Tim P Hughes

Summary

Affiliation: South Australia
Country: Australia

Publications

  1. pmc Cancer treatment with kinase inhibitors: what have we learnt from imatinib?
    D M Ross
    Division of Haematology, Institute of Medical and Veterinary Science, PO Box 14 Rundle Mall, Adelaide SA 5000, Australia
    Br J Cancer 90:12-9. 2004
  2. doi request reprint Impact of baseline BCR-ABL mutations on response to nilotinib in patients with chronic myeloid leukemia in chronic phase
    Timothy Hughes
    Institute of Medical and Veterinary Science, Hanson Center for Cancer Research, Department of Hematology, Adelaide, 5000, Australia
    J Clin Oncol 27:4204-10. 2009
  3. ncbi request reprint Clinical strategies to achieve an early and successful response to tyrosine kinase inhibitor therapy
    Timothy Hughes
    Division of Haematology, Institute of Medical and Veterinary Science, Adelaide, SA, Australia
    Semin Hematol 46:S11-5. 2009
  4. doi request reprint Impact of early dose intensity on cytogenetic and molecular responses in chronic- phase CML patients receiving 600 mg/day of imatinib as initial therapy
    Timothy P Hughes
    Institute of Medical and Veterinary Science, Adelaide, Australia
    Blood 112:3965-73. 2008
  5. ncbi request reprint Molecular monitoring of BCR-ABL as a guide to clinical management in chronic myeloid leukaemia
    Timothy Hughes
    Institute of Medical and Veterinary Science, Frome Road, Adelaide, 5000 SA, Australia
    Blood Rev 20:29-41. 2006
  6. ncbi request reprint Frequency of major molecular responses to imatinib or interferon alfa plus cytarabine in newly diagnosed chronic myeloid leukemia
    Tim P Hughes
    Institute of Medical and Veterinary Science, Adelaide, SA, Australia
    N Engl J Med 349:1423-32. 2003
  7. ncbi request reprint Renal toxicity after total body irradiation
    Martin Borg
    Department of Radiation Oncology, Royal Adelaide Hospital, The University of Adelaide, North Terrace, Adelaide, SA 5000, Australia
    Int J Radiat Oncol Biol Phys 54:1165-73. 2002
  8. ncbi request reprint In vitro sensitivity to imatinib-induced inhibition of ABL kinase activity is predictive of molecular response in patients with de novo CML
    Deborah White
    Division of Haematology, Institute of Medical and Veterinary Science IMVS and Hanson Institute, Adelaide, Australia
    Blood 106:2520-6. 2005
  9. ncbi request reprint Efficacy and safety of imatinib in patients with chronic myeloid leukemia and complete or near-complete cytogenetic response to interferon-alpha
    Susan Branford
    Division of Molecular Pathology, Institute of Medical and Veterinary Science, Adelaide, SA, Australia
    Cancer 110:801-8. 2007
  10. ncbi request reprint Most CML patients who have a suboptimal response to imatinib have low OCT-1 activity: higher doses of imatinib may overcome the negative impact of low OCT-1 activity
    Deborah L White
    Division of Haematology, Institute of Medical and Veterinary Science, Adelaide, Australia
    Blood 110:4064-72. 2007

Detail Information

Publications33

  1. pmc Cancer treatment with kinase inhibitors: what have we learnt from imatinib?
    D M Ross
    Division of Haematology, Institute of Medical and Veterinary Science, PO Box 14 Rundle Mall, Adelaide SA 5000, Australia
    Br J Cancer 90:12-9. 2004
    ..It is clear that the identification of appropriate targets (activated kinases) and monitoring levels of response (to recognise emerging resistance) are essential to optimise clinical management...
  2. doi request reprint Impact of baseline BCR-ABL mutations on response to nilotinib in patients with chronic myeloid leukemia in chronic phase
    Timothy Hughes
    Institute of Medical and Veterinary Science, Hanson Center for Cancer Research, Department of Hematology, Adelaide, 5000, Australia
    J Clin Oncol 27:4204-10. 2009
    ..In this subanalysis of a phase II study of nilotinib in patients with imatinib-resistant or imatinib-intolerant CML-CP, the occurrence and impact of baseline and newly detectable BCR-ABL mutations were assessed...
  3. ncbi request reprint Clinical strategies to achieve an early and successful response to tyrosine kinase inhibitor therapy
    Timothy Hughes
    Division of Haematology, Institute of Medical and Veterinary Science, Adelaide, SA, Australia
    Semin Hematol 46:S11-5. 2009
    ..Regular monitoring of response is crucial to maximize therapeutic success, and improved understanding of the factors affecting response will guide future clinical strategies...
  4. doi request reprint Impact of early dose intensity on cytogenetic and molecular responses in chronic- phase CML patients receiving 600 mg/day of imatinib as initial therapy
    Timothy P Hughes
    Institute of Medical and Veterinary Science, Adelaide, Australia
    Blood 112:3965-73. 2008
    ..Superior responses achieved in patients able to tolerate imatinib at 600 mg suggests that early dose intensity may be critical to optimize response in CP-CML. The trial was registered at www.ANZCTR.org.au as #ACTRN12607000614493...
  5. ncbi request reprint Molecular monitoring of BCR-ABL as a guide to clinical management in chronic myeloid leukaemia
    Timothy Hughes
    Institute of Medical and Veterinary Science, Frome Road, Adelaide, 5000 SA, Australia
    Blood Rev 20:29-41. 2006
    ..Therefore, these assays can be used as a screening strategy for mutation analysis. As second generation kinase inhibitors commence clinical trials, the molecular response will be a primary end-point that determines efficacy...
  6. ncbi request reprint Frequency of major molecular responses to imatinib or interferon alfa plus cytarabine in newly diagnosed chronic myeloid leukemia
    Tim P Hughes
    Institute of Medical and Veterinary Science, Adelaide, SA, Australia
    N Engl J Med 349:1423-32. 2003
    ..We measured levels of BCR-ABL transcripts in the blood of all patients in this trial who had a complete cytogenetic remission...
  7. ncbi request reprint Renal toxicity after total body irradiation
    Martin Borg
    Department of Radiation Oncology, Royal Adelaide Hospital, The University of Adelaide, North Terrace, Adelaide, SA 5000, Australia
    Int J Radiat Oncol Biol Phys 54:1165-73. 2002
    ..To evaluate the incidence of renal dysfunction after total body irradiation (TBI)...
  8. ncbi request reprint In vitro sensitivity to imatinib-induced inhibition of ABL kinase activity is predictive of molecular response in patients with de novo CML
    Deborah White
    Division of Haematology, Institute of Medical and Veterinary Science IMVS and Hanson Institute, Adelaide, Australia
    Blood 106:2520-6. 2005
    ..The IC50imatinib potentially provides a new prognostic indicator for molecular response in patients treated with imatinib...
  9. ncbi request reprint Efficacy and safety of imatinib in patients with chronic myeloid leukemia and complete or near-complete cytogenetic response to interferon-alpha
    Susan Branford
    Division of Molecular Pathology, Institute of Medical and Veterinary Science, Adelaide, SA, Australia
    Cancer 110:801-8. 2007
    ..Imatinib offers clear quality of life advantages. Furthermore, patients who achieve a major molecular response (MMR) while receiving imatinib are likely to remain progression free...
  10. ncbi request reprint Most CML patients who have a suboptimal response to imatinib have low OCT-1 activity: higher doses of imatinib may overcome the negative impact of low OCT-1 activity
    Deborah L White
    Division of Haematology, Institute of Medical and Veterinary Science, Adelaide, Australia
    Blood 110:4064-72. 2007
    ..This pretherapy assay identifies patients at greatest risk of suboptimal response where dose intensity is critical, and those likely to respond equally well to standard dose imatinib...
  11. ncbi request reprint Measurement of in vivo BCR-ABL kinase inhibition to monitor imatinib-induced target blockade and predict response in chronic myeloid leukemia
    Deborah White
    Division of Hematology, Institute of Medical and Veterinary Science, Adelaide, Australia
    J Clin Oncol 25:4445-51. 2007
    ..This suggests that patient-tailored dosing may be more rational than a fixed dose for all. Dose optimization potentially could be based on accurate measurement of the level of BCR-ABL kinase inhibition achieved in vivo...
  12. ncbi request reprint BCR-ABL messenger RNA levels continue to decline in patients with chronic phase chronic myeloid leukemia treated with imatinib for more than 5 years and approximately half of all first-line treated patients have stable undetectable BCR-ABL using strict se
    Susan Branford
    Institute of Medical and Veterinary Science, Adelaide, Australia
    Clin Cancer Res 13:7080-5. 2007
    ..We determined whether BCR-ABL continues to decline with longer imatinib exposure and the incidence and consequence of undetectable BCR-ABL...
  13. doi request reprint Desirable performance characteristics for BCR-ABL measurement on an international reporting scale to allow consistent interpretation of individual patient response and comparison of response rates between clinical trials
    Susan Branford
    Institute of Medical and Veterinary Science, Adelaide, Australia
    Blood 112:3330-8. 2008
    ..This indicates that the IS can deliver accurate comparison of molecular response rates between clinical trials when measured by different laboratories...
  14. doi request reprint Managing imatinib resistance in chronic myeloid leukaemia
    Michael Osborn
    Directorate of Haematology, Australia, SA Pathology, Adelaide, South Australia, Australia
    Curr Opin Hematol 17:97-103. 2010
    ..The aim of this review is to aid clinicians in the recognition, investigation and appropriate treatment of imatinib resistance...
  15. pmc Monitoring CML patients responding to treatment with tyrosine kinase inhibitors: review and recommendations for harmonizing current methodology for detecting BCR-ABL transcripts and kinase domain mutations and for expressing results
    Timothy Hughes
    Institute of Medical and Veterinary Science, Adelaide, Australia
    Blood 108:28-37. 2006
    ..We recognize that our recommendations are provisional and will require revision as new evidence emerges...
  16. ncbi request reprint Non-HLA immunogenetic polymorphisms and the risk of complications after allogeneic hemopoietic stem-cell transplantation
    Charles Mullighan
    Research and Development, Australian Red Cross Blood Service SA, Adelaide, Australia
    Transplantation 77:587-96. 2004
    ..However, prior studies have been limited by small sample size and limited genotyping...
  17. ncbi request reprint Detection of BCR-ABL mutations and resistance to imatinib mesylate
    Susan Branford
    Division of Molecular Pathology, Institute of Medical and Veterinary Science, South Australia
    Methods Mol Med 125:93-106. 2006
    ..The sequence is compared to an ABL kinase domain reference sequence using sequencing analysis software, which aligns the sequences and highlights single or multiple mutations...
  18. ncbi request reprint Imatinib compared with interferon and low-dose cytarabine for newly diagnosed chronic-phase chronic myeloid leukemia
    Stephen G O'Brien
    University of Newcastle, Newcastle, United Kingdom
    N Engl J Med 348:994-1004. 2003
    ..We compared the efficacy of imatinib with that of interferon alfa combined with low-dose cytarabine in newly diagnosed chronic-phase CML...
  19. doi request reprint Intermittent target inhibition with dasatinib 100 mg once daily preserves efficacy and improves tolerability in imatinib-resistant and -intolerant chronic-phase chronic myeloid leukemia
    Neil P Shah
    Division of Hematology Oncology, University of California, San Francisco School of Medicine, Box 1270, 505 Parnassus Ave, San Francisco, CA 94143, USA
    J Clin Oncol 26:3204-12. 2008
    ..Once-daily treatment resulted in less toxicity, suggesting that toxicity results from continuous inhibition of unintended targets. Here, a dose- and schedule-optimization study is reported...
  20. doi request reprint Optimizing outcomes for patients with advanced disease in chronic myelogenous leukemia
    Francis J Giles
    Professor of Medicine, and Chief, Division of Hematology and Medical Oncology, University of Texas Health Science Center at San Antonio, San Antonio, TX 78229, USA
    Semin Oncol 35:S1-17; quiz S18-20. 2008
    ..Other areas such as microRNA profiling and DNA methylation patterns are likely to provide important information...
  21. ncbi request reprint Nilotinib (formerly AMN107), a highly selective BCR-ABL tyrosine kinase inhibitor, is active in patients with imatinib-resistant or -intolerant accelerated-phase chronic myelogenous leukemia
    Philipp Le Coutre
    Campus Virchow Klinikum, Charite Universitatsmedizin, Berlin, Germany
    Blood 111:1834-9. 2008
    ..In conclusion, nilotinib is an effective and well-tolerated treatment in imatinib-resistant and -intolerant CML-AP. This trial is registered at www.clinicaltrials.gov as NCT00384228...
  22. ncbi request reprint Evolving concepts in the management of chronic myeloid leukemia: recommendations from an expert panel on behalf of the European LeukemiaNet
    Michele Baccarani
    Department of Hematology Oncology L and A Seràgnoli, S Orsola Malpighi Hospital, Via Massarenti 9, 40138 Bologna, Italy
    Blood 108:1809-20. 2006
    ..The importance of regular monitoring at experienced centers was highlighted...
  23. ncbi request reprint Clinical resistance to imatinib: mechanisms and implications
    Andreas Hochhaus
    III Medizinische Klinik, Fakultät für Klinische Medizin Mannheim, Universitat Heidelberg, Wiesbadener Strasse 7 11, 68305 Mannheim, Germany
    Hematol Oncol Clin North Am 18:641-56, ix. 2004
    ..Cytogenetic and molecular analyses at the time of resistance are suggested to guide therapy...
  24. ncbi request reprint Dasatinib or high-dose imatinib for chronic-phase chronic myeloid leukemia after failure of first-line imatinib: a randomized phase 2 trial
    Hagop Kantarjian
    Department of Leukemia, University of Texas M D Anderson Cancer Center, Houston, TX 77230 1402, USA
    Blood 109:5143-50. 2007
    ..Dasatinib represents a safe and effective therapy for CP-CML resistant to conventional imatinib doses with improved cytogenetic and molecular response rates and progression-free survival relative to high-dose imatinib...
  25. ncbi request reprint Five-year follow-up of patients receiving imatinib for chronic myeloid leukemia
    Brian J Druker
    Oregon Health and Science University Cancer Institute, L592, 3181 SW Sam Jackson Park Rd, Portland, OR 97239, USA
    N Engl J Med 355:2408-17. 2006
    ..Imatinib inhibits this kinase, and in a short-term study was superior to interferon alfa plus cytarabine for newly diagnosed CML in the chronic phase. For 5 years, we followed patients with CML who received imatinib as initial therapy...
  26. ncbi request reprint Role of allogeneic stem cell transplantation for adult chronic myeloid leukemia in the imatinib era
    Andrew Grigg
    Department of Clinical Haematology and Bone Marrow Transplantation, Royal Melbourne Hospital, Melbourne, Australia
    Biol Blood Marrow Transplant 12:795-807. 2006
    ..The potential efficacy and safety of clinical trials combining reduced intensity alloSCT with ABL kinase inhibitor therapy warrants further consideration...
  27. ncbi request reprint Monitoring of minimal residual disease in chronic myeloid leukemia
    Stefan Faderl
    Department of Leukemia, University of Texas M D Anderson Cancer Center, Box 428, 1515 Holcombe Bouelvard, Houston, TX 77030, USA
    Hematol Oncol Clin North Am 18:657-70, ix-x. 2004
    ..Although correlations have been established between positive test results and probability of relapse, no absolute guidelines for monitoring exist, especially for patients treated with imatinib...
  28. ncbi request reprint Diagnosis and monitoring of chronic myeloid leukemia by qualitative and quantitative RT-PCR
    Susan Branford
    Division of Molecular Pathology, Institute of Medical and Veterinary Science, South Australia
    Methods Mol Med 125:69-92. 2006
    ....
  29. ncbi request reprint Organization and function of APT, a subcomplex of the yeast cleavage and polyadenylation factor involved in the formation of mRNA and small nucleolar RNA 3'-ends
    Eduard Nedea
    Banting and Best Department of Medical Research and Department of Molecular and Medical Genetics, University of Toronto, Toronto, Ontario M5G 1L6, Canada
    J Biol Chem 278:33000-10. 2003
    ..Ref2 and Pta1 similarly affect at least one snoRNA transcript...
  30. ncbi request reprint Functional genomics and proteomics: charting a multidimensional map of the yeast cell
    Gary D Bader
    Computational Biology Center, Memorial Sloan Kettering Cancer Center, 1275 York Avenue, Box 460, 10021, New York, NY, USA
    Trends Cell Biol 13:344-56. 2003
    ..Here we review several different genomics and proteomics technologies and describe bioinformatics methods for exploring these data to make new discoveries...
  31. pmc From microarrays to genome duplications
    Christian Roth
    Computational Biology Unit, Bergen Centre for Computational Science, University of Bergen, 5020 Bergen, Norway
    Genome Biol 4:332. 2003
    ..A report on the fifth annual conference of the Society for Bioinformatics in the Nordic Countries (SOCBIN), 'Bioinformatics 2003', Helsinki, Finland, 22-24 May 2003...
  32. ncbi request reprint The Shwachman-Bodian-Diamond syndrome protein family is involved in RNA metabolism
    Alexei Savchenko
    Ontario Center for Structural Proteomics, University of Toronto, Canada
    J Biol Chem 280:19213-20. 2005
    ..Our observations, taken together with previous reports, support the conclusion that SBDS and its homologues play a role in RNA metabolism...
  33. pmc Assembly factors Rpf2 and Rrs1 recruit 5S rRNA and ribosomal proteins rpL5 and rpL11 into nascent ribosomes
    Jingyu Zhang
    Department of Biological Sciences, Carnegie Mellon University, Pittsburgh, Pennsylvania 15213, USA
    Genes Dev 21:2580-92. 2007
    ..Consequently, the abortive 66S pre-rRNPs are prematurely released from the nucleolus to the nucleoplasm, and cannot be exported to the cytoplasm...