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COX-2 regulation of vaccination responses in lung cancer

Institution: University of California, Los Angeles
Investigator(s): Steven Dubinett, M.D.
Award Cycle: 2004 (Cycle 13) Grant #: 13RT-0031 Award: $379,362
Subject Area: Cancer
Award Type: Research Project Awards
Abstracts
Initial Award Abstract
New targeted therapies are needed for lung cancer chemoprevention in high-risk patients and for therapy in all clinical stages of the disease. Cyclooxygenase 2 (COX-2) is an enzyme that is found in lung cancer cells that is responsible for suppressing patients’ immune systems and therefore contributing to the growth of lung cancer. This research is designed to evaluate the importance of COX-2 in lung cancer and to test in laboratory models the capacity of specific COX-2 inhibitor drugs to boost the immune system against lung cancer. COX-2 inhibitors are currently being evaluated in clinical trials for lung cancer and other malignancies. This proposal evaluates COX-2 inhibition as a means to augment the immune response against lung cancer. COX-2 inhibitors may be beneficial when combined with other standard and experimental therapies. These agents may also be utilized in various vaccination strategies to enhance the response to tumors. We are focused on understanding how COX-2 expression regulates the progression of tumor growth in lung cancer in an effort to foster an informed approach for the use of COX-2 inhibitors in prevention and therapy for lung cancer. In addition, the studies described in this proposal will contribute to understanding the complex relationship between tumor and host immune cells in the generation of immune suppression in lung cancer.
Publications
COX-2-dependent stabilization of survivin in non-small cell lung cancer.
Periodical: FASEB Journal Index Medicus:
Authors: Dubinett SM, Krysan K, Merchant FH, Zhu L, Dohadwala M. Luo J, Lin Y, et al. ART
Yr: 2004 Vol: 18 Nbr: 1 Abs: Pg: 206 - 208
Cyclooxygenase-2 dependent expression of angiogenic CXC chemokines, ENA-78/CXCL5 and IL-8/CXCL8, in human non-small cell lung cancer.
Periodical: Cancer Research Index Medicus:
Authors: Dubinett SM, Pold M, Zhu L, Sharma S, Burdick M, Ying L, Lee PN, Pold A, et al. ART
Yr: 2004 Vol: 64 Nbr: Abs: Pg: 1853 - 1860
Cyclooxygenase-2 modulates the insulin-like growth factor axis in non-small cell lung cancer.
Periodical: Cancer Research Index Medicus:
Authors: Dubinett SM, Pold M, Krysan K, Pold A, Dohadwala M. Heuze-Vourc'h Mao JT, et al. ART
Yr: 2004 Vol: 64 Nbr: Abs: Pg: 6549 - 6555
Cyclooxygenase 2-dependent expression of survivin is critical for apoptosis resistance in non-small cell lung cancer.
Periodical: Cancer Research Index Medicus:
Authors: Krysan K, Dalwadi H, Sharma S, Pold M, Dubinett SM ART
Yr: 2004 Vol: 64 Nbr: Abs: Pg: 6359 - 6362
Prostaglandin E2-Dependent enhancement of tissue inhibitors of metalloproteinases-1 production limits dendritic cell migration through extracellular matrix.
Periodical: Journal of Immunology Index Medicus:
Authors: Dubinett SM, Baratelli F, Heuze-Vourc'h N, Krysan K, Dohadwala M, Riedl K, Sharma S ART
Yr: 2004 Vol: 173 Nbr: Abs: Pg: 5458 - 5466
Modulation of pulmonary leukotriene B4 production by cyclooygenase-2 inhibitors and lipopolysaccharide.
Periodical: Clinical Cancer Research Index Medicus:
Authors: Mao JT, Tsu IH, Dubinett SM, Adams B, Sarafian T, Baratelli F, Roth MD, Serio KJ ART
Yr: 2004 Vol: 10 Nbr: Abs: Pg: 6872 - 6878
Tumor cyclooxygenase-2/prostaglandin E2-dependent promotion of FOXP3 expression and CD4+CD25+T regulatory cell activities in lung cancer.
Periodical: Cancer Research Index Medicus:
Authors: Dubinett SM, Sharma S, Yang SC, Zhu L, Reckamp K, Gardner B, Baratelli F, et al. ART
Yr: 2005 Vol: 65 Nbr: 12 Abs: Pg: 5211 - 5220
PGE2 confers survivin-dependent apoptosis resistance in human monocyte-derived dendritic cells.
Periodical: Journal of Leukocyte Biology Index Medicus:
Authors: Dubinett SM, Baratelli F, Krysan K, Heuze-Vourc'h N, Zhu L. Escuadro B, Sharma S, et al. ART
Yr: 2005 Vol: Nbr: Abs: Pg:
IL-20, an anti-angiogenic cytokine that inhibits COX-2 expression.
Periodical: Biochem Biophys Res Commun Index Medicus:
Authors: Dubinett SM, Heuze-Vourc'h N, Liu M, Dalwadi H, Baratelli FE, Zhu L, Goodglick L, et al. ART
Yr: 2005 Vol: 333 Nbr: 2 Abs: Pg: 470 - 475
COX-2 inhibition, promotes IFNy-dependent enhancement of anti-tumor immunity.
Periodical: Journal of Immunology Index Medicus:
Authors: Dubinett SM, Sharma S, Zhu L, Hillinger S, Yang SC, Atianzar K, Gardner B, et al. ART
Yr: 2005 Vol: 175 Nbr: 2 Abs: Pg: 813 - 819
PGE2 activates MAPK/Erk pathway signaling and cell proliferation in non-small cell lung cancer cells in an EGF receptor-independent manner.
Periodical: Cancer Research Index Medicus:
Authors: Dubinett SM, Krysan K, Reckamp K, Dalwadi H, Sharma S Rozengurt E, Dohadwala M ART
Yr: 2005 Vol: 65 Nbr: 14 Abs: Pg: 6275 - 6281
PGE2 induces FOXP3 gene expression and T regulatory cell function in human CD4+ T cells.
Periodical: Journal of Immunology Index Medicus:
Authors: Dubinett SM, Baratelli F, Lin Y, Zhu L, Yang SC, Hueze-Vourc'h N,Zeng G, et al. ART
Yr: 2005 Vol: 175 Nbr: Abs: Pg: 1483 - 1490
COX-2-Dependent gene expresssion in non-small cell lung cancer.
Periodical: Proceedings of the American Association for Cancer Research Index Medicus:
Authors: Dubinett SM, Dalwadi H, Cohadwala M, Luo J, Lin Y, Krysan K, Pold M, Sharma S ABS
Yr: 2004 Vol: 45 Nbr: Abs: Pg: 1627
COX-2 inhibition promotes IFNy-dependent enhancement of anti-tumor immunity.
Periodical: American Journal of Respiratory and Critical Care Medicine Index Medicus:
Authors: Dubinett SM, Yang SC, Sharma S, Zhu L, Hillinger S, Zhang L, Atlanzar K, Gardner B, et al. ABS
Yr: 2004 Vol: 169 Nbr: Abs: Pg: A291
Cyciooxygenase-2 dependent expression of angiogenic CXC chemokines, ENA-78/CXCL5 and IL-8/CXCL8, in human non-small cell lung cancer.
Periodical: Proceedings of the American Association for Cancer Research Index Medicus:
Authors: Dubinett SM, Pold M, Zhu LX, Sharma S, Burdick MD, Lin Y, Pold A, Luo J Krysan K, et al. ABS
Yr: 2004 Vol: 45 Nbr: Abs: Pg: 4942
Tumor COX-2 expression: A window to pathways and targets in non-small cell lung cancer.
Periodical: Lung Cancer Index Medicus:
Authors: Dubinett SM, Dalwadi H, Krysan K, Dohadwala M, Sharma Sm Mao JT, Pold M, et al. ABS
Yr: 2004 Vol: 46 Nbr: Abs: Pg: S10
STAT6 mediates IL-4 inhibition of cyclooxygenase-2 (COX-2): Defining native COX-2 regulation to develop new targets for lung cancer chemoprevention.
Periodical: Proceedings of the American Association for Cancer Research Index Medicus:
Authors: Cui X, Yang SC, Dalwadi H, Sharma S, Caculano N, Dubinett SM ABS
Yr: 2004 Vol: Nbr: Abs: Pg: B52
Cyclooxygenase-2 regulates cytokine balance and apoptosis resistance in non-small cell lung cancer.
Periodical: International Society for Biological Therapy of Cancer Index Medicus:
Authors: Dubinett SM, Riedl K, Yang SC, Baratelli F, Dohadwala M, Huang M, Krysan K, et al. ABS
Yr: 0 Vol: Nbr: Abs: Pg:
Tumor cyclooxygenase 2 controls PGE2 dependent promotion of FOXP3 expression and CD4+CD25+ T regulatory cell activities in non-small cell lung cancer.
Periodical: Proceedings of the American Association for Cancer Research Index Medicus:
Authors: Dubinett SM, Baratelli FE, Yang SC, Lin Y, Zhu L, Reckamp K, Gardner B, et al. ABS
Yr: 2005 Vol: 46 Nbr: Abs: Pg: 2657
Cyclooxygenase-2-dependent activation of signal transducer and activator of transcription 3 by interleukin-6 in non-small cell lung cancer.
Periodical: Proceedings of the American Association for Cancer Research Index Medicus:
Authors: Dubinett SM, Dalwadi H, Krysan K Heusze-Vourc'h N, Pold M, et al. ABS
Yr: 2005 Vol: 46 Nbr: Abs: Pg: 5237
Determining the optimal biologic dose of COX-2 inhibition by celecoxib through measurement of urinary PGE-M in advanced non small cell lung cancer.
Periodical: Proceedings of the American Association for Cancer Research Index Medicus:
Authors: Dubinett SM, Reckamp K, Krysan K, Morrow J, Figlin R ABS
Yr: 2005 Vol: 46 Nbr: Abs: Pg: 467
PGE2-stimulated proliferation of NSCLC cells is epidermal growth factor receptor-independent and resistant to erlotinib.
Periodical: Proceedings of the American Association for Cancer Research Index Medicus:
Authors: Dubinett SM, Krysan K, Reckamp KL, Escuadro B, Bando J ABS
Yr: 2005 Vol: 46 Nbr: Abs: Pg: 154
COX-2 inhibition promotes IFNy-dependent enhancement of anti-tumor immunity and vaccine responses in lung cancer models.
Periodical: Proceedings of the American Association for Cancer Research Index Medicus:
Authors: Dubinett SM, Yang SC, Zhu L, Gardner B, Riedl K, Strieter RM, Batra RK, et al. ABS
Yr: 2005 Vol: 46 Nbr: Abs: Pg: 6056
STAT6 Mediates IL-4 inhibition of cyclooxygenase-2 in non-small cell lung cancer.
Periodical: Proceedings of the American Association for Cancer Research Index Medicus:
Authors: Dubinett SM, Cui X, Yang SC, Dalwadi H, Sharma S, Heuze-Vourc'h N, Cacalano N ABS
Yr: 2005 Vol: 46 Nbr: Abs: Pg: 5017
Arginase I in myeloid suppressor cells is induced by cox-2 in lung carcinoma
Periodical: Journal of Experimental Medicine Index Medicus:
Authors: Rodriquez PC, Hernandez PC, Quiceno D, Dubinett SM, Zabaleta J, Ochoa JB Gilbert J OChoa A ART
Yr: 2005 Vol: 202 Nbr: 7 Abs: Pg: 931-9
Cycloooxygenase 2 dependent regulation of STAT3 pathways in NSCLC
Periodical: Clinical Cancer Research Index Medicus:
Authors: Dalwadi H, Krysan K, Heuze-Vourch N, Sharma S, Dohadwala M, Riedi K, Cacalano N, Dubinett ART
Yr: 2005 Vol: 11 Nbr: 21 Abs: Pg: 7674-82
IL-4 regulates COX-2 and PGE2 production in Human non-small cell lung cancer
Periodical: Biochem Biophys Res Commun Index Medicus:
Authors: Cui X, Yang SC, Sharma S, Heuze Vourch N, Dubinett SM ART
Yr: 2006 Vol: 343 Nbr: 4 Abs: Pg: 995-1001
Cyclooxygenase 2 dependent regulation of E-Cadherin prostaglandin E2 induces transcriptional repressors ZEB1 and snail in non small cell lung cancer
Periodical: Cancer Research Index Medicus:
Authors: Dohadwala M, Yang SC , Luo J, Sharma S, Batra RK, Huang M, Lin Y Good Glick L, Krysan K, F ART
Yr: 2006 Vol: 66 Nbr: 10 Abs: Pg: 5338-45
Tumor cyclooxgenase 2 controls PGE2 dependent promation of FOX P3 expression and CD4 CD25 T regulatory cell activities in non-small cell lung cancer
Periodical: Proceedings of the American Association for Cancer Research Index Medicus:
Authors: Dubinett , SM ABS
Yr: 2005 Vol: 46 Nbr: Abs: Pg: 2657
COX-2-dependent stabilization of survivin in non-small cell lung cancer.
Periodical: FASEB Journal Index Medicus:
Authors: Dubinett SM, Krysan K, Merchant FH, Zhu L, Dohadwala M. Luo J, Lin Y, et al. ART
Yr: 2004 Vol: 18 Nbr: 1 Abs: Pg: 206 - 208
Cyclooxygenase-2 dependent expression of angiogenic CXC chemokines, ENA-78/CXCL5 and IL-8/CXCL8, in human non-small cell lung cancer.
Periodical: Cancer Research Index Medicus:
Authors: Dubinett SM, Pold M, Zhu L, Sharma S, Burdick M, Ying L, Lee PN, Pold A, et al. ART
Yr: 2004 Vol: 64 Nbr: Abs: Pg: 1853 - 1860
Cyclooxygenase-2 modulates the insulin-like growth factor axis in non-small cell lung cancer.
Periodical: Cancer Research Index Medicus:
Authors: Dubinett SM, Pold M, Krysan K, Pold A, Dohadwala M. Heuze-Vourc'h Mao JT, et al. ART
Yr: 2004 Vol: 64 Nbr: Abs: Pg: 6549 - 6555
Cyclooxygenase 2-dependent expression of survivin is critical for apoptosis resistance in non-small cell lung cancer.
Periodical: Cancer Research Index Medicus:
Authors: Krysan K, Dalwadi H, Sharma S, Pold M, Dubinett SM ART
Yr: 2004 Vol: 64 Nbr: Abs: Pg: 6359 - 6362
Prostaglandin E2-Dependent enhancement of tissue inhibitors of metalloproteinases-1 production limits dendritic cell migration through extracellular matrix.
Periodical: Journal of Immunology Index Medicus:
Authors: Dubinett SM, Baratelli F, Heuze-Vourc'h N, Krysan K, Dohadwala M, Riedl K, Sharma S ART
Yr: 2004 Vol: 173 Nbr: Abs: Pg: 5458 - 5466
Modulation of pulmonary leukotriene B4 production by cyclooygenase-2 inhibitors and lipopolysaccharide.
Periodical: Clinical Cancer Research Index Medicus:
Authors: Mao JT, Tsu IH, Dubinett SM, Adams B, Sarafian T, Baratelli F, Roth MD, Serio KJ ART
Yr: 2004 Vol: 10 Nbr: Abs: Pg: 6872 - 6878
Tumor cyclooxygenase-2/prostaglandin E2-dependent promotion of FOXP3 expression and CD4+CD25+T regulatory cell activities in lung cancer.
Periodical: Cancer Research Index Medicus:
Authors: Dubinett SM, Sharma S, Yang SC, Zhu L, Reckamp K, Gardner B, Baratelli F, et al. ART
Yr: 2005 Vol: 65 Nbr: 12 Abs: Pg: 5211 - 5220
PGE2 confers survivin-dependent apoptosis resistance in human monocyte-derived dendritic cells.
Periodical: Journal of Leukocyte Biology Index Medicus:
Authors: Dubinett SM, Baratelli F, Krysan K, Heuze-Vourc'h N, Zhu L. Escuadro B, Sharma S, et al. ART
Yr: 2005 Vol: Nbr: Abs: Pg:
IL-20, an anti-angiogenic cytokine that inhibits COX-2 expression.
Periodical: Biochem Biophys Res Commun Index Medicus:
Authors: Dubinett SM, Heuze-Vourc'h N, Liu M, Dalwadi H, Baratelli FE, Zhu L, Goodglick L, et al. ART
Yr: 2005 Vol: 333 Nbr: 2 Abs: Pg: 470 - 475
COX-2 inhibition, promotes IFNy-dependent enhancement of anti-tumor immunity.
Periodical: Journal of Immunology Index Medicus:
Authors: Dubinett SM, Sharma S, Zhu L, Hillinger S, Yang SC, Atianzar K, Gardner B, et al. ART
Yr: 2005 Vol: 175 Nbr: 2 Abs: Pg: 813 - 819
PGE2 activates MAPK/Erk pathway signaling and cell proliferation in non-small cell lung cancer cells in an EGF receptor-independent manner.
Periodical: Cancer Research Index Medicus:
Authors: Dubinett SM, Krysan K, Reckamp K, Dalwadi H, Sharma S Rozengurt E, Dohadwala M ART
Yr: 2005 Vol: 65 Nbr: 14 Abs: Pg: 6275 - 6281
PGE2 induces FOXP3 gene expression and T regulatory cell function in human CD4+ T cells.
Periodical: Journal of Immunology Index Medicus:
Authors: Dubinett SM, Baratelli F, Lin Y, Zhu L, Yang SC, Hueze-Vourc'h N,Zeng G, et al. ART
Yr: 2005 Vol: 175 Nbr: Abs: Pg: 1483 - 1490
COX-2-Dependent gene expresssion in non-small cell lung cancer.
Periodical: Proceedings of the American Association for Cancer Research Index Medicus:
Authors: Dubinett SM, Dalwadi H, Cohadwala M, Luo J, Lin Y, Krysan K, Pold M, Sharma S ABS
Yr: 2004 Vol: 45 Nbr: Abs: Pg: 1627
COX-2 inhibition promotes IFNy-dependent enhancement of anti-tumor immunity.
Periodical: American Journal of Respiratory and Critical Care Medicine Index Medicus:
Authors: Dubinett SM, Yang SC, Sharma S, Zhu L, Hillinger S, Zhang L, Atlanzar K, Gardner B, et al. ABS
Yr: 2004 Vol: 169 Nbr: Abs: Pg: A291
Cyciooxygenase-2 dependent expression of angiogenic CXC chemokines, ENA-78/CXCL5 and IL-8/CXCL8, in human non-small cell lung cancer.
Periodical: Proceedings of the American Association for Cancer Research Index Medicus:
Authors: Dubinett SM, Pold M, Zhu LX, Sharma S, Burdick MD, Lin Y, Pold A, Luo J Krysan K, et al. ABS
Yr: 2004 Vol: 45 Nbr: Abs: Pg: 4942
Tumor COX-2 expression: A window to pathways and targets in non-small cell lung cancer.
Periodical: Lung Cancer Index Medicus:
Authors: Dubinett SM, Dalwadi H, Krysan K, Dohadwala M, Sharma Sm Mao JT, Pold M, et al. ABS
Yr: 2004 Vol: 46 Nbr: Abs: Pg: S10
STAT6 mediates IL-4 inhibition of cyclooxygenase-2 (COX-2): Defining native COX-2 regulation to develop new targets for lung cancer chemoprevention.
Periodical: Proceedings of the American Association for Cancer Research Index Medicus:
Authors: Cui X, Yang SC, Dalwadi H, Sharma S, Caculano N, Dubinett SM ABS
Yr: 2004 Vol: Nbr: Abs: Pg: B52
Cyclooxygenase-2 regulates cytokine balance and apoptosis resistance in non-small cell lung cancer.
Periodical: International Society for Biological Therapy of Cancer Index Medicus:
Authors: Dubinett SM, Riedl K, Yang SC, Baratelli F, Dohadwala M, Huang M, Krysan K, et al. ABS
Yr: 0 Vol: Nbr: Abs: Pg:
Tumor cyclooxygenase 2 controls PGE2 dependent promotion of FOXP3 expression and CD4+CD25+ T regulatory cell activities in non-small cell lung cancer.
Periodical: Proceedings of the American Association for Cancer Research Index Medicus:
Authors: Dubinett SM, Baratelli FE, Yang SC, Lin Y, Zhu L, Reckamp K, Gardner B, et al. ABS
Yr: 2005 Vol: 46 Nbr: Abs: Pg: 2657
Cyclooxygenase-2-dependent activation of signal transducer and activator of transcription 3 by interleukin-6 in non-small cell lung cancer.
Periodical: Proceedings of the American Association for Cancer Research Index Medicus:
Authors: Dubinett SM, Dalwadi H, Krysan K Heusze-Vourc'h N, Pold M, et al. ABS
Yr: 2005 Vol: 46 Nbr: Abs: Pg: 5237
Determining the optimal biologic dose of COX-2 inhibition by celecoxib through measurement of urinary PGE-M in advanced non small cell lung cancer.
Periodical: Proceedings of the American Association for Cancer Research Index Medicus:
Authors: Dubinett SM, Reckamp K, Krysan K, Morrow J, Figlin R ABS
Yr: 2005 Vol: 46 Nbr: Abs: Pg: 467
PGE2-stimulated proliferation of NSCLC cells is epidermal growth factor receptor-independent and resistant to erlotinib.
Periodical: Proceedings of the American Association for Cancer Research Index Medicus:
Authors: Dubinett SM, Krysan K, Reckamp KL, Escuadro B, Bando J ABS
Yr: 2005 Vol: 46 Nbr: Abs: Pg: 154
COX-2 inhibition promotes IFNy-dependent enhancement of anti-tumor immunity and vaccine responses in lung cancer models.
Periodical: Proceedings of the American Association for Cancer Research Index Medicus:
Authors: Dubinett SM, Yang SC, Zhu L, Gardner B, Riedl K, Strieter RM, Batra RK, et al. ABS
Yr: 2005 Vol: 46 Nbr: Abs: Pg: 6056
STAT6 Mediates IL-4 inhibition of cyclooxygenase-2 in non-small cell lung cancer.
Periodical: Proceedings of the American Association for Cancer Research Index Medicus:
Authors: Dubinett SM, Cui X, Yang SC, Dalwadi H, Sharma S, Heuze-Vourc'h N, Cacalano N ABS
Yr: 2005 Vol: 46 Nbr: Abs: Pg: 5017
Arginase I in myeloid suppressor cells is induced by cox-2 in lung carcinoma
Periodical: Journal of Experimental Medicine Index Medicus:
Authors: Rodriquez PC, Hernandez PC, Quiceno D, Dubinett SM, Zabaleta J, Ochoa JB Gilbert J OChoa A ART
Yr: 2005 Vol: 202 Nbr: 7 Abs: Pg: 931-9
Cycloooxygenase 2 dependent regulation of STAT3 pathways in NSCLC
Periodical: Clinical Cancer Research Index Medicus:
Authors: Dalwadi H, Krysan K, Heuze-Vourch N, Sharma S, Dohadwala M, Riedi K, Cacalano N, Dubinett ART
Yr: 2005 Vol: 11 Nbr: 21 Abs: Pg: 7674-82
IL-4 regulates COX-2 and PGE2 production in Human non-small cell lung cancer
Periodical: Biochem Biophys Res Commun Index Medicus:
Authors: Cui X, Yang SC, Sharma S, Heuze Vourch N, Dubinett SM ART
Yr: 2006 Vol: 343 Nbr: 4 Abs: Pg: 995-1001
Cyclooxygenase 2 dependent regulation of E-Cadherin prostaglandin E2 induces transcriptional repressors ZEB1 and snail in non small cell lung cancer
Periodical: Cancer Research Index Medicus:
Authors: Dohadwala M, Yang SC , Luo J, Sharma S, Batra RK, Huang M, Lin Y Good Glick L, Krysan K, F ART
Yr: 2006 Vol: 66 Nbr: 10 Abs: Pg: 5338-45
Tumor cyclooxgenase 2 controls PGE2 dependent promation of FOX P3 expression and CD4 CD25 T regulatory cell activities in non-small cell lung cancer
Periodical: Proceedings of the American Association for Cancer Research Index Medicus:
Authors: Dubinett , SM ABS
Yr: 2005 Vol: 46 Nbr: Abs: Pg: 2657