John Isaacs

Summary

Affiliation: Johns Hopkins University
Country: USA

Publications

  1. ncbi request reprint Does PSA play a role as a promoting agent during the initiation and/or progression of prostate cancer?
    Simon A Williams
    The Sidney Kimmel Comprehensive Cancer Center, The Johns Hopkins University School of Medicine, Baltimore, Maryland, USA
    Prostate 67:312-29. 2007
  2. pmc Rational design of novel antiandrogens for neutralizing androgen receptor function in hormone refractory prostate cancer
    Pratap Singh
    Chemical and Biomolecular Engineering, Whiting School of Engineering, Baltimore, Maryland, USA
    Prostate 68:1570-81. 2008
  3. ncbi request reprint New strategies for the medical treatment of prostate cancer
    John T Isaacs
    Sidney Kimmel Comprehensive Cancer Center, Johns Hopkins University, 1650 Orlerans Street, CRB 1M44, Baltimore, MD 21231 1001, USA
    BJU Int 96:35-40. 2005
  4. ncbi request reprint PC3, but not DU145, human prostate cancer cells retain the coregulators required for tumor suppressor ability of androgen receptor
    Ivan V Litvinov
    Chemical Therapeutics Program, The Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins, Baltimore, Maryland 21231, USA
    Prostate 66:1329-38. 2006
  5. ncbi request reprint A dimeric peptide that binds selectively to prostate-specific membrane antigen and inhibits its enzymatic activity
    Saurabh Aggarwal
    The Sidney Kimmel Comprehensive Cancer Center, The Johns Hopkins University School of Medicine, Baltimore, Maryland 21231, USA
    Cancer Res 66:9171-7. 2006
  6. pmc Quantification of Mesenchymal Stem Cells (MSCs) at sites of human prostate cancer
    W Nathaniel Brennen
    Chemical Therapeutics Program, The Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins, Baltimore, MD, USA
    Oncotarget 4:106-17. 2013
  7. pmc Engineering enzymatically activated "molecular grenades" for cancer
    Samuel R Denmeade
    The Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins, Baltimore MD
    Oncotarget 3:666-7. 2012
  8. pmc Tasquinimod Is an Allosteric Modulator of HDAC4 survival signaling within the compromised cancer microenvironment
    John T Isaacs
    Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins, The Johns Hopkins University, 1650 Orleans St, Baltimore, MD 21287, USA
    Cancer Res 73:1386-99. 2013
  9. pmc Adaptive auto-regulation of androgen receptor provides a paradigm shifting rationale for bipolar androgen therapy (BAT) for castrate resistant human prostate cancer
    John T Isaacs
    The Chemical Therapeutic Program, The Sidney Kimmel Comprehensive Cancer Center, The Johns Hopkins University School of Medicine, Baltimore, Maryland, USA
    Prostate 72:1491-505. 2012
  10. pmc Tasquinimod (ABR-215050), a quinoline-3-carboxamide anti-angiogenic agent, modulates the expression of thrombospondin-1 in human prostate tumors
    Anders Olsson
    Active Biotech AB, Box 724, 22007 Lund, Sweden
    Mol Cancer 9:107. 2010

Detail Information

Publications66

  1. ncbi request reprint Does PSA play a role as a promoting agent during the initiation and/or progression of prostate cancer?
    Simon A Williams
    The Sidney Kimmel Comprehensive Cancer Center, The Johns Hopkins University School of Medicine, Baltimore, Maryland, USA
    Prostate 67:312-29. 2007
    ....
  2. pmc Rational design of novel antiandrogens for neutralizing androgen receptor function in hormone refractory prostate cancer
    Pratap Singh
    Chemical and Biomolecular Engineering, Whiting School of Engineering, Baltimore, Maryland, USA
    Prostate 68:1570-81. 2008
    ..In this refractory stage, AR continues to play a significant role in the growth of cancer cells even though the cancer cells are no longer dependent on the level of circulating androgens...
  3. ncbi request reprint New strategies for the medical treatment of prostate cancer
    John T Isaacs
    Sidney Kimmel Comprehensive Cancer Center, Johns Hopkins University, 1650 Orlerans Street, CRB 1M44, Baltimore, MD 21231 1001, USA
    BJU Int 96:35-40. 2005
    ..Preclinical data suggest the PSA-targeting abilities of this novel therapy are associated with a nearly complete cessation of tumour growth with minimal toxicity...
  4. ncbi request reprint PC3, but not DU145, human prostate cancer cells retain the coregulators required for tumor suppressor ability of androgen receptor
    Ivan V Litvinov
    Chemical Therapeutics Program, The Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins, Baltimore, Maryland 21231, USA
    Prostate 66:1329-38. 2006
    ..While these cells do not express AR, it is unclear whether they retained the coactivators necessary for AR-dependent tumor suppression. To answer this question the response to AR protein expression by PC3 and DU145 cells was evaluated...
  5. ncbi request reprint A dimeric peptide that binds selectively to prostate-specific membrane antigen and inhibits its enzymatic activity
    Saurabh Aggarwal
    The Sidney Kimmel Comprehensive Cancer Center, The Johns Hopkins University School of Medicine, Baltimore, Maryland 21231, USA
    Cancer Res 66:9171-7. 2006
    ..These dimeric peptides, therefore, represent putative PSMA-selective targeting agents that are currently being evaluated for selective binding in vivo...
  6. pmc Quantification of Mesenchymal Stem Cells (MSCs) at sites of human prostate cancer
    W Nathaniel Brennen
    Chemical Therapeutics Program, The Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins, Baltimore, MD, USA
    Oncotarget 4:106-17. 2013
    ....
  7. pmc Engineering enzymatically activated "molecular grenades" for cancer
    Samuel R Denmeade
    The Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins, Baltimore MD
    Oncotarget 3:666-7. 2012
    ..These combinatorial approaches are currently under pre-clinical evaluation in our laboratories...
  8. pmc Tasquinimod Is an Allosteric Modulator of HDAC4 survival signaling within the compromised cancer microenvironment
    John T Isaacs
    Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins, The Johns Hopkins University, 1650 Orleans St, Baltimore, MD 21287, USA
    Cancer Res 73:1386-99. 2013
    ..Cancer Res; 73(4); 1386-99. ©2012 AACR...
  9. pmc Adaptive auto-regulation of androgen receptor provides a paradigm shifting rationale for bipolar androgen therapy (BAT) for castrate resistant human prostate cancer
    John T Isaacs
    The Chemical Therapeutic Program, The Sidney Kimmel Comprehensive Cancer Center, The Johns Hopkins University School of Medicine, Baltimore, Maryland, USA
    Prostate 72:1491-505. 2012
    ..BAT therapy is effective in xenografts and based upon positive results has entered clinical testing...
  10. pmc Tasquinimod (ABR-215050), a quinoline-3-carboxamide anti-angiogenic agent, modulates the expression of thrombospondin-1 in human prostate tumors
    Anders Olsson
    Active Biotech AB, Box 724, 22007 Lund, Sweden
    Mol Cancer 9:107. 2010
    ..The array data were validated by real-time semiquantitative reversed transcriptase polymerase chain reaction (sqRT-PCR) and protein expression techniques...
  11. doi request reprint The long and winding road for the development of tasquinimod as an oral second-generation quinoline-3-carboxamide antiangiogenic drug for the treatment of prostate cancer
    John T Isaacs
    The Johns Hopkins University, Baltimore, MD 21287, Maryland, USA
    Expert Opin Investig Drugs 19:1235-43. 2010
    ..To effect curative therapy, additional drugs must be developed that enhance the response when combined with androgen ablation/taxane therapy...
  12. ncbi request reprint Identification of ABR-215050 as lead second generation quinoline-3-carboxamide anti-angiogenic agent for the treatment of prostate cancer
    John T Isaacs
    The Sidney Kimmel Comprehensive Cancer Center, The Johns Hopkins University School of Medicine, Baltimore, Maryland, USA
    Prostate 66:1768-78. 2006
    ..MS clinical trials were discontinued because of unacceptable toxicity, due to dose-dependent induction of proinflammation...
  13. pmc Prostate stem cells and benign prostatic hyperplasia
    John T Isaacs
    Department of Oncology, The Chemical Therapeutics Program, The Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins, Baltimore, Maryland, USA
    Prostate 68:1025-34. 2008
    ....
  14. ncbi request reprint The quinoline-3-carboxamide anti-angiogenic agent, tasquinimod, enhances the anti-prostate cancer efficacy of androgen ablation and taxotere without effecting serum PSA directly in human xenografts
    Susan L Dalrymple
    Department of Urology, The Sidney Kimmel Comprehensive Cancer Center and the Brady Urological Institute, The Johns Hopkins University School of Medicine, Baltimore, Maryland, USA
    Prostate 67:790-7. 2007
    ..Androgen ablation and taxanes are standard therapies for metastatic prostate cancer. This raises the issue of whether combining tasquinimod with either of these approaches enhances therapeutic efficacy...
  15. ncbi request reprint A prostate-specific antigen-activated channel-forming toxin as therapy for prostatic disease
    Simon A Williams
    Department of Oncology, The Johns Hopkins University School of Medicine, Baltimore, MD 21231, USA
    J Natl Cancer Inst 99:376-85. 2007
    ..Prostate-specific antigen (PSA) is a serine protease that is secreted at high levels by the normal and diseased prostate. Therapies that are activated by PSA may prove effective in treating prostatic malignancies...
  16. ncbi request reprint Pharmacologic basis for the enhanced efficacy of dutasteride against prostatic cancers
    Yi Xu
    Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins, Baltimore, Maryland 21231, USA
    Clin Cancer Res 12:4072-9. 2006
    ..Therefore, the levels of expression SRD5A1 and SRD5A2 and the antiprostatic cancer growth response to finasteride, a selective SRD5A2 inhibitor, versus the dual SRD5A1 and SRD5A2 inhibitor, dutasteride, were compared...
  17. pmc Androgen receptor as a licensing factor for DNA replication in androgen-sensitive prostate cancer cells
    Ivan V Litvinov
    Chemical Therapeutics Program, Division of Immunology and Hematopoiesis, The Sidney Kimmel Comprehensive Cancer Center, Department of Pathology, and The Brady Urological Institute, Johns Hopkins University School of Medicine, Baltimore, MD 21231, USA
    Proc Natl Acad Sci U S A 103:15085-90. 2006
    ..Thus, AS prostate cancer cells do not express AR protein during mitosis, either in vitro or in vivo, consistent with AR functioning as a licensing factor for DNA replication in AS prostate cancer cells...
  18. ncbi request reprint Enhanced redundancy in Akt and mitogen-activated protein kinase-induced survival of malignant versus normal prostate epithelial cells
    Aarti R Uzgare
    Anti Cancer Drug Discovery Development Program, The Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins, Baltimore, Maryland 21231, USA
    Cancer Res 64:6190-9. 2004
    ..These results demonstrate that prostate cancer progression to a lethal androgen-independent state involves the acquisition of an enhanced redundancy in downstream survival signaling...
  19. ncbi request reprint Preclinical and clinical studies with the multi-kinase inhibitor CEP-701 as treatment for prostate cancer demonstrate the inadequacy of PSA response as a primary endpoint
    Connie Collins
    The Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins, The Johns Hopkins University School of Medicine, Baltimore, Maryland, USA
    Cancer Biol Ther 6:1360-7. 2007
    ..CEP-701 binds to serum proteins and a preprostatectomy study was performed to assess prostate tissue penetration and clinical response to CEP-701...
  20. pmc Loss of androgen receptor-dependent growth suppression by prostate cancer cells can occur independently from acquiring oncogenic addiction to androgen receptor signaling
    Jason M D'Antonio
    Department of Oncology, The Sidney Kimmel Comprehensive Cancer Center, The Johns Hopkins University School of Medicine, Baltimore, Maryland, United States of America
    PLoS ONE 5:e11475. 2010
    ..Thus, patients with prostate cancer cells harboring such AR loss-of-function mutations will not benefit from aggressive hormone or anti-AR therapies even though they express AR protein...
  21. doi request reprint Bipolar androgen therapy: the rationale for rapid cycling of supraphysiologic androgen/ablation in men with castration resistant prostate cancer
    Samuel R Denmeade
    The Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins, Baltimore, Maryland, USA
    Prostate 70:1600-7. 2010
    ..The goal is to determine if a clinical response can be achieved through this non-adaptive rapid cycling approach in men with CRPC...
  22. pmc Prostate-specific antigen (PSA) is activated by KLK2 in prostate cancer ex vivo models and in prostate-targeted PSA/KLK2 double transgenic mice
    Simon A Williams
    The Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins, Baltimore, Maryland 21231, USA
    Prostate 70:788-96. 2010
    ..Previously, cell-free biochemical studies have identified various kallikreins (KLK) as candidate activating proteases. In this study, KLK2-mediated activation of PSA in cell-based in vitro, xenograft, and transgenic models was evaluated...
  23. pmc Cell-autonomous intracellular androgen receptor signaling drives the growth of human prostate cancer initiating cells
    Donald J Vander Griend
    Chemical Therapeutics Program, The Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins, The Johns Hopkins University School of Medicine, Baltimore, Maryland 21231, USA
    Prostate 70:90-9. 2010
    ..Such mechanisms may involve cancer cell-dependent induction of tumor stromal cells to produce paracrine growth factors or could involve cancer cell autonomous autocrine and/or intracellular AR signaling pathways...
  24. doi request reprint Detection and quantification of the evolution dynamics of apoptosis using the PET voltage sensor 18F-fluorobenzyl triphenyl phosphonium
    Igal Madar
    Russell H Morgan Department of Radiology, Johns Hopkins Medical Institutions, Baltimore, MD, USA
    J Nucl Med 50:774-80. 2009
    ..Here, we have characterized the ability of the novel PET voltage sensor (18)F-fluorobenzyl triphenyl phosphonium ((18)F-FBnTP) to quantify the time-dependent apoptotic action of the taxanes paclitaxel and docetaxel in vitro and in vivo...
  25. ncbi request reprint Pharmacokinetics, biodistribution, and antitumor efficacy of a human glandular kallikrein 2 (hK2)-activated thapsigargin prodrug
    Samuel Janssen
    The Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins, The Johns Hopkins University School of Medicine, Baltimore, Maryland 21231, USA
    Prostate 66:358-68. 2006
    ....
  26. ncbi request reprint The SERCA pump as a therapeutic target: making a "smart bomb" for prostate cancer
    Samuel R Denmeade
    The Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins, The Johns Hopkins University School of Medicine, Baltimore, Maryland 21231, USA
    Cancer Biol Ther 4:14-22. 2005
    ..These prodrugs are currently undergoing preclinical evaluation as potential targeted therapy for prostate cancer...
  27. ncbi request reprint A history of prostate cancer treatment
    Samuel R Denmeade
    Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins, Baltimore, Maryland 21231, USA
    Nat Rev Cancer 2:389-96. 2002
    ..What were the first ways in which prostate cancer was treated, and how did these evolve into the variety of therapeutic strategies from which patients have to choose today?..
  28. ncbi request reprint A 5-fluorodeoxyuridine prodrug as targeted therapy for prostate cancer
    Annastasiah Mhaka
    Department of Experimental Therapeutics, Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins, Baltimore, Maryland 21231, USA
    Bioorg Med Chem Lett 12:2459-61. 2002
    ..This approach permitted efficient conversion of the inactive prodrug back to the active cytotoxic state by the enzymatic activity of PSA which is highly expressed by prostate cells...
  29. ncbi request reprint Dissociation between androgen responsiveness for malignant growth vs. expression of prostate specific differentiation markers PSA, hK2, and PSMA in human prostate cancer models
    Samuel R Denmeade
    The Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins, Baltimore, Maryland 21231, USA
    Prostate 54:249-57. 2003
    ..regulation of expression of prostate differentiation specific markers PSA, hK2, and PSMA...
  30. ncbi request reprint Nonimmunosuppressant immunophilin ligand GPI-1046 does not promote in vitro growth of prostate cancer cells
    Arthur L Burnett
    Department of Urology, James Buchanan Brady Urological Institute, Johns Hopkins Medical Institutions, Baltimore, Maryland 21287 2411, USA
    Urology 65:1003-7. 2005
    ..Before establishing their clinical roles, however, it would be useful to evaluate whether they exert mitogenic effects on malignant prostate cells...
  31. ncbi request reprint Prostate-specific antigen-activated thapsigargin prodrug as targeted therapy for prostate cancer
    Samuel R Denmeade
    The Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins, Baltimore, MD 21231, USA
    J Natl Cancer Inst 95:990-1000. 2003
    ..e., G0-arrested) cells. However, thapsigargin's mechanism of action indicates that it is unlikely to be selective for cancer cells or prostate cells...
  32. ncbi request reprint Hedgehog signalling in prostate regeneration, neoplasia and metastasis
    Sunil S Karhadkar
    Department of Molecular Biology and Genetics and the Howard Hughes Medical Institute, The Johns Hopkins University School of Medicine, Baltimore, Maryland 21205, USA
    Nature 431:707-12. 2004
    ..Monitoring and manipulating Hh pathway activity may thus offer significant improvements in diagnosis and treatment of prostate cancers with metastatic potential...
  33. ncbi request reprint Development of prostate cancer treatment: the good news
    Samuel R Denmeade
    The Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins, The Johns Hopkins University School of Medicine, Baltimore, Maryland, USA
    Prostate 58:211-24. 2004
    ..Continued allocation of appropriate human and material resources should yield new, more effective therapies for prostate cancer that will further impact patient quality of life and survival in the 21st century...
  34. ncbi request reprint Prostate-specific antigen (PSA) protein does not affect growth of prostate cancer cells in vitro or prostate cancer xenografts in vivo
    Samuel R Denmeade
    The Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins, Baltimore, Maryland 21231, USA
    Prostate 56:45-53. 2003
    ..Recent data also suggest that the PSA protein itself, independent of enzymatic activity, may also function as an endothelial cell-specific inhibitor of angiogenesis...
  35. ncbi request reprint CEP-7055: a novel, orally active pan inhibitor of vascular endothelial growth factor receptor tyrosine kinases with potent antiangiogenic activity and antitumor efficacy in preclinical models
    Bruce Ruggeri
    Department of Oncology, Cephalon, Inc, West Chester, Pennsylvania 19380, USA
    Cancer Res 63:5978-91. 2003
    ..Orally administered CEP-7055 has entered Phase I clinical trials in cancer patients...
  36. pmc Tissue culture media supplemented with 10% fetal calf serum contains a castrate level of testosterone
    J P Michiel Sedelaar
    Department of Oncology, Sidney Kimmel Comprehensive Cancer Center, The Johns Hopkins University, School of Medicine, Baltimore, MD 21231, USA
    Prostate 69:1724-9. 2009
    ..e., DC-FCS) is often used instead of FCS to minimize the level of androgen provided in 10% serum supplemented media. Therefore, total and free testosterone levels in 10%DC-FCS containing media were likewise determined...
  37. pmc Potent and selective peptidyl boronic acid inhibitors of the serine protease prostate-specific antigen
    Aaron M LeBeau
    Department of Pharmacology and Molecular Sciences, The Johns Hopkins University School of Medicine, Baltimore, MD 21231, USA
    Chem Biol 15:665-74. 2008
    ..The inhibitor had a 60-fold higher K(i) for chymotrypsin. A validated model of PSA's catalytic site confirmed the critical interactions between the inhibitor and residues within the PSA enzyme...
  38. ncbi request reprint Trk receptor inhibition induces apoptosis of proliferating but not quiescent human osteoblasts
    Jacek Pinski
    Johns Hopkins Oncology Center, Baltimore, Maryland 21231 1000, USA
    Cancer Res 62:986-9. 2002
    ..These combined results demonstrate that proliferating osteoblasts acquire a sensitivity to trk inhibition- induced apoptosis not shared with normally quiescent osteoblasts...
  39. ncbi request reprint Modulating paclitaxel bioavailability for targeting prostate cancer
    Srinivas K Kumar
    The Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins, The Johns Hopkins School of Medicine, 1650 Orleans Street, Baltimore, MD 21231, USA
    Bioorg Med Chem 15:4973-84. 2007
    ....
  40. ncbi request reprint Low-calcium serum-free defined medium selects for growth of normal prostatic epithelial stem cells
    Ivan V Litvinov
    Chemical Therapeutics Program, The Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins, The Johns Hopkins University School of Medicine, Baltimore, MD 21231, USA
    Cancer Res 66:8598-607. 2006
    ....
  41. ncbi request reprint Applying linear interaction energy method for rational design of noncompetitive allosteric inhibitors of the sarco- and endoplasmic reticulum calcium-ATPase
    Pratap Singh
    Department of Chemical and Biomolecular Engineering, Johns Hopkins University, Baltimore, Maryland 21218, USA
    J Med Chem 48:3005-14. 2005
    ....
  42. ncbi request reprint In vitro culturing and characteristics of transit amplifying epithelial cells from human prostate tissue
    Aarti R Uzgare
    Division of Experimental Therapeutics, Department of Oncology, The Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins, Baltimore, Maryland 21231, USA
    J Cell Biochem 91:196-205. 2004
    ..This study validates that these cells are a useful and relevant system for the determination of molecular events involved in prostatic carcinogenesis...
  43. ncbi request reprint Role of notch-1 and E-cadherin in the differential response to calcium in culturing normal versus malignant prostate cells
    Susan Dalrymple
    Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins and Departments of Urology and Pathology, Johns Hopkins School of Medicine, Baltimore, MD 21231 1000, USA
    Cancer Res 65:9269-79. 2005
    ..These characteristic changes are consistent with prostate cancer cells' ability to metastasize to bone, a site of high-Ca2+ levels...
  44. doi request reprint Molecular insights into substrate specificity of prostate specific antigen through structural modeling
    Pratap Singh
    Department of Chemical and Biomolecular Engineering, Johns Hopkins University Whiting School of Engineering, Baltimore, Maryland 21218, USA
    Proteins 77:984-93. 2009
    ....
  45. ncbi request reprint Molecular characterization of an improved vector for evaluation of the tumor suppressor versus oncogene abilities of the androgen receptor
    Ivan V Litvinov
    The Sidney Kimmel Comprehensive Cancer Center, the Graduate Training Program in Cellular and Molecular Medicine, The Johns Hopkins University School of Medicine, Baltimore, Maryland, USA
    Prostate 61:299-304. 2004
    ..Thus, many groups are attempting to understand the biochemistry and signaling cascade differences involved in the switching of AR from a tumor suppressor to an oncogene...
  46. ncbi request reprint Stabilizing androgen receptor in mitosis inhibits prostate cancer proliferation
    Donald J Vander Griend
    Chemical Therapeutics Program, The Johns Hopkins University School of Medicine, Baltimore, Maryland, USA
    Cell Cycle 6:647-51. 2007
    ..These data provide a unifying paradigm to clarify a number of unresolved observations in prostate cancer research. In addition, they provide a rationale for a new therapeutic approach for prostate cancer based upon stabilization of AR...
  47. ncbi request reprint Is the Achilles' heel for prostate cancer therapy a gain of function in androgen receptor signaling?
    Ivan V Litvinov
    The Sidney Kimmel Comprehensive Cancer Center, The Johns Hopkins University School of Medicine, Baltimore, Maryland 21231, USA
    J Clin Endocrinol Metab 88:2972-82. 2003
  48. pmc Prostate-specific antigen is a "chymotrypsin-like" serine protease with unique P1 substrate specificity
    Aaron M LeBeau
    Department of Pharmacology and Molecular Sciences, The Johns Hopkins University, Baltimore, Maryland 21231, USA
    Biochemistry 48:3490-6. 2009
    ..In conclusion, these results provide experimental and structural evidence that the S1 specificity pocket of PSA is distinctly different from that of chymotrypsin and that the development of highly specific PSA inhibitors is feasible...
  49. ncbi request reprint Benzoylphenylurea sulfur analogues with potent antitumor activity
    Gurulingappa Hallur
    Division of Chemical Therapeutics, The Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins, Baltimore, Maryland 21231, USA
    J Med Chem 49:2357-60. 2006
    ..6n was more effective than 1 in causing apoptosis of MCF-7 cells. When compared to other drugs with a similar mechanism of action, 6n retained significant ability to inhibit tubulin assembly, with an IC(50) of 2.1 microM...
  50. ncbi request reprint Cyclin-dependent kinase 5 activity controls cell motility and metastatic potential of prostate cancer cells
    Christopher J Strock
    Sidney Kimmel Comprehensive Cancer Center, Johns Hopkins University School of Medicine, 1650 Orleans Street, Baltimore, MD 21231, USA
    Cancer Res 66:7509-15. 2006
    ..3 cells expressing the empty vector. These results show that CDK5 activity controls cell motility and metastatic potential in prostate cancer...
  51. ncbi request reprint Prostate cancer: potential targets of anti-proliferative and apoptotic signaling pathways
    Aarti R Uzgare
    Anti Cancer Drug Discovery Development Program, The Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins, 1650 Orleans Street, CRB 1M44, Baltimore, MD 21231 1000, USA
    Int J Biochem Cell Biol 37:707-14. 2005
    ..Prostate cancer cells, however, develop an enhanced redundancy in downstream survival signaling. Hence, new combinational therapies must be developed with the understanding that compensatory mechanisms evolve under selective pressure...
  52. doi request reprint Dual-label centromere and telomere FISH identifies human, rat, and mouse cell contribution to Multispecies recombinant urogenital sinus xenografts
    Donald J Vander Griend
    Chemical Therapeutics Program, The Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins, Baltimore, Maryland 21231, USA
    Prostate 69:1557-64. 2009
    ..Of critical importance is the correct interpretation of the cellular composition of such xenografts...
  53. ncbi request reprint Mechanistic insights into the inhibition of prostate specific antigen by beta-lactam class compounds
    Pratap Singh
    Department of Chemical and Biomolecular Engineering, Whiting School of Engineering, The Johns Hopkins University, Baltimore, Maryland 21218, USA
    Proteins 70:1416-28. 2008
    ..The close agreement of our docking results with the experimental data validates the mechanistic insights revealed through the docking studies and paves the way for the design and development of potent and specific inhibitors of PSA...
  54. pmc DNA licensing as a novel androgen receptor mediated therapeutic target for prostate cancer
    Jason M D'Antonio
    Department of Urology, Brady Urologic Institute, The Johns Hopkins University School of Medicine, Room 1M43, Baltimore, Maryland 21231, USA
    Endocr Relat Cancer 16:325-32. 2009
    ....
  55. pmc The role of CD133 in normal human prostate stem cells and malignant cancer-initiating cells
    Donald J Vander Griend
    Chemical Therapeutics Program, The Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins, The Brady Urological Institute, and Department of Pathology, The Johns Hopkins University School of Medicine, Baltimore, Maryland 21231, USA
    Cancer Res 68:9703-11. 2008
    ....
  56. pmc Amino acid containing thapsigargin analogues deplete androgen receptor protein via synthesis inhibition and induce the death of prostate cancer cells
    Donald J Vander Griend
    The Sidney Kimmel Comprehensive Cancer Center, The Brady Urological Institute, The Johns Hopkins University School of Medicine, Baltimore, Maryland, USA
    Mol Cancer Ther 8:1340-9. 2009
    ..Based on these results, these prodrugs are undergoing clinical development...
  57. ncbi request reprint Molecular characterization of the commonly used human androgen receptor expression vector, pSG5-AR
    Ivan V Litvinov
    The Sidney Kimmel Comprehensive Cancer Center, the Graduate Training Program in Cellular and Molecular Medicine, The Johns Hopkins University School of Medicine, Baltimore, Maryland 21231, USA
    Prostate 58:319-24. 2004
    ..However, a detailed molecular characterization of this construct has not been published. In this study, we describe the molecular organization of the above plasmid and analyze the AR transcript coded by the above construct...
  58. pmc The current state of preclinical prostate cancer animal models
    Kenneth J Pienta
    University of Michigan, Department of Internal Medicine, Ann Arbor, MI, USA
    Prostate 68:629-39. 2008
    ..It should be possible to apply the knowledge gained molecular and epigenetic studies to develop new cell lines and models that mimic progressive and fatal prostate cancer and ultimately improve interventions...
  59. ncbi request reprint Androgens and prostate cancer: are the descriptors valid?
    Pradip Roy-Burman
    Cancer Biol Ther 4:4-5. 2005
    ..It is thus suggested that "androgen-independent (AI)" cancer should be more accurately termed "androgen depletion-independent (ADI)" cancer...
  60. ncbi request reprint Total synthesis of two novel subpicomolar sarco/endoplasmatic reticulum Ca2+-ATPase inhibitors designed by an analysis of the binding site of thapsigargin
    Helmer Søhoel
    Department of Medicinal Chemistry, The Danish University of Pharmaceutical Sciences, Universitetsparken 2, DK 2100 Copenhagen Ø, Denmark
    J Med Chem 48:7005-11. 2005
    ..The two inhibitors were synthesized using (S)-carvone as starting material and found to be 3 and 10 times more potent than thapsigargin...
  61. ncbi request reprint Effects of steroidal and non-steroidal antiandrogens on wild-type and mutant androgen receptors
    Masayasu Urushibara
    Department of Urology, Graduate School, Tokyo Medical and Dental University, Tokyo, Japan
    Prostate 67:799-807. 2007
    ..Molecular basis for secondary antiandrogen therapy in prostate cancer with mutant androgen receptors (ARs) is not fully elucidated...
  62. ncbi request reprint Cytotoxic phenylpropanoids and an additional thapsigargin analogue isolated from Thapsia garganica
    Huizhen Liu
    Department of Medicinal Chemistry, The Danish University of Pharmaceutical Sciences, Universitetsparken 2, DK 2100 Copenhagen Ø, Denmark
    Phytochemistry 67:2651-8. 2006
    ..A spectroscopic method for elucidating the relative stereochemistry at the two pairs of stereogenic centers in the phenylpropanoids has been developed. The phenylpropanoids were found to be potent cytotoxins...
  63. ncbi request reprint Androgen receptor outwits prostate cancer drugs
    John T Isaacs
    Nat Med 10:26-7. 2004
  64. ncbi request reprint Natural products as starting materials for development of second-generation SERCA inhibitors targeted towards prostate cancer cells
    Helmer Søhoel
    Department of Medicinal Chemistry, The Danish University of Pharmaceutical Sciences, Universitetsparken 2, DK 2100 Copenhagen, Denmark
    Bioorg Med Chem 14:2810-5. 2006
    ..Only the 12-Boc-aminododecaonoyl derivative, however, was found to be apoptotic...
  65. ncbi request reprint Defining regulatory elements in the human KAI1 (CD 82) metastasis suppressor gene
    Allen C Gao
    Grace Cancer Drug Center, Roswell Park Cancer Institute, Buffalo, New York, USA
    Prostate 57:256-60. 2003
    ..Additional studies of Marreiros et al. (Gene 302:155, 2003) have documented that a third regulatory element even further 5' (i.e., -922 to -846 bp) encodes an enhancer for the KAI1 gene...

Research Grants8

  1. CELL/CELL INTERACTION AND PROSTATE GROWTH
    John Isaacs; Fiscal Year: 1999
    ....
  2. CELL/CELL INTERACTION AND PROSTATE GROWTH
    John Isaacs; Fiscal Year: 2000
    ....
  3. Targeting of the Androgen Receptor in Prostate Cancer
    John Isaacs; Fiscal Year: 2002
    ..These peptide prodrugs will be designed so that they are substrates for the enzymatic activity of either Prostate Specific Antigen. ..
  4. Targeting of the Androgen Receptor in Prostate Cancer
    John Isaacs; Fiscal Year: 2003
    ..These peptide prodrugs will be designed so that they are substrates for the enzymatic activity of either Prostate Specific Antigen. ..
  5. Targeting of the Androgen Receptor in Prostate Cancer
    John Isaacs; Fiscal Year: 2004
    ..These peptide prodrugs will be designed so that they are substrates for the enzymatic activity of either Prostate Specific Antigen. ..
  6. Targeting of the Androgen Receptor in Prostate Cancer
    John Isaacs; Fiscal Year: 2005
    ..These peptide prodrugs will be designed so that they are substrates for the enzymatic activity of either Prostate Specific Antigen. ..