STAT3与Survivin及VEGF在胃癌组织中的表达及意义
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摘要
目的
探讨信号传导及转录活化因子3(STAT3)、生存素(Survivin)及血管内皮生长因子(VEGF)在胃癌组织中的表达及其与临床病理特征之间的关系。
方法
采用免疫组织化学SP法检测56例胃癌组织及其癌旁正常组织中STAT3和survivin及VEGF的表达情况。
结果
1、STAT3与Survivin及VEGF三者在56例胃癌组织中的表达阳性率分别为75.0%、71.4%及76.8%,均明显高于三者在癌旁正常组织中的表达率(X2=17.75-25.84,P<0.01)；
2、三者在Ⅲ、Ⅳ期胃癌中的表达水平明显高于Ⅰ、Ⅱ期胃癌(P<0.001),胃壁浆膜受侵及、淋巴结有转移及低、未分化的胃癌中三者表达水平高于浆膜未侵及、淋巴结无转移及高、中分化的胃癌(P<0.05)；
3、STAT3、Survivin及VEGF在胃癌组织的表达两两之间均表现出正相关关系。
结论
STAT3、Survivin及VEGF的过度表达与胃癌的发生发展密切相关,STAT3的活化导致其下游靶基因Survivin及VEGF的表达明显升高,促使肿瘤迅速增长、浸润及转移。
Objective
To investigate the expression of signal transducers and activators of transcription (STAT3), Survivin and vascular endothelial growth factor (VEGF) in gastric carcinoma and the relationship between clinicopathological features.
Methods
Immunohistochemistry SP method was used to detect the expression of STAT3、survivin and VEGF in 56 cases of gastric carcinoma and adjacent normal tissue.
Results
1. The expression rate of STAT3、survivin and VEGF in 56 cases of gastric cancer tissue were 75.0%71.4% and 76.8% respectively, much higher than that cancer around tissue (X2= 17.75-25.84, P<0.01);
2. The expression rate in phaseⅢandⅣof gastric cancer was much higher than that of cancer phaseⅠandⅡ(P< 0.01).The expression rate in serous membrane invasion of gasttic wall, lymph nodes metastasis, poorly differentiated and undifferentiated gastric cancer were higher than that of no membrane invasion,no metastasis and moderately and welldifferentiated gastric cancer (P<0.05).
3. Positive correlation was found between the expression of STAT3、survivin and VEGF.
Conclusion
STAT3, Survivin and VEGF over-expression is closely related to the genesis and development of gastric cancer, STAT3 activation leads to downstream target genes of Survivin and VEGF expression was significantly increased, prompting the rapid tumor growth, invasion and metastasis.
探讨信号传导及转录活化因子3(STAT3)、生存素(Survivin)及血管内皮生长因子(VEGF)在胃癌组织中的表达及其与临床病理特征之间的关系。
方法
采用免疫组织化学SP法检测56例胃癌组织及其癌旁正常组织中STAT3和survivin及VEGF的表达情况。
结果
1、STAT3与Survivin及VEGF三者在56例胃癌组织中的表达阳性率分别为75.0%、71.4%及76.8%,均明显高于三者在癌旁正常组织中的表达率(X2=17.75-25.84,P<0.01)；
2、三者在Ⅲ、Ⅳ期胃癌中的表达水平明显高于Ⅰ、Ⅱ期胃癌(P<0.001),胃壁浆膜受侵及、淋巴结有转移及低、未分化的胃癌中三者表达水平高于浆膜未侵及、淋巴结无转移及高、中分化的胃癌(P<0.05)；
3、STAT3、Survivin及VEGF在胃癌组织的表达两两之间均表现出正相关关系。
结论
STAT3、Survivin及VEGF的过度表达与胃癌的发生发展密切相关,STAT3的活化导致其下游靶基因Survivin及VEGF的表达明显升高,促使肿瘤迅速增长、浸润及转移。
Objective
To investigate the expression of signal transducers and activators of transcription (STAT3), Survivin and vascular endothelial growth factor (VEGF) in gastric carcinoma and the relationship between clinicopathological features.
Methods
Immunohistochemistry SP method was used to detect the expression of STAT3、survivin and VEGF in 56 cases of gastric carcinoma and adjacent normal tissue.
Results
1. The expression rate of STAT3、survivin and VEGF in 56 cases of gastric cancer tissue were 75.0%71.4% and 76.8% respectively, much higher than that cancer around tissue (X2= 17.75-25.84, P<0.01);
2. The expression rate in phaseⅢandⅣof gastric cancer was much higher than that of cancer phaseⅠandⅡ(P< 0.01).The expression rate in serous membrane invasion of gasttic wall, lymph nodes metastasis, poorly differentiated and undifferentiated gastric cancer were higher than that of no membrane invasion,no metastasis and moderately and welldifferentiated gastric cancer (P<0.05).
3. Positive correlation was found between the expression of STAT3、survivin and VEGF.
Conclusion
STAT3, Survivin and VEGF over-expression is closely related to the genesis and development of gastric cancer, STAT3 activation leads to downstream target genes of Survivin and VEGF expression was significantly increased, prompting the rapid tumor growth, invasion and metastasis.
引文
1 Haura EB, Turkson J, Jove R. Mechanisms of diease:in-sights into the emerging role of signal transducers and activators of transcription in cancer[J]. Nat Clin Pract Oncol,2005, 2(6):315-324.
2 Hoey T,Grusby M J. STATs as mediators of cytokine-induced response[J]. Adv Immunol,1998,71 (1):145-160
3 LU B, MU Y, CAO C, et al. Survivin as a therapeutic target for radiation sensitization in lung cancer [J]. Cancer Res,2004,64:284022845.
4 Sung BJ, Cho YS, Kim HJ, et al. An anti2apoptotic p rotein,human survivin is a direct inhibitor of caspase23 and caspase 27 [J]. Biochemist ry,2001,40 (4):111721123.
5 Hoey T, Grusby MJ.STATs as mediators of cytokine2induced response[J].Adv Immumol,1999;71:145-62.
6 Ma XT, Wang S, Ye YJ, et al. Constitutive activation of Stat3 signaling pathway in human colorectal carcinoma[J]. World J Gastroenterol,2004,10(11):1569-1573.
7 Niu G,Wright KL,Huang M, et al. Constitutive STAT3 activity upregulates VEGF expression and tumor angiogenesis[J]. Oncogene,2002,21(13):2000-2008.
8 Yakata Y,Nakayama T,Yoshizaki A,et al.Expression of p-STAT3 in human gastric carcinoma:significant correlation in tumour invasion and prognosis. [J]International Journal Of Oncology,2007,30(2),437-42.
9 俞丽芬,朱延波,乔敏敏,等Stat3在人胃癌细胞株和组织中的组成性激活及其临床意义[J].中华医学杂志,2004,84(24)：2064-2069.
10 梁斌,王杉,祝学光,等.转录信号传导子和激活子3在人胃癌组织中的表达及意义[J].中华实验外科杂志,2001,18(4)：313-314.
11 Lkeguchi M,Ueta T,Yamane Yet al.Inducible mitric oxide synthase and Survivin messnger RNA expression in hepatocellular carcinoma. [J] Clin Cancer Res,2002,8 (10):3131
12 Sun Y, Lin R, Dai J, et al. Suppression of tumor growthusing antisense oligonucleotide against survivin in an orthotopic transpiant model of human hepatocellular carcinoma in nude mice[J]. Oligonucleotides,2006,16(4):365-374.
13 俞继卫,姜波健,倪晓春,等.联合评估survivin和p53在胃癌组织中表达的临床意义及对预后的影响[J].国际外科学杂志,2007,34(13)：156-160.
14 郑江华.血液中血管内皮生长因子和肿瘤的研究进展[J].中国普通外科杂志,2004,13(1)：50-51.
15王安华Survivin和VEGF在胃癌的表达及其意义[J].临床医学杂志,2006,26(2)：77-79
16 Gritsko T, Williams A, Turkson J, et al. Persistent activation of stat3 signaling induces survivin gene expression and confers resistance to apoptosis in human breast cancer cells[J]. Clin Cancer Res,2006,12(1):11-19.
17 Kanda N, Seno H, Konda Y, et al. STAT3 is constitutively activated and supports cell survival in association with survivin expression in gastric cancer cells [J]. Oncogene,2004, 23(28):4921-4929.
18 Mesri M,Morales Ruiz M,Ackkermann E,et al. Supression of vascular endothelial growth factor mediated endothelial ceel protection by Survivin targeting. Am [J] Pathol,2001,158 (5):1757-17651
19 Takeda K, Clausen BE, Kaisho T, et al. Enhanced Thl activity and development of chronic enterocolitis in mice devoid of STAT3 in macrophages and neutrophils[J]. Immunity,1999,10 (1):39-49
20 Ford A C, Grandis, J R. Targeting epidermal growth factor receptor in head and neck cancer[J]. Head Neck,2003,25(1):67-73
21 Chattopadhyay A, Vecchi M, Ji Q, et al. The, role of individual SH2 domainsin mediating, association of phospholipase C-gammal with the activated EGF receptor[J]. J Biol Chem,1999, 274(37):26091-26097
22 Xia L, Wang L, Chung A S, et al. Indentification of Both Positive and Negative Domains within the Epidermal Growth Factor Receptor COOH-terminal, Region for Signal Transducer and Activator of Transcription(STAT) Activation[J]. J Biol Chem,2002,277(34): 30716-30723
1 Chak raborty A, Tweardy DJ. STAT3 and G-CSF-induced myeloid differentiation[J]. Leuk lymphoma,1998,30 (5-6):433-442
2 Hoey T,Grusby M J. STATs as mediators of cytokine-induced response[J]. Advlmmunol,1998,71 (1):145-160
3 Niu G, Heller R, Catlett-Falcone R, et al. Gene therapy with dominantneagative STAT3 suppresses growth of the murine B16 tumor in vivo[J]. Cancer Res,1999,59 (20):5059-5063
4 Yakata Y,Nakayama T,Yoshizaki A,et al.Expression of p-STAT3 in human gastric carcinoma:significant correlation in tumour invasion and prognosis. [J] International Journal Of Oncology,2007,30(2),437-42.
5 Fernandes A,Hamburger A W,Gerwin B I.ErbB-2 kinase is required for constitutive Stat3 activation in malignant human lung epithelial cells[J]. Int J Cancer,1999,83(4):564-570
6 Bromberg JF, W rzeszczynska M H, Devgan G, et al.STAT3 as an oncogene[J]. Cell,1999, 98(3):295-303
7 Grandis JR, Drenning SD, Zeng Q, et al. Constitutive activation of Stat3 signaling abrogates apoptosis in squamous cell carcinogenesis in vivo[J]. Proc Natl Acad Sci USA,2000,97(8): 4227-4232
8 Masuda M, Suzui M, Yasumatu R, et al. Constitutive Activation of signal transducers and activators of transcription 3 correlates with cyclin D1 overexpression and may provide a novel prognostic marker in head and neck squamous cell carcinoma[J]. Cancer Res,2002,62(12): 3351-3355
9 Watson CJ. Stat transcription factors in mammary gland development and tumorigenesis [J]. J Mammary Gland Biol Neoplasia,2001,6(1):115-127
10 Akira S. Roles of STAT3 defined by tissue specific gene targeting[J]. Oncogene,2000,19 (21):2607-2611
11 Chapman RS, Lourenco PC, Tonner E, et al. Suppression of epithet-lialapoptosis and delayed mammary gland involution in mice with a conditional knockout of Stat3 [J]. Genes Dev.1999, 13 (19):2604-2616
12 Wang S, Evers BM. Caco-2 cell differentiation is associate with a decrease in Stat protein levels and binding[J]. Castrointest Surg,1999,3(2):200-207
13. Ni Z, Lou W, Leman ES, et al. Inhibition of constitutively activated STAT3 signaling pathway suppresses growth of prostate cancer cells[J]. Cancer Res,2000,60 (5):1225-1228
14 Demoulin JB, van Roost E, Steven M, et al. Distinct roles for STAT1、 STAT3 and STAT5 in differentiation gene induction and apoptosis inhibition by interleukin-9[J]. J Biol Chem,1999, 274 (36):25855-25861
15 Takeda K, Clausen BE, Kaisho T, et al. Enhanced Thl activity and development of chronic enterocolitis in mice devoid of STAT3 in macrophages and neutrophils[J]. Immunity,1999,10 (1):39-49
16 Chakraborty A, Tweardy DJ. STAT3 and G-CSF-induced myeloid differentiation[J]. Leuk lymphoma,1998,30 (5-6):433-442
17 Hoey T, Grusby M J. STATs as mediators of cytokine-induced response[J]. Adv Immunol,1998,71 (1):145-160
18 Pfeffer L M, Mullersman J E, Pfeffer S R, Murti A, et al. Stat3 as an adapter to couple phosphotidylinositol 3-kinase to the IFNAR1 chain of the type Ⅰ interferon receptor[J]. Science, 1997,276 (5317):1418-1420
19 Ford A C, Grandis, J R. Targeting epidermal growth factor receptor in head and neck cancer[J]. Head Neck,2003,25(1):67-73
20 Chattopadhyay A, Vecchi M, Ji Q, et al. The, role of individual SH2 domainsin mediating, association of phospholipase C-gammal with the activated EGF receptor[J]. J Biol Chem,1999, 274(37):26091-26097
21 Xia L, Wang L, Chung A S, et al.Indentification of Both Positive and Negative Domains within the Epidermal Growth Factor Receptor COOH-terminal, Region for Signal Transducer and Activator of Transcription(STAT) Activation[J]. J Biol Chem,2002,277(34): 30716-30723
22 Gritsko T, Williams A, Turkson J, et al. Persistent activation of stat3 signaling induces survivin gene expression and confers resistance to apoptosis in human breast cancer cells[J]. Clin Cancer Res,2006,12(1):11-19.
23 Lee TL, Yeh J, Friedman J, et al. A signal network involving Coactivated NF-kappaB and STAT3 and altered p53 modulates BAX/BCl-XL expression and promotes cell survival of head and neck squamous cell carcinomas [J]. Int J Cancer,2008,122 (9): 1987-1998
24 Zhang C, Li B, Gaikwad AS, et al. Avicin D selectively induces apoptosis and downregulates p-STAT-3, bcl-2, and survivin in cutaneous T-cell lymphoma cells [J]. J Invest Dematol,2008,128 (11):2728-2735
25 Yu LJ, Wu ML, Li H, et al. Inhibition of STAT3 expression and signaling in resveratrol-differentiated medulloblastoma cells [J]. Neoplasia,2008,10 (7):736-744
26 Bowman T, Broome MA, Sinibaldi D, et al. STAT3-mediated Myc expression is required for Src transformation and PDGF-induced mitogenesis [J]. PNAS,2001,98 (13):
7319-7324
27 Xi S, Gooding WE, Grandis JR. In vivo antitumor efficacy of STAT3 blockade using a transcription factor decoy approach:implications for cancer therapy [J]. Oncogene,2005, 24 (6):970-979
28 Kunnumakkara AB, Nair AS, Sung B, et al. Boswellic acid blocks signal transducers and acticators of transcription3 signaling, proliferation, and survival of multiple myeloma via the protein tyrosine phosphatase SHP-1 [J]. Mol Cancer Res,2009,7 (1):118-128
29 Lkeguchi M,Ueta T,Yamane Yet al.Inducible mitric oxide synthase and Survivin messnger RNA expression in hepatocellular carcinoma. [J] Clin Cancer Res,2002,8 (10):3131
30 Gritsko T, Williams A, Turkson J, et al. Persistent activation of stat3 signaling induces survivin gene expression and confers resistance to apoptosis in human breast cancer cells[J]. Clin Cancer Res,2006,12(1):11-19.
31 Wei LH, Kuo ML, Chen CA, et al. Interleukin-6 promotes cervical tumor growth by VEGF-dependent angiogenesis via a STAT3 pathway[J]. Oncogene,2003,22 (10): 1517-1527
32 Yhata Y, Shirakata Y, Tokumaru S, et al. Nuclear translocation of phosphorylated STAT3 is essential for vascular endothelial growth factor-induced human dermal microvascular endothelial cell migration and tube formation[J]. J Biol Chem,2003,278 (41):40026-40031
33 Reed JC. Mechanisms of apoptosis avoidance in cancer[J]. Curr Opin Oncol,1999,11(1): 68-75
34 Kiuchi N, Nakajima K, Ichiba M, et al. STAT3 is required for the gp130-mediated full activation of the c-myc gene[J]. J Exp Med,1999,189 (1):63-73
35 Ivanov VN, Bhoumik A, Krasilnikov M, et al. Cooperation between STAT3 and c-jun suppresses Fas transcription[J]. Mol Cell,2001,7 (3):517-528
36 Turkson J and Jove R. STAT prteins:novel molecular target for cancer drug discovery[J]. Oncogene,2000,19(56):6613-6626
37 梁斌,王杉,祝学光,等.信号转导和转录活化因子3在人胃癌组织中的表达意义[J].中华实验外科杂志,2001,18(4)：313-314
38 Kanda N, Seno H, Konda Y, et al. STAT3 is constitutively activated and supports cell survival in association with survivin expression in gastric cancer cells [J]. Oncogene,2004, 23(28):4921-4929.
39 Yoshikawa T, Tsuburaya A, Kobayashi O, et al. Plasma concentration of VFGF and bFGF in patients with gastric carcinoma[J]. Cancer Lett,2000,153 (1-2):7-12
40 Niu G, Bowman T, Huang M, et al. Roles of activated Src and STAT3 signaling in melanoma tumor cell growth[J]. Onconene,2002,21(46):7001-7010
41 Kube D, Holtick U, Vockerodt M, et al. STAT3 is constitutively activated in Hodgkin cell lines[J]. Blood,2001,98(3):762-770
42 Turkson J, Ryan D, Kim JS, et al. Phosphotyrosyl peptides block STAT3-mediated DNA binding activity, gene regulation, and cell transformation[J]. Biol Chem,2001,276(48):45443-45455
2 Hoey T,Grusby M J. STATs as mediators of cytokine-induced response[J]. Adv Immunol,1998,71 (1):145-160
3 LU B, MU Y, CAO C, et al. Survivin as a therapeutic target for radiation sensitization in lung cancer [J]. Cancer Res,2004,64:284022845.
4 Sung BJ, Cho YS, Kim HJ, et al. An anti2apoptotic p rotein,human survivin is a direct inhibitor of caspase23 and caspase 27 [J]. Biochemist ry,2001,40 (4):111721123.
5 Hoey T, Grusby MJ.STATs as mediators of cytokine2induced response[J].Adv Immumol,1999;71:145-62.
6 Ma XT, Wang S, Ye YJ, et al. Constitutive activation of Stat3 signaling pathway in human colorectal carcinoma[J]. World J Gastroenterol,2004,10(11):1569-1573.
7 Niu G,Wright KL,Huang M, et al. Constitutive STAT3 activity upregulates VEGF expression and tumor angiogenesis[J]. Oncogene,2002,21(13):2000-2008.
8 Yakata Y,Nakayama T,Yoshizaki A,et al.Expression of p-STAT3 in human gastric carcinoma:significant correlation in tumour invasion and prognosis. [J]International Journal Of Oncology,2007,30(2),437-42.
9 俞丽芬,朱延波,乔敏敏,等Stat3在人胃癌细胞株和组织中的组成性激活及其临床意义[J].中华医学杂志,2004,84(24)：2064-2069.
10 梁斌,王杉,祝学光,等.转录信号传导子和激活子3在人胃癌组织中的表达及意义[J].中华实验外科杂志,2001,18(4)：313-314.
11 Lkeguchi M,Ueta T,Yamane Yet al.Inducible mitric oxide synthase and Survivin messnger RNA expression in hepatocellular carcinoma. [J] Clin Cancer Res,2002,8 (10):3131
12 Sun Y, Lin R, Dai J, et al. Suppression of tumor growthusing antisense oligonucleotide against survivin in an orthotopic transpiant model of human hepatocellular carcinoma in nude mice[J]. Oligonucleotides,2006,16(4):365-374.
13 俞继卫,姜波健,倪晓春,等.联合评估survivin和p53在胃癌组织中表达的临床意义及对预后的影响[J].国际外科学杂志,2007,34(13)：156-160.
14 郑江华.血液中血管内皮生长因子和肿瘤的研究进展[J].中国普通外科杂志,2004,13(1)：50-51.
15王安华Survivin和VEGF在胃癌的表达及其意义[J].临床医学杂志,2006,26(2)：77-79
16 Gritsko T, Williams A, Turkson J, et al. Persistent activation of stat3 signaling induces survivin gene expression and confers resistance to apoptosis in human breast cancer cells[J]. Clin Cancer Res,2006,12(1):11-19.
17 Kanda N, Seno H, Konda Y, et al. STAT3 is constitutively activated and supports cell survival in association with survivin expression in gastric cancer cells [J]. Oncogene,2004, 23(28):4921-4929.
18 Mesri M,Morales Ruiz M,Ackkermann E,et al. Supression of vascular endothelial growth factor mediated endothelial ceel protection by Survivin targeting. Am [J] Pathol,2001,158 (5):1757-17651
19 Takeda K, Clausen BE, Kaisho T, et al. Enhanced Thl activity and development of chronic enterocolitis in mice devoid of STAT3 in macrophages and neutrophils[J]. Immunity,1999,10 (1):39-49
20 Ford A C, Grandis, J R. Targeting epidermal growth factor receptor in head and neck cancer[J]. Head Neck,2003,25(1):67-73
21 Chattopadhyay A, Vecchi M, Ji Q, et al. The, role of individual SH2 domainsin mediating, association of phospholipase C-gammal with the activated EGF receptor[J]. J Biol Chem,1999, 274(37):26091-26097
22 Xia L, Wang L, Chung A S, et al. Indentification of Both Positive and Negative Domains within the Epidermal Growth Factor Receptor COOH-terminal, Region for Signal Transducer and Activator of Transcription(STAT) Activation[J]. J Biol Chem,2002,277(34): 30716-30723
1 Chak raborty A, Tweardy DJ. STAT3 and G-CSF-induced myeloid differentiation[J]. Leuk lymphoma,1998,30 (5-6):433-442
2 Hoey T,Grusby M J. STATs as mediators of cytokine-induced response[J]. Advlmmunol,1998,71 (1):145-160
3 Niu G, Heller R, Catlett-Falcone R, et al. Gene therapy with dominantneagative STAT3 suppresses growth of the murine B16 tumor in vivo[J]. Cancer Res,1999,59 (20):5059-5063
4 Yakata Y,Nakayama T,Yoshizaki A,et al.Expression of p-STAT3 in human gastric carcinoma:significant correlation in tumour invasion and prognosis. [J] International Journal Of Oncology,2007,30(2),437-42.
5 Fernandes A,Hamburger A W,Gerwin B I.ErbB-2 kinase is required for constitutive Stat3 activation in malignant human lung epithelial cells[J]. Int J Cancer,1999,83(4):564-570
6 Bromberg JF, W rzeszczynska M H, Devgan G, et al.STAT3 as an oncogene[J]. Cell,1999, 98(3):295-303
7 Grandis JR, Drenning SD, Zeng Q, et al. Constitutive activation of Stat3 signaling abrogates apoptosis in squamous cell carcinogenesis in vivo[J]. Proc Natl Acad Sci USA,2000,97(8): 4227-4232
8 Masuda M, Suzui M, Yasumatu R, et al. Constitutive Activation of signal transducers and activators of transcription 3 correlates with cyclin D1 overexpression and may provide a novel prognostic marker in head and neck squamous cell carcinoma[J]. Cancer Res,2002,62(12): 3351-3355
9 Watson CJ. Stat transcription factors in mammary gland development and tumorigenesis [J]. J Mammary Gland Biol Neoplasia,2001,6(1):115-127
10 Akira S. Roles of STAT3 defined by tissue specific gene targeting[J]. Oncogene,2000,19 (21):2607-2611
11 Chapman RS, Lourenco PC, Tonner E, et al. Suppression of epithet-lialapoptosis and delayed mammary gland involution in mice with a conditional knockout of Stat3 [J]. Genes Dev.1999, 13 (19):2604-2616
12 Wang S, Evers BM. Caco-2 cell differentiation is associate with a decrease in Stat protein levels and binding[J]. Castrointest Surg,1999,3(2):200-207
13. Ni Z, Lou W, Leman ES, et al. Inhibition of constitutively activated STAT3 signaling pathway suppresses growth of prostate cancer cells[J]. Cancer Res,2000,60 (5):1225-1228
14 Demoulin JB, van Roost E, Steven M, et al. Distinct roles for STAT1、 STAT3 and STAT5 in differentiation gene induction and apoptosis inhibition by interleukin-9[J]. J Biol Chem,1999, 274 (36):25855-25861
15 Takeda K, Clausen BE, Kaisho T, et al. Enhanced Thl activity and development of chronic enterocolitis in mice devoid of STAT3 in macrophages and neutrophils[J]. Immunity,1999,10 (1):39-49
16 Chakraborty A, Tweardy DJ. STAT3 and G-CSF-induced myeloid differentiation[J]. Leuk lymphoma,1998,30 (5-6):433-442
17 Hoey T, Grusby M J. STATs as mediators of cytokine-induced response[J]. Adv Immunol,1998,71 (1):145-160
18 Pfeffer L M, Mullersman J E, Pfeffer S R, Murti A, et al. Stat3 as an adapter to couple phosphotidylinositol 3-kinase to the IFNAR1 chain of the type Ⅰ interferon receptor[J]. Science, 1997,276 (5317):1418-1420
19 Ford A C, Grandis, J R. Targeting epidermal growth factor receptor in head and neck cancer[J]. Head Neck,2003,25(1):67-73
20 Chattopadhyay A, Vecchi M, Ji Q, et al. The, role of individual SH2 domainsin mediating, association of phospholipase C-gammal with the activated EGF receptor[J]. J Biol Chem,1999, 274(37):26091-26097
21 Xia L, Wang L, Chung A S, et al.Indentification of Both Positive and Negative Domains within the Epidermal Growth Factor Receptor COOH-terminal, Region for Signal Transducer and Activator of Transcription(STAT) Activation[J]. J Biol Chem,2002,277(34): 30716-30723
22 Gritsko T, Williams A, Turkson J, et al. Persistent activation of stat3 signaling induces survivin gene expression and confers resistance to apoptosis in human breast cancer cells[J]. Clin Cancer Res,2006,12(1):11-19.
23 Lee TL, Yeh J, Friedman J, et al. A signal network involving Coactivated NF-kappaB and STAT3 and altered p53 modulates BAX/BCl-XL expression and promotes cell survival of head and neck squamous cell carcinomas [J]. Int J Cancer,2008,122 (9): 1987-1998
24 Zhang C, Li B, Gaikwad AS, et al. Avicin D selectively induces apoptosis and downregulates p-STAT-3, bcl-2, and survivin in cutaneous T-cell lymphoma cells [J]. J Invest Dematol,2008,128 (11):2728-2735
25 Yu LJ, Wu ML, Li H, et al. Inhibition of STAT3 expression and signaling in resveratrol-differentiated medulloblastoma cells [J]. Neoplasia,2008,10 (7):736-744
26 Bowman T, Broome MA, Sinibaldi D, et al. STAT3-mediated Myc expression is required for Src transformation and PDGF-induced mitogenesis [J]. PNAS,2001,98 (13):
7319-7324
27 Xi S, Gooding WE, Grandis JR. In vivo antitumor efficacy of STAT3 blockade using a transcription factor decoy approach:implications for cancer therapy [J]. Oncogene,2005, 24 (6):970-979
28 Kunnumakkara AB, Nair AS, Sung B, et al. Boswellic acid blocks signal transducers and acticators of transcription3 signaling, proliferation, and survival of multiple myeloma via the protein tyrosine phosphatase SHP-1 [J]. Mol Cancer Res,2009,7 (1):118-128
29 Lkeguchi M,Ueta T,Yamane Yet al.Inducible mitric oxide synthase and Survivin messnger RNA expression in hepatocellular carcinoma. [J] Clin Cancer Res,2002,8 (10):3131
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