P J Houghton

Summary

Affiliation: St. Jude Children's Research Hospital
Country: USA

Publications

  1. doi request reprint Molecular characterization of the pediatric preclinical testing panel
    Geoffrey Neale
    Hartwell Center of Bioinformatics and Biotechnology, St Jude Children s Research Hospital, Memphis, Tennessee 38105, USA
    Clin Cancer Res 14:4572-83. 2008
  2. ncbi request reprint Initial testing (stage 1) of the proteasome inhibitor bortezomib by the pediatric preclinical testing program
    Peter J Houghton
    St Jude Children s Research Hospital, Memphis, Tennessee, USA
    Pediatr Blood Cancer 50:37-45. 2008
  3. pmc Initial testing of a monoclonal antibody (IMC-A12) against IGF-1R by the Pediatric Preclinical Testing Program
    Peter J Houghton
    Department of Molecular Pharmacology, St Jude Children s Research Hospital, Memphis, Tennessee 38105, USA
    Pediatr Blood Cancer 54:921-6. 2010
  4. ncbi request reprint Initial testing (stage 1) of the mTOR inhibitor rapamycin by the pediatric preclinical testing program
    Peter J Houghton
    St Jude Children s Research Hospital, Memphis, Tennessee, USA
    Pediatr Blood Cancer 50:799-805. 2008
  5. doi request reprint Evaluation of cytarabine against Ewing sarcoma xenografts by the pediatric preclinical testing program
    Peter J Houghton
    Department of Molecular Pharmacology, St Jude Children s Research Hospital, Memphis, Tennessee 38105, USA
    Pediatr Blood Cancer 55:1224-6. 2010
  6. ncbi request reprint The pediatric preclinical testing program: description of models and early testing results
    Peter J Houghton
    Department of Molecular Pharmacology, St Jude Children s Research Hospital, Memphis, Tennessee 38105, USA
    Pediatr Blood Cancer 49:928-40. 2007
  7. ncbi request reprint Imatinib mesylate is a potent inhibitor of the ABCG2 (BCRP) transporter and reverses resistance to topotecan and SN-38 in vitro
    Peter J Houghton
    Department of Molecular Pharmacology, St Jude Children s Research Hospital, Memphis, Tennessee 38105 2794, USA
    Cancer Res 64:2333-7. 2004
  8. ncbi request reprint Antitumor activity of temozolomide combined with irinotecan is partly independent of O6-methylguanine-DNA methyltransferase and mismatch repair phenotypes in xenograft models
    P J Houghton
    Department of Molecular Pharmacology, St Jude Children s Research Hospital, Memphis, Tennessee 38105 2794, USA
    Clin Cancer Res 6:4110-8. 2000
  9. ncbi request reprint mTOR as a target for cancer therapy
    P J Houghton
    Department of Molecular Pharmacology, St Jude Children s Research Hospital, 332 N Lauderdale, Memphis, TN 38105 2794, USA
    Curr Top Microbiol Immunol 279:339-59. 2004
  10. ncbi request reprint Biochemical correlates of temozolomide sensitivity in pediatric solid tumor xenograft models
    D S Middlemas
    Department of Molecular Pharmacology, St Jude Children s Research Hospital, Memphis, Tennessee 38105, USA
    Clin Cancer Res 6:998-1007. 2000

Research Grants

  1. STUDIES OF CHILDHOOD SOLID TUMORS
    Peter Houghton; Fiscal Year: 2007

Collaborators

Detail Information

Publications97

  1. doi request reprint Molecular characterization of the pediatric preclinical testing panel
    Geoffrey Neale
    Hartwell Center of Bioinformatics and Biotechnology, St Jude Children s Research Hospital, Memphis, Tennessee 38105, USA
    Clin Cancer Res 14:4572-83. 2008
    ..Identifying novel therapeutic agents for the treatment of childhood cancers requires preclinical models that recapitulate the molecular characteristics of their respective clinical histotypes...
  2. ncbi request reprint Initial testing (stage 1) of the proteasome inhibitor bortezomib by the pediatric preclinical testing program
    Peter J Houghton
    St Jude Children s Research Hospital, Memphis, Tennessee, USA
    Pediatr Blood Cancer 50:37-45. 2008
    ..The purpose of the current study was to evaluate the antitumor activity of bortezomib against the in vitro and in vivo childhood cancer preclinical models of the Pediatric Preclinical Testing Program (PPTP)...
  3. pmc Initial testing of a monoclonal antibody (IMC-A12) against IGF-1R by the Pediatric Preclinical Testing Program
    Peter J Houghton
    Department of Molecular Pharmacology, St Jude Children s Research Hospital, Memphis, Tennessee 38105, USA
    Pediatr Blood Cancer 54:921-6. 2010
    ..IMC-A12 is a fully human IgG1 antibody that prevents ligand binding to the IGF-1R...
  4. ncbi request reprint Initial testing (stage 1) of the mTOR inhibitor rapamycin by the pediatric preclinical testing program
    Peter J Houghton
    St Jude Children s Research Hospital, Memphis, Tennessee, USA
    Pediatr Blood Cancer 50:799-805. 2008
    ..Here we report the activity of rapamycin against the in vitro and in vivo panels of the Pediatric Preclinical Testing Program (PPTP)...
  5. doi request reprint Evaluation of cytarabine against Ewing sarcoma xenografts by the pediatric preclinical testing program
    Peter J Houghton
    Department of Molecular Pharmacology, St Jude Children s Research Hospital, Memphis, Tennessee 38105, USA
    Pediatr Blood Cancer 55:1224-6. 2010
    ..Cytarabine shows no differential in vitro activity against Ewing sarcoma cell lines and is ineffective in vivo against Ewing sarcoma xenografts at the dose and schedule studied...
  6. ncbi request reprint The pediatric preclinical testing program: description of models and early testing results
    Peter J Houghton
    Department of Molecular Pharmacology, St Jude Children s Research Hospital, Memphis, Tennessee 38105, USA
    Pediatr Blood Cancer 49:928-40. 2007
    ..Here, we describe the characteristics of the in vivo tumor panels and report results for the in vivo evaluation of two standard agents, vincristine and cyclophosphamide...
  7. ncbi request reprint Imatinib mesylate is a potent inhibitor of the ABCG2 (BCRP) transporter and reverses resistance to topotecan and SN-38 in vitro
    Peter J Houghton
    Department of Molecular Pharmacology, St Jude Children s Research Hospital, Memphis, Tennessee 38105 2794, USA
    Cancer Res 64:2333-7. 2004
    ..These results suggest that imatinib mesylate inhibits the function of ABCG2 but is not a substrate for this transporter...
  8. ncbi request reprint Antitumor activity of temozolomide combined with irinotecan is partly independent of O6-methylguanine-DNA methyltransferase and mismatch repair phenotypes in xenograft models
    P J Houghton
    Department of Molecular Pharmacology, St Jude Children s Research Hospital, Memphis, Tennessee 38105 2794, USA
    Clin Cancer Res 6:4110-8. 2000
    ..Pharmacokinetic studies indicated no detectable interaction between these two agents. Further, coadministration of CPT-11 appeared to reduce the toxicity of temozolomide in tumor-bearing mice...
  9. ncbi request reprint mTOR as a target for cancer therapy
    P J Houghton
    Department of Molecular Pharmacology, St Jude Children s Research Hospital, 332 N Lauderdale, Memphis, TN 38105 2794, USA
    Curr Top Microbiol Immunol 279:339-59. 2004
    ..Further, a rationale for anticipating tumor-selective activity based on transforming events frequently identified in malignant disease is becoming established...
  10. ncbi request reprint Biochemical correlates of temozolomide sensitivity in pediatric solid tumor xenograft models
    D S Middlemas
    Department of Molecular Pharmacology, St Jude Children s Research Hospital, Memphis, Tennessee 38105, USA
    Clin Cancer Res 6:998-1007. 2000
    ..These results indicate that MGMT is the primary mechanism for temozolomide resistance, but in the absence of MGMT, proficient mismatch repair determines sensitivity to this agent...
  11. ncbi request reprint Development, characterization and therapy of a disseminated model of childhood neuroblastoma in SCID mice
    J Thompson
    Department of Molecular Pharmacology, St Jude Children's Research Hospital, 332 N. Lauderdale, Memphis, TN 38105-2794, USA
    Cancer Chemother Pharmacol 47:211-21. 2001
    ..As this model may more closely simulate childhood disease it may be a valuable adjunct in developing new approaches to advanced stage, poor prognosis neuroblastoma...
  12. ncbi request reprint Gefitinib enhances the antitumor activity and oral bioavailability of irinotecan in mice
    Clinton F Stewart
    Department of Pharmaceutical Sciences, St Jude Children s Research Hospital, Memphis, Tennessee, USA
    Cancer Res 64:7491-9. 2004
    ....
  13. ncbi request reprint Relation between Irofulven (MGI-114) systemic exposure and tumor response in human solid tumor xenografts
    Markos Leggas
    Department of Pharmaceutical Sciences, St Jude Children s Research Hospital, Memphis, Tennessee 38105, USA
    Clin Cancer Res 8:3000-7. 2002
    ....
  14. ncbi request reprint Relation between 9-aminocamptothecin systemic exposure and tumor response in human solid tumor xenografts
    M N Kirstein
    Department of Pharmaceutical Sciences, St. Jude Children's Research Hospital, Memphis, Tennessee 38105, USA
    Clin Cancer Res 7:358-66. 2001
    ..Tumors were highly sensitive to 9-AC therapy, but the systemic exposure required for antitumor effect is in excess of that achievable in patients...
  15. ncbi request reprint Biochemical correlates of mTOR inhibition by the rapamycin ester CCI-779 and tumor growth inhibition
    L Dudkin
    Department of Molecular Pharmacology, St. Jude Children's Research Hospital, Memphis, Tennessee 38105-2794, USA
    Clin Cancer Res 7:1758-64. 2001
    ..99). The results indicate that an assay of decreases in phosphorylation of Thr(70) of 4E-BP1 may be a useful surrogate for determining the inhibition of mTOR activity in tumor specimens...
  16. ncbi request reprint Direct translation of a protracted irinotecan schedule from a xenograft model to a phase I trial in children
    W L Furman
    Department of Hematology Oncology, St Jude Children s Research Hospital, Memphis, TN 38105 2794, USA
    J Clin Oncol 17:1815-24. 1999
    ..We evaluated this protracted schedule in children...
  17. ncbi request reprint In vivo evaluation of ixabepilone (BMS247550), a novel epothilone B derivative, against pediatric cancer models
    Jennifer K Peterson
    Department of Molecular Pharmacology, St Jude Children s Research Hospital, Memphis, Tennessee 38105, USA
    Clin Cancer Res 11:6950-8. 2005
    ..The purpose of the current study was to evaluate the antitumor activity of ixabepilone, an epothilone B derivative representing a new class of microtubule-stabilizing antimitotic agent in a wide variety of pediatric solid tumor models...
  18. ncbi request reprint Clinical trials using irinotecan
    Peter J Houghton
    Department of Molecular Pharmacology, St Jude Children s Research Hospital, Memphis, Tennessee, USA
    J Pediatr Hematol Oncol 24:84-5. 2002
  19. ncbi request reprint p53/p21(CIP1) cooperate in enforcing rapamycin-induced G(1) arrest and determine the cellular response to rapamycin
    S Huang
    Department of Molecular Pharmacology, St. Jude Children's Research Hospital, Memphis, Tennessee 38105-2794, USA
    Cancer Res 61:3373-81. 2001
    ..In contrast, in tumor cells, or MEFs, having deficient p53 function the response to this agent may be cell cycle progression and apoptosis...
  20. ncbi request reprint Clinical use of topoisomerase I inhibitors in anticancer treatment
    C Rodriguez-Galindo
    Department of Hematology Oncology, St Jude Children s Research Hospital, Memphis, Tennessee 38105 2794, USA
    Med Pediatr Oncol 35:385-402. 2000
    ..These studies have shown promising results, and have placed topotecan and irinotecan in the first line treatment for some malignancies. However, studies to better determine the optimal schedules and sequence of combinations are needed...
  21. pmc The insulin-like growth factor-1 receptor-targeting antibody, CP-751,871, suppresses tumor-derived VEGF and synergizes with rapamycin in models of childhood sarcoma
    Raushan T Kurmasheva
    Departments of Molecular Pharmacology, Biostatistics, and Pathology, St Jude Children s Research Hospital, Memphis, TN38105, USA
    Cancer Res 69:7662-71. 2009
    ..These data suggest a model in which blockade of IGF-1R suppresses tumor-derived VEGF to a level where rapamycin can effectively suppress the response in vascular endothelial cells...
  22. ncbi request reprint Effect of polyglutamylation of 5,10-methylenetetrahydrofolate on the binding of 5-fluoro-2'-deoxyuridylate to thymidylate synthase purified from a human colon adenocarcinoma xenograft
    S Radparvar
    Department of Biochemical and Clinical Pharmacology, St Jude Children s Research Hospital, Memphis, TN 38101
    Biochem Pharmacol 38:335-42. 1989
    ....
  23. ncbi request reprint P53 mutation and MDM2 amplification frequency in pediatric rhabdomyosarcoma tumors and cell lines
    A C Taylor
    Department of Molecular Pharmacology, St Jude Children s Research Hospital, Memphis, Tennessee 38105, USA
    Med Pediatr Oncol 35:96-103. 2000
    ..Wild-type p53 functions as a regulator of apoptosis, so mutations in the p53 gene are generally associated with aggressive tumors and a poor prognosis...
  24. pmc Initial testing of the replication competent Seneca Valley virus (NTX-010) by the pediatric preclinical testing program
    Christopher L Morton
    St Jude Children s Research Hospital, Memphis, Tennessee, USA
    Pediatr Blood Cancer 55:295-303. 2010
    ..Here we have evaluated the antitumor activity of NTX-010 administered systemically...
  25. ncbi request reprint Comparison of the conversion of 5-formyltetrahydrofolate and 5-methyltetrahydrofolate to 5,10-methylenetetrahydrofolates and tetrahydrofolates in human colon tumors
    J A Houghton
    Department of Biochemical and Clinical Pharmacology, St Jude Children s Research Hospital, Memphis, TN 38101
    Cancer Commun 1:167-74. 1989
    ..The data suggest that [6RS]5-CH3-H4PteGlu is less effective than [6RS]5-CHO-H4PteGlu as a precursor for pools of CH2-H4PteGlun and H4PteGlun in colon tumors...
  26. doi request reprint An improved human carboxylesterase for enzyme/prodrug therapy with CPT-11
    M Wierdl
    Department of Molecular Pharmacology, St Jude Children s Research Hospital, Memphis, TN 38105, USA
    Cancer Gene Ther 15:183-92. 2008
    ..We propose that this enzyme should likely be less immunogenic than rCE and would be suitable for the in vivo application of CE/CPT-11 enzyme/prodrug therapy...
  27. ncbi request reprint Resistance to rapamycin: a novel anticancer drug
    S Huang
    Department of Molecular Pharmacology, St. Jude Children's Research Hospital, Memphis, TN 38105-2794, USA
    Cancer Metastasis Rev 20:69-78. 2001
    ..Thus, increasing interest is being directed to this class of antibiotic as potential antitumor agents. Here we summarize the history, mechanism of action, and mechanisms of resistance to rapamycin...
  28. pmc Predicted mechanisms of resistance to mTOR inhibitors
    R T Kurmasheva
    Department of Molecular Pharmacology, St Jude Children s Research Hospital, 332 N Lauderdale, Memphis, TN 38105 2794, USA
    Br J Cancer 95:955-60. 2006
    ..Results indicate that many human cancers have intrinsic resistance and tumours initially sensitive to rapamycins become refractory, demonstrating acquired resistance. Here, we consider mechanisms of resistance to inhibitors of mTOR...
  29. ncbi request reprint A pilot study of protracted topotecan dosing using a pharmacokinetically guided dosing approach in children with solid tumors
    Victor M Santana
    Department of Hematology, St Jude Children s Research Hospital, University of Tennessee, Memphis, Tennessee 38103, USA
    Clin Cancer Res 9:633-40. 2003
    ..To assess the use of a pharmacokinetically guided topotecan strategy and evaluate the toxicity of protracted i.v. topotecan in children with recurrent solid tumors...
  30. ncbi request reprint Gefitinib modulates the function of multiple ATP-binding cassette transporters in vivo
    Markos Leggas
    Departments of Pharmaceutical Sciences, Hematology Oncology, and Molecular Pharmacology, St Jude Children s Research Hospital, Memphis, Tennessee 38105, USA
    Cancer Res 66:4802-7. 2006
    ..4-AQ molecules may offer a means to increase the low and variable oral drug absorption of transporter substrates while decreasing interpatient variability and reversing tumor drug resistance...
  31. ncbi request reprint Evaluation of the antitumor efficacy, pharmacokinetics, and pharmacodynamics of the histone deacetylase inhibitor depsipeptide in childhood cancer models in vivo
    Claire Graham
    Department of Molecular Pharmacology, St Jude Children s Research Hospital, Memphis, Tennessee 38105 2794, USA
    Clin Cancer Res 12:223-34. 2006
    ..Here, we have evaluated depsipeptide, a natural tetrapeptide HDAC inhibitor, against a panel of pediatric solid tumor models in vivo and evaluated pharmacokinetic and pharmacodynamic variables with tumor sensitivity...
  32. ncbi request reprint mTOR and cancer therapy
    J B Easton
    Department of Molecular Pharmacology, St Jude Children s Research Hospital, Memphis, TN 38105, USA
    Oncogene 25:6436-46. 2006
    ..This review will summarize the preclinical and clinical data and recent discoveries of the function of mTOR in cancer and growth regulation...
  33. ncbi request reprint Integrating pharmacology and in vivo cancer models in preclinical and clinical drug development
    J K Peterson
    Department of Molecular Pharmacology, St Jude Children s Research Hospital, Memphis, TN, USA
    Eur J Cancer 40:837-44. 2004
    ..Here we review the value and limitations of xenograft models, and the role of integrating preclinical pharmacology in developing new treatments for solid tumours of childhood...
  34. ncbi request reprint Mechanisms of resistance to rapamycins
    S Huang
    Department of Molecular Pharmacology, St Jude Children s Research Hospital, Memphis, TN 38105 2794, USA
    Drug Resist Updat 4:378-91. 2001
    ..To better explore the role of rapamycins against tumors, this review will summarize the current knowledge of the mechanism of action of rapamycins, and progress in understanding mechanisms of acquired or intrinsic resistance...
  35. ncbi request reprint Improved response in high-risk neuroblastoma with protracted topotecan administration using a pharmacokinetically guided dosing approach
    Victor M Santana
    Department of Hematology Oncology, Mail Stop 260, St Jude Children s Research Hospital, 332 N Lauderdale St, Memphis, TN 38105, USA
    J Clin Oncol 23:4039-47. 2005
    ..To estimate the response rate and toxicity associated with intravenous topotecan when it is administered on a protracted schedule according to a pharmacokinetically guided dosing approach to treat childhood high-risk neuroblastoma...
  36. ncbi request reprint Therapeutic potential of target of rapamycin inhibitors
    John B Easton
    St Jude Childrens Research Hospital, Department of Molecular Pharmacology, 332 N Lauderdale Street, Memphis, TN 38105 2794, USA
    Expert Opin Ther Targets 8:551-64. 2004
    ....
  37. ncbi request reprint Activation and antitumor activity of CPT-11 in plasma esterase-deficient mice
    Christopher L Morton
    Department of Molecular Pharmacology, St Jude Children s Research Hospital, 332 N Lauderdale, Memphis, TN 38105, USA
    Cancer Chemother Pharmacol 56:629-36. 2005
    ..To examine the antitumor activity and the pharmacokinetics of CPT-11 (irinotecan, 7-ethyl-10-[4-(1-piperidino)-1-piperidino] carbonyloxycamptothecin) in a plasma esterase-deficient scid mouse model, bearing human tumor xenografts...
  38. ncbi request reprint Temozolomide after radiotherapy for newly diagnosed high-grade glioma and unfavorable low-grade glioma in children
    Alberto Broniscer
    Department of Hematology Oncology, St Jude Children s Research Hospital, Memphis, TN, USA
    J Neurooncol 76:313-9. 2006
    ..Although the heterogeneity of prognostic factors in our patients made assessment of treatment outcome more difficult, the addition of 6 cycles of temozolomide after radiotherapy did not seem to alter the poor outcome of these patients...
  39. pmc Tyrosine kinase inhibitor enhances the bioavailability of oral irinotecan in pediatric patients with refractory solid tumors
    Wayne L Furman
    Department of Oncology, St Jude Children s Research Hospital, 262 Danny Thomas Pl, Memphis, TN 38105 3678, USA
    J Clin Oncol 27:4599-604. 2009
    ..To assess the effect of gefitinib on the pharmacokinetics of IV irinotecan and on the bioavailability of a single oral dose of irinotecan...
  40. pmc Assessing cytotoxic treatment effects in preclinical tumor xenograft models
    Jianrong Wu
    Department of Biostatistics, St Jude Children s Research Hospital, Memphis, Tennessee 38105 3678, USA
    J Biopharm Stat 19:755-62. 2009
    ..Monte Carlo simulations are conducted to study the coverage probabilities of the proposed interval for small samples. Tumor xenograft data from a real experiment are analyzed to illustrate the proposed method...
  41. ncbi request reprint Phase I study of everolimus in pediatric patients with refractory solid tumors
    Maryam Fouladi
    Department of Oncology, St Jude Children s Research Hospital, Memphis, TN 38105 2794, USA
    J Clin Oncol 25:4806-12. 2007
    ....
  42. pmc Interval approach to assessing antitumor activity for tumor xenograft studies
    Jianrong Wu
    Department of Biostatistics, St Jude Children s Research Hospital, Memphis, TN 38105 3678, USA
    Pharm Stat 9:46-54. 2010
    ..A nonparametric bootstrap t-interval of the aAUC ratio is also proposed for assessing the significance of the antitumor activity of the agents. The proposed method is then applied to a real tumor xenograft study...
  43. pmc Initial testing of aplidin by the pediatric pre-clinical testing program
    Christopher L Morton
    Department of Molecular Pharmacology, St Jude Children s Research Hospital, Memphis, Tennessee 38105, USA
    Pediatr Blood Cancer 53:509-12. 2009
    ..Aplidin showed potent in vitro activity and induced significant in vivo tumor growth inhibition in some xenografts, but did not induce tumor regressions...
  44. ncbi request reprint Cefixime allows greater dose escalation of oral irinotecan: a phase I study in pediatric patients with refractory solid tumors
    Wayne L Furman
    Department of Hematology Oncology, St Jude Children s Research Hospital, Memphis, TN 38105 2794l, USA
    J Clin Oncol 24:563-70. 2006
    ....
  45. ncbi request reprint Results of a phase II upfront window of pharmacokinetically guided topotecan in high-risk medulloblastoma and supratentorial primitive neuroectodermal tumor
    Clinton F Stewart
    Department of Pharmaceutical Sciences, St Jude Children s Research Hospital, 332 N Lauderdale, Memphis, TN 38105 2794, USA
    J Clin Oncol 22:3357-65. 2004
    ....
  46. ncbi request reprint Altered irinotecan pharmacokinetics in pediatric high-grade glioma patients receiving enzyme-inducing anticonvulsant therapy
    Kristine R Crews
    Departments of Pharmaceutical Sciences, St Jude Children s Research Hospital, Memphis, Tennessee 38105, USA
    Clin Cancer Res 8:2202-9. 2002
    ..The purpose of this study was to determine the effect of enzyme-inducing anticonvulsants (EIAs) on the disposition of irinotecan and metabolites in pediatric patients with high-grade glioma...
  47. ncbi request reprint Inhibition of mammalian target of rapamycin activates apoptosis signal-regulating kinase 1 signaling by suppressing protein phosphatase 5 activity
    Shile Huang
    Department of Molecular Pharmacology, St Jude Children s Research Hospital, 332 Lauderdale, Memphis, TN 38105 2794, USA
    J Biol Chem 279:36490-6. 2004
    ..The findings suggest that in the absence of serum factors, mTOR signaling suppresses apoptosis through positive regulation of PP5 activity and suppression of cellular stress...
  48. ncbi request reprint Phase I and pharmacokinetic study of topotecan administered orally once daily for 5 days for 2 consecutive weeks to pediatric patients with refractory solid tumors
    Najat C Daw
    Department of Hematology Oncology, Mail Stop 260, St Jude Children s Research Hospital, 332 N Lauderdale, Memphis, TN 38105 2794, USA
    J Clin Oncol 22:829-37. 2004
    ..We conducted a phase I trial of the injectable formulation of topotecan given orally once daily for 5 days for 2 consecutive weeks (qd x 5 x 2) in pediatric patients with refractory solid tumors...
  49. ncbi request reprint Small-sample inference for incomplete longitudinal data with truncation and censoring in tumor xenograft models
    Ming Tan
    Department of Biostatistics, St Jude Children s Research Hospital, Memphis, Tennessee 38105, USA
    Biometrics 58:612-20. 2002
    ..A real xenograft study on a new antitumor agent, temozolomide, combined with irinotecan is analyzed using the proposed methods...
  50. ncbi request reprint Inhibitors of mammalian target of rapamycin as novel antitumor agents: from bench to clinic
    Shile Huang
    Department of Molecular Pharmacology, St Jude Children s Research Hospital, Memphis, TN 38105 2794, USA
    Curr Opin Investig Drugs 3:295-304. 2002
    ..Here we discuss potential antitumor mechanisms and resistance mechanisms of mTOR inhibitors, and summarize the current status of these compounds as novel antitumor agents...
  51. ncbi request reprint Topotecan-filgrastim combination is an effective regimen for mobilizing peripheral blood stem cells
    E J Yeoh
    Department of Hematology-Oncology, St Jude Children's Research Hospital, Memphis, TN 38105-2794, USA
    Bone Marrow Transplant 28:563-71. 2001
    ..Compared with filgrastim mobilization, topotecan-filgrastim mobilization resulted in a mean cost saving of $3966 per patient. Topotecan-filgrastim is an efficacious, minimally toxic, and cost-saving combination for PBSC mobilization...
  52. ncbi request reprint Efficacy and toxicity of a virus-directed enzyme prodrug therapy purging method: preclinical assessment and application to bone marrow samples from neuroblastoma patients
    Lars M Wagner
    Department of Molecular Pharmacology, St Jude Children s Research Hospital, Memphis, Tennessee 38105, USA
    Cancer Res 62:5001-7. 2002
    ..Assessment of purging efficacy with additional samples from NB patients is ongoing...
  53. ncbi request reprint Rapamycins: mechanism of action and cellular resistance
    Shile Huang
    Department of Molecular Pharmacology, St Jude Children s Research Hospital, 332 N Lauderdale, Memphis, Tennessee 38105, USA
    Cancer Biol Ther 2:222-32. 2003
    ..Here we review the conserved TOR signaling pathways, conceptual basis for tumor selectivity, and the mechanisms of resistance to this class of antitumor agent...
  54. ncbi request reprint Insulin-like growth factor I-mediated protection from rapamycin-induced apoptosis is independent of Ras-Erk1-Erk2 and phosphatidylinositol 3'-kinase-Akt signaling pathways
    Kuntebommanahalli N Thimmaiah
    Department of Molecular Pharmacology, St Jude Children s Research Hospital, Memphis, Tennessee 38105 2794, USA
    Cancer Res 63:364-74. 2003
    ..Therefore, we conclude that a novel pathway(s) is responsible for the IGF-I-mediated protection against rapamycin-induced apoptosis in these rhabdomyosarcoma cells...
  55. ncbi request reprint Evaluation of ABT-751 against childhood cancer models in vivo
    Christopher L Morton
    Department of Molecular Pharmacology, St Jude Children s Research Hospital, 332 North Lauderdale St, Memphis, TN 38105, USA
    Invest New Drugs 25:285-95. 2007
    ..ABT-751 is a novel antimitotic agent that binds tubulin at the colchicine binding site. ABT-751 is undergoing Phase I trials in children, but has not been evaluated against a range of pediatric tumor models in vivo...
  56. ncbi request reprint Establishment of human tumor xenografts in immunodeficient mice
    Christopher L Morton
    Department of Molecular Pharmacology, St Jude Children s Research Hospital, Memphis, Tennessee 38105, USA
    Nat Protoc 2:247-50. 2007
    ..The procedure relies on immunodeficient mice to provide a host for the establishment of human xenografts. The procedure can be completed in 1-2 h with results being obtained in 1-4 months...
  57. ncbi request reprint Developing new agents for the treatment of childhood cancer
    Raushan Kurmasheva
    St Jude Children s Research Hospital, Molecular Pharmacology, 332 North Lauderdale Street, Memphis, TN 38105 2794, USA
    Curr Opin Investig Drugs 6:1215-27. 2005
    ....
  58. ncbi request reprint 4E-binding proteins, the suppressors of eukaryotic initiation factor 4E, are down-regulated in cells with acquired or intrinsic resistance to rapamycin
    Michael B Dilling
    Department of Molecular Pharmacology, St Jude Children s Research Hospital, Memphis, Tennessee 38105 2794, USA
    J Biol Chem 277:13907-17. 2002
    ..These results suggest that the 4E-BP:eIF4E ratio is an important determinant of rapamycin resistance and controls certain aspects of the malignant phenotype...
  59. ncbi request reprint Testing of new agents in childhood cancer preclinical models: meeting summary
    Peter J Houghton
    St Jude Children s Research Hospital, Memphis, Tennessee 38101, USA
    Clin Cancer Res 8:3646-57. 2002
    ..This report is a synthesis of the workshop's presentations and discussions...
  60. pmc Protection from rapamycin-induced apoptosis by insulin-like growth factor-I is partially dependent on protein kinase C signaling
    Kuntebommanahalli N Thimmaiah
    Department of Molecular Pharmacology, St Jude Children s Research Hospital, Memphis, Tennessee, USA
    Cancer Res 70:2000-9. 2010
    ..Collectively, these data suggest that IGF-I-induced phosphorylation of Bad at multiple sites via a pathway involving PI3K and PKCs is important for protecting sarcoma cells from rapamycin-induced apoptosis...
  61. ncbi request reprint Phase I study of depsipeptide in pediatric patients with refractory solid tumors: a Children's Oncology Group report
    Maryam Fouladi
    Department of Hematology Oncology, St Jude Children s Research Hospital, Memphis, TN 38105 2794, USA
    J Clin Oncol 24:3678-85. 2006
    ..To determine the maximum-tolerated dose (MTD), dose-limiting toxicities (DLT), pharmacokinetic profile, and pharmacodynamics of the histone deacetylase inhibitor, depsipeptide, in children with refractory or recurrent solid tumors...
  62. ncbi request reprint Pharmacologic inhibition of cyclin-dependent kinase 4/6 activity arrests proliferation in myoblasts and rhabdomyosarcoma-derived cells
    Raya Saab
    Department of Hematology Oncology, St Jude Children s Research Hospital, 332 North Lauderdale Street, Memphis, TN 38105, USA
    Mol Cancer Ther 5:1299-308. 2006
    ..Our findings support the concept that pharmacologic inhibition of Cdk4/Cdk6 may represent a useful therapeutic strategy to control cell proliferation and possibly promote myogenic differentiation in rhabdomyosarcoma...
  63. pmc The mTORC2 complex regulates terminal differentiation of C2C12 myoblasts
    Lili Shu
    Department of Molecular Pharmacology, St Jude Children s Research Hospital, Memphis, Tennessee 38105 2794, USA
    Mol Cell Biol 29:4691-700. 2009
    ..Further, the ROCK inhibitor Y-27632 restored terminal differentiation in rapamycin-treated myoblasts. These results provide the first evidence of a specific role for mTORC2 signaling in terminal myogenic differentiation...
  64. pmc FOXO1a acts as a selective tumor suppressor in alveolar rhabdomyosarcoma
    Philippe R J Bois
    Department of Biochemistry, St Jude Children s Research Hospital, Memphis, TN 38105, USA
    J Cell Biol 170:903-12. 2005
    ..We conclude that FOXO1a is a potent and specific tumor suppressor in ARMS, suggesting that agents that restore or augment FOXO1a activity may be effective as ARMS therapeutics...
  65. ncbi request reprint Targeting mTOR signaling for cancer therapy
    Shile Huang
    Department of Molecular Pharmacology, St Jude Children s Research Hospital, 332 N Lauderdale, Memphis, TN 38105 2794, USA
    Curr Opin Pharmacol 3:371-7. 2003
    ..These trials have demonstrated promising anti-cancer activity and relatively mild side effects of CCI-779. Emerging results suggest that inhibition of mTOR signaling can be exploited as a potential tumour-selective therapeutic strategy...
  66. ncbi request reprint mTORC1 signaling can regulate growth factor activation of p44/42 mitogen-activated protein kinases through protein phosphatase 2A
    Franklin C Harwood
    Department of Molecular Pharmacology, St Jude Children s Research Hospital, 332 N Lauderdale Street, Memphis, TN 38105, USA
    J Biol Chem 283:2575-85. 2008
    ..These results indicate complex regulation of p44/42 by phosphatases downstream of mTORC1. This suggests a model in which mTORC1 modulates the phosphorylation of Thr(202) on p44/42 MAPKs through direct or indirect regulation of PP2Ac...
  67. ncbi request reprint Myogenic differentiation is dependent on both the kinase function and the N-terminal sequence of mammalian target of rapamycin
    Lili Shu
    Department of Molecular Pharmacology, St Jude Children s Research Hospital, Memphis, Tennessee 38105 2794, USA
    J Biol Chem 277:16726-32. 2002
    ..In contrast, constitutive activation of S6K1 does not abrogate rapamycin inhibition of either proliferation or myogenic differentiation...
  68. pmc Pediatric oncology
    Raushan T Kurmasheva
    Department of Molecular Pharmacology, St Jude Children s Research Hospital, 332 North Lauderdale Street, Memphis, TN 38105 2794, United States
    Curr Opin Chem Biol 11:424-32. 2007
    ....
  69. ncbi request reprint Sustained activation of the JNK cascade and rapamycin-induced apoptosis are suppressed by p53/p21(Cip1)
    Shile Huang
    Department of Molecular Pharmacology, St Jude Children s Research Hospital, Memphis, TN 38105, USA
    Mol Cell 11:1491-501. 2003
    ..These results suggest that inhibition of mTOR triggers a potentially lethal response that is prevented only in cells expressing p21(Cip1)...
  70. ncbi request reprint Predominant nuclear localization of mammalian target of rapamycin in normal and malignant cells in culture
    Xiongwen Zhang
    Department of Molecular Pharmacology, St Jude Children s Research Hospital, Memphis, Tennessee 38105 2794, USA
    J Biol Chem 277:28127-34. 2002
    ..eIF4E was detected in all fractions derived from rhabdomyosarcoma cells but was not detectable in nuclear fractions from colon carcinoma HEK293 or IMR90 cells...
  71. pmc Negative regulation of ASK1 by p21Cip1 involves a small domain that includes Serine 98 that is phosphorylated by ASK1 in vivo
    Jun Zhan
    Department of Molecular Pharmacology, St Jude Children s Research Hospital, Memphis, TN 38105 2794, USA
    Mol Cell Biol 27:3530-41. 2007
    ..Binding of p21(Cip1) to ASK1 requires ASK1 kinase function and may involve phosphorylation of S98...
  72. ncbi request reprint IRS-1: auditing the effectiveness of mTOR inhibitors
    John B Easton
    Department of Molecular Pharmacology, St Jude Children s Research Hospital, Memphis, Tennessee 38105, USA
    Cancer Cell 9:153-5. 2006
    ..In the second paper, Kaper et al. address the impact of pathway activation on hypoxia-mediated downregulation of mTOR signaling, raising the possibility that rapalogs could selectively inhibit hypoxic cells...
  73. ncbi request reprint IGF-I mediated survival pathways in normal and malignant cells
    Raushan T Kurmasheva
    Department of Molecular Pharmacology, St Jude Children s Research Hospital, 332 N Lauderdale St, Memphis, TN 38105 2794, USA
    Biochim Biophys Acta 1766:1-22. 2006
    ..IGFs are implicated also in acute renal failure, traumatic injury to brain tissue, and cardiac disease. This article focuses on the role of IGFs and their cellular signaling pathways that provide survival signals in stressed cells...
  74. ncbi request reprint The TOR pathway: a target for cancer therapy
    Mary Ann Bjornsti
    Department of Molecular Pharmacology, St Jude Children s Research Hospital, Memphis, Tennessee 38105, USA
    Nat Rev Cancer 4:335-48. 2004
  75. ncbi request reprint Lost in translation: dysregulation of cap-dependent translation and cancer
    Mary Ann Bjornsti
    Department of Molecular Pharmacology, St Jude Children s Research Hospital, 332 N Lauderdale St, Memphis, TN 38105, USA
    Cancer Cell 5:519-23. 2004
    ....
  76. ncbi request reprint Differential regulation of vascular endothelial growth factor by Akt and mammalian target of rapamycin inhibitors in cell lines derived from childhood solid tumors
    Raushan T Kurmasheva
    Department of Molecular Pharmacology, St Jude Children s Research Hospital, 332 North Lauderdale Street, Memphis, TN 38105 2794, USA
    Mol Cancer Ther 6:1620-8. 2007
    ..However, this will require formal testing in vivo using animal models of childhood cancer...
  77. ncbi request reprint Characterization of ARC-111 as a novel topoisomerase I-targeting anticancer drug
    Tsai Kun Li
    Department of Pharmacology, University of Medicine and Dentistry of New Jersey Robert Wood Johnson Medical School, Piscataway, New Jersey 08854, USA
    Cancer Res 63:8400-7. 2003
    ..These results suggest that ARC-111 is a promising new TOP1-targeting antitumor drug with a different drug resistance profile than CPT...
  78. ncbi request reprint Enhanced antitumor activity of irofulven in combination with irinotecan in pediatric solid tumor xenograft models
    Michael H Woo
    Clinical Discovery, Bristol Myers Squibb, P O Box 4000, Princeton, NJ 08543, USA
    Cancer Chemother Pharmacol 55:411-9. 2005
    ..The objective of this study was to evaluate the antitumor activity of irofulven in combination with irinotecan administered on a protracted schedule in a panel of pediatric solid tumor xenografts...
  79. ncbi request reprint Phase I trial of temozolomide and protracted irinotecan in pediatric patients with refractory solid tumors
    Lars M Wagner
    Division of Pediatric Hematology Oncology, University of Utah Primary Children s Medical Center, Salt Lake City, Utah, USA
    Clin Cancer Res 10:840-8. 2004
    ..The purpose is to estimate the maximum-tolerated dose (MTD) of temozolomide and irinotecan given on a protracted schedule in 28-day courses to pediatric patients with refractory solid tumors...
  80. ncbi request reprint Repeated-measures models with constrained parameters for incomplete data in tumour xenograft experiments
    Ming Tan
    Division of Biostatistics, University of Maryland Greenebaum Cancer Center, 22 South Greene Street, Baltimore, MD 21201, USA
    Stat Med 24:109-19. 2005
    ..A real xenograft study on a new anti-tumour agent temozolomide combined with irinotecan is analysed using the proposed method...
  81. pmc The mTOR inhibitor CCI-779 induces apoptosis and inhibits growth in preclinical models of primary adult human ALL
    David T Teachey
    Division of Oncology, Department of Pediatrics, Children s Hospital of Philadelphia, Philadelphia, PA 19104, USA
    Blood 107:1149-55. 2006
    ..We conclude that MTIs can inhibit the growth of adult human ALL and deserve close examination as therapeutic agents against a disease that is often not curable with current therapy...
  82. ncbi request reprint 5-(2-aminoethyl)dibenzo[c,h][1,6]naphthyridin-6-ones: variation of n-alkyl substituents modulates sensitivity to efflux transporters associated with multidrug resistance
    Alexander L Ruchelman
    Department of Pharmaceutical Chemistry, Rutgers, The State University of New Jersey, 160 Frelinghuysen Road, Piscataway, New Jersey 08854 8020, USA
    J Med Chem 48:792-804. 2005
    ....
  83. ncbi request reprint Synthesis and chemical characterization of 2-methoxy-N(10)-substituted acridones needed to reverse vinblastine resistance in multidrug resistant (MDR) cancer cells
    Gowdahalli Krishnegowda
    Department of Biochemistry and Molecular Biology, Georgetown University Medical Center, 3900 Reservoir Road, NW, 20007 219, Washington DC 20007, USA
    Bioorg Med Chem 10:2367-80. 2002
    ..Examination of the relationship between lipophilicity and antagonism of MDR showed a reasonable correlation suggesting that hydrophobicity is one of the determinants of potency for anti-MDR activity of 2-methoxyacridones...
  84. pmc Initial testing of VNP40101M (Cloretazine) by the pediatric preclinical testing program
    Stephen T Keir
    Preston Robert Tisch Brain Tumor Center, Duke University Medical Center, Durham, North Carolina 27710, USA
    Pediatr Blood Cancer 51:439-41. 2008
    ..VNP4010M antitumor activity was observed only in the absence of MGMT expression, with resistance to VNP4010M seen even with low MGMT expression...
  85. ncbi request reprint Potentiation of neuroblastoma metastasis by loss of caspase-8
    Dwayne G Stupack
    Department of Pathology and The John and Rebecca Moores Cancer Center, The University of California at San Diego, La Jolla, California 92093 0803, USA
    Nature 439:95-9. 2006
    ..These findings define caspase-8 as a metastasis suppressor gene that, together with integrins, regulates the survival and invasive capacity of neuroblastoma cells...
  86. doi request reprint Stage 1 testing and pharmacodynamic evaluation of the HSP90 inhibitor alvespimycin (17-DMAG, KOS-1022) by the pediatric preclinical testing program
    Malcolm A Smith
    Cancer Therapy Evaluation Program, NCI, Bethesda, Maryland
    Pediatr Blood Cancer 51:34-41. 2008
    ..Alvespimycin (17-DMAG, KOS-1022), a potent small-molecule inhibitor of the protein chaperone Hsp90, is being developed as an anticancer agent because of the multiple Hsp90 client proteins involved in cancer cell growth and survival...
  87. ncbi request reprint Initial testing of the VEGFR inhibitor AZD2171 by the pediatric preclinical testing program
    John M Maris
    Children s Hospital of Philadelphia, University of Pennsylvania School of Medicine and Abramson Family Cancer Research Institute, Philadelphia, Pennsylvania, USA
    Pediatr Blood Cancer 50:581-7. 2008
    ..This study was designed to screen for antitumor activity of AZD2171 against the in vitro and in vivo childhood cancer preclinical models of the Pediatric Preclinical Testing Program (PPTP)...
  88. ncbi request reprint O6-benzylguanine-mediated enhancement of chemotherapy
    Henry S Friedman
    Departments of Surgery, Pathology and Medicine, Duke University Medical Center, Room 047, Baker House, Trent Drive, Durham, North Carolina 27710, USA
    Mol Cancer Ther 1:943-8. 2002
    ..These results suggest that a Phase I trial of CPT-11 plus temozolomide plus O6-BG in AGT-positive tumors may be an important intervention to maximize the therapeutic benefits of the combination of CPT-11 and temozolomide...
  89. ncbi request reprint Insulin-like growth factor-I has different effects on myogenin induction and cell cycle progression in human alveolar and embryonal rhabdomyosarcoma cells
    Kunihiko Tsuchiya
    Department of Pediatrics, Graduate School of Medical Science, Kyoto Prefectural University of Medicine, Kyoto, Kamigyo ku, Kyoto 602 8566, Japan
    Int J Oncol 31:41-7. 2007
    ..These different responses to IGF-I help to explain immunohistochemical and clinical behavioral differences between alveolar and embryonal RMS...
  90. ncbi request reprint Initial testing of cisplatin by the pediatric preclinical testing program
    Mimi Tajbakhsh
    Children s Cancer Institute Australia for Medical Research, Randwick, New South Wales, Australia
    Pediatr Blood Cancer 50:992-1000. 2008
    ..Cisplatin is one of the most widely used drugs for the treatment of solid tumors in adults and children. Here, we report the activity of cisplatin against the PPTP panels of childhood cancer xenografts...
  91. ncbi request reprint The emerging role of irinotecan (CPT-11) in the treatment of malignant glioma in brain tumors
    Henry S Friedman
    Department of Surgery, Duke University Medical Center, Durham, North Carolina 27710, USA
    Cancer 97:2359-62. 2003
    ..Studies currently are addressing the role of O(6)-alkylguanine-DNA alkyltransferase (AGT) in reducing the benefits of combining CPT-11 with temozolomide and the potential therapeutic gain from utilizing an inhibitor of AGT...
  92. ncbi request reprint Experimental design and sample size determination for testing synergism in drug combination studies based on uniform measures
    Ming Tan
    Division of Biostatistics, University of Maryland Greenebaum Cancer Center, 22 South Greene Street, Baltimore, MD 21201, USA
    Stat Med 22:2091-100. 2003
    ..We illustrate the method with a study of the joint action of two new anticancer agents: temozolomide and irinotecan...
  93. ncbi request reprint Initial testing of dasatinib by the pediatric preclinical testing program
    E Anders Kolb
    The Children s Hospital at Montefiore, Bronx, New York, USA
    Pediatr Blood Cancer 50:1198-206. 2008
    ..Dasatinib, a dual inhibitor of the src and abl tyrosine kinases, was recently approved by the Federal Drug Administration for the treatment of imatinib mesylate-resistant chronic myeloid leukemia...
  94. ncbi request reprint Biological properties of different extracts of two Senecio species
    Filomena Conforti
    Department of Pharmaceutical Sciences, University of Calabria, Rende, Italy
    Int J Food Sci Nutr 57:1-8. 2006
    ..Both Senecio species also show appreciable alpha-amylase inhibition, particularly the methanolic and dichloromethane extracts, and this may confer anti-diabetic properties on the extract...
  95. ncbi request reprint Initial testing (stage 1) of the BH3 mimetic ABT-263 by the pediatric preclinical testing program
    Richard Lock
    Children s Cancer Institute Australia for Medical Research, Randwick, NSW, Australia
    Pediatr Blood Cancer 50:1181-9. 2008
    ....
  96. doi request reprint Initial testing (stage 1) of a monoclonal antibody (SCH 717454) against the IGF-1 receptor by the pediatric preclinical testing program
    E Anders Kolb
    Albert Einstein College of Medicine, The Children s Hospital at Montefiore, Bronx, New York, USA
    Pediatr Blood Cancer 50:1190-7. 2008
    ..The activity of SCH 717454 was evaluated against the in vitro and in vivo panels of the Pediatric Preclinical Testing Program (PPTP)...
  97. doi request reprint Initial testing (stage 1) of sunitinib by the pediatric preclinical testing program
    John M Maris
    Children s Hospital of Philadelphia, University of Pennsylvania School of Medicine and Abramson Family Cancer Research Institute, Philadelphia, Pennsylvania, USA
    Pediatr Blood Cancer 51:42-8. 2008
    ..Sunitinib is an orally bioavailable, multi-targeted tyrosine kinase inhibitor with selectivity for PDGF receptors, VEGF receptors, FLT3, and KIT...

Research Grants2

  1. STUDIES OF CHILDHOOD SOLID TUMORS
    Peter Houghton; Fiscal Year: 2007
    ..Our intent remains to advance preclinical information to the design of clinical trials, and extend these to cooperative groups. ..