A Levitzki

Summary

Affiliation: The Hebrew University
Country: Israel

Publications

  1. pmc Optimization of energy-consuming pathways towards rapid growth in HPV-transformed cells
    Sarit Mizrachy-Schwartz
    Unit of Cellular Signaling, Department of Biological Chemistry, Alexander Silberman Institute of Life Sciences, Hebrew University of Jerusalem, Jerusalem, Israel
    PLoS ONE 2:e628. 2007
  2. pmc Loss of robustness and addiction to IGF1 during early keratinocyte transformation by human Papilloma virus 16
    Tamar Geiger
    Unit of Cellular Signaling, Department of Biological Chemistry, Alexander Silverman Institute of Life Sciences, Hebrew University of Jerusalem, Jerusalem, Israel
    PLoS ONE 2:e605. 2007
  3. pmc Anomalous features of EMT during keratinocyte transformation
    Tamar Geiger
    Department of Biological Chemistry, Institute of Life Science, The Hebrew University, Jerusalem, Israel
    PLoS ONE 3:e1574. 2008
  4. ncbi request reprint PDGF receptor kinase inhibitors for the treatment of restenosis
    Alexander Levitzki
    Unit of Cellular Signaling, Department of Biological Chemistry, The Alexander Silberman Institute of Life Sciences, The Hebrew University of Jerusalem, Jerusalem 91904, Israel
    Cardiovasc Res 65:581-6. 2005
  5. ncbi request reprint EGF receptor as a therapeutic target
    Alexander Levitzki
    Unit of Cellular Signaling, Department of Biological Chemistry, The Alexander Silberman Institute of Life Sciences, The Hebrew University of Jerusalem, Jerusalem, 91904, Israel
    Lung Cancer 41:S9-14. 2003
  6. ncbi request reprint Tyrphostins and other tyrosine kinase inhibitors
    Alexander Levitzki
    The Silberman Institute for Life Sciences, Department of Biological Chemistry, The Hebrew University, Givat Ram Campus, Jerusalem 91904, Israel
    Annu Rev Biochem 75:93-109. 2006
  7. ncbi request reprint Protein kinase inhibitors as a therapeutic modality
    Alexander Levitzki
    Unit of Cellular Signaling, Department of Biological Chemistry, The Alexander Silberman Institute of Life Sciences, The Hebrew University of Jerusalem, Jerusalem 91904, Israel
    Acc Chem Res 36:462-9. 2003
  8. ncbi request reprint Tyrosine kinases as targets for cancer therapy
    Alexander Levitzki
    Unit of Cellular Signaling, Department of Biological Chemistry, The Silverman Institute for Life Sciences, The Hebrew University of Jerusalem, Jerusalem 91904, Israel
    Eur J Cancer 38:S11-8. 2002
  9. ncbi request reprint Targeting signal transduction for disease therapy
    A Levitzki
    Department of Biological Chemistry, Alexander Silberman Institute of Life Sciences, Hebrew University of Jerusalem, Givat Ram, Israel
    Med Oncol 14:83-9. 1997
  10. ncbi request reprint Targeting signal transduction for disease therapy
    A Levitzki
    Department of Biological Chemistry, Institute of Life Sciences, The Hebrew University of Jerusalem, Givat Ram, Jerusalem 91904, Israel
    Curr Opin Cell Biol 8:239-44. 1996

Research Grants

Collaborators

Detail Information

Publications76

  1. pmc Optimization of energy-consuming pathways towards rapid growth in HPV-transformed cells
    Sarit Mizrachy-Schwartz
    Unit of Cellular Signaling, Department of Biological Chemistry, Alexander Silberman Institute of Life Sciences, Hebrew University of Jerusalem, Jerusalem, Israel
    PLoS ONE 2:e628. 2007
    ..The cap to IRES-dependent switch seems to be part of a gradual optimization of energy-consuming mechanisms that redirects cellular processes to enhance cell growth, in the course of transformation...
  2. pmc Loss of robustness and addiction to IGF1 during early keratinocyte transformation by human Papilloma virus 16
    Tamar Geiger
    Unit of Cellular Signaling, Department of Biological Chemistry, Alexander Silverman Institute of Life Sciences, Hebrew University of Jerusalem, Jerusalem, Israel
    PLoS ONE 2:e605. 2007
    ..We conclude that transformation in this model induces higher susceptibility of cells to stress due to reduced anti-apoptotic signaling and hyper-activation of p53 upon stress...
  3. pmc Anomalous features of EMT during keratinocyte transformation
    Tamar Geiger
    Department of Biological Chemistry, Institute of Life Science, The Hebrew University, Jerusalem, Israel
    PLoS ONE 3:e1574. 2008
    ..We monitored reduced Rac1-dependent migration also in the cervical cancer cell line SiHa. Therefore we can conclude that up to the stage of tumor formation migratory activity is eliminated...
  4. ncbi request reprint PDGF receptor kinase inhibitors for the treatment of restenosis
    Alexander Levitzki
    Unit of Cellular Signaling, Department of Biological Chemistry, The Alexander Silberman Institute of Life Sciences, The Hebrew University of Jerusalem, Jerusalem 91904, Israel
    Cardiovasc Res 65:581-6. 2005
    ..In this review, we describe the development of these inhibitors and their implementation as antirestenosis agents by localized delivery to the site of injury...
  5. ncbi request reprint EGF receptor as a therapeutic target
    Alexander Levitzki
    Unit of Cellular Signaling, Department of Biological Chemistry, The Alexander Silberman Institute of Life Sciences, The Hebrew University of Jerusalem, Jerusalem, 91904, Israel
    Lung Cancer 41:S9-14. 2003
    ..These findings prompted us to re-visit the oncogenic pathways, which play a role in lung cancers, with special emphasis on the way EGFR/Her-2 signaling cooperates with other signaling pathways...
  6. ncbi request reprint Tyrphostins and other tyrosine kinase inhibitors
    Alexander Levitzki
    The Silberman Institute for Life Sciences, Department of Biological Chemistry, The Hebrew University, Givat Ram Campus, Jerusalem 91904, Israel
    Annu Rev Biochem 75:93-109. 2006
    ....
  7. ncbi request reprint Protein kinase inhibitors as a therapeutic modality
    Alexander Levitzki
    Unit of Cellular Signaling, Department of Biological Chemistry, The Alexander Silberman Institute of Life Sciences, The Hebrew University of Jerusalem, Jerusalem 91904, Israel
    Acc Chem Res 36:462-9. 2003
    ..Thus, most of the effort is directed toward the development of tyrosine phosphorylation inhibitors. The success of Gleevec in the treatment of chronic myeloid leukemia and of Iressa for lung cancer validates the approach...
  8. ncbi request reprint Tyrosine kinases as targets for cancer therapy
    Alexander Levitzki
    Unit of Cellular Signaling, Department of Biological Chemistry, The Silverman Institute for Life Sciences, The Hebrew University of Jerusalem, Jerusalem 91904, Israel
    Eur J Cancer 38:S11-8. 2002
    ..STI 571 is now approved for the treatment of chronic myeloid leukemia and shows activity against gastrointestinal stromal tumors. The chemistry, kinetics, biological activity, and clinical potential of these compounds will be discussed...
  9. ncbi request reprint Targeting signal transduction for disease therapy
    A Levitzki
    Department of Biological Chemistry, Alexander Silberman Institute of Life Sciences, Hebrew University of Jerusalem, Givat Ram, Israel
    Med Oncol 14:83-9. 1997
    ..This recognition which began to emerge in the early 1980s induced us to explore the possibility of targetting the aberrant signalling pathways for disease therapy. I now present evidence for the validity of the approach...
  10. ncbi request reprint Targeting signal transduction for disease therapy
    A Levitzki
    Department of Biological Chemistry, Institute of Life Sciences, The Hebrew University of Jerusalem, Givat Ram, Jerusalem 91904, Israel
    Curr Opin Cell Biol 8:239-44. 1996
    ....
  11. ncbi request reprint PDGF receptor kinase inhibitors for the treatment of PDGF driven diseases
    Alexander Levitzki
    Unit of Cellular Signaling, Department of Biological Chemistry, The Alexander Silberman Institute of Life Sciences, The Hebrew University of Jerusalem, Givat Ram, 91904 Jerusalem, Israel
    Cytokine Growth Factor Rev 15:229-35. 2004
    ..The possible utilization of PDGFR kinase inhibitors as anti-restenosis agents is likely to move ahead of the utilization of these agents to treat human malignancies...
  12. ncbi request reprint Local delivery of platelet-derived growth factor receptor-specific tyrphostin inhibits neointimal formation in rats
    I Fishbein
    Department of Pharmaceutics, School of Pharmacy, Faculty of Medicine, Institute of Life Sciences, The Hebrew University of Jerusalem, Israel
    Arterioscler Thromb Vasc Biol 20:667-76. 2000
    ..It can be concluded that AG-1295 reduces neointimal formation by inhibiting PDGFbeta-triggered tyrosine phosphorylation...
  13. ncbi request reprint Interaction between the Saccharomyces cerevisiae CDC25 gene product and mammalian ras
    M Segal
    Department of Biological Chemistry, Alexander Silberman Institute of Life Sciences, Hebrew University of Jerusalem, Israel
    J Biol Chem 267:22747-51. 1992
    ..It follows that the yeast system can be used for characterizing the interaction between guanyl nucleotide exchangers of Ras proteins and mammalian p21H-ras...
  14. pmc Enhanced ROS production in oncogenically transformed cells potentiates c-Jun N-terminal kinase and p38 mitogen-activated protein kinase activation and sensitization to genotoxic stress
    M Benhar
    Department of Biological Chemistry, The Alexander Silberman Institute of Life Sciences, The Hebrew University of Jerusalem, Jerusalem 91904, Israel
    Mol Cell Biol 21:6913-26. 2001
    ..Taken together, our findings suggest that ROS-dependent potentiation of stress kinase pathways accounts for the sensitization of transformed cells to stress and anticancer drugs...
  15. ncbi request reprint Controlled delivery of a tyrphostin inhibits intimal hyperplasia in a rat carotid artery injury model
    G Golomb
    School of Pharmacy, Faculty of Medicine, Hebrew University of Jerusalem, Israel
    Atherosclerosis 125:171-82. 1996
    ..Perivascular controlled release delivery of the tyrphostin AG-17 inhibits neointimal formation in the rat carotid injury model...
  16. pmc Dimerization of Ste5, a mitogen-activated protein kinase cascade scaffold protein, is required for signal transduction
    D Yablonski
    Department of Biological Chemistry, Hebrew University of Jerusalem, Givat Ram, Israel
    Proc Natl Acad Sci U S A 93:13864-9. 1996
    ..A precise correlation between the biological activity of various Ste5 fragments and dimerization suggests that dimerization is essential for Ste5 function...
  17. ncbi request reprint Inhibitors of epidermal growth factor receptor kinase and of cyclin-dependent kinase 2 activation induce growth arrest, differentiation, and apoptosis of human papilloma virus 16-immortalized human keratinocytes
    H Ben-Bassat
    Laboratory of Experimental Surgery, Hadassah University Hospital, Jerusalem, Israel
    Cancer Res 57:3741-50. 1997
    ..The growth-arresting properties of AG 1478 and AG 555 identifies them as possible lead antipapilloma agents...
  18. pmc Differential activation of yeast adenylyl cyclase by Ras1 and Ras2 depends on the conserved N terminus
    N Hurwitz
    Department of Biological Chemistry, Alexander Silberman Institute of Life Sciences, Hebrew University of Jerusalem, Israel
    Proc Natl Acad Sci U S A 92:11009-13. 1995
    ....
  19. pmc Cloning of the STE5 gene of Saccharomyces cerevisiae as a suppressor of the mating defect of cdc25 temperature-sensitive mutants
    R Perlman
    Department of Biological Chemistry, Alexander Silberman Institute of Life Sciences, Hebrew University of Jerusalem, Israel
    Proc Natl Acad Sci U S A 90:5474-8. 1993
    ..RNA blot analysis reveals that STE5 gene transcription is regulated by the mating type of the cell and depends on an intact pheromone-response pathway...
  20. pmc The inhibition of EGF-dependent proliferation of keratinocytes by tyrphostin tyrosine kinase blockers
    A Dvir
    Department of Biological Chemistry, Hebrew University of Jerusalem, Israel
    J Cell Biol 113:857-65. 1991
    ..Because of the nontoxic nature of these compounds and their growth-arresting properties, we suggest their use as agents to treat hyperproliferative conditions of human skin...
  21. ncbi request reprint A Candida albicans homolog of CDC25 is functional in Saccharomyces cerevisiae
    D Goldberg
    Department of Biological Chemistry, Hebrew University of Jerusalem, Israel
    Eur J Biochem 213:195-204. 1993
    ..cerevisiae. In addition to the full length protein (approximately 150 kDa), we have found a approximately 50-kDa polypeptide which seems to include the C-terminus of the CSC25 gene product...
  22. ncbi request reprint Cisplatin induces PKB/Akt activation and p38(MAPK) phosphorylation of the EGF receptor
    S E Winograd-Katz
    Unit of Cellular Signaling, Department of Biological Chemistry, The Alexander Silberman Institute of Life Sciences, The Hebrew University of Jerusalem, Jerusalem, Israel
    Oncogene 25:7381-90. 2006
    ..Together, these results suggest that Cisplatin has side effects, which may alter the signaling pattern of cancer cells and modulate the desired effects of Cisplatin treatment...
  23. ncbi request reprint Isolation of hyperactive mutants of the MAPK p38/Hog1 that are independent of MAPK kinase activation
    M Bell
    Department of Biological Chemistry, The Alexander Silberman Institute of Life Sciences, The Hebrew University of Jerusalem, Jerusalem 91904, Israel
    J Biol Chem 276:25351-8. 2001
    ..It implies that the activating mutations could be directly used for production of active forms of MAPKs from yeasts to humans and could open the way to revealing their biological functions...
  24. ncbi request reprint Labeled EGFr-TK irreversible inhibitor (ML03): in vitro and in vivo properties, potential as PET biomarker for cancer and feasibility as anticancer drug
    Giuseppina Ortu
    Hebrew University, Hadassah University Hospital Campus, Department of Medical Biophysics and Nuclear Medicine, Jerusalem, Israel
    Int J Cancer 101:360-70. 2002
    ..Derivatives of ML03 with lower metabolic clearance rate and higher bioavailability should be synthesized and their potential as anticancer drugs and PET bioprobes evaluated...
  25. ncbi request reprint Targeted cancer therapy: promise and reality
    Shoshana Klein
    Department of Biological Chemistry, The Alexander Silberman Institute of Life Sciences, The Hebrew University of Jerusalem, Jerusalem, Israel
    Adv Cancer Res 97:295-319. 2007
    ..We discuss the use of preclinical animal models to predict successful signal transduction therapy in the clinic, and conclude that their utility is limited...
  26. ncbi request reprint PDGF-receptor tyrosine kinase blocker AG1295 selectively attenuates smooth muscle cell growth in vitro and reduces neointimal formation after balloon angioplasty in swine
    S Banai
    Heiden Department of Cardiology, Bikur Cholim Hospital, Jerusalem, Israel
    Circulation 97:1960-9. 1998
    ....
  27. ncbi request reprint Development of new insulin-like growth factor-1 receptor kinase inhibitors using catechol mimics
    Galia Blum
    Department of Biological Chemistry, The Alexander Silberman Institute of Life Sciences, The Hebrew University of Jerusalem, Givat Ram, Jerusalem 91904, Israel
    J Biol Chem 278:40442-54. 2003
    ..The ability to replace catechol groups with a moiety that is more stable in cells may aid in developing non-catechol-containing substrate-competitive inhibitors targeted toward IGF-1R and possibly against other protein-tyrosine kinases...
  28. ncbi request reprint ATP non-competitive IGF-1 receptor kinase inhibitors as lead anti-neoplastic and anti-papilloma agents
    Lilach Steiner
    Unit of Cellular Signaling, Department of Biological Chemistry, The Alexander Silberman Institute of Life Sciences, The Hebrew University of Jerusalem, Jerusalem 91904, Israel
    Eur J Pharmacol 562:1-11. 2007
    ..This new family of non-ATP competitive, IGF-1 receptor inhibitors can serve as a lead for the development of anti-cancer, anti-psoriatic and anti-papilloma agents...
  29. doi request reprint Status of p53 in human cancer cells does not predict efficacy of CHK1 kinase inhibitors combined with chemotherapeutic agents
    S Zenvirt
    Unit of Cellular Signaling, Department of Biological Chemistry, The Hebrew University of Jerusalem, Jerusalem, Israel
    Oncogene 29:6149-59. 2010
    ..Thus, combining CHK1 inhibition with DNA damage does not lead to preferential killing of p53-deficient over p53-proficient cells, and inhibiting CHK1 does not appear to be a promising approach for potentiation of cancer chemotherapy...
  30. pmc Signal transduction by a nondissociable heterotrimeric yeast G protein
    S Klein
    Department of Biological Chemistry, Alexander Silverman Institute of Life Sciences, The Hebrew University of Jerusalem, Givat Ram, Jerusalem 91904, Israel
    Proc Natl Acad Sci U S A 97:3219-23. 2000
    ..Hence, dissociation of this G protein is not required for its activation. Rather, a conformational change in the heterotrimeric complex is likely to be involved in signal transduction...
  31. ncbi request reprint Potential (18)F-labeled biomarkers for epidermal growth factor receptor tyrosine kinase
    T A Bonasera
    Hebrew University, Hadassah University Hospital Campus, Department of Medical Biophysics and Nuclear Medicine, IL-91120, Jerusalem, Israel
    Nucl Med Biol 28:359-74. 2001
    ..From our results, we concluded that while in vitro experiments indicates efficacy of 4-(anilino)quinazoline compounds, kinetic factors and rapid blood clearance make them unsuitable as tracers for nuclear medicine imaging of EGFr-TK...
  32. ncbi request reprint High-affinity epidermal growth factor receptor (EGFR) irreversible inhibitors with diminished chemical reactivities as positron emission tomography (PET)-imaging agent candidates of EGFR overexpressing tumors
    Eyal Mishani
    Department of Medical Biophysics and Nuclear Medicine, Hadassah Hebrew University, Jerusalem 91120, Israel
    J Med Chem 48:5337-48. 2005
    ..Since group C presented a greater promise for tumor accumulation, it represents, to date, the most suitable candidate for radiolabeling with long-lived positron emission tomography (PET) radioisotopes...
  33. ncbi request reprint Novel carbon-11 labeled 4-dimethylamino-but-2-enoic acid [4-(phenylamino)-quinazoline-6-yl]-amides: potential PET bioprobes for molecular imaging of EGFR-positive tumors
    Eyal Mishani
    Department of Nuclear Medicine, Hadassah Hebrew University Hospital, P O B 12000, Jerusalem 91120, Israel
    Nucl Med Biol 31:469-76. 2004
    ..7 Ci/micromol EOB. The high potency of these new labeled bioprobes towards the EGFR establishes their potential to serve as PET agents for molecular imaging of EGFR-positive tumors...
  34. ncbi request reprint Tyrosine kinase inhibitors suppress the growth of non-hodgkin B lymphomas
    Hannah Ben-Bassat
    Laboratory of Experimental Surgery, Hadassah University Hospital, The Hebrew University, Jerusalem, Israel
    J Pharmacol Exp Ther 303:163-71. 2002
    ..AGL 2592 induces a dose-dependent and time-dependent inhibition of tyrosine phosphorylation of numerous proteins, including Stat3, and an increase of Bcl-2 phosphorylation, both biochemical hallmarks of growth inhibition and apoptosis...
  35. ncbi request reprint Tumor specific activation of PKR as a non-toxic modality of cancer treatment
    Alexei Shir
    Unit of Cellular Signaling, Department of Biological Chemistry, The Alexander Silberman Institute of Life Sciences, The Hebrew University of Jerusalem, Givat Ram, Jerusalem 91904, Israel
    Semin Cancer Biol 13:309-14. 2003
    ..Over the past few years a few modalities of cancer gene therapies have emerged. In this short review we shall summarize our efforts to develop methods to activate PKR selectively in cancer cells...
  36. ncbi request reprint Signal transduction therapy of cancer
    Alexander Levitzki
    Unit of Cellular Signaling, Department of Biological Chemistry, The Hebrew University of Jerusalem, Givat Ram, Jerusalem 91904, Israel
    Mol Aspects Med 31:287-329. 2010
    ....
  37. doi request reprint Targeting the EGFR and the PKB pathway in cancer
    Shoshana Klein
    Unit of Cellular Signaling, Department of Biological Chemistry, The Hebrew University of Jerusalem, Givat Ram, Jerusalem, Israel
    Curr Opin Cell Biol 21:185-93. 2009
    ..Inhibition of the EGFR and PKB pathways also sensitizes cancer cells to chemotherapy. Thus, EGFR and PI3K/PKB inhibitors will be most effective when used in rational combinations of targeted inhibitors and traditional chemotherapy...
  38. ncbi request reprint The pp60c-Src inhibitor PP1 is non-competitive against ATP
    Rotem Karni
    Department of Biological Chemistry, The Alexander Silberman Institute of Life Sciences, The Hebrew University of Jerusalem, Israel
    FEBS Lett 537:47-52. 2003
    ..Since Src in its active form is the hallmark of numerous cancers, understanding how PP1 inhibits activated Src will aid in the discovery of potent and selective Src kinase inhibitors...
  39. ncbi request reprint Toward a PKB inhibitor: modification of a selective PKA inhibitor by rational design
    Hadas Reuveni
    Department of Biological Chemistry, The Silverman Institute of Life Sciences, The Hebrew University of Jerusalem, Jerusalem, Israel, and Peptor Ltd, Rehovot, Israel
    Biochemistry 41:10304-14. 2002
    ..We have identified structural features in NL-71-101 that are significant for the specificity and that can be used for future development and optimization of PKB inhibitors...
  40. ncbi request reprint Activation of dsRNA dependent protein kinase PKR in Karpas299 does not lead to cell death
    Inbar Friedrich
    Unit of Cellular Signaling, Department of Biological Chemistry, The Alexander Silberman Institute of Life Sciences, The Hebrew University of Jerusalem, Givat Ram, Jerusalem, Israel
    Cancer Biol Ther 4:734-9. 2005
    ..Infection with these adenoviruses, however, did not promote growth inhibition. These findings imply that anti-apoptotic mechanisms counteract PKR signaling in this T-cell non-Hodgkin's lymphoma...
  41. ncbi request reprint Phosphorylation of the S. cerevisiae Cdc25 in response to glucose results in its dissociation from Ras
    E Gross
    Department of Biological Chemistry, Alexander Silberman Institute of Life Sciences, Hebrew University of Jerusalem, Israel
    Nature 360:762-5. 1992
    ..These results are of general significance because of the highly conserved sequence of Ras-guanyl nucleotide exchange factors from yeasts to mammals...
  42. ncbi request reprint Stochastic algorithm for kinase homology model construction
    A Rayan
    Department of Medicinal Chemistry, School of Pharmacy, The Hebrew University of Jerusalem, Jerusalem, Israel
    Curr Med Chem 11:675-92. 2004
    ..00 A and 3.46 A, respectively. Models for the "open" structures of c-Src and of Jak-2 were constructed on the basis of 1QPE. The Jak-2 model is found to be more flexible in the loops region than its c-Src counterpart...
  43. ncbi request reprint Killing time for cancer cells
    Shoshana Klein
    Unit of Cellular Signalling, Department of Biological Chemistry, The Alexander Silberman Institute of Life Sciences, The Hebrew University of Jerusalem, Jerusalem 91904, Israel
    Nat Rev Cancer 5:573-80. 2005
    ..Can cancer be cured, or will it have to be controlled as a chronic disease?..
  44. pmc Active Src elevates the expression of beta-catenin by enhancement of cap-dependent translation
    Rotem Karni
    Department of Biological Chemistry, The Alexander Silberman Institute of Life Sciences, The Hebrew University of Jerusalem, 91904 Jerusalem, Israel
    Mol Cell Biol 25:5031-9. 2005
    ..This novel activation of the Wnt pathway by Src most probably contributes to the oncogenic phenotype of cancer cells...
  45. ncbi request reprint Synthesis and structure-activity relationship studies of peptidomimetic PKB/Akt inhibitors: the significance of backbone interactions
    Yftah Tal-Gan
    Institute of Chemistry, The Hebrew University of Jerusalem, 91904 Jerusalem, Israel
    Bioorg Med Chem 18:2976-85. 2010
    ..Two N-terminal members of the N-methyl library did not decrease potency and can be used as future drug leads...
  46. pmc EGF receptor-targeted synthetic double-stranded RNA eliminates glioblastoma, breast cancer, and adenocarcinoma tumors in mice
    Alexei Shir
    Department of Biological Chemistry, The Hebrew University of Jerusalem, Givat Ram, Jerusalem, Israel
    PLoS Med 3:e6. 2006
    ..Using a non-viral delivery vector that homes to the EGF receptor, we target synthetic anti-proliferative dsRNA (polyinosine-cytosine [poly IC]), a strong activator of apoptosis, selectively to cancer cells...
  47. ncbi request reprint RNA molecules as anti-cancer agents
    Inbar Friedrich
    Unit of Cellular Signaling, Department of Biological Chemistry, The Alexander Silberman Institute of Life Sciences, The Hebrew University of Jerusalem, Givat Ram, Jerusalem 91904, Israel
    Semin Cancer Biol 14:223-30. 2004
    ..DKS has the potential to be applicable to a wide range of cancers. Thus dsRNA-based anti-cancer strategies could be powerful tools for cancer treatment...
  48. ncbi request reprint Locally delivered nanoencapsulated tyrphostin (AGL-2043) reduces neointima formation in balloon-injured rat carotid and stented porcine coronary arteries
    Shmuel Banai
    Heiden Department of Cardiology, Bikur Cholim Hospital, Jerusalem, Israel
    Biomaterials 26:451-61. 2005
    ..The results of this study suggest that locally delivered tyrphostin AGL-2043 formulated in biodegradable NP may be applicable for antirestenotic therapy independent of stent design or type of injury...
  49. pmc Analytical determination of receptor-ligand dissociation constants of two populations of receptors from displacement curves
    H Almagor
    Fritz Haber Research Center for Molecular Dynamics, Hebrew University of Jerusalem, Israel
    Proc Natl Acad Sci U S A 87:6482-6. 1990
    ..The application of the method is demonstrated for the analysis of the binding of beta-adrenergic receptors to the agonist isoproterenol as monitored by the displacement of the beta-antagonist 125I-labeled cyanopindolol...
  50. ncbi request reprint Cisplatin-induced activation of the EGF receptor
    Moran Benhar
    Department of Biological Chemistry, The Alexander Silberman Institute of Life Sciences, The Hebrew University of Jerusalem, Jerusalem 91904, Israel
    Oncogene 21:8723-31. 2002
    ..These findings show that signals generated by DNA damage can modulate EGFR activity, and argue that interfering with CDDP-induced EGFR activation in tumor cells might be a useful approach to sensitize these cells to genotoxic agents...
  51. ncbi request reprint Tricyclic quinoxalines as potent kinase inhibitors of PDGFR kinase, Flt3 and Kit
    Aviv Gazit
    Department of Biological Chemistry, The Alexander Silberman Institute of Life Sciences, The Hebrew University of Jerusalem, Givat Ram, Jerusalem 91904, Israel
    Bioorg Med Chem 11:2007-18. 2003
    ..The chemical, biochemical and cellular properties of these compounds as well as the solubility properties make them suitable for development as anti-restenosis and anti-cancer agents...
  52. ncbi request reprint The inhibition of Ras farnesylation leads to an increase in p27Kip1 and G1 cell cycle arrest
    Hadas Reuveni
    Department of Biological Chemistry, Institute of Life Sciences, The Hebrew University of Jerusalem, Jerusalem, Israel
    Eur J Biochem 270:2759-72. 2003
    ..The data suggest a new mechanism for FTI action, whereby in ras-transformed cells, the FTI causes an increase in p27Kip1 levels, which in turn inhibit cyclin E/Cdk2 activity, leading to G1 arrest...
  53. ncbi request reprint Inhibition of glioma growth by tumor-specific activation of double-stranded RNA-dependent protein kinase PKR
    Alexei Shir
    Unit of Cellular Signaling, Department of Biological Chemistry, The Alexander Silberman Institute of Life Sciences, The Hebrew University of Jerusalem, Givat Ram, Jerusalem 91904, Israel
    Nat Biotechnol 20:895-900. 2002
    ..This PKR-mediated killing strategy may be useful in treating many cancers that express a unique RNA species...
  54. ncbi request reprint A cellular screening assay to test the ability of PKR to induce cell death in mammalian cells
    Inbar Friedrich
    Unit of Cellular Signaling, Department of Biological Chemistry, The Alexander Silberman Institute of Life Sciences, The Hebrew University of Jerusalem, Givat Ram, Jerusalem 91904, Israel
    Mol Ther 12:969-75. 2005
    ..The PKR killing screen may also serve as a tool for exploring PKR signaling and other related pathways, by identifying new cases in which PKR signaling is inhibited or impaired...
  55. pmc Shift from apoptotic to necrotic cell death during human papillomavirus-induced transformation of keratinocytes
    Nataly Kravchenko-Balasha
    Unit of Cellular Signaling, Department of Biological Chemistry, Alexander Silberman Institute of Life Sciences, The Hebrew University of Jerusalem, Safra Campus, Givat Ram, Jerusalem 91904, Israel
    J Biol Chem 284:11717-27. 2009
    ..This study supports the hypothesis that the process of cancer transformation may be accompanied by a shift from apoptosis to necrosis...
  56. doi request reprint Contribution of gross chromosomal changes to HPV16-induced transformation
    Nataly Kravchenko-Balasha
    Unit of Cellular Signaling, Department of Biological Chemistry, The Alexander Silberman Institute of Life Sciences, The Hebrew University of Jerusalem, Safra Campus, Givat Ram, Jerusalem 91904, Israel
    Mol Biosyst 7:1501-11. 2011
    ..Our data are consistent with the theory that global chromosomal change is a necessary step in the process of cervical transformation...
  57. ncbi request reprint Activated pp60c-Src leads to elevated hypoxia-inducible factor (HIF)-1alpha expression under normoxia
    Rotem Karni
    Department of Biological Chemistry, The Alexander Silberman Institute of Life Sciences, The Hebrew University of Jerusalem, Jerusalem 91904, Israel
    J Biol Chem 277:42919-25. 2002
    ..Furthermore, we show that the Src-induced increase in protein synthesis is due to the global increase in the rate of cap-dependent translation and does not involve inhibition of HIF-1alpha degradation...
  58. pmc ROS, stress-activated kinases and stress signaling in cancer
    Moran Benhar
    Department of Biological Chemistry, The Alexander Silberman Institute of Life Sciences, The Hebrew University of Jerusalem, Jerusalem 91904, Israel
    EMBO Rep 3:420-5. 2002
    ..Such changes in ROS and SAPK activity levels during the course of tumor development may underlie the changes in responsiveness to anticancer therapy...
  59. ncbi request reprint Subunit S5a of the 26S proteasome is regulated by antiapoptotic signals
    Yael Gus
    The Hebrew University, Department of Biological Chemistry, Silberman Institute, Givat Ram, Jerusalem 91904, Israel
    FEBS J 274:2815-31. 2007
    ..These results suggest that S5a is regulated during apoptosis at the transcriptional level and that S5a upregulation by antiapoptotic signals can contribute to cell survival...
  60. ncbi request reprint Expression and purification of active PKB kinase from Escherichia coli
    Shoshana Klein
    Unit of Cellular Signaling, Department of Biological Chemistry, The Hebrew University of Jerusalem, Safra Campus, Jerusalem 91904, Israel
    Protein Expr Purif 41:162-9. 2005
    ..The final purification step, anion exchange over a monoQ column, separated phosphorylated from unphosphorylated protein. Active recombinant PKB kinase was thus produced from E. coli, by a simple, reproducible procedure...
  61. ncbi request reprint Combination therapy with AG-490 and interleukin 12 achieves greater antitumor effects than either agent alone
    Lyudmila Burdelya
    Immunology Program, H Lee Moffitt Cancer Center and Research Institute, 12902 Magnolia Drive, Tampa, FL 33612, USA
    Mol Cancer Ther 1:893-9. 2002
    ..These results suggest that JAK/STAT inhibitors deserve further investigation for use with IL-12 therapy in treating human cancers with elevated JAK/STAT activity...
  62. ncbi request reprint The kinase inhibitor PP1 blocks tumorigenesis induced by RET oncogenes
    Francesca Carlomagno
    Centro di Endocrinologia ed Oncologia Sperimentale del CNR c o Dipartimento di Biologia e Patologia Cellulare e Molecolare L Califano, Facolta di Medicina e Chirurgia, Universita di Napoli Federico II, 80131 Naples, Italy
    Cancer Res 62:1077-82. 2002
    ..These findings suggest targeting RET oncogenes with PP1 or related compounds as a novel treatment strategy for RET-associated neoplasms...
  63. ncbi request reprint The effect of the [18F]-PEG group on tracer qualification of [4-(phenylamino)-quinazoline-6-YL]-amide moiety--an EGFR putative irreversible inhibitor
    Samar Dissoki
    Department of Medical Biophysics and Nuclear Medicine, Hadassah Hebrew University, Hadassah University Hospital, POB 12000, Jerusalem 91120, Israel
    Appl Radiat Isot 65:1140-51. 2007
    ..The labeled final products were obtained with a 13-32% decay corrected radiochemical yield, 99% radiochemical purity, and high specific activity...
  64. ncbi request reprint The Tyr-kinase inhibitor AG879, that blocks the ETK-PAK1 interaction, suppresses the RAS-induced PAK1 activation and malignant transformation
    Hong He
    Ludwig Institute for Cancer Research, Royal Melbourne Hospital, Parkville Melbourne, Australia
    Cancer Biol Ther 3:96-101. 2004
    ....
  65. ncbi request reprint Evaluation of radiolabeled ML04, a putative irreversible inhibitor of epidermal growth factor receptor, as a bioprobe for PET imaging of EGFR-overexpressing tumors
    Galith Abourbeh
    Department of Medical Biophysics and Nuclear Medicine, Hadassah Hebrew University, Jerusalem 91120, Israel
    Nucl Med Biol 34:55-70. 2007
    ..Detailed pharmacokinetic characterization of this bioprobe could assist in the development of a kinetic model that would afford accurate measurement of EGFR content in tumors...
  66. ncbi request reprint Signal therapy of human pancreatic cancer and NF1-deficient breast cancer xenograft in mice by a combination of PP1 and GL-2003, anti-PAK1 drugs (Tyr-kinase inhibitors)
    Yumiko Hirokawa
    Ludwig Institute for Cancer Research, Melbourne Branch, P O Box 2008, Royal Melbourne Hospital, Parkville Melbourne 3050, Australia
    Cancer Lett 245:242-51. 2007
    ..Also, this PP1/GL-2003 combination therapy has been proven to be very effective to suppress the estrogen-independent growth of an NF1-deficient multidrug/FK228-resistant human breast cancer (MDA-MB-231) xenograft in mice...
  67. ncbi request reprint Novel iodine-124 labeled EGFR inhibitors as potential PET agents for molecular imaging in cancer
    Mazal Shaul
    Department of Medical Biophysics and Nuclear Medicine, Hadassah Hebrew University, Hadassah Hospital, Jerusalem 91120, Israel
    Bioorg Med Chem 12:3421-9. 2004
    ..The high potency of compounds 5 and 6 toward the EGFR establishes their potential as PET agents for molecular imaging of EGFR positive tumors. Their prospect as PET biomarkers is further being investigated...
  68. ncbi request reprint Tyrphostin AGL-2043 eluting stent reduces neointima formation in porcine coronary arteries
    Shmuel Banai
    Department of Cardiology, Hadassah University Hospital, P O Box 12000, Jerusalem 91120, Israel
    Cardiovasc Res 64:165-71. 2004
    ..The present study was designed to determine the effect of AGL-2043 delivered from a stent-based, biodegradable polymeric coating on neointima formation in the porcine coronary artery model...
  69. ncbi request reprint The effect of tyrphostin AG-556 on intimal thickening in a mouse model of arterial injury
    Jacob George
    Department of Cardiology, Tel Aviv Sourasky Medical Center, affiliated to the Sackler Faculty of Medicine, 6 Weizman Street, Tel Aviv University, Israel
    Exp Mol Pathol 78:233-8. 2005
    ..In the current study, we investigated the effect of the tyrphostin AG-556 on neointimal thickening and cytokine profile in a model of arterial injury in the mouse...
  70. ncbi request reprint The effect of early and late treatment with the tyrphostin AG-556 on the progression of experimental autoimmune myocarditis
    Jacob George
    Department of Cardiology and the Cardiovascular Research Laboratory, Tel Aviv Medical Center, Tel Aviv University, Sackler School of Medicine, Tel Aviv, Israel
    Exp Mol Pathol 76:234-41. 2004
    ..Thus, AG-556 may represent a novel strategy of ameliorating the progression of myocarditis without non-selectively compromising the immune system...
  71. ncbi request reprint A novel substrate mimetic inhibitor of PKB/Akt inhibits prostate cancer tumor growth in mice by blocking the PKB pathway
    Pninit Litman
    DeveloGen Israel Ltd, Kiryat Weizmann, Building 16, Rehovot, Israel
    Biochemistry 46:4716-24. 2007
    ..This compound and its potential analogues may be developed into novel, potent, and safe anticancer agents, both as stand-alone treatment and in combination with other chemotherapy agents...
  72. ncbi request reprint Tyrphostin AG 555 inhibits bovine papillomavirus transcription by changing the ratio between E2 transactivator/repressor function
    Sabine Baars
    Angewandte Tumorvirologie, Abteilung Virale Transformationsmechanismen, Deutsches Krebsforschungszentrum, Im Neuenheimer Feld 242, Heidelberg 69120, Germany
    J Biol Chem 278:37306-13. 2003
    ..These data indicate that tyrphostin AG 555 disturbs the balance of negative and positive regulatory factors necessary to maintain the homeostasis of a virus-transformed phenotype...
  73. ncbi request reprint Inhibition of aortic allograft vasculopathy by local delivery of platelet-derived growth factor receptor tyrosine-kinase blocker AG-1295
    Matthias Karck
    Department of Cardiothoracic Surgery, Hannover Medical School, Hannover, Germany
    Transplantation 74:1335-41. 2002
    ..This study describes the effect of the tyrphostin AG-1295, a specific PDGFR tyrosine-kinase inhibitor, on neointimal formation in this disease...
  74. ncbi request reprint Tyrphostin AG-556 reduces myocardial infarct size and improves cardiac performance in the rat
    Jacob George
    Department of Cardiology and the Cardiovascular Research Laboratory, Tel Aviv Medical Center, Tel Aviv, Israel
    Exp Mol Pathol 74:314-8. 2003
    ..AG-556 has proven beneficial in reducing myocardial infarct size and attenuated consequent hemodynamic deterioration in the rat model. If reconfirmed, AG-556 may be of potential clinical use in post-MI patients...
  75. ncbi request reprint The closure of Sugen
    Alexander Levitzki
    Nat Biotechnol 21:969. 2003

Research Grants2

  1. Novel cancer therapy by EGFR targeted transfection of synthetic dsRNA
    Alexander Levitzki; Fiscal Year: 2009
    ..Our preliminary results (shown here) support our contention. If successful, this form of therapy could benefit or even cure many cancer patients, without the need for lengthy and expensive procedures. ..