌、乳腺癌等实体肿瘤中大量表达,其表达对肿瘤早期诊断及治疗和预后起到重要的作用。目前关于ASIC1在肿瘤中的具体调控机制仍不是十分清楚。     

Caveolin-1在肿瘤中的作用机制的研究进展

小窝蛋白-1(Caveolin-1)是caveolae上的主要结构功能蛋白,通过它的脚手架区(CSD)与多个重要蛋白直接结合,形成信号通路的枢纽中心,在细胞增殖、迁移和分化,肿瘤的发生和转移等生理、病理过程中发挥重要作用。在正常生理条件下和结肠癌、肝癌、乳腺癌等肿瘤的早期,Caveolin-1-信号分子复合物负性调控各种信号通路。而在泌尿系肿瘤的各个时期和其他大多数肿瘤的晚期,Caveolin-1异常表达,激活各种生长信号的传导,促进肿瘤细胞生长、增殖和转移。Caveolin-1在肿瘤中表现出的双重效应与它调控的信号通路相关。本文将就Caveolin-1在肿瘤细胞中调控的信号通路做具体阐述。     

循环肿瘤细胞致肿瘤血行转移研究进展

众所周知，肿瘤转移是造成肿瘤死亡的重要原因之一。原发肿瘤释放成千上万的肿瘤细胞入血，但仅有不足0.01%的循环肿瘤细胞（CTCs）能够在外周血存活下来并形成转移[1]，CTCs检测在肺癌、乳腺癌、前列腺癌等多种癌症中具有诊断、判断预后等价值[2]。以往认为肿瘤转移发生在原发肿瘤形成之后，经典的肿瘤转移经过原发灶肿瘤、肿瘤细胞播散入血并在外周血中存活、组织侵袭、形成转移灶等阶段[3]，但最近研究发现[4]，上皮细胞播散可发生于癌前病变的极早期，在形成明显的原发灶之前，上皮细胞或已脱落入血并在远处定植。肿瘤细胞脱落入血，并进行血行转移的过程中，CTCs受到宿主细胞和血液微环境等多方面因素的调控，需要不断获得适应微环境的生存能力，因此认识和探讨CTCs的血行转移调控机制能够为临床监测肿瘤播散转移提供重要价值。本文就肿瘤细胞如何在外周血中存活并形成转移做一简要概述。     

SR-BI在动脉粥样硬化、恶性肿瘤和感染性疾病中的作用

B族I型清道夫受体(SR-BI)是高密度脂蛋白(HDL)的高亲和力受体。它最主要的作用是通过肝脏在胆固醇逆向转运(RCT)中选择性的摄取高密度脂蛋白(HDLs)。SR-BI与HDL相互作用调节脂质代谢和影响参与动脉粥样硬化(As)过程的各种血管细胞功能。此外,SR-BI还参与了恶性肿瘤和感染性疾病的发生发展。本文综述了SR-BI的功能及其在动脉粥样硬化、恶性肿瘤和感染性疾病中的作用及潜在治疗靶点。     

PD-1/PD-L1信号通路及其在乳腺癌治疗中的研究进展

PD-1/PD-L1信号通路是T细胞免疫反应过程中的一对协同刺激分子,通过负性调节T淋巴细胞活化、增殖和效应功能诱导抗原特异性T细胞凋亡,发挥免疫抑制作用。研究发现PD-L1在多种肿瘤细胞包括乳腺癌中表达上调,提示PD-1/PD-L1通路可能参与肿瘤的免疫逃逸,因此阻断PD-1/PD-L1信号通路已成为肿瘤治疗研究的新热点,其中抗PD-1单克隆抗体(Keytruda)的临床疗效研究为乳腺癌尤其是转移性三阴性乳腺癌的治疗带来了突破。目前,已有多个抗PD-1、PD-L1单克隆抗体被FDA批准进入临床试验,用于各类癌症的治疗,疗效显著。     

双调蛋白在肿瘤发生和进展中的作用

<正>人类双调蛋白是一个含有84个氨基酸的糖蛋白,最早于1980年由Shoyab从人乳腺癌细胞中发现并分离出来~([1])。双调蛋白作为表皮生长因子受体(epidermal growth factor receptor,EGFR)的配体,在多种组织和器官中表达,并通过维持肿瘤细胞生长信号的自给自足、抑制肿瘤细胞凋亡、帮助肿瘤细胞获得无限复制潜能、维持血管生成、参与Warburg效应、促进肿瘤组织侵袭和转移以及参与肿瘤治疗抵抗等效应,参     

海水青鳉雌激素受体基因的克隆、组织表达特性及环境雌激素EE2对其表达的影响

为了获得海水青鳉Oryzias melastigma雌激素受体的基因信息及其表达特性,采用RACE-PCR技术和实时荧光定量PCR方法,进行了雌激素受体基因的克隆、表达特性分析及其在17α-炔雌醇(EE2)暴露下的基因响应研究。结果表明:海水青鳉雌激素受体基因与其他脊椎动物雌激素受体基因同源性较高,特别是DNA结合结构域(DBD)在进化上高度保守,配体结合结构域(LBD)次之;OM-ERα/β1/β2在所检测的10种组织中均有表达,其中在青鳉肝脏、性腺、脾脏和肠中表达量较高;OM-ERα在肝脏中的表达和OM-ERβ1/β2在性腺中的表达,雌雄间存在显著性差异(P<0.05);在EE2浓度为5、50、500ng/L的水体中暴露96 h后,海水青鳉仔鱼中的分子标志物卵黄蛋白原基因(vtg1)被显著诱导(P<0.05),且呈浓度依赖关系;中浓度(50 ng/L)的EE2诱导仔鱼OM-ERβ1基因表达,OM-ERβ2对EE2暴露呈现低浓度诱导、高浓度抑制的趋势;攻毒试验结果表明,OM-ERα和vtg1之间存在一种正相关关系,暗示EE2可能主要通过ERα调控vtg1基因的表达;EE2攻毒下,β亚型存在一种倒U型的剂量-反应关系。研究表明:克隆获得的海水青鳉3个雌激素受体亚型基因OM-ERα/β1/β2,为后续开展海水模式鱼类雌激素受体相关研究提供了基础信息;OM-ERα/β1/β2的组织表达特性及EE2对仔鱼OM-ERα/β1/β2表达的不同调控,显示出海水青鳉3种ER亚型基因存在着不同的生理功能,且其对环境污染物的应答模式不同。     

海水青鳉雌激素受体基因的克隆、组织表达特性及环境雌激素EE2对其表达的影响

为了获得海水青鳉Oryzias melastigma雌激素受体的基因信息及其表达特性,采用RACE-PCR技术和实时荧光定量PCR方法,进行了雌激素受体基因的克隆、表达特性分析及其在17α-炔雌醇(EE2)暴露下的基因响应研究。结果表明:海水青鳉雌激素受体基因与其他脊椎动物雌激素受体基因同源性较高,特别是DNA结合结构域(DBD)在进化上高度保守,配体结合结构域(LBD)次之;OM-ERα/β1/β2在所检测的10种组织中均有表达,其中在青鳉肝脏、性腺、脾脏和肠中表达量较高;OM-ERα在肝脏中的表达和OM-ERβ1/β2在性腺中的表达,雌雄间存在显著性差异(P<0.05);在EE2浓度为5、50、500ng/L的水体中暴露96 h后,海水青鳉仔鱼中的分子标志物卵黄蛋白原基因(vtg1)被显著诱导(P<0.05),且呈浓度依赖关系;中浓度(50 ng/L)的EE2诱导仔鱼OM-ERβ1基因表达,OM-ERβ2对EE2暴露呈现低浓度诱导、高浓度抑制的趋势;攻毒试验结果表明,OM-ERα和vtg1之间存在一种正相关关系,暗示EE2可能主要通过ERα调控vtg1基因的表达;EE2攻毒下,β亚型存在一种倒U型的剂量-反应关系。研究表明:克隆获得的海水青鳉3个雌激素受体亚型基因OM-ERα/β1/β2,为后续开展海水模式鱼类雌激素受体相关研究提供了基础信息;OM-ERα/β1/β2的组织表达特性及EE2对仔鱼OM-ERα/β1/β2表达的不同调控,显示出海水青鳉3种ER亚型基因存在着不同的生理功能,且其对环境污染物的应答模式不同。     

环状RNA与头颈部肿瘤

环状RNA是一类共价闭合的环状非编码RNA,在各种组织和细胞中丰富且稳定,具有高度的组织特异性。研究发现,环状RNA分子具有microRNA(miRNA)海绵,RNA结合蛋白(RBP)海绵和调节蛋白质的转录和翻译的功能,从而在疾病的发生和发展中起重要作用。头颈部肿瘤(HNC)部位的特异性和治疗的复杂性导致HNC患者的生活质量普遍较低。为了提高对HNC的认识,寻求更好的治疗方法,提高患者的生活质量,因此本文综述了近年来环状RNA的研究进展及其在HNC中的作用,为HNC的治疗提供了新的思路。     

Drinking water and cancer mortality

The problem of understanding the possible adverse health effects of organic chemical contaminants in drinking water is not new, but national concern has intensified in recent years. Despite this concern and regulatory efforts, no definitive relationship has been established between organic contamination and human health effects. This paper examines some of the sources of possible organic contamination, current knowledge concerning human health effects and the most current epidemiological data. Historic CCE and CAE data were extracted from STORET and used in regression analyses. Age-adjusted 20-year average cancer mortality rates were regressed against the sum of CAE and CCE for those counties with STORET monitoring data of their drinking water source. Results indicate statistically highly significant relationships particularly for GI-urinary tract cancers.     

The Iowa radon lung cancer study--phase I: Residential radon gas exposure and lung cancer

Exposure to high concentrations of radon (222Rn) progeny produces lung cancer in both underground miners and experimentally-exposed laboratory animals. The goal of the study was to determine whether or not residential radon exposure exhibits a statistically significant association with lung cancer in a state with high residential radon concentrations. A population-based, case-control epidemiologic study was conducted examining the relationship between residential radon gas exposure and lung cancer in Iowa females who occupied their current home for at least 20 years. The study included 413 incident lung cancer cases and 614 age-frequency-matched controls. Participant information was obtained by a mailed-out questionnaire with face-to-face follow-up. Radon dosimetry assessment consisted of five components: (1) on-site residential assessment survey; (2) on-site radon measurements; (3) regional outdoor radon measurements; (4) assessment of subjects' exposure when in another building; and (5) linkage of historic subject mobility with residential, outdoor, and other building radon concentrations. Histologic review was performed for 96% of the cases. Approximately 60% of the basement radon concentrations and 30% of the first floor radon concentrations of study participants' homes exceeded the US Environmental Protection Agency action level of 150 Bq m(-3) (4 pCi l(-1)). Large areas of western Iowa had outdoor radon concentrations comparable to the national average indoor value of 55 Bq m(-3) (1.5 pCi l(-1)). Excess odds of 0.24 (95% CI = -0.05-0.92) and 0.49 (95% CI = 0.03-1.84) per 11 WLM(5-19) were calculated using the continuous radon exposure estimates for all cases and live cases, respectively. Slightly higher excess odds of 0.50 (95% CI = 0.004-1.80) and 0.83 (CI = 0.11-3.34) per 11 WLM(5-19) were noted for the categorical radon exposure estimates for all cases and the live cases. A positive association between cumulative radon gas exposure and lung cancer was demonstrated using both categorical and continuous analyses. The risk estimates obtained in this study indicate that cumulative radon exposure presents an important environmental health hazard.     

Urbanization and cancer: changing mortality patterns?

"Analysis of the relationship between cancer rates and urbanization for United States counties for the period 1950-54 reveals the expected urban/rural differences for many digestive, urinary and respiratory organ cancers and for female breast cancer. Similar urban/rural differences existed in many other Western countries. By 1970-75, however, urban/rural differences in the United States had substantially narrowed." It is noted that "available data do not allow formal tests of the relationship between these changes and specific etiological factors, but the data suggest that the spatial convergence is related to the changing geography of such risk factors as smoking, alcohol consumption, manufacturing, and socioeconomic status and to the diminished size and role of the white foreign-born population, as well as to such confounding factors as medical practices and population migration."     

一种抗卵巢癌多肽药物的合成及研究

卵巢癌是威胁女性健康的常见恶性肿瘤之一。针对这一恶性肿瘤,本研究以细胞穿透肽为基础设计并合成了一种修饰有半菁染料荧光团(Cy5)的多肽药物。通过荧光成像、流式细胞分析及细胞毒性实验,证实了该多肽药物具有良好的抗卵巢癌细胞活性。本研究为开发新的抗肿瘤药提供了一种新的思路。     

Geographical distribution of cancer in India with special reference to stomach cancer

There are regional variations in the occurrence of different types of cancers in India. A cancer intensity map has been prepared in order to identify the dominance of different types of carcinomas in various geographical regions. The study shows that the pattern of cancer distribution is apparently linked to a great extent with the type of nutrition habits and socio‐economic and cultural environment in each region. Various types of nutrition habits are discussed in order to study the relationship between the type of diet and the incidence to stomach cancer in India.     

Lung cancer and natural radiation in an Italian province

The possible association between the geological nature of the soil, as related to radioactivity, and lung cancer occurence has been explored in an Italian province. Lung cancer mortality rates for the period '69–'78, in population 35–74 years old, have been calculated for two areas with different lithological features and radioactivity levels.Direct standardization has been used to take into account possible confounding factors such as age, degree of urbanization and cigarette sales. The area with high background radioactivity levels has higher lung cancer mortality rates in both sexes but the results are not statistically significant.     

Air pollution and lung cancer risks in China--a meta-analysis

Lung cancer is a serious health problem in China, as in the rest of the world. Many studies have already proved that air pollution as well as other environmental factors can increase the risk of lung cancer. Based on epidemiological studies carried out in China, this paper proposes odds ratios (OR) to evaluate the risk of lung cancer from indoor air pollution for the Chinese population by applying the method of meta-analysis. For domestic coal use for heating and cooking, the pooled OR values are 1.83 (95% CI: 0.62-5.41) and 2.66 (1.39-5.07) for women and both sexes, respectively. For indoor exposure to coal dust, the OR values are 2.52 (95% CI: 1.94-3.28) and 2.42 (1.62-3.63) for women and both sexes, respectively. Cooking oil vapor is another factor increasing lung cancer risk. The OR values are 2.12 (95%CI: 1.81-2.47), 1.78 (1.50-2.12) and 6.20 (2.88-13.32) for nonsmoking women, women, and both sexes, respectively. Regarding environmental tobacco smoke, the pooled OR values are 1.70 (95% CI: 1.32-2.18) and 1.64 (1.29-2.07) for nonsmoking women and both sexes, respectively. Funnel plots with statistical test have been applied to examine the publication bias, and the results implied that the analysis of coal consumption and cooking oil pollution might be affected by publication bias. The meta-analysis results confirm the association between lung cancer and indoor air pollution for the Chinese population.     

PTEN蛋白在胃癌中的表达及临床病理意义

目的研究10号染色体缺失的张力蛋白同源磷酸酶基因(PTEN)蛋白在胃癌中的表达与临床病理的关系,为寻找胃癌肿瘤标记物提供一定的实验依据。方法应用组织芯片及免疫组化方法检测140例胃癌组织、54例癌旁胃黏膜组织与64例正常胃黏膜组织中PTEN的表达情况,研究PTEN与胃癌发生发展的关系。结果PTEN蛋白在正常组织表达85.94%(55/64)明显高于癌前病变51.85%(28/54)与胃癌20.71%(29/140)(P<0.05),而癌前病变表达显著高于胃癌(P<0.05)。PTEN在高分化、中分化、低分化腺癌、黏液癌与印戒细胞癌分别表达44.83%(13/29)、26.08%(6/23)、14.58%(7/48)、7.40%(2/27)与7.69%(1/13),各组间差异具有显著性(P<0.05)。PTEN在淋巴结转移组表达11.53%(12/104)明显低于无淋巴结转移组47.22%(17/36)(P<0.05)。在Ⅰ+Ⅱ期表达38.30%(18/47)明显高于Ⅲ+Ⅳ期11.83%(11/93)(P<0.05)。结论 PTEN蛋白下调与胃癌的发生、分化程度、淋巴结转移和临床分期有关。     

Review of occupational epidemiology of chromium chemicals and respiratory cancer

Several epidemiologic studies have investigated the association between cancer risk and employment in chromium producing and using industries. Strong and consistent associations have been found between employment in the primary chemical producing industry and the risk for respiratory cancer. Workers employed in chromate pigment production and possibly spray painters of chromate pigment paints appear to be at excess risk of respiratory cancer. Chrome platers may also be at excess risk, although the evidence is limited. A few studies indicate that chromium alloy welding may also be an exposure source of concern. Some studies of ferrochromium alloy workers have shown an excess risk for respiratory cancer, although the risk may in part be due to concomitant exposures. The evidence indicates that the hexavalent form of chromium is the primary agent of chromium carcinogenesis. Solubility and other characteristics of chromium compounds may also play a role in determining risk.