J A McCubrey

Summary

Affiliation: East Carolina University
Country: USA

Publications

  1. ncbi request reprint Targeting the cancer initiating cell: the ultimate target for cancer therapy
    James A McCubrey
    Department of Microbiology and Immunology, Brody School of Medicine at East Carolina University, Greenville, NC 27858, USA
    Curr Pharm Des 18:1784-95. 2012
  2. pmc Mutations and deregulation of Ras/Raf/MEK/ERK and PI3K/PTEN/Akt/mTOR cascades which alter therapy response
    James A McCubrey
    Department of Microbiology and Immunology, Brody School of Medicine at East Carolina University, Greenville, NC, USA
    Oncotarget 3:954-87. 2012
  3. pmc One-carbon metabolism: an aging-cancer crossroad for the gerosuppressant metformin
    Javier A Menendez
    Metabolism and Cancer Group, Translational Research Laboratory, Catalan Institute of Oncology Girona ICO Girona, Girona, Spain
    Aging (Albany NY) 4:894-8. 2012
  4. pmc Advances in targeting signal transduction pathways
    James A McCubrey
    Department of Microbiology and Immunology, Brody School of Medicine at East Carolina University, USA
    Oncotarget 3:1505-21. 2012
  5. pmc Recent discoveries in the cycling, growing and aging of the p53 field
    James A McCubrey
    Department of Microbiology and Immunology, Brody School of Medicine, East Carolina University, NC 27858, USA
    Aging (Albany NY) 4:887-93. 2012
  6. pmc PI3K activation is associated with intracellular sodium/iodide symporter protein expression in breast cancer
    Katherine A B Knostman
    Department of Veterinary Biosciences, The Ohio State University, Columbus, Ohio 43210, USA
    BMC Cancer 7:137. 2007
  7. doi request reprint Involvement of p53 and Raf/MEK/ERK pathways in hematopoietic drug resistance
    J A McCubrey
    Department of Microbiology and Immunology, Brody School of Medicine, East Carolina University, Greenville, NC 27858, USA
    Leukemia 22:2080-90. 2008
  8. doi request reprint Therapeutic resistance resulting from mutations in Raf/MEK/ERK and PI3K/PTEN/Akt/mTOR signaling pathways
    James A McCubrey
    Department of Microbiology and Immunology, Brody School of Medicine at East Carolina University, Greenville, North Carolina 27858, USA
    J Cell Physiol 226:2762-81. 2011
  9. doi request reprint Targeting the cancer initiating cell: the Achilles' heel of cancer
    James A McCubrey
    Department of Microbiology and Immunology, Brody School of Medicine, East Carolina University, Greenville, NC 27834, USA
    Adv Enzyme Regul 51:152-62. 2011
  10. doi request reprint Emerging MEK inhibitors
    James A McCubrey
    Brody School of Medicine at East Carolina University, Department of Microbiology and Immunology, 600 Moye Boulevard, Greenville, NC 27858, USA
    Expert Opin Emerg Drugs 15:203-23. 2010

Research Grants

Collaborators

Detail Information

Publications97

  1. ncbi request reprint Targeting the cancer initiating cell: the ultimate target for cancer therapy
    James A McCubrey
    Department of Microbiology and Immunology, Brody School of Medicine at East Carolina University, Greenville, NC 27858, USA
    Curr Pharm Des 18:1784-95. 2012
    ..New approaches should be developed to effectively target the CIC which could vastly improve cancer therapies and outcomes. This review will discuss recent concepts of targeting CICs in certain leukemia models...
  2. pmc Mutations and deregulation of Ras/Raf/MEK/ERK and PI3K/PTEN/Akt/mTOR cascades which alter therapy response
    James A McCubrey
    Department of Microbiology and Immunology, Brody School of Medicine at East Carolina University, Greenville, NC, USA
    Oncotarget 3:954-87. 2012
    ..This review will first describe these pathways and discuss how genetic mutations and epigenetic alterations can result in resistance to various inhibitors...
  3. pmc One-carbon metabolism: an aging-cancer crossroad for the gerosuppressant metformin
    Javier A Menendez
    Metabolism and Cancer Group, Translational Research Laboratory, Catalan Institute of Oncology Girona ICO Girona, Girona, Spain
    Aging (Albany NY) 4:894-8. 2012
    ....
  4. pmc Advances in targeting signal transduction pathways
    James A McCubrey
    Department of Microbiology and Immunology, Brody School of Medicine at East Carolina University, USA
    Oncotarget 3:1505-21. 2012
    ....
  5. pmc Recent discoveries in the cycling, growing and aging of the p53 field
    James A McCubrey
    Department of Microbiology and Immunology, Brody School of Medicine, East Carolina University, NC 27858, USA
    Aging (Albany NY) 4:887-93. 2012
    ....
  6. pmc PI3K activation is associated with intracellular sodium/iodide symporter protein expression in breast cancer
    Katherine A B Knostman
    Department of Veterinary Biosciences, The Ohio State University, Columbus, Ohio 43210, USA
    BMC Cancer 7:137. 2007
    ..We previously identified PI3K signaling as important in NIS upregulation in transgenic mouse models of breast cancer, and the PI3K pathway is commonly activated in human breast cancer...
  7. doi request reprint Involvement of p53 and Raf/MEK/ERK pathways in hematopoietic drug resistance
    J A McCubrey
    Department of Microbiology and Immunology, Brody School of Medicine, East Carolina University, Greenville, NC 27858, USA
    Leukemia 22:2080-90. 2008
    ..Thus the p53 and Raf/MEK/ERK pathways play key roles in drug sensitivity. Targeting these pathways may be effective in certain drug-resistant leukemias that are WT at p53...
  8. doi request reprint Therapeutic resistance resulting from mutations in Raf/MEK/ERK and PI3K/PTEN/Akt/mTOR signaling pathways
    James A McCubrey
    Department of Microbiology and Immunology, Brody School of Medicine at East Carolina University, Greenville, North Carolina 27858, USA
    J Cell Physiol 226:2762-81. 2011
    ..Controlling the expression of these pathways could improve cancer therapy and ameliorate human health...
  9. doi request reprint Targeting the cancer initiating cell: the Achilles' heel of cancer
    James A McCubrey
    Department of Microbiology and Immunology, Brody School of Medicine, East Carolina University, Greenville, NC 27834, USA
    Adv Enzyme Regul 51:152-62. 2011
    ..It is clear from our studies that low doses of genistein can increase the sensitivity of prostate CICs to drugs such as docetaxel and cyclopamine, two drugs either used or under consideration for prostate cancer therapy...
  10. doi request reprint Emerging MEK inhibitors
    James A McCubrey
    Brody School of Medicine at East Carolina University, Department of Microbiology and Immunology, 600 Moye Boulevard, Greenville, NC 27858, USA
    Expert Opin Emerg Drugs 15:203-23. 2010
    ..This review will cover the scientific literature from 1980 to present and is a follow on from a review which focused on Emerging Raf Inhibitors published in this same review series...
  11. ncbi request reprint Targeting the Raf/MEK/ERK pathway with small-molecule inhibitors
    James A McCubrey
    Brody School of Medicine at East Carolina University, Department of Microbiology and Immunology, 600 Moye Boulevard, Greenville, NC 27858, USA
    Curr Opin Investig Drugs 9:614-30. 2008
    ..The effective targeting of this pathway may result in the suppression of cell growth, and death of malignant cells. This review focuses on targeting the Raf/MEK/ERK pathway with small-molecule inhibitors for the treatment of cancer...
  12. doi request reprint Targeting survival cascades induced by activation of Ras/Raf/MEK/ERK, PI3K/PTEN/Akt/mTOR and Jak/STAT pathways for effective leukemia therapy
    J A McCubrey
    Department of Microbiology and Immunology, Brody School of Medicine at East Carolina University, Greenville, NC 27858, USA
    Leukemia 22:708-22. 2008
    ..Furthermore, we discuss how targeting of the leukemia microenvironment and the leukemia stem cell are emerging fields and challenges in targeted therapies...
  13. doi request reprint Emerging Raf inhibitors
    James A McCubrey
    Department of Microbiology and Immunology, Brody School of Medicine at East Carolina University, Greenville, NC 27858, USA
    Expert Opin Emerg Drugs 14:633-48. 2009
    ..The Raf/MAPK kinase/extracellular-signal-regulated kinase pathway has profound effects on proliferative, apoptotic and differentiation pathways as well as the sensitivity and resistance to chemotherapeutic drugs...
  14. ncbi request reprint Roles of the RAF/MEK/ERK and PI3K/PTEN/AKT pathways in malignant transformation and drug resistance
    James A McCubrey
    Department of Microbiology and Immunology, Brody School of Medicine at East Carolina University, Greenville, NC 27858, USA
    Adv Enzyme Regul 46:249-79. 2006
    ..These signaling and anti-apoptotic pathways can have different effects on growth, prevention of apoptosis and induction of drug resistance in cells of various lineages which may be due to the expression of lineage-specific factors...
  15. pmc Roles of the Raf/MEK/ERK pathway in cell growth, malignant transformation and drug resistance
    James A McCubrey
    Department of Microbiology and Immunology, Leo Jenkins Cancer Center, Brody School of Medicine at East Carolina University, Greenville, NC 27858, USA
    Biochim Biophys Acta 1773:1263-84. 2007
    ....
  16. ncbi request reprint GSK-3beta is a critical mediator of tetrandrine induced cell cycle arrest and cytotoxicity
    James A McCubrey
    Department of Microbiology and Immunology, Brody School of Medicine at East Carolina University, Greenville, North Carolina 27858, USA
    Cancer Biol Ther 7:1079. 2008
  17. pmc Targeting the RAF/MEK/ERK, PI3K/AKT and p53 pathways in hematopoietic drug resistance
    James A McCubrey
    Department of Microbiology and Immunology, Brody School of Medicine at East Carolina University Greenville, NC 27858, USA
    Adv Enzyme Regul 47:64-103. 2007
  18. ncbi request reprint Effects of inducible MEK1 activation on the cytokine dependency of lymphoid cells
    W L Blalock
    Department of Microbiology and Immunology, Brody School of Medicine at East Carolina University, Greenville, NC 27858, USA
    Leukemia 15:794-807. 2001
    ..GM-CSF was found to enhance the viability of FL5.12 cells. The cell lines described here will be useful for elaborating the ability of the MAP kinase pathway to regulate cell proliferation in hematopoietic cells...
  19. ncbi request reprint Differential effects of kinase cascade inhibitors on neoplastic and cytokine-mediated cell proliferation
    J G Shelton
    Department of Microbiology and Immunology, Brody School of Medicine, East Carolina University, Greenville 27858, USA
    Leukemia 17:1765-82. 2003
    ..Simultaneous inhibition of both Raf/MEK/ERK and PI3K/Akt pathways proved a more efficient means to suppress DNA synthesis and induce apoptosis at lower drug concentrations...
  20. ncbi request reprint Requirement for the PI3K/Akt pathway in MEK1-mediated growth and prevention of apoptosis: identification of an Achilles heel in leukemia
    W L Blalock
    Department of Microbiology and Immunology, Brody School of Medicine at East Carolina University, Greenville, NC 27858, USA
    Leukemia 17:1058-67. 2003
    ..Leukemia treatment targeting multiple signal transduction pathways may be more efficacious than therapy aimed at inhibiting a single pathway...
  21. ncbi request reprint Interactions between the PI3K and Raf signaling pathways can result in the transformation of hematopoietic cells
    J A McCubrey
    Department of Microbiology and Immunology, Brody School of Medicine at East Carolina University, Greenville, NC 27858, USA
    Cancer Detect Prev 25:375-93. 2001
    ..Thus, the antiapoptotic PI3K/Akt and Bcl-2/Bcl-XL proteins can interact with the growth-promoting Raf/MEK/ERK pathway and annul the cytokine dependence of certain hematopoietic cells...
  22. ncbi request reprint Synergy between an IGF-1R antibody and Raf/MEK/ERK and PI3K/Akt/mTOR pathway inhibitors in suppressing IGF-1R-mediated growth in hematopoietic cells
    F E Bertrand
    Department of Microbiology and Immunology, Brody School of Medicine at East Carolina University, Greenville, NC 27384, USA
    Leukemia 20:1254-60. 2006
    ..These results validate the use of the FD/IGF-1R cells to evaluate the effectiveness and mechanisms of targeted IGF-1R therapeutic strategies...
  23. doi request reprint Roles of the Ras/Raf/MEK/ERK pathway in leukemia therapy
    L S Steelman
    Department of Microbiology and Immunology, Brody School of Medicine at East Carolina University, Greenville, NC 27858, USA
    Leukemia 25:1080-94. 2011
    ..Controlling the expression of this pathway could improve leukemia therapy and ameliorate human health...
  24. ncbi request reprint Synergy between Raf and BCL2 in abrogating the cytokine dependency of hematopoietic cells
    P W Moye
    Department of Microbiology and Immunology, East Carolina University School of Medicine, Greenville, NC 27858, USA
    Leukemia 14:1060-79. 2000
    ..These cells will be useful in furthering our understanding of the roles of the Raf and BCL2 oncoproteins in hematopoietic cell growth, cell cycle progression and prevention of apoptosis...
  25. pmc Targeting the leukemic stem cell: the Holy Grail of leukemia therapy
    N Misaghian
    Department of Microbiology and Immunology, Brody School of Medicine at East Carolina University, Greenville, NC 27858, USA
    Leukemia 23:25-42. 2009
    ..Although the specific targeting of LSCs is a relatively new field, it is a highly promising battleground that may reveal the Holy Grail of cancer therapy...
  26. ncbi request reprint Role of the Raf signal transduction cascade in the in vitro resistance to the anticancer drug doxorubicin
    C R Weinstein-Oppenheimer
    Department of Microbiology and Immunology, Brody School of Medicine at East Carolina University, Greenville, North Carolina 27858, USA
    Clin Cancer Res 7:2898-907. 2001
    ..These observations suggest a role for the Raf-1 protooncogene in the regulation of DR...
  27. ncbi request reprint Signal transduction mediated by the Ras/Raf/MEK/ERK pathway from cytokine receptors to transcription factors: potential targeting for therapeutic intervention
    F Chang
    Department of Microbiology and Immunology, Brody School of Medicine at East Carolina University, Greenville, NC 27858, USA
    Leukemia 17:1263-93. 2003
    ..The prospects of targeting this pathway for therapeutic intervention in leukemia and other cancers will be evaluated...
  28. doi request reprint Contributions of the Raf/MEK/ERK, PI3K/PTEN/Akt/mTOR and Jak/STAT pathways to leukemia
    L S Steelman
    Department of Microbiology and Immunology, Brody School of Medicine, East Carolina University, Greenville, NC 27858, USA
    Leukemia 22:686-707. 2008
    ..In this review, we describe the Raf/MEK/ERK, PI3K/PTEN/Akt/mTOR and Jak/STAT signaling cascades and summarize recent data regarding the regulation and mutation status of these pathways and their involvement in leukemia...
  29. ncbi request reprint P21(Cip1) induced by Raf is associated with increased Cdk4 activity in hematopoietic cells
    F Chang
    Department of Microbiology and Immunology, Brody School of Medicine at East Carolina University, Greenville, North Carolina, NC 27858, USA
    Oncogene 20:4354-64. 2001
    ..Thus Raf mediated growth was associated with elevated p21(Cip1) expression, which may specifically bind with and activate Cdk4/cyclin D complexes and with decreased p27(Kip1) expression...
  30. ncbi request reprint Enhanced ability of daniplestim and myelopoietin-1 to suppress apoptosis in human hematopoietic cells
    J A McCubrey
    Department of Microbiology and Immunology, Leo Jenkins Cancer Center, Brody School of Medicine at East Carolina University, Greenville, NC 27858, USA
    Leukemia 15:1203-16. 2001
    ..These effects of daniplestim and myelopoietin-1 may contribute to their effective ability to repopulate hematopoietic precursor cells after chemotherapy...
  31. ncbi request reprint Involvement of PI3K/Akt pathway in cell cycle progression, apoptosis, and neoplastic transformation: a target for cancer chemotherapy
    F Chang
    Department of Microbiology and Immunology, Brody School of Medicine at East Carolina University, Greenville 27858, USA
    Leukemia 17:590-603. 2003
    ..Furthermore, strategies used to inhibit the PI3K/Akt pathway are presented. The potential for cancer treatment with agents inhibiting this pathway is also addressed...
  32. pmc Suppression of PTEN function increases breast cancer chemotherapeutic drug resistance while conferring sensitivity to mTOR inhibitors
    L S Steelman
    Department of Microbiology and Immunology, Brody School of Medicine, East Carolina University, Greenville, NC 27858, USA
    Oncogene 27:4086-95. 2008
    ..Mutations in the key residues which control PTEN lipid and protein phosphatase may act as dominant-negative mutants to suppress endogenous PTEN and alter the sensitivity of breast cancer patients to chemo- and targeted therapies...
  33. ncbi request reprint Autocrine transformation of hemopoietic cells resulting from cytokine message stabilization after intracisternal A particle transposition
    P A Algate
    Department of Microbiology and Immunology, East Carolina University School of Medicine, Greenville, North Carolina 27858
    Oncogene 8:1221-32. 1993
    ..Therefore, IAP proviral transposition can activate IL-3 gene expression by prolonging mRNA stability, and this mechanism can contribute to the autocrine transformation of the hemopoietic cells...
  34. ncbi request reprint The Raf/MEK/ERK signal transduction cascade as a target for chemotherapeutic intervention in leukemia
    J T Lee
    Department of Microbiology and Immunology, Brody School of Medicine at East Carolina University, Greenville, NC 27858, USA
    Leukemia 16:486-507. 2002
    ..In addition, mounting evidence suggests that the PI3K/Akt pathway may play a role in the effects elicited via MAPK signaling; as such, potential interactions and their possible cellular ramifications are discussed...
  35. ncbi request reprint Differential effects of retroviral long terminal repeats on interleukin-3 gene expression and autocrine transformation
    X Y Wang
    Department of Microbiology and Immunology, East Carolina University School of Medicine, Greenville, North Carolina 27858, USA
    Leukemia 11:1711-25. 1997
    ..In contrast, the enhancers contained in PC-IAP-LTRs and TCR enhancers may be more effective in inducing abnormal gene expression and malignant transformation...
  36. ncbi request reprint JAK/STAT, Raf/MEK/ERK, PI3K/Akt and BCR-ABL in cell cycle progression and leukemogenesis
    L S Steelman
    Department of Microbiology and Immunology, Brody School of Medicine at East Carolina University, Greenville, NC 27858, USA
    Leukemia 18:189-218. 2004
    ..This review will tie together three important signal transduction pathways involved in the regulation of hematopoietic cell growth and indicate how their expression is dysregulated by the BCR-ABL oncoprotein...
  37. ncbi request reprint Inhibition of PI3K, mTOR and MEK signaling pathways promotes rapid apoptosis in B-lineage ALL in the presence of stromal cell support
    F E Bertrand
    Department of Microbiology and Immunology, Brody School of Medicine at East Carolina University, 600 Moye Boulevard, Greenville, NC 27858, USA
    Leukemia 19:98-102. 2005
    ..Our data suggest that stromal cell-mediated apoptotic protection in B-lineage ALL is mediated by PI3K/mTOR and MEK via a synergistic mechanism(s)...
  38. ncbi request reprint Signal transduction, cell cycle regulatory, and anti-apoptotic pathways regulated by IL-3 in hematopoietic cells: possible sites for intervention with anti-neoplastic drugs
    W L Blalock
    Department of Microbiology and Immunology, East Carolina University School of Medicine Greenville, NC 27858, USA
    Leukemia 13:1109-66. 1999
    ..Finally, anti-neoplastic drugs that target crucial constituents in these pathways are evaluated...
  39. pmc Multifaceted roles of GSK-3 and Wnt/β-catenin in hematopoiesis and leukemogenesis: opportunities for therapeutic intervention
    J A McCubrey
    Department of Microbiology and Immunology, Brody School of Medicine at East Carolina University, Greenville, NC, USA
    Leukemia 28:15-33. 2014
    ..GSK-3 and Wnt are clearly intriguing therapeutic targets. ..
  40. ncbi request reprint Calcium-induced ERK activation in human T lymphocytes occurs via p56(Lck) and CaM-kinase
    R A Franklin
    Department of Microbiology and Immunology, East Carolina University School of Medicine, Brody Building, Greenville, NC 27858, USA
    Mol Immunol 37:675-83. 2000
    ..Our data suggests that increases in intracellular calcium induce the activation of ERK1 and 2 in human T lymphocytes via sequential activation of CaM-kinase and phosphorylation of p56(Lck)...
  41. ncbi request reprint Raf and VEGF: emerging therapeutic targets in Kaposi's sarcoma-associated herpesvirus infection and angiogenesis in hematopoietic and nonhematopoietic tumors
    K E Hamden
    Department of Microbiology and Immunology, Brody School of Medicine, East Carolina University, 600 Moye Boulevard, Greenville, NC 27834, USA
    Leukemia 19:18-26. 2005
    ..In this review, we discuss the effect of the Raf-GF/IC autocrine/paracrine loop on KSHV infection of both hematopoietic and nonhematopietic cells, and associated disease conditions...
  42. ncbi request reprint Phorbol esters support the proliferation of a hematopoietic cell line by upregulating c-jun expression
    M W Mayo
    Department of Microbiology and Immunology, East Carolina University School of Medicine, Greenville, North Carolina 27858
    Oncogene 9:1999-2008. 1994
    ....
  43. ncbi request reprint Targeting the PI3K and MAPK pathways to treat Kaposi's-sarcoma-associated herpes virus infection and pathogenesis
    Phelps J Lambert
    Brody School of Medicine at East Carolina University, Department of Microbiology and Immunology, Greenville, NC 27834, USA
    Expert Opin Ther Targets 11:589-99. 2007
    ..Manipulation of the PI3K and MAPK pathways also plays a role in malignant transformation. Here, the authors review the potential to target the PI3K and MAPK signaling pathways to inhibit KSHV infection and pathogenesis...
  44. ncbi request reprint Molecular pathways leading to oxidative stress-induced phosphorylation of Akt
    Michelle M Lahair
    Department of Microbiology and Immunology, Brody School of Medicine at East Carolina University, Greenville, North Carolina 27834, USA
    Antioxid Redox Signal 8:1749-56. 2006
    ..In this pathway, neither the Src kinases nor PI3K are required. The other pathway mediated by hydrogen peroxide results in the phosphorylation of Akt on S473 and requires CaM-K, PI3K, and Src activity...
  45. ncbi request reprint Cell death of MCF-7 human breast cancer cells induced by EGFR activation in the absence of other growth factors
    Ruben Garcia
    Department of Microbiology and Immunology, Brody School of Medicine at East Carolina University, Greenville, North Carolina 27858, USA
    Cell Cycle 5:1840-6. 2006
    ..These results indicate that EGFR activation by itself is not sufficient for the proliferation of breast cancer cells and suggest the existence of a mechanism that induces apoptosis upon EGFR activation...
  46. ncbi request reprint Inhibition of the CaM-kinases augments cell death in response to oxygen radicals and oxygen radical inducing cancer therapies in MCF-7 human breast cancer cells
    Oswaldo G Rodriguez-Mora
    Department of Microbiology and Immunology, Brody School of Medicine at East Carolina University, Greenville, North Carolina 27834, USA
    Cancer Biol Ther 5:1022-30. 2006
    ..This is the first time that CaM-K inhibition is reported to sensitize cancer cells to reactive oxygen intermediate inducing cancer treatments...
  47. ncbi request reprint Raf-induced cell cycle progression in human TF-1 hematopoietic cells
    Fumin Chang
    Department of Microbiology and Immunology Brody School of Medicine at East Carolina University Greenville, North Carolina 27858, USA
    Cell Cycle 1:220-6. 2002
    ..Furthermore, the differences that the various Raf isoforms have on Cdk4 activity and other cell cycle regulatory molecules can be determined in these cells...
  48. ncbi request reprint OSU-03012 in the treatment of glioblastoma
    James A McCubrey
    Department of Microbiology and Immunology, Brody School of Medicine at East Carolina University, Brody Building, Greenville, NC 27834, USA
    Mol Pharmacol 70:437-9. 2006
    ..Overall, these are exciting results and suggest that new more effective treatment options may be obtainable for people suffering from these deadly tumors...
  49. ncbi request reprint Detection of BRAF gene mutation in primary choroidal melanoma tissue
    Grazia Malaponte
    Department of Biomedical Sciences, Vittorio Emanuele II Hospital, Catania, Italy
    Cancer Biol Ther 5:225-7. 2006
    ..The presence of V600E mutation indicates that the RAF/MEK/ERK pathway, in addition to cutaneous melanoma progression, may play a role in the choroidal melanoma development...
  50. ncbi request reprint Reactive oxygen species-induced activation of the MAP kinase signaling pathways
    James A McCubrey
    Department of Microbiology and Immunology, and the Leo W Jenkins Cancer Center, Brody School of Medicine at East Carolina University, Greenville, North Carolina 27834, USA
    Antioxid Redox Signal 8:1775-89. 2006
    ..The purpose of this review is to provide the reader with an overall understanding and appreciation of oxidative stress-induced MAPK signaling...
  51. pmc Targeting prostate cancer based on signal transduction and cell cycle pathways
    John T Lee
    Department of Microbiology and Immunology, Brody School of Medicine at East Carolina University, Greenville, North Carolina 27858, USA
    Cell Cycle 7:1745-62. 2008
    ..g., p53, p21(Cip1), p27(Kip1), Rb, etc.,). This review focuses on the aberrant interactions of signal transduction and cell cycle genes products and how they can contribute to prostate cancer and alter therapeutic effectiveness...
  52. ncbi request reprint EGF induces cell motility and multi-drug resistance gene expression in breast cancer cells
    Ruben Garcia
    Department of Microbiology and Immunology, Brody School of Medicine at East Carolina University, Greenville, North Carolina 27858, USA
    Cell Cycle 5:2820-6. 2006
    ..In conclusion, treatment of MCF-7 breast cancer cells with EGF, in the absence of other growth factors, resulted in activation of EGFR signal transduction pathways; which were related with cell motility and drug resistance...
  53. ncbi request reprint Polyphenols in breast cancer treatment
    Richard A Franklin
    Department of Microbiology and Immunology, Brody School of Medicine at East Carolina University, Brody Building, Greenville, North Carolina 27834, USA
    Cancer Biol Ther 6:62-3. 2007
  54. pmc Overcoming resistance to molecularly targeted anticancer therapies: Rational drug combinations based on EGFR and MAPK inhibition for solid tumours and haematologic malignancies
    Giampaolo Tortora
    Dipartimento di Endocrinologia e Oncologia Molecolare e Clinica, Universita di Napoli Federico II, Naples, Italy
    Drug Resist Updat 10:81-100. 2007
    ....
  55. pmc Proapoptotic activity and chemosensitizing effect of the novel Akt inhibitor (2S)-1-(1H-Indol-3-yl)-3-[5-(3-methyl-2H-indazol-5-yl)pyridin-3-yl]oxypropan2-amine (A443654) in T-cell acute lymphoblastic leukemia
    Federica Fala
    Department of Human Anatomical Sciences, University of Bologna, 40126 Bologna, Italy
    Mol Pharmacol 74:884-95. 2008
    ..Because activated AKT is seen in a large percentage of patients with T-ALL, A443654, either alone or in combination with existing drugs, may be a useful therapy for primary and drug-resistant T-ALL...
  56. ncbi request reprint Akt inactivates ERK causing decreased response to chemotherapeutic drugs in advanced CaP cells
    John T Lee
    Department of Microbiology and Immunology, Brody School of Medicine at East Carolina University, Greenville, North Carolina 27858, USA
    Cell Cycle 7:631-6. 2008
    ..The genotype of the tumor must be considered for an effective response to these and other antineoplastic drugs...
  57. pmc Distinct roles for p107 and p130 in Rb-independent cellular senescence
    Brian D Lehmann
    Department of Anatomy and Cell Biology, Brody School of Medicine at East Carolina University, Greenville, North Carolina, USA
    Cell Cycle 7:1262-8. 2008
    ....
  58. ncbi request reprint Two targets are better than one. Promising combination therapy to treat breast cancer
    Richard A Franklin
    Department of Microbiology and Immunology, Brody School of Medicine at East Carolina University, Greenville, North Carolina 27834, USA
    Cancer Biol Ther 4:1190-1. 2005
  59. ncbi request reprint Development of a conditional in vivo model to evaluate the efficacy of small molecule inhibitors for the treatment of Raf-transformed hematopoietic cells
    Marina Konopleva
    Department of Blood and Marrow Transplantation, The University of Texas M D Anderson Cancer Center, Houston, Texas 77030, USA
    Cancer Res 65:9962-70. 2005
    ..This DeltaRaf:ER system can serve as a preclinical model to evaluate the effects of signal transduction inhibitors which target the Raf and MEK proteins...
  60. ncbi request reprint Phosphatidylinositol 3'-kinase activation leads to multidrug resistance protein-1 expression and subsequent chemoresistance in advanced prostate cancer cells
    John T Lee
    Department of Microbiology and Immunology, Brody School of Medicine at East Carolina University, Greenville, North Carolina, USA
    Cancer Res 64:8397-404. 2004
    ..Thus, inhibition of PI3K activity with concomitant administration of chemotoxic compounds may prove beneficial in preventing the development of drug resistance in patients with hormone-refractory prostate cancer...
  61. pmc Raf-induced vascular endothelial growth factor augments Kaposi's sarcoma-associated herpesvirus infection
    Khalief E Hamden
    Department of Microbiology and Immunology, Brody School of Medicine, East Carolina University, Greenville, NC 27834, USA
    J Virol 78:13381-90. 2004
    ..In addition, we observed enhancement of the KSHV infection in HFF cells transfected with human VEGF(121). These results confirm the ability of Raf-induced VEGF to augment KSHV infection of cells...
  62. ncbi request reprint Integrin signaling links protein kinase Cepsilon to the protein kinase B/Akt survival pathway in recurrent prostate cancer cells
    Daqing Wu
    Department of Anatomy and Cell Biology, Brody School of Medicine, East Carolina University, Greenville, NC 27858, USA
    Oncogene 23:8659-72. 2004
    ....
  63. ncbi request reprint Effects of a conditionally active v-ErbB and an EGF-R inhibitor on transformation of NIH-3T3 cells and abrogation of cytokine dependency of hematopoietic cells
    James A McCubrey
    Department of Microbiology and Immunology, Brody School of Medicine at East Carolina University, Greenville, NC 27858, USA
    Oncogene 23:7810-20. 2004
    ....
  64. ncbi request reprint Role for Raf in the entry of viruses associated with AIDS (review)
    Audy G Whitman
    Department of Microbiology and Immunology, Brody School of Medicine, East Carolina University, Greenville, NC 28578, USA
    Int J Oncol 25:469-80. 2004
    ..In this review we present an update on entry of various viruses commonly associated with AIDS and yet another novel way of analyzing virus entry...
  65. ncbi request reprint Vascular endothelial growth factor augments human herpesvirus-8 (HHV-8/KSHV) infection
    Patrick W Ford
    Department of Microbiology and Immunology, Brody School of Medicine, East Carolina University, Greenville, North Carolina 27834, USA
    Cancer Biol Ther 3:876-81. 2004
    ..These findings suggest that targeting VEGF/VEGFR may prove efficacious in controlling HHV-8 associated pathogenesis...
  66. ncbi request reprint Raf promotes human herpesvirus-8 (HHV-8/KSHV) infection
    Shaw M Akula
    Department of Microbiology and Immunology, Brody School of Medicine, East Carolina University, Greenville, NC 27858, USA
    Oncogene 23:5227-41. 2004
    ..Here we report Raf expression to significantly enhance HHV-8 infection of target cells. These findings implicate a role for Raf not only in the infectious entry of HHV-8 but also in modulating KS pathogenesis...
  67. ncbi request reprint Ability of the activated PI3K/Akt oncoproteins to synergize with MEK1 and induce cell cycle progression and abrogate the cytokine-dependence of hematopoietic cells
    John G Shelton
    Department of Microbiology and Immunology, Brody School of Medicine, East Carolina University, Greenville, North Carolina 27858, USA
    Cell Cycle 3:503-12. 2004
    ..Likewise, suppression of multiple signal transduction pathways is a more effective means to inhibit cell cycle progression and induce apoptosis in leukemic cells...
  68. ncbi request reprint Neosis and its potential role in cancer development and chemoresistance
    Patrick M Navolanic
    Department of Microbiology and Immunology, Brody School of Medicine at East Carolina University, Greenville, North Carolina 27858, USA
    Cancer Biol Ther 3:219-20. 2004
  69. ncbi request reprint Synergy between PI3K/Akt and Raf/MEK/ERK pathways in IGF-1R mediated cell cycle progression and prevention of apoptosis in hematopoietic cells
    John G Shelton
    Department of Microbiology and Immunology, Brody School of Medicine, East Carolina University, Greenville, North Carolina 27858, USA
    Cell Cycle 3:372-9. 2004
    ..These results demonstrate that the PI3K/Akt and Raf/MEK/ERK pathways are intimately involved in IGF-1R-mediated cell cycle progression and prevention of apoptosis in hematopoietic cells...
  70. ncbi request reprint B-raf and insulin synergistically prevent apoptosis and induce cell cycle progression in hematopoietic cells
    John G Shelton
    Department of Microbiology and Immunology, Brody School of Medicine, East Carolina University, Greenville, North Carolina 27858, USA
    Cell Cycle 3:189-96. 2004
    ..Raf isoforms differ in their abilities to control apoptosis and cell cycle progression and B-Raf requires insulin-activated pathways for full antiapoptotic and proliferative activity...
  71. ncbi request reprint Docetaxel cytotoxicity is enhanced by inhibition of the Raf/MEK/ERK signal transduction pathway
    Patrick M Navolanic
    Department of Microbiology and Immunology, Brody School of Medicine at East Carolina University, Greenville, North Carolina 27858, USA
    Cancer Biol Ther 2:677-8. 2003
  72. ncbi request reprint Effects of the RAF/MEK/ERK and PI3K/AKT signal transduction pathways on the abrogation of cytokine-dependence and prevention of apoptosis in hematopoietic cells
    John G Shelton
    Department of Microbiology and Immunology, Brody School of Medicine, East Carolina University, Greenville, NC 27858, USA
    Oncogene 22:2478-92. 2003
    ....
  73. ncbi request reprint Raf-1 and Bcl-2 induce distinct and common pathways that contribute to breast cancer drug resistance
    Julianne M Davis
    Department of Microbiology and Immunology, Brody School of Medicine at East Carolina University, Greenville, NC 27858, USA
    Clin Cancer Res 9:1161-70. 2003
    ..These observations suggest both independent and overlapping roles for Raf-1 and Bcl-2 oncogenes in the resistance to growth inhibition by doxorubicin...
  74. ncbi request reprint Regulation of cell cycle progression and apoptosis by the Ras/Raf/MEK/ERK pathway (Review)
    Fumin Chang
    Department of Microbiology and Immunology, Brody School of Medicine at East Carolina University, Greenville, NC 27858, USA
    Int J Oncol 22:469-80. 2003
    ..This review will discuss the regulation of the Ras/Raf/MEK/ERK pathway and how it modulates cell cycle progression and cell survival...
  75. ncbi request reprint EGFR family signaling and its association with breast cancer development and resistance to chemotherapy (Review)
    Patrick M Navolanic
    Department of Microbiology and Immunology, Brody School of Medicine, East Carolina University, Greenville, NC 27858, USA
    Int J Oncol 22:237-52. 2003
    ..An appreciation of how these signaling pathways relate to development of breast cancer and its response to chemotherapy may lead to improved prevention, diagnosis, and treatment of this disease...
  76. ncbi request reprint Targeting the Raf kinase cascade in cancer therapy--novel molecular targets and therapeutic strategies
    John T Lee
    Department of Microbiology and Immunology, Brody School of Medicine at East Carolina University, Greenville, NC, USA
    Expert Opin Ther Targets 6:659-78. 2002
    ..Finally, the potential therapeutic promise of many of these compounds is addressed in a manner that encompasses the complexities of MAPK signal transduction, in addition to concerns surrounding the development of drug resistance...
  77. ncbi request reprint The complexity of PTEN: mutation, marker and potential target for therapeutic intervention
    Linda S Steelman
    East Carolina University, Department of Microbiology and Immunology, Brody School of Medicine, Brody Building 5N98C, Greenville, NC 27834, USA
    Expert Opin Ther Targets 8:537-50. 2004
    ..This review will discuss the role of PTEN in signal transduction and cancer as well as pharmacological approaches to combat PTEN loss in human cancer...
  78. ncbi request reprint Activated EGFR promotes the survival of B-lineage acute leukemia in the absence of stromal cells
    Justin D Spengeman
    Department of Microbiology and Immunology, The Brody School of Medicine at East Carolina University, Greenville, North Carolina 27834, USA
    Cell Cycle 4:483-7. 2005
    ..These data provide evidence that stimulation of the EGFR pathway is one mechanism by which the bone marrow microenvironment may contribute to the growth and survival of B-cell acute leukemia...
  79. ncbi request reprint Pharmacological breast cancer therapy (review)
    Patrick M Navolanic
    Department of Microbiology and Immunology, East Carolina University, Greenville, NC 27858, USA
    Int J Oncol 27:1341-4. 2005
    ..These agents inhibit breast cancer progression by a variety of different mechanisms. This review describes each of these drugs and the varying effects each of them have upon breast cancer cells...
  80. ncbi request reprint The epidermal growth factor receptor gene family as a target for therapeutic intervention in numerous cancers: what's genetics got to do with it?
    John G Shelton
    Brody School of Medicine at East Carolina University, Department of Microbiology and Immunology, Greenville, NC 27858, USA
    Expert Opin Ther Targets 9:1009-30. 2005
    ..Clearly, the EGF/EGFR signalling cascade has, and continues to play, an important role in the development of novel anticancer targeted therapies...
  81. ncbi request reprint Upping the bid on engineered inducible cell death
    James A McCubrey
    Department of Microbiology and Immunology, Leo Jenkins Cancer Center, Brody School of Medicine at East Carolina University, Greenville, NC 27858, USA
    Cancer Biol Ther 4:537. 2005
  82. ncbi request reprint Acquired immunodeficiency syndrome associated lymphoma
    Fred E Bertrand
    Department of Microbiology and Immunology, Brody School of Medicine at East Carolina University, 600 Moye Blvd, Greenville, NC 27834, USA
    Front Biosci 10:2972-7. 2005
    ..The treatment and etiology of lymphoma is a burgeoning issue in the care of HIV positive populations. This review will provide a basic overview of the association between HIV and lymphoma...
  83. ncbi request reprint Biology of Kaposi's sarcoma-associated herpesvirus
    Benjaman A Bryan
    Department of Microbiology and Immunology, Brody School of Medicine, East Carolina University, Greenville, NC 27834, USA
    Front Biosci 10:2882-91. 2005
    ..In this chapter, we delineate some of the latest findings about KSHV infection and pathogenesis...
  84. ncbi request reprint Calcium/calmodulin-dependent kinase I and calcium/calmodulin-dependent kinase kinase participate in the control of cell cycle progression in MCF-7 human breast cancer cells
    Oswaldo G Rodriguez-Mora
    Department of Microbiology and Immunology and the Leo Jenkins Cancer Center, Brody School of Medicine at East Carolina University, Greenville, North Carolina 27834, USA
    Cancer Res 65:5408-16. 2005
    ..To the best of our knowledge, this is the first time that CaM-KK has been reported to be involved in mammalian cell cycle regulation and that CaM-Ks are regulating breast cancer cell cycle...
  85. ncbi request reprint Conditional EGFR promotes cell cycle progression and prevention of apoptosis in the absence of autocrine cytokines
    John G Shelton
    Department of Microbiology and Immunology, Brody School of Medicine, East Carolina University, Greenville, North Carolina 27858, USA
    Cell Cycle 4:822-30. 2005
    ..Thus this conditional ErbB construct is useful to elucidate EGFR signaling and anti-apoptotic pathways in the absence of autocrine cytokine expression...
  86. ncbi request reprint Effects of endogenous epidermal growth factor receptor signaling on DNA synthesis and ERK activation in a cytokine-dependent hematopoietic cell line
    John G Shelton
    Department of Microbiology and Immunology, Brody School of Medicine, East Carolina University, Greenville, North Carolina 27858, USA
    Cell Cycle 4:818-21. 2005
    ..These results document the functional importance of endogenous EGFR signaling pathway in some hematopoietic cells...
  87. ncbi request reprint B-Raf-dependent expression of vascular endothelial growth factor-A in Kaposi sarcoma-associated herpesvirus-infected human B cells
    Shaw M Akula
    Department of Microbiology and Immunology, Brody School of Medicine, East Carolina University, Greenville, NC 27834, USA
    Blood 105:4516-22. 2005
    ..Taken together, we report for the first time the ability of Raf-associated signaling to play a role in the expression of VEGF-A in KSHV-infected hematopoietic cells...
  88. ncbi request reprint A novel ring-substituted diindolylmethane,1,1-bis[3'-(5-methoxyindolyl)]-1-(p-t-butylphenyl) methane, inhibits extracellular signal-regulated kinase activation and induces apoptosis in acute myelogenous leukemia
    Rooha Contractor
    Department of Blood and Marrow Transplantation, University of Texas M D Anderson Cancer Center, Houston 77030, USA
    Cancer Res 65:2890-8. 2005
    ..Together, these findings suggest that diindolylmethanes are a new class of compounds that selectively induce apoptosis in AML cells through the modulation of the extracellular signal-regulated kinase and PPARgamma signaling pathways...
  89. ncbi request reprint The effects of beta-estradiol on Raf activity, cell cycle progression and growth factor synthesis in the MCF-7 breast cancer cell line
    Caroline R Weinstein-Oppenheimer
    Department of Microbiology ond Immunology, Brody School of Medicine at East Carolina University, Greenville, North Carolina 27858, USA
    Cancer Biol Ther 1:256-62. 2002
    ..These findings suggest that targeting Raf may prove efficacious in breast cancer therapies...
  90. ncbi request reprint Kinase-addiction and bi-phasic sensitivity-resistance of Bcr-Abl- and Raf-1-expressing cells to imatinib and geldanamycin
    Zoya N Demidenko
    Brander Cancer Research Institute, New York Medical College, Valhalla, New York, USA
    Cancer Biol Ther 4:484-90. 2005
    ..Although Bcr-Abl renders cells hyper-sensitive, an excess of Bcr-Abl results in resistance (due to the remaining activity). We discuss therapeutic approaches to overcome bi-phasic resistance to mechanisms-based agents...
  91. ncbi request reprint Modulation of Raf/MEK/ERK kinase activity does not affect the chemoresistance profile of advanced prostate cancer cells
    John T Lee
    Department of Microbiology and Immunology, Brody School of Medicine at East Carolina University, Greenville, NC 27858, USA
    Int J Oncol 26:1637-44. 2005
    ..Together, these data demonstrate that the response of prostatic tumors to the chemotherapeutic compounds doxorubicin and paclitaxel is independent of Raf/MEK/ERK signaling...
  92. ncbi request reprint Selective killing of adriamycin-resistant (G2 checkpoint-deficient and MRP1-expressing) cancer cells by docetaxel
    Zoya N Demidenko
    Brander Cancer Research Institute, New York Medical College, Valhalla, New York, USA
    Cancer Res 65:4401-7. 2005
    ..We propose a therapeutic strategy to prevent normal cells from entering mitosis while increasing apoptosis selectively in mitotic cancer cells...
  93. ncbi request reprint Calcium/calmodulin-dependent protein kinases as potential targets in cancer therapy
    Oswaldo Rodriguez-Mora
    Department of Microbiology and Immunology, Brody School of Medicine, East Carolina University, Greenville, NC 27834, USA
    Expert Opin Ther Targets 9:791-808. 2005
    ..Based on these roles the authors suggest that inhibition of the CaM-kinases not only has the potential to sensitise cancer cells, but also has the potential to induce cytostasis in these cells...
  94. ncbi request reprint Increased protein expression of the PTEN tumor suppressor in the presence of constitutively active Notch-1
    William H Chappell
    Department of Microbiology and Immunology, The Brody School of Medicine at East Carolina University, Greenville, North Carolina 27834, USA
    Cell Cycle 4:1389-95. 2005
    ..These data indicate that Notch-1 can participate in cross-talk with other signaling pathways such as Ras/Raf/MEK/ERK through the regulation of the PTEN tumor suppressor...
  95. ncbi request reprint Elucidation of signal transduction pathways by retroviral infection of cells with modified oncogenes
    Linda S Steelman
    Department of Microbiology and Immunology, Brody School of Medicine at East Carolina University, Greenville, NC, USA
    Methods Mol Biol 218:221-52. 2003
    ....
  96. ncbi request reprint Signaling through 3',5'-cyclic adenosine monophosphate and phosphoinositide-3 kinase induces sodium/iodide symporter expression in breast cancer
    Katherine A B Knostman
    Department of Veterinary Biosciences, The Ohio State University, Columbus, Ohio 43210, USA
    J Clin Endocrinol Metab 89:5196-203. 2004
    ..This study is the first to demonstrate that NIS expression is induced by cAMP and/or PI3K in breast cancer both in vivo and in vitro...
  97. ncbi request reprint Absence of BRAF gene mutation in non-melanoma skin tumors
    Massimo Libra
    Department of Biomedical Sciences, University of Catania, Italy
    Cell Cycle 5:968-70. 2006
    ..Our results indicate that the BRAF gene does not appear to be frequently mutated in nonmelanoma skin tumors such as BCC. These data suggest that other gene alterations may cause tumor development...

Research Grants14

  1. Ras/Raf & PI3K/Akt Induced Breast Cancer Drug Resistance
    JAMES MC CUBREY; Fiscal Year: 2006
    ..Through these studies, more information will be available to treat breast and other cancer patients with combinations of drugs, which inhibit signal transduction and anti-apoptotic pathways leading to drug resistance. ..
  2. Ras/Raf & PI3K/Akt Induced Breast Cancer Drug Resistance
    JAMES MC CUBREY; Fiscal Year: 2003
    ..Through these studies, more information will be available to treat breast and other cancer patients with combinations of drugs, which inhibit signal transduction and anti-apoptotic pathways leading to drug resistance. ..
  3. MECHANISMS OF TRANSFORMATION OF HEMATOPOIETIC CELLS
    JAMES MC CUBREY; Fiscal Year: 2001
    ..An understanding of how these signal transduction and apoptotic pathways impinge upon one another will further our comprehension of the consequences of abnormal oncogene activation and tumor progression. ..
  4. MECHANISMS OF TRANSFORMATION OF HEMOPOIETIC CELLS
    JAMES MC CUBREY; Fiscal Year: 1993
    ....
  5. Ras/Raf & PI3K/Akt Induced Breast Cancer Drug Resistance
    JAMES MC CUBREY; Fiscal Year: 2007
    ..Throughthese studies,moreinformationwillbe availableto treatbreast andothercancerpatientswithcombinationsof drugs,whichinhibitsignaltransductionand anti-apoptoticpathwaysleadingtodrug resistance. ..