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Published in: Journal of Translational Medicine 1/2009

Open Access 01-12-2009 | Research

yuDetecting the percent of peripheral blood mononuclear cells displaying p-STAT-3 in malignant glioma patients

Authors: William Humphries, Yongtao Wang, Wei Qiao, Chantal Reina-Ortiz, Mohamed K Abou-Ghazal, Lamonne M Crutcher, Jun Wei, Ling-Yuan Kong, Raymond Sawaya, Ganesh Rao, Jeffrey Weinberg, Sujit S Prabhu, Gregory N Fuller, Amy B Heimberger

Published in: Journal of Translational Medicine | Issue 1/2009

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Abstract

Background

The signal transducer and activator of transcription 3 (STAT-3) is frequently overexpressed in cancer cells, propagates tumorigenesis, and is a key regulator of immune suppression in cancer patients. The presence of phosphorylated STAT-3 (p-STAT-3) in the tumor can induce p-STAT-3 in tumor-associated immune cells that can return to the circulatory system. We hypothesized that the number of peripheral blood mononuclear cells (PBMCs) displaying p-STAT-3 would be increased in glioma patients, which would correlate with the extent of tumor-expressed p-STAT-3, and that higher p-STAT-3 levels in peripheral blood would correlate with a higher fraction of immune-suppressive regulatory T cells (Tregs).

Methods

We measured the percentage of PBMCs displaying p-STAT-3 in 19 healthy donors and 45 patients with primary brain tumors. The level of p-STAT-3 in tumor tissue was determined by immunohistochemistry. The degree of immune suppression was determined based on the fraction of Tregs in the CD4 compartment.

Results

Healthy donors had 4.8 ± 3.6% of PBMCs that expressed p-STAT-3, while the mean proportion of PBMCs displaying p-STAT-3 in patients with GBM was 11.8 ± 13.5% (P = 0.03). We did not observe a correlation by Spearman correlation between the degree of p-STAT-3 levels in the tumor and the percent of PBMCs displaying p-STAT-3. Furthermore, the percent of PBMCs displaying p-STAT-3 in glioma patients was not directly correlated with the fraction of Tregs in the CD4 compartment.

Conclusion

We conclude that the percent of PBMCs displaying p-STAT-3 may be increased in malignant glioma patients.
Appendix
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Literature
1.
go back to reference Yu H, Jove R: The STATs of cancer--new molecular targets come of age. Nat Rev Cancer. 2004, 4: 97-105. 10.1038/nrc1275.CrossRefPubMed Yu H, Jove R: The STATs of cancer--new molecular targets come of age. Nat Rev Cancer. 2004, 4: 97-105. 10.1038/nrc1275.CrossRefPubMed
2.
go back to reference Yu H, Kortylewski M, Pardoll D: Crosstalk between cancer and immune cells: role of STAT3 in the tumour microenvironment. Nat Rev Immunol. 2007, 7: 41-51. 10.1038/nri1995.CrossRefPubMed Yu H, Kortylewski M, Pardoll D: Crosstalk between cancer and immune cells: role of STAT3 in the tumour microenvironment. Nat Rev Immunol. 2007, 7: 41-51. 10.1038/nri1995.CrossRefPubMed
3.
go back to reference Abou-Ghazal M, Yang DS, Qiao W, Reina-Ortiz C, Wei J, Kong LY, Fuller GN, Hiraoka N, Priebe W, Sawaya R, Heimberger AB: The incidence, correlation with tumor-infiltrating inflammation, and prognosis of phosphorylated STAT3 expression in human gliomas. Clin Cancer Res. 2008, 14: 8228-8235. 10.1158/1078-0432.CCR-08-1329.PubMedCentralCrossRefPubMed Abou-Ghazal M, Yang DS, Qiao W, Reina-Ortiz C, Wei J, Kong LY, Fuller GN, Hiraoka N, Priebe W, Sawaya R, Heimberger AB: The incidence, correlation with tumor-infiltrating inflammation, and prognosis of phosphorylated STAT3 expression in human gliomas. Clin Cancer Res. 2008, 14: 8228-8235. 10.1158/1078-0432.CCR-08-1329.PubMedCentralCrossRefPubMed
4.
go back to reference Lau LT, Yu AC: Astrocytes produce and release interleukin-1, interleukin-6, tumor necrosis factor alpha and interferon-gamma following traumatic and metabolic injury. J Neurotrauma. 2001, 18: 351-359. 10.1089/08977150151071035.CrossRefPubMed Lau LT, Yu AC: Astrocytes produce and release interleukin-1, interleukin-6, tumor necrosis factor alpha and interferon-gamma following traumatic and metabolic injury. J Neurotrauma. 2001, 18: 351-359. 10.1089/08977150151071035.CrossRefPubMed
5.
go back to reference Li B, Chang CM, Yuan M, McKenna WG, Shu HK: Resistance to small molecule inhibitors of epidermal growth factor receptor in malignant gliomas. Cancer Res. 2003, 63: 7443-7450.PubMed Li B, Chang CM, Yuan M, McKenna WG, Shu HK: Resistance to small molecule inhibitors of epidermal growth factor receptor in malignant gliomas. Cancer Res. 2003, 63: 7443-7450.PubMed
6.
go back to reference Steinbrink K, Wolfl M, Jonuleit H, Knop J, Enk AH: Induction of tolerance by IL-10-treated dendritic cells. J Immunol. 1997, 159: 4772-4780.PubMed Steinbrink K, Wolfl M, Jonuleit H, Knop J, Enk AH: Induction of tolerance by IL-10-treated dendritic cells. J Immunol. 1997, 159: 4772-4780.PubMed
7.
go back to reference Williams L, Bradley L, Smith A, Foxwell B: Signal transducer and activator of transcription 3 is the dominant mediator of the anti-inflammatory effects of IL-10 in human macrophages. J Immunol. 2004, 172: 567-576.CrossRefPubMed Williams L, Bradley L, Smith A, Foxwell B: Signal transducer and activator of transcription 3 is the dominant mediator of the anti-inflammatory effects of IL-10 in human macrophages. J Immunol. 2004, 172: 567-576.CrossRefPubMed
8.
go back to reference DiMeo D, Tian J, Zhang J, Narushima S, Berg DJ: Increased interleukin-10 production and Th2 skewing in the absence of 5-lipoxygenase. Immunology. 2008, 123: 250-262.PubMedCentralPubMed DiMeo D, Tian J, Zhang J, Narushima S, Berg DJ: Increased interleukin-10 production and Th2 skewing in the absence of 5-lipoxygenase. Immunology. 2008, 123: 250-262.PubMedCentralPubMed
9.
go back to reference Asseman C, Mauze S, Leach MW, Coffman RL, Powrie F: An essential role for interleukin 10 in the function of regulatory T cells that inhibit intestinal inflammation. J Exp Med. 1999, 190: 995-1004. 10.1084/jem.190.7.995.PubMedCentralCrossRefPubMed Asseman C, Mauze S, Leach MW, Coffman RL, Powrie F: An essential role for interleukin 10 in the function of regulatory T cells that inhibit intestinal inflammation. J Exp Med. 1999, 190: 995-1004. 10.1084/jem.190.7.995.PubMedCentralCrossRefPubMed
10.
go back to reference Niu G, Bowman T, Huang M, Shivers S, Reintgen D, Daud A, Chang A, Kraker A, Jove R, Yu H: Roles of activated Src and Stat3 signaling in melanoma tumor cell growth. Oncogene. 2002, 21: 7001-7010. 10.1038/sj.onc.1205859.CrossRefPubMed Niu G, Bowman T, Huang M, Shivers S, Reintgen D, Daud A, Chang A, Kraker A, Jove R, Yu H: Roles of activated Src and Stat3 signaling in melanoma tumor cell growth. Oncogene. 2002, 21: 7001-7010. 10.1038/sj.onc.1205859.CrossRefPubMed
11.
go back to reference Gabrilovich DI, Chen HL, Girgis KR, Cunningham HT, Meny GM, Nadaf S, Kavanaugh D, Carbone DP: Production of vascular endothelial growth factor by human tumors inhibits the functional maturation of dendritic cells[erratum appears in Nat Med 1996 Nov;2(11):1267]. Nat Med. 1996, 2: 1096-1103. 10.1038/nm1096-1096.CrossRefPubMed Gabrilovich DI, Chen HL, Girgis KR, Cunningham HT, Meny GM, Nadaf S, Kavanaugh D, Carbone DP: Production of vascular endothelial growth factor by human tumors inhibits the functional maturation of dendritic cells[erratum appears in Nat Med 1996 Nov;2(11):1267]. Nat Med. 1996, 2: 1096-1103. 10.1038/nm1096-1096.CrossRefPubMed
12.
go back to reference Rummel C, Sachot C, Poole S, Luheshi GN: Circulating interleukin-6 induces fever through a STAT3-linked activation of COX-2 in the brain. Am J Physiol Regul Integr Comp Physiol. 2006, 291: R1316-1326.CrossRefPubMed Rummel C, Sachot C, Poole S, Luheshi GN: Circulating interleukin-6 induces fever through a STAT3-linked activation of COX-2 in the brain. Am J Physiol Regul Integr Comp Physiol. 2006, 291: R1316-1326.CrossRefPubMed
13.
go back to reference Boniface K, Bak-Jensen KS, Li Y, Blumenschein WM, McGeachy MJ, McClanahan TK, McKenzie BS, Kastelein RA, Cua DJ, de Waal Malefyt R: Prostaglandin E2 regulates Th17 cell differentiation and function through cyclic AMP and EP2/EP4 receptor signaling. J Exp Med. 2009, 206: 535-548. 10.1084/jem.20082293.PubMedCentralCrossRefPubMed Boniface K, Bak-Jensen KS, Li Y, Blumenschein WM, McGeachy MJ, McClanahan TK, McKenzie BS, Kastelein RA, Cua DJ, de Waal Malefyt R: Prostaglandin E2 regulates Th17 cell differentiation and function through cyclic AMP and EP2/EP4 receptor signaling. J Exp Med. 2009, 206: 535-548. 10.1084/jem.20082293.PubMedCentralCrossRefPubMed
14.
go back to reference Kinjyo I, Inoue H, Hamano S, Fukuyama S, Yoshimura T, Koga K, Takaki H, Himeno K, Takaesu G, Kobayashi T, Yoshimura A: Loss of SOCS3 in T helper cells resulted in reduced immune responses and hyperproduction of interleukin 10 and transforming growth factor-β1. J Exp Med. 2006, 203: 1021-1031. 10.1084/jem.20052333.PubMedCentralCrossRefPubMed Kinjyo I, Inoue H, Hamano S, Fukuyama S, Yoshimura T, Koga K, Takaki H, Himeno K, Takaesu G, Kobayashi T, Yoshimura A: Loss of SOCS3 in T helper cells resulted in reduced immune responses and hyperproduction of interleukin 10 and transforming growth factor-β1. J Exp Med. 2006, 203: 1021-1031. 10.1084/jem.20052333.PubMedCentralCrossRefPubMed
15.
go back to reference Kortylewski M, Kujawski M, Wang T, Wei S, Zhang S, Pilon-Thomas S, Niu G, Kay H, Mule J, Kerr WG: Inhibiting Stat3 signaling in the hematopoietic system elicits multicomponent antitumor immunity. Nat Med. 2005, 11: 1314-1321. 10.1038/nm1325.CrossRefPubMed Kortylewski M, Kujawski M, Wang T, Wei S, Zhang S, Pilon-Thomas S, Niu G, Kay H, Mule J, Kerr WG: Inhibiting Stat3 signaling in the hematopoietic system elicits multicomponent antitumor immunity. Nat Med. 2005, 11: 1314-1321. 10.1038/nm1325.CrossRefPubMed
16.
go back to reference Matsukawa A, Kudo S, Maeda T, Numata K, Watanabe H, Takeda K, Akira S, Ito T: Stat3 in resident macrophages as a repressor protein of inflammatory response. J Immunol. 2005, 175: 3354-3359.CrossRefPubMed Matsukawa A, Kudo S, Maeda T, Numata K, Watanabe H, Takeda K, Akira S, Ito T: Stat3 in resident macrophages as a repressor protein of inflammatory response. J Immunol. 2005, 175: 3354-3359.CrossRefPubMed
17.
go back to reference Frisullo G, Angelucci F, Caggiula M, Nociti V, Iorio R, Patanella AK, Sancricca C, Mirabella M, Tonali PA, Batocchi AP: pSTAT1, pSTAT3, and T-bet expression in peripheral blood mononuclear cells from relapsing-remitting multiple sclerosis patients correlates with disease activity. J Neurosci Res. 2006, 84: 1027-1036. 10.1002/jnr.20995.CrossRefPubMed Frisullo G, Angelucci F, Caggiula M, Nociti V, Iorio R, Patanella AK, Sancricca C, Mirabella M, Tonali PA, Batocchi AP: pSTAT1, pSTAT3, and T-bet expression in peripheral blood mononuclear cells from relapsing-remitting multiple sclerosis patients correlates with disease activity. J Neurosci Res. 2006, 84: 1027-1036. 10.1002/jnr.20995.CrossRefPubMed
18.
go back to reference Lin T, Bost K: STAT3 activation in macrophages following infection with Salmonella. Biochem Biophys Res Commun. 2004, 321: 828-834. 10.1016/j.bbrc.2004.07.039.CrossRefPubMed Lin T, Bost K: STAT3 activation in macrophages following infection with Salmonella. Biochem Biophys Res Commun. 2004, 321: 828-834. 10.1016/j.bbrc.2004.07.039.CrossRefPubMed
19.
go back to reference Yaroslavskiy B, Watkins SC, Alber S, Steinman RA: Dynamic changes in p27kip1 variant expression in activated lymphocytes. J Cell Biochem. 2001, 83: 380-389. 10.1002/jcb.1243.CrossRefPubMed Yaroslavskiy B, Watkins SC, Alber S, Steinman RA: Dynamic changes in p27kip1 variant expression in activated lymphocytes. J Cell Biochem. 2001, 83: 380-389. 10.1002/jcb.1243.CrossRefPubMed
20.
go back to reference Zorn E, Nelson EA, Mohseni M, Porcheray F, Kim H, Litsa D, Bellucci R, Raderschall E, Canning C, Soiffer RJ: IL-2 regulates FOXP3 expression in human CD4+CD25+ regulatory T cells through a STAT-dependent mechanism and induces the expansion of these cells in vivo. Blood. 2006, 108: 1571-1579. 10.1182/blood-2006-02-004747.PubMedCentralCrossRefPubMed Zorn E, Nelson EA, Mohseni M, Porcheray F, Kim H, Litsa D, Bellucci R, Raderschall E, Canning C, Soiffer RJ: IL-2 regulates FOXP3 expression in human CD4+CD25+ regulatory T cells through a STAT-dependent mechanism and induces the expansion of these cells in vivo. Blood. 2006, 108: 1571-1579. 10.1182/blood-2006-02-004747.PubMedCentralCrossRefPubMed
22.
go back to reference Lang R, Patel D, Morris JJ, Rutschman RL, Murray PJ: Shaping gene expression in activated and resting primary macrophages by IL-10. J Immunol. 2002, 169: 2253-2263.CrossRefPubMed Lang R, Patel D, Morris JJ, Rutschman RL, Murray PJ: Shaping gene expression in activated and resting primary macrophages by IL-10. J Immunol. 2002, 169: 2253-2263.CrossRefPubMed
23.
go back to reference O'Farrell AM, Liu Y, Moore KW, Mui AL: IL-10 inhibits macrophage activation and proliferation by distinct signaling mechanisms: evidence for Stat3-dependent and -independent pathways. EMBO J. 1998, 17: 1006-1018. 10.1093/emboj/17.4.1006.PubMedCentralCrossRefPubMed O'Farrell AM, Liu Y, Moore KW, Mui AL: IL-10 inhibits macrophage activation and proliferation by distinct signaling mechanisms: evidence for Stat3-dependent and -independent pathways. EMBO J. 1998, 17: 1006-1018. 10.1093/emboj/17.4.1006.PubMedCentralCrossRefPubMed
24.
go back to reference Urbani F, Maleci A, La Sala A, Lande R, Ausiello CM: Defective expression of interferon-gamma, granulocyte-macrophage colony-stimulating factor, tumor necrosis factor alpha, and interleukin-6 in activated peripheral blood lymphocytes from glioma patients. J Interferon Cytokine Res. 1995, 15: 421-429. 10.1089/jir.1995.15.421.CrossRefPubMed Urbani F, Maleci A, La Sala A, Lande R, Ausiello CM: Defective expression of interferon-gamma, granulocyte-macrophage colony-stimulating factor, tumor necrosis factor alpha, and interleukin-6 in activated peripheral blood lymphocytes from glioma patients. J Interferon Cytokine Res. 1995, 15: 421-429. 10.1089/jir.1995.15.421.CrossRefPubMed
25.
go back to reference Hussain SF, Kong LY, Jordan J, Conrad C, Madden T, Fokt I, Priebe W, Heimberger AB: A novel small molecule inhibitor of signal transducers and activators of transcription 3 reverses immune tolerance in malignant glioma patients. Cancer Res. 2007, 67: 9630-9636. 10.1158/0008-5472.CAN-07-1243.CrossRefPubMed Hussain SF, Kong LY, Jordan J, Conrad C, Madden T, Fokt I, Priebe W, Heimberger AB: A novel small molecule inhibitor of signal transducers and activators of transcription 3 reverses immune tolerance in malignant glioma patients. Cancer Res. 2007, 67: 9630-9636. 10.1158/0008-5472.CAN-07-1243.CrossRefPubMed
26.
go back to reference Kong LY, Abou-Ghazal MK, Wei J, Chakraborty A, Sun W, Qiao W, Fuller GN, Fokt I, Grimm EA, Schmittling RJ: A novel inhibitor of signal transducers and activators of transcription 3 activation is efficacious against established central nervous system melanoma and inhibits regulatory T cells. Clin Cancer Res. 2008, 14: 5759-5768. 10.1158/1078-0432.CCR-08-0377.PubMedCentralCrossRefPubMed Kong LY, Abou-Ghazal MK, Wei J, Chakraborty A, Sun W, Qiao W, Fuller GN, Fokt I, Grimm EA, Schmittling RJ: A novel inhibitor of signal transducers and activators of transcription 3 activation is efficacious against established central nervous system melanoma and inhibits regulatory T cells. Clin Cancer Res. 2008, 14: 5759-5768. 10.1158/1078-0432.CCR-08-0377.PubMedCentralCrossRefPubMed
27.
go back to reference Takeda K, Clausen BE, Kaisho T, Tsujimura T, Terada N, Forster I, Akira S: Enhanced Th1 activity and development of chronic enterocolitis in mice devoid of Stat3 in macrophages and neutrophils. Immunity. 1999, 10: 39-49. 10.1016/S1074-7613(00)80005-9.CrossRefPubMed Takeda K, Clausen BE, Kaisho T, Tsujimura T, Terada N, Forster I, Akira S: Enhanced Th1 activity and development of chronic enterocolitis in mice devoid of Stat3 in macrophages and neutrophils. Immunity. 1999, 10: 39-49. 10.1016/S1074-7613(00)80005-9.CrossRefPubMed
28.
go back to reference Heimberger AB, Sun W, Kong L-Y, Abou-Ghazal M, Wei J, Gumin J, Coleman H, Priebe W, Lang FF: Glioblastoma multiforme stem cells mediate immune suppression that can be inhibited with JAK2/STAT3 blockade. J Clin Oncol. 2008, 26 ((Suppl, part 1 of 2)15S): Heimberger AB, Sun W, Kong L-Y, Abou-Ghazal M, Wei J, Gumin J, Coleman H, Priebe W, Lang FF: Glioblastoma multiforme stem cells mediate immune suppression that can be inhibited with JAK2/STAT3 blockade. J Clin Oncol. 2008, 26 ((Suppl, part 1 of 2)15S):
29.
go back to reference Calzascia T, Masson F, Di Berardino-Besson W, Contassot E, Wilmotte R, Aurrand-Lions M, Ruegg C, Dietrich PY, Walker PR: Homing phenotypes of tumor-specific CD8 T cells are predetermined at the tumor site by crosspresenting APCs. Immunity. 2005, 22: 175-184. 10.1016/j.immuni.2004.12.008.CrossRefPubMed Calzascia T, Masson F, Di Berardino-Besson W, Contassot E, Wilmotte R, Aurrand-Lions M, Ruegg C, Dietrich PY, Walker PR: Homing phenotypes of tumor-specific CD8 T cells are predetermined at the tumor site by crosspresenting APCs. Immunity. 2005, 22: 175-184. 10.1016/j.immuni.2004.12.008.CrossRefPubMed
30.
go back to reference Hickey WF, Hsu BL, Kimura H: T-lymphocyte entry into the central nervous system. J Neurosci Res. 1991, 28: 254-260. 10.1002/jnr.490280213.CrossRefPubMed Hickey WF, Hsu BL, Kimura H: T-lymphocyte entry into the central nervous system. J Neurosci Res. 1991, 28: 254-260. 10.1002/jnr.490280213.CrossRefPubMed
31.
go back to reference Williams KC, Hickey WF: Traffic of hematogenous cells through the central nervous system. Curr Top Microbiol Immunol. 1995, 202: 221-245.PubMed Williams KC, Hickey WF: Traffic of hematogenous cells through the central nervous system. Curr Top Microbiol Immunol. 1995, 202: 221-245.PubMed
32.
go back to reference Hickey WF: Basic principles of immunological surveillance of the normal central nervous system. GLIA. 2001, 36: 118-124. 10.1002/glia.1101.CrossRefPubMed Hickey WF: Basic principles of immunological surveillance of the normal central nervous system. GLIA. 2001, 36: 118-124. 10.1002/glia.1101.CrossRefPubMed
33.
go back to reference Cserr HF, Harling-Berg CJ, Knopf PM: Drainage of brain extracellular fluid into blood and deep cervical lymph and its immunological significance. Brain Pathol. 1992, 2: 269-276. 10.1111/j.1750-3639.1992.tb00703.x.CrossRefPubMed Cserr HF, Harling-Berg CJ, Knopf PM: Drainage of brain extracellular fluid into blood and deep cervical lymph and its immunological significance. Brain Pathol. 1992, 2: 269-276. 10.1111/j.1750-3639.1992.tb00703.x.CrossRefPubMed
34.
go back to reference Cserr HF, Knopf PM: Cervical lymphatics, the blood-brain barrier and the immunoreactivity of the brain: a new view. Immunol Today. 1992, 13: 507-512. 10.1016/0167-5699(92)90027-5.CrossRefPubMed Cserr HF, Knopf PM: Cervical lymphatics, the blood-brain barrier and the immunoreactivity of the brain: a new view. Immunol Today. 1992, 13: 507-512. 10.1016/0167-5699(92)90027-5.CrossRefPubMed
35.
go back to reference Fecci PE, Mitchell DA, Whitesides JF, Xie W, Friedman AH, Archer GE, Herndon JE, Bigner DD, Dranoff G, Sampson JH: Increased regulatory T-cell fraction amidst a diminished CD4 compartment explains cellular immune defects in patients with malignant glioma. Cancer Res. 2006, 66: 3294-3302. 10.1158/0008-5472.CAN-05-3773.CrossRefPubMed Fecci PE, Mitchell DA, Whitesides JF, Xie W, Friedman AH, Archer GE, Herndon JE, Bigner DD, Dranoff G, Sampson JH: Increased regulatory T-cell fraction amidst a diminished CD4 compartment explains cellular immune defects in patients with malignant glioma. Cancer Res. 2006, 66: 3294-3302. 10.1158/0008-5472.CAN-05-3773.CrossRefPubMed
36.
go back to reference Kong LK, Wei J, Sharma AK, Barr J, Abou-Ghazal MK, Fokt I, Weinberg J, Rao G, Grimm E, Priebe W, Heimberger AB: A novel phosphorylated STAT3 inhibitor enhances T cell cytotoxicity against melanoma through inhibition of regulatory T cells. Cancer Immunol Immunother. 2008, 58: 1023-1032. 10.1007/s00262-008-0618-y.PubMedCentralCrossRefPubMed Kong LK, Wei J, Sharma AK, Barr J, Abou-Ghazal MK, Fokt I, Weinberg J, Rao G, Grimm E, Priebe W, Heimberger AB: A novel phosphorylated STAT3 inhibitor enhances T cell cytotoxicity against melanoma through inhibition of regulatory T cells. Cancer Immunol Immunother. 2008, 58: 1023-1032. 10.1007/s00262-008-0618-y.PubMedCentralCrossRefPubMed
37.
go back to reference Louis DN, Ohgaki H, Wiestler OD, Cavenee WK, Burger PC, Jouvet A, Scheithauer BW, Kleihues P: The 2007 WHO classification of tumours of the central nervous system[erratum appears in Acta Neuropathol. 2007 Nov;114(5):547]. Acta Neuropathol. 2007, 114: 97-109. 10.1007/s00401-007-0243-4.PubMedCentralCrossRefPubMed Louis DN, Ohgaki H, Wiestler OD, Cavenee WK, Burger PC, Jouvet A, Scheithauer BW, Kleihues P: The 2007 WHO classification of tumours of the central nervous system[erratum appears in Acta Neuropathol. 2007 Nov;114(5):547]. Acta Neuropathol. 2007, 114: 97-109. 10.1007/s00401-007-0243-4.PubMedCentralCrossRefPubMed
38.
go back to reference Fujita M, Zhu X, Sasaki K, Ueda R, Low KL, Pollack IF, Okada H: Inhibition of STAT3 promotes the efficacy of adoptive transfer therapy using type-1 CTLs by modulation of the immunological microenvironment in a murine intracranial glioma. J Immunol. 2008, 180: 2089-2098.CrossRefPubMed Fujita M, Zhu X, Sasaki K, Ueda R, Low KL, Pollack IF, Okada H: Inhibition of STAT3 promotes the efficacy of adoptive transfer therapy using type-1 CTLs by modulation of the immunological microenvironment in a murine intracranial glioma. J Immunol. 2008, 180: 2089-2098.CrossRefPubMed
39.
go back to reference Bael TE, Peterson BL, Gollob JA: Phase II trial of arsenic trioxide and ascorbic acid with temozolomide in patients with metastatic melanoma with or without central nervous system metastases. Melanoma Res. 2008, 18: 147-151. 10.1097/CMR.0b013e3282f2a7ae.CrossRefPubMed Bael TE, Peterson BL, Gollob JA: Phase II trial of arsenic trioxide and ascorbic acid with temozolomide in patients with metastatic melanoma with or without central nervous system metastases. Melanoma Res. 2008, 18: 147-151. 10.1097/CMR.0b013e3282f2a7ae.CrossRefPubMed
40.
go back to reference Kim KB, Bedikian AY, Camacho LH, Papadopoulos NE, McCullough C: A phase II trial of arsenic trioxide in patients with metastatic melanoma. Cancer. 2005, 104: 1687-1692. 10.1002/cncr.21386.CrossRefPubMed Kim KB, Bedikian AY, Camacho LH, Papadopoulos NE, McCullough C: A phase II trial of arsenic trioxide in patients with metastatic melanoma. Cancer. 2005, 104: 1687-1692. 10.1002/cncr.21386.CrossRefPubMed
41.
go back to reference Tarhini AA, Kirkwood JM, Tawbi H, Gooding WE, Islam MF, Agarwala SS: Safety and efficacy of arsenic trioxide for patients with advanced metastatic melanoma. Cancer. 2008, 112: 1131-1138. 10.1002/cncr.23284.CrossRefPubMed Tarhini AA, Kirkwood JM, Tawbi H, Gooding WE, Islam MF, Agarwala SS: Safety and efficacy of arsenic trioxide for patients with advanced metastatic melanoma. Cancer. 2008, 112: 1131-1138. 10.1002/cncr.23284.CrossRefPubMed
42.
go back to reference Leong PL, Andrews GA, Johnson DE, Dyer KF, Xi S, Mai JC, Robbins PD, Gadiparthi S, Burke NA, Watkins SF, Grandis JR: Targeted inhibition of Stat3 with a decoy oligonucleotide abrogates head and neck cancer cell growth. Proc Natl Acad Sci USA. 2003, 100: 4138-4143. 10.1073/pnas.0534764100.PubMedCentralCrossRefPubMed Leong PL, Andrews GA, Johnson DE, Dyer KF, Xi S, Mai JC, Robbins PD, Gadiparthi S, Burke NA, Watkins SF, Grandis JR: Targeted inhibition of Stat3 with a decoy oligonucleotide abrogates head and neck cancer cell growth. Proc Natl Acad Sci USA. 2003, 100: 4138-4143. 10.1073/pnas.0534764100.PubMedCentralCrossRefPubMed
43.
go back to reference Mizoguchi M, Betensky RA, Batchelor TT, Bernay DC, Louis DN, Nutt CL: Activation of STAT3, MAPK, and AKT in malignant astrocytic gliomas: correlation with EGFR status, tumor grade, and survival. J Neuropathol Exp Neurol. 2006, 65: 1181-1188. 10.1097/01.jnen.0000248549.14962.b2.CrossRefPubMed Mizoguchi M, Betensky RA, Batchelor TT, Bernay DC, Louis DN, Nutt CL: Activation of STAT3, MAPK, and AKT in malignant astrocytic gliomas: correlation with EGFR status, tumor grade, and survival. J Neuropathol Exp Neurol. 2006, 65: 1181-1188. 10.1097/01.jnen.0000248549.14962.b2.CrossRefPubMed
44.
go back to reference Nakajima K, Yamanaka Y, Nakae K, Kojima H, Ichiba M, Kiuchi N, Kitaoka T, Fukada T, Hibi M, Hirano T: A central role for Stat3 in IL-6-induced regulation of growth and differentiation in M1 leukemia cells. EMBO J. 1996, 15: 3651-3658.PubMedCentralPubMed Nakajima K, Yamanaka Y, Nakae K, Kojima H, Ichiba M, Kiuchi N, Kitaoka T, Fukada T, Hibi M, Hirano T: A central role for Stat3 in IL-6-induced regulation of growth and differentiation in M1 leukemia cells. EMBO J. 1996, 15: 3651-3658.PubMedCentralPubMed
45.
go back to reference Ghirnikar RS, Lee YL, Eng LF: Inflammation in traumatic brain injury: role of cytokines and chemokines. Neurochem Res. 1998, 23: 329-340. 10.1023/A:1022453332560.CrossRefPubMed Ghirnikar RS, Lee YL, Eng LF: Inflammation in traumatic brain injury: role of cytokines and chemokines. Neurochem Res. 1998, 23: 329-340. 10.1023/A:1022453332560.CrossRefPubMed
46.
go back to reference Winston LA, Hunter T: JAK2, Ras, and Raf are required for activation of extracellular signal-regulated kinase/mitogen-activated protein kinase by growth hormone. J Biol Chem. 1995, 270: 30837-30840. 10.1074/jbc.270.52.30837.CrossRefPubMed Winston LA, Hunter T: JAK2, Ras, and Raf are required for activation of extracellular signal-regulated kinase/mitogen-activated protein kinase by growth hormone. J Biol Chem. 1995, 270: 30837-30840. 10.1074/jbc.270.52.30837.CrossRefPubMed
47.
go back to reference Kortylewski M, Xin H, Kujawski M, Lee H, Liu Y, Harris T, Drake C, Pardoll D, Yu H: Regulation of the IL-23 and IL-12 balance by Stat3 signaling in the tumor microenvironment. Cancer Cell. 2009, 15: 114-123. 10.1016/j.ccr.2008.12.018.PubMedCentralCrossRefPubMed Kortylewski M, Xin H, Kujawski M, Lee H, Liu Y, Harris T, Drake C, Pardoll D, Yu H: Regulation of the IL-23 and IL-12 balance by Stat3 signaling in the tumor microenvironment. Cancer Cell. 2009, 15: 114-123. 10.1016/j.ccr.2008.12.018.PubMedCentralCrossRefPubMed
48.
go back to reference Fontenot JD, Rudensky AY: A well adapted regulatory contrivance: regulatory T cell development and the forkhead family transcription factor Foxp3. Nat Immunol. 2005, 6: 331-337. 10.1038/ni1179.CrossRefPubMed Fontenot JD, Rudensky AY: A well adapted regulatory contrivance: regulatory T cell development and the forkhead family transcription factor Foxp3. Nat Immunol. 2005, 6: 331-337. 10.1038/ni1179.CrossRefPubMed
Metadata
Title
yuDetecting the percent of peripheral blood mononuclear cells displaying p-STAT-3 in malignant glioma patients
Authors
William Humphries
Yongtao Wang
Wei Qiao
Chantal Reina-Ortiz
Mohamed K Abou-Ghazal
Lamonne M Crutcher
Jun Wei
Ling-Yuan Kong
Raymond Sawaya
Ganesh Rao
Jeffrey Weinberg
Sujit S Prabhu
Gregory N Fuller
Amy B Heimberger
Publication date
01-12-2009
Publisher
BioMed Central
Published in
Journal of Translational Medicine / Issue 1/2009
Electronic ISSN: 1479-5876
DOI
https://doi.org/10.1186/1479-5876-7-92

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