磁热化疗对人胶质母细胞瘤U251及其uPA系统的抑制作用

目的 研究磁热化疗联合作用对人胶质母细胞瘤U251的抑制作用及其机制分析.方法 采用溶剂挥发法制备纳米Fe3O4粒子及抗肿瘤药物多西紫杉醇共混的复合膜,植入U251荷瘤裸鼠皮下模型肿瘤,通过体外交变磁场加热,观察裸鼠肿瘤体积及生存期,通过免疫组化方法观察检测肿瘤组织的尿激酶型纤溶酶原激活物(urokinase plasminogen activation,uPA),尿激酶型纤溶酶原激活物受体(urokinase plasminogen activation receptor,uPAR)及纤溶酶原激活物抑制剂1(plasminogenactivator inhibitor 1,PAI-1)的表达.结果 对照组肿瘤终末体积为3 683.16mm3,中位生存期13d;热疗组1 156.12mm3,中位生存期30d;化疗组2 749.943mm3,中位生存期18d;热化疗组71.882 25mm3,中位生存期41d.与对照组相比,热化疗组uPA,uPAR及PAI-1表达均有明显下调(P＜0.05).结论 热化疗联合应用可通过下调U251的uPA系统表达而抑制胶质瘤的侵袭和复发.     

Fe3O4磁性纳米颗粒/CD/5-FC系统对U251细胞化疗作用

目的：建立以Fe3O4磁性纳米颗粒（Fe3O4,MNP）/胞嘧啶脱氨酶（CD）/5-氟胞嘧啶（5-FC）系统为基础的神经系统胶质瘤治疗方法.方法：利用高温分解铁有机物法以2-吡咯烷酮和乙酰丙酮铁为原料制备出Fe3O4 MNP,用γ-氨丙基三乙氧基硅烷对磁性材料进行表面修饰.以Fe3O4 MNP为载体将CD基因转染U251胶质瘤细胞,检测Fe3O4 MNP对质粒pCMVCD的结合与保护能力.通过RT-PCR,Western Blot法和免疫荧光等方法检测CD基因在U251细胞的表达.噻唑蓝（MTT）法检测5-FC化疗后U251-CD细胞生长曲线的变化.结果：制备出粒径为（10±2）nm的Fe3O4 MNP;使用Fe3O4 MNP作为载体将CD基因成功转染U251细胞;脂质体转染组转染率为（39.23±12.12）%,而示Fe3O4 MNP转染组转染率为（67.35±11.19）%,2组相比较差异显著（P〈0.01）.Fe3O4 MNP作为载体转染的U251-CD细胞CD基因稳定表达,并呈时间相关性增强表达模式;U251-CD细胞加入5-FC后能显著抑制U251细胞生长.结论：Fe3O4 MNP可作为胶质瘤基因治疗的理想载体;Fe3O4 MNP/CD/5-FC系统可作为脑胶质瘤辅助治疗手段之一.     

Fe2O3 纳米磁流体热疗治疗小鼠结肠癌实验研究

目的研究Fe2O3纳米磁流体热疗对小鼠结肠癌的治疗效果。方法磁流体直接局部注射到小鼠皮下肿瘤组织,交变磁场下加热至43℃,计算瘤体积抑制率,肿瘤组织及各个脏器做病理检测。结果 Fe2O3纳米磁流体在交变磁场(alternatingmagnetic field,AMF)中升温迅速。热疗组相比磁流体对照组、磁场对照组、空白对照组,热疗6天后瘤体体积抑制率分别为50.87%、50.50%、76.57%,P<0.05,差异有统计学意义。病理检测证实肿瘤组织部分凋亡,而正常脏器无变化。结论 Fe2O3纳米磁流体热疗可抑制小鼠结肠癌的增长,对结肠癌的治疗有一定作用,但并不能完全抑制肿瘤的生长。实验证明热疗安全可靠。     

载药磁性微囊用于脑胶质瘤可控热化疗的研究

目的研究负载γ-Fe2O3磁性纳米颗粒(MNPs)及阿霉素(doxorubicin,Dox)的海藻酸钠磁性载药微囊(DAMMs)对脑胶质瘤C6细胞热化联合治疗的可行性及治疗效果。方法脑胶质瘤C6细胞和荷瘤鼠分为对照组、加DAMMs组、MNPs磁热疗组和DAMMs磁热疗组;通过集落形成实验检测各组细胞的存活分数;AnnexinⅤ-FITC结合PI检测各组细胞的凋亡率;免疫组化检测DAMMs对荷瘤鼠磁流体热疗凋亡的影响。结果外加交变磁场(ACMF)能够诱导微囊中MNPs升温,同时ACMF又能诱导微囊快速释放出药物Dox,引起脑胶质瘤C6细胞在接受DAMMs磁热疗后凋亡率显著提高(P<0.05)。结论 DAMMs在脑胶质瘤的热化联合治疗中具有潜在应用价值。     

As4S4/Mn0.5Zn0.5Fe2O4复合纳米粒的制备及其杀伤宫颈癌Hela细胞的实验研究

目的:通过制备As4S4/Mn0.5Zn0.5Fe2O4 复合纳米粒研究体外热化疗对宫颈癌Hela细胞株的作用?方法:采用改良的化学沉淀-浸渍法制备As4S4/Mn0.5Zn0.5Fe2O4复合纳米粒,通过扫描电镜?能谱仪?原子荧光光谱仪来表征;检测As4S4/Mn0.5Zn0.5Fe2O4 复合纳米粒的释药水平及在交变磁场中的升温能力;通过MTT比色法和流式细胞仪检测化疗组?热疗组及热化疗组对宫颈癌的治疗效果?结果:制备的复合纳米粒粒径为20~40 nm;复合纳米粒体外升温能达到肿瘤的有效治疗温度(41~46℃);释药缓慢,48 h释药为13.28%?在MTT实验中,As4S4/Mn0.5Zn0.5Fe2O4 复合纳米粒组细胞抑制率明显高于单纯纳米雄黄溶液组和Mn0.5Zn0.5Fe2O4 联合交变磁场加热组 (P < 0.05);在凋亡率检测中,As4S4/Mn0.5Zn0.5Fe2O4复合纳米粒联合磁流体热疗组细胞凋亡率明显高于单纯纳米雄黄溶液组和Mn0.5Zn0.5Fe2O4 联合交变磁场加热组(P < 0.05)?结论:采用改良的化学沉淀-浸渍法可以成功制备As4S4/Mn0.5Zn0.5Fe2O4 复合纳米粒,体外实验证明该复合纳米粒联合交变磁场热疗对宫颈癌细胞具有很强的生长抑制和诱导凋亡作用?     

替莫唑胺-尼莫地平-O6-苄基鸟嘌呤联用对胶质瘤细胞株U251抑制作用的研究

目的观察替莫唑胺（TMZ）、尼莫地平（NIM）、O6-苄基鸟嘌呤（O6-BG）联用对脑胶质瘤细胞株的抑制作用。探讨胶质瘤耐药发生的机制,寻找有效的多药耐药逆转剂,克服耐药性的产生,提高化疗效果,增加肢质瘤细胞对化疗药物的敏感性,最大限度地抑制胶质瘤细胞增殖,延缓肿瘤复发。方法用免疫细胞化学法检测胶质瘤细胞中MGMT蛋白表达,观察比较MGMT在用O6-BG处理前后表达的差异。分别以尼莫地平和O6-BG作为耐药逆转剂,与替莫唑胺单独或联合应用于体外培养的脑胶质瘤细胞U251。用MTT法检测细胞抑制率;观察TMZ、NIM、O6-BG联用对脑胶质瘤细胞的抑制作用。结果与对照组相比,MGMT在用O6-BG处理后表达明显减少。MTT比色法分别检测TMZ、TMZ＋NIM、TMZ＋O6-BG组及TMZ＋NIM＋O6-BG组对胶质瘤细胞U251的抑制作用,结果显示各组对胶质瘤细胞的抑制作用为TMZ＋NIM＋O6-BG联合组〉TMZ＋O6-BG〉TMZ＋NIM〉TMZ。与TMZ组比较,TMZ＋NIM组、TMZ＋O6-BG组对U251细胞株的抑制率显著升高,差异有统计学意义（P〈0．01）;同样,与TMZ组比较,TMZ＋NIM＋O6-BG组对U251细胞株的抑制率也显著升高,差异有统计学意义（P〈O．05）。结论O6-BG能够有效抑制MGMT表达,从而能逆转人脑胶质瘤细胞株U251对替莫唑胺的耐药性。尼莫地平、O6-BG二者均可增强替莫唑胺时脑胶质瘤细胞株U251的细胞毒作用,对于替莫唑胺的耐药有较好的逆转效果,因而可望作为临床化疗增敏剂与替莫唑胺联合使用。替莫唑胺、尼莫地平、O6-BG三者联用对肢质瘤细胞株U251有更好的抑制作用,其效果优于二者联合应用,强于单独应用替莫唑胺。     

榄香烯对人脑胶质瘤U251细胞放射敏感性的影响

目的观察榄香烯对人脑胶质瘤U251细胞放射敏感性的影响。方法应用MTT法检测不同浓度榄香烯对人脑胶质瘤U251细胞的增殖抑制率。采用榄香烯单独或联合放射线作用于脑胶质瘤U251细胞,用集落形成实验和单击多靶模型拟合细胞存活曲线,获得放射增敏比;应用流式细胞技术分析榄香烯对U251细胞凋亡率的影响。结果榄香烯可抑制脑胶质瘤U251细胞的增殖,且与浓度相关;97.86μmoL和195.72μmoL榄香烯分别作用脑胶质瘤U251细胞24 h后,联合放射的放射增敏比(SER)分别为1.179和1.429;195.72μmoL榄香烯分别作用脑胶质瘤U251细胞3 h和6 h后,联合放射的SER分别为1.139和1.356;流式细胞仪分析表明榄香烯作用24 h后,随着榄香烯浓度的增加,U251细胞凋亡率越高,比较差异均有统计学意义(P<0.05)。结论榄香烯能够抑制人脑胶质瘤U251细胞的增殖,并有放射增敏作用,且放射增敏作用的大小与药物作用浓度及作用时间有关系。     

As2O3/ Mn0.5Zn0.5Fe2O4复合纳米粒的制备及其对乳腺癌细胞增殖、凋亡的实验研究

目的：通过制备As2O3/Mn0.5Zn0.5Fe2O4复合纳米粒来研究热化疗对乳腺癌的治疗效果。方法：采用改良的化学沉淀-浸渍法制备As2O3/Mn0.5Zn0.5Fe2O4复合纳米粒,通过透射电镜、扫描电镜、能谱仪、原子荧光光谱仪来表征;检测As2O3/Mn0.5Zn0.5Fe2O4复合纳米粒的释药水平及在交变磁场中的升温能力;通过MTT比色法和流式细胞仪检测化疗组、热疗组及热化疗组乳腺癌的治疗效果。结果：制备的复合纳米粒粒径为20～40 nm;复合纳米粒体外升温能达到肿瘤的有效治疗温度（41～46℃）;释药缓慢,48 h释药为14.67%。结论：采用改良的化学沉淀-浸渍法可以成功制备As2O3/Mn0.5Zn0.5Fe2O4复合纳米粒,体外实验证明该复合纳米粒联合交变磁场热疗对乳腺癌细胞具有很强的生长抑制和凋亡诱导作用。     

顺铂热化疗对骨肉瘤细胞株细胞毒性的实验研究

目的：研究顺铂热化疗对骨肉瘤细胞株(OS-732)细胞毒性的影响，探讨热疗在骨肉瘤顺铂化疗中增效作用的机理。方法：OS-732细胞株分别经不同温度的热疗、不同浓度顺铂化疗、43℃热疗 顺铂联合作用各1h，采用体外细胞毒性试验(MTT法)、流式细胞仪(FCM)分析及电子显微镜观察其对细胞毒性和细胞周期的影响，以及诱导细胞凋亡的情况。结果：41℃、43℃、45℃热疗对OS-732细胞株有明显的细胞毒性作用。在37℃恒温条件下，细胞株单独与不同浓度的顺铂作用1h，随着顺铂浓度的升高，其细胞毒性作用明显增加。43℃热疗 顺铂共同作用1h，其细胞毒性作用进一步增加，细胞毒性指数最高达72．37％；FCM分析显示对细胞周期有明显的影响，S期细胞比例明显增加，G2与M期细胞比例明显减少。43℃热疗、43℃热疗 顺铂联合作用各1h均出现凋亡细胞峰(亚G1峰)，细胞凋亡比例最高达56．47％；透射电镜观察有典型的细胞凋亡特征性变化。结论：顺铂热化疗有明显的增强OS-732细胞株的细胞毒性作用。43℃热疗、43℃热疗 顺铂均可诱导骨肉瘤细胞凋亡。43℃热疗诱导骨肉瘤细胞凋亡可能是热疗在骨肉瘤顺铂化疗中增效作用的潜在机制之一。     

木香内酯DSPE-PEG纳米胶束的制备、表征及对胶质瘤细胞凋亡的诱导作用

目的：制备木香内酯（MCL）聚乙二醇衍生化磷脂酰乙醇胺（MCL@DSPE-PEG）纳米胶束,并对其进行表征和诱导胶质瘤细胞凋亡的研究。方法：采用薄膜水化法制备MCL@DSPE-PEG纳米胶束,观察其外观特征,检测其粒径、多分散系数（PDI）、载药量、包封率。比较MCL原料药和MCL@DSPE-PEG纳米胶束在pH 7.4枸橼酸盐缓冲液中的药物释药情况。将U87 和U251胶质瘤细胞分为模型组和MCL@DSPE-PEG纳米胶束组;观察U87和U251胶质瘤细胞生长抑制情况和细胞内凋亡相关Caspase3、Caspase8、Bcl-2蛋白表达水平变化情况。结果：所制备的MCL@DSPE-PEG纳米胶束呈现大小比较均一的椭球形,其粒径为（123.8±0.5）nm,PDI为0.236±0.005,载药量为8.96%±0.56%,包封率为85.49%±3.66%,144 h的累积释放度为73.30%,而MCL原料药在48 h内已基本释放完全。 MCL@DSPE-PEG纳米胶束可抑制U87和U251胶质瘤细胞生长及细胞克隆形成。与模型组比较,MCL@DSPE-PEG纳米胶束组U87和U251胶质瘤细胞的Bcl-2蛋白表达水平下降,Caspase3、Caspase8 蛋白表达水平升高,差异均有统计学意义（P ＜0.05）。结论：成功制得MCL@DSPE-PEG纳米胶束,其具有诱导U87和U251胶质瘤细胞凋亡从而抑制肿瘤生长的作用。     

磁性附着体的衔铁对磁共振成像的影响

目的：研究磁性附着体的衔铁对磁共振成像的影响。方法：体外实验选用MAGFIT EX400,MAGFIT EX600及MAGNEDISC 800型磁性附着体的衔铁,分别设计为不铸接、与镍铬合金铸接和与金钯合金铸接3种形式,并完成衔铁根帽的制作。体内实验选择需行磁性附着体可摘义齿修复的患者作为研究对象。用Siemens SONATA 1.5-T磁共振仪对所有样本及研究对象进行扫描,对体外样本伪影最大径进行测量和比较,对体内实验的伪影对头颈部解剖结构成像的影响进行分析。结果：MAGFIT EX400型、MAGFIT EX600型及MAGNEDISC 800型衔铁的伪影最大纵径分别为158.94、168.52和173.00 mm。衔铁伪影对颏部、舌、唇、软硬腭、颌骨的磁共振成像造成明显影响,位于后牙区的衔铁对脑及脊髓的成像造成影响。采用SE序列及左右向的频率编码,可以减小衔铁对头颈部MRI的影响。结论：磁性附着体的衔铁对磁共振成像有明显影响。     

Dysembryoplastic neuroepithelial tumors: magnetic resonance imaging and magnetic resonance spectroscopy evaluation

Background Dysembryoplastic neuroepithelial tumor （DNT） is a rare benign neoplasm of the central nervous system affecting young people. A correct preoperative diagnosis is helpful for planning surgical strategies and improving prognosis. The purpose of this study was to characterize DNTs using magnetic resonance imaging （MRI） and magnetic resonance spectroscopy （MRS） and to analyze the value of these two techniques in the diagnosis of DNTs. Methods MR images of 13 patients with DNTs were reviewed retrospectively; and five of the patients also underwent MRS. Tumors were confirmed by surgery. The distribution, extension and signal features of the lesions were assessed, and the MRS results were analyzed. Results All tumors were supratentorial. The cortex was the main area involved, with nine tumors located in the temporal lobe, three in the frontal lobe, and one on the boundary between the temporal and occipital lobes. All cases had decreased signal intensity on Tl-weighted MR images and increased signal intensity on T2-weighted images. On fluid attenuated inversion recovery weighted images, the hyperintense ＂ring sign＂ and internal septation of the lesion were seen in 9 cases. Eight tumors had well-demarcated borders. Peritumoral edema or mass effect was absent in all cases. A contrast enhancement examination was performed in 9 cases. Contrast enhancement was absent in five cases, and four cases showed significant enhancement. The MRS showed a low N-acetylaspartate peak and a lack of elevated choline-containing component （Cho） or Cho-Cr ratio （Cho/Cr） in five patients. Conclusions The MRI findings of DNTs were stereotypical. The combination of MRI and MRS techniques were helpful in making a correct presurgical diagnosis.     

Peripheral magnetic resonance angiography

Magnetic Resonance Angiography [MRA] has become a useful imaging modality in the evaluation of vascular anatomy and a variety of vascular disorders in the last several years. Many recent publications have demonstrated that MRA can be an accurate, fast and safe tool in the workup of patients with lower extremity ischemia. It has become a less invasive alternative to catheter angiography, and in some radiology departments MRA has replaced conventional catheter angiography in the initial workup of lower extremity ischemia.     

Cardiac magnetic resonance imaging

Recent advances in technology have allowed magnetic resonance imaging to be exploited in cardiology. It is capable of giving high definition structural and functional information. The current applications of this technique and how it may develop in the future are reviewed.     

基于3D⁃MATRIX序列的压缩感知技术在膝关节成像中的临床应用价值

目的：探讨基于3D可调制翻转角超长回波链回聚脉冲成像（three?dimensional modulated flip angles technique in refocusing imaging with extended echo train,3D?MATRIX）的压缩感知（compressed sensing,CS）技术在膝关节中的临床应用价值。方法：对26例患者的26个膝关节均采用CS?3D?MATRIX（CS?3D）和3D?MATRIX（传统3D）扫描。对两组图像的伪影（0~4）、锐利度（0~4）和图像综合质量（0~4）进行评分;分析两组膝关节图像中的软骨、肌肉、滑膜液、骨髓腔和前交叉韧带的信噪比（signal to noise ratio,SNR）,骨髓腔?软骨、骨髓腔?滑膜液、软骨?肌肉、滑膜液?软骨、滑膜液?前交叉韧带的对比噪声比（contrast to noise ratio,CNR）,并进行统计学分析。结果：两序列图像伪影和总体图像质量无明显差异,CS?3D图像锐利度略低于传统3D［（3.39±0.50）分 vs. （3.79±0.42）分,P=0.008］。与传统3D相比,除骨髓腔和前交叉韧带外,CS?3D获得的SNR均升高;CS?3D滑膜液?前交叉韧带、滑膜液与软骨的CNR显著提高,其他组织的CNR值略有升高但无统计学差异。CS?3D扫描时间较传统3D减少了46%。结论：与传统3D扫描序列相比,CS?3D?MATRIX序列的扫描时间缩短,但图像质量无明显差异。     

Localization and distribution of magnetic chemotherapeutic drugs with magnetic targeting in rat brain

Background Magnetic targeting therapy may be a new method for the treatment of malignent tumors. The purpose of this study was to investigate the localization and distribution of ferrofluid microsphere of human serum albumin methotrexate (FM-HSA-MTX) carriers in the brain and to explore the magnetic targeting chemotherapy for malignant brain tumor.Methods Ninety SD rats were divided into three groups: targeting group, non-magnetic targeting group, and control group. Synthesized FM-HSA-MTX carriers (MTX 25 mg/kg) were injected into the systemic circulation via the caudal vein (magnetic targeting group, n=30). A 0.6 T magnetic field was placed around the right hemisphere. The non-magnetic targeting group (n=30) was administered with FM-HSA-MTX without external magnetic field, meanwhile the control group (n=30) was treated with MTX and a magnetic field. Random serial sacrifices (n=10) were conducted at 15, 30 and 45 minutes after drug administration. Bilateral hemispheres were collected respectively, and analyzed for total MTX content. Results MTX content in the right hemisphere of the magnetic targeting group was significantly higher than that in the other two groups at 15, 30 and 45 minutes after drug administration （P＜0.05) No difference was seen between the non-targeting group and control group. In the magnetic targeting group, MTX returned to the peak level ［(0.564±0.018） mg/g, q15-45=32.252, P＜0.05］ 45 minutes after the injection but it deceased in the other two groups ［non-magnetic targeting group: （0.060±0.015） mg/g, q15-45=9.245, P＜0.05, control group: （0.074±0.045） mg/g, q15-45=6.299, P＜0.05］. In the magnetic targeting group, the concentration of MTX in the right hemisphere was significantly higher than that in the left hemisphere (t45min=21.135, P=0.000) but no difference was observed between bilateral hemispheres in the other two groups （non-magnetic targeting group： t45min=0.434, P=0.670; control group： t45min=0.533, P=0.600）. Conclusion In the presence of the external magnetic field, FM-HSA-MTX can distribute successfully in the targeting areas of the brain.     

颞叶癫先癇的磁共振和质子磁共振波谱定位研究

目的探讨磁共振(MR)和质子磁共振波谱(MRS)在颞叶癫癇定位诊断中的作用.方法15例经脑电图(EEG)检查确诊为颞叶癫癇并接受手术治疗的顽固性颞叶癫癇患者进行MR和MRS检查,MR检查包括海马区域,MRS检查测定N-乙酰天门冬氨酸(NAA)、肌酸(Cr)及胆碱复合物(Cho)的浓度并计算NAA/(Cr+Cho)值.结果MR检查发现15例中海马硬化11例,4例未发现异常;MRS检查13例患者颞叶NAA/(Cr+Cho)值异常,其中单侧异常8例,双侧异常5例,以患侧为重.两者结合可对14例患者定位.结论MR和MRS可分别从影像学和化学递质改变的角度为颞叶癫癇定位提供依据,两者结合可对颞叶癫癇进行定位诊断.