晚期胃癌患者癌组织人表皮生长因子受体-2蛋白表达及与生存时间的关系

目的:观察人表皮生长因子受体-2(HER-2/neu)蛋白表达在晚期胃癌患者不同情况下的分布及与患者生存时间的关系。方法:收集60例胃癌患者的临床资料和HER-2/neu免疫组化检测结果,分析HER-2/neu蛋白表达在不同性别、年龄、病理分型、癌变部位及转移器官数量胃癌患者中的阳性率,并比较HER-2/neu阳性、阴性患者的生存时间。结果:60例胃癌患者中HER-2/neu蛋白阳性者10例,阳性率为16.67%;不同性别及≤60岁和60岁患者间HER-2/neu阳性表达率差异无统计学意义(P0.05)。不同癌变部位、不同病理分型和不同转移器官数量胃癌患者间HER-2/neu阳性表达率差异均有统计学意义(P0.05)。10例HER-2/neu蛋白阳性者中位生存期为2.89个月,而HER-2/neu蛋白阴性者中位生存期为11.9个月,生存时间12个月者多于其总数的1/2(32例),生存时间24个月者6例。HER-2/neu阴性胃癌患者预后显著好于HER-2/neu阳性胃癌患者。结论:胃癌患者HER-2/neu蛋白表达阳性,提示预后不佳。     

小分子酪氨酸激酶抑制剂A2B通过调控PI3K/Akt通路诱导胃癌细胞凋亡

目的：探讨小分子酪氨酸激酶抑制剂A2B诱导人胃癌SGC-7901细胞凋亡的分子机制。方法：体外培养人胃癌SGC-7901细胞并加入2.5～160μmol/L梯度浓度的A2B分别干预24、48和72 h，利用CCK-8法检测细胞活力的半数抑制浓度（IC50），筛选出药物最适浓度。后续实验将SGC-7901细胞随机分为对照组（正常培养组）、溶剂组（含0.08%DMSO培养液处理）、A2B 10μmol/L实验组和A2B 20μmol/L实验组，每组每项实验均重复3次。利用EdU细胞染色实验和平板集落形成实验检测各组细胞增殖能力；Annexin V-FITC/PI双染法检测各组细胞凋亡率；线粒体膜电位检测试剂盒（JC-1染色法）检测各组细胞线粒体膜电位变化；Western blot检测各组细胞中表皮生长因子受体（EGFR）、人表皮生长因子受体2(HER2)、细胞间充质-表皮转化因子（c-Met）、B细胞淋巴瘤2(Bcl-2)、Bcl-2相关X蛋白（Bax）、caspase-3、cleaved caspase-3、蛋白激酶B(PKB/Akt)和磷酸化Akt(p-Akt)蛋白的表达情况。结果：（...     

乳腺癌易感基因1的表达与乳腺癌亚型关系的实验研究

目的 探讨乳腺癌易基因1（BRCA1）的表达与乳腺癌分子亚型的关系.方法 运用免疫组化法检测乳腺癌组织中BRCA1的表达与雌二醇受体（ER）和人表皮生长因子受体-2（Her-2）的关系,分析BRCA1的表达在乳腺癌各亚型中的意义.结果 ER阳性和阴性时,BRCA1的阳性率分别为40.2％和60.0％,表明BRCA1表达与ER有关（P＜0.05）,与Her-2无关（P＞0.05）.在乳腺癌各分子亚型中,Luminal B型和Her-2过表达型的BRCA1阳性率（66.7％和70.0％）与Basal-like型的BRCA1阳性率（75.0％）差别无统计学意义（P＞0.05）;Luminal A型的BRCA1阳性率（23.7％）低于Basal-like型的BRCA1阳性率（75.0％）,差别具有统计学意义（P＜0.05）.结论 BRCA1在Luminal B型、Her-2过表达型和Basal-like型乳腺癌中表达较高,在Luminal A型乳腺癌中表达不高,提示BRCA1可成为治疗乳腺癌的重要靶点.     

HER-2阳性胃癌的研究进展

胃癌是我国最常见的消化道恶性肿瘤之一,随着我国社会经济的发展、人们食物谱的改变,我国的胃癌发病率呈显著上升趋势。人类表皮生长因子受体2（HER-2）是一种原癌基因,在部分胃癌患者中存在高表达,针对HER-2的靶向治疗,可使HER-2阳性的晚期胃癌患者获得显著的生存收益。ToGA研究是胃癌靶向治疗史上的一座里程碑,它首次在大规模样本中证实看联合应用化疗药及曲妥珠单抗可有效延长患者生存期。本文就HER-2阳性胃癌的研究进展作一综述。     

表皮生长因子受体与胃癌的研究进展

胃癌的发生与发展机制十分复杂，涉及多种细胞病理改变。表皮生长因子受体(epidermal growth factor receptor，EGFR)及其参与的信号转导通路在胃癌的发生发展中起着重要的作用。近年来，发现多数肿瘤对放化疗存在的耐药性，因此在肿瘤的基因水平寻找诊断指标以及靶向治疗，已经成为近年来研究热点之一。本文综述表皮生长因子与胃癌的研究进展。     

表皮生长因子受体与他莫西芬耐药机制

雌激素受体及其信号通路在乳腺癌的发生发展中发挥着关键作用.到目前为止,抑制或阻断雌激素信号通路的内分泌治疗尤其是他莫西芬,仍是对雌激素受体阳性乳腺癌患者最有效的治疗手段之一.然而,他莫西芬的耐药问题直接影响了乳腺癌患者的治疗及预后.最近多项研究表明雌激素受体与表皮生长因子受体家族尤其是HER2介导的信号传导通路在多个点上相互交叉,彼此影响,与他莫西芬的耐药密切相关     

人HER2胞外区基因重组及重组蛋白的纯化

为在体外纯化可溶性HER2胞外区蛋白并提高其原核表达产量，将多聚酶链式反应（PCR）方法获得的HER2基因胞外段编码区重组至pGEX-6P-1质粒，转化大肠杆菌BL21，采用不同的诱导条件分析融合蛋白的表达及其溶解性，不溶的包涵体经变性复性，与裂解液上清分别经Olutathione Sepharose4B亲合纯化融合蛋白。结果发现，重组蛋白在原核细胞中以可溶和不可溶两种表达形式存在，但以不溶的包涵体形式为主。低温（30℃）、较高的细菌密度（A600—1．8）和适当的培养基添加剂能有利于可溶性融合蛋白的表达。Olutathione Sepharose4B亲合纯化细菌裂解液上清和复性后的融合蛋白，其产量为1．23mg／L菌液，最大限度地获得了可溶性的HER2蛋白胞外段，为HER2特异性抗体的制备及其功能研究打下了良好的基础。     

HER2分子与肿瘤靶向治疗

HER2分子是表皮生长因子受体家族的第二位成员,对细胞的生长、分化及存活有着重要的调节作用,在乳腺癌、卵巢癌、肺腺癌、肾细胞癌中其过表达与否是患者预后的重要指标。研究表明它与表皮生长因子受体家族其他3位成员形成异二聚体,通过多种信号转导途径促进肿瘤的增殖、转移、耐药性的产生,是肿瘤基因治疗的重要靶位点。     

化学发光免疫分析法HER-2测定试剂盒的初步临床评价

目的评价试验产品HER-2测定试剂盒(化学发光免疫分析法,深圳市新产业生物医学工程股份有限公司)与参比产品HER-2/neu蛋白测定试剂盒(化学发光法,西门子)的临床使用的等效性。方法使用两种试剂对临床收集的样本进行平行盲法检测。试验结束后对参比产品和试验产品的测定结果进行离群值检验、回归分析、Bland-Altman一致性分析、医学决定水平处的预期偏倚分析以及定性结果的一致性分析。结果共测定 360例临床样本,均为女性样本。对纳入定量分析的355例样本测定结果进行方法间离群值检验,无离群值。线性回归方程: Y =0.9758 X +0.1668, R 2 = 0.9910 。试验产品与参比产品差值百分比的95%一致性界限(LoA)为(-21.80%,18.87%);其中98.87%(351/355)的点在95%一致性界限内。两种方法在医学决定水平15 ng/mL处的预期偏倚百分比为-1.31%,满足评价标准。试验产品与参比产品阳性符合率为98.76%,阴性符合率为98.49%,总符合率为98.61%。其中有5例标本两种方法检测定性结果不一致,但均为非恶性组且结果在参考值附近。定性结果经Kappa一致性检验,κ值=0.9719。结论试验产品HER-2测定试剂盒与参比产品HER-2/neu蛋白测定试剂盒临床应用中具有等效性,即临床应用上的有效性和安全性。     

抗乳腺癌单克隆抗体mAb109的放射性标记与生物评价

目的探索单克隆抗体mAb109的标记方法,并进行荷瘤动物模型的生物分布和显像研究。方法采用2-巯基乙醇(2-mercaptoethanol,2-ME)法还原单克隆抗体mAb109,并测定还原抗体浓度和巯基含量。通过葡庚糖转络合法用放射性核素99Tcm标记mAb109,测定标记抗体的标记效率和稳定性。建立乳腺癌动物模型,并进行体内分布和显像研究。结果还原抗体保持了较高的完整性,平均每分子抗体含有5.38个巯基。葡庚糖转络合法标记mAb109具有较高的标记率(>90%)和体外稳定性。标记抗体在肿瘤部位有显著的富集,且具有较长的滞留时间。荷瘤动物模型注射99Tcm-mAb109后,可以得到清晰的肿瘤影像。结论99Tcm-mAb109具有较高的标记效率,对所采用的葡萄糖调节蛋白78(glucose-related protein 78,GRP-78)阳性动物模型具有一定的靶向性。     

S-99和S-100止血作用研究

PT、APTT、TT、血小板粘附率和血栓形成试验表明S-99可溶性止血纺织材料和S·100吸收性止血綾的止血效果无显著差异。但是S-99和S-100止血纺织材料的止血机理不尽相同,S-100止血绫主要是通过溶解后的负电性液相激活内源性止血系统;而S-99止血纺织材料主要是通过溶胀胶粒粘附血小板,进而激活血小板。     

Tumor targeting HPMA-porphyrin-99mTc copolymer molecular imaging agent

Porphyrins typically show preferential uptake and retention by tumor tissues via receptor-mediated endocytosis of low-density lipoproteins. To investigate the relative importance of active and passive targeting strategies, the synthesis, characterization, in vitro uptake, and in vivo biodistribution of specific targeting porphyrin HPMA [HPMA: N-(2-hydroxypropyl)methacrylamide] copolymer tracer poly(HPMA)-porphyrin-DTPA-^99mTc (DTPA: diethylenetriaminepentaacetic acid), nonspecific targeting HPMA copolymer tracer poly(HPMA)-DTPA-^99mTc, and nontargeting tracer DTPA-^99mTc are described in this study. The results showed that the cellular accumulation of poly(HPMA)-porphyrin-DTPA-^99mTc complex was found to be time-dependent. The uptake of poly(HPMA)-porphyrin-DTPA-^99mTc was significantly higher than that of poly(HPMA)-DTPA-^99mTc, indicating that uptake of the poly(HPMA)-porphyrin-DTPA-^99mTc was active binding. The uptake of poly(HPMA)-DTPA-^99mTc was significantly higher than that of DTPA-^99mTc, suggesting that uptake of the poly(HPMA)-DTPA-^99mTc was passive binding. Twenty-four hour necropsy data in the hepatocellular carcinoma tumor model showed significantly higher (p < 0.001) tumor localization for poly(HPMA)-porphyrin-DTPA-^99mTc (5.18 ± 0.50% ID/g [percentage injected dose per gram tissue]) compared with poly(HPMA)-DTPA-^99mTc (2.69 ± 0.15% ID/g) and DTPA-^99mTc (0.83 ± 0.03% ID/g). Moreover, higher T/B for poly(HPMA)-porphyrin-DTPA-^99mTc indicated reduced extravasation of the targeted polymeric conjugates in normal tissues. Thus, the poly(HPMA)-porphyrin-DTPA-^99mTc is a potential macromolecular tumor targeting molecular agent.     

^99Tc^m-MIBI亲肿瘤显像对甲状腺癌的诊断价值

目的 探讨99Tcm-MIBI显像在甲状腺癌诊断中的价值.方法 对52例99TcmO4-甲状腺显像为"冷"结节的患者行99Tcm-MIBI显像.患者均行外科手术治疗,并作病理检查.计算其10 min和60 min患侧/健侧摄取放射性比值(T/N),分析假阳性和假阴性.结果 甲状腺癌组10 min和60 minT/N值分别为1.87±0.57和1.61±0.45,而甲状腺良性病变组分别为0.79±0.22和0.89±0.25,两组两时相T/N值比较均有显著性差异(P＜0.01).99Tcm-MIBI显像对甲状腺癌诊断的灵敏度、特异性和准确性分别为77.8%、82.4%和80.8%.结论 甲状腺"冷"结节行99Tcm-MIBI显像对于甲状腺癌的诊断具有较高的临床参考价值.     

动脉粥样硬化发病机制及影像学研究进展

动脉粥样硬化（AS）是多因素疾病,病因复杂,它与血管异常及血管壁成分改变有关,主要累及大、中动脉,可引起心、脑等多个器官病变,致组织缺血和坏死,发生心肌梗死、脑卒中等严重疾病.其发病机制目前尚未最后阐明.主要就AS病理改变、病因与发生机制及影像学表现作一阐述.     

Optical imaging of Tc-99m-based tracers: in vitro and in vivo results

It has been recently shown that optical imaging (OI) methods can be used to image the in vivo biodistribution of several radiopharmaceuticals labeled with beta or alpha emitters. In this work particular attention has been focused on investigating the weaker optical signal induced by an almost pure gamma emitter like Tc-99m. Visible light emission measurements of a water solution containing Tc-99m were performed using a small animal OI system. A sequence of images was acquired for 24 h in order to study the decay of the luminescence signal. The difference between the luminescence decay half life and well-known Tc-99m half life was equal to 1%. in vivo imaging was performed by injecting one control nude mice with Tc-99m-MDP. Optical images obtained with equipment designed for bioluminescence imaging showed that a visible light emission was distinguishable and correctly localized in the bladder region where a higher concentration of Tc-99m-MDP was expected. The bladder to background ratio was always greater than 1. We conclude that the experimental data presented in this paper show that it is possible to detect in vivo luminescence optical photons induced by Tc-99m. This is important especially considering the large number of Tc-99m-based radiopharmaceutical currently available.     

乳腺肿物^99mTc-MDP平面显像的临床评价

探讨了~99nzTc-亚锡亚甲基二膦酸盐(MDP)鉴别诊断乳腺肿物的临床价值.对82乳腺肿物病例均同期进行了~99nzTc-MDP平面显像、红外线和针吸活组织检查,以病理为标准比较3种方法的诊断效能.结果3种方法的灵敏度和特异性分别为87.0%和 89.3%、70.4%和53.6%、64.8%和100%显示~99nzTc-MDP平面显像是诊断和鉴别诊断乳腺肿物的较好方法.     

Tc-99m-ECD SPECT brain imaging in children with Tourette's syndrome

We undertook this study to assess the patterns of regional cerebral perfusion (RCP) with SPECT using Technetium- 99m-ethyl cysteinate dimer (Tc-99m-ECD) in children with Tourette's Syndrome (TS), and to compare these with the patterns in a group of normal controls. The study sample consisted of 38 children (7 to 14 years) who met the ICD-10 and DSM/IV criteria for Tourette's Syndrome, and a control group of 18 children (9 to 14 years). The Children's Depression Inventory and Maudsley Obsessional-Compulsive Questionnaire were used for assessment, and the severity of motor and vocal tics were assessed using the Goetz Rating Scale. The RCP values were significantly lower in the TS group in left caudate, cingulum, right cerebellum, left dorsolateral prefrontal, and the left orbital frontal region. A positive correlation was found between the severity of vocal tics and blood flow of mid-cerebellum, right dorsolateral prefrontal and left dorsolateral prefrontal regions. Although no depressive or obsessive patients were included in the study, the depression and obsession scores were found to be negatively correlated with all RCP values, especially in the temporal regions. Further studies are needed to explore the relationship between the hypoperfusion of certain brain areas and the underlying neurophysiology and neurobiology of patients with TS. Additional disturbances such as obsessive-compulsive symptoms and depressive symptoms should also be assessed     

A multiwire proportional gamma camera for imaging 99Tcm radionuclide distributions

A gamma camera made of multiple multiwire proportional chambers with thin converter foils has been evaluated for clinical application. Results are presented from a small prototype (10 cm x 10 cm)showing good imaging of 99Tcm radionuclide distributions and comfirming the predictions of the theory regarding quantum efficiency and spatial resolution. The technique is especially aimed at creating a gamma camera with an active area greater than or approximately equal to 1 m2, a quantum efficiency of 15% and a spatial resolution approximately 3 mm, to be applied in whole body scanning and tomographic applications. The results generated by the current prototype indicate that the above requirements can be met using relatively cheap mass production techniques from the electronic industry. This apparatus is covered by patent applcation number 26595/77.     

The use of 99Tc-pyrophosphate for imaging and measuring of calcification caused by implanted polymers

Pyrophosphate labeled with 99Tc was evaluated as an indicator of the calcification which occurs after implantation of polymeric materials in rats. Poly(2-hydroxyethyl methacrylate), both porous and homogeneous, had been implanted. 99Tc pyrophosphate was applied intravenously to rats in intervals from 14 days to 15 months. Scintigraphy, x-ray examination, and histology were carried out. The ratio of specific activity in the capsule around the implant to specific activity in the reference tissue was determined. The cumulation of activity was parallel with the development of calcification as revealed by histology. The method can be used not only in the screening test of new polymeric materials, but also in a quantitative determination of the degree of calcification in general.