异黄酮改构化合物F11对人乳腺癌裸鼠移植瘤的影响

目的研究异黄酮改构化合物F11对人乳腺癌裸鼠移植瘤影响。方法体外培养人乳腺癌MCF-7细胞,裸鼠皮下接种MCF-7细胞建立裸鼠移植瘤动物模型,用金雀异黄素（Genistein）和环磷酰胺为对照研究化合物F11在体抗MCF-7效应。结果通过裸鼠移植瘤模型检测,认为异黄酮改构化合物F11在体有显著的抗癌效应,效果优于Genistein。结论异黄酮改构化合物F11有较强的抑制肿瘤的作用,有值得进一步研究开发的潜在价值。     

雌二醇衍生物分子结构与雌激素受体的亲和力及雌活性构效关系的分析

雌激素和受体的相互作用表现出高度的亲和性特异性,可在离体简单体系中显示出来.为此利用标记雌二醇[~3H]E_2与家兔胞液受体结合的实验模型,研究了雌二醇衍生物对这种结合反应的竞争性抑制作用和对小鼠子宫增重雌活性作用,总结了40多种衍生物的构效关系.     

辛基酚和三羟异黄酮对大鼠子宫和血雌激素的影响

目的：探讨辛基酚和三羟异黄酮对大鼠子宫和血雌激素的影响。方法：雌性大鼠随机分为正常对照组（Con）、乙烯雌酚组（DES）、三羟异黄酮（GEN）高浓度（G500）和低浓度组（G125）、辛基酚高浓度（OP120）和低浓度组（OP30），观察大鼠体重、子宫、卵巢、肝脏的质量指数和大鼠子宫组织形态学的改变，用化学发光免疫测定血中雌二醇和孕酮的含量。结果：G500、OP和DES均能明显增加大鼠子宫和肝脏的质量指数，降低大鼠血中雌二醇的含量，呈剂量-效应关系，但OP明显增加血中孕酮的水平。形态学发现DES、OP、GEN组子宫的间质细胞下的腔上皮细胞中核仁大而园，细胞增殖能力强。结论：GEN、OP与DES一样，具有雌激素的特性活性，可影响大鼠生长发育。     

对工作场所F类铀化合物空气浓度限值的推导探讨

目的 从辐射和化学危害角度分别推算F类铀化合物导出空气浓度,为工作场所职业危害因素的管理与评价提供参考.方法 用模拟计算的方法,分别推算F类铀化合物达到个人年剂量限值、急慢性机体损害效应阈值时工作场所的空气浓度.结果 正常运行情况下,将工作场所空气中F类铀化合物浓度控制在5 μg/m³以内,可以满足辐射危害和化学危害控制的要求;短时间开放性接触时,控制在1.1 mg/m³是可以接受的.结论 制定F类铀化合物空气浓度限值是可行的.     

大豆异黄酮对UUO大鼠肾间质ILK表达影响的研究

目的 观察单侧输尿管梗阻(UUO)大鼠肾小管间质中整合素连接激酶(integrin-linked kinase,ILK)的表达及大豆异黄酮对其的影响.方法 将36只雄性SD大鼠随机分为假手术组、对照组及异黄酮组,每组12只.对照组与异黄酮组大鼠均行左侧UUO手术,假手术组分离左侧输尿管后不结扎.术前3 d开始,异黄酮组用大豆异黄酮[200 mg/(kg·d)]饲喂,其余两组予等量普通饲料饲喂.术后第3、7、14 d分别处死各组中的4只大鼠,取左肾行HE和Masson染色,免疫组化方法 检测肾小管间质中TGF-β1、ILK和纤维连接蛋白(fibronectin,FN)的表达,并用计算机真彩色图像分析系统对其进行半定量分析.结果 对照组肾小管间质TGF-β1、ILK及FN高表达,与肾小管间质病变程度一致;ILK与TGF-β1、FN表达呈正相关.异黄酮组肾小管间质病变程度较同期对照组明显减轻(P＜0.01),TGF-β1、ILK 及FN的表达较同期对照组明显减少(P＜0.01),肾功能损害也较同期对照组明显减轻(P＜0.01).结论 UUO大鼠肾小管间质ILK高表达,ILK的表达强度与肾小管间质纤维化程度相一致,ILK可能参与TGF-β1介导的UUO大鼠肾小管间质纤维化过程;大豆异黄酮可能是通过抑制ILK的表达而实现抗肾小管间质纤维化作用,并保护肾功能.     

雌激素对宫腔粘连纤维化进程及叉头框F2表达的影响

目的 探讨雌激素对宫腔粘连纤维化进程及叉头框(Fox)F2表达的影响.方法 采用0.2％Ⅰ型胶原酶消化-筛网过滤-差时贴壁分离法获取原代人子宫内膜基质细胞(HESCs)并进行鉴定.采用l0ng/ml转化生长因子β1(TGF-β1)作用于HESCs48h建立宫腔粘连细胞模型.以0、10-6、10-8、10-10、10-12mol/L雌二醇(E2)作用于模型组48h,采用qPCR及Western blotting检测α平滑肌肌动蛋白(α-SMA)、Ⅰ型胶原蛋白(COL Ⅰ)及FoxF2的mRNA和蛋白表达.结果 免疫细胞化学法检测显示HESCs波形蛋白阳性,角蛋白18阴性.模型组α-SMA、COL Ⅰ、FoxF2的mRNA和蛋白表达均高于对照组(p＜0.05),模型构建成功.qPCR检测结果显示,与模型组相比,10-6、10-8、10-10mol/LE2组α-SMA、COL Ⅰ、FoxF2的mRNA表达除10-10mol/L E2组COL Ⅰ表达无差异外,其余各组表达均下降(P＜0.05),10-12mol/LE2组α-SMA及COL Ⅰ mRNA表达上升,但差异无统计学意义(P＞0.05),FoxF2mRNA表达下降(P＜0.05).Western blotting检测结果显示,与模型组相比,10-6、10-8、10-10mol/L E2组α-SMA、COL Ⅰ及FoxF2蛋白表达下降(P＜0.05),10-12mol/LE2组α-SMA蛋白表达上升,但差异无统计学意义(P＞0.05),COL Ⅰ及FoxF2蛋白表达下降(P＜0.05).结论 FoxF2在宫腔粘连中的表达增加.雌激素可在一定范围内逆转宫腔粘连的纤维化进程,并抑制FoxF2的表达.     

哥纳香醇甲类似物对KB瘤株的抑制作用的构效关系研究

 目的研究哥纳香醇甲的抗肿瘤活性构效关系.方法经MTT法筛选了55个哥纳香醇甲类似物及中间体对KB瘤株的抑制作用.研究了以a-D-葡庚糖酸-δ-内酯为原料经9～10步合成的55个哥纳香醇甲类似物的抗KB瘤株活性与结构的关系.结果化合物9、11、21、25、34、38、49、KB对KB瘤株的抑制作用强于哥纳香醇甲.结论哥纳香醇甲类似物8R构型、不饱和内酯及8位芳香酯为其活性的关键构型和基团.5,7-位的环状结构有利于增强活性.     

补充活性肽对大鼠1次离心运动后骨骼肌微细损伤作用的形态学研究

目的:本研究从形态学角度,观察补充活性肽对大鼠运动后骨骼肌微细损伤的作用。方法:雄性SD大鼠150只,按照补充不同物质(水、大豆分离蛋白和活性肽),运动与不运动,以及运动后0 hr、12 hr2、4 hr和48hr不同时间随机分为15组,所有动物平衡膳食1周后进行实验。运动组大鼠进行持续跑台训练120分钟。实验组和对照组所有动物在平衡膳食期间每天分别以15%活性肽饮料2毫升、15%大豆分离蛋白2毫升和等量的纯净水灌胃。结果:补充活性肽和大豆分离蛋白均可减轻大鼠1次离心运动后骨骼肌微细损伤的形态学改变和超微结构变化,其中活性肽的作用有强于大豆分离蛋白的趋势。     

脑脊液生物标志物与 11C-PIB PET/CT显像对阿尔茨海默病的诊断准确率及相关性研究

目的:探讨脑脊液生物标志物与 11C-匹兹堡化合物B （PIB）PET/CT显像在阿尔茨海默病（AD）中的诊断准确率及相关性,确定脑脊液生物标志物诊断AD的最佳临界值。 方法:回顾性分析2011年1月至2020年3月在北部战区总医院行 11C-PIB PET/CT显像和腰椎穿刺的66名...     

Automated synthesis of 11beta-methoxy-4,16alpha-[16alpha-(18)F]difluoroestradiol (4F-M[(18)F]FES) for estrogen receptor imaging by positron emission tomography

Addition of both a 4-fluoro and 11beta-methoxy group onto 16alpha-[(18)F]fluoroestradiol ([(18)F]FES) yields 11beta-methoxy-4,16alpha-[16alpha-(18)F]difluoroestradiol (4F-M[(18)F]FES) with potential improved properties for positron emission tomography (PET) imaging of estrogen receptor densities in breast cancer patients. In order to provide 4F-M[(18)F]FES as a radiopharmaceutical for clinical trials, we developed an automated synthesis procedure using 3-O-methoxymethyl-11beta-methoxy-4-fluoro-16,17-O-sulfuryl-16-epiestriol as precursor. The radio synthesis involves stereoselective opening of the protected cyclic sulfone precursor via nucleophilic fluorination with [(18)F]fluoride in acetonitrile. After removal of the protecting ether and 17beta-sulphate groups by rapid hydrolysis in acidic ethanol and subsequent reversed-phase HPLC purification, the pure 4F-M[(18)F]FES was obtained as a sterile physiological saline solution in 45-50% radiochemical yield (decay corrected). The radiochemical purity of the final product was >98% and the effective specific activity (ESA) of 4F-M[(18)F]FES prepared under optimized conditions was >15,000 Ci/mmol. The total preparation time was 110+/-5 min and the product was shown to be stable for at least 6 h.     

COBRA1抑制雌激素受体α转录活性

目的：研究COBRA1（cofactor for BRCA1）在雌激素受体α（ERα）信号途径中的潜在作用。方法：用GST pull-down实验检测COBRA1与ERα的相互作用、定位相互作用的区域，探讨不同配体对相互作用的影响。用免疫共沉淀方法检测COBRA1与ERα在细胞内的相互作用。利用含有雌激素应答元件（estrogen responsive element，ERE）的荧光素酶（luciferase，LUC）报告基因（C3-LUC）检测COBRA1对ERα转录活性的影响。结果：在体内外，COBRA1与ERα存在相互作用，COBRA1和ERα的中间区域是它们相互作用的区域。抗雌激素可增强COBRA1与ERα的结合。COBRA1以激素依赖方式抑制ERα的转录活性。结论：COBRA1是一新型ERα共抑制因子，可能在ERα信号途径中起重要作用。     

Metabolic assessment of gliomas using 11C-methionine, [18F] fluorodeoxyglucose, and 11C-choline positron-emission tomography

BACKGROUND AND PURPOSE: Positron-emission tomography (PET) is a useful tool in oncology. The aim of this study was to assess the metabolic activity of gliomas using ¹¹C-methionine (MET), [¹⁸F] fluorodeoxyglucose (FDG), and ¹¹C-choline (CHO) PET and to explore the correlation between the metabolic activity and histopathologic features.MATERIALS AND METHODS: PET examinations were performed for 95 primary gliomas (37 grade II, 37 grade III, and 21 grade IV). We measured the tumor/normal brain uptake ratio (T/N ratio) on each PET and investigated the correlations among the tracer uptake, tumor grade, tumor type, and tumor proliferation activity. In addition, we compared the ease of visual evaluation for tumor detection.RESULTS: All 3 of the tracers showed positive correlations with astrocytic tumor (AT) grades (II/IV and III/IV). The MET T/N ratio of oligodendroglial tumors (OTs) was significantly higher than that of ATs of the same grade. The CHO T/N ratio showed a significant positive correlation with histopathologic grade in OTs. Tumor grade and type influenced MET uptake only. MET T/N ratios of more than 2.0 were seen in 87% of all of the gliomas. All of the tracers showed significantly positive correlations with Mib-1 labeling index in ATs but not in OTs and oligoastrocytic tumors.CONCLUSION: MET PET appears to be useful in evaluating grade, type, and proliferative activity of ATs. CHO PET may be useful in evaluating the potential malignancy of OTs. In terms of visual evaluation of tumor localization, MET PET is superior to FDG and CHO PET in all of the gliomas, due to its straightforward detection of “hot lesions”.

Positron-emission tomography (PET) can provide valuable metabolic information and is used for grading and characterizing brain tumors, evaluating treatment response, and predicting prognosis. In brain tumors, the 2 most widely used tracers are [¹⁸F] fluorodeoxyglucose (FDG) and ¹¹C-methionine (MET). In previous reports, a relationship was found between FDG uptake and glioma grade and between MET uptake and glioma grade.^1–8 FDG allows detection of the increased glucose uptake characteristic of malignant cells, so FDG PET has previously been used successfully in oncology. Recent studies of other organ systems have demonstrated a close correlation with FDG uptake and the proliferative activity of tumors.^9–12 Due to the high-glucose metabolism in normal brain tissue, however, FDG may not be the ideal tracer for detection of gliomas. MET is more appropriate to image the size and spread of gliomas, even without enhancement on contrast-enhanced MR imaging, because MET PET has the advantage of showing selective uptake in the brain tumor compared with normal brain tissue. More recently, ¹¹C-choline (CHO) was introduced as another novel agent to evaluate different aspects of tumors.^13–16In both low-grade and high-grade oligodendrogliomas (ODs) increased vascular attenuation was seen, in contrast to astrocytic tumors (ATs), for which microvascular proliferation was seen in only high-grade tumors.^17,18 Using conventional modalities, there are no specific neuroradiologic features that can differentiate between ATs and oligodendroglial tumors (OTs); however, clinical management of OTs differs from other gliomas due to the specific chemotherapeutic sensitivities of OTs.^19,20 We hypothesized that a multitracer investigation that examined pretreatment tumor uptake compared with normal brain would provide valuable information about glioma grade and type; therefore, we studied metabolic activity by using MET, FDG, and CHO PET and compared them with tumor pathology. In addition, we compared the ease with which tumors could be visually evaluated in each system and investigated each tumor''s proliferation index, comparing this with the metabolic activity as measured with PET.     

Effect of reserpine on the brain uptake of carbon 11 methamphetamine and itsN-propagyl derivative,deprenyl

The enantiomers of methamphetamine (MAMP) and itsN-propagyl derivative, deprenyl, were labelled with carbon 11, and the tissue distribution of these labelled compounds in mice was studied. Both enantiomers of¹¹C-MAMP rapidly entered into the brain and then disappeared according to a single exponential curve. The enantiomers of¹¹C-deprenyl were also rapidly distributed to various organs in the same manner. With regard to elimination, however, a stereoselective, long-term retention of radioactivity in the brain, heart and lung, due to its irreversible binding with monoamine oxidase B, was observed forl-¹¹C-deprenyl. In reserpinized mice, the initial brain uptake of both thel andd forms of¹¹C-MAMP was significantly decreased. On the other hand, the brain uptake of both enantiomers of¹¹C-deprenyl was slightly increased by pretreatment with reserpine. A significant and non-stereoselective elevation of the lung uptake of¹¹C-deprenyl was also seen in reserpinized mice. In addition, both the relative tissue distribution and ratios of radioactivity in the brain compared with blood or heart at 1 and 5 min after the injection of¹¹C-labelled methanol in mice were not changed by reserpine. These results indicate that the transport or binding processes of these amines rather than the blood flow might be altered by reserpine. There would be an important role of the pK_a values of amines in both processes. The reduction of brain uptake as well as the change in ratio between brain and heart ofl-11C-MAMP in reserpinized mice 1 min after injection were reversed by treatment with amphetamine in a dose-related manner. D-Amphetamine was found to be several times more potent than the correspondingl-form in this regard. The present results reveal some possibility that the transport or binding processes of MAMP in the brain may be regulated by cathecholaminergic neurotransmission.     

Synthesis of a [18F]labeled chelidonine derivative as a possible antitumor agent.

[(+/-)-[5bRS-(5b alpha, 6beta, 12b alpha)]-5b,6,7,12b,13,14-hexahydro-13-methyl[1,3]benzodioxolo[5,6-c]-1,3-dioxolo[4,5-1] phenanthridin-6-yl]-4-[18F]fluorobenzoate (6b) an aromatic ester of chelidonine was prepared as a possible PET radiotracer. Compound (6b) was prepared in no-carrier-added (n.c.a) form from the 4-N,N,N-trimethylanilinium triflate derivative (5) in one step. The best results were obtained using Kryptofix(2.2.2)/[18F] and DMSO as the solvent at 90 degrees C. Column chromatography afforded the desired compound in overall radiochemical yield of 65-70% (EOS) with a specific activity of about 3000 Ci/mmole and radiochemical purity greater than 95% in 15 min.     

An improved synthesis of dopamine D2/D3 receptor radioligands [11C]fallypride and [18F]fallypride

Improved syntheses of dopamine D₂/D₃ receptor radioligands [¹¹C]Fallypride and [¹⁸F]Fallypride are reported. The phenolic precursor (9) for C-11 labeling and the Fallypride (10) reference standard were synthesized from the starting material 2-hydroxy-3-methoxy-5-(2-propenyl)benzoic acid methyl ester (1) in 7 and 8 steps with 16% and 5% overall chemical yields, respectively. The tosylated precursor (15) for F-18 labeling was synthesized from compound 1 in 5 steps with 32% overall chemical yield. An alternate synthetic approach for Fallypride has been developed using the same starting material 1 in 5 steps with 26% overall chemical yield. [¹¹C]Fallypride ([¹¹C]10) was prepared by O-[¹¹C]methylation of the phenolic precursor with [¹¹C]methyl triflate and purified with a semi-preparative HPLC method in 50–60% radiochemical yield, decay corrected to end of bombardment (EOB), based on [¹¹C]CO₂, and 370±185 GBq/μmol specific radioactivity at EOB. [¹⁸F]Fallypride ([¹⁸F]10) was prepared by nucleophilic substitution of the tosylated precursor with K[¹⁸F]F/Kryptofix 2.2.2 and HPLC combined with solid-phase extraction (SPE) purification in variable (up to 50%) decay corrected radiochemical yield from K[¹⁸F]F and 111–222 GBq/μmol specific activity at EOB.