E J Bernhard

Summary

Affiliation: University of Pennsylvania
Country: USA

Publications

  1. ncbi request reprint Farnesyltransferase inhibition: who are the Aktors?
    Eric J Bernhard
    Department of Rediation Oncology, University of Pennsylvania, 185 John Morgan Bldg, 3620 Hamilton Walk, Philadelphia, Pennsylvania 19104, USA
    Cancer Biol Ther 3:1099-101. 2004
  2. ncbi request reprint Re-evaluating gadolinium(III) texaphyrin as a radiosensitizing agent
    E J Bernhard
    University of Pennsylvania, Department of Radiation Oncology, Philadelphia 19104, USA
    Cancer Res 60:86-91. 2000
  3. ncbi request reprint Direct evidence for the contribution of activated N-ras and K-ras oncogenes to increased intrinsic radiation resistance in human tumor cell lines
    E J Bernhard
    Department of Radiation Oncology, University of Pennsylvania, Philadelphia 19104 6072, USA
    Cancer Res 60:6597-600. 2000
  4. ncbi request reprint RhoB and the cellular response to farnesyltransferase inhibitors: the search for clues to cell death mechanisms
    Eric J Bernhard
    Department of Radiation Oncology, University of Pennsylvania School of Medicine, Philadelphia, Pennsylvania, USA
    Cancer Biol Ther 2:281-2. 2003
  5. ncbi request reprint The Ras radiation resistance pathway
    A K Gupta
    Department of Radiation Oncology, University of Pennsylvania, 195 John Morgan Building, 3620 Hamilton Walk, Philadelphia, PA 19104, USA
    Cancer Res 61:4278-82. 2001
  6. ncbi request reprint The farnesyltransferase inhibitor L744,832 reduces hypoxia in tumors expressing activated H-ras
    E Cohen-Jonathan
    Department of Radiation Oncology, University of Pennsylvania School of Medicine, Philadelphia 19104, USA
    Cancer Res 61:2289-93. 2001
  7. ncbi request reprint DNA as an important target in radiation-induced apoptosis of MYC and MYC plus RAS transfected rat embryo fibroblasts
    I S Ayene
    University of Pennsylvania School of Medicine, Department of Radiation Oncology, Philadelphia 19104 6072, USA
    Int J Radiat Biol 76:343-54. 2000
  8. ncbi request reprint Selective inhibition of Ras, phosphoinositide 3 kinase, and Akt isoforms increases the radiosensitivity of human carcinoma cell lines
    In Ah Kim
    Department of Radiation Oncology, University of Pennsylvania, Philadelphia 19104 6072, USA
    Cancer Res 65:7902-10. 2005
  9. ncbi request reprint Mutant epidermal growth factor receptor displays increased signaling through the phosphatidylinositol-3 kinase/AKT pathway and promotes radioresistance in cells of astrocytic origin
    Bin Li
    1Department of Radiation Oncology, University of Pennsylvania School of Medicine, John Morgan Bldg, Room 195, 3620 Hamilton Walk, Philadelphia, PA 19104 4215, USA
    Oncogene 23:4594-602. 2004
  10. ncbi request reprint Farnesyltransferase inhibitors as radiation sensitizers
    T B Brunner
    University of Pennsylvania, Department of Radiation Oncology, Philadelphia 19104 6072, USA
    Int J Radiat Biol 79:569-76. 2003

Research Grants

Collaborators

Detail Information

Publications39

  1. ncbi request reprint Farnesyltransferase inhibition: who are the Aktors?
    Eric J Bernhard
    Department of Rediation Oncology, University of Pennsylvania, 185 John Morgan Bldg, 3620 Hamilton Walk, Philadelphia, Pennsylvania 19104, USA
    Cancer Biol Ther 3:1099-101. 2004
  2. ncbi request reprint Re-evaluating gadolinium(III) texaphyrin as a radiosensitizing agent
    E J Bernhard
    University of Pennsylvania, Department of Radiation Oncology, Philadelphia 19104, USA
    Cancer Res 60:86-91. 2000
    ..Our results raise questions about the efficacy of Gd-tex as a radiosensitizing agent...
  3. ncbi request reprint Direct evidence for the contribution of activated N-ras and K-ras oncogenes to increased intrinsic radiation resistance in human tumor cell lines
    E J Bernhard
    Department of Radiation Oncology, University of Pennsylvania, Philadelphia 19104 6072, USA
    Cancer Res 60:6597-600. 2000
    ..These findings support the development of strategies that target ras for inactivation in the treatment of cancer...
  4. ncbi request reprint RhoB and the cellular response to farnesyltransferase inhibitors: the search for clues to cell death mechanisms
    Eric J Bernhard
    Department of Radiation Oncology, University of Pennsylvania School of Medicine, Philadelphia, Pennsylvania, USA
    Cancer Biol Ther 2:281-2. 2003
  5. ncbi request reprint The Ras radiation resistance pathway
    A K Gupta
    Department of Radiation Oncology, University of Pennsylvania, 195 John Morgan Building, 3620 Hamilton Walk, Philadelphia, PA 19104, USA
    Cancer Res 61:4278-82. 2001
    ..These experiments have indicated the importance of PI3K in mediating enhanced radioresistance and have implicated PI3K as a potential target for specific radiosensitization of tumors...
  6. ncbi request reprint The farnesyltransferase inhibitor L744,832 reduces hypoxia in tumors expressing activated H-ras
    E Cohen-Jonathan
    Department of Radiation Oncology, University of Pennsylvania School of Medicine, Philadelphia 19104, USA
    Cancer Res 61:2289-93. 2001
    ..These results indicate that treatment with farnesyltransferase inhibitors can alter the oxygenation of certain tumors and suggest that such treatment might be useful in the radiosensitization of these tumors...
  7. ncbi request reprint DNA as an important target in radiation-induced apoptosis of MYC and MYC plus RAS transfected rat embryo fibroblasts
    I S Ayene
    University of Pennsylvania School of Medicine, Department of Radiation Oncology, Philadelphia 19104 6072, USA
    Int J Radiat Biol 76:343-54. 2000
    ..This study uses a radiation chemistry approach to determine if DNA is an important target for radiation-induced apoptosis of myc (MR4) and myc plus ras (3.7) transfected rat embryo fibroblast cell lines...
  8. ncbi request reprint Selective inhibition of Ras, phosphoinositide 3 kinase, and Akt isoforms increases the radiosensitivity of human carcinoma cell lines
    In Ah Kim
    Department of Radiation Oncology, University of Pennsylvania, Philadelphia 19104 6072, USA
    Cancer Res 65:7902-10. 2005
    ..This study further shows that selective inhibition of the PI3 kinase P110alpha + p85beta isoforms or Akt-1 could be a viable approach to sensitizing many tumor cells to cytotoxic therapies...
  9. ncbi request reprint Mutant epidermal growth factor receptor displays increased signaling through the phosphatidylinositol-3 kinase/AKT pathway and promotes radioresistance in cells of astrocytic origin
    Bin Li
    1Department of Radiation Oncology, University of Pennsylvania School of Medicine, John Morgan Bldg, Room 195, 3620 Hamilton Walk, Philadelphia, PA 19104 4215, USA
    Oncogene 23:4594-602. 2004
    ....
  10. ncbi request reprint Farnesyltransferase inhibitors as radiation sensitizers
    T B Brunner
    University of Pennsylvania, Department of Radiation Oncology, Philadelphia 19104 6072, USA
    Int J Radiat Biol 79:569-76. 2003
    ..The inhibition of activated Ras combined with radiotherapy was identified as a potential method for radiosensitization...
  11. ncbi request reprint Signaling inhibition with radiation in colorectal cancer: clinical trials
    W Gillies McKenna
    Department of Radiation Oncology, University of Pennsylvania, Philadelphia, PA 19004, USA
    Semin Oncol 30:56-67. 2003
    ..Identifying a common signal for EGFR, Ras, or PTEN that results in radiation resistance may uncover targets for developing molecular-based radiosensitization protocols for tumors resistant to radiation and thus improve local control...
  12. ncbi request reprint Apoptosis: an early event in metastatic inefficiency
    C W Wong
    Department of Pathology and Laboratory Medicine, University of Pennsylvania, Philadelphia 19104, USA
    Cancer Res 61:333-8. 2001
    ..Although prior work has shown an association between apoptosis in culture and metastasis in vivo, this work shows that apoptosis in vivo corresponds to decreased metastasis in vivo...
  13. ncbi request reprint Bnip3L is induced by p53 under hypoxia, and its knockdown promotes tumor growth
    Peiwen Fei
    University of Pennsylvania School of Medicine, Philadelphia, PA 19104, USA
    Cancer Cell 6:597-609. 2004
    ..Thus, Bnip3L, capable of attenuating tumorigenicity, mediates p53-dependent apoptosis under hypoxia, which provides a novel understanding of p53 in tumor suppression...
  14. ncbi request reprint Farnesyltransferase inhibitor effects on prostate tumor micro-environment and radiation survival
    Yuquan Shi
    Department of Radiation Oncology, University of Pennsylvania, 185 John Morgan Bldg, Philadelphia, PA 19104 6072, USA
    Prostate 62:69-82. 2005
    ..Ras activation by mutation, overexpression, or receptor signaling can increase tumor cell survival after irradiation...
  15. ncbi request reprint Nelfinavir down-regulates hypoxia-inducible factor 1alpha and VEGF expression and increases tumor oxygenation: implications for radiotherapy
    Nabendu Pore
    Department of Radiation Oncology, University of Pennsylvania School of Medicine, Philadelphia, Pennsylvania 19104, USA
    Cancer Res 66:9252-9. 2006
    ..These data support the use of nelfinavir in combination with radiation in future clinical trials...
  16. ncbi request reprint Pancreatic cancer cell radiation survival and prenyltransferase inhibition: the role of K-Ras
    Thomas B Brunner
    Department of Radiation Oncology, University of Pennsylvania, Philadelphia, Pennsylvania 19104 6072, USA
    Cancer Res 65:8433-41. 2005
    ..Farnesyltransferase inhibitors could therefore be of use as sensitizers for pancreatic carcinoma radiotherapy...
  17. pmc RhoB is required to mediate apoptosis in neoplastically transformed cells after DNA damage
    - Liu Ax
    The Wistar Institute, Philadelphia, PA 19104, USA
    Proc Natl Acad Sci U S A 98:6192-7. 2001
    ..Our findings identify a pivotal role for RhoB in the apoptotic response of neoplastic cells to DNA damage at a novel regulatory point that may involve the actin cytoskeleton...
  18. ncbi request reprint Farnesyltransferase inhibitors as radiation sensitizers
    W Gillies McKenna
    Department of Radiation Oncology, University of Pennsylvania, Philadelphia 19104, USA
    Semin Radiat Oncol 12:27-32. 2002
    ..Additional clinical trials should shed light on the potential of this and other farnesyltransferase inhibitors to serve as radiosensitizers and may identify molecular markers that could predict a response to these agents...
  19. ncbi request reprint A phase I trial of the dual farnesyltransferase and geranylgeranyltransferase inhibitor L-778,123 and radiotherapy for locally advanced pancreatic cancer
    Neil E Martin
    Department of Radiation Oncology, University of Pennsylvania School of Medicine, Philadelphia, Pennsylvania, USA
    Clin Cancer Res 10:5447-54. 2004
    ....
  20. ncbi request reprint Radiosensitizing effects of the prenyltransferase inhibitor AZD3409 against RAS mutated cell lines
    Keith A Cengel
    Department of Radiation Oncology, University of Pennsylvania, Philadelphia, Pennsylvania, USA
    Cancer Biol Ther 5:1206-10. 2006
    ..Thus, radiosensitization of human cancer cells that express mutated K-RAS occurred under conditions where AZD3409 inihibits the activation of farneyslated H-RAS, but did not inhibit K-RAS activation...
  21. ncbi request reprint Local recurrence in head and neck cancer: relationship to radiation resistance and signal transduction
    Anjali K Gupta
    Department of Radiation Oncology, University of Pennsylvania, Philadelphia, Pennsylvania 19104 6072, USA
    Clin Cancer Res 8:885-92. 2002
    ..We have shown previously that radioresistance could be conferred via the Ras-PI3K pathway. Here we investigate the contribution of EGFR to this pathway and its impact on treatment outcome...
  22. ncbi request reprint A Phase I trial of the farnesyltransferase inhibitor L-778,123 and radiotherapy for locally advanced lung and head and neck cancer
    Stephen M Hahn
    Department of Radiation Oncology, University of Pennsylvania School of Medicine, Philadelphia 19104 4283, USA
    Clin Cancer Res 8:1065-72. 2002
    ..The objective of this Phase I trial was to determine the maximally tolerated dose of the FTI L-778,123 in combination with radiotherapy in non-small cell lung cancer (NSCLC) and head and neck cancer (HNC)...
  23. ncbi request reprint The RAS signal transduction pathway and its role in radiation sensitivity
    W Gillies McKenna
    Departments of Radiation Oncology, University of Pennsylvania, Philadelphia, PA 19103, USA
    Oncogene 22:5866-75. 2003
    ..Identifying a common signal for EGFR, RAS, or PTEN that results in radiation resistance may uncover targets for developing molecular-based radiosensitization protocols for tumors resistant to radiation and thus improve local control...
  24. ncbi request reprint C-Raf-1 protein kinase is not essential for Ras transformation of mouse embryo fibroblasts
    Anjali K Gupta
    Department of Radiation Oncology, University of Pennsylvania, Philadelphia, Pennsylvania 19104 6072, USA
    Cancer Biol Ther 2:73-5. 2003
    ..Both cell lines were however able to form tumors in nude mice. These results suggest that c-Raf-1 is not required for Ras transformation in this system...
  25. pmc Oncogenic K-Ras signals through epidermal growth factor receptor and wild-type H-Ras to promote radiation survival in pancreatic and colorectal carcinoma cells
    Keith A Cengel
    Department of Radiation Oncology, University of Pennsylvania, Philadelphia, PA, USA
    Neoplasia 9:341-8. 2007
    ..Taken together, these findings suggest that EGFR-activated H-Ras signaling is initiated by oncogenic K-Ras to promote radiation survival in pancreatic and colorectal cancers...
  26. ncbi request reprint Tissue specific expression of p53 target genes suggests a key role for KILLER/DR5 in p53-dependent apoptosis in vivo
    T F Burns
    Laboratory of Molecular Oncology and Cell Cycle Regulation, University of Pennsylvania School of Medicine, Philadelphia, Pennsylvania, PA 19104, USA
    Oncogene 20:4601-12. 2001
    ..Surprisingly, KILLER/DR5 is the dominantly induced transcript in both the spleen and small intestine suggesting a potentially important role for this p53 target gene in vivo...
  27. ncbi request reprint Phosphatase and tensin homologue deficiency in glioblastoma confers resistance to radiation and temozolomide that is reversed by the protease inhibitor nelfinavir
    Zibin Jiang
    Department of Radiation Oncology, University of Pennsylvania School of Medicine, Philadelphia, Pennsylvania 19104, USA
    Cancer Res 67:4467-73. 2007
    ..These results support the clinical investigation of nelfinavir in combination with radiation and temozolomide in future clinical trials for patients with glioblastomas...
  28. ncbi request reprint Effects of hyperbaric oxygen exposure on experimental head and neck tumor growth, oxygenation, and vasculature
    Yuquan Shi
    Department of Radiation Oncology, University of Pennsylvania, 195 John Morgan Building, 37th and Hamilton Walk, Philadelphia, PA 19104 6072, USA
    Head Neck 27:362-9. 2005
    ..Hyperbaric oxygen (HBO2) is used to promote healing in irradiated tissues, but concern persists about the possibility that it may promote residual tumor growth...
  29. ncbi request reprint The influence of Ras pathway signaling on tumor radiosensitivity
    In Ah Kim
    Department of Radiation Oncology, 185 John Morgan Bldg, 37th and Hamilton Walk, University of Pennsylvania, Philadelphia, PA 19104 6072
    Cancer Metastasis Rev 23:227-36. 2004
    ..We will also point out new means of studying the contribution of Ras and Ras pathway components that could contribute to defining new targets for inhibition in the context of radiation therapy...
  30. ncbi request reprint Farnesyltransferase inhibitors: an overview of the results of preclinical and clinical investigations
    Thomas B Brunner
    Department of Radiation Oncology, University of Pennsylvania, Philadelphia 19104 6072, USA
    Cancer Res 63:5656-68. 2003
    ..We conclude that the rational combination of FTIs with other therapies, taking into account the biological activities of the individual agents, may improve the clinical results obtained with FTIs...
  31. pmc Requirement for matrix metalloproteinase-9 (gelatinase B) expression in metastasis by murine prostate carcinoma
    G Sehgal
    Department of Pathology and Laboratory Medicine, University of Pennsylvania, Philadelphia 19104, USA
    Am J Pathol 152:591-6. 1998
    ..Thus, MMP-9 expression is required for hematogenous metastasis in a murine prostate model system raising the possibility that it may play an equivalent role in human prostate cancer...
  32. ncbi request reprint How does radiation kill cells?
    E C Jonathan
    Department of Radiation Oncology, University of Pennsylvania, Philadelphia, PA 19104, USA
    Curr Opin Chem Biol 3:77-83. 1999
    ..Particular progress has been made in defining molecular controls of apoptosis and radiation-induced cell cycle arrest, as well as the possible role of telomerase activity in stabilizing DNA breaks...
  33. ncbi request reprint Successful growth and characterization of mouse pancreatic ductal cells: functional properties of the Ki-RAS(G12V) oncogene
    Franz S Schreiber
    Department of Medicine, Abramson Cancer Center, University of Pennsylvania, Philadelphia 19104 2144, USA
    Gastroenterology 127:250-60. 2004
    ..Because Ki-RAS mutation has prognostic significance in patients treated with radiation, we studied the influence of Ki-RAS status on radiation survival...
  34. ncbi request reprint Tissue-specific induction of p53 targets in vivo
    Peiwen Fei
    Laboratory of Molecular Oncology and Cell Cycle Regulation, Howard Hughes Medical Institute, Department of Medicine, University of Pennsylvania School of Medicine and Abramson Cancer Center, Philadelphia, Pennsylvania 19104, USA
    Cancer Res 62:7316-27. 2002
    ..Our findings indicate that the selectivity of p53 in transactivation following DNA damage in vivo results in unique tissue and cell type specificity, which may correlate with growth arrest or variable sensitivity to gamma-irradiation...
  35. pmc Modulating tumor vasculature through signaling inhibition to improve cytotoxic therapy
    Amit Maity
    Department of Radiation Oncology, University of Pennsylvania School of Medicine, Philadelphia, Pennsylvania, USA
    Cancer Res 70:2141-5. 2010
    ..Recent work has shown that changes in the tumor vasculature can be achieved by inhibiting tumor cell signaling, resulting in enhanced tumor oxygenation. These changes could promote responses to both chemo- and radiation therapy...
  36. ncbi request reprint Radiation sensitization by inhibition of activated Ras
    Thomas B Brunner
    Department of Radiation Oncology, University Hospital, Erlangen, Germany
    Strahlenther Onkol 180:731-40. 2004
    ..This article reviews preclinical and phase I clinical studies that reported on combining inhibition of activated Ras and downstream effectors of Ras with radiotherapy...
  37. ncbi request reprint Pancreatic cancer inhibition by specific knockdown of K-ras mutant allele expression
    Eric J Bernhard
    Radiation Oncology and Biology, Radiation Biology Institute, Oxford University, Headington, Oxford, UK
    Cancer Biol Ther 6:293-4. 2007
  38. doi request reprint Class I PI3 kinase inhibition by the pyridinylfuranopyrimidine inhibitor PI-103 enhances tumor radiosensitivity
    Remko Prevo
    Radiobiology Research Institute, Oxford University, Oxford, United Kingdom
    Cancer Res 68:5915-23. 2008
    ..These results indicate that pharmacologic inhibitors with enhanced specificity for class I PI3K may be of benefit when combined with radiotherapy...
  39. ncbi request reprint Progress towards the use of HIV protease inhibitors in cancer therapy
    Eric J Bernhard
    Oxford University, Radiation Oncology and Biology, Radiobiology Research Institute, Headington, Oxford, United Kingdom
    Cancer Biol Ther 7:636-7. 2008
    ..It is this point that Plasteras et al. address in the current issue of Cancer Biology & Therapy, by examining the effects of combined treatment with radiation and HIV protease inhibitors.(3)...

Research Grants10

  1. TUMOR RADIOSENSITIZATION BY PRENYLTRANSFERASE INHIBITORS
    Eric Bernhard; Fiscal Year: 2007
    ..They may also provide a rationale for the application of FTIs in the treatment of tumors with RAS activation that is due to EGFR signaling. ..
  2. TUMOR RADIOSENSITIZATION BY PRENYLTRANSFERASE INHIBITORS
    Eric Bernhard; Fiscal Year: 2001
    ..The goal of this study is to determine whether the specificity of these inhibitors for the activated ras in tumor cells can be exploited such that these agents can be used as tumor cell radiosensitizers during radiation therapy. ..