alkylating antineoplastic agents

Summary

Summary: A class of drugs that differs from other alkylating agents used clinically in that they are monofunctional and thus unable to cross-link cellular macromolecules. Among their common properties are a requirement for metabolic activation to intermediates with antitumor efficacy and the presence in their chemical structures of N-methyl groups, that after metabolism, can covalently modify cellular DNA. The precise mechanisms by which each of these drugs acts to kill tumor cells are not completely understood. (From AMA, Drug Evaluations Annual, 1994, p2026)

Top Publications

  1. ncbi Radiotherapy plus concomitant and adjuvant temozolomide for glioblastoma
    Roger Stupp
    Multidisciplinary Oncology Center, Centre Hospitalier Universitaire Vaudois, Lausanne, Switzerland
    N Engl J Med 352:987-96. 2005
  2. ncbi Correlation of O6-methylguanine methyltransferase (MGMT) promoter methylation with clinical outcomes in glioblastoma and clinical strategies to modulate MGMT activity
    Monika E Hegi
    Laboratory of Tumor Biology and Genetics, Department of Neurosurgery BH 19 110, Centre Hospitalier Universitaire Vaudois and University of Lausanne, CH 1011 Lausanne, Switzerland
    J Clin Oncol 26:4189-99. 2008
  3. ncbi Clinical trial substantiates the predictive value of O-6-methylguanine-DNA methyltransferase promoter methylation in glioblastoma patients treated with temozolomide
    Monika E Hegi
    Laboratory of Tumor Biology and Genetics of the Neurosurgery Departments of the University Hospitals, Lausanne, Switzerland
    Clin Cancer Res 10:1871-4. 2004
  4. ncbi MGMT gene silencing and benefit from temozolomide in glioblastoma
    Monika E Hegi
    Laboratory of Tumor Biology and Genetics, Department of Neurosurgery, University Hospital Lausanne, Lausanne, Switzerland
    N Engl J Med 352:997-1003. 2005
  5. ncbi Apoptosis in malignant glioma cells triggered by the temozolomide-induced DNA lesion O6-methylguanine
    W P Roos
    Department of Toxicology, University of Mainz, Mainz, Germany
    Oncogene 26:186-97. 2007
  6. ncbi O6-methylguanine DNA methyltransferase and p53 status predict temozolomide sensitivity in human malignant glioma cells
    Mirjam Hermisson
    Laboratory of Molecular Neuro Oncology, Department of General Neurology, Hertie Institute for Clinical Brain Research, University of Tubingen, School of Medicine, Tubingen, Germany
    J Neurochem 96:766-76. 2006
  7. ncbi p53 effects both the duration of G2/M arrest and the fate of temozolomide-treated human glioblastoma cells
    Y Hirose
    Brain Tumor Research Center, Department of Neurological Surgery, University of California San Francisco, 94143-0875, USA
    Cancer Res 61:1957-63. 2001
  8. ncbi Phase I and pharmacokinetic study of temozolomide on a daily-for-5-days schedule in patients with advanced solid malignancies
    L A Hammond
    Institute for Drug Development, Cancer Therapy and Research Center, San Antonio, TX 78829, USA
    J Clin Oncol 17:2604-13. 1999
  9. ncbi Isolated limb perfusion with high-dose tumor necrosis factor-alpha in combination with interferon-gamma and melphalan for nonresectable extremity soft tissue sarcomas: a multicenter trial
    A M Eggermont
    Department of Surgical Oncology, University Hospital Rotterdam Daniel den Hoed Cancer Center, The Netherlands
    J Clin Oncol 14:2653-65. 1996
  10. ncbi O6-Methylguanine-DNA methyltransferase inactivation and chemotherapy
    Barbara Verbeek
    Cancer Research UK Carcinogenesis Group, Paterson Institute for Cancer Research, University of Manchester, Wilmslow Road, Manchester M20 4BX, UK
    Br Med Bull 85:17-33. 2008

Research Grants

Detail Information

Publications274 found, 100 shown here

  1. ncbi Radiotherapy plus concomitant and adjuvant temozolomide for glioblastoma
    Roger Stupp
    Multidisciplinary Oncology Center, Centre Hospitalier Universitaire Vaudois, Lausanne, Switzerland
    N Engl J Med 352:987-96. 2005
    ..In this trial we compared radiotherapy alone with radiotherapy plus temozolomide, given concomitantly with and after radiotherapy, in terms of efficacy and safety...
  2. ncbi Correlation of O6-methylguanine methyltransferase (MGMT) promoter methylation with clinical outcomes in glioblastoma and clinical strategies to modulate MGMT activity
    Monika E Hegi
    Laboratory of Tumor Biology and Genetics, Department of Neurosurgery BH 19 110, Centre Hospitalier Universitaire Vaudois and University of Lausanne, CH 1011 Lausanne, Switzerland
    J Clin Oncol 26:4189-99. 2008
    ..Herein we review the data supporting MGMT as a major mechanism of chemotherapy resistance in malignant gliomas and describe ongoing studies that are testing resistance-modulating strategies...
  3. ncbi Clinical trial substantiates the predictive value of O-6-methylguanine-DNA methyltransferase promoter methylation in glioblastoma patients treated with temozolomide
    Monika E Hegi
    Laboratory of Tumor Biology and Genetics of the Neurosurgery Departments of the University Hospitals, Lausanne, Switzerland
    Clin Cancer Res 10:1871-4. 2004
    ..Expression of this excision repair enzyme has been associated with resistance to alkylating chemotherapy...
  4. ncbi MGMT gene silencing and benefit from temozolomide in glioblastoma
    Monika E Hegi
    Laboratory of Tumor Biology and Genetics, Department of Neurosurgery, University Hospital Lausanne, Lausanne, Switzerland
    N Engl J Med 352:997-1003. 2005
    ....
  5. ncbi Apoptosis in malignant glioma cells triggered by the temozolomide-induced DNA lesion O6-methylguanine
    W P Roos
    Department of Toxicology, University of Mainz, Mainz, Germany
    Oncogene 26:186-97. 2007
    ..Overall, the data demonstrate that cell death induced by TMZ in gliomas is due to apoptosis and that determinants of sensitivity of gliomas to TMZ are MGMT, p53, proliferation rate and DSB repair...
  6. ncbi O6-methylguanine DNA methyltransferase and p53 status predict temozolomide sensitivity in human malignant glioma cells
    Mirjam Hermisson
    Laboratory of Molecular Neuro Oncology, Department of General Neurology, Hertie Institute for Clinical Brain Research, University of Tubingen, School of Medicine, Tubingen, Germany
    J Neurochem 96:766-76. 2006
    ..Collectively, these results suggest that the determination of MGMT expression and p53 status will help to identify glioma patients who will or will not respond to TMZ...
  7. ncbi p53 effects both the duration of G2/M arrest and the fate of temozolomide-treated human glioblastoma cells
    Y Hirose
    Brain Tumor Research Center, Department of Neurological Surgery, University of California San Francisco, 94143-0875, USA
    Cancer Res 61:1957-63. 2001
    ..Therefore, the integrity of the G2-M cell cycle checkpoint may be important in the cytotoxicity of TMZ in glioma cells...
  8. ncbi Phase I and pharmacokinetic study of temozolomide on a daily-for-5-days schedule in patients with advanced solid malignancies
    L A Hammond
    Institute for Drug Development, Cancer Therapy and Research Center, San Antonio, TX 78829, USA
    J Clin Oncol 17:2604-13. 1999
    ....
  9. ncbi Isolated limb perfusion with high-dose tumor necrosis factor-alpha in combination with interferon-gamma and melphalan for nonresectable extremity soft tissue sarcomas: a multicenter trial
    A M Eggermont
    Department of Surgical Oncology, University Hospital Rotterdam Daniel den Hoed Cancer Center, The Netherlands
    J Clin Oncol 14:2653-65. 1996
    ....
  10. ncbi O6-Methylguanine-DNA methyltransferase inactivation and chemotherapy
    Barbara Verbeek
    Cancer Research UK Carcinogenesis Group, Paterson Institute for Cancer Research, University of Manchester, Wilmslow Road, Manchester M20 4BX, UK
    Br Med Bull 85:17-33. 2008
    ..This group of drugs mediates cell death by damaging DNA and therefore, understandably, cellular DNA repair mechanisms can influence both their antitumour efficacy and their dose-limiting toxicities...
  11. ncbi Temozolomide for the treatment of brain metastases associated with metastatic melanoma: a phase II study
    Sanjiv S Agarwala
    Division of Hematology Oncology, University of Pittsburgh Medical Center Pavilion, 5150 Centre Ave, Pittsburgh, PA 15232, USA
    J Clin Oncol 22:2101-7. 2004
    ..A multicenter, open-label, phase II study was conducted to assess the safety and efficacy of temozolomide in patients with brain metastases from metastatic melanoma (MM) who did not require immediate radiotherapy...
  12. ncbi Triazene compounds: mechanism of action and related DNA repair systems
    Francesco Marchesi
    Department of Neuroscience, School of Medicine, University of Rome, Tor Vergata, Italy
    Pharmacol Res 56:275-87. 2007
    ..Moreover, the susceptibility of neoplastic cells to these compounds can be substantially increased through pharmacological modulation of the expression level and functional activity of DNA repair enzymes...
  13. pmc Triptolide induces caspase-dependent cell death mediated via the mitochondrial pathway in leukemic cells
    Bing Z Carter
    Section of Molecular Hematology and Therapy, Department of Blood and Marrow Transplantation, The University of Texas, MD Anderson Cancer Center, Houston, 77030, USA
    Blood 108:630-7. 2006
    ..The potent antileukemic activity of triptolide in vitro warrants further investigation of this compound for the treatment of leukemias and other malignancies...
  14. ncbi Absorption, metabolism, and excretion of 14C-temozolomide following oral administration to patients with advanced cancer
    S D Baker
    The Johns Hopkins Oncology Center, Baltimore, Maryland 21287, USA
    Clin Cancer Res 5:309-17. 1999
    ..The primary elimination pathway for TMZ is by pH-dependent degradation to MTIC and further degradation to AIC. Incomplete recovery of radioactivity may be explained by the incorporation of AIC into nucleic acids...
  15. ncbi A senescence program controlled by p53 and p16INK4a contributes to the outcome of cancer therapy
    Clemens A Schmitt
    Cold Spring Harbor Laboratory, 1 Bungtown Road, New York 11724, USA
    Cell 109:335-46. 2002
    ..Therefore, cellular senescence contributes to treatment outcome in vivo...
  16. ncbi Clinical features, mechanisms, and management of pseudoprogression in malignant gliomas
    Dieta Brandsma
    Department of Neuro Oncology, Daniel den Hoed Cancer Centre, Erasmus Medical Centre, Rotterdam, Netherlands
    Lancet Oncol 9:453-61. 2008
    ..Further research is needed to establish reliable imaging parameters that distinguish between true tumour progression and pseudoprogression or treatment-related necrosis...
  17. pmc Temozolomide induces apoptosis and senescence in glioma cells cultured as multicellular spheroids
    W Gunther
    Department of Neurosurgery, Medical University of Lubeck, Germany
    Br J Cancer 88:463-9. 2003
    ..We suggest that temozolomide is a strong initiator of apoptosis in glioblastoma tumour cells in a spheroid cell culture system, when cells are already in a stressful environment...
  18. ncbi Temozolomide in metastatic breast cancer (MBC): a phase II trial of the National Cancer Institute of Canada - Clinical Trials Group (NCIC-CTG)
    M E Trudeau
    Toronto Sunnybrook Regional Cancer Centre, ON, Canada
    Ann Oncol 17:952-6. 2006
    ..This phase II trial sought to determine the activity and toxicity of temozolomide in metastatic breast cancer (MBC). Temozolomide was administered in a dose dense schedule of 150 mg/m(2) on days 1-7 and 15-21 in a 28-day cycle...
  19. ncbi ET-743: the US experience in sarcomas of soft tissues
    George D Demetri
    Center for Sarcoma and Bone Oncology, Dana Farber Cancer Institute, Harvard Medical School, Boston, Massachusetts, USA
    Anticancer Drugs 13:S7-9. 2002
    ..There were no treatment-associated deaths. In conclusion, ET-743 is an active chemotherapeutic agent that can induce objective responses and clinical benefit in a subset of patients with metastatic or advanced soft-tissue sarcoma...
  20. ncbi Temozolomide in malignant gliomas of childhood: a United Kingdom Children's Cancer Study Group and French Society for Pediatric Oncology Intergroup Study
    L S Lashford
    Christie National Health Service Trust, Manchester
    J Clin Oncol 20:4684-91. 2002
    ..To determine the response rate of the malignant gliomas of childhood to an oral, daily schedule of temozolomide...
  21. ncbi Health-related quality of life in patients with glioblastoma: a randomised controlled trial
    Martin J B Taphoorn
    Medical Centre Haaglanden, The Hague, The Netherlands
    Lancet Oncol 6:937-44. 2005
    ..This paper reports the health-related quality of life (HRQOL) of the patients in this trial...
  22. ncbi Clinical pharmacokinetics of cyclophosphamide
    Milly E de Jonge
    Department of Pharmacy and Pharmacology, The Netherlands Cancer Institute Slotervaart Hospital, Amsterdam, The Netherlands
    Clin Pharmacokinet 44:1135-64. 2005
    ..Knowledge of the pharmacokinetics of cyclophosphamide, and possibly monitoring the pharmacokinetics of cyclophosphamide in individuals, may be useful for improving its therapeutic index...
  23. pmc Induction of MGMT expression is associated with temozolomide resistance in glioblastoma xenografts
    Gaspar J Kitange
    Department of Radiation Oncology, Mayo Clinic, Rochester, MN 55905, USA
    Neuro Oncol 11:281-91. 2009
    ..In conclusion, MGMT expression is dynamically regulated in some MGMT nonmethylated tumors, and in these tumors, protracted dosing regimens may not be effective...
  24. ncbi High-dose ifosfamide in bone and soft tissue sarcomas: results of phase II and pilot studies--dose-response and schedule dependence
    S R Patel
    The Sarcoma Center, The University of Texas M D Anderson Cancer Center, Houston 77030, USA
    J Clin Oncol 15:2378-84. 1997
    ..There is a definite positive dose-response curve, and bolus administration appears to be more active than continuous infusion...
  25. ncbi Adenovirus-based strategies overcome temozolomide resistance by silencing the O6-methylguanine-DNA methyltransferase promoter
    Marta M Alonso
    Department of Neuro Oncology, The University of Texas M D Anderson Cancer Center, Houston, Texas 77030, USA
    Cancer Res 67:11499-504. 2007
    ..Collectively, our data provide a strong mechanistic rationale for the combination of oncolytic adenoviruses and temozolomide, and should propel the clinical testing of this therapy approach in patients with malignant gliomas...
  26. ncbi Selective CD4+ lymphopenia in melanoma patients treated with temozolomide: a toxicity with therapeutic implications
    Y B Su
    Department of Medicine, Memorial Sloan Kettering Cancer Center, 1275 York Avenue, New York, NY 10021, USA
    J Clin Oncol 22:610-6. 2004
    ..Using an extended dosing schedule, we noted a high incidence of lymphopenia and occasional opportunistic infections (OIs). Here we report our retrospective experience in the first 97 patients...
  27. ncbi Temozolomide: a novel oral alkylating agent
    S J Danson
    Department of Medical Oncology, Christie Hospital NHS Trust, Wilmslow Road, Manchester, M20 9BX, UK
    Expert Rev Anticancer Ther 1:13-9. 2001
    ..Studies of new drug schedules and of drugs to ameliorate temozolomide resistance offer the prospect of increased efficacy...
  28. ncbi Overcoming multidrug drug resistance in P-glycoprotein/MDR1-overexpressing cell lines by ecteinascidin 743
    Atsuko Kanzaki
    Department of Pathology, Institute of Development, Aging and Cancer, Tohoku University, Sendai 980 8575, Japan
    Mol Cancer Ther 1:1327-34. 2002
    ..Et-743 can potentiate the activity of other chemotherapeutic agents by down-regulating P-gp/MDR1, suggesting that the combination of Et-743 and chemotherapeutic agents that are substrates for P-gp/MDR1 may be valuable in the clinic...
  29. ncbi Multifaceted resistance of gliomas to temozolomide
    Dora B Bocangel
    Department of Pathology, The University of Pittsburgh Cancer Institute, Pittsburgh, Pennsylvania 15261, USA
    Clin Cancer Res 8:2725-34. 2002
    ....
  30. ncbi Inhibition of DNA repair for sensitizing resistant glioma cells to temozolomide
    Takao Kanzawa
    Department of Neurosurgery, Mount Sinai School of Medicine, New York, New York, USA
    J Neurosurg 99:1047-52. 2003
    ..In this study the authors investigated the ability of O6-benzylguanine (BG), an AGT inhibitor, to sensitize a glioblastoma cell line resistant to TMZ...
  31. ncbi DNA mismatch repair and O6-alkylguanine-DNA alkyltransferase analysis and response to Temodal in newly diagnosed malignant glioma
    H S Friedman
    Department of Surgery, Howard Hughes Medical Institute, Duke University Medical Center, Durham, NC 27710, USA
    J Clin Oncol 16:3851-7. 1998
    ....
  32. ncbi MS-MLPA: an attractive alternative laboratory assay for robust, reliable, and semiquantitative detection of MGMT promoter hypermethylation in gliomas
    Judith W M Jeuken
    Department of Pathology, Nijmegen Center for Molecular Life Sciences, Radboud University Nijmegen Medical Centre, Nijmegen, The Netherlands
    Lab Invest 87:1055-65. 2007
    ..The semiquantitative aspect of MS-MLPA may prove to be of great value, especially in predicting response to alkylating agents, not only for gliomas as evaluated in this study but also for tumors in general...
  33. pmc Tumour necrosis factor alpha increases melphalan concentration in tumour tissue after isolated limb perfusion
    J H de Wilt
    Department of Surgical Oncology, University Hospital Rotterdam Dijkzigt Daniel den Hoed Cancer Centre, The Netherlands
    Br J Cancer 82:1000-3. 2000
    ....
  34. ncbi Salvage therapy for primary CNS lymphoma with a combination of rituximab and temozolomide
    Roelien H Enting
    Department of Neurology, University Hospital, Groningen, The Netherlands
    Neurology 63:901-3. 2004
    ..7 months. This combination merits further study and provides a reasonable therapeutic alternative for older patients with progressive PCNSL...
  35. ncbi Unique pattern of ET-743 activity in different cellular systems with defined deficiencies in DNA-repair pathways
    G Damia
    Department of Oncology, Istituto di Ricerche Farmacologiche Mario Negri, Milan, Italy
    Int J Cancer 92:583-8. 2001
    ..An increase in ET-743 sensitivity was also observed in ataxia telangiectasia-mutated cells. Our data strongly suggest that ET-743 has a unique mechanism of interaction with DNA...
  36. ncbi Histone acetyltransferase 1 is dispensable for replication-coupled chromatin assembly but contributes to recover DNA damages created following replication blockage in vertebrate cells
    Hirak Kumar Barman
    Section of Biochemistry and Molecular Biology, Department of Medical Sciences, Miyazaki Medical College, Japan
    Biochem Biophys Res Commun 345:1547-57. 2006
    ..These results indicate that HAT1 participates in recovering replication block-mediated DNA damages, probably through chromatin modulation based on acetylation of Lys-5 and Lys-12 of histone H4...
  37. ncbi The role of base excision repair in the sensitivity and resistance to temozolomide-mediated cell death
    Ram N Trivedi
    Hillman Cancer Center, University of Pittsburgh Cancer Institute, Pittsburgh, Pennsylvania 15213 1863, USA
    Cancer Res 65:6394-400. 2005
    ..Thus, the BER pathway is a major contributor to cellular resistance to temozolomide and its efficacy depends on specific BER gene expression and activity...
  38. pmc A phase II study of extended low-dose temozolomide in recurrent malignant gliomas
    Raja B Khan
    Department of Neurology, Memorial Sloan Kettering Cancer Center, New York, NY 10021, USA
    Neuro Oncol 4:39-43. 2002
    ..We conclude that the extended low-dose schedule of temozolomide is well tolerated in heavily pre-treated patients; however, our results do not support an improved rate of response or survival...
  39. ncbi Nomograms for predicting survival of patients with newly diagnosed glioblastoma: prognostic factor analysis of EORTC and NCIC trial 26981-22981/CE.3
    Thierry Gorlia
    EORTC Data Centre, Brussels, Belgium
    Lancet Oncol 9:29-38. 2008
    ....
  40. ncbi Promising survival for patients with newly diagnosed glioblastoma multiforme treated with concomitant radiation plus temozolomide followed by adjuvant temozolomide
    Roger Stupp
    Department of Medical Oncology, Centre Hospitalier Universitaire Vaudois, Lausanne, Switzerland
    J Clin Oncol 20:1375-82. 2002
    ..This phase II study was performed to determine the safety, tolerability, and efficacy of concomitant radiation plus temozolomide therapy followed by adjuvant temozolomide therapy in patients with newly diagnosed GBM...
  41. ncbi Distinct responses of xenografted gliomas to different alkylating agents are related to histology and genetic alterations
    Pascal Leuraud
    Institut National de la Santé et de la Recherche Médicale U495, Laboratoire de Biologie des Interactions Neurones Glie, Groupe Hospitalier Pitie Salpetriere, AP HP, Paris, France
    Cancer Res 64:4648-53. 2004
    ..These results suggest that the combined use of histology and molecular markers should eventually be helpful selecting the most appropriate agents for treatment of malignant oligodendrogliomas and astrocytomas...
  42. ncbi Disposition and pharmacokinetics of temozolomide in rat
    L Reyderman
    Drug Metabolism and Pharmacokinetics, Schering Plough Research Institute, Kenilworth, NJ 07033 1300, USA
    Xenobiotica 34:487-500. 2004
    ..Temozolomide was rapidly eliminated (t(1/2) = 1.2 h) and converted to MTIC. 4. Systemic exposure to MTIC was about 2% that of temozolomide. Overall, the disposition of temozolomide in rats was similar to that observed in humans...
  43. ncbi Chemoimmunotherapy for melanoma with dacarbazine and 2,4-dinitrochlorobenzene: results from a murine tumour model
    C Wack
    Department of Toxicology, , Versbacher Strasse 9, , Germany
    Melanoma Res 11:247-53. 2001
    ..In conclusion, we have established a model system that seems to be appropriate for both the optimization of this therapeutic regimen and the characterization of effector mechanisms...
  44. pmc Prerequisites for effective isolated limb perfusion using tumour necrosis factor alpha and melphalan in rats
    J H de Wilt
    Department of Surgical Oncology, University Hospital Rotterdam Dijkzigt Daniel den Hoed Cancer Centre, Rotterdam, The Netherlands
    Br J Cancer 80:161-6. 1999
    ..Moreover, the dose of TNF could be lowered to 10 microg per 5 ml perfusate, which might allow the use of TNF in less leakage-free or less inert perfusion settings...
  45. ncbi Alkylating agents and DNA polymerases
    Leon P Bignold
    Institute of Medical and Veterinary Science, Adelaide, SA 5001, Australia
    Anticancer Res 26:1327-36. 2006
    ....
  46. ncbi Temozolomide: a milestone in neuro-oncology and beyond?
    Nicole Mutter
    Multidisciplinary Oncology Center University of Lausanne Hospitals 46 Rue du Bugnon, 1011 Lausanne, Switzerland
    Expert Rev Anticancer Ther 6:1187-204. 2006
    ..Temozolomide is under investigation for other disease entities, in particular lower-grade glioma, brain metastases and melanoma...
  47. ncbi Isolated hepatic perfusion with tumor necrosis factor and melphalan for unresectable cancers confined to the liver
    H R Alexander
    Surgical Metabolism Section, Surgery Branch, National Cancer Institute, National Institutes of Health, Bethesda, MD 20892 1502, USA
    J Clin Oncol 16:1479-89. 1998
    ....
  48. ncbi The past decade of experience with isolated hepatic perfusion
    Amelia Grover
    Surgical Metabolism Section, National Cancer Institute NIH, 10 Center Drive, Building 10, Room 2B07, Bethesda, Maryland 20892 1502, USA
    Oncologist 9:653-64. 2004
    ..Patient selection is important to ensure good results with minimal morbidity and mortality. Work to define the appropriate clinical groups is ongoing at many clinical centers...
  49. ncbi Protection and in vivo selection of hematopoietic stem cells using temozolomide, O6-benzylguanine, and an alkyltransferase-expressing retroviral vector
    N Sawai
    Department of Hematology/Oncology, St. Jude Children's Research Hospital, 332 North Lauderdale, Tennessee 38105, USA
    Mol Ther 3:78-87. 2001
    ....
  50. ncbi Combined effects of adenovirus-mediated wild-type p53 transduction, temozolomide and poly (ADP-ribose) polymerase inhibitor in mismatch repair deficient and non-proliferating tumor cells
    L Tentori
    Pharmacology and Medical Oncology Section, Department of Neuroscience, University of Rome Tor Vergata, Via di Tor Vergata 135, 00133 Rome, Italy
    Cell Death Differ 8:457-69. 2001
    ..It is conceivable to envisage future possible strategies to enhance cytostatic or cytotoxic effects induced by Ad-p53, based on the use of TZM, alone or combined with PARP inhibitor for the therapy of resistant tumors...
  51. pmc A rapid and systematic review of the effectiveness of temozolomide for the treatment of recurrent malignant glioma
    J Dinnes
    Southampton Health Technology Assessment Centre, Wessex Institute for Health Research and Development, University of Southampton, Mailpoint 728, Boldrewood, Southampton SO16 7PX, UK
    Br J Cancer 86:501-5. 2002
    ..Overall the evidence-base is weak and few strong conclusions can be drawn regarding the effectiveness of temozolomide. Large, well-designed randomized controlled trails conducted in a wider patient population are needed...
  52. ncbi The palliative value of tumor necrosis factor alpha-based isolated limb perfusion in patients with metastatic sarcoma and melanoma
    Dirk J Grunhagen
    Department of Surgical Oncology, Erasmus MC Daniel den Hoed Cancer Center, Rotterdam, The Netherlands
    Cancer 106:156-62. 2006
    ..In this study, the authors investigated the palliative value of the ILP procedure to avoid amputation in patients who had Stage IV STS and melanoma...
  53. ncbi Randomised trial of high-dose chemotherapy and haemopoietic progenitor-cell support in operable breast cancer with extensive axillary lymph-node involvement
    S Rodenhuis
    Department of Medical Oncology, Netherlands Cancer Institute, Amsterdam
    Lancet 352:515-21. 1998
    ..Many physicians accept this treatment as standard care. We aimed to assess adjuvant high-dose chemotherapy in breast cancer in a phase II randomised trial...
  54. ncbi Chemotherapy in the treatment of recurrent glioblastoma multiforme: ifosfamide versus temozolomide
    F Paulsen
    Department of Radiotherapy, University of Tubingen, Germany
    J Cancer Res Clin Oncol 125:411-8. 1999
    ..In vitro analysis revealed activity for ifosfamide and temozolomide. The usefulness of these agents in recurrent disease was investigated...
  55. ncbi Inhibition of O6-alkylguanine DNA-alkyltransferase or poly(ADP-ribose) polymerase increases susceptibility of leukemic cells to apoptosis induced by temozolomide
    L Tentori
    Department of Experimental Medicine and Biochemical Sciences, University of Rome Tor Vergata, Italy
    Mol Pharmacol 52:249-58. 1997
    ..This study also supports the possible use of TZM for the treatment of acute leukemias and suggests new strategies to increase the susceptibility of tumor cells to methylating triazenes in the clinic...
  56. pmc Mechanisms of chemoresistance to alkylating agents in malignant glioma
    Jann N Sarkaria
    Department of Radiation Oncology and Pathology, Mayo Clinic, Rochester, Minnesota 55905, USA
    Clin Cancer Res 14:2900-8. 2008
    ..This article describes the diverse mechanisms of chemoresistance operating in malignant glioma and efforts to develop reliable preclinical models and novel pharmacologic approaches to overcome resistance to alkylating agents...
  57. ncbi Thresholds of O6-alkylguanine-DNA alkyltransferase which confer significant resistance of human glial tumor xenografts to treatment with 1,3-bis(2-chloroethyl)-1-nitrosourea or temozolomide
    D M Kokkinakis
    Department of Neurosurgery, University of Texas Southwestern Medical Center at Dallas, 75235 8855, USA
    Clin Cancer Res 7:421-8. 2001
    ..This study further demonstrates that there is a significant benefit of depleting AGT with nonspecific AGT inhibitors prior to treatment with either BCNU or TMZ in tumors having AGT activity >45 fmol/mg protein...
  58. pmc Allogeneic granulocyte macrophage colony-stimulating factor-secreting tumor immunotherapy alone or in sequence with cyclophosphamide for metastatic pancreatic cancer: a pilot study of safety, feasibility, and immune activation
    Dan Laheru
    Department of Oncology, The Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins, The Johns Hopkins University School of Public Health, Baltimore, Maryland 21231, USA
    Clin Cancer Res 14:1455-63. 2008
    ....
  59. pmc Synergistic effects of TNF-alpha and melphalan in an isolated limb perfusion model of rat sarcoma: a histopathological, immunohistochemical and electron microscopical study
    P T Nooijen
    Department of Pathology, University Hospital Nijmegen, The Netherlands
    Br J Cancer 74:1908-15. 1996
    ..This may result in additive cytotoxicity or inhibition of growth of residual tumour cells...
  60. ncbi Hematopoietic cell transplantation in acute lymphoblastic leukemia: better long term event-free survival with conditioning regimens containing total body irradiation
    E Granados
    Haematology Department, Hospital Universitario de la Princesa, C Diego de Leon 62, 28006 Madrid, Spain
    Haematologica 85:1060-7. 2000
    ....
  61. ncbi The use of temozolomide in recurrent malignant gliomas
    A Gaya
    Department of Radiotherapy, Hammersmith Hospitals NHS Trust, Fulham Palace Road, London W6 8RF, UK
    Cancer Treat Rev 28:115-20. 2002
    ..Further clinical studies investigating its role in neoadjuvant treatment or in combination with radiotherapy or other chemotherapeutic approaches are ongoing...
  62. ncbi Maximum tolerable dose and low-dose metronomic chemotherapy have opposite effects on the mobilization and viability of circulating endothelial progenitor cells
    Francesco Bertolini
    Division of Hematology Oncology, Department of Medicine, IFOM Fondazione Italiana per la Ricerca sul Cancro, Institute of Molecular Oncology, European Institute of Oncology, Via Ripamonti 435, 20141 Milan, Italy
    Cancer Res 63:4342-6. 2003
    ..Our findings suggest that metronomic low-dose chemotherapy regimens are particularly promising for avoiding CEP mobilization and, hence, to potentially reduce vasculogenesis-dependent mechanisms of tumor growth...
  63. pmc Temozolomide 3 weeks on and 1 week off as first-line therapy for recurrent glioblastoma: phase II study from gruppo italiano cooperativo di neuro-oncologia (GICNO)
    A A Brandes
    Department of Medical Oncology, Bellaria Hospital, 40139 Bologna, Italy
    Br J Cancer 95:1155-60. 2006
    ..The prolonged temozolomide schedule considered in the present study is followed by a high PFS-6 rate; toxicity is acceptable. Further randomised trials should therefore be conducted to confirm the efficacy of this regimen...
  64. ncbi Plasma and cerebrospinal fluid population pharmacokinetics of temozolomide in malignant glioma patients
    Sandrine Ostermann
    Multidisciplinary Oncology Center, Division of Clinical Pharmacology, Centre Hospitalier Universitaire Vaudois, Lausanne, Switzerland
    Clin Cancer Res 10:3728-36. 2004
    ....
  65. ncbi CD4+CD25+ regulatory T cells suppress tumor immunity but are sensitive to cyclophosphamide which allows immunotherapy of established tumors to be curative
    Francois Ghiringhelli
    INSERM U517, Faculty of Medicine, Dijon, France
    Eur J Immunol 34:336-44. 2004
    ..These results demonstrate the role of CD4(+)CD25(+) regulatory T cells in tumor-induced immune tolerance and the interest of regulatory T cell depletion to sensitize established tumors to immunotherapy...
  66. ncbi Antitumor effects in mice of low-dose (metronomic) cyclophosphamide administered continuously through the drinking water
    Shan Man
    Departments of Medical Biophysics, Sunnybrook and Women s College Health Sciences Centre, University of Toronto, 2075 Bayview Avenue, Toronto, Ontario, M4N 3M5 Canada
    Cancer Res 62:2731-5. 2002
    ..o. metronomic chemotherapy regimen, which proved safe, reasonably efficacious, and potentially applicable to chronic treatment. Such a regimen may be particularly well suited for integration with antiangiogenic drugs...
  67. ncbi Health-related quality of life in patients treated with temozolomide versus procarbazine for recurrent glioblastoma multiforme
    D Osoba
    Quality of Life Consulting, Vancouver, British Columbia, Canada
    J Clin Oncol 18:1481-91. 2000
    ..To determine whether chemotherapy with temozolomide (TMZ) versus procarbazine (PCB) for recurrent glioblastoma multiforme (GBM) was associated with improvement in health-related quality of life (HRQOL)...
  68. ncbi Multicenter phase II trial of temozolomide in patients with glioblastoma multiforme at first relapse
    M Brada
    The Royal Marsden Hospital, Surrey, UK
    Ann Oncol 12:259-66. 2001
    ..There are no clearly established chemotherapeutic regimens and the aim of treatment is palliation with improvement in the quality of life...
  69. pmc Phase I dose-escalation and pharmacokinetic study of temozolomide (SCH 52365) for refractory or relapsing malignancies
    M Brada
    The Royal Marsden NHS Trust, and the Institute of Cancer Research, Sutton, Surrey, UK
    Br J Cancer 81:1022-30. 1999
    ..8 h). Food produced a slight reduction (9%) in absorption of temozolomide. Temozolomide 200 mg m(-2) day(-1) for 5 days, every 28 days, is recommended for phase II studies...
  70. ncbi Phase II trial of temozolomide plus the matrix metalloproteinase inhibitor, marimastat, in recurrent and progressive glioblastoma multiforme
    Morris D Groves
    Department of Neuro Oncology, University of Texas M D Anderson Cancer Center, Houston, TX 77030, USA
    J Clin Oncol 20:1383-8. 2002
    ....
  71. ncbi Long-term follow-up of a phase II trial of oral altretamine for consolidation of clinical complete remission in women with stage III epithelial ovarian cancer in the Southwest Oncology Group
    D S Alberts
    University of Arizona Cancer Center, 1515 North Campbell Avenue, PO Box 245024, Tucson, AZ 85724 5024, USA
    Int J Gynecol Cancer 14:224-8. 2004
    ....
  72. ncbi Chemotherapeutic management of soft tissue sarcoma
    Katherine Thornton
    Department of Medical Oncology, The Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins, Baltimore, MD 21231, USA
    Surg Clin North Am 88:647-60, viii. 2008
    ..In addition, the utility of newer biologic agents in the treatment for sarcomas is considered...
  73. ncbi Inhibition of angiogenesis by non-toxic doses of temozolomide
    Hjalmar Kurzen
    Department of Dermatology, University of Heidelberg, Germany
    Anticancer Drugs 14:515-22. 2003
    ..Therefore, the antitumor activity of TMZ may, at least in part, be due to its antiangiogenic properties. The precise mechanism of its antiangiogenic action remains to be elucidated...
  74. ncbi Isolated limb perfusions with tumor necrosis factor and melphalan for locally recurrent soft tissue sarcoma in previously irradiated limbs
    T E Lans
    Department of Surgical Oncology, Erasmus MC Daniel den Hoed Cancer Center, PO Box 5201, 3008 AE Rotterdam, The Netherlands
    Ann Surg Oncol 12:406-11. 2005
    ..Because radiotherapy is known to destroy vasculature, we wanted to evaluate retrospectively whether the outcome of ILP in patients with radiotherapy for their primary tumor nonetheless showed a benefit from TNF treatment...
  75. ncbi Fifty tumor necrosis factor-based isolated limb perfusions for limb salvage in patients older than 75 years with limb-threatening soft tissue sarcomas and other extremity tumors
    Boudewijn van Etten
    Department of Surgical Oncology, University Hospital Rotterdam Daniel den Hoed Cancer Center, Rotterdam, The Netherlands
    Ann Surg Oncol 10:32-7. 2003
    ....
  76. pmc Marked inactivation of O6-alkylguanine-DNA alkyltransferase activity with protracted temozolomide schedules
    A W Tolcher
    Institute of Drug Development, Cancer Therapy and Research Center, San Antonio, TX 78229, USA
    Br J Cancer 88:1004-11. 2003
    ..5+/-16.1%, P<0.045). In conclusion, protracted administration of temozolomide, even at relatively low daily doses, leads to significant and prolonged depletion of AGAT activity, which may enhance the antitumour activity of the agent...
  77. ncbi Ecteinascidin-743 inhibits activated but not constitutive transcription
    Debbie Friedman
    Fox Chase Cancer Center, Philadelphia, Pennsylvania 19111, USA
    Cancer Res 62:3377-81. 2002
    ..These results, taken together with previous reports, leads us to suggest a mechanism whereby ET-743 is a novel, potent, and general inhibitor of activated but not uninduced transcription...
  78. ncbi Careful exclusion of non-neoplastic brain components is required for an appropriate evaluation of O6-methylguanine-DNA methyltransferase status in glioma: relationship between immunohistochemistry and methylation analysis
    Ken Sasai
    Laboratory of Molecular and Cellular Pathology, Hokkaido University Graduate School of Medicine, Sapporo, Japan
    Am J Surg Pathol 32:1220-7. 2008
    ..Therefore, to correctly establish MGMT expression in the tumor, which could be informative of glioma sensitivity to alkylating agents, exclusion of non-neoplastic brain components from analysis is required...
  79. ncbi High antitumour activity of ET743 against human tumour xenografts from melanoma, non-small-cell lung and ovarian cancer
    H R Hendriks
    NDDO Oncology, University Hospital Vrije Universiteit, Amsterdam, The Netherlands
    Ann Oncol 10:1233-40. 1999
    ..The aim of the present study was to further explore the antitumour activity of ET743 in human tumour xenografts from melanoma, non-small-cell lung and ovarian cancer...
  80. ncbi Low dose metronomic oral cyclophosphamide for hormone resistant prostate cancer: a phase II study
    R Lord
    Department of Oncology and Urology, St George s, University of London, London, UK
    J Urol 177:2136-40; discussion 2140. 2007
    ..In this study we tested the observations from animal models and evaluated the safety and efficacy of continuous low dose oral cyclophosphamide in patients with hormone resistant prostate cancer...
  81. ncbi Heterogeneity of O(6)-alkylguanine-DNA alkyltransferase activity in colorectal cancer: implications for treatment
    Nicholas P Lees
    Cancer Research UK Carcinogenesis Group, Paterson Institute for Cancer Research, The University of Manchester, UK
    Oncology 63:393-7. 2002
    ..The aim of this study was to assess whether measurement of MGMT activity in a single tumour biopsy is representative of the whole tumour...
  82. ncbi Prognostic significance of O6-methylguanine-DNA methyltransferase protein expression in patients with recurrent glioblastoma treated with temozolomide
    Motoo Nagane
    Department of Neurosurgery, Kyorin University School of Medicine, 6 20 2 Shinkawa, Mitaka, Tokyo 181 8611, Japan
    Jpn J Clin Oncol 37:897-906. 2007
    ....
  83. ncbi Metronomic low-dose oral cyclophosphamide and methotrexate plus or minus thalidomide in metastatic breast cancer: antitumor activity and biological effects
    M Colleoni
    Division of Medical Oncology, University of Milan School of Medicine, European Institute of Oncology, Milan, Italy
    Ann Oncol 17:232-8. 2006
    ..We previously demonstrated efficacy and impact on serum vascular endothelial growth factor (VEGF) for metronomic cyclophosphamide (C) and methotrexate (M) in patients with breast cancer. New metronomic schedules were investigated...
  84. ncbi Randomized phase II study of temozolomide and radiotherapy compared with radiotherapy alone in newly diagnosed glioblastoma multiforme
    Helen Athanassiou
    Radiation Oncology, St Savas Cancer Hospital, 79 Zimbrakaki St, 10445 Athens, Greece
    J Clin Oncol 23:2372-7. 2005
    ..We conducted a multicenter randomized phase II study comparing the efficacy and safety of TMZ administered concomitantly and sequentially to RT versus RT alone in patients with newly diagnosed GBM...
  85. ncbi Effect of temozolomide on central nervous system relapse in patients with advanced melanoma
    M J Paul
    Cancer Research UK Department of Medical Oncology, Christie Hospital NHS Trust, Manchester, UK
    Melanoma Res 12:175-8. 2002
    ..03). These results support the investigation of temozolomide as a replacement for DTIC in systemic treatment regimens for melanoma...
  86. ncbi Tumor necrosis factor-alpha-induced protein 3 as a putative regulator of nuclear factor-kappaB-mediated resistance to O6-alkylating agents in human glioblastomas
    Markus Bredel
    Division of Oncology, Center for Clinical Sciences Research, Institute for Computational and Mathematical Engineering, Department of Neurosurgery, Stanford University School of Medicine, Stanford, CA 94305 5151, USA
    J Clin Oncol 24:274-87. 2006
    ..Pre-existing and acquired drug resistance are major obstacles to the successful treatment of glioblastomas...
  87. ncbi Metronomic therapy with cyclophosphamide induces rat lymphoma and sarcoma regression, and is devoid of toxicity
    V R Rozados
    Instituto de Genética Experimental, Facultad de Ciencias Medicas, Universidad Nacional de Rosario, Santa Fe 3100 2000 Rosario, Argentina
    Ann Oncol 15:1543-50. 2004
    ..Our aim was to investigate the clinical efficacy and toxicity of metronomic administration of low-dose cyclophosphamide (Cy) in lymphoma and sarcoma rat tumour models...
  88. ncbi Four-hourly scheduling of temozolomide improves tumour growth delay but not therapeutic index in A375M melanoma xenografts
    M R Middleton
    Cancer Research Campaign Department of Medical Oncology, Christie Hospital NHS Trust, Manchester, UK
    Cancer Chemother Pharmacol 45:15-20. 2000
    ....
  89. ncbi Temozolomide pharmacodynamics in patients with metastatic melanoma: dna damage and activity of repair enzymes O6-alkylguanine alkyltransferase and poly(ADP-ribose) polymerase-1
    E Ruth Plummer
    Northern Institute for Cancer Research, University of Newcastle upon Tyne, Newcastle upon Tyne, United Kingdom
    Clin Cancer Res 11:3402-9. 2005
    ..The current study was done to define the effect of temozolomide on DNA integrity and relevant repair enzymes as a prelude to a phase I trial of the combination of temozolomide with a PARP inhibitor...
  90. ncbi Thyroid hormone and insulin-like growth factor-I in patients with multiple myeloma treated with melphalan and prednisone
    Antoni Hrycek
    Department of Internal Disease and Clinical Pharmacology, Medical University of Silesia, Katowice, Poland
    Arch Med Res 37:74-8. 2006
    ..The aim of this study was the comparative assessment of serum levels of selected hormones and insulin-like growth factor-I (IGF-I) in patients with multiple myeloma (MM) during applied therapy...
  91. pmc Effective treatment of advanced human melanoma metastasis in immunodeficient mice using combination metronomic chemotherapy regimens
    William Cruz-Munoz
    Sunnybrook Health Sciences Centre, Molecular and Cellular Biology Research, Toronto, Ontario, Canada
    Clin Cancer Res 15:4867-74. 2009
    ..Although dacarbazine chemotherapy remains the standard therapy, it mediates only low response rates, usually of short duration, even when combined with other chemotherapeutic agents. Thus, new therapeutic strategies are urgently needed...
  92. ncbi A multitargeted, metronomic, and maximum-tolerated dose "chemo-switch" regimen is antiangiogenic, producing objective responses and survival benefit in a mouse model of cancer
    Kristian Pietras
    Department of Biochemistry and Biophysics, Diabetes and Comprehensive Cancer Centers, University of California San Francisco, 513 Parnassas Avenue, San Francisco, CA 94143, USA
    J Clin Oncol 23:939-52. 2005
    ..Additionally, vascular endothelial growth factor receptor (VEGFR) inhibitors and metronomic chemotherapy show modest benefit against early- but not late-stage disease...
  93. ncbi Chemotherapy for brain tumors--a new beginning
    Lisa M DeAngelis
    N Engl J Med 352:1036-8. 2005
  94. ncbi Ecteinascidin-743 (ET-743): early test or effective treatment in soft tissue sarcomas?
    Jaap Verweij
    J Clin Oncol 23:5420-3. 2005
  95. ncbi Outcome and prognostic factor analysis of 217 consecutive isolated limb perfusions with tumor necrosis factor-alpha and melphalan for limb-threatening soft tissue sarcoma
    Dirk J Grunhagen
    Department of Surgical Oncology, Erasmus MC Daniel den Hoed Cancer Center, Rotterdam, The Netherlands
    Cancer 106:1776-84. 2006
    ..A mature, large, single-institution experience with 217 consecutive ILPs for STS of the extremity is reported...
  96. ncbi Bioluminescence monitoring of intracranial glioblastoma xenograft: response to primary and salvage temozolomide therapy
    Eduard B Dinca
    Neuroscience Graduate Program, Mayo Clinic, Rochester, Minnesota, USA
    J Neurosurg 107:610-6. 2007
    ..In the current study we have applied BLI to the analysis of clinically relevant issues involving use of the DNA methylating agent temozolomide (TMZ) in a mouse model...
  97. ncbi Hepatic artery infusion of high-dose melphalan at reduced flow during isolated hepatic perfusion for the treatment of colorectal metastases confined to the liver: a clinical and pharmacologic evaluation
    L B J van Iersel
    Department of Clinical Oncology, Leiden University Medical Center, Albinusdreef 2, 2333 ZA Leiden, The Netherlands
    Eur J Surg Oncol 33:874-81. 2007
    ..We believe that the low flow and pressure rates found in this study can result in reduced drug penetration of the tumour and thus limited tumour response...
  98. ncbi Non-sufficient cell cycle control as possible clue for the resistance of human malignant glioma cells to clinically relevant treatment conditions
    D Trog
    Department of Radiology, Friedrich Wilhelms University of Bonn, Bonn, Germany
    Amino Acids 32:373-9. 2007
    ....
  99. pmc Effects of photochemically activated alkylating agents of the FR900482 family on chromatin
    Vidya Subramanian
    Department of Biochemistry and Molecular Biology, Colorado State University, Fort Collins, CO 80523, USA
    Chem Biol 14:553-63. 2007
    ..Finally, crosslinked plasmid DNA is inefficiently assembled into chromatin. Our studies suggest pathways for the clinical effectiveness of this class of reagents...
  100. ncbi Pharmacokinetic study of temozolomide on a daily-for-5-days schedule in Japanese patients with relapsed malignant gliomas: first study in Asians
    Tomokazu Aoki
    Department of Neurosurgery, Kitano Hospital Medical Research Institute, 2 4 2 Ogimachi, Kita ku, Osaka 530 8480, Japan
    Int J Clin Oncol 12:341-9. 2007
    ..Temozolomide (TMZ) is widely used in Europe and the United States. For the safe use of TMZ in the Japanese, as representative of Asians, the pharmacokinetics of TMZ was investigated in Japanese patients and compared to that in Caucasians...
  101. ncbi ET-743: a novel agent with activity in soft-tissue sarcomas
    Jerome Fayette
    Hopital Edouard Herriot, Service d Oncologie Medicale, France
    Curr Opin Oncol 18:347-53. 2006
    ..ET-743 (ecteinascidin-743, trabectedin, Yondelis) is a natural marine product that has shown clinical activity in sarcoma. This paper reviews the current knowledge on this compound...

Research Grants66

  1. OREGON CHILD HEALTH RESEARCH CENTER
    HENRY NICHOLSON; Fiscal Year: 2005
    ..An effective formal educational program has been implemented and will be provided during the first two years of training for each Junior Investigator. ..
  2. Ape1, oxidative stress and glioma alkylator resistance
    JOHN SILBER; Fiscal Year: 2008
    ..Evidence for a contribution of Ap endo to resistance would identify a new target for anti-resistance strategies directed against Ape1/Ref-1 (the major human Ap endo), either alone or together with MGMT. ..
  3. Prognostic Modeling of High-Risk Primary Breast Cancer
    Yago Nieto; Fiscal Year: 2003
    ..abstract_text> ..
  4. NABTC CENTRAL OPERATION GRANT (UCSF PROJECT LEADER)
    Michael Prados; Fiscal Year: 2008
    ..The NABTC will treat patients using novel therapeutic agents with the ultimate goal to increase quality, and hopefully, overall survival in this patient population. ..
  5. NABTC Member Intitution Grant (UCSF Project Leader)
    Susan Chang; Fiscal Year: 2008
    ..The overall goal of this program is to more effectively treat patients with primary brain tumors, especially malignant glioma, with the purpose of increasing the duration and quality of survival. ..
  6. PEDIATRIC BRAIN TUMOR CLINICAL TRIAL CONSORTIUM
    Michael Prados; Fiscal Year: 2003
    ..The aim of these treatment approaches is to increase disease-free and overall survival in children with brain tumors. ..
  7. Phase I Clinical Trials of Anti-Cancer Agents
    Francis Giles; Fiscal Year: 2007
    ..abstract_text> ..
  8. SYNTHESIS AND EVALUATION OF NOVEL PHOSPHORAMIDATES
    RICHARD BORCH; Fiscal Year: 2005
    ..The ultimate goal is to exploit the unique properties of phosphoramidate chemistry to develop new drugs that exhibit clinical efficacy against resistant or poorly responsive solid tumors. ..
  9. Phase II Trial of Thalidomide in Primary Amyloidosis
    Angela Dispenzieri; Fiscal Year: 2002
    ..The ultimate goal of the proposed studies is to improve the prognosis of patient with this fatal disease. ..
  10. QUALITY OF LIFE FOLLOWING SUCCESSFUL THERAPY OF AML
    HENRY NICHOLSON; Fiscal Year: 2001
    ..Completion of this study should help pediatric oncologists fight AML in ways that optimize both survival and QOL. ..
  11. Halogenated Alkenes and Microsomal GSH-transferases
    Michael J Kelner; Fiscal Year: 2010
    ..4] To determine the relative contribution of MGST1 and MGST2 to cellular antioxidant capacity through studies utilizing human MGST1 and MGST2 null cells. ..
  12. GPX1 ENZYME REGULATION BY OXIDATIVE XENOBIOTICS
    Michael Kelner; Fiscal Year: 2002
    ..These studies will provide critical information regarding cellular response to oxidative stress and aid in determining if a common regulatory mechanism exists for GSH-dependent enzymes. ..
  13. COMBATING ALKYLATING AGENT RESISTANCE IN HUMAN GLIOMAS
    JOHN SILBER; Fiscal Year: 2002
    ..In an effort to define the role of 3-MAG in clinical drug resistance, enzyme levels will be correlated with response to alkylator adjuvant therapy and clinical course. ..
  14. NABTT-Consortium Therapeutic Studies of CNS Malignancies
    Stuart Grossman; Fiscal Year: 2008
    ..abstract_text> ..
  15. Ap endo as a predictor of response to glioma therapy
    JOHN SILBER; Fiscal Year: 2006
    ..unreadable] [unreadable]..
  16. Fostriecin and Related Protein Phosphatase Inhibitors
    Dale Boger; Fiscal Year: 2005
    ....
  17. COORDINATED REGULATION OF ANTIOXIDANT ENZYMES
    Michael Kelner; Fiscal Year: 2005
    ..abstract_text> ..
  18. B7-CD28/CTLA-4 INTERACTIONS IN IMMUNITY TO TUMORS
    MARGALIT MOKYR; Fiscal Year: 2001
    ..This information will in turn facilitate the design of rational approaches to manipulate this key immunoregulatory pathway to the benefit of the tumor bearers. ..
  19. Toll-Like Receptor 3 Activation in Astrocytes
    GREGORY KONAT; Fiscal Year: 2006
    ..Moreover, because TLR3 can also be activated by RNA released from damaged cells, the outcomes of this study will also be applicable to neurodegenerative conditions of non-viral etiology. [unreadable] [unreadable]..
  20. Molecular Dissection of T Cell Anergy
    Thomas Gajewski; Fiscal Year: 2005
    ..Ultimately, a complete understanding of the anergic state on the molecular level should guide the development of novel pharmacologic therapies to promote or reverse peripheral tolerance in vivo. ..
  21. Topoisomerase II Site-Directed Alkylation of DNA
    Laurence Hurley; Fiscal Year: 2006
    ..A variety of techniques, including solution and parallel synthesis, in vitro cytotoxicity assays, DNA chip array analysis, gel electrophoresis, promoter assays, and LM-PCR, will be used to carry out these objectives. ..
  22. Treatment of Early Stage Multiple Myeloma
    S Rajkumar; Fiscal Year: 2006
    ..BM angiogenesis will be studied using immunostaining (IHC) for CD34 and an in vitro human angiogenesis assay. VEGF expression will be studied using IHC and quantitative RT-PCR. ..
  23. Irradiation Damage and Protection of Pulmonary Endothelium Oxidative Lipidomics
    Valerian E Kagan; Fiscal Year: 2010
    ....
  24. T Cell Immunotherapy of Pediatric Brain Tumors
    GREGORY PLAUTZ; Fiscal Year: 2005
    ..Alternatively if cross -reactive glioma Ags are identified it would stimulate future studies for molecular characterization of the antigens and provide the rationale for development of a uniform glioma vaccine. ..
  25. FUNCTION OF NOGGIN IN HAIR FOLLICLE GROWTH AND DISEASE
    Vladimir Botchkarev; Fiscal Year: 2006
    ....
  26. CNS Gene Delivery and Imaging in Brain Tumor Therapy
    Edward Neuwelt; Fiscal Year: 2007
    ..abstract_text> ..
  27. AAV-Based Plasmacytoid Dendritic Cell Cancer Vaccine
    Pierre L Triozzi; Fiscal Year: 2010
    ....
  28. Temodar Resistance in CNS Tumors
    Henry Friedman; Fiscal Year: 2008
    ..abstract_text> ..
  29. VEGF Function in B-CLL
    Neil E Kay; Fiscal Year: 2010
    ..3) Does the VEGF/VEGF-R pathway(s) found in CLL B cells correlate with either clinical and/or critical biologic parameters in B-CLL? ..
  30. DGK in T Cell Regulation and Tolerance
    Thomas F Gajewski; Fiscal Year: 2010
    ..Ti U,0 ._0 ... ur tow 5a' c' OUP O-0 N-0 0-0 V,12 oar aux. :E, -'1 .., (gyp afl' coo COD m='(Dm o03-' _=c 3m03 l17 CDG'O COB 111 ..
  31. Gene Transfer to Facilitate Dose-Intensification in the Treatment of Pediatric B*
    Lars Wagner; Fiscal Year: 2007
    ..We hypothesize this strategy will be well tolerated and allow for meaningful dose escalation through chemoprotection afforded by gene transfer into hematopoietic stem cells. [unreadable] [unreadable] [unreadable]..
  32. Uveal Melanoma Micrometastasis
    Pierre L Triozzi; Fiscal Year: 2010
    ..Micrometastases, microscopic deposits of tumor that have spread via the bloodstream, are present in many patients with uveal melanoma at diagnosis. This project will test new methods of identifying and inhibiting these deposits. ..
  33. Mentored Research in Ovarian Cancer
    Michael Seiden; Fiscal Year: 2006
    ..The P.l.'s dual role as a clinical research director and laboratory P.I. provides fertile opportunity for translation between the clinic and the laboratory. [unreadable] [unreadable] [unreadable] [unreadable]..
  34. G-Quadruplexes as Targets for Drug Design
    Laurence Hurley; Fiscal Year: 2007
    ..In vitro and in vivo evaluation will be carried out to evaluate these leads prior to preclinical development and phase 1 clinical trials carried out in collaboration with Cylene Pharmaceuticals. ..
  35. Biochemical/Molecular Changes Upon Naive T Cell Priming
    Thomas Gajewski; Fiscal Year: 2005
    ....
  36. Diepoxide Cross-Linking of DNA
    JULIE MILLARD; Fiscal Year: 2003
    ..Denaturing PAGE will also be used to characterize DNA reaction products of epichiorohydrin to elucidate the impact of a three-carbon chain length in cross-linking. ..
  37. ZD1839 Therapy of Glioblastoma Multiforme
    Henry Friedman; Fiscal Year: 2002
    ....
  38. INVESTIGATING THE MECHANISMS OF PRB TUMOR SUPPRESSION
    Arnab Chakravarti; Fiscal Year: 2003
    ..Specific Aim number 3: To determine whether the deregulation of E2F dependent transcription is correlated with the tumorigenic potential of RB -/- cells in-vivo. ..
  39. PREMATURE MENOPAUSE IN SURVIVORS OF CHILDHOOD CANCER
    Charles Sklar; Fiscal Year: 2002
    ..The large size of the study population, the heterogeneity of diagnoses and exposures, combined with the extensive treatment data, will allow assessment of interaction between the major risk factors of interest. ..
  40. MESNA METABOLISM AND DISPOSITION
    MARSHALL GOREN; Fiscal Year: 2001
    ..These studies also will position us to test the effect of complex combinatorial therapies on cardiac and multi-organ toxicity. ..
  41. OXIDATIVE STRESS, APOPTOSIS AND DRUG RESISTANCE
    Istvan Boldogh; Fiscal Year: 2003
    ..abstract_text> ..
  42. PEDIATRIC BRAIN TUMOR CLINICAL TRIALS CONSORTIUM
    Henry Friedman; Fiscal Year: 2003
    ..abstract_text> ..
  43. COPPER/ALBUMIN REDOX-CYCLING IN PREECLAMPSIA
    Valerian Kagan; Fiscal Year: 2003
    ....
  44. Colorectal Screening Capacity Building Conference
    David Alberts; Fiscal Year: 2003
    ..Continued capacity building and future collaboration will also be woven into this conference to serve as a stone to build upon in the future. ..
  45. PATHOBIOCHEMISTRY OF ACUTE PROMYELOCYTIC LEUKEMIA
    Edward Yeh; Fiscal Year: 2004
    ..These studies should provide novel insights into the mechanism and function of sentrinization and increase our understanding of the pathogenesis of acute promyelocytic leukemia. ..
  46. FLT PET imaging for evaluating molecular therapeutics
    Jann Sarkaria; Fiscal Year: 2005
    ..abstract_text> ..
  47. TARGETED RADIOTHERAPY FOR EWING'S SARCOMA
    Douglas Hawkins; Fiscal Year: 2005
    ....
  48. INFLAMMATORY APOPTOSIS AFTER SPINAL CORD INJURY
    Chung Hsu; Fiscal Year: 2001
    ..The ultimate goal of this project is to enhance functional recovery after SCI through a reduction in ODC death. ..
  49. Overcoming Barriers to Early Phase Clinical Trials
    Bruce Chabner; Fiscal Year: 2004
    ....
  50. PLASTICITY OF LUT INTERNEURONS FOLLOWING SPINAL CORD INJ
    MARGARET VIZZARD; Fiscal Year: 2004
    ....
  51. FT-IR/GC-MS MODELS FOR PREDICTING PROSTATE CANCER
    DONALD MALINS; Fiscal Year: 2002
    ..At the conclusion of these studies we expect to have significantly increased understanding of the etiology of prostate cancer and established a promising basis for cancer prediction. ..
  52. B CLL Subtypes--Correlation with Clinical Outcome
    Neil Kay; Fiscal Year: 2002
    ....
  53. Therapy of Temodar plus O6-Benzylguanine in Malignant G*
    Jennifer Quinn; Fiscal Year: 2004
    ..abstract_text> ..
  54. TRIGGERING OF ABERRANT CPG ISLAND METHYLATION
    Russ Pieper; Fiscal Year: 2002
    ..These studies represent a first step in understanding the gene silencing process and will ultimately contribute to the development of therapies addressed at controlling gene expression. ..
  55. THERAPEUTIC STUDIES OF ANAPLASTIC GLIOMAS
    LOUIS NABORS; Fiscal Year: 2008
    ..This proposal thus builds on our extensive clinical investigative expertise within the context of a well-established multi-institutional brain tumor treatment consortium. ..
  56. DENDRITIC CELL BASED VACCINATION FOR MULTIPLE MYELOMA
    Cristina Gasparetto; Fiscal Year: 2007
    ..abstract_text> ..
  57. Endpoint Analyses of Anti-Integrin Therapy for Gliomas
    LOUIS NABORS; Fiscal Year: 2004
    ..Data from these studies will be critically important in developing, refining and validating non-invasive methodologies for timely assessment of specific anti-angiogenic therapies for malignant brain tumors in patients. ..
  58. Post-transcriptional Regulation Requires Phosphorylation of HuR in Glioma
    LOUIS NABORS; Fiscal Year: 2009
    ..at the top of each printed page and each continuation page. RESEARCH GRANT TABLE OF CONTENTS Page Numbers Face Page 1 Description, ..
  59. INTEGRIN ANTAGONISTS IN GLIOMA BIOLOGY, IMAGING, THERAPY
    Tom Mikkelsen; Fiscal Year: 2003
    ..abstract_text> ..
  60. NEW APPLICATIONS IN BRAIN TUMOR THERAPY
    Tom Mikkelsen; Fiscal Year: 2008
    ..These efforts speak to the ultimate goal of our group and NABTT Consortium: improving the outcome of brain tumor patients. ..
  61. DNA Adducts Formed by Dopamine
    William Bodell; Fiscal Year: 2004
    ..In addition, the results of these studies will provide unique molecular markers that will be used in future studies to evaluate whether this process is occurring in the substantia nigra of human brain. ..
  62. A MULTI-USE GLIOMA BIOREPOSITORY
    Tom Mikkelsen; Fiscal Year: 2006
    ..We seek support to expand this multi-use glioma biorepository into an ongoing resource of the best characterized glioma material with clinical correlative and genomic data available. ..
  63. MOLECULAR GLIOMA THERAPIES AND DIAGNOSTICS
    Tom Mikkelsen; Fiscal Year: 2004
    ..abstract_text> ..
  64. DNA ADDUCTS FORMED DURING BRAIN TUMOR THERAPY
    William Bodell; Fiscal Year: 2001
    ..Number of treatment. These studies will be the first to investigate the formation of BCNU derived DNA abducts in a ic. Brain tumor model. ..