MicroRNA-2抑制肺癌细胞增殖、侵袭和转移的生物学作用研究
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摘要
微小RNA,即nicroRNA(miRNA),是由18到25个核苷酸组成的非编码、小分子单链RNA,具有较高的保守性,几乎所有的多细胞生物都可以表达。MicroRNA以完全或者部分互补结合的方式促进mRNA降解,影响mRNA翻译,对许多基因具有调控作用,在细胞的凋亡、分化及细胞增殖等细胞生物学过程中具有重要作用。近来有越来越多的研究发现,在一些肿瘤组织,特别是在肺癌组织中microRNA有过表达或者低表达的现象,并且找到不同肿瘤组织中的miRNAs表达谱。提示在肿瘤的发生发展过程中,microRNA可能发挥着重要的生物学作用。
我们在前期临床研究中发现microRNA-2可以预测小细胞肺癌患者治疗的临床疗效,与预后呈正相关。MicroRNA-2表达水平高的患者具有更好的总体生存率。生存分析表明microRNA-2是小细胞肺癌患者肿瘤复发和生存率的独立预后因子。
在本研究中,我们发现通过瞬时转染NCI-H446、NCI-H520、A549以及Anip973肺癌细胞,上调microRNA-2的表达可在体外抑制JNCI-H446、A549以及Anip973肺癌细胞的增殖、侵袭、迁移以及粘附能力。在进一步研究miRNA-2是如何发挥生物学功能的过程中,我们的实验发现miRNA-2能够直接调控PLK1和TGF β1的3'UTR区域,在转录水平影响PLK1和TGF β1的表达,使PLK1和TGF β1的mRNA表达水平下调。考虑到瞬时转染不能完全模拟体内miRNA的生成和加工过程,我们在NCI-H446细胞的基础上构建了miRNA-2持续稳定高表达的细胞系,验证持续稳定高表达miRNA-2对小细胞肺癌细胞系的增殖、侵袭以及迁移能力均有抑制作用,并且能够下调PLK1和’TGFβ1在mRNA和蛋白水平的表达。在miRNA-2引起肺癌细胞系迁移能力下降的机制研究中,我们发现主要是由于miRNA-2的高表达引起TGFβ1的表达下调后,抑制NCI-H446细胞的上皮间质转化,从而在肿瘤转移的初始阶段即抑制了其发生转移。我们运用稳定高表达miRNA-2的细胞系进行动物皮下移植瘤的实验发现,miRNA-2在体内仍能抑制肿瘤细胞增殖、侵袭以及转移能力。而且在高表达miRNA-2的细胞系皮下移植瘤实验中,免疫组化表明PLK1和TGF β1的表达下调。为了验证在临床小细胞肺癌患者中miRNA-2的表达是否也是通过对PLK1和TGFβ1的调节影响患者的生存预后,我们找到前期临床研究中miRNA高表达生存预后好以及miRNAf(?)表达生存预后差病例的病理标本,进行免疫组化检测PLK1,结果提示miRNA-2高表达预后好的病例PLK1低表达。证明人体外实验的结果在人体内可能也以同样的生物学机制发挥作用。
综上所述,本研究从临床人体标本中发现有预后和生存指示作用的niRNA-2,并在细胞水平和实验动物水平均阐明了miRNA-2发挥作用的生物学机制,再回到临床的人体标本中证实miRNA-2的靶基因,从而较完整的解释了miRNA-2生物学功能和它对肺癌患者预后影响的原因,为肺癌发生发展的机制研究提供更多研究思路和理论支持。
目的研究同一患者分前后两个阶段并在不同体位条件下完成总疗程的治疗中,将两阶段治疗计划相叠加后评价总疗程靶区和危及器官剂量的可行性和临床应用。方法回顾性分析小细胞肺癌的患者10例,每例患者在总疗程中采用不同体位重新定位一次,分两个阶段完成治疗,每个阶段分别制定三维适形计划,疗程总剂量为50Gy。均采用Cadplan R3.1.2三维治疗计划系统完成治疗计划的设计。通过治疗计划系统叠加每例患者总疗程中两个阶段的治疗计划,分析将两个阶段治疗计划叠加的可行性以及第一个阶段与第二阶段治疗计划相叠加后临床应用的可行性。结果1.前后两个阶段气管隆突在左右、前后以及头尾方向运动密切正相关(相关性检验P值均<0.05),证明以气管隆突做为两个阶段的治疗计划叠加标识的可行性；2.前后两个阶段靶区和危及器官体积变化显示除PTV2(计划靶区2)的体积变异大有统计学差异外,其余均无统计学差异,并且各危及器官的剂量学相关性分析中仅脊髓最大剂量在复制计划和原计划之间无相关性外(r=0.337,P=0.341),其余剂量参数均显示出密切正相关。结论运用三维治疗计划系统将同一患者两个阶段不同体位的治疗计划叠加时，在保证与叠加计划等中心点坐标密切相关的解剖结构在两个阶段空间位置一致,以及两个阶段的靶区和危及器官体积无明显差异的前提下；可以对体位不同的两个阶段的治疗计划进行叠加,并在临床上运用叠加计划总体评价全疗程中的靶区和危及器官剂量。
MicroRNAs (miRNAs) are evolutionarily conserved, endogenous, small, noncoding RNA molecules of about22nucleotides in length that are discovered in C.elegans about20years ago. MiRNAs spread wide in multicellular organisms and develop in a step-wise process through hairpin precursors cleaved by the dsRNA-specific endonucleases Drosha, Dicer and Argonaute. MiRNAs interact with target messenger RNA at specific sites to induce cleavage or inhibit translation. MiRNAs have been implicated in various important biological processes including embryogenesis, differentiation, organogenesis, cell cycle progression, apoptosis, stress response and metabolism. A number of investigations have demonstrated that altered expression of miRNAs are closely relevant to the clinical malignancies in both solid organs and hematological system, several miRNAs have been implicated in non-small cell lung carcinoma (NSCLC).
In previous clinical research, we examined the miRNA expression profiles in human small cell lung cancer(SCLC), and found that downregulation of miRNA-2expression was correlated with poor survival among patients with SCLC.Compared with the patients in low miRNA-2expression group, the patients in high expression group had longer overall survival.
NCI-H446, NCI-H520, A549and Anip973were transient transfected with chemically synthesized mature miRNA-2mimic oligonucleotides, introduction of miRNA-2clearly led to a significant decrease in proliferation, invasion and migration in NCI-H446A549and Anip973cell line. Analysis with TargetScan4.0indicates that there is a miRNA-2binding site in the3'UTR regions of the PLK1and TGF-β1.We also measured the mRNA and protein levels of these miRNA-2targeted genes and found that PLK1and TGF-β1expression were substantially reduced following the introduction of miRNA-2into the cells. We further investigated the suppressive role of miRNA-2in SCLC malignancy using animal model. The miRNA-2expression vector was stably transfected into NCI-H446cells and pooled clones were obtained. These pooled clones (NCI-H446-miRNA-2) expressed much higher levels of miRNA-2, exhibited slow-growing capabilities and reduced levels for PLK1and TGF-β1in both mRNA and protein expression. NCI-H446-miRNA-2and NCI-H446-control cells were implanted subcutaneously into the right upper back of nude mice, we measured the volumes of the implanted tumors weekly and found that expression of miR-886-3p significantly suppressed the growth of SCLC tumors in vivo. Interestingly, NCI-H446-miR-886-3p cells and NCI-H446-control cells differed dramatically in their invasive and metastatic potentials. In seeking the the mechanism of migration reduction in lung cancer cell lines, We found that miRNA-2expression downregulated of TGFβ1, which can inhibit epithelial mesenchymal transition in NCI-H446cells. To examine whether dysregulated expressions of miRNA-2targeted genes were linked to clinical outcome of SCLC. Totally,40SCLC specimens with known states of miRNA-2expression were analyzed for PLK1protein staining using an immunohistochemical approach. In the low miRNA-2expression group, strong cytoplasmic staining of PLK1. In contrast, among20samples from high miRNA-2expression group, all most all samples revealed weak or negative staining of PLK1. The difference of Plkl expression between two groups is statistically significant.
In this report, we choose miRNA-2which was correlated with survival among patients with SCLC. As to the molecular mechanism(s) by which miRNA-2exerts its role as tumor suppressor, we have shown that miRNA-2negatively regulates PLK.1and TGF-β1, which function in promoting cell proliferation, cell migration, tumor invasive growth and metastasis. Furthermore, we demonstrated that miRNA-2may act as a tumor-suppressor to inhibit SCLC cell proliferation, migration and invasion in both cell and animal models. Therefore, it is reasonably interpreted that during the malignant development of SCLC. The better understanding of SCLC biology would substantially improve the effective therapies available for this challenging disease and promote the development of novel therapeutic agents as well.
Objective To analyze the feasibility and the practicability of combining two-course treatment plans of one patient who was localized in different positions during two-course. Methods Ten patients with small cell lung cancer were chosen in the present study. According to the clinical requirement, all patients were localized twice with different positions in total course. Using the Cadplan R3.1.2treatment planning system, conformal planning was designed for each patient in two-course. Total radiation dose was50Gy.The reproductive plans can be applied to evaluate the dosimetric distribution to target volume and the surrounding organs at risk in the total course. Results1.The movements of carina in three-dimensional directions were closely correlated between two courses (P<0.05).2.No significant disparities in target volumes and normal tissue volumes were found except for the volume of PTV2. Except for maximum dose of spinal cord (r=0.337, P=0.341), positive correlations of dosimetric parameters were displayed between reproductive plans and original plans. Conclusions To assure the accuracy of isocenter's coordinate in combined treatment plans and the positive correlations of dosimetric parameters between reproductive plans and original plans, it is feasible and the practicable to combine two-course treatment plans of one patient who was localized in different position during two-course.
我们在前期临床研究中发现microRNA-2可以预测小细胞肺癌患者治疗的临床疗效,与预后呈正相关。MicroRNA-2表达水平高的患者具有更好的总体生存率。生存分析表明microRNA-2是小细胞肺癌患者肿瘤复发和生存率的独立预后因子。
在本研究中,我们发现通过瞬时转染NCI-H446、NCI-H520、A549以及Anip973肺癌细胞,上调microRNA-2的表达可在体外抑制JNCI-H446、A549以及Anip973肺癌细胞的增殖、侵袭、迁移以及粘附能力。在进一步研究miRNA-2是如何发挥生物学功能的过程中,我们的实验发现miRNA-2能够直接调控PLK1和TGF β1的3'UTR区域,在转录水平影响PLK1和TGF β1的表达,使PLK1和TGF β1的mRNA表达水平下调。考虑到瞬时转染不能完全模拟体内miRNA的生成和加工过程,我们在NCI-H446细胞的基础上构建了miRNA-2持续稳定高表达的细胞系,验证持续稳定高表达miRNA-2对小细胞肺癌细胞系的增殖、侵袭以及迁移能力均有抑制作用,并且能够下调PLK1和’TGFβ1在mRNA和蛋白水平的表达。在miRNA-2引起肺癌细胞系迁移能力下降的机制研究中,我们发现主要是由于miRNA-2的高表达引起TGFβ1的表达下调后,抑制NCI-H446细胞的上皮间质转化,从而在肿瘤转移的初始阶段即抑制了其发生转移。我们运用稳定高表达miRNA-2的细胞系进行动物皮下移植瘤的实验发现,miRNA-2在体内仍能抑制肿瘤细胞增殖、侵袭以及转移能力。而且在高表达miRNA-2的细胞系皮下移植瘤实验中,免疫组化表明PLK1和TGF β1的表达下调。为了验证在临床小细胞肺癌患者中miRNA-2的表达是否也是通过对PLK1和TGFβ1的调节影响患者的生存预后,我们找到前期临床研究中miRNA高表达生存预后好以及miRNAf(?)表达生存预后差病例的病理标本,进行免疫组化检测PLK1,结果提示miRNA-2高表达预后好的病例PLK1低表达。证明人体外实验的结果在人体内可能也以同样的生物学机制发挥作用。
综上所述,本研究从临床人体标本中发现有预后和生存指示作用的niRNA-2,并在细胞水平和实验动物水平均阐明了miRNA-2发挥作用的生物学机制,再回到临床的人体标本中证实miRNA-2的靶基因,从而较完整的解释了miRNA-2生物学功能和它对肺癌患者预后影响的原因,为肺癌发生发展的机制研究提供更多研究思路和理论支持。
目的研究同一患者分前后两个阶段并在不同体位条件下完成总疗程的治疗中,将两阶段治疗计划相叠加后评价总疗程靶区和危及器官剂量的可行性和临床应用。方法回顾性分析小细胞肺癌的患者10例,每例患者在总疗程中采用不同体位重新定位一次,分两个阶段完成治疗,每个阶段分别制定三维适形计划,疗程总剂量为50Gy。均采用Cadplan R3.1.2三维治疗计划系统完成治疗计划的设计。通过治疗计划系统叠加每例患者总疗程中两个阶段的治疗计划,分析将两个阶段治疗计划叠加的可行性以及第一个阶段与第二阶段治疗计划相叠加后临床应用的可行性。结果1.前后两个阶段气管隆突在左右、前后以及头尾方向运动密切正相关(相关性检验P值均<0.05),证明以气管隆突做为两个阶段的治疗计划叠加标识的可行性；2.前后两个阶段靶区和危及器官体积变化显示除PTV2(计划靶区2)的体积变异大有统计学差异外,其余均无统计学差异,并且各危及器官的剂量学相关性分析中仅脊髓最大剂量在复制计划和原计划之间无相关性外(r=0.337,P=0.341),其余剂量参数均显示出密切正相关。结论运用三维治疗计划系统将同一患者两个阶段不同体位的治疗计划叠加时，在保证与叠加计划等中心点坐标密切相关的解剖结构在两个阶段空间位置一致,以及两个阶段的靶区和危及器官体积无明显差异的前提下；可以对体位不同的两个阶段的治疗计划进行叠加,并在临床上运用叠加计划总体评价全疗程中的靶区和危及器官剂量。
MicroRNAs (miRNAs) are evolutionarily conserved, endogenous, small, noncoding RNA molecules of about22nucleotides in length that are discovered in C.elegans about20years ago. MiRNAs spread wide in multicellular organisms and develop in a step-wise process through hairpin precursors cleaved by the dsRNA-specific endonucleases Drosha, Dicer and Argonaute. MiRNAs interact with target messenger RNA at specific sites to induce cleavage or inhibit translation. MiRNAs have been implicated in various important biological processes including embryogenesis, differentiation, organogenesis, cell cycle progression, apoptosis, stress response and metabolism. A number of investigations have demonstrated that altered expression of miRNAs are closely relevant to the clinical malignancies in both solid organs and hematological system, several miRNAs have been implicated in non-small cell lung carcinoma (NSCLC).
In previous clinical research, we examined the miRNA expression profiles in human small cell lung cancer(SCLC), and found that downregulation of miRNA-2expression was correlated with poor survival among patients with SCLC.Compared with the patients in low miRNA-2expression group, the patients in high expression group had longer overall survival.
NCI-H446, NCI-H520, A549and Anip973were transient transfected with chemically synthesized mature miRNA-2mimic oligonucleotides, introduction of miRNA-2clearly led to a significant decrease in proliferation, invasion and migration in NCI-H446A549and Anip973cell line. Analysis with TargetScan4.0indicates that there is a miRNA-2binding site in the3'UTR regions of the PLK1and TGF-β1.We also measured the mRNA and protein levels of these miRNA-2targeted genes and found that PLK1and TGF-β1expression were substantially reduced following the introduction of miRNA-2into the cells. We further investigated the suppressive role of miRNA-2in SCLC malignancy using animal model. The miRNA-2expression vector was stably transfected into NCI-H446cells and pooled clones were obtained. These pooled clones (NCI-H446-miRNA-2) expressed much higher levels of miRNA-2, exhibited slow-growing capabilities and reduced levels for PLK1and TGF-β1in both mRNA and protein expression. NCI-H446-miRNA-2and NCI-H446-control cells were implanted subcutaneously into the right upper back of nude mice, we measured the volumes of the implanted tumors weekly and found that expression of miR-886-3p significantly suppressed the growth of SCLC tumors in vivo. Interestingly, NCI-H446-miR-886-3p cells and NCI-H446-control cells differed dramatically in their invasive and metastatic potentials. In seeking the the mechanism of migration reduction in lung cancer cell lines, We found that miRNA-2expression downregulated of TGFβ1, which can inhibit epithelial mesenchymal transition in NCI-H446cells. To examine whether dysregulated expressions of miRNA-2targeted genes were linked to clinical outcome of SCLC. Totally,40SCLC specimens with known states of miRNA-2expression were analyzed for PLK1protein staining using an immunohistochemical approach. In the low miRNA-2expression group, strong cytoplasmic staining of PLK1. In contrast, among20samples from high miRNA-2expression group, all most all samples revealed weak or negative staining of PLK1. The difference of Plkl expression between two groups is statistically significant.
In this report, we choose miRNA-2which was correlated with survival among patients with SCLC. As to the molecular mechanism(s) by which miRNA-2exerts its role as tumor suppressor, we have shown that miRNA-2negatively regulates PLK.1and TGF-β1, which function in promoting cell proliferation, cell migration, tumor invasive growth and metastasis. Furthermore, we demonstrated that miRNA-2may act as a tumor-suppressor to inhibit SCLC cell proliferation, migration and invasion in both cell and animal models. Therefore, it is reasonably interpreted that during the malignant development of SCLC. The better understanding of SCLC biology would substantially improve the effective therapies available for this challenging disease and promote the development of novel therapeutic agents as well.
Objective To analyze the feasibility and the practicability of combining two-course treatment plans of one patient who was localized in different positions during two-course. Methods Ten patients with small cell lung cancer were chosen in the present study. According to the clinical requirement, all patients were localized twice with different positions in total course. Using the Cadplan R3.1.2treatment planning system, conformal planning was designed for each patient in two-course. Total radiation dose was50Gy.The reproductive plans can be applied to evaluate the dosimetric distribution to target volume and the surrounding organs at risk in the total course. Results1.The movements of carina in three-dimensional directions were closely correlated between two courses (P<0.05).2.No significant disparities in target volumes and normal tissue volumes were found except for the volume of PTV2. Except for maximum dose of spinal cord (r=0.337, P=0.341), positive correlations of dosimetric parameters were displayed between reproductive plans and original plans. Conclusions To assure the accuracy of isocenter's coordinate in combined treatment plans and the positive correlations of dosimetric parameters between reproductive plans and original plans, it is feasible and the practicable to combine two-course treatment plans of one patient who was localized in different position during two-course.
引文
Al-Mehdi, A. B., K. Tozawa, et al. (2000). "Intravascular origin of metastasis from the proliferation of endothelium-attached tumor cells:a new model for metastasis." Nat Med 6(1):100-102.
Asangani, I. A., S. A. Rasheed, et al. (2008). "MicroRNA-21 (miR-21) post-transcriptionally downregulates tumor suppressor Pdcd4 and stimulates invasion, intravasation and metastasis in colorectal cancer." Oncogene 27(15): 2128-2136.
Bartel, D. P. (2004). "MicroRNAs:genomics, biogenesis, mechanism, and function." Cell 116(2):281-297.
Calin, G. A. and C. M. Croce (2006). "MicroRNA signatures in human cancers." Nature Reviews Cancer 6:857-866.
Calin, G. A., C. D. Dumitru, et al. (2002). "Frequent deletions and down-regulation of micro-RNA genes miR15 and miR16 at 13q14 in chronic lymphocytic leukemia." Proc Natl Acad Sci U S A 99(24):15524-15529.
Calin, G. A., M. Ferracin, et al. (2005). "A MicroRNA signature associated with prognosis and progression in chronic lymphocytic leukemia." N Engl J Med 353(17):1793-1801.
Calin, G. A., C. Sevignani, et al. (2004). "Human microRNA genes are frequently located at fragile sites and genomic regions involved in cancers." Proc Natl Acad Sci U S A 101(9):2999-3004.
Cameron, D. A., W. M. Gregory, et al. (2000). "Identification of long-term survivors in primary breast cancer by dynamic modelling of tumour response." Br J Cancer 83(1):98-103.
Chambers, A. F., A. C. Groom, et al. (2002). "Dissemination and growth of cancer cells in metastatic sites." Nat Rev Cancer 2(8):563-572.
Chang, J., E. Nicolas, et al. (2004). "miR-122, a mammalian liver-specific microRNA, is processed from her mRNA and may downregulate the high affinity cationic amino acid transporter CAT-1." RNA Biol 1(2):106-113.
Ciafre, S. A., S. Galardi, et al. (2005). "Extensive modulation of a set of microRNAs in primary glioblastoma." Biochem Biophys Res Commun 334(4): 1351-1358.
Consortium, E. P., E. Birney, et al. (2007). "Identification and analysis of functional elements in 1% of the human genome by the ENCODE pilot project." Nature 447(7146):799-816.
Crivellari, G., S. Monfardini, et al. (2007). "Increasing chemotherapy in small-cell lung cancer:from dose intensity and density to megadoses." Oncologist 12(1):79-89.
Dews, M., A. Homayouni, et al. (2006). "Augmentation of tumor angiogenesis by a Myc-activated microRNA cluster." Nat Genet 38(9): 1060-1065.
Duan, R., C. Pak, et al. (2007). "Single nucleotide polymorphism associated with mature miR-125a alters the processing of pri-miRNA." Hum Mol Genet 16(9):1124-1131.
Eis, P. S., W. Tam, et al. (2005). "Accumulation of miR-155 and BIC RNA in human B cell lymphomas." Proc Natl Acad Sci U S A 102(10):3627-3632.
Elias, A. D. (1997). "Small cell lung cancer:state-of-the-art therapy in 1996." Chest 112(4 Suppl):251S-258S.
Endoh, H., S. Tomida, et al. (2004). "Prognostic model of pulmonary adenocarcinoma by expression profiling of eight genes as determined by quantitative real-time reverse transcriptase polymerase chain reaction." J Clin Oncol 22(5):811-819.
Esau, C., S. Davis, et al. (2006). "miR-122 regulation of lipid metabolism revealed by in vivo antisense targeting." Cell Metab 3(2):87-98.
Fidler, I. J. (2002). "The organ microenvironment and cancer metastasis." Differentiation 70(9-10):498-505.
Fidler, I. J. (2003). "The pathogenesis of cancer metastasis:the 'seed and soil' hypothesis revisited." Nat Rev Cancer 3(6):453-458.
Gramantieri, L., M. Ferracin, et al. (2007). "Cyclin G1 is a target of miR-122a, a microRNA frequently down-regulated in human hepatocellular carcinoma." Cancer Res 67(13):6092-6099.
Grimson, A., K. K. Farh, et al. (2007). "MicroRNA targeting specificity in mammals:determinants beyond seed pairing." Mol Cell 27(1):91-105.
Guaita, S., I. Puig, et al. (2002). "Snail induction of epithelial to mesenchymal transition in tumor cells is accompanied by MUC1 repression and ZEB1 expression." J Biol Chem 277(42):39209-39216.
Gupta, P. B., T. T. Onder, et al. (2009). "Identification of selective inhibitors of cancer stem cells by high-throughput screening." Cell 138(4):645-659.
Hader, C., A. Marlier, et al. (2010). "Mesenchymal-epithelial transition in epithelial response to injury:the role of Foxc2." Oncogene 29(7):1031-1040.
Harris, T. A., M. Yamakuchi, et al. (2008). "MicroRNA-126 regulates endothelial expression of vascular cell adhesion molecule 1." Proc Natl Acad Sci U S A 105(5):1516-1521.
Hayashita, Y., H. Osada, et al. (2005). "A polycistronic microRNA cluster, miR-17-92, is overexpressed in human lung cancers and enhances cell proliferation." Cancer Res 65(21):9628-9632.
He, H., K. Jazdzewski, et al. (2005). "The role of microRNA genes in papillary thyroid carcinoma." Proc Natl Acad Sci U S A 102(52):19075-19080.
Iorio, M. V., P. Casalini, et al. (2009). "microRNA-205 regulates HER3 in human breast cancer." Cancer Res 69(6):2195-2200.
Iorio, M. V., M. Ferracin, et al. (2005). "MicroRNA gene expression deregulation in human breast cancer." Cancer Res 65(16):7065-7070.
Jemal, A., R. Siegel, et al. (2010). "Cancer statistics,2010." CA Cancer J Clin 60(5):277-300.
Kang, Y. and J. Massague (2004). "Epithelial-mesenchymal transitions:twist in development and metastasis." Cell 118(3):277-279.
Karube, Y., H. Tanaka, et al. (2005). "Reduced expression of Dicer associated with poor prognosis in lung cancer patients." Cancer Sci 96(2): 111-115.
Kim, D. H., M. A. Behlke, et al. (2005). "Synthetic dsRNA Dicer substrates enhance RNAi potency and efficacy." Nat Biotechnol 23(2):222-226.
Kluiver, J., S. Poppema, et al. (2005). "BIC and miR-155 are highly expressed in Hodgkin, primary mediastinal and diffuse large B cell lymphomas." J Pathol 207(2):243-249.
Lee, I., S. S. Ajay, et al. (2008). "Discriminating single-base difference miRNA expressions using microarray Probe Design Guru (ProDeG)." Nucleic Acids Res 36(5):e27.
Lee, R. C., R. L. Feinbaum, et al. (1993). "The C. elegans heterochronic gene lin-4 encodes small RNAs with antisense complementarity to lin-14." Cell 75(5):843-854.
Lee, Y., C. Ahn, et al. (2003). "The nuclear RNase Ⅲ Drosha initiates microRNA processing." Nature 425(6956):415-419.
Lewis, B. P., C. B. Burge, et al. (2005). "Conserved seed pairing, often flanked by adenosines, indicates that thousands of human genes are microRNA targets." Cell 120(1):15-20.
Lin, C. J., H. Y. Gong, et al. (2008). "miR-122 targets an anti-apoptotic gene, Bcl-w, in human hepatocellular carcinoma cell lines." Biochem Biophys Res Commun 375(3):315-320.
Liu, B., J. Li, et al. (2009). "Exploring complex miRNA-mRNA interactions with Bayesian networks by splitting-averaging strategy." Bmc Bioinformatics 10: 408.
Lu, J., G. Getz, et al. (2005). "MicroRNA expression profiles classify human cancers." Nature 435(7043):834-838.
Lund, E., S. Guttinger, et al. (2004). "Nuclear export of microRNA precursors." Science 303(5654):95-98.
Ma, L., J. Teruya-Feldstein, et al. (2007). "Tumour invasion and metastasis initiated by microRNA-10b in breast cancer." Nature 449(7163):682-688.
Ma, L. and R. A. Weinberg (2008). "Micromanagers of malignancy:role of micro RNAs in regulating metastasis." Trends Genet 24(9):448-456.
Markou, A., E. G. Tsaroucha, et al. (2008). "Prognostic value of mature microRNA-21 and microRNA-205 overexpression in non-small cell lung cancer by quantitative real-time RT-PCR." Clin Chem 54(10):1696-1704.
Michael, M. Z., O. C. SM, et al. (2003). "Reduced accumulation of specific microRNAs in colorectal neoplasia." Mol Cancer Res 1(12):882-891.
Michalak, P. (2006). "RNA world-the dark matter of evolutionary genomics." J Evol Biol 19(6):1768-1774.
Morita, T. (1990). "[Chronological changes of lung sarcoma and lung cancer incidence based on the annual of the pathological autopsy cases in Japan (1958-1986)1." Nihon Kyobu Shikkan Gakkai Zasshi 28(1):126-134.
Murakami, Y., T. Yasuda, et al. (2006). "Comprehensive analysis of microRNA expression patterns in hepatocellular carcinoma and non-tumorous tissues." Oncogene 25(17):2537-2545.
O'Donnell, K. A., E. A. Wentzel, et al. (2005). "c-Myc-regulated microRNAs modulate E2F1 expression." Nature 435(7043):839-843.
Ota, A., H. Tagawa, et al. (2004). "Identification and characterization of a novel gene, C13orf25, as a target for 13q31-q32 amplification in malignant lymphoma." Cancer Res 64(9):3087-3095.
Parkin, D. M. and S. M. Moss (2000). "Lung cancer screening:improved survival but no reduction in deaths--the role of "overdiagnosis"." Cancer 89(11 Suppl):2369-2376.
Pisani, P., D. M. Parkin, et al. (1999). "Erratum:Estimates of the worldwide mortality from 25 cancers in 1990. Int. J. Cancer,83,18-29 (1999)." Int J Cancer 83(6):870-873.
Polyak, K. and R. A. Weinberg (2009). "Transitions between epithelial and mesenchymal states:acquisition of malignant and stem cell traits." Nat Rev Cancer 9(4):265-273.
Potti, A. and A. K. Ganti (2006). "Adjuvant chemotherapy for early-stage non-small cell lung cancer:the past, the present and the future." Expert Opin Biol Ther 6(7):709-716.
Prasad, C. P., S. Mirza, et al. (2008). "Epigenetic alterations of CDH1 and APC genes:relationship with activation of Wnt/beta-catenin pathway in invasive ductal carcinoma of breast." Life Sci 83(9-10):318-325.
Saito, Y., G. Liang, et al. (2006). "Specific activation of microRNA-127 with downregulation of the proto-oncogene BCL6 by chromatin-modifying drugs in human cancer cells." Cancer Cell 9(6):435-443.
Sandler, A. B. (2003). "Chemotherapy for small cell lung cancer." Semin Oncol 30(1):9-25.
Seifter, E. J. and D. C. Ihde (1988). "Therapy of small cell lung cancer:a perspective on two decades of clinical research." Semin Oncol 15(3):278-299.
Shackel, N. A., P. H. McGuinness, et al. (2002). "Insights into the pathobiology of hepatitis C virus-associated cirrhosis:analysis of intrahepatic differential gene expression." Am J Pathol 160(2):641-654.
Spaderna, S., O. Schmalhofer, et al. (2008). "The transcriptional repressor ZEB1 promotes metastasis and loss of cell polarity in cancer." Cancer Res 68(2): 537-544.
Takakura, S., N. Mitsutake, et al. (2008). "Oncogenic role of miR-17-92 cluster in anaplastic thyroid cancer cells." Cancer Sci 99(6):1147-1154.
Takamizawa, J., H. Konishi, et al. (2004). "Reduced expression of the let-7 microRNAs in human lung cancers in association with shortened postoperative survival." Cancer Res 64(11):3753-3756.
Tavazoie, S. F., C. Alarcon, et al. (2008). "Endogenous human microRNAs that suppress breast cancer metastasis." Nature 451(7175):147-152.
Thiery, J. P. (2002). "Epithelial-mesenchymal transitions in tumour progression." Nat Rev Cancer 2(6):442-454.
Tsai, W. C., P. W. Hsu, et al. (2009). "MicroRNA-122, a tumor suppressor microRNA that regulates intrahepatic metastasis of hepatocellular carcinoma." Hepatology 49(5):1571-1582.
Vandewalle, C., J. Comijn, et al. (2005). "SIP1/ZEB2 induces EMT by repressing genes of different epithelial cell-cell junctions." Nucleic Acids Res 33(20):6566-6578.
Volinia, S., G. A. Calin, et al. (2006). "A microRNA expression signature of human solid tumors defines cancer gene targets." Proc Natl Acad Sci U S A 103(7):2257-2261.
Voorhoeve, P. M., C. le Sage, et al. (2006). "A genetic screen implicates miRNA-372 and miRNA-373 as oncogenes in testicular germ cell tumors." Cell 124(6):1169-1181.
Wang, Z., Y. Li, et al. (2010). "The role of Notch signaling pathway in epithelial-mesenchymal transition (EMT) during development and tumor aggressiveness." Curr Drug Targets 11(6):745-751.
Wu, W., M. Sun, et al. (2007). "MicroRNA and cancer:Current status and prospective." Int J Cancer 120(5):953-960.
Wu, Y., J. Deng, et al. (2009). "Stabilization of snail by NF-kappaB is required for inflammation-induced cell migration and invasion." Cancer Cell 15(5):416-428.
Xu, J., S. Lamouille, et al. (2009). "TGF-beta-induced epithelial to mesenchymal transition." Cell Res 19(2):156-172.
Yan, L. X., X. F. Huang, et al. (2008). "MicroRNA miR-21 overexpression in human breast cancer is associated with advanced clinical stage, lymph node metastasis and patient poor prognosis." RNA 14(11):2348-2360.
Yanaihara, N., N. Caplen, et al. (2006). "Unique microRNA molecular profiles in lung cancer diagnosis and prognosis." Cancer Cell 9(3):189-198.
Yu, X., J. Lin, et al. (2008). "Analysis of regulatory network topology reveals functionally distinct classes of microRNAs." Nucleic Acids Res 36(20): 6494-6503.
Zhang, J., Y. Y. Du, et al. (2008). "The cell growth suppressor, mir-126, targets IRS-1." Biochem Biophys Res Commun 377(1):136-140.
Giraud P, Elles S, Helfre S et al. (2002). "Conformal radiotherapy for lung cancer:different delineation of the gross tumor volume (GTV) by radiologists and radiation oncologists. "Radiother & Oncol 62 (1):27-36.
Hristov, D., L. Liu, et al. (2011). "Technique for targeting arteriovenous malformations using frameless image-guided robotic radiosurgery." Int J Radiat Oncol Biol Phys 79(4): 1232-1240.
Jeffrey A. Bogart. James E. Herndon Ⅱ, et al. (2004). "70Gy Thoracic radiotherapy is feasible concurrent with chemotherapy for limited-stage small cell lung cancer:Analysis of Cancer and Leukemia Group B Study 39808." Int. J. Radiat. Oncol. Biol.Phys 59(2):460-468.
Jenkens P, Salemon C, Mannion C. (2005). "Analysis of the movement of calcified lymph nodes during breathing. " Int. J. Radiat. Oncol. Biol.Phys 61 (2):329-334.
Madu N, Douglas J,Daniel P, et al. (2002). "Definition of superaclavicular nodes: Implications for three-dimensional CT-based conformal radiation therapy. " Radiology 221(2):333-339.
Noblet, V., C. Heinrich, et al. (2006). "Retrospective evaluation of a topology preserving non-rigid registration method." Med Image Anal 10(3):366-384
Osareh, A. and B. Shadgar (2010). "A segmentation method of lung cavities using region aided geometric snakes." J Med Syst 34(4):419-433.
Pevsner, A., B. Davis, et al. (2006). "Evaluation of an automated deformable image matching method for quantifying lung motion in respiration-correlated CT images." Med Phys 33(2):369-376.
Uno T, Sumi M, Ishihara Y, et al. (2008). "Changes in patterns of care for limited-stage small-cell lung cancer:results of the 99-01 patterns of care study-a nationwide survey in Japan. "Int J Radiat Oncol Biol Phys 71(2):414-419.
van Loon J, Offermann C, Bosmans G, et al. (2008). "18FDG-PET based radiation planning of mediastinal lymph nodes in limited disease small cell lung cancer changes radiotherapy fields: a planning study. " Radiother Oncol 87(1):49-54.
卢洁,李建彬,尹勇等.(2008).”两种方法评估肺癌患者三维适形放疗重复计划肺总体受照剂量体积效果比较.”山东医药48(27)97-99.
沈捷,张福泉,邱杰等.(2006).”应用EPID对放射治疗摆位误差的研究.”中华放射医学与防护杂志26(3)：308.
吴开良,蒋国梁,廖源等.(2002).”肺癌不同放射治疗技术剂量学比较.”中华放射胜瘤堂杂志11(4)：231-234.
殷蔚伯,余子豪,徐国镇等主编.(2008).肿瘤放射治疗学(第四版).中国协和医科大学. 出版社第二篇,第三章：87-95.
云惟康,胡洪涛,徐向英等.(2009).”利用影像融合技术评估肺癌放射治疗全疗程剂量体积直方图”.实用肿瘤学杂志23(5)：441-443.
张金忠,戈伟,张园如等.(2011).”CT/CT图像融合用于非小细胞肺癌放射治疗对V20及放射性肺炎影响的临床研究”.临床肿瘤堂杂志16(2)：154-157.
朱慧,王绿化.(2011).”放射治疗对小细胞肺癌预后的影响.”中华肿瘤防治杂查17(24)：2070-2074.
Bartel, D. P. (2004). "MicroRNAs:genomics, biogenesis, mechanism, and function." Cell 116(2):281-297.
Bartel, D. P. (2009). "MicroRNAs:target recognition and regulatory functions." Cell 136(2):215-233.
Batlle, E., E. Sancho, et al. (2000). "The transcription factor snail is a repressor of E-cadherin gene expression in epithelial tumour cells." Nat Cell Biol 2(2):84-89.
Bolos, V., H. Peinado, et al. (2003). "The transcription factor Slug represses E-cadherin expression and induces epithelial to mesenchymal transitions:a comparison with Snail and E47 repressors." J Cell Sci 116(Pt 3):499-511.
Bonnomet, A., A. Brysse, et al. (2010). "Epithelial-to-mesenchymal transitions and circulating tumor cells." J Mammary Gland Biol Neoplasia 15(2):261-273.
Bracken, C. P., P. A. Gregory, et al. (2008). "A double-negative feedback loop between ZEB1-SIP1 and the microRNA-200 family regulates epithelial-mesenchymal transition." Cancer Res 68(19):7846-7854.
Braun, J., C. Hoang-Vu, et al. (2010). "Downregulation of microRNAs directs the EMT and invasive potential of anaplastic thyroid carcinomas." Oncogene 29(29):4237-4244.
Burk, U., J. Schubert, et al. (2008). "A reciprocal repression between ZEB1 and members of the miR-200 family promotes EMT and invasion in cancer cells." EMBO Rep 9(6):582-589.
Calin, G. A. and C. M. Croce (2006). "MicroRNA signatures in human cancers." Nature Reviews Cancer 6:857-866.
Carmona-Fontaine, C., H. K. Matthews, et al. (2008). "Contact inhibition of locomotion in vivo controls neural crest directional migration." Nature 456(7224):957-961.
Christoffersen, N. R., A. Silahtaroglu, et al. (2007). "miR-200b mediates post-transcriptional repression of ZFHX1B." RNA 13(8):1172-1178.
Comijn, J., G. Berx, et al. (2001). "The two-handed E box binding zinc finger protein SIP1 downregulates E-cadherin and induces invasion." Mol Cell 7(6):1267-1278.
Du, J., S. Yang, et al. (2009). "BMP-6 inhibits microRNA-21 expression in breast cancer through repressing deltaEF1 and AP-1." Cell Res 19(4):487-496.
Fujita, S., T. Ito, et al. (2008). "miR-21 Gene expression triggered by AP-1 is sustained through a double-negative feedback mechanism." J Mol Biol 378(3):492-504.
Gregory, P. A., A. G. Bert, et al. (2008). "The miR-200 family and miR-205 regulate epithelial to mesenchymal transition by targeting ZEB1 and SDP1." Nat Cell Biol 10(5): 593-601.
Guaita, S., I. Puig, et al. (2002). "Snail induction of epithelial to mesenchymal transition in tumor cells is accompanied by MUC1 repression and ZEB1 expression." J Biol Chem 277(42):39209-39216.
Gupta, G. P. and J. Massague (2006). "Cancer metastasis:building a framework." Cell 127(4):679-695.
Gupta, P. B., T. T. Onder, et al. (2009). "Identification of selective inhibitors of cancer stem cells by high-throughput screening." Cell 138(4):645-659.
Hader, C., A. Marlier, et al. (2010). "Mesenchymal-epithelial transition in epithelial response to injury:the role of Foxc2." Oncogene 29(7):1031-1040.
Hartwell, K. A., B. Muir, et al. (2006). "The Spemann organizer gene, Goosecoid, promotes tumor metastasis." Proc Natl Acad Sci U S A 103(50):18969-18974.
Hazan, R. B., R. Qiao, et al. (2004). "Cadherin switch in tumor progression." Ann N Y Acad Sci 1014:155-163.
Huber, M. A., N. Kraut, et al. (2005). "Molecular requirements for epithelial-mesenchymal transition during tumor progression." Curr Opin Cell Biol 17(5): 548-558.
Hurteau, G. J., J. A. Carlson, et al. (2007). "Overexpression of the microRNA hsa-miR-200c leads to reduced expression of transcription factor 8 and increased expression of E-cadherin." Cancer Res 67(17):7972-7976.
Iorio, M. V., M. Ferracin, et al. (2005). "MicroRNA gene expression deregulation in human breast cancer." Cancer Res 65(16):7065-7070.
Kalluri, R. and E. G. Neilson (2003). "Epithelial-mesenchymal transition and its implications for fibrosis." J Clin Invest 112(12):1776-1784.
Kalluri, R. and R. A. Weinberg (2009). "The basics of epithelial-mesenchymal transition." J Clin Invest 119(6):1420-1428.
Kang, Y. and J. Massague (2004). "Epithelial-mesenchymal transitions:twist in development and metastasis." Cell 118(3):277-279.
Karolchik, D., R. Baertsch, et al. (2003). "The UCSC Genome Browser Database." Nucleic Acids Res 31(1):51-54.
Kong, W., H. Yang, et al. (2008). "MicroRNA-155 is regulated by the transforming growth factor beta/Smad pathway and contributes to epithelial cell plasticity by targeting RhoA." Mol Cell Biol 28(22):6773-6784.
Korpal, M., E. S. Lee, et al. (2008). "The miR-200 family inhibits epithelial-mesenchymal transition and cancer cell migration by direct targeting of E-cadherin transcriptional repressors ZEB1 and ZEB2." J Biol Chem 283(22):14910-14914.
Krutzfeldt, J., N. Rajewsky, et al. (2005). "Silencing of microRNAs in vivo with 'antagomirs'." Nature 438(7068):685-689.
Lamouille, S. and R. Derynck (2007). "Cell size and invasion in TGF-beta-induced epithelial to mesenchymal transition is regulated by activation of the mTOR pathway." JCell Biol 178(3):437-451.
Le, X. F., O. Merchant, et al. (2010). "The Roles of MicroRNAs in the Cancer Invasion-Metastasis Cascade." Cancer Microenviron 3(1):137-147.
Lee, E. J., M. Baek, et al. (2008). "Systematic evaluation of microRNA processing patterns in tissues, cell lines, and tumors." RNA 14(1):35-42.
Lee, Y. S., K. Nakahara, et al. (2004). "Distinct roles for Drosophila Dicer-1 and Dicer-2 in the siRNA/miRNA silencing pathways." Cell 117(1):69-81.
Lu, J., G. Getz, et al. (2005). "MicroRNA expression profiles classify human cancers." Nature 435(7043):834-838.
Lund, E., S. Guttinger, et al. (2004). "Nuclear export of microRNA precursors." Science 303(5654):95-98.
Ma, L., J. Young, et al. (2010). "miR-9, a MYC/MYCN-activated microRNA, regulates E-cadherin and cancer metastasis." Nat Cell Biol 12(3):247-256.
Maeda, M., K. R. Johnson, et al. (2005). "Cadherin switching:essential for behavioral but not morphological changes during an epithelium-to-mesenchyme transition." J Cell Sci 118(Pt 5):873-887.
Mani, S. A., W. Guo, et al. (2008). "The epithelial-mesenchymal transition generates cells with properties of stem cells." Cell 133(4):704-715.
Nicoloso, M. S., R. Spizzo, et al. (2009). "MicroRNAs-the micro steering wheel of tumour metastases." Nat Rev Cancer 9(4):293-302.
Park, S. M., A. B. Gaur, et al. (2008). "The miR-200 family determines the epithelial phenotype of cancer cells by targeting the E-cadherin repressors ZEB1 and ZEB2." Genes Dev 22(7):894-907.
Polyak, K. and R. A. Weinberg (2009). "Transitions between epithelial and mesenchymal states:acquisition of malignant and stem cell traits." Nat Rev Cancer 9(4): 265-273.
Postigo, A. A. and D. C. Dean (1997). "ZEB, a vertebrate homolog of Drosophila Zfh-1, is a negative regulator of muscle differentiation." EMBO J 16(13):3935r3943.
Prasad, C. P., S. Mirza, et al. (2008). "Epigenetic alterations of CDH1 and APC genes: relationship with activation of Wnt/beta-catenin pathway in invasive ductal carcinoma of breast." Life Sci 83(9-10):318-325.
Roldo, C., E. Missiaglia, et al. (2006). "MicroRNA expression abnormalities in pancreatic endocrine and acinar tumors are associated with distinctive pathologic features and clinical behavior." J Clin Oncol 24(29):4677-4684.
Saini, H. K., S. Griffiths-Jones, et al. (2007). "Genomic analysis of human microRNA transcripts." Proc Natl Acad Sci U S A 104(45):17719-17724.
Savagner, P. (2001). "Leaving the neighborhood:molecular mechanisms involved during epithelial-mesenchymal transition." Bioessays 23(10):912-923.
Savagner, P. (2010). "The epithelial-mesenchymal transition (EMT) phenomenon." Ann Oncol 21 Suppl 7:vii89-92.
Shimono, Y., M. Zabala, et al. (2009). "Downregulation of miRNA-200c links breast cancer stem cells with normal stem cells." Cell 138(3):592-603.
Spaderna, S., O. Schmalhofer, et al. (2008). "The transcriptional repressor ZEB1 promotes metastasis and loss of cell polarity in cancer." Cancer Res 68(2):537-544.
Thiery, J. P. (2002). "Epithelial-mesenchymal transitions in tumour progression." Nat Rev Cancer 2(6):442-454.
Thiery, J. P. and J. P. Sleeman (2006). "Complex networks orchestrate epithelial-mesenchymal transitions." Nat Rev Mol Cell Biol 7(2):131-142.
Thompson, E. W., D. F. Newgreen, et al. (2005). "Carcinoma invasion and metastasis:a role for epithelial-mesenchymal transition?" Cancer Res 65(14):5991-5995; discussion 5995.
Vandewalle, C., J. Comijn, et al. (2005). "SIP1/ZEB2 induces EMT by repressing genes of different epithelial cell-cell junctions." Nucleic Acids Res 33(20):6566-6578.
Vetter, G., A. Saumet, et al. (2010). "miR-661 expression in SNAI1-induced epithelial to mesenchymal transition contributes to breast cancer cell invasion by targeting Nectin-1 and StarD10 messengers." Oncogene 29(31):4436-4448.
Wang, Z., Y. Li, et al. (2010). "The role of Notch signaling pathway in epithelial-mesenchymal transition (EMT) during development and tumor aggressiveness." Curr Drug Targets 11(6):745-751.
Wienholds, E., M. J. Koudijs, et al. (2003). "The microRNA-producing enzyme Dicerl is essential for zebrafish development." Nat Genet 35(3):217-218.
Wu, Y., J. Deng, et al. (2009). "Stabilization of snail by NF-kappaB is required for inflammation-induced cell migration and invasion." Cancer Cell 15(5):416-428.
Xia, H., S. S. Ng, et al. (2010). "miR-200a-mediated downregulation of ZEB2 and CTNNB1 differentially inhibits nasopharyngeal carcinoma cell growth, migration and invasion." Biochem Biophys Res Commun 391(1):535-541.
Xu, J., S. Lamouille, et al. (2009). "TGF-beta-induced epithelial to mesenchymal transition." Cell Res 19(2):156-172.
Yang, H., W. Kong, et al. (2008). "MicroRNA expression profiling in human ovarian cancer:miR-214 induces cell survival and cisplatin resistance by targeting PTEN." Cancer Res 68(2):425-433.
Yang, J., S. A. Mani, et al. (2004). "Twist, a master regulator of morphogenesis, plays an essential role in tumor metastasis." Cell 117(7):927-939.
Yi, R., D. O'Carroll, et al. (2006). "Morphogenesis in skin is governed by discrete sets of differentially expressed microRNAs." Nat Genet 38(3):356-362.
Zavadil, J., M. Narasimhan, et al. (2007). "Transforming growth factor-beta and microRNA:mRNA regulatory networks in epithelial plasticity." Cells Tissues Organs 185(1-3):157-161.
Zeisberg, M. and E. G. Neilson (2009). "Biomarkers for epithelial-mesenchymal transitions." J Clin Invest 119(6):1429-1437.
Asangani, I. A., S. A. Rasheed, et al. (2008). "MicroRNA-21 (miR-21) post-transcriptionally downregulates tumor suppressor Pdcd4 and stimulates invasion, intravasation and metastasis in colorectal cancer." Oncogene 27(15): 2128-2136.
Bartel, D. P. (2004). "MicroRNAs:genomics, biogenesis, mechanism, and function." Cell 116(2):281-297.
Calin, G. A. and C. M. Croce (2006). "MicroRNA signatures in human cancers." Nature Reviews Cancer 6:857-866.
Calin, G. A., C. D. Dumitru, et al. (2002). "Frequent deletions and down-regulation of micro-RNA genes miR15 and miR16 at 13q14 in chronic lymphocytic leukemia." Proc Natl Acad Sci U S A 99(24):15524-15529.
Calin, G. A., M. Ferracin, et al. (2005). "A MicroRNA signature associated with prognosis and progression in chronic lymphocytic leukemia." N Engl J Med 353(17):1793-1801.
Calin, G. A., C. Sevignani, et al. (2004). "Human microRNA genes are frequently located at fragile sites and genomic regions involved in cancers." Proc Natl Acad Sci U S A 101(9):2999-3004.
Cameron, D. A., W. M. Gregory, et al. (2000). "Identification of long-term survivors in primary breast cancer by dynamic modelling of tumour response." Br J Cancer 83(1):98-103.
Chambers, A. F., A. C. Groom, et al. (2002). "Dissemination and growth of cancer cells in metastatic sites." Nat Rev Cancer 2(8):563-572.
Chang, J., E. Nicolas, et al. (2004). "miR-122, a mammalian liver-specific microRNA, is processed from her mRNA and may downregulate the high affinity cationic amino acid transporter CAT-1." RNA Biol 1(2):106-113.
Ciafre, S. A., S. Galardi, et al. (2005). "Extensive modulation of a set of microRNAs in primary glioblastoma." Biochem Biophys Res Commun 334(4): 1351-1358.
Consortium, E. P., E. Birney, et al. (2007). "Identification and analysis of functional elements in 1% of the human genome by the ENCODE pilot project." Nature 447(7146):799-816.
Crivellari, G., S. Monfardini, et al. (2007). "Increasing chemotherapy in small-cell lung cancer:from dose intensity and density to megadoses." Oncologist 12(1):79-89.
Dews, M., A. Homayouni, et al. (2006). "Augmentation of tumor angiogenesis by a Myc-activated microRNA cluster." Nat Genet 38(9): 1060-1065.
Duan, R., C. Pak, et al. (2007). "Single nucleotide polymorphism associated with mature miR-125a alters the processing of pri-miRNA." Hum Mol Genet 16(9):1124-1131.
Eis, P. S., W. Tam, et al. (2005). "Accumulation of miR-155 and BIC RNA in human B cell lymphomas." Proc Natl Acad Sci U S A 102(10):3627-3632.
Elias, A. D. (1997). "Small cell lung cancer:state-of-the-art therapy in 1996." Chest 112(4 Suppl):251S-258S.
Endoh, H., S. Tomida, et al. (2004). "Prognostic model of pulmonary adenocarcinoma by expression profiling of eight genes as determined by quantitative real-time reverse transcriptase polymerase chain reaction." J Clin Oncol 22(5):811-819.
Esau, C., S. Davis, et al. (2006). "miR-122 regulation of lipid metabolism revealed by in vivo antisense targeting." Cell Metab 3(2):87-98.
Fidler, I. J. (2002). "The organ microenvironment and cancer metastasis." Differentiation 70(9-10):498-505.
Fidler, I. J. (2003). "The pathogenesis of cancer metastasis:the 'seed and soil' hypothesis revisited." Nat Rev Cancer 3(6):453-458.
Gramantieri, L., M. Ferracin, et al. (2007). "Cyclin G1 is a target of miR-122a, a microRNA frequently down-regulated in human hepatocellular carcinoma." Cancer Res 67(13):6092-6099.
Grimson, A., K. K. Farh, et al. (2007). "MicroRNA targeting specificity in mammals:determinants beyond seed pairing." Mol Cell 27(1):91-105.
Guaita, S., I. Puig, et al. (2002). "Snail induction of epithelial to mesenchymal transition in tumor cells is accompanied by MUC1 repression and ZEB1 expression." J Biol Chem 277(42):39209-39216.
Gupta, P. B., T. T. Onder, et al. (2009). "Identification of selective inhibitors of cancer stem cells by high-throughput screening." Cell 138(4):645-659.
Hader, C., A. Marlier, et al. (2010). "Mesenchymal-epithelial transition in epithelial response to injury:the role of Foxc2." Oncogene 29(7):1031-1040.
Harris, T. A., M. Yamakuchi, et al. (2008). "MicroRNA-126 regulates endothelial expression of vascular cell adhesion molecule 1." Proc Natl Acad Sci U S A 105(5):1516-1521.
Hayashita, Y., H. Osada, et al. (2005). "A polycistronic microRNA cluster, miR-17-92, is overexpressed in human lung cancers and enhances cell proliferation." Cancer Res 65(21):9628-9632.
He, H., K. Jazdzewski, et al. (2005). "The role of microRNA genes in papillary thyroid carcinoma." Proc Natl Acad Sci U S A 102(52):19075-19080.
Iorio, M. V., P. Casalini, et al. (2009). "microRNA-205 regulates HER3 in human breast cancer." Cancer Res 69(6):2195-2200.
Iorio, M. V., M. Ferracin, et al. (2005). "MicroRNA gene expression deregulation in human breast cancer." Cancer Res 65(16):7065-7070.
Jemal, A., R. Siegel, et al. (2010). "Cancer statistics,2010." CA Cancer J Clin 60(5):277-300.
Kang, Y. and J. Massague (2004). "Epithelial-mesenchymal transitions:twist in development and metastasis." Cell 118(3):277-279.
Karube, Y., H. Tanaka, et al. (2005). "Reduced expression of Dicer associated with poor prognosis in lung cancer patients." Cancer Sci 96(2): 111-115.
Kim, D. H., M. A. Behlke, et al. (2005). "Synthetic dsRNA Dicer substrates enhance RNAi potency and efficacy." Nat Biotechnol 23(2):222-226.
Kluiver, J., S. Poppema, et al. (2005). "BIC and miR-155 are highly expressed in Hodgkin, primary mediastinal and diffuse large B cell lymphomas." J Pathol 207(2):243-249.
Lee, I., S. S. Ajay, et al. (2008). "Discriminating single-base difference miRNA expressions using microarray Probe Design Guru (ProDeG)." Nucleic Acids Res 36(5):e27.
Lee, R. C., R. L. Feinbaum, et al. (1993). "The C. elegans heterochronic gene lin-4 encodes small RNAs with antisense complementarity to lin-14." Cell 75(5):843-854.
Lee, Y., C. Ahn, et al. (2003). "The nuclear RNase Ⅲ Drosha initiates microRNA processing." Nature 425(6956):415-419.
Lewis, B. P., C. B. Burge, et al. (2005). "Conserved seed pairing, often flanked by adenosines, indicates that thousands of human genes are microRNA targets." Cell 120(1):15-20.
Lin, C. J., H. Y. Gong, et al. (2008). "miR-122 targets an anti-apoptotic gene, Bcl-w, in human hepatocellular carcinoma cell lines." Biochem Biophys Res Commun 375(3):315-320.
Liu, B., J. Li, et al. (2009). "Exploring complex miRNA-mRNA interactions with Bayesian networks by splitting-averaging strategy." Bmc Bioinformatics 10: 408.
Lu, J., G. Getz, et al. (2005). "MicroRNA expression profiles classify human cancers." Nature 435(7043):834-838.
Lund, E., S. Guttinger, et al. (2004). "Nuclear export of microRNA precursors." Science 303(5654):95-98.
Ma, L., J. Teruya-Feldstein, et al. (2007). "Tumour invasion and metastasis initiated by microRNA-10b in breast cancer." Nature 449(7163):682-688.
Ma, L. and R. A. Weinberg (2008). "Micromanagers of malignancy:role of micro RNAs in regulating metastasis." Trends Genet 24(9):448-456.
Markou, A., E. G. Tsaroucha, et al. (2008). "Prognostic value of mature microRNA-21 and microRNA-205 overexpression in non-small cell lung cancer by quantitative real-time RT-PCR." Clin Chem 54(10):1696-1704.
Michael, M. Z., O. C. SM, et al. (2003). "Reduced accumulation of specific microRNAs in colorectal neoplasia." Mol Cancer Res 1(12):882-891.
Michalak, P. (2006). "RNA world-the dark matter of evolutionary genomics." J Evol Biol 19(6):1768-1774.
Morita, T. (1990). "[Chronological changes of lung sarcoma and lung cancer incidence based on the annual of the pathological autopsy cases in Japan (1958-1986)1." Nihon Kyobu Shikkan Gakkai Zasshi 28(1):126-134.
Murakami, Y., T. Yasuda, et al. (2006). "Comprehensive analysis of microRNA expression patterns in hepatocellular carcinoma and non-tumorous tissues." Oncogene 25(17):2537-2545.
O'Donnell, K. A., E. A. Wentzel, et al. (2005). "c-Myc-regulated microRNAs modulate E2F1 expression." Nature 435(7043):839-843.
Ota, A., H. Tagawa, et al. (2004). "Identification and characterization of a novel gene, C13orf25, as a target for 13q31-q32 amplification in malignant lymphoma." Cancer Res 64(9):3087-3095.
Parkin, D. M. and S. M. Moss (2000). "Lung cancer screening:improved survival but no reduction in deaths--the role of "overdiagnosis"." Cancer 89(11 Suppl):2369-2376.
Pisani, P., D. M. Parkin, et al. (1999). "Erratum:Estimates of the worldwide mortality from 25 cancers in 1990. Int. J. Cancer,83,18-29 (1999)." Int J Cancer 83(6):870-873.
Polyak, K. and R. A. Weinberg (2009). "Transitions between epithelial and mesenchymal states:acquisition of malignant and stem cell traits." Nat Rev Cancer 9(4):265-273.
Potti, A. and A. K. Ganti (2006). "Adjuvant chemotherapy for early-stage non-small cell lung cancer:the past, the present and the future." Expert Opin Biol Ther 6(7):709-716.
Prasad, C. P., S. Mirza, et al. (2008). "Epigenetic alterations of CDH1 and APC genes:relationship with activation of Wnt/beta-catenin pathway in invasive ductal carcinoma of breast." Life Sci 83(9-10):318-325.
Saito, Y., G. Liang, et al. (2006). "Specific activation of microRNA-127 with downregulation of the proto-oncogene BCL6 by chromatin-modifying drugs in human cancer cells." Cancer Cell 9(6):435-443.
Sandler, A. B. (2003). "Chemotherapy for small cell lung cancer." Semin Oncol 30(1):9-25.
Seifter, E. J. and D. C. Ihde (1988). "Therapy of small cell lung cancer:a perspective on two decades of clinical research." Semin Oncol 15(3):278-299.
Shackel, N. A., P. H. McGuinness, et al. (2002). "Insights into the pathobiology of hepatitis C virus-associated cirrhosis:analysis of intrahepatic differential gene expression." Am J Pathol 160(2):641-654.
Spaderna, S., O. Schmalhofer, et al. (2008). "The transcriptional repressor ZEB1 promotes metastasis and loss of cell polarity in cancer." Cancer Res 68(2): 537-544.
Takakura, S., N. Mitsutake, et al. (2008). "Oncogenic role of miR-17-92 cluster in anaplastic thyroid cancer cells." Cancer Sci 99(6):1147-1154.
Takamizawa, J., H. Konishi, et al. (2004). "Reduced expression of the let-7 microRNAs in human lung cancers in association with shortened postoperative survival." Cancer Res 64(11):3753-3756.
Tavazoie, S. F., C. Alarcon, et al. (2008). "Endogenous human microRNAs that suppress breast cancer metastasis." Nature 451(7175):147-152.
Thiery, J. P. (2002). "Epithelial-mesenchymal transitions in tumour progression." Nat Rev Cancer 2(6):442-454.
Tsai, W. C., P. W. Hsu, et al. (2009). "MicroRNA-122, a tumor suppressor microRNA that regulates intrahepatic metastasis of hepatocellular carcinoma." Hepatology 49(5):1571-1582.
Vandewalle, C., J. Comijn, et al. (2005). "SIP1/ZEB2 induces EMT by repressing genes of different epithelial cell-cell junctions." Nucleic Acids Res 33(20):6566-6578.
Volinia, S., G. A. Calin, et al. (2006). "A microRNA expression signature of human solid tumors defines cancer gene targets." Proc Natl Acad Sci U S A 103(7):2257-2261.
Voorhoeve, P. M., C. le Sage, et al. (2006). "A genetic screen implicates miRNA-372 and miRNA-373 as oncogenes in testicular germ cell tumors." Cell 124(6):1169-1181.
Wang, Z., Y. Li, et al. (2010). "The role of Notch signaling pathway in epithelial-mesenchymal transition (EMT) during development and tumor aggressiveness." Curr Drug Targets 11(6):745-751.
Wu, W., M. Sun, et al. (2007). "MicroRNA and cancer:Current status and prospective." Int J Cancer 120(5):953-960.
Wu, Y., J. Deng, et al. (2009). "Stabilization of snail by NF-kappaB is required for inflammation-induced cell migration and invasion." Cancer Cell 15(5):416-428.
Xu, J., S. Lamouille, et al. (2009). "TGF-beta-induced epithelial to mesenchymal transition." Cell Res 19(2):156-172.
Yan, L. X., X. F. Huang, et al. (2008). "MicroRNA miR-21 overexpression in human breast cancer is associated with advanced clinical stage, lymph node metastasis and patient poor prognosis." RNA 14(11):2348-2360.
Yanaihara, N., N. Caplen, et al. (2006). "Unique microRNA molecular profiles in lung cancer diagnosis and prognosis." Cancer Cell 9(3):189-198.
Yu, X., J. Lin, et al. (2008). "Analysis of regulatory network topology reveals functionally distinct classes of microRNAs." Nucleic Acids Res 36(20): 6494-6503.
Zhang, J., Y. Y. Du, et al. (2008). "The cell growth suppressor, mir-126, targets IRS-1." Biochem Biophys Res Commun 377(1):136-140.
Giraud P, Elles S, Helfre S et al. (2002). "Conformal radiotherapy for lung cancer:different delineation of the gross tumor volume (GTV) by radiologists and radiation oncologists. "Radiother & Oncol 62 (1):27-36.
Hristov, D., L. Liu, et al. (2011). "Technique for targeting arteriovenous malformations using frameless image-guided robotic radiosurgery." Int J Radiat Oncol Biol Phys 79(4): 1232-1240.
Jeffrey A. Bogart. James E. Herndon Ⅱ, et al. (2004). "70Gy Thoracic radiotherapy is feasible concurrent with chemotherapy for limited-stage small cell lung cancer:Analysis of Cancer and Leukemia Group B Study 39808." Int. J. Radiat. Oncol. Biol.Phys 59(2):460-468.
Jenkens P, Salemon C, Mannion C. (2005). "Analysis of the movement of calcified lymph nodes during breathing. " Int. J. Radiat. Oncol. Biol.Phys 61 (2):329-334.
Madu N, Douglas J,Daniel P, et al. (2002). "Definition of superaclavicular nodes: Implications for three-dimensional CT-based conformal radiation therapy. " Radiology 221(2):333-339.
Noblet, V., C. Heinrich, et al. (2006). "Retrospective evaluation of a topology preserving non-rigid registration method." Med Image Anal 10(3):366-384
Osareh, A. and B. Shadgar (2010). "A segmentation method of lung cavities using region aided geometric snakes." J Med Syst 34(4):419-433.
Pevsner, A., B. Davis, et al. (2006). "Evaluation of an automated deformable image matching method for quantifying lung motion in respiration-correlated CT images." Med Phys 33(2):369-376.
Uno T, Sumi M, Ishihara Y, et al. (2008). "Changes in patterns of care for limited-stage small-cell lung cancer:results of the 99-01 patterns of care study-a nationwide survey in Japan. "Int J Radiat Oncol Biol Phys 71(2):414-419.
van Loon J, Offermann C, Bosmans G, et al. (2008). "18FDG-PET based radiation planning of mediastinal lymph nodes in limited disease small cell lung cancer changes radiotherapy fields: a planning study. " Radiother Oncol 87(1):49-54.
卢洁,李建彬,尹勇等.(2008).”两种方法评估肺癌患者三维适形放疗重复计划肺总体受照剂量体积效果比较.”山东医药48(27)97-99.
沈捷,张福泉,邱杰等.(2006).”应用EPID对放射治疗摆位误差的研究.”中华放射医学与防护杂志26(3)：308.
吴开良,蒋国梁,廖源等.(2002).”肺癌不同放射治疗技术剂量学比较.”中华放射胜瘤堂杂志11(4)：231-234.
殷蔚伯,余子豪,徐国镇等主编.(2008).肿瘤放射治疗学(第四版).中国协和医科大学. 出版社第二篇,第三章：87-95.
云惟康,胡洪涛,徐向英等.(2009).”利用影像融合技术评估肺癌放射治疗全疗程剂量体积直方图”.实用肿瘤学杂志23(5)：441-443.
张金忠,戈伟,张园如等.(2011).”CT/CT图像融合用于非小细胞肺癌放射治疗对V20及放射性肺炎影响的临床研究”.临床肿瘤堂杂志16(2)：154-157.
朱慧,王绿化.(2011).”放射治疗对小细胞肺癌预后的影响.”中华肿瘤防治杂查17(24)：2070-2074.
Bartel, D. P. (2004). "MicroRNAs:genomics, biogenesis, mechanism, and function." Cell 116(2):281-297.
Bartel, D. P. (2009). "MicroRNAs:target recognition and regulatory functions." Cell 136(2):215-233.
Batlle, E., E. Sancho, et al. (2000). "The transcription factor snail is a repressor of E-cadherin gene expression in epithelial tumour cells." Nat Cell Biol 2(2):84-89.
Bolos, V., H. Peinado, et al. (2003). "The transcription factor Slug represses E-cadherin expression and induces epithelial to mesenchymal transitions:a comparison with Snail and E47 repressors." J Cell Sci 116(Pt 3):499-511.
Bonnomet, A., A. Brysse, et al. (2010). "Epithelial-to-mesenchymal transitions and circulating tumor cells." J Mammary Gland Biol Neoplasia 15(2):261-273.
Bracken, C. P., P. A. Gregory, et al. (2008). "A double-negative feedback loop between ZEB1-SIP1 and the microRNA-200 family regulates epithelial-mesenchymal transition." Cancer Res 68(19):7846-7854.
Braun, J., C. Hoang-Vu, et al. (2010). "Downregulation of microRNAs directs the EMT and invasive potential of anaplastic thyroid carcinomas." Oncogene 29(29):4237-4244.
Burk, U., J. Schubert, et al. (2008). "A reciprocal repression between ZEB1 and members of the miR-200 family promotes EMT and invasion in cancer cells." EMBO Rep 9(6):582-589.
Calin, G. A. and C. M. Croce (2006). "MicroRNA signatures in human cancers." Nature Reviews Cancer 6:857-866.
Carmona-Fontaine, C., H. K. Matthews, et al. (2008). "Contact inhibition of locomotion in vivo controls neural crest directional migration." Nature 456(7224):957-961.
Christoffersen, N. R., A. Silahtaroglu, et al. (2007). "miR-200b mediates post-transcriptional repression of ZFHX1B." RNA 13(8):1172-1178.
Comijn, J., G. Berx, et al. (2001). "The two-handed E box binding zinc finger protein SIP1 downregulates E-cadherin and induces invasion." Mol Cell 7(6):1267-1278.
Du, J., S. Yang, et al. (2009). "BMP-6 inhibits microRNA-21 expression in breast cancer through repressing deltaEF1 and AP-1." Cell Res 19(4):487-496.
Fujita, S., T. Ito, et al. (2008). "miR-21 Gene expression triggered by AP-1 is sustained through a double-negative feedback mechanism." J Mol Biol 378(3):492-504.
Gregory, P. A., A. G. Bert, et al. (2008). "The miR-200 family and miR-205 regulate epithelial to mesenchymal transition by targeting ZEB1 and SDP1." Nat Cell Biol 10(5): 593-601.
Guaita, S., I. Puig, et al. (2002). "Snail induction of epithelial to mesenchymal transition in tumor cells is accompanied by MUC1 repression and ZEB1 expression." J Biol Chem 277(42):39209-39216.
Gupta, G. P. and J. Massague (2006). "Cancer metastasis:building a framework." Cell 127(4):679-695.
Gupta, P. B., T. T. Onder, et al. (2009). "Identification of selective inhibitors of cancer stem cells by high-throughput screening." Cell 138(4):645-659.
Hader, C., A. Marlier, et al. (2010). "Mesenchymal-epithelial transition in epithelial response to injury:the role of Foxc2." Oncogene 29(7):1031-1040.
Hartwell, K. A., B. Muir, et al. (2006). "The Spemann organizer gene, Goosecoid, promotes tumor metastasis." Proc Natl Acad Sci U S A 103(50):18969-18974.
Hazan, R. B., R. Qiao, et al. (2004). "Cadherin switch in tumor progression." Ann N Y Acad Sci 1014:155-163.
Huber, M. A., N. Kraut, et al. (2005). "Molecular requirements for epithelial-mesenchymal transition during tumor progression." Curr Opin Cell Biol 17(5): 548-558.
Hurteau, G. J., J. A. Carlson, et al. (2007). "Overexpression of the microRNA hsa-miR-200c leads to reduced expression of transcription factor 8 and increased expression of E-cadherin." Cancer Res 67(17):7972-7976.
Iorio, M. V., M. Ferracin, et al. (2005). "MicroRNA gene expression deregulation in human breast cancer." Cancer Res 65(16):7065-7070.
Kalluri, R. and E. G. Neilson (2003). "Epithelial-mesenchymal transition and its implications for fibrosis." J Clin Invest 112(12):1776-1784.
Kalluri, R. and R. A. Weinberg (2009). "The basics of epithelial-mesenchymal transition." J Clin Invest 119(6):1420-1428.
Kang, Y. and J. Massague (2004). "Epithelial-mesenchymal transitions:twist in development and metastasis." Cell 118(3):277-279.
Karolchik, D., R. Baertsch, et al. (2003). "The UCSC Genome Browser Database." Nucleic Acids Res 31(1):51-54.
Kong, W., H. Yang, et al. (2008). "MicroRNA-155 is regulated by the transforming growth factor beta/Smad pathway and contributes to epithelial cell plasticity by targeting RhoA." Mol Cell Biol 28(22):6773-6784.
Korpal, M., E. S. Lee, et al. (2008). "The miR-200 family inhibits epithelial-mesenchymal transition and cancer cell migration by direct targeting of E-cadherin transcriptional repressors ZEB1 and ZEB2." J Biol Chem 283(22):14910-14914.
Krutzfeldt, J., N. Rajewsky, et al. (2005). "Silencing of microRNAs in vivo with 'antagomirs'." Nature 438(7068):685-689.
Lamouille, S. and R. Derynck (2007). "Cell size and invasion in TGF-beta-induced epithelial to mesenchymal transition is regulated by activation of the mTOR pathway." JCell Biol 178(3):437-451.
Le, X. F., O. Merchant, et al. (2010). "The Roles of MicroRNAs in the Cancer Invasion-Metastasis Cascade." Cancer Microenviron 3(1):137-147.
Lee, E. J., M. Baek, et al. (2008). "Systematic evaluation of microRNA processing patterns in tissues, cell lines, and tumors." RNA 14(1):35-42.
Lee, Y. S., K. Nakahara, et al. (2004). "Distinct roles for Drosophila Dicer-1 and Dicer-2 in the siRNA/miRNA silencing pathways." Cell 117(1):69-81.
Lu, J., G. Getz, et al. (2005). "MicroRNA expression profiles classify human cancers." Nature 435(7043):834-838.
Lund, E., S. Guttinger, et al. (2004). "Nuclear export of microRNA precursors." Science 303(5654):95-98.
Ma, L., J. Young, et al. (2010). "miR-9, a MYC/MYCN-activated microRNA, regulates E-cadherin and cancer metastasis." Nat Cell Biol 12(3):247-256.
Maeda, M., K. R. Johnson, et al. (2005). "Cadherin switching:essential for behavioral but not morphological changes during an epithelium-to-mesenchyme transition." J Cell Sci 118(Pt 5):873-887.
Mani, S. A., W. Guo, et al. (2008). "The epithelial-mesenchymal transition generates cells with properties of stem cells." Cell 133(4):704-715.
Nicoloso, M. S., R. Spizzo, et al. (2009). "MicroRNAs-the micro steering wheel of tumour metastases." Nat Rev Cancer 9(4):293-302.
Park, S. M., A. B. Gaur, et al. (2008). "The miR-200 family determines the epithelial phenotype of cancer cells by targeting the E-cadherin repressors ZEB1 and ZEB2." Genes Dev 22(7):894-907.
Polyak, K. and R. A. Weinberg (2009). "Transitions between epithelial and mesenchymal states:acquisition of malignant and stem cell traits." Nat Rev Cancer 9(4): 265-273.
Postigo, A. A. and D. C. Dean (1997). "ZEB, a vertebrate homolog of Drosophila Zfh-1, is a negative regulator of muscle differentiation." EMBO J 16(13):3935r3943.
Prasad, C. P., S. Mirza, et al. (2008). "Epigenetic alterations of CDH1 and APC genes: relationship with activation of Wnt/beta-catenin pathway in invasive ductal carcinoma of breast." Life Sci 83(9-10):318-325.
Roldo, C., E. Missiaglia, et al. (2006). "MicroRNA expression abnormalities in pancreatic endocrine and acinar tumors are associated with distinctive pathologic features and clinical behavior." J Clin Oncol 24(29):4677-4684.
Saini, H. K., S. Griffiths-Jones, et al. (2007). "Genomic analysis of human microRNA transcripts." Proc Natl Acad Sci U S A 104(45):17719-17724.
Savagner, P. (2001). "Leaving the neighborhood:molecular mechanisms involved during epithelial-mesenchymal transition." Bioessays 23(10):912-923.
Savagner, P. (2010). "The epithelial-mesenchymal transition (EMT) phenomenon." Ann Oncol 21 Suppl 7:vii89-92.
Shimono, Y., M. Zabala, et al. (2009). "Downregulation of miRNA-200c links breast cancer stem cells with normal stem cells." Cell 138(3):592-603.
Spaderna, S., O. Schmalhofer, et al. (2008). "The transcriptional repressor ZEB1 promotes metastasis and loss of cell polarity in cancer." Cancer Res 68(2):537-544.
Thiery, J. P. (2002). "Epithelial-mesenchymal transitions in tumour progression." Nat Rev Cancer 2(6):442-454.
Thiery, J. P. and J. P. Sleeman (2006). "Complex networks orchestrate epithelial-mesenchymal transitions." Nat Rev Mol Cell Biol 7(2):131-142.
Thompson, E. W., D. F. Newgreen, et al. (2005). "Carcinoma invasion and metastasis:a role for epithelial-mesenchymal transition?" Cancer Res 65(14):5991-5995; discussion 5995.
Vandewalle, C., J. Comijn, et al. (2005). "SIP1/ZEB2 induces EMT by repressing genes of different epithelial cell-cell junctions." Nucleic Acids Res 33(20):6566-6578.
Vetter, G., A. Saumet, et al. (2010). "miR-661 expression in SNAI1-induced epithelial to mesenchymal transition contributes to breast cancer cell invasion by targeting Nectin-1 and StarD10 messengers." Oncogene 29(31):4436-4448.
Wang, Z., Y. Li, et al. (2010). "The role of Notch signaling pathway in epithelial-mesenchymal transition (EMT) during development and tumor aggressiveness." Curr Drug Targets 11(6):745-751.
Wienholds, E., M. J. Koudijs, et al. (2003). "The microRNA-producing enzyme Dicerl is essential for zebrafish development." Nat Genet 35(3):217-218.
Wu, Y., J. Deng, et al. (2009). "Stabilization of snail by NF-kappaB is required for inflammation-induced cell migration and invasion." Cancer Cell 15(5):416-428.
Xia, H., S. S. Ng, et al. (2010). "miR-200a-mediated downregulation of ZEB2 and CTNNB1 differentially inhibits nasopharyngeal carcinoma cell growth, migration and invasion." Biochem Biophys Res Commun 391(1):535-541.
Xu, J., S. Lamouille, et al. (2009). "TGF-beta-induced epithelial to mesenchymal transition." Cell Res 19(2):156-172.
Yang, H., W. Kong, et al. (2008). "MicroRNA expression profiling in human ovarian cancer:miR-214 induces cell survival and cisplatin resistance by targeting PTEN." Cancer Res 68(2):425-433.
Yang, J., S. A. Mani, et al. (2004). "Twist, a master regulator of morphogenesis, plays an essential role in tumor metastasis." Cell 117(7):927-939.
Yi, R., D. O'Carroll, et al. (2006). "Morphogenesis in skin is governed by discrete sets of differentially expressed microRNAs." Nat Genet 38(3):356-362.
Zavadil, J., M. Narasimhan, et al. (2007). "Transforming growth factor-beta and microRNA:mRNA regulatory networks in epithelial plasticity." Cells Tissues Organs 185(1-3):157-161.
Zeisberg, M. and E. G. Neilson (2009). "Biomarkers for epithelial-mesenchymal transitions." J Clin Invest 119(6):1429-1437.