3.0T MRI对人胰腺癌裸鼠原位模型的成像及病理对照研究
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摘要
本研究采用Siemens Magnetom Trio Tim 3.0 T超导磁共振成像仪、临床型乳腺线圈和腹腔注射增强扫描技术,以人胰腺癌裸鼠原位模型为实验对象进行MRI成像研究,并与病理检查结果相对照,分为三个部分:
第一部分:人胰腺癌Panc-1裸鼠原位模型的建立
目的:建立人胰腺癌裸小鼠原位移植瘤模型,为胰腺癌生物学特性研究提供一种稳定的肿瘤体内实验系统。
材料和方法:人胰腺癌细胞株Panc-1体外常规传代后建立皮下移植瘤模型,将皮下移植瘤细胞悬液植入20只BALB/c-nu/nu裸鼠的胰腺包膜下,构建人胰腺癌原位移植模型;通过MRI监测并记录肿瘤的成瘤率、成瘤时间及生长情况;于第7周末,所有标本行组织病理学检查。
结果:20只裸鼠接种后肿瘤生长迅速,至接种后27天成瘤率为100%(20/20),病理学检查确诊为胰腺低分化腺癌,并保持原发瘤的生物学特征。
结论:人胰腺癌细胞株Panc-1裸小鼠原位模型可以为胰腺癌的临床研究提供一个有效、稳定的体内实验体系,是胰腺癌体内研究理想动物模型。
第二部分:经腹腔注射对比剂裸小鼠MRI增强扫描的实验研究
目的:评价腹腔注射对比剂裸小鼠MRI增强扫描的可行性,选择适宜的增强扫描时相,以获得满意的裸鼠MRI图像。
方法:采用Siemens Magnetom Trio Tim 3.0T超导磁共振成像仪,使用临床型乳腺线圈对20只裸小鼠体部进行TSE-T_1WI、TSE-T_2WI平扫,然后经腹腔注射钆喷酸葡胺注射液后1.5min、3min、6min、9min及12min后,在相同参数条件下行连续增强扫描。测量平扫和增强扫描各时相肝脏、左侧肾脏、左下肢肌肉的信号强度,并计算强化率。
结果:在相同参数条件下,各时相肝脏、左肾、左下肢肌肉的信号强度均高于平扫(Dunnett—t检验,P值均＜0.01),增强扫描各时相肝脏、左肾、左下肢肌肉强化率间均无统计学差异(方差分析P值均大于0.05)。
结论:采用经腹腔注射对比剂钆喷酸葡胺后1.5min裸小鼠组织、器官信号即明显增高且持续时间长,表明腹腔注射是一种简单易行安全的MRI增强扫描方法。
第三部分:人胰腺癌原位移植模型MRI增强扫描特征及病理对照研究
目的:探讨人胰腺癌原位移植瘤的MRI增强扫描方法、影像学表现及其病理机制。
材料和方法:应用3.0T磁共振成像仪及临床型乳腺线圈对30只胰腺癌裸鼠原位模型行冠状位及横断位TSE-T_1WI,TSE-T_2WI平扫后,经腹腔注射钆喷酸葡胺(Gd-DTPA)后分别于1.5min、3min、6min、9min、12min行连续动态增强扫描,测量平扫和增强扫描各时相肿瘤信号强度,计算强化率,分析MR图像特征并与病理对照。
结果:术后四周末,30只裸鼠荷瘤成功率为100%,组织学检查符合胰腺低分化腺癌。与邻近组织信号相比,瘤灶平扫T_1WI序列90%(27/30)呈均匀稍低信号,10%(3/30)信号欠均匀;T_2WI序列80%(24/30)呈不均匀高信号、内见斑片状更高或等信号区,20%(6/30)呈均匀等高信号。增强扫描各时相瘤灶信号强度均明显高于平扫(P＜0.01),各时相强化率间均有统计学差异(P＜0.01)。与病理结果对照,MR强化明显区为供血丰富的肿瘤生长活跃区域,中央无强化区为坏死组织和(或)肿瘤细胞致密且毛细血管较少区域。
结论:经腹腔注射对比剂后获得的原位移植瘤MRI动态增强图像,与病理检查结果具有很好的一致性,有助于从病理学角度深入理解和解释动物模型的MRI表现。
This study adopted Siemens Magnetom Trio Tim 3.0 Tesla superconductive MRI,enhancement scanning by means of injecting contrast agent intraperitoneally and clinical breast coil.Perform a comparative study of MR imaging and pathology of a orthotopic nude mouse model with human pancreatic cancer,which was divided into three parts.
Part One:Establishment the Orthotopic Transplantation Nude Mouse Model with Human Pancreatic Cancer Celllines PANC-1
Objective:To establish orthotopic transplantation nude mouse model of the human pancreatic cancer for the study of its biological characteristics.
Materials and Methods:The subcutaneous tumors cells suspension made by the subcutaneous injection of human pancreatic cancer cell lines Panc-1 were used as the source of tissue for orthotopic implantation of tissue onto the pancreas of 20 nude mice.After implantation,the growth of the tumor was monitored noninvasively by Magnetic Resonance Imaging (MRI).Then the successful rate,time and the growth status of the tumor were monitored and recorded.At the end of the 7th week,all the specimens were examined by pathological methods.
Result:Thirty-five percent(7/20) mice with implantation of primary human Panc-1 adenocarcinoma cells were accurately detected orthotopic implanted tumors by MRI after 15 days,and all the 20 nude mice developed pancreatic tumor within 27 days after operations.At last,the tumor formation of all mice were detected and confirmed histological as poorly differentiated adenocarcinoma.
Conclusion:The orthotopic transplantation nude mouse model of the human pancreatic cancer render a useful,stable,ideal tools to expose the human pancreatic cancer in vivo furtherly.
Part Two:Experimental study of injecting contrast agent intraperitoneally to nude mouse for MRI enhancement scanning
Objective:To evaluate the feasibility of injecting contrast agent intraperitoneally to mouse for MRI enhancement scanning,and find the best phase and the imagines of enhancement.
Materials and methods:Adopting Siemens Magnetom Trio Tim 3.0 Tesla superconductive MRI and breast coil,The 20 nude mouse were examined to acquire TSE-T1-weighted images of plain scanning and contrast enhancement scanning after injecting contrast agent intraperitoneally.The successive scanning was performed at 1.5min、3min、6min、9min、12 min after injection of Gadodiamide intraperitoneally with the same parameter.Signal intensities of Liver、left kidney、muscle of left-posterior limb were measured,plain scan and every phase's enhancement scanning images were measured respectively.Intensification rates of these three tissues were calculated.
Result:Signal intensities of Liver、left kidney、muscle of left-posterior limb on every phase's enhancement scanning images were higher than plain scan's(Dunnett-t test,P value＜0.01).No statistically significant differences were found among intensification rates of Liver、left kidney、muscle of left-posterior limb among every phase's enhancement scanning images(analysis of variance,p value＞0.05)
Conclusion:Mice's tissue and organ on T_1WI could be intensified after 1.5min injecting Gadobenate Dimeglumine intraperitoneally,and duration of intensification was long.It was confirmed that intraperitoneal injection was a simple and feasible means to perform MRI enhancement scanning in the experiment of the small rodent.
Part Three:a Comparative Study of Pathology and MRI Ehancement Scanning Features of the Orthotopic Transplantation Nude Mouse Model with Human Pancreatic Cancer
Objective:To find 3.0T clinic MRI examination technique and the pathomechanism of MRI enhancement scanning features of the human pancreatic orthotopic transplanted tumor.
Materials and Methods:Adopting Siemens Magnetom Trio Tim 3.0 Tesla superconductive MRI and breast coil,The 30 orthotopic transplantation nude mouse models of the human pancreatic cancer were sampling at 28 days after the operation to acquire TSE-T1-weighted and T2-weighted transverse axial images and contrast enhancement scanning.
The successive scanning was performed at 1.5min、3min、6min、9min、12 min after injection of Gadodiamide intraperitoneally.MRI features of the tumor and its surrounding tissues were observed.Signal intensities of tumors were measured.Plain scan and every phase's enhancement scanning images were measured respectively.Intensification rates of tumors were calculated.Pathologic examination was done after MRI scanning.A comparative analysis was made between pathological and MRI results.
Results:The successful rate of inoculation of 30 nude mice was 100%.the tumor formation of all mice were detected and confirmed histological as poorly differentiated adenocarcinoma.The MRI findings of the tumors were uniformly slightly hypointensity(90%,27/30),or unevenly(10%,3/30)on TSE-T_1WI,uniformly(20%,6/30)or unevenly (80%,24/30) hyperintensity with equal or more hyper signal spots on TSE-T2WI;during post-contrast dynamic scanning,all the tumors were demonstrated gradually obviously enhancement.Signal intensities and intensification rates of tumors on every phase's enhancement scanning images were higher than plain scan images(P＜0.01),and statistically significant differences were found among intensification rates of tumors on every phase's enhancement scanning.In a word,MRI could estimate pathologic exhibition of tumors according to tumor's internal signal.At the same time,the surrounding tissues invaded by tumor could be imaged.
With comparison,It was demonstrated that MRI features of implanted tumors had corresponding pathomechanism.The area intensified significantly is on where the tumor cells grown actively with rich capillaries;signal intensity obviously was not observed on the central area, which corresponded to the area of necrotic tissue and(or) more densely packed cells on histologic sections.
Conclusion:It was demonstrated that MRI features of implanted tumors had corresponding pathomechanism.
第一部分:人胰腺癌Panc-1裸鼠原位模型的建立
目的:建立人胰腺癌裸小鼠原位移植瘤模型,为胰腺癌生物学特性研究提供一种稳定的肿瘤体内实验系统。
材料和方法:人胰腺癌细胞株Panc-1体外常规传代后建立皮下移植瘤模型,将皮下移植瘤细胞悬液植入20只BALB/c-nu/nu裸鼠的胰腺包膜下,构建人胰腺癌原位移植模型;通过MRI监测并记录肿瘤的成瘤率、成瘤时间及生长情况;于第7周末,所有标本行组织病理学检查。
结果:20只裸鼠接种后肿瘤生长迅速,至接种后27天成瘤率为100%(20/20),病理学检查确诊为胰腺低分化腺癌,并保持原发瘤的生物学特征。
结论:人胰腺癌细胞株Panc-1裸小鼠原位模型可以为胰腺癌的临床研究提供一个有效、稳定的体内实验体系,是胰腺癌体内研究理想动物模型。
第二部分:经腹腔注射对比剂裸小鼠MRI增强扫描的实验研究
目的:评价腹腔注射对比剂裸小鼠MRI增强扫描的可行性,选择适宜的增强扫描时相,以获得满意的裸鼠MRI图像。
方法:采用Siemens Magnetom Trio Tim 3.0T超导磁共振成像仪,使用临床型乳腺线圈对20只裸小鼠体部进行TSE-T_1WI、TSE-T_2WI平扫,然后经腹腔注射钆喷酸葡胺注射液后1.5min、3min、6min、9min及12min后,在相同参数条件下行连续增强扫描。测量平扫和增强扫描各时相肝脏、左侧肾脏、左下肢肌肉的信号强度,并计算强化率。
结果:在相同参数条件下,各时相肝脏、左肾、左下肢肌肉的信号强度均高于平扫(Dunnett—t检验,P值均＜0.01),增强扫描各时相肝脏、左肾、左下肢肌肉强化率间均无统计学差异(方差分析P值均大于0.05)。
结论:采用经腹腔注射对比剂钆喷酸葡胺后1.5min裸小鼠组织、器官信号即明显增高且持续时间长,表明腹腔注射是一种简单易行安全的MRI增强扫描方法。
第三部分:人胰腺癌原位移植模型MRI增强扫描特征及病理对照研究
目的:探讨人胰腺癌原位移植瘤的MRI增强扫描方法、影像学表现及其病理机制。
材料和方法:应用3.0T磁共振成像仪及临床型乳腺线圈对30只胰腺癌裸鼠原位模型行冠状位及横断位TSE-T_1WI,TSE-T_2WI平扫后,经腹腔注射钆喷酸葡胺(Gd-DTPA)后分别于1.5min、3min、6min、9min、12min行连续动态增强扫描,测量平扫和增强扫描各时相肿瘤信号强度,计算强化率,分析MR图像特征并与病理对照。
结果:术后四周末,30只裸鼠荷瘤成功率为100%,组织学检查符合胰腺低分化腺癌。与邻近组织信号相比,瘤灶平扫T_1WI序列90%(27/30)呈均匀稍低信号,10%(3/30)信号欠均匀;T_2WI序列80%(24/30)呈不均匀高信号、内见斑片状更高或等信号区,20%(6/30)呈均匀等高信号。增强扫描各时相瘤灶信号强度均明显高于平扫(P＜0.01),各时相强化率间均有统计学差异(P＜0.01)。与病理结果对照,MR强化明显区为供血丰富的肿瘤生长活跃区域,中央无强化区为坏死组织和(或)肿瘤细胞致密且毛细血管较少区域。
结论:经腹腔注射对比剂后获得的原位移植瘤MRI动态增强图像,与病理检查结果具有很好的一致性,有助于从病理学角度深入理解和解释动物模型的MRI表现。
This study adopted Siemens Magnetom Trio Tim 3.0 Tesla superconductive MRI,enhancement scanning by means of injecting contrast agent intraperitoneally and clinical breast coil.Perform a comparative study of MR imaging and pathology of a orthotopic nude mouse model with human pancreatic cancer,which was divided into three parts.
Part One:Establishment the Orthotopic Transplantation Nude Mouse Model with Human Pancreatic Cancer Celllines PANC-1
Objective:To establish orthotopic transplantation nude mouse model of the human pancreatic cancer for the study of its biological characteristics.
Materials and Methods:The subcutaneous tumors cells suspension made by the subcutaneous injection of human pancreatic cancer cell lines Panc-1 were used as the source of tissue for orthotopic implantation of tissue onto the pancreas of 20 nude mice.After implantation,the growth of the tumor was monitored noninvasively by Magnetic Resonance Imaging (MRI).Then the successful rate,time and the growth status of the tumor were monitored and recorded.At the end of the 7th week,all the specimens were examined by pathological methods.
Result:Thirty-five percent(7/20) mice with implantation of primary human Panc-1 adenocarcinoma cells were accurately detected orthotopic implanted tumors by MRI after 15 days,and all the 20 nude mice developed pancreatic tumor within 27 days after operations.At last,the tumor formation of all mice were detected and confirmed histological as poorly differentiated adenocarcinoma.
Conclusion:The orthotopic transplantation nude mouse model of the human pancreatic cancer render a useful,stable,ideal tools to expose the human pancreatic cancer in vivo furtherly.
Part Two:Experimental study of injecting contrast agent intraperitoneally to nude mouse for MRI enhancement scanning
Objective:To evaluate the feasibility of injecting contrast agent intraperitoneally to mouse for MRI enhancement scanning,and find the best phase and the imagines of enhancement.
Materials and methods:Adopting Siemens Magnetom Trio Tim 3.0 Tesla superconductive MRI and breast coil,The 20 nude mouse were examined to acquire TSE-T1-weighted images of plain scanning and contrast enhancement scanning after injecting contrast agent intraperitoneally.The successive scanning was performed at 1.5min、3min、6min、9min、12 min after injection of Gadodiamide intraperitoneally with the same parameter.Signal intensities of Liver、left kidney、muscle of left-posterior limb were measured,plain scan and every phase's enhancement scanning images were measured respectively.Intensification rates of these three tissues were calculated.
Result:Signal intensities of Liver、left kidney、muscle of left-posterior limb on every phase's enhancement scanning images were higher than plain scan's(Dunnett-t test,P value＜0.01).No statistically significant differences were found among intensification rates of Liver、left kidney、muscle of left-posterior limb among every phase's enhancement scanning images(analysis of variance,p value＞0.05)
Conclusion:Mice's tissue and organ on T_1WI could be intensified after 1.5min injecting Gadobenate Dimeglumine intraperitoneally,and duration of intensification was long.It was confirmed that intraperitoneal injection was a simple and feasible means to perform MRI enhancement scanning in the experiment of the small rodent.
Part Three:a Comparative Study of Pathology and MRI Ehancement Scanning Features of the Orthotopic Transplantation Nude Mouse Model with Human Pancreatic Cancer
Objective:To find 3.0T clinic MRI examination technique and the pathomechanism of MRI enhancement scanning features of the human pancreatic orthotopic transplanted tumor.
Materials and Methods:Adopting Siemens Magnetom Trio Tim 3.0 Tesla superconductive MRI and breast coil,The 30 orthotopic transplantation nude mouse models of the human pancreatic cancer were sampling at 28 days after the operation to acquire TSE-T1-weighted and T2-weighted transverse axial images and contrast enhancement scanning.
The successive scanning was performed at 1.5min、3min、6min、9min、12 min after injection of Gadodiamide intraperitoneally.MRI features of the tumor and its surrounding tissues were observed.Signal intensities of tumors were measured.Plain scan and every phase's enhancement scanning images were measured respectively.Intensification rates of tumors were calculated.Pathologic examination was done after MRI scanning.A comparative analysis was made between pathological and MRI results.
Results:The successful rate of inoculation of 30 nude mice was 100%.the tumor formation of all mice were detected and confirmed histological as poorly differentiated adenocarcinoma.The MRI findings of the tumors were uniformly slightly hypointensity(90%,27/30),or unevenly(10%,3/30)on TSE-T_1WI,uniformly(20%,6/30)or unevenly (80%,24/30) hyperintensity with equal or more hyper signal spots on TSE-T2WI;during post-contrast dynamic scanning,all the tumors were demonstrated gradually obviously enhancement.Signal intensities and intensification rates of tumors on every phase's enhancement scanning images were higher than plain scan images(P＜0.01),and statistically significant differences were found among intensification rates of tumors on every phase's enhancement scanning.In a word,MRI could estimate pathologic exhibition of tumors according to tumor's internal signal.At the same time,the surrounding tissues invaded by tumor could be imaged.
With comparison,It was demonstrated that MRI features of implanted tumors had corresponding pathomechanism.The area intensified significantly is on where the tumor cells grown actively with rich capillaries;signal intensity obviously was not observed on the central area, which corresponded to the area of necrotic tissue and(or) more densely packed cells on histologic sections.
Conclusion:It was demonstrated that MRI features of implanted tumors had corresponding pathomechanism.
引文
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[9]Zervox EE,Franz MG,Salhab KF,et al.Matrix metalloproteinase inhibition improves survival in an orthotopic model of human pancreatic cancer[J].J Gastrointest Srug.2000(4):614-619.
[10]吴深宝,周国雄,黄介飞等.实验性胰腺癌动物模型研究进展.胰腺病学.2005(5):187-189.
[1]卢光明,王中秋,郑玲等.动态增强磁共振成像对胰腺癌及胰腺内分泌肿瘤的诊断价值探讨.中华医学杂志.2006:86(114):951-954.
[2]钟喨.胰腺肿瘤的磁共振成像检测.Chin J Gastroenterol.2006(11):642-644.
[3]王静,高磊,陆建平等.联合应用多种MR成像技术对胰腺癌的诊断价值.医学影像学杂志.2007,17(1):55-59.
[4]王冬青,曾蒙苏,靳大勇等.2D和3D MRI结合技术胰腺癌诊断中的应用.中华肿瘤杂志.2007(29):216-220.
[5]Bibby M.C.Orthotopic models of cancer for preclinical drugevaluation:advantages and disadvantages.European Journal of Cancer.2004(40):852-857.
[6]王虹,彭卫斌,许云飞等.裸鼠3.0T MRI线圈选择的实验研究.中华放射学杂志.2008(42):1210-1212.
[7]王虹,彭卫斌,许云飞等.胰腺癌裸鼠模型3.0T MRI早期表现.临床放射学杂志2008(27):957-960.
[8]Grimm J,Potthast A,Wunder A,el at.Magnetic resonance imagine of the pancreas and pancreatic tumors in a mouse orthotopic model of human cancer.Int.J Cancer.2003(106):806-811.
[9]Kumaga M,Mitsunobu R.Kano,Morishita Y,et al.Enhanced magnetic resonance imaging of experimental pancreatic tumor in vivo by block copolymer-coated magnetite nanoparticles with TGF-β inhibitor.Journal of Controlled Release.2009(140):306-311.
[10]Peter B,Howard A.R,Robert S.L,et al.Tumor hypoxia correlates with metastatic tumor growth of pancreatic cancer in an orthotopic murine model.[J]Surgical Research.2004(120):295-303.
[11]Hellwig D,Menges M,Schneider G,et al.Radioiodinated phenylalanine derivatives to image pancreatic cancer:a comparative study with[~(18)F]fluoro -2-deoxy-d-glucose in human pancreatic carcinoma xenografts and in inflammation models.Nuclear Medicine and Biology.2005(32)137-145.
[12]孟令新,李强,郭仁德等.裸鼠胰腺癌动物模型及其应用进展.中华实验外科杂志.2006.23(12):1583-1584.
[13]He Z,Evelhoch JL,Mohammad RM,et al.Magnetic resonance imaging to measure therapeutic response using an orthotopic model of human pancreatic cancer.Pancreas.2000(21):69-76.
[1]倪泉兴,张延龄.重视胰腺癌病人治疗后远期生存率的评估.外科理论与实践.2005.10(3):201-202.
[2]Yoshizawa K,Nagai H,Kurihara K,et al.Longterm survival after surgical resection for pancreatic cancer[J].Hepatogast roentology.2001.48(40):1153-1156.
[3]Wray CJ,Ahmad SA,Mattews JB,et al.Surgery for pancreatic cancer:recent cont roversies and current practice[J].Gastroenterology.2005.128(6):1626-1241.
[4]Cardillo T M,Karacay H,GoldenbergDM,et al.Improved targeting of pancreatic cancer:experimental studies of a new bis pecific antibody,pretargeting enhancement system for immunoscintigraphy.Clinical Cancer Research.2004.10:35-52.
[5]何杨,吴翼伟,阮长耿.Tcm标记抗人粒细胞单抗SZ2 102在荷人胰腺癌裸鼠的显像研究.中华核医学杂志.2004(24):276.
[6]Kim SK,Cargioli TG,MachlufM,et al.PEX-producing human neural stem cells inhibit tumor growth in a mouse glioma model.Clin Cancer Res.2005(11):59-65.
[7]Tsurusaki M,Richard C,Mauricio Zapparoli,et al.Quantitative and qualitative comparison of 3.0 T and 1.5 T MR imaging of the liver in patients with diffuse parenchymal liver disease.European Journal of Radiology.2009(72):314-320.
[8]Bouvet M,Spernyak J,Katz MH,et al.High correlation of whole-body red fluorescent protein imaging and magnetic resonance imaging on an orthotopic model of pancreatic cancer.Cancer Research.2005(65):9829-9833.
[9]Jan G,Andreas P,Andreas W,et al.Magnetic Resonance imagine of the pancreas and pancreatic tumors in a mouse orthotopic model of human cancer.Int.J.Cancer.2003(106):806-811.
[10]Kobayashi H,Kawamoto S,Jo SK,et al.Renal tubular damage detected by dynamic micro-MRI with a dendrimer-based magnetic resonance contrast agent.Kidney Int.2002(61):1980-1985.
[11]Herborn CU,Waldschuetz R,Lauenstein TC,et al.Contrast-enhanced magnetic resonance imaging(MS-325) in a murine model of systemic lupus erythematosus.Invest Radiol.2002(37):464-469.
[12]Weissleder R,Moore A,Mahmood U,et al.In vivo magnetic resonance imaging of transgene expression.Nat Med.2000(6):351-355.
[13]王虹,彭卫斌,许云飞等.裸鼠3.0T MRI线圈选择的实验研究.中华放射学杂 志,.2008(42):1210-1212.
[14]卢光明,王中秋,郑玲等.动态增强磁共振成像对胰腺癌及胰腺内分泌肿瘤的诊断价值探讨.中华医学杂志.2006.86(114):951-954.
[15]钟喨.胰腺肿瘤的磁共振成像检测.Chin J Gastroenterol.2006(11)642-644.
[16]王静,高磊,陆建平等.联合应用多种MR成像技术对胰腺癌的诊断价值.医学影像学杂志.2007.17(1):55-59.
[17]王冬青,曾蒙苏,靳大勇等.2D和3D MRI结合技术胰腺癌诊断中的应用.中华肿瘤杂志.2007(29):216-220.
[18]Kumaga M,Mitsunobu R.Kano,Morishita Y,et al.Enhanced magnetic resonance imaging of experimental pancreatic tumor in vivo by block copolymer-coated magnetite nanoparticles with TGF-β inhibitor.Journal of Controlled Release.2009(140):306-311.
[19]He Z,Evelhoch JL,Mohammad RM,et al.Magnetic resonance imaging to measure therapeutic response using an orthotopic model of human pancreatic cancer.Pancreas.2000(21):69-76.
[1]Butturini G, Stocken DD, Wente MN, et al. Influence of resection margins and treatment on survival in patients with pancreatic cancer: meta-analysis of randomized controlled trials. Arch Surg.2008(143):75-83.
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[7]Sawada N,MurataM, Kikuchi K, et al. Tight junctions and human diseases[J]. Med ElectronMicrosc.2003.36(3):147-156.
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[22]Bouvet M,Spernyak J,Katz MH,et al.High correlation of whole-body red fluorescent protein imaging and magnetic resonance imaging on an orthotopic model of pancreatic cancer.Cancer Research.2005(65):9829-9833.
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[5]成谦,孙慧,李强等.医学实验肝癌动物模型的研究进展[J].中华实验外科杂志.2006(23):377-378.
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[7]王虹,彭卫斌,许云飞等.人胰腺癌裸鼠模型3.0T MRI早期表现[J].临床放射学杂志.2008(27):957-960.
[8]Teresa Troiani,Clorinda Schettino,Erika Martinelli,et al.The use of xenograft models for the selection of cancer treatments with the EGFR as an example[J].Critical Reviews in Oncology/Hematology.2008(65):200-211.
[9]Zervox EE,Franz MG,Salhab KF,et al.Matrix metalloproteinase inhibition improves survival in an orthotopic model of human pancreatic cancer[J].J Gastrointest Srug.2000(4):614-619.
[10]吴深宝,周国雄,黄介飞等.实验性胰腺癌动物模型研究进展.胰腺病学.2005(5):187-189.
[1]卢光明,王中秋,郑玲等.动态增强磁共振成像对胰腺癌及胰腺内分泌肿瘤的诊断价值探讨.中华医学杂志.2006:86(114):951-954.
[2]钟喨.胰腺肿瘤的磁共振成像检测.Chin J Gastroenterol.2006(11):642-644.
[3]王静,高磊,陆建平等.联合应用多种MR成像技术对胰腺癌的诊断价值.医学影像学杂志.2007,17(1):55-59.
[4]王冬青,曾蒙苏,靳大勇等.2D和3D MRI结合技术胰腺癌诊断中的应用.中华肿瘤杂志.2007(29):216-220.
[5]Bibby M.C.Orthotopic models of cancer for preclinical drugevaluation:advantages and disadvantages.European Journal of Cancer.2004(40):852-857.
[6]王虹,彭卫斌,许云飞等.裸鼠3.0T MRI线圈选择的实验研究.中华放射学杂志.2008(42):1210-1212.
[7]王虹,彭卫斌,许云飞等.胰腺癌裸鼠模型3.0T MRI早期表现.临床放射学杂志2008(27):957-960.
[8]Grimm J,Potthast A,Wunder A,el at.Magnetic resonance imagine of the pancreas and pancreatic tumors in a mouse orthotopic model of human cancer.Int.J Cancer.2003(106):806-811.
[9]Kumaga M,Mitsunobu R.Kano,Morishita Y,et al.Enhanced magnetic resonance imaging of experimental pancreatic tumor in vivo by block copolymer-coated magnetite nanoparticles with TGF-β inhibitor.Journal of Controlled Release.2009(140):306-311.
[10]Peter B,Howard A.R,Robert S.L,et al.Tumor hypoxia correlates with metastatic tumor growth of pancreatic cancer in an orthotopic murine model.[J]Surgical Research.2004(120):295-303.
[11]Hellwig D,Menges M,Schneider G,et al.Radioiodinated phenylalanine derivatives to image pancreatic cancer:a comparative study with[~(18)F]fluoro -2-deoxy-d-glucose in human pancreatic carcinoma xenografts and in inflammation models.Nuclear Medicine and Biology.2005(32)137-145.
[12]孟令新,李强,郭仁德等.裸鼠胰腺癌动物模型及其应用进展.中华实验外科杂志.2006.23(12):1583-1584.
[13]He Z,Evelhoch JL,Mohammad RM,et al.Magnetic resonance imaging to measure therapeutic response using an orthotopic model of human pancreatic cancer.Pancreas.2000(21):69-76.
[1]倪泉兴,张延龄.重视胰腺癌病人治疗后远期生存率的评估.外科理论与实践.2005.10(3):201-202.
[2]Yoshizawa K,Nagai H,Kurihara K,et al.Longterm survival after surgical resection for pancreatic cancer[J].Hepatogast roentology.2001.48(40):1153-1156.
[3]Wray CJ,Ahmad SA,Mattews JB,et al.Surgery for pancreatic cancer:recent cont roversies and current practice[J].Gastroenterology.2005.128(6):1626-1241.
[4]Cardillo T M,Karacay H,GoldenbergDM,et al.Improved targeting of pancreatic cancer:experimental studies of a new bis pecific antibody,pretargeting enhancement system for immunoscintigraphy.Clinical Cancer Research.2004.10:35-52.
[5]何杨,吴翼伟,阮长耿.Tcm标记抗人粒细胞单抗SZ2 102在荷人胰腺癌裸鼠的显像研究.中华核医学杂志.2004(24):276.
[6]Kim SK,Cargioli TG,MachlufM,et al.PEX-producing human neural stem cells inhibit tumor growth in a mouse glioma model.Clin Cancer Res.2005(11):59-65.
[7]Tsurusaki M,Richard C,Mauricio Zapparoli,et al.Quantitative and qualitative comparison of 3.0 T and 1.5 T MR imaging of the liver in patients with diffuse parenchymal liver disease.European Journal of Radiology.2009(72):314-320.
[8]Bouvet M,Spernyak J,Katz MH,et al.High correlation of whole-body red fluorescent protein imaging and magnetic resonance imaging on an orthotopic model of pancreatic cancer.Cancer Research.2005(65):9829-9833.
[9]Jan G,Andreas P,Andreas W,et al.Magnetic Resonance imagine of the pancreas and pancreatic tumors in a mouse orthotopic model of human cancer.Int.J.Cancer.2003(106):806-811.
[10]Kobayashi H,Kawamoto S,Jo SK,et al.Renal tubular damage detected by dynamic micro-MRI with a dendrimer-based magnetic resonance contrast agent.Kidney Int.2002(61):1980-1985.
[11]Herborn CU,Waldschuetz R,Lauenstein TC,et al.Contrast-enhanced magnetic resonance imaging(MS-325) in a murine model of systemic lupus erythematosus.Invest Radiol.2002(37):464-469.
[12]Weissleder R,Moore A,Mahmood U,et al.In vivo magnetic resonance imaging of transgene expression.Nat Med.2000(6):351-355.
[13]王虹,彭卫斌,许云飞等.裸鼠3.0T MRI线圈选择的实验研究.中华放射学杂 志,.2008(42):1210-1212.
[14]卢光明,王中秋,郑玲等.动态增强磁共振成像对胰腺癌及胰腺内分泌肿瘤的诊断价值探讨.中华医学杂志.2006.86(114):951-954.
[15]钟喨.胰腺肿瘤的磁共振成像检测.Chin J Gastroenterol.2006(11)642-644.
[16]王静,高磊,陆建平等.联合应用多种MR成像技术对胰腺癌的诊断价值.医学影像学杂志.2007.17(1):55-59.
[17]王冬青,曾蒙苏,靳大勇等.2D和3D MRI结合技术胰腺癌诊断中的应用.中华肿瘤杂志.2007(29):216-220.
[18]Kumaga M,Mitsunobu R.Kano,Morishita Y,et al.Enhanced magnetic resonance imaging of experimental pancreatic tumor in vivo by block copolymer-coated magnetite nanoparticles with TGF-β inhibitor.Journal of Controlled Release.2009(140):306-311.
[19]He Z,Evelhoch JL,Mohammad RM,et al.Magnetic resonance imaging to measure therapeutic response using an orthotopic model of human pancreatic cancer.Pancreas.2000(21):69-76.
[1]Butturini G, Stocken DD, Wente MN, et al. Influence of resection margins and treatment on survival in patients with pancreatic cancer: meta-analysis of randomized controlled trials. Arch Surg.2008(143):75-83.
[2]Furuse M, Fujita K, Hiiragi T, et al. Claudin-1 and -2: Novel integral membrane proteins localizing at tight junctions with nosequence similarity to occludin [J]. J Cell Biol.1998(141): 1539-1550.
[3]Turksen K, Troy TC. Barriers built on claudins [J]. J Cell Sci.2004(117):2435-2447.
[4]Laurila T, Karttunen V, Koivukangas P.A, et al. Tight junction proteins in gallbladder epithelium: different expression in acute acalculous and calculous cholecystitis J. Histochem. Cytochem. 2007(55) :567-573.
[5]Kitajiri M,Furuse K,Morita Y,et al.Expression patterns of claudins, tight junction adhesion molecules in the inner ear.Hear Res. 2004(187):25-34.
[6]Krause G, Winkler L, Sebastian L. Structure and function of claudins. Biochimica et BiophysicaActa.2008(1778):631-645.
[7]Sawada N,MurataM, Kikuchi K, et al. Tight junctions and human diseases[J]. Med ElectronMicrosc.2003.36(3):147-156.
[8]Duan Zhao, Zhang Xin, Gao Ya. Expressions of claudin-4 and claudin-1 in endometrial cancer and their significance. Journal of Medical Colleges of PLA.2008(23):162-166.
[9]Nichols LS, Ashfaq R, Donahue CA. Claudin 4 protein expression in primary and metastatic pancreatic cancer: Support for use as a therapeutic target[J]. Am J Clin Pathol.2004.121 (2):226-230.
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