核因子-κB圈套寡脱氧核苷酸联合紫杉醇治疗肺癌的探讨
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摘要
背景：
肺癌是目前严重威害人类健康和生命的恶性肿瘤之一,根据流行病学相关研究结果,近年来,肺癌的发病率和死亡率呈上升趋势,据统计,占所有恶性肿瘤发病率的12%。在欧美某些国家和我国大中城市,其发病率已居于首位,且发病年龄趋于年轻化,与吸烟、环境污染物密切相关,其治疗难度大、迅速转移、死亡率高为特点。肿瘤的浸润与转移己成为当今导致治疗失败和患者死亡的主要原因,因此寻找关键靶位点抑制肺癌血管生成,为肺癌的临床治疗开辟一条新的途径。
核因子-kB (nuclear factor-kappa B, NF-kB)是一种多显性基因转录因子,与多种基因的转录密切相关,在肿瘤细胞中高表达,与多种细胞基因的启动子和增强子发生特异性结合,与血管内皮生长因子(Vascular endothelial growth factor, VEGF)、环氧合酶-2(Cyclooxygenase -2, COX-2)关系密切,参与炎症反应、损伤应激、免疫防御、细胞增殖及凋亡等过程。核因子-кB圈套寡脱氧核苷酸(NF-kB decoy ODN)是目前研究发现进行体内外基因调控的强有力工具,含有转录因子识别序列的寡核苷酸或质粒转入细胞,与核内基因启动子区相应顺势作用元件竞争结合转录因子,从而抑制启动子活化,达到抑制基因转录和翻译的目的,其能明显抑制癌细胞的增殖,并可提高肿瘤细胞对化疗药物(紫杉醇)的敏感性。
目的：
研究NF-κB圈套寡脱氧核苷酸(NF-κB decoy ODN)联合紫杉醇对肺癌A549细胞增殖、凋亡、血管生成的影响及其作用机制,为临床实践提供理论依据。
方法：
1、培养人肺癌细胞A549。
2、脂质体瞬时转染法介导核因子-кB圈套寡核苷酸(NF-κB decoy ODN)和核因子-кB错义圈套寡核苷酸(NF-κB scramble decoy ODN)处理A549细胞。
3、MTT试验观察干预96 h经NF-κB decoy ODN及NF-κB Scramble decoyODN作用后肺癌A549细胞生长曲线。
4、设对照组、NF-κB decoy ODN组、紫杉醇组(1000 ng/mL)和NF-κB decoyODN+紫杉醇组,RT-PCR法测环氧合酶-2(COX-2) mRNA水平表达,免疫组织化学法测血管内皮生长因子(VEGF)蛋白表达,流式细胞术检测各组48 h后细胞凋亡率。
结果：
1、核因子-кB圈套寡脱氧核苷酸(NF-κB decoy ODN)使细胞生长明显受到抑制,时间越长抑制作用越明显。
2、核因子-кB圈套寡脱氧核苷酸(NF-κB decoy ODN)、紫杉醇干预后A549细胞的环氧合酶-2(COX-2) mRNA水平表达及血管内皮生长因子(VEGF)蛋白表达均下降,COX-2mRNA水平表达各组浓度分别是：0.71±1.4μg/μL、0.44±1.8μg/μL、0.51±7.2μg/μL、0.34±9.5μg/μL (F=7.8, P<0.05), VEGF蛋白表达各组细胞阳性率分别是：85±0.50%,63±0.26%,57±1.5%,21±0.34%(F=21,P<0.05)。
3、核因子-кB圈套寡脱氧核苷酸(NF-κB decoy ODN)联合紫杉醇可促使A549细胞凋亡增加,二者联用呈协同或相加作用,各组细胞的总凋亡率分别是：(16.8±0.01)%、(5.6±0.02)%、(32.6±0.04)%,均高于对照组(6.0±0.02)%(F=14,P<0.05)。
结论：
1.核因子-кB圈套寡脱氧核苷酸(NF-kB decoy ODN)能明显抑制肺癌A549细胞的生长。
2.核因子-кB圈套寡脱氧核苷酸(NF-kB decoy ODN)联合紫杉醇可明显抑制肺癌A549细胞的生长,该作用可能与环氧合酶-2(COX-2)、血管内皮生长因子(VEGF)的表达相关。
3.核因子-кB圈套寡脱氧核苷酸(NF-kB decoy ODN)联合紫杉醇可增强对肺癌A549细胞增殖的抑制及凋亡的诱导,二者具有协同抗肿瘤作用。
Background:
Lung cancer is a serious threat to harm human health and life of the malignant tumor, according to the results of epidemiological studies in recent years, incidence and mortality lung cancer is rising, according to statistics, the incidence of all malignant tumors accounted for 12%. Some countries in Europe, America and our cities, the incidence rate has primacy, and the younger age of onset tends to, and smoking, environmental pollutants are closely related, the treatment is difficult, rapid transfer, high mortality characterized. Tumor invasion and metastasis has become the lead to treatment failure and the leading cause of death in patients, so look for the key target sites of angiogenesis inhibition of lung cancer, for lung cancer treatment to open up a new way.
Nuclear factor (nuclear factor- kappa B, NF-kB) is a multi-dominant gene transcription factor, and transcription of multiple genes closely related to high expression in tumor cells, with a variety of cellular gene promoter and enhancer specific binding occurs, and cyclooxygenase 2 (Cyclooxygenase -2,COX2), vascular endothelial growth factor (Vascular endothelial growth factor,VEGF) is closely related, is involved in inflammation, injury stress, immune defense, cell proliferation and apoptosis process. NF-kB decoy oligodeoxynucleotide (NF-kB decoy ODN) is carried out in vivo study found a powerful tool for gene regulation, transcription factor recognition sequence containing oligonucleotides or plasmids into cells, and nuclear genes the role of the promoter region of the corresponding advantage of the opportunity component competitive binding transcription factor, thereby inhibiting the activation of the promoter, to inhibit gene transcription and translation purposes, its value can inhibit cancer cells, and enhance the tumor cells to chemotherapeutic drugs (paclitaxel) sensitivity
Objective:
Research NF-kB decoy oligodeoxynucleotide (NF-kB decoy ODN) combined with paclitaxel on lung cancer A549 cell proliferation, apoptosis, angiogenesis and its mechanism of action, provide the theoretical basis for clinical practice.
Methods:
1. Cultivate human lung cancer cell A549.
2. Using liposome-mediated transient transfection method full phosphorothioate NF-kB decoy oligonucleotides (decoy ODN), and all missense phosphorothioate decoy oligonucleotides (scramble decoy ODN) treatment A549 cells.
3. MTT test interventions observed 96 h after NF-kB decoy ODN and NF-kB Scramble decoy ODN role in lung cancer A549 cells after growth curve.
4. Divided into the control group, NF-kB decoy ODN group, paclitaxel group (1000ng/ml) and NF-KBdecoy ODN + paclitaxel group, RT-PCR method to measure the level of Cyclooxygenase -2(COX-2)mRNA expression measured by immunohistochemistry the expression of Vascular endothelial growth factor (VEGF) protein in the flow Type cells 48 h after surgery to detect the apoptotic rate.
Results:
1. NF-κB decoy oligodeoxynucleotide (NF-κB decoy ODN) significantly inhibited the cell growth, the more obvious the longer inhibited.
2. NF-κB decoy oligodeoxynucleotide (NF-κB decoy ODN), paclitaxel A549 cells after the intervention levels of Cyclooxygenase -2(COX-2)mRNA expression and VEGF protein expression decreased, COX-2 mRNA expression levels of concentration in each group were:0.71±1.4μg/μL,0.44±1.8μg/μL,0.51±7.2μg/μL,0.34±9.5μg/μL (F=7.8, P<0.05), Vascular endothelial growth factor(VEGF) protein expression positive rate of cells in each group were:85±0.50%,63±0.26%,57±1.5%,21±0.34%(F= 21, P＜0.05).
3. NF-κB decoy oligodeoxynucleotide (NF-κB decoy ODN) combined with paclitaxel can promote apoptosis of A549 cells, the two together were synergistic or additive effect with each group the apoptosis of cells is:(16.8±0.01)%, (5.6±0.02)%, (32.6±0.04)%, were higher (6.0±0.02)%(F=14, P<0.05).
Conclusion:
1. Nuclear factor-κB decoy oligodeoxynucleotide (NF-κB decoy ODN) significantly inhibited the growth of lung cancer A549 cells.
2. The nuclear factor-κB snare widowed deaeration nucleotide (NF-κB decoy ODN) unites the taxus mellowly to be possible to suppress the lung cancer A549 cell's growth obviously, this function is possible and epoxy synthase-2 (COX-2), blood vessel bast growth factor (VEGF) expression related.
3. The nuclear factor -κB snare widowed deaeration nucleotide (NF-κB decoy ODN) unites the taxus mellowly to be possible to strengthen the induction which and perishes weakly to lung cancer A549 cell multiplication's suppression, the two have coordinate the anti-tumor function
肺癌是目前严重威害人类健康和生命的恶性肿瘤之一,根据流行病学相关研究结果,近年来,肺癌的发病率和死亡率呈上升趋势,据统计,占所有恶性肿瘤发病率的12%。在欧美某些国家和我国大中城市,其发病率已居于首位,且发病年龄趋于年轻化,与吸烟、环境污染物密切相关,其治疗难度大、迅速转移、死亡率高为特点。肿瘤的浸润与转移己成为当今导致治疗失败和患者死亡的主要原因,因此寻找关键靶位点抑制肺癌血管生成,为肺癌的临床治疗开辟一条新的途径。
核因子-kB (nuclear factor-kappa B, NF-kB)是一种多显性基因转录因子,与多种基因的转录密切相关,在肿瘤细胞中高表达,与多种细胞基因的启动子和增强子发生特异性结合,与血管内皮生长因子(Vascular endothelial growth factor, VEGF)、环氧合酶-2(Cyclooxygenase -2, COX-2)关系密切,参与炎症反应、损伤应激、免疫防御、细胞增殖及凋亡等过程。核因子-кB圈套寡脱氧核苷酸(NF-kB decoy ODN)是目前研究发现进行体内外基因调控的强有力工具,含有转录因子识别序列的寡核苷酸或质粒转入细胞,与核内基因启动子区相应顺势作用元件竞争结合转录因子,从而抑制启动子活化,达到抑制基因转录和翻译的目的,其能明显抑制癌细胞的增殖,并可提高肿瘤细胞对化疗药物(紫杉醇)的敏感性。
目的：
研究NF-κB圈套寡脱氧核苷酸(NF-κB decoy ODN)联合紫杉醇对肺癌A549细胞增殖、凋亡、血管生成的影响及其作用机制,为临床实践提供理论依据。
方法：
1、培养人肺癌细胞A549。
2、脂质体瞬时转染法介导核因子-кB圈套寡核苷酸(NF-κB decoy ODN)和核因子-кB错义圈套寡核苷酸(NF-κB scramble decoy ODN)处理A549细胞。
3、MTT试验观察干预96 h经NF-κB decoy ODN及NF-κB Scramble decoyODN作用后肺癌A549细胞生长曲线。
4、设对照组、NF-κB decoy ODN组、紫杉醇组(1000 ng/mL)和NF-κB decoyODN+紫杉醇组,RT-PCR法测环氧合酶-2(COX-2) mRNA水平表达,免疫组织化学法测血管内皮生长因子(VEGF)蛋白表达,流式细胞术检测各组48 h后细胞凋亡率。
结果：
1、核因子-кB圈套寡脱氧核苷酸(NF-κB decoy ODN)使细胞生长明显受到抑制,时间越长抑制作用越明显。
2、核因子-кB圈套寡脱氧核苷酸(NF-κB decoy ODN)、紫杉醇干预后A549细胞的环氧合酶-2(COX-2) mRNA水平表达及血管内皮生长因子(VEGF)蛋白表达均下降,COX-2mRNA水平表达各组浓度分别是：0.71±1.4μg/μL、0.44±1.8μg/μL、0.51±7.2μg/μL、0.34±9.5μg/μL (F=7.8, P<0.05), VEGF蛋白表达各组细胞阳性率分别是：85±0.50%,63±0.26%,57±1.5%,21±0.34%(F=21,P<0.05)。
3、核因子-кB圈套寡脱氧核苷酸(NF-κB decoy ODN)联合紫杉醇可促使A549细胞凋亡增加,二者联用呈协同或相加作用,各组细胞的总凋亡率分别是：(16.8±0.01)%、(5.6±0.02)%、(32.6±0.04)%,均高于对照组(6.0±0.02)%(F=14,P<0.05)。
结论：
1.核因子-кB圈套寡脱氧核苷酸(NF-kB decoy ODN)能明显抑制肺癌A549细胞的生长。
2.核因子-кB圈套寡脱氧核苷酸(NF-kB decoy ODN)联合紫杉醇可明显抑制肺癌A549细胞的生长,该作用可能与环氧合酶-2(COX-2)、血管内皮生长因子(VEGF)的表达相关。
3.核因子-кB圈套寡脱氧核苷酸(NF-kB decoy ODN)联合紫杉醇可增强对肺癌A549细胞增殖的抑制及凋亡的诱导,二者具有协同抗肿瘤作用。
Background:
Lung cancer is a serious threat to harm human health and life of the malignant tumor, according to the results of epidemiological studies in recent years, incidence and mortality lung cancer is rising, according to statistics, the incidence of all malignant tumors accounted for 12%. Some countries in Europe, America and our cities, the incidence rate has primacy, and the younger age of onset tends to, and smoking, environmental pollutants are closely related, the treatment is difficult, rapid transfer, high mortality characterized. Tumor invasion and metastasis has become the lead to treatment failure and the leading cause of death in patients, so look for the key target sites of angiogenesis inhibition of lung cancer, for lung cancer treatment to open up a new way.
Nuclear factor (nuclear factor- kappa B, NF-kB) is a multi-dominant gene transcription factor, and transcription of multiple genes closely related to high expression in tumor cells, with a variety of cellular gene promoter and enhancer specific binding occurs, and cyclooxygenase 2 (Cyclooxygenase -2,COX2), vascular endothelial growth factor (Vascular endothelial growth factor,VEGF) is closely related, is involved in inflammation, injury stress, immune defense, cell proliferation and apoptosis process. NF-kB decoy oligodeoxynucleotide (NF-kB decoy ODN) is carried out in vivo study found a powerful tool for gene regulation, transcription factor recognition sequence containing oligonucleotides or plasmids into cells, and nuclear genes the role of the promoter region of the corresponding advantage of the opportunity component competitive binding transcription factor, thereby inhibiting the activation of the promoter, to inhibit gene transcription and translation purposes, its value can inhibit cancer cells, and enhance the tumor cells to chemotherapeutic drugs (paclitaxel) sensitivity
Objective:
Research NF-kB decoy oligodeoxynucleotide (NF-kB decoy ODN) combined with paclitaxel on lung cancer A549 cell proliferation, apoptosis, angiogenesis and its mechanism of action, provide the theoretical basis for clinical practice.
Methods:
1. Cultivate human lung cancer cell A549.
2. Using liposome-mediated transient transfection method full phosphorothioate NF-kB decoy oligonucleotides (decoy ODN), and all missense phosphorothioate decoy oligonucleotides (scramble decoy ODN) treatment A549 cells.
3. MTT test interventions observed 96 h after NF-kB decoy ODN and NF-kB Scramble decoy ODN role in lung cancer A549 cells after growth curve.
4. Divided into the control group, NF-kB decoy ODN group, paclitaxel group (1000ng/ml) and NF-KBdecoy ODN + paclitaxel group, RT-PCR method to measure the level of Cyclooxygenase -2(COX-2)mRNA expression measured by immunohistochemistry the expression of Vascular endothelial growth factor (VEGF) protein in the flow Type cells 48 h after surgery to detect the apoptotic rate.
Results:
1. NF-κB decoy oligodeoxynucleotide (NF-κB decoy ODN) significantly inhibited the cell growth, the more obvious the longer inhibited.
2. NF-κB decoy oligodeoxynucleotide (NF-κB decoy ODN), paclitaxel A549 cells after the intervention levels of Cyclooxygenase -2(COX-2)mRNA expression and VEGF protein expression decreased, COX-2 mRNA expression levels of concentration in each group were:0.71±1.4μg/μL,0.44±1.8μg/μL,0.51±7.2μg/μL,0.34±9.5μg/μL (F=7.8, P<0.05), Vascular endothelial growth factor(VEGF) protein expression positive rate of cells in each group were:85±0.50%,63±0.26%,57±1.5%,21±0.34%(F= 21, P＜0.05).
3. NF-κB decoy oligodeoxynucleotide (NF-κB decoy ODN) combined with paclitaxel can promote apoptosis of A549 cells, the two together were synergistic or additive effect with each group the apoptosis of cells is:(16.8±0.01)%, (5.6±0.02)%, (32.6±0.04)%, were higher (6.0±0.02)%(F=14, P<0.05).
Conclusion:
1. Nuclear factor-κB decoy oligodeoxynucleotide (NF-κB decoy ODN) significantly inhibited the growth of lung cancer A549 cells.
2. The nuclear factor-κB snare widowed deaeration nucleotide (NF-κB decoy ODN) unites the taxus mellowly to be possible to suppress the lung cancer A549 cell's growth obviously, this function is possible and epoxy synthase-2 (COX-2), blood vessel bast growth factor (VEGF) expression related.
3. The nuclear factor -κB snare widowed deaeration nucleotide (NF-κB decoy ODN) unites the taxus mellowly to be possible to strengthen the induction which and perishes weakly to lung cancer A549 cell multiplication's suppression, the two have coordinate the anti-tumor function
引文
[1]Sousa JR, Silva AC, de Paiva AC, et al. Methodology for automatic detection of lung nodules in computerized tomography images. Comput Methods Programs Biomed [J]. 2010Apr,98(1):1-14.
[2]Dufey DC,Crawl BCV,Chen Z,et al. Inhibiyion of transcription factor nuclear factor-Kappa B by a mutant inhibitor-kappa B alphaattenuates resistance of human head and neck squamous cell carcinoma to TNF-alpha caspase mediated cell death[J].BrJ Cancer,2000, 83(10):1367-1374.
[3]Sarkar P, Hayes BE, et al. Induction of COX-2 by acrolein in rat lung epithelial cells [J]. Mol Cell Biochem,2007 Jul; 301(1-2):191-220.
[4]Voant C, Hendrickx N, Vanlint J,et al. Distinct transduction meehanism of cycloxygenase2 gene activation in tumour cells after photodynamic therapy [J]. Oneogene,2005, 24(18):2981-2991.
[5]Krupitskaya Y, Wakelee HA, et al. Ramucirumab, a fully human mAb to the transmembrane signaling tyrosine kinase VEGFR-2 for the potential treatment of cancer [J]. Curr Opin Investig Drugs,2009 Jun;10(6):597-605.
[6]McLachlan A, Kekre N, McNulty J, et al. Pancratistatin:a natural anti-cancer compound that targets mitochondria specifically in cancer cells to induce apoptosis [J]. Apoptosis. 2005 May;10(3):619-630
[7]Huang CC, Lo CP, Chiu CY, et al. Deoxyelephantopin, a novel multifunctional agent, suppresses mammary tumour growth and lung metastasis and doubles survival time in mice [J]. Br J Pharmacol.2010 Feb; 159(4):856-871.
[8]Marrs J.Zubal BA,et al. Oncology nursing in a new era:optimizing treatment with bevacizumab[J]. Clin J Oncol Nurs,2009 Oct; 13(5):564-72.
[9]Voant C, Hendrickx N, Vanlint J,et al. Distinet transduction meehanism of cycloxygenase2 gene activation in tumour cells after photodynamic therapy [J].Oneogene,2005, 24(18):2981-2991.
[10]Masfrrer J L,Leahy K M,Koki A T,et al. Antiangiogenic and antitumor activities of cyclooxygenase-2 inhibitors [J]. Ca-ncer Res,2000,60:1306-1311.
[11]Tang X,liu D,Shishodia S,et al Nuclear factor-kappa B(NF-Kappa B) is frequently expressedin lung cancer and preneoplasticlesions[J].cancer,2006,107(11):263-2646.
[12]Adach A, Ellert-Miklaszewska A, Kaminska B,et al.Molecular characterization of STAT signaling in inflammation and tumorigenesis[J]. Methods Mol Biol.2009; 512:265-78.
[13]De Stefano D, De Rosa G, Maiuri MC,et al.Oligonucleotide decoy to NF-kappaB slowly released from PLGA microspheres reduces chronic inflammation in rat[J]. Pharmacol Res. 2009 Jul; 60(1):33-40.
[14]Hoel AW, Conte MS,et al. Edifoligide: a transcription factor decoy to modulate smooth muscle cell proliferation in vein bypass [J]. Cardiovasc Drug Rev.2007 Fall; 25(3):221-34.
[15]Seki Y, Yamamoto H, Ngan CY, et al.Construction of a novel DNA decoy that inhibits the oncogenic beta-catenin/T-cell factor pathway [J]. Mol Cancer Ther.2006 Apr; 5(4):985-94.
[16]Kim SJ, Park JH, Kim KH, Lee WR,et al.Effect of NF-kB decoy oligodeoxynucleotide on LPS/high-fat diet-induced atherosclerosis in an animal model[J].Basic Clin Phannacol Toxicol.2010 Dec; 107(6):925-30.
[17]Shiraya S, Miwa K, Aoki M, et al. Hypertension accelerated experimental abdominal aortic aneurysm through upregulation of nuclear factor kappaB and Ets [J].Hypertension.2006 Oct; 48(4):628-36.
[18]Miyake T, Aoki M, Osako MK, et al.Systemic administration of ribbon-type decoy oligodeoxynucleotide against nuclear factor kB and ets prevents abdominal aortic aneurysm in rat model [J]. Mol Ther.2011 Jan; 19(1):181-7.
[19]Egashira K, Suzuki J, Ito H,et al.. Long-term follow up of initial clinical cases with NF-kappaB decoy oligodeoxynucleotide transfection at the site of coronary stenting [J]. J Gene Med.2008 Jul; 10 (7):805-9.
[20]Aoki T, Kataoka H, Shimamura M,et al. NF-kappaB is a key mediator of cerebral aneurysm formation [J]. Circulation.2007 Dec 11; 116(24):2830-40.
[21]Nakagami H, Tomita N, Kaneda Y, et al.Anti-oxidant gene therapy by NF kappa B decoy oligodeoxy nucleotide [J]. Curr Pharm Biotechnol.2006 Apr; 7(2):95-100.
[22]Nishimura A, Akeda K, Matsubara T,et al. Transfection of NF-kB decoy oligodeoxynucleotide suppresses pulmonary metastasis by murine osteosarcoma [J]. Cancer Gene Ther.2011 Apr; 18(4):250-9.
[23]Tomita T, Kunugiza Y, Nomura K, et al.Application of NFkappaB inhibitor for arthritis [J].Nihon Rinsho Meneki Gakkai Kaishi.2009 Apr; 32(2):71-6.
[24]Igwe OJ, et al.Modulation of peripheral inflammation in sensory ganglia by nuclear factor (kappa) B decoy oligodeoxynucleotide: involvement of SRC kinase pathway [J]. Neurosci Lett.2005 Jun 10-17; 381(1-2):114-9.
[25]Matsuda N, Teramae H, Futatsugi M, et al.Up-regulation of histamine H4 receptors contributes to splenic apoptosis in septic mice: counteraction of the antiapoptotic action of nuclear factor-kappaB [J]. J Phannacol Exp Ther.2010 Mar; 332(3):730-7.
[26]Wagner AH, Wittjen I, Stojanovic T, et al. Signal transducer and activator of transcription 1 decoy oligodeoxynucleotide suppression of contact hypersensitivity [J]. J Allergy Clin Immunol.2008 Jan; 121 (1):158-165.
[27]Hwang SY, Woo CW, Au-Yeung KK, et al. Homocysteine stimulates monocyte chemoattractant protein-1 expression in the kidney via nuclear factor-kappaB activation [J]. Am J Physiol Renal Physiol.2008 Jan; 294(1):F236-44.
[28]Moriyama Ⅰ, Ishihara S, Rumi MA,et al. Decoy oligodeoxynucleotide targeting activator protein-1 (AP-1) attenuates intestinal inflammation in murine experimental colitis[J]. Lab Invest.2008 Jun; 88(6):652-63.
[29]De Stefano D, Nicolaus G, Maiuri MC, et al.NF-kappaB blockade upregulates Bax, TSP-1, and TSP-2 expression in rat granulation tissue [J]. J Mol Med.2009 May; 87(5):481-92.
[30]Kim KH, Lee ES, Cha SH,et al.Transcriptional regulation of NF-kappaB by ring type decoy oligodeoxynucleotide in an animal model of nephropathy[J]. Exp Mol Pathol.2009 Apr; 86(2):114-20.
[31]Son G, Iimuro Y, Seki E,, et al.Selective inactivation of NF-kappaB in the liver using NF-kappaB decoy suppresses CC14-induced liver injury and fibrosis[J]. Am J Physiol Gastrointest Liver Physiol.2007 Sep; 293(3):G631-9.
[32]Hoffmann F, Sass G, Zillies J, et al.A novel technique for selective NF-kappaB inhibition in Kupffer cells: contrary effects in fulminant hepatitis and ischaemia-reperfusion [J]. Gut. 2009 Dec; 58(12):1670-8.
[33]Park JH, Jo JH, Kim KH,et al.Antifibrotic effect through the regulation of transcription factor using ring type-Spl decoy oligodeoxynucleotide in carbon tetrachloride-induced liver fibrosis[J]. J Gene Med.2009 Sep; 11(9):824-33.
[34]Tadlaoui Hbibi A, Laguillier C, Souissi I, et al.Efficient killing of SW480 colon carcinoma cells by a signal transducer and activator of transcription (STAT) 3 hairpin decoy oligodeoxynucleotide--interference with interferon-gamma-STATl-mediated killing [J]. FEBS J.2009 May; 276(9):2505-15.
[35]Luhrmann A, Tschernig T, von der Leyen H, et al.Decoy oligodeoxynucleotide against STAT transcription factors decreases allergic inflammation in a rat asthma model [J]. Exp Lung Res.2010 Mar; 36(2):85-93.
[36]Zhang X, Liu P, Zhang B, et al.Role of STAT3 decoy oligodeoxynucleotides on cell invasion and chemosensitivity in human epithelial ovarian cancer cell [J]s. Cancer Genet Cytogenet.2010 Feb; 197(1):46-53.
[37]Isomura I, Tsujimura K, Morita A,et al.Antigen-specific peripheral tolerance induced by topical application of NF-kappaB decoy oligodeoxynucleotide [J].J Invest Dermatol.2006 Jan; 126(1):97-104.
[38]Tomita T, Kunugiza Y, Tomita N,et al.E2F decoy oligodeoxynucleotide ameliorates cartilage invasion by infiltrating synovium derived from rheumatoid arthritis[J]. Int J Mol Med.2006 Aug; 18(2):257-65.
[39]Zhu K, Amin MA, Zha Y, et al.Mechanism by which H-2g, a glucose analog of blood group H antigen, mediates angiogenesis [J]. Blood.2005 Mar 15; 105(6):2343-9.
[40]Zhang X, Zhang J, Wang L, et al.Therapeutic effects of STAT3 decoy oligodeoxynucleotide on human lung cancer in xenograft mice [J]. BMC Cancer.2007 Aug 4; 7:149.
[41]Zhang X, Zhang J, Wei H, et al.STAT3-decoy oligodeoxynucleotide inhibits the growth of human lung cancer via down-regulating its target genes [J]. Oncol Rep.2007 Jun;17(6):1377-82.
[42]Tang CH, Tan TW, Fu WM, et al. Involvement of matrix metalloproteinase-9 in stromal cell-derived factor-1/CXCR4 pathway of lung cancer metastasis [J]. Carcinogenesis.2008 Jan; 29(1):35-43.
[43]Gao H, Xiao J, Sun Q, et al, A single decoy oligodeoxynucleotides targeting multiple oncoproteins produces strong anticancer effects[J]. Mol Pharmacol.2006 Nov; 70(5):1621-9.
[44]Voant C, Hendrickx N, Vanlint J,et al. Distinet transduction meehanism of cycloxygenase2 gene activation in tumour cells after photodynamic therapy [J]. Oneogene,2005, 24(18):2981-2991.
[45]Laguillier C,Hbibi AT, et al. Cell death in NF-kappaB-dependent tumour cell lines as a result of NF-kappaB trapping by linker-modified hairpin decoy oligonucleotide [J]. FEBS Lett.2007 Mar 20; 581 (6):1143-50.
[46]Parry TJ,Brosius R, et al. Drug-eluting stents: sirolimus and paclitaxel differentially affect cultured cells and injured arteries [J]. Eur J Pharmacol,2005 Nov 7; 524(1-3):19-29.
[47]Mi J, Zhang X, Rabbani ZN, et al. RNA aptamer-targeted inhibition of NF-kappa B suppresses non-small cell lung cancer resistance to doxorubicin[J]. Mol Ther,2008 Jan;16(1):66-73.
[48]Kim SJ, Seo JH, Lee YJ, et al. Autocrine vascular endothelial growth factor/vascular endothelial growth factor receptor-2 growth pathway represents a cyclooxygenase-2-independent target for the cyclooxygenase-2 inhibitor NS-398 in colon cancer cells [J]. Oncology,2005;68(2-3):204-11.
[49]Shishodia S, Gutierrez AM, Lotan R,et al. N-(4-hydroxyphenyl)retinamide inhibits invasion, suppresses osteoclastogenesis, and potentiates apoptosis through down-regulation of I(kappa)B(alpha) kinase and nuclear factor-kappaB-regulated gene products[J]. Cancer Res,2005 Oct 15; 65(20):9555-65.
[50]Lu JP, Sun H, Cao CC, et al.Influence of nuclear factor-kappaB decoy transfection on nuclear factor-kappaB activity and vascular endothelial growth factor/urokinase-type plasminogen activator/intercellular cell adhesion molecule-1 level of SKOV3 cells [J].Zhonghua Fu Chan Ke Za Zhi,2004,39(8):533-566.
[51]Eibl G,Bruemmer D,Okada Y,et al.PGE(2) is generated by specific COX-2 activity and increases VEGF production in COX-2 expressing human pancreatic cancer cells[J]. Biochem Biophys Res Commun,2003,306(4):887-897.
[52]Campa D, Zienolddiny S, Maggini V,et al. Association of a common polymorphism in the cyclooxygenase 2 gene with risk of non-small cell lung cancer [J]. Carcinogenesis,2004 Feb;25(2):229-35.
[53]Boldrini L, Gisfredi S, Ursino S, et al. lnterleukin-8 in non-small cell lung carcinoma: relation with angiogenic pattern and p53 alterations[J].Lung Cancer,2005 Dec;50(3): 309-17.
[54]Spano JP, Chouahnia K, Morere JF,et al. Cyclooxygenase 2 inhibitors and lung carcinoma [J].Bull Cancer,2004 May 1;91 Suppl 2:S109-12.
[55]Liu H, Yang Y, Xiao J,et al. Inhibition of cyclooxygenase-2 suppresses lymph node metastasis via VEGF-C [J]. Anat Rec (Hoboken).2009 Oct; 292(10):1577-83.
[56]Koch A, Gustafsson B, Fohlin H,et al. Cyclooxygenase-2 expression in lung cancer cells evaluated by immunocytochemistry[J]. Diagn Cytopathol,2011 Mar; 39(3):188-93.
[57]Rovina N, Hillas G, Dima E, et al. VEGF and IL-18 in induced sputum of lung cancer patients [J]. Cytokine.2011 Mar 11.
[58]Homsi J, Daud AI, et al. Spectrum of activity and mechanism of action of VEGF/PDGF inhibitors [J]. Cancer Control,2007 Jul; 14(3):285-94.
[59]Rohrer Bley C, Orlowski K, Furmanova P, et al. Regulation of VEGF-expression by patupilone and ionizing radiation in lung adenocarcinoma cells. [J] Lung Cancer.2011 Feb 16.
[60]]Li M, Chen H, Diao L,et al.Caveolin-1 and VEGF-C promote lymph node metastasis in the absence of intratumoral lymphangiogenesis in non-small cell lung cancer[J]. Tumori. 2010 Sep-Oct;96(5):734-43.
[61]Awasthi N, Schwarz MA, Verma V,et al. Endothelial monocyte activating polypeptide II interferes with VEGF-induced proangiogenic signaling [J]. Lab Invest.2009 Jan;89(1): 38-46.
[62]Strieth S, Eichhorn ME, et al. Paclitaxel encapsulated in cationic liposomes increases tumor microvessel leakiness and improves therapeutic efficacy in combination with Cisplatin [J]. Clin Cancer Res,2008 Jul 15; 14(14):4603-11.
[1]Sousa JR, Silva AC, de Paiva AC, et al. Methodology for automatic detection of lung nodes in computerized tomography images [J]. Comput Methods Programs Biomed.2010 Apr; 98(1):1-14.
[2]Sun H, Wang S, Ou W, Zhang B, Yang H, Fang Q, Li P, et al. A Prospective Randomized Study of Adjuvant Chemotherapy in Resected Stage ⅢA-N2 Non-small Cell Lung Cancer [J]. Zhongguo Fei Ai Za Zhi.2009 Sep 20; 12(9):975-82.
[3]Pandey S, Kekre N, Naderi J, et al. Induction of apoptotic cell death specifically in rat and human cancer cells by pancratistatin [J]. Artif Cells Blood Substit Immobil Biotechnol. 2005; 33(3):279-95.
[4]Zhao Y, Wu S, Wu J, et al. Introduction of hypoxia-targeting p53 fusion protein for the selective therapy of non-small cell lung cancer [J]. Cancer Biol Ther. 2011 Jan 1; 11(1): 95-107.
[5]Banerjee S, Manna S, Saha P, et al. Black tea polyphenols suppress cell proliferation and induce apoptosis during benzo (a) pyrene-induced lung carcinogenesis [J]. Eur J Cancer Prev.2005 Jun; 14(3):215-21.
[6]Huang CC, Lo CP, Chiu CY, et al. Deoxyelephantopin, a novel mtifunctional agent, suppresses mammary tumour growth and lung metastasis and doubles survival time in mice [J]. Br J Pharmacol.2010 Feb; 159 (4):856-71.
[7]Cheng ZD, Chen YG, et al.Effect of acupuncture combined with intraperitoneal injection of paclitaxel on apoptosis in Lewis mice with lung carcinoma [J]. Zhen Ci Yan Jiu.2007; 32(3):153-7.
[8]Balcerek M, et al. Chemoprevention of tobacco-related lung cancer by cruciferous vegetable [J]. Przegl Lek.2007; 64(10):903-5.
[9]Hoel AW, Conte MS, et al. Edifoligide: a transcription factor decoy to modate smooth muscle cell proliferation in vein bypass [J]. Cardiovasc Drug Rev.2007 Fall; 25(3):221-34.
[10]Voant C, Hendrickx N, Vanlint J,et al. Distinet transduction meehanism of cycloxygenase2 gene activation in tumour cells after photodynamic therapy [J].Oneogene,2005,24(18): 2981-2991.
[11]Wang JH,Huang QK,Chen MX Expression and significance of nuclear factor kappa B in liver cancer line of SMMC 7721 [J]. Chinese J of Gastroenterol and Hepatol,2002, 11(1):25-28.
[12]J VoantC, Hendrickx N, Vanlint J,et al Distinet transduction meehanism of cycloxygenase2 gene activation in tumour cells after photodynamic therapy[J].Oneogene,2005,24.
[13]Eibl G,Bruemmer D,Okada Y,et al.PGE(2) is generated by specific COX-2 activity and increases VEGF production inCOX-2 expressing human pancreatic cancer cells [J]. Biochem Biophys ResCommun,2003,306(4):887-897.
[14]Tang X,liu D,Shishodia S,et al Nuclear factor-kappa B(NF-Kappa B) is frequently expressed in lung cancer and preneoplasticlesions[J].cancer,2006,107(11):263-2646):25-28.
[15]Lin CH, Hsiao YM, Ou CC, et al. GMI, a Ganoderma immunomodulatory protein, down-regulates tumor necrosis factor a-induced expression of matrix metalloproteinase 9 via NF-κB pathway in human alveolar epithelial A549 cells [J]. J Agric Food Chem.2010 Nov 24;58(22):12014-21.
[16]Guo J, Jie W, Kuang D, et al. Ischaemia/reperfusion induced cardiac stem cell homing to the injured myocardium by stimulating stem cell factor expression via NF-kappaB pathway [J]. Int J Exp Pathol.2009 Jun; 90(3):355-64.
[17]Tan W, Zhang W, Strasner A, et al. Tumour-infiltrating regulatory T cells stimulate mammary cancer metastasis through RANKL-RANK. signaling [J]. Nature.2011 Feb 24; 470(7335):548-53.
[18]Sethi G, Ahn KS, Sandur SK, et al. Indirubin enhances tumor necrosis factor-induced apoptosis through modulation of nuclear factor-kappa B signaling pathway [J]. J Biol Chem.2006 Aug 18; 281(33):23425-35.
[19]Sarkar P, Hayes BE,et al. Induction of COX-2 by acrolein in rat lung epithelial cells[J]. Mol Cell Biochem [J],2007 Jul; 301(1-2):191-220.
[20]Werynska B, Dziegiel P, Jankowska R, et al. Role of lymphangiogenesis in lung cancer. Folia Histochem Cytobiol [J].2009 Jan; 47(3):333-42.
[21]Gill JS, Zhu X, Moore MJ, et al. Effects of NFκB decoy oligonucleotides released from biodegradable polymer micropar2 ticles on a glioblastoma cell line [J]. Biomaterials 2002,23:2773-2781.
[22]Karin M,Berrneriah Y, et al. Phorylation meets nbiquition.The Control of NF-kB activity [J].AnnuRer Immunol,2000,18:621-663.
[23]Zhang X, Liu P, Zhang B, et al. Role of STAT3 decoy oligodeoxynucleotides on cell invasion and chemosensitivity in human epithelial ovarian cancer cells [J]. Cancer Genet Cytogenet.2010 Feb; 197(1):46-53.
[24]Zhang N, Xu YJ, Zhang ZX, et al.In vivo transfection of cis element'decoy'against nuclear factor-kappaB binding site modulates function of T lymphocytes in asthma[J]. Zhonghua Jie He He Hu Xi Za Zhi.2004 Jan; 27(1):36-40.
[25]Parry TJ,Brosius R, et al. Drug-eluting stents: sirolimus and paclitaxel differentially affect cultured cells and injured arteries [J]. Eur J Pharmacol,2005 Nov 7; 524 (1-3):19-29.
[26]McLachlan A, Kekre N, McNulty J, et al. Pancratistatin:a natural anti-cancer compound that targets mitochondria specifically in cancer cells to induce apoptosis [J]. Apoptosis. 2005 May; 10(3):619-30.
[27]Kim H, Chung H, Kim HJ, et al. Id-1 regulates Bcl-2 and Bax expression through p53 and NF-kappaB in MCF-7 breast cancer cells.[J] Breast Cancer Res Treat.2008 Nov; 112(2):287-96.
[28]Huang CC, Lo CP, Chiu CY, et al. Deoxyelephantopin, a novel multifunctional agent, suppresses mammary tumour growth and lung metastasis and doubles survival time in mice [J]. BrJ Pharmacol.2010 Feb; 159(4):856-71.
[29]Chung WH, Sung BH, Kim SS, et al. Synergistic interaction between tetra-arsenic oxide and paclitaxel in human cancer cells in vitro [J].Int J Oncol.2009 Jun; 34(6):1669-79.
[30]Baratt A, Arkhipov SN, Maly Ⅳ., et al. An experimental and computational study of effects of microtubule stabilization on T-cell polarity[J]. PLoS One.2008;3(12):e3861.
[31]de Mareuil J, Carre M, Barbier P, et al. HIV-1 Tat protein enhances microtubule polymerization[J]. Retrovirology.2005 Feb 3;2:5.
[32]Lee KH, Yim EK, Kim CJ, et al. Proteomic analysis of anti-cancer effects by paclitaxel treatment in cervical cancer cells[J].Gynecol Oncol.2005 Jul;98(1):45-53.
[33]Lim Soo P, Cho J, Grant J, et al. Drug release mechanism of paclitaxel from a chitosan-lipid implant system:effect of swelling, degradation and morphology [J]. Eur J Pharm Biopharm.2008 May; 69(1):149-57.
[34]Krupitskaya Y, Wakelee HA, et al. Ramucirumab, a fully human mAb to the transmembrane signaling tyrosine kinase VEGFR-2 for the potential treatment of cancer [J]. Curr Opin Investig Drugs,2009 Jun;10(6):597-605.
[35]Voant C, Hendrickx N, Vanlint J,et al. Distinet transduction meehanism of cycloxygenase2 gene activation in tumour cells after photodynamic therapy [J]. Oneogene,2005,24(18): 2981-2991.
[36]Ohta M,Konno H,Tanak T,et al.Effect of combination therapy with matrix metalloproteinase inhibitor MMI-166 and mitomycin C on the growth and liver metastasis of human colon cancer[J].Jpn J Cancer Res,2002,92(6):168-195.
[2]Dufey DC,Crawl BCV,Chen Z,et al. Inhibiyion of transcription factor nuclear factor-Kappa B by a mutant inhibitor-kappa B alphaattenuates resistance of human head and neck squamous cell carcinoma to TNF-alpha caspase mediated cell death[J].BrJ Cancer,2000, 83(10):1367-1374.
[3]Sarkar P, Hayes BE, et al. Induction of COX-2 by acrolein in rat lung epithelial cells [J]. Mol Cell Biochem,2007 Jul; 301(1-2):191-220.
[4]Voant C, Hendrickx N, Vanlint J,et al. Distinct transduction meehanism of cycloxygenase2 gene activation in tumour cells after photodynamic therapy [J]. Oneogene,2005, 24(18):2981-2991.
[5]Krupitskaya Y, Wakelee HA, et al. Ramucirumab, a fully human mAb to the transmembrane signaling tyrosine kinase VEGFR-2 for the potential treatment of cancer [J]. Curr Opin Investig Drugs,2009 Jun;10(6):597-605.
[6]McLachlan A, Kekre N, McNulty J, et al. Pancratistatin:a natural anti-cancer compound that targets mitochondria specifically in cancer cells to induce apoptosis [J]. Apoptosis. 2005 May;10(3):619-630
[7]Huang CC, Lo CP, Chiu CY, et al. Deoxyelephantopin, a novel multifunctional agent, suppresses mammary tumour growth and lung metastasis and doubles survival time in mice [J]. Br J Pharmacol.2010 Feb; 159(4):856-871.
[8]Marrs J.Zubal BA,et al. Oncology nursing in a new era:optimizing treatment with bevacizumab[J]. Clin J Oncol Nurs,2009 Oct; 13(5):564-72.
[9]Voant C, Hendrickx N, Vanlint J,et al. Distinet transduction meehanism of cycloxygenase2 gene activation in tumour cells after photodynamic therapy [J].Oneogene,2005, 24(18):2981-2991.
[10]Masfrrer J L,Leahy K M,Koki A T,et al. Antiangiogenic and antitumor activities of cyclooxygenase-2 inhibitors [J]. Ca-ncer Res,2000,60:1306-1311.
[11]Tang X,liu D,Shishodia S,et al Nuclear factor-kappa B(NF-Kappa B) is frequently expressedin lung cancer and preneoplasticlesions[J].cancer,2006,107(11):263-2646.
[12]Adach A, Ellert-Miklaszewska A, Kaminska B,et al.Molecular characterization of STAT signaling in inflammation and tumorigenesis[J]. Methods Mol Biol.2009; 512:265-78.
[13]De Stefano D, De Rosa G, Maiuri MC,et al.Oligonucleotide decoy to NF-kappaB slowly released from PLGA microspheres reduces chronic inflammation in rat[J]. Pharmacol Res. 2009 Jul; 60(1):33-40.
[14]Hoel AW, Conte MS,et al. Edifoligide: a transcription factor decoy to modulate smooth muscle cell proliferation in vein bypass [J]. Cardiovasc Drug Rev.2007 Fall; 25(3):221-34.
[15]Seki Y, Yamamoto H, Ngan CY, et al.Construction of a novel DNA decoy that inhibits the oncogenic beta-catenin/T-cell factor pathway [J]. Mol Cancer Ther.2006 Apr; 5(4):985-94.
[16]Kim SJ, Park JH, Kim KH, Lee WR,et al.Effect of NF-kB decoy oligodeoxynucleotide on LPS/high-fat diet-induced atherosclerosis in an animal model[J].Basic Clin Phannacol Toxicol.2010 Dec; 107(6):925-30.
[17]Shiraya S, Miwa K, Aoki M, et al. Hypertension accelerated experimental abdominal aortic aneurysm through upregulation of nuclear factor kappaB and Ets [J].Hypertension.2006 Oct; 48(4):628-36.
[18]Miyake T, Aoki M, Osako MK, et al.Systemic administration of ribbon-type decoy oligodeoxynucleotide against nuclear factor kB and ets prevents abdominal aortic aneurysm in rat model [J]. Mol Ther.2011 Jan; 19(1):181-7.
[19]Egashira K, Suzuki J, Ito H,et al.. Long-term follow up of initial clinical cases with NF-kappaB decoy oligodeoxynucleotide transfection at the site of coronary stenting [J]. J Gene Med.2008 Jul; 10 (7):805-9.
[20]Aoki T, Kataoka H, Shimamura M,et al. NF-kappaB is a key mediator of cerebral aneurysm formation [J]. Circulation.2007 Dec 11; 116(24):2830-40.
[21]Nakagami H, Tomita N, Kaneda Y, et al.Anti-oxidant gene therapy by NF kappa B decoy oligodeoxy nucleotide [J]. Curr Pharm Biotechnol.2006 Apr; 7(2):95-100.
[22]Nishimura A, Akeda K, Matsubara T,et al. Transfection of NF-kB decoy oligodeoxynucleotide suppresses pulmonary metastasis by murine osteosarcoma [J]. Cancer Gene Ther.2011 Apr; 18(4):250-9.
[23]Tomita T, Kunugiza Y, Nomura K, et al.Application of NFkappaB inhibitor for arthritis [J].Nihon Rinsho Meneki Gakkai Kaishi.2009 Apr; 32(2):71-6.
[24]Igwe OJ, et al.Modulation of peripheral inflammation in sensory ganglia by nuclear factor (kappa) B decoy oligodeoxynucleotide: involvement of SRC kinase pathway [J]. Neurosci Lett.2005 Jun 10-17; 381(1-2):114-9.
[25]Matsuda N, Teramae H, Futatsugi M, et al.Up-regulation of histamine H4 receptors contributes to splenic apoptosis in septic mice: counteraction of the antiapoptotic action of nuclear factor-kappaB [J]. J Phannacol Exp Ther.2010 Mar; 332(3):730-7.
[26]Wagner AH, Wittjen I, Stojanovic T, et al. Signal transducer and activator of transcription 1 decoy oligodeoxynucleotide suppression of contact hypersensitivity [J]. J Allergy Clin Immunol.2008 Jan; 121 (1):158-165.
[27]Hwang SY, Woo CW, Au-Yeung KK, et al. Homocysteine stimulates monocyte chemoattractant protein-1 expression in the kidney via nuclear factor-kappaB activation [J]. Am J Physiol Renal Physiol.2008 Jan; 294(1):F236-44.
[28]Moriyama Ⅰ, Ishihara S, Rumi MA,et al. Decoy oligodeoxynucleotide targeting activator protein-1 (AP-1) attenuates intestinal inflammation in murine experimental colitis[J]. Lab Invest.2008 Jun; 88(6):652-63.
[29]De Stefano D, Nicolaus G, Maiuri MC, et al.NF-kappaB blockade upregulates Bax, TSP-1, and TSP-2 expression in rat granulation tissue [J]. J Mol Med.2009 May; 87(5):481-92.
[30]Kim KH, Lee ES, Cha SH,et al.Transcriptional regulation of NF-kappaB by ring type decoy oligodeoxynucleotide in an animal model of nephropathy[J]. Exp Mol Pathol.2009 Apr; 86(2):114-20.
[31]Son G, Iimuro Y, Seki E,, et al.Selective inactivation of NF-kappaB in the liver using NF-kappaB decoy suppresses CC14-induced liver injury and fibrosis[J]. Am J Physiol Gastrointest Liver Physiol.2007 Sep; 293(3):G631-9.
[32]Hoffmann F, Sass G, Zillies J, et al.A novel technique for selective NF-kappaB inhibition in Kupffer cells: contrary effects in fulminant hepatitis and ischaemia-reperfusion [J]. Gut. 2009 Dec; 58(12):1670-8.
[33]Park JH, Jo JH, Kim KH,et al.Antifibrotic effect through the regulation of transcription factor using ring type-Spl decoy oligodeoxynucleotide in carbon tetrachloride-induced liver fibrosis[J]. J Gene Med.2009 Sep; 11(9):824-33.
[34]Tadlaoui Hbibi A, Laguillier C, Souissi I, et al.Efficient killing of SW480 colon carcinoma cells by a signal transducer and activator of transcription (STAT) 3 hairpin decoy oligodeoxynucleotide--interference with interferon-gamma-STATl-mediated killing [J]. FEBS J.2009 May; 276(9):2505-15.
[35]Luhrmann A, Tschernig T, von der Leyen H, et al.Decoy oligodeoxynucleotide against STAT transcription factors decreases allergic inflammation in a rat asthma model [J]. Exp Lung Res.2010 Mar; 36(2):85-93.
[36]Zhang X, Liu P, Zhang B, et al.Role of STAT3 decoy oligodeoxynucleotides on cell invasion and chemosensitivity in human epithelial ovarian cancer cell [J]s. Cancer Genet Cytogenet.2010 Feb; 197(1):46-53.
[37]Isomura I, Tsujimura K, Morita A,et al.Antigen-specific peripheral tolerance induced by topical application of NF-kappaB decoy oligodeoxynucleotide [J].J Invest Dermatol.2006 Jan; 126(1):97-104.
[38]Tomita T, Kunugiza Y, Tomita N,et al.E2F decoy oligodeoxynucleotide ameliorates cartilage invasion by infiltrating synovium derived from rheumatoid arthritis[J]. Int J Mol Med.2006 Aug; 18(2):257-65.
[39]Zhu K, Amin MA, Zha Y, et al.Mechanism by which H-2g, a glucose analog of blood group H antigen, mediates angiogenesis [J]. Blood.2005 Mar 15; 105(6):2343-9.
[40]Zhang X, Zhang J, Wang L, et al.Therapeutic effects of STAT3 decoy oligodeoxynucleotide on human lung cancer in xenograft mice [J]. BMC Cancer.2007 Aug 4; 7:149.
[41]Zhang X, Zhang J, Wei H, et al.STAT3-decoy oligodeoxynucleotide inhibits the growth of human lung cancer via down-regulating its target genes [J]. Oncol Rep.2007 Jun;17(6):1377-82.
[42]Tang CH, Tan TW, Fu WM, et al. Involvement of matrix metalloproteinase-9 in stromal cell-derived factor-1/CXCR4 pathway of lung cancer metastasis [J]. Carcinogenesis.2008 Jan; 29(1):35-43.
[43]Gao H, Xiao J, Sun Q, et al, A single decoy oligodeoxynucleotides targeting multiple oncoproteins produces strong anticancer effects[J]. Mol Pharmacol.2006 Nov; 70(5):1621-9.
[44]Voant C, Hendrickx N, Vanlint J,et al. Distinet transduction meehanism of cycloxygenase2 gene activation in tumour cells after photodynamic therapy [J]. Oneogene,2005, 24(18):2981-2991.
[45]Laguillier C,Hbibi AT, et al. Cell death in NF-kappaB-dependent tumour cell lines as a result of NF-kappaB trapping by linker-modified hairpin decoy oligonucleotide [J]. FEBS Lett.2007 Mar 20; 581 (6):1143-50.
[46]Parry TJ,Brosius R, et al. Drug-eluting stents: sirolimus and paclitaxel differentially affect cultured cells and injured arteries [J]. Eur J Pharmacol,2005 Nov 7; 524(1-3):19-29.
[47]Mi J, Zhang X, Rabbani ZN, et al. RNA aptamer-targeted inhibition of NF-kappa B suppresses non-small cell lung cancer resistance to doxorubicin[J]. Mol Ther,2008 Jan;16(1):66-73.
[48]Kim SJ, Seo JH, Lee YJ, et al. Autocrine vascular endothelial growth factor/vascular endothelial growth factor receptor-2 growth pathway represents a cyclooxygenase-2-independent target for the cyclooxygenase-2 inhibitor NS-398 in colon cancer cells [J]. Oncology,2005;68(2-3):204-11.
[49]Shishodia S, Gutierrez AM, Lotan R,et al. N-(4-hydroxyphenyl)retinamide inhibits invasion, suppresses osteoclastogenesis, and potentiates apoptosis through down-regulation of I(kappa)B(alpha) kinase and nuclear factor-kappaB-regulated gene products[J]. Cancer Res,2005 Oct 15; 65(20):9555-65.
[50]Lu JP, Sun H, Cao CC, et al.Influence of nuclear factor-kappaB decoy transfection on nuclear factor-kappaB activity and vascular endothelial growth factor/urokinase-type plasminogen activator/intercellular cell adhesion molecule-1 level of SKOV3 cells [J].Zhonghua Fu Chan Ke Za Zhi,2004,39(8):533-566.
[51]Eibl G,Bruemmer D,Okada Y,et al.PGE(2) is generated by specific COX-2 activity and increases VEGF production in COX-2 expressing human pancreatic cancer cells[J]. Biochem Biophys Res Commun,2003,306(4):887-897.
[52]Campa D, Zienolddiny S, Maggini V,et al. Association of a common polymorphism in the cyclooxygenase 2 gene with risk of non-small cell lung cancer [J]. Carcinogenesis,2004 Feb;25(2):229-35.
[53]Boldrini L, Gisfredi S, Ursino S, et al. lnterleukin-8 in non-small cell lung carcinoma: relation with angiogenic pattern and p53 alterations[J].Lung Cancer,2005 Dec;50(3): 309-17.
[54]Spano JP, Chouahnia K, Morere JF,et al. Cyclooxygenase 2 inhibitors and lung carcinoma [J].Bull Cancer,2004 May 1;91 Suppl 2:S109-12.
[55]Liu H, Yang Y, Xiao J,et al. Inhibition of cyclooxygenase-2 suppresses lymph node metastasis via VEGF-C [J]. Anat Rec (Hoboken).2009 Oct; 292(10):1577-83.
[56]Koch A, Gustafsson B, Fohlin H,et al. Cyclooxygenase-2 expression in lung cancer cells evaluated by immunocytochemistry[J]. Diagn Cytopathol,2011 Mar; 39(3):188-93.
[57]Rovina N, Hillas G, Dima E, et al. VEGF and IL-18 in induced sputum of lung cancer patients [J]. Cytokine.2011 Mar 11.
[58]Homsi J, Daud AI, et al. Spectrum of activity and mechanism of action of VEGF/PDGF inhibitors [J]. Cancer Control,2007 Jul; 14(3):285-94.
[59]Rohrer Bley C, Orlowski K, Furmanova P, et al. Regulation of VEGF-expression by patupilone and ionizing radiation in lung adenocarcinoma cells. [J] Lung Cancer.2011 Feb 16.
[60]]Li M, Chen H, Diao L,et al.Caveolin-1 and VEGF-C promote lymph node metastasis in the absence of intratumoral lymphangiogenesis in non-small cell lung cancer[J]. Tumori. 2010 Sep-Oct;96(5):734-43.
[61]Awasthi N, Schwarz MA, Verma V,et al. Endothelial monocyte activating polypeptide II interferes with VEGF-induced proangiogenic signaling [J]. Lab Invest.2009 Jan;89(1): 38-46.
[62]Strieth S, Eichhorn ME, et al. Paclitaxel encapsulated in cationic liposomes increases tumor microvessel leakiness and improves therapeutic efficacy in combination with Cisplatin [J]. Clin Cancer Res,2008 Jul 15; 14(14):4603-11.
[1]Sousa JR, Silva AC, de Paiva AC, et al. Methodology for automatic detection of lung nodes in computerized tomography images [J]. Comput Methods Programs Biomed.2010 Apr; 98(1):1-14.
[2]Sun H, Wang S, Ou W, Zhang B, Yang H, Fang Q, Li P, et al. A Prospective Randomized Study of Adjuvant Chemotherapy in Resected Stage ⅢA-N2 Non-small Cell Lung Cancer [J]. Zhongguo Fei Ai Za Zhi.2009 Sep 20; 12(9):975-82.
[3]Pandey S, Kekre N, Naderi J, et al. Induction of apoptotic cell death specifically in rat and human cancer cells by pancratistatin [J]. Artif Cells Blood Substit Immobil Biotechnol. 2005; 33(3):279-95.
[4]Zhao Y, Wu S, Wu J, et al. Introduction of hypoxia-targeting p53 fusion protein for the selective therapy of non-small cell lung cancer [J]. Cancer Biol Ther. 2011 Jan 1; 11(1): 95-107.
[5]Banerjee S, Manna S, Saha P, et al. Black tea polyphenols suppress cell proliferation and induce apoptosis during benzo (a) pyrene-induced lung carcinogenesis [J]. Eur J Cancer Prev.2005 Jun; 14(3):215-21.
[6]Huang CC, Lo CP, Chiu CY, et al. Deoxyelephantopin, a novel mtifunctional agent, suppresses mammary tumour growth and lung metastasis and doubles survival time in mice [J]. Br J Pharmacol.2010 Feb; 159 (4):856-71.
[7]Cheng ZD, Chen YG, et al.Effect of acupuncture combined with intraperitoneal injection of paclitaxel on apoptosis in Lewis mice with lung carcinoma [J]. Zhen Ci Yan Jiu.2007; 32(3):153-7.
[8]Balcerek M, et al. Chemoprevention of tobacco-related lung cancer by cruciferous vegetable [J]. Przegl Lek.2007; 64(10):903-5.
[9]Hoel AW, Conte MS, et al. Edifoligide: a transcription factor decoy to modate smooth muscle cell proliferation in vein bypass [J]. Cardiovasc Drug Rev.2007 Fall; 25(3):221-34.
[10]Voant C, Hendrickx N, Vanlint J,et al. Distinet transduction meehanism of cycloxygenase2 gene activation in tumour cells after photodynamic therapy [J].Oneogene,2005,24(18): 2981-2991.
[11]Wang JH,Huang QK,Chen MX Expression and significance of nuclear factor kappa B in liver cancer line of SMMC 7721 [J]. Chinese J of Gastroenterol and Hepatol,2002, 11(1):25-28.
[12]J VoantC, Hendrickx N, Vanlint J,et al Distinet transduction meehanism of cycloxygenase2 gene activation in tumour cells after photodynamic therapy[J].Oneogene,2005,24.
[13]Eibl G,Bruemmer D,Okada Y,et al.PGE(2) is generated by specific COX-2 activity and increases VEGF production inCOX-2 expressing human pancreatic cancer cells [J]. Biochem Biophys ResCommun,2003,306(4):887-897.
[14]Tang X,liu D,Shishodia S,et al Nuclear factor-kappa B(NF-Kappa B) is frequently expressed in lung cancer and preneoplasticlesions[J].cancer,2006,107(11):263-2646):25-28.
[15]Lin CH, Hsiao YM, Ou CC, et al. GMI, a Ganoderma immunomodulatory protein, down-regulates tumor necrosis factor a-induced expression of matrix metalloproteinase 9 via NF-κB pathway in human alveolar epithelial A549 cells [J]. J Agric Food Chem.2010 Nov 24;58(22):12014-21.
[16]Guo J, Jie W, Kuang D, et al. Ischaemia/reperfusion induced cardiac stem cell homing to the injured myocardium by stimulating stem cell factor expression via NF-kappaB pathway [J]. Int J Exp Pathol.2009 Jun; 90(3):355-64.
[17]Tan W, Zhang W, Strasner A, et al. Tumour-infiltrating regulatory T cells stimulate mammary cancer metastasis through RANKL-RANK. signaling [J]. Nature.2011 Feb 24; 470(7335):548-53.
[18]Sethi G, Ahn KS, Sandur SK, et al. Indirubin enhances tumor necrosis factor-induced apoptosis through modulation of nuclear factor-kappa B signaling pathway [J]. J Biol Chem.2006 Aug 18; 281(33):23425-35.
[19]Sarkar P, Hayes BE,et al. Induction of COX-2 by acrolein in rat lung epithelial cells[J]. Mol Cell Biochem [J],2007 Jul; 301(1-2):191-220.
[20]Werynska B, Dziegiel P, Jankowska R, et al. Role of lymphangiogenesis in lung cancer. Folia Histochem Cytobiol [J].2009 Jan; 47(3):333-42.
[21]Gill JS, Zhu X, Moore MJ, et al. Effects of NFκB decoy oligonucleotides released from biodegradable polymer micropar2 ticles on a glioblastoma cell line [J]. Biomaterials 2002,23:2773-2781.
[22]Karin M,Berrneriah Y, et al. Phorylation meets nbiquition.The Control of NF-kB activity [J].AnnuRer Immunol,2000,18:621-663.
[23]Zhang X, Liu P, Zhang B, et al. Role of STAT3 decoy oligodeoxynucleotides on cell invasion and chemosensitivity in human epithelial ovarian cancer cells [J]. Cancer Genet Cytogenet.2010 Feb; 197(1):46-53.
[24]Zhang N, Xu YJ, Zhang ZX, et al.In vivo transfection of cis element'decoy'against nuclear factor-kappaB binding site modulates function of T lymphocytes in asthma[J]. Zhonghua Jie He He Hu Xi Za Zhi.2004 Jan; 27(1):36-40.
[25]Parry TJ,Brosius R, et al. Drug-eluting stents: sirolimus and paclitaxel differentially affect cultured cells and injured arteries [J]. Eur J Pharmacol,2005 Nov 7; 524 (1-3):19-29.
[26]McLachlan A, Kekre N, McNulty J, et al. Pancratistatin:a natural anti-cancer compound that targets mitochondria specifically in cancer cells to induce apoptosis [J]. Apoptosis. 2005 May; 10(3):619-30.
[27]Kim H, Chung H, Kim HJ, et al. Id-1 regulates Bcl-2 and Bax expression through p53 and NF-kappaB in MCF-7 breast cancer cells.[J] Breast Cancer Res Treat.2008 Nov; 112(2):287-96.
[28]Huang CC, Lo CP, Chiu CY, et al. Deoxyelephantopin, a novel multifunctional agent, suppresses mammary tumour growth and lung metastasis and doubles survival time in mice [J]. BrJ Pharmacol.2010 Feb; 159(4):856-71.
[29]Chung WH, Sung BH, Kim SS, et al. Synergistic interaction between tetra-arsenic oxide and paclitaxel in human cancer cells in vitro [J].Int J Oncol.2009 Jun; 34(6):1669-79.
[30]Baratt A, Arkhipov SN, Maly Ⅳ., et al. An experimental and computational study of effects of microtubule stabilization on T-cell polarity[J]. PLoS One.2008;3(12):e3861.
[31]de Mareuil J, Carre M, Barbier P, et al. HIV-1 Tat protein enhances microtubule polymerization[J]. Retrovirology.2005 Feb 3;2:5.
[32]Lee KH, Yim EK, Kim CJ, et al. Proteomic analysis of anti-cancer effects by paclitaxel treatment in cervical cancer cells[J].Gynecol Oncol.2005 Jul;98(1):45-53.
[33]Lim Soo P, Cho J, Grant J, et al. Drug release mechanism of paclitaxel from a chitosan-lipid implant system:effect of swelling, degradation and morphology [J]. Eur J Pharm Biopharm.2008 May; 69(1):149-57.
[34]Krupitskaya Y, Wakelee HA, et al. Ramucirumab, a fully human mAb to the transmembrane signaling tyrosine kinase VEGFR-2 for the potential treatment of cancer [J]. Curr Opin Investig Drugs,2009 Jun;10(6):597-605.
[35]Voant C, Hendrickx N, Vanlint J,et al. Distinet transduction meehanism of cycloxygenase2 gene activation in tumour cells after photodynamic therapy [J]. Oneogene,2005,24(18): 2981-2991.
[36]Ohta M,Konno H,Tanak T,et al.Effect of combination therapy with matrix metalloproteinase inhibitor MMI-166 and mitomycin C on the growth and liver metastasis of human colon cancer[J].Jpn J Cancer Res,2002,92(6):168-195.