修回日期: 2011-12-19
接受日期: 2012-01-06
在线出版日期: 2012-01-28
胃癌的发病率及死亡率均较高, 严重危害人类健康, 其早期诊断及根治性手术对胃癌患者预后至关重要. 目前全世界范围内都在努力探索对胃癌早期诊断的新方法新技术, 从传统的消化内镜诊断到病理组织学诊断, 人们一直在寻求一种能够早期准确高效的诊断胃癌的有力手段, 而共聚焦显微镜的诞生实现了这一愿望, 达到了早期、快速、准确的诊断胃癌的目的, 实现了多种技术优点的完美结合. 本文通过深度阅读大量新近国内外文献, 探讨通过借助目前最先进的激光共聚焦显微镜技术达到对胃癌患者的早期诊断、提高患者术后生存质量及生存率的可行性.
引文著录: 李守震, 王权. 共聚焦显微镜辅助下诊断早期胃癌的可行性. 世界华人消化杂志 2012; 20(3): 205-209
Revised: December 19, 2011
Accepted: January 6, 2012
Published online: January 28, 2012
Gastric cancer has high incidence and mortality and does serious harm to the health of human beings. Early diagnosis and radical operation are crucial for prognosis in patients with gastric cancer. Worldwide efforts have been taken to search new methods and technologies that can enable early, accurate and efficient diagnosis of gastric cancer. The birth of the confocal microscope makes the dream come true. It perfectly combines the advantages of various kinds of technologies and allows early, rapid and accurate diagnosis of gastric cancer. In this paper, we discuss the possibility of using laser confocal microscopy for the early diagnosis of gastric cancer to improve patients' life quality and survival rate.
- Citation: Li SZ, Wang Q. Feasibility of diagnosis of early gastric cancer assisted by confocal microscopy. Shijie Huaren Xiaohua Zazhi 2012; 20(3): 205-209
- URL: https://www.wjgnet.com/1009-3079/full/v20/i3/205.htm
- DOI: https://dx.doi.org/10.11569/wcjd.v20.i3.205
目前, 胃癌是世界范围内死亡率第2位的恶性肿瘤, 其5年生存率约20%. 我国胃癌患者占全世界三分之一, 其发病率居各类肿瘤的首位, 早期诊断及手术治疗对预后至关重要. 应用最普遍的是传统内镜检查, 但是由于其分辨率有限, 组织活检随机性较大[1-3], 难以高效的诊断早期胃癌. 因此, 利用目前最先进的共聚焦显微镜技术[4-6]提高胃癌患者早期诊断率及手术治愈率对改善患者预后意义极其重大. 1957年Minsky提出了共聚焦显微镜技术的某些基本原理, 并获得了专利; 1967年Egger和Petran成功的应用共聚焦显微镜产生了一个光学横断面; 1987年第一台商业化的共焦扫描显微镜诞生. 激光扫描共聚焦显微镜是20世纪80年代发展起来的一项具有划时代意义的高科技产品, 他是在荧光显微镜成像基础上加装了激光扫描装置, 利用计算机进行图像处理, 把光学成像的分辨率提高了30%-40%, 使用紫外或可见光激发荧光探针, 从而得到放大1 000倍的组织表面和表面下的虚拟组织学图像[7-9]即组织、细胞或亚细胞结构的荧光图像, 可以在亚细胞水平上[10-12]观察诸如Ca2+、pH值, 膜电位等生理信号及细胞形态的变化, 成为形态学、分子生物学、神经科学、药理学、遗传学等领域中新一代强有力的研究工具. 在我国, 这项技术主要应用与共聚焦显微内镜. 查阅国内外文献, 这一技术在胃癌的早期诊断方面已有诸多显著成果. 通过观察正常胃黏膜, 胃癌黏膜的共聚焦图像如胃小凹形态结构、微血管形态、管径、数目、面积、微血管渗漏现象[13-15]等特征, 隐窝形态、隐窝细胞明暗度[16-18]、腺体结构、基质染色情况、基底膜完整性、细胞核形态[19-21]、核质比例、染色模式变化等确定共聚焦内镜诊断参数. 通过与组织学图像进行对比, 并请病理医师对2种图像分别进行诊断, 发现共聚焦图像与组织学图像具有良好的对应性[22,23], 诊断准确率非常高, 提示依据共聚焦图像完全可进行实时体内组织学诊断[24-26]. 并进一步确立了应用共聚焦图像根据以上参数诊断早期胃肿瘤的诊断标准, 明确了色素内镜指导的共聚焦激光显微内镜对胃癌诊断的真实性和可重复性.
共聚焦激光显微内镜可清楚地观察到胃黏膜表面的胃小凹的结构[27-29], 包括组成胃小凹的表面柱状上皮细胞、胃小凹的开口、胃小凹之间的间质. 正常的胃底腺黏膜表现为具有圆形开口的圆形胃小凹; 正常幽门腺黏膜表现为裂隙样开口的连续的短棒状胃小凹. 而胃癌患者的共聚焦图像与正常者明显不同[30-32], 正常的胃小凹结构消失, 而代之以具有肿瘤特征的明显异型的细胞及结构即胃小凹结构的完整性破坏或消失, 取代为分散排列的黑色团块状的肿瘤细胞, 细胞着色差, 细胞极性消失, 黏膜微血管网[33-35]紊乱、增粗、扭曲、变形. 根据2名医师对共聚焦图像的判定结果, 共聚焦激光显微内镜对胃癌诊断的准确度分别为95%和92.5%.
胃小凹形态分为7型. 正常胃底腺黏膜主要表现为A型(圆形开口的圆形胃小凹), 而出现组织学胃炎的胃体黏膜表现为B型(非连续性短棒状胃小凹); 正常幽门腺黏膜表现为C型(开口为裂隙样的连续性短棒状胃小凹), 出现组织学胃炎的胃窦黏膜表现为D型(延长、扭曲的树枝状胃小凹): 随着萎缩性胃炎的出现, 表现为E型, 胃小凹的数目减少, 开口常扩大; 出现肠上皮化生[36-38]则表现为F型, 出现易于辨认的大而黑的杯状细胞, 伴有或不伴有绒毛样结构; 胃癌则表现为G型, 其中, 未分化型腺癌为G1型, 表现为正常的胃小凹的结构消失, 出现散在的异型的肿瘤细胞. 分化型腺癌为G2型, 表现为正常的胃小凹的结构消失, 出现形态各异、大小不一的异型的腺体; E型对于萎缩性胃炎诊断的敏感度、特异度分别为83.6%和99.6%. G型对于胃癌诊断的敏感度、特异度分别为90.0%和99.4%[13,39,40]. 色素内镜指导的共聚焦激光显微内镜对于胃癌诊断的敏感度、特异度、准确度分别为93.8%、99.2%、98.3%.
微血管诊断参数主要有微血管形态、管径、数目、面积、微血管渗漏等; 微血管形态分为5型: Ⅰ: 微血管数目增多, 粗细不等, 排列不规则; Ⅱ: 微血管数目减少, 排列不规则; Ⅲ: 分支增多, 管径基本均匀一致; Ⅳ: 规则排列的微血管网呈蜂窝状沿胃小凹排列; Ⅴ: 规则排列的微血管网呈线圈状沿胃小凹排列. 病理组织学中的分化型早期胃癌69.6%为Ⅰ型微血管形态; 未分化型早期胃癌75%为Ⅱ型微血管形态; 高级上皮内瘤变80.6%为Ⅲ型微血管形态; 低级上皮内瘤变34%为Ⅳ型; 48.9%为Ⅴ型微血管形态; 正常胃黏膜98.4%为Ⅴ型微血管形态. 管径: 应用共聚焦图像微血管分析专用软件-齐鲁美迪康医学图像分析软件可测量, 研究结果表明分化型早期胃癌>未分化型早期胃癌>高级上皮内瘤变>低级上皮内瘤变、正常胃底黏膜、正常胃窦黏膜. 数目: 测量同上, 研究结果, 分化型早期胃癌高于正常胃黏膜及未分化型早期胃癌、高级上皮内瘤变、低级上皮内瘤变. 面积: 测量同上, 渗漏, 表现为微血管周围出现均匀一致的明亮区域, 测量同上, 研究表明早期胃癌的微血管渗漏阳性率高于上皮内瘤变及正常胃黏膜. 综合评价, 微血管形态, 管径及数目是最有价值的参数, 因其在早期胃癌及高级上皮内瘤变有显著不同于低级上皮内瘤变及正常胃黏膜的特征, 面积由于受横切纵切影响变异较大, 不是理想参数, 微血管渗漏现象具有较高特异性, 但敏感性较差.
另有研究表明胃癌组织隐窝形态不规则, 隐窝细胞明暗度变暗, 腺体形态高度不规则, 细胞变暗, 基质染色不规则, 血管增生, 基底膜不完整, 细胞核形态改变, 核质比增加, 染色质浓缩, 染色模式变得明亮(由于肿瘤细胞PH改变, 使PH依赖荧光素产生相应变化). 共聚焦显微镜还可通过杯状细胞, 绒毛样胃小凹, 高柱状吸收细胞伴刷状缘[9,41,42], 3个特征诊断肠上皮化生, 此外, 也可通过共聚焦显微镜观察胃黏膜表型及测量黏膜细胞糖蛋白含量诊断早期胃癌.
总之, 共聚焦显微镜的诊断效果等同于传统的组织学诊断, 其诊断准确率在99%以上, 根据目前数据显示其诊断灵敏度为99.4%, 特异度为99.4%, 精确度为99.2%.
共聚焦图像质量也是影响组织学诊断的重要原因. 对早期胃癌患者进行共聚焦内镜检查, 发现影响诊断准确性的主要因素是图像的质量. 影响共聚焦图像质量的最大的问题是存在伪影, 许多伪影是因为内镜的头端与黏膜表面没有平坦的接触, 以及呼吸、动脉搏动、胃肠蠕动引起, 应用解痉剂及通过工作通道吸引一下使黏膜表面与内镜的头端正确接触可以减少此类伪影. 对比剂荧光素钠和盐酸吖啶黄的应用, 当前的临床实践证明, 尚无严重不良反应报道, 荧光素钠仅在一少部分人中发生皮疹、瘙痒类的不良反应, 大多较轻, 激光共聚焦经抗过敏治疗后均可好转. 但其临床风险需进一步评估. 此外, 荧光素钠仅对细胞及微血管有较好的显像, 并不能显示细胞核形态, 其他对比剂如白蛋白、甲紫酚、四环素、光卟啉等显像效果不十分理想, 亟需研究新型的对比剂, 同时对细胞、微血管及细胞核有较好的显像. 另外, 氩激光束的穿透性也有一定局限性. 最后, 共聚焦显微镜观察深度限于黏膜表层, 有待增加观察深度. 临床应用: 其国内外应用形式普遍是以共聚焦显微内镜应用于临床, 目前国内开展该检查项目的单位包括山东大学齐鲁医院和北京301医院等多家医院, 其中山东大学齐鲁医院是国内最早开展共聚焦激光显微内镜的医疗单位[43-45], 在胃肠道疾病的共聚焦显微内镜诊断方面积累了丰富的经验, 国外2011年有文献首次报道利用共聚焦显微内镜成功诊断一例胃印戒细胞癌分期为cT3N3M1患者[46-52].
对于胃癌的诊断, 传统内镜分辨率低, 组织活检随机性大, 诊断率不高, 对手术范围也无指导意义; 病理检查较多用于术后, 达不到早期诊断的目的, 也不能为手术提供指导, 快速病理检查; 所取标本有限, 而且不连续, 加之成本较高, 应用有限. 而共聚焦显微镜既可以诊断早期胃癌, 又可以快速准确地确定肿瘤组织侵及范围, 可以为手术范围提供明确的指示, 目前, 研究的比较深入、具体、 系统、较有价值的诊断参数主要为胃小凹形态、黏膜微血管特征等, 也建立了比较完善可靠的诊断标准, 对于激光共聚焦显微镜在胃癌早期诊断方面提供了非常有价值的借鉴及参考.
胃癌是目前世界范围内死亡率第2位的恶性肿瘤, 其5年生存率约20%. 早期诊断及手术治疗对预后至关重要. 应用最普遍的是传统内镜检查, 但是由于其分辨率有限, 组织活检随机性较大难以高效的诊断早期胃癌. 利用目前最先进的共聚焦显微镜技术提高胃癌患者早期诊断率及手术治愈率对改善患者预后意义重大.
肖恩华, 教授, 中南大学湘雅二医院放射教研室
国内外大量研究聚焦于通过观察正常胃黏膜, 胃癌黏膜的共聚焦图像确定共聚焦内镜诊断参数. 但共聚焦图像质量的保证仍急需解决.
山东大学齐鲁医院是国内最早开展共聚焦激光显微内镜的医疗单位, 在胃肠道疾病的共聚焦显微内镜诊断方面积累了丰富的经验, 得出许多较为可靠的诊断参数, 国外2011年有文献首次报道利用共聚焦显微内镜成功诊断一例胃印戒细胞癌分期为cT3N3M1患者.
本文纵向探讨胃癌早期诊断方法, 着重介绍目前最先进的共聚焦显微镜技术, 并认真总结国内外最新研究成果, 集中分析并介绍了其中较为可靠系统的诊断参数.
激光扫描共聚焦显微镜: 在荧光显微镜成像基础上加装了激光扫描装置, 利用计算机进行图像处理, 把光学成像的分辨率提高了30%-40%, 使用紫外或可见光激发荧光探针, 从而得到放大1 000倍的组织表面和表面下的虚拟组织学图像.
本文专论激光共聚焦显微镜技术在胃癌早期诊断的应用和局限性, 对临床应用有一定参考价值, 选题实用, 引用文献新, 学术价值好.
编辑:曹丽鸥 电编:闫晋利
| 4. | Leong RW. Confocal endomicroscopy in the evaluation of celiac disease. Endoscopy. 2010;42:606; author reply 607. [PubMed] [DOI] |
| 6. | 刘 吴, 陈 美兰, 郭 仁舆. 激光荧光检查法在肿瘤定位诊断中的应用. 西安交通大学学报(医学版). 2007;28:455-457. |
| 9. | Sanduleanu S, Driessen A, Gomez-Garcia E, Hameeteman W, de Bruïne A, Masclee A. In vivo diagnosis and classification of colorectal neoplasia by chromoendoscopy-guided confocal laser endomicroscopy. Clin Gastroenterol Hepatol. 2010;8:371-378. [PubMed] [DOI] |
| 10. | Deinert K, Kiesslich R, Vieth M, Neurath MF, Neuhaus H. In-vivo microvascular imaging of early squamous-cell cancer of the esophagus by confocal laser endomicroscopy. Endoscopy. 2007;39:366-368. [PubMed] [DOI] |
| 11. | Kiesslich R, Neurath MF. Endomicroscopy is born--do we still need the pathologist? Gastrointest Endosc. 2007;66:150-153. [PubMed] [DOI] |
| 12. | Kiesslich R, Goetz M, Neurath MF. Virtual histology. Best Pract Res Clin Gastroenterol. 2008;22:883-897. [PubMed] [DOI] |
| 13. | Gheorghe C, Iacob R, Becheanu G, Dumbrav Abreve M. Confocal endomicroscopy for in vivo microscopic analysis of upper gastrointestinal tract premalignant and malignant lesions. J Gastrointestin Liver Dis. 2008;17:95-100. [PubMed] |
| 14. | Meining A, Saur D, Bajbouj M, Becker V, Peltier E, Höfler H, von Weyhern CH, Schmid RM, Prinz C. In vivo histopathology for detection of gastrointestinal neoplasia with a portable, confocal miniprobe: an examiner blinded analysis. Clin Gastroenterol Hepatol. 2007;5:1261-1267. [PubMed] [DOI] |
| 15. | Wallace MB, Fockens P. Probe-based confocal laser endomicroscopy. Gastroenterology. 2009;136:1509-1513. [PubMed] [DOI] |
| 16. | Gheonea DI, Cârţână T, Ciurea T, Popescu C, Bădărău A, Săftoiu A. Confocal laser endomicroscopy and immunoendoscopy for real-time assessment of vascularization in gastrointestinal malignancies. World J Gastroenterol. 2011;17:21-27. [PubMed] [DOI] |
| 17. | De Palma GD. Confocal laser endomicroscopy in the "in vivo" histological diagnosis of the gastrointestinal tract. World J Gastroenterol. 2009;15:5770-5775. [PubMed] [DOI] |
| 18. | Kiesslich R, Galle PR, Neurath MF. Atlas of Endomicroscopy. Springer Medizin Verlag Heidelberg. 2007;55-79. |
| 19. | Banno K, Niwa Y, Miyahara R, Nakamura M, Nagaya T, Nagasaka T, Watanabe O, Ando T, Kawashima H, Ohmiya N. Confocal endomicroscopy for phenotypic diagnosis of gastric cancer. J Gastroenterol Hepatol. 2010;25:712-718. [PubMed] [DOI] |
| 20. | Goetz M, Wang TD. Molecular imaging in gastrointestinal endoscopy. Gastroenterology. 2010;138:828-33. e1. [PubMed] |
| 21. | Hsiung PL, Hardy J, Friedland S, Soetikno R, Du CB, Wu AP, Sahbaie P, Crawford JM, Lowe AW, Contag CH. Detection of colonic dysplasia in vivo using a targeted heptapeptide and confocal microendoscopy. Nat Med. 2008;14:454-458. [PubMed] [DOI] |
| 22. | Foersch S, Kiesslich R, Waldner MJ, Delaney P, Galle PR, Neurath MF, Goetz M. Molecular imaging of VEGF in gastrointestinal cancer in vivo using confocal laser endomicroscopy. Gut. 2010;59:1046-1055. [PubMed] [DOI] |
| 23. | Goetz M, Ziebart A, Foersch S, Vieth M, Waldner MJ, Delaney P, Galle PR, Neurath MF, Kiesslich R. In vivo molecular imaging of colorectal cancer with confocal endomicroscopy by targeting epidermal growth factor receptor. Gastroenterology. 2010;138:435-446. [PubMed] [DOI] |
| 24. | Hoffman A, Goetz M, Vieth M, Galle PR, Neurath MF, Kiesslich R. Confocal laser endomicroscopy: technical status and current indications. Endoscopy. 2006;38:1275-1283. [PubMed] [DOI] |
| 25. | Kiesslich R, Gossner L, Goetz M, Dahlmann A, Vieth M, Stolte M, Hoffman A, Jung M, Nafe B, Galle PR. In vivo histology of Barrett's esophagus and associated neoplasia by confocal laser endomicroscopy. Clin Gastroenterol Hepatol. 2006;4:979-987. [PubMed] [DOI] |
| 26. | Becker V, Vieth M, Bajbouj M, Schmid RM, Meining A. Confocal laser scanning fluorescence microscopy for in vivo determination of microvessel density in Barrett's esophagus. Endoscopy. 2008;40:888-891. [PubMed] [DOI] |
| 27. | Li WB, Zuo XL, Zuo F, Gu XM, Yu T, Zhao YA, Zhang TG, Zhang JP, Li YQ. Characterization and identification of gastric hyperplastic polyps and adenomas by confocal laser endomicroscopy. Surg Endosc. 2010;24:517-524. [PubMed] [DOI] |
| 28. | Guo YT, Li YQ, Yu T, Zhang TG, Zhang JN, Liu H, Liu FG, Xie XJ, Zhu Q, Zhao YA. Diagnosis of gastric intestinal metaplasia with confocal laser endomicroscopy in vivo: a prospective study. Endoscopy. 2008;40:547-553. [PubMed] [DOI] |
| 29. | Zhang JN, Li YQ, Zhao YA, Yu T, Zhang JP, Guo YT, Liu H. Classification of gastric pit patterns by confocal endomicroscopy. Gastrointest Endosc. 2008;67:843-853. [PubMed] [DOI] |
| 30. | Kakeji Y, Yamaguchi S, Yoshida D, Tanoue K, Ueda M, Masunari A, Utsunomiya T, Imamura M, Honda H, Maehara Y. Development and assessment of morphologic criteria for diagnosing gastric cancer using confocal endomicroscopy: an ex vivo and in vivo study. Endoscopy. 2006;38:886-890. [PubMed] [DOI] |
| 31. | Liu H, Li YQ, Yu T, Zhao YA, Zhang JP, Zhang JN, Guo YT, Xie XJ, Zhang TG, Desmond PV. Confocal endomicroscopy for in vivo detection of microvascular architecture in normal and malignant lesions of upper gastrointestinal tract. J Gastroenterol Hepatol. 2008;23:56-61. [PubMed] |
| 32. | Meining A, Bajbouj M, Schmid RM. Confocal fluorescence microscopy for detection of gastric angiodysplasia. Endoscopy. 2007;39 Suppl 1:E145. [PubMed] [DOI] |
| 33. | Reitan NK, Thuen M, Goa PE, de Lange Davies C. Characterization of tumor microvascular structure and permeability: comparison between magnetic resonance imaging and intravital confocal imaging. J Biomed Opt. 2010;15:036004. [PubMed] [DOI] |
| 34. | Ziefle S, Schüle D, Breuninger H, Schippert W, Moehrle M. Confocal laser scanning microscopy vs 3-dimensional histologic imaging in basal cell carcinoma. Arch Dermatol. 2010;146:843-847. [PubMed] [DOI] |
| 35. | Lennerz JK, Kim SH, Oates EL, Huh WJ, Doherty JM, Tian X, Bredemeyer AJ, Goldenring JR, Lauwers GY, Shin YK. The transcription factor MIST1 is a novel human gastric chief cell marker whose expression is lost in metaplasia, dysplasia, and carcinoma. Am J Pathol. 2010;177:1514-1533. [PubMed] [DOI] |
| 36. | Goetz M, Kiesslich R. Confocal endomicroscopy: in vivo diagnosis of neoplastic lesions of the gastrointestinal tract. Anticancer Res. 2008;28:353-360. [PubMed] |
| 37. | Adam P, Schmausser B, Göbeler-Kolve M, Müller-Hermelink HK, Eck M. Gastric extranodal marginal zone B-cell lymphomas of MALT type exclusively express Toll-like receptor 4 in contrast to other lymphomas infiltrating the stomach. Ann Oncol. 2008;19:566-569. [PubMed] [DOI] |
| 38. | Burgermeister E, Xing X, Röcken C, Juhasz M, Chen J, Hiber M, Mair K, Shatz M, Liscovitch M, Schmid RM. Differential expression and function of caveolin-1 in human gastric cancer progression. Cancer Res. 2007;67:8519-8526. [PubMed] [DOI] |
| 39. | Hurlstone DP, Baraza W, Brown S, Thomson M, Tiffin N, Cross SS. In vivo real-time confocal laser scanning endomicroscopic colonoscopy for the detection and characterization of colorectal neoplasia. Br J Surg. 2008;95:636-645. [PubMed] [DOI] |
| 40. | Kim HK, Park WS, Kang SH, Warda M, Kim N, Ko JH, Prince Ael-B, Han J. Mitochondrial alterations in human gastric carcinoma cell line. Am J Physiol Cell Physiol. 2007;293:C761-C771. [PubMed] [DOI] |
| 41. | Oldani A, Cormont M, Hofman V, Chiozzi V, Oregioni O, Canonici A, Sciullo A, Sommi P, Fabbri A, Ricci V. Helicobacter pylori counteracts the apoptotic action of its VacA toxin by injecting the CagA protein into gastric epithelial cells. PLoS Pathog. 2009;5:e1000603. [PubMed] [DOI] |
| 42. | Filip MM, Gheonea DI, Georgescu CV, Popescu C, Ciurea T, Saftoiu A. Quadri-modal imaging for real-time diagnosis of early gastric cancer. J Gastrointestin Liver Dis. 2009;18:271-272. [PubMed] |
| 44. | Ponnusamy MP, Lakshmanan I, Jain M, Das S, Chakraborty S, Dey P, Batra SK. MUC4 mucin-induced epithelial to mesenchymal transition: a novel mechanism for metastasis of human ovarian cancer cells. Oncogene. 2010;29:5741-5754. [PubMed] [DOI] |
| 45. | Necchi V, Sommi P, Ricci V, Solcia E. In vivo accumulation of Helicobacter pylori products, NOD1, ubiquitinated proteins and proteasome in a novel cytoplasmic structure. PLoS One. 2010;5:e9716. [PubMed] [DOI] |
| 46. | Neumann H, Vieth M, Siebler J, Bernatik T, Neurath MF, Boxberger F. Fluorescein-aided endomicroscopy for detection of signet ring cell carcinoma. Endoscopy. 2011;43 Suppl 2 UCTN:E199-E200. [PubMed] |
| 47. | Wang P, Ji R, Yu T, Zuo XL, Zhou CJ, Li CQ, Li Z, Li YQ. Classification of histological severity of Helicobacter pylori-associated gastritis by confocal laser endomicroscopy. World J Gastroenterol. 2010;16:5203-5210. [PubMed] [DOI] |
| 48. | Liu TW, Ho CW, Huang HH, Chang SM, Popat SD, Wang YT, Wu MS, Chen YJ, Lin CH. Role for alpha-L-fucosidase in the control of Helicobacter pylori-infected gastric cancer cells. Proc Natl Acad Sci U S A. 2009;106:14581-14586. [PubMed] [DOI] |
| 49. | Tang XL, Yang XY, Jung HJ, Kim SY, Jung SY, Choi DY, Park WC, Park H. Asiatic acid induces colon cancer cell growth inhibition and apoptosis through mitochondrial death cascade. Biol Pharm Bull. 2009;32:1399-1405. [PubMed] [DOI] |
| 50. | Wang F, Xia P, Wu F, Wang D, Wang W, Ward T, Liu Y, Aikhionbare F, Guo Z, Powell M. Helicobacter pylori VacA disrupts apical membrane-cytoskeletal interactions in gastric parietal cells. J Biol Chem. 2008;283:26714-26725. [PubMed] [DOI] |
| 51. | Lai CH, Chang YC, Du SY, Wang HJ, Kuo CH, Fang SH, Fu HW, Lin HH, Chiang AS, Wang WC. Cholesterol depletion reduces Helicobacter pylori CagA translocation and CagA-induced responses in AGS cells. Infect Immun. 2008;76:3293-3303. [PubMed] [DOI] |
| 52. | Xiao YF, Wu DD, Liu SX, Chen X, Ren LF. Effect of arsenic trioxide on vascular endothelial cell proliferation and expression of vascular endothelial growth factor receptors Flt-1 and KDR in gastric cancer in nude mice. World J Gastroenterol. 2007;13:6498-6505. [PubMed] [DOI] |