Aaron D Schimmer

Summary

Affiliation: University of Toronto
Country: Canada

Publications

  1. ncbi request reprint Induction of apoptosis in lymphoid and myeloid leukemia
    Aaron D Schimmer
    Princess Margaret Hospital, Room 9 516, 610 University Avenue, Toronto, ON, M5G 2M9, Canada
    Curr Oncol Rep 8:430-6. 2006
  2. ncbi request reprint Critical role for Fas-associated death domain-like interleukin-1-converting enzyme-like inhibitory protein in anoikis resistance and distant tumor formation
    Imtiaz A Mawji
    Ontario Cancer Institute, Princess Margaret Hospital, 610 University Ave, Toronto, ON, Canada, M5G 2M9
    J Natl Cancer Inst 99:811-22. 2007
  3. ncbi request reprint A chemical screen identifies anisomycin as an anoikis sensitizer that functions by decreasing FLIP protein synthesis
    Imtiaz A Mawji
    Ontario Cancer Institute, Princess Margaret Hospital, Mt Sinai Hospital, Toronto, Ontario, Canada
    Cancer Res 67:8307-15. 2007
  4. doi request reprint Apoptosis in leukemia: from molecular pathways to targeted therapies
    Aaron D Schimmer
    Princess Margaret Hospital, 610 University Ave, Toronto, ON, Canada M5G 2M9
    Best Pract Res Clin Haematol 21:5-11. 2008
  5. ncbi request reprint Clioquinol - a novel copper-dependent and independent proteasome inhibitor
    A D Schimmer
    The Princess Margaret Hospital, The Ontario Cancer Institute, Toronto, ON, Canada
    Curr Cancer Drug Targets 11:325-31. 2011
  6. pmc Metabolic adaptation to chronic inhibition of mitochondrial protein synthesis in acute myeloid leukemia cells
    Bozhena Jhas
    The Princess Margaret Hospital and the Ontario Cancer Institute, University Health Network, Toronto, Canada
    PLoS ONE 8:e58367. 2013
  7. pmc Inhibition of SREBP1 sensitizes cells to death ligands
    Yanina Eberhard
    Princess Margaret Hospital, Ontario Cancer Institute, Toronto, ON, Canada
    Oncotarget 2:186-96. 2011
  8. pmc Suppression of cancer progression by MGAT1 shRNA knockdown
    Reza Beheshti Zavareh
    Ontario Cancer Institute, Princess Margaret Hospital, and Department of Medical Biophysics, University of Toronto, Toronto, Ontario, Canada
    PLoS ONE 7:e43721. 2012
  9. pmc An evidence-based review of obatoclax mesylate in the treatment of hematological malignancies
    Carolyn A Goard
    Princess Margaret Cancer Centre, Ontario Cancer Institute, University Health Network, Toronto, ON, Canada
    Core Evid 8:15-26. 2013
  10. doi request reprint A phase I study of the metal ionophore clioquinol in patients with advanced hematologic malignancies
    Aaron D Schimmer
    Princess Margaret Hospital, Ontario Cancer Institute, Toronto, Ontario, Canada
    Clin Lymphoma Myeloma Leuk 12:330-6. 2012

Collaborators

Detail Information

Publications90

  1. ncbi request reprint Induction of apoptosis in lymphoid and myeloid leukemia
    Aaron D Schimmer
    Princess Margaret Hospital, Room 9 516, 610 University Avenue, Toronto, ON, M5G 2M9, Canada
    Curr Oncol Rep 8:430-6. 2006
    ..This review highlights compounds that target the mitochondrial, death receptor, and convergence pathways of caspase activation that are being developed for the treatment of acute leukemia...
  2. ncbi request reprint Critical role for Fas-associated death domain-like interleukin-1-converting enzyme-like inhibitory protein in anoikis resistance and distant tumor formation
    Imtiaz A Mawji
    Ontario Cancer Institute, Princess Margaret Hospital, 610 University Ave, Toronto, ON, Canada, M5G 2M9
    J Natl Cancer Inst 99:811-22. 2007
    ..We hypothesized that c-Fas-associated death domain-like interleukin-1-converting enzyme-like inhibitory protein (FLIP), an endogenous inhibitor of death receptor signaling, may suppress anoikis...
  3. ncbi request reprint A chemical screen identifies anisomycin as an anoikis sensitizer that functions by decreasing FLIP protein synthesis
    Imtiaz A Mawji
    Ontario Cancer Institute, Princess Margaret Hospital, Mt Sinai Hospital, Toronto, Ontario, Canada
    Cancer Res 67:8307-15. 2007
    ..Our results suggest that FLIP is a suppressor of anoikis and inhibiting FLIP protein synthesis may be a useful antimetastatic strategy...
  4. doi request reprint Apoptosis in leukemia: from molecular pathways to targeted therapies
    Aaron D Schimmer
    Princess Margaret Hospital, 610 University Ave, Toronto, ON, Canada M5G 2M9
    Best Pract Res Clin Haematol 21:5-11. 2008
    ..This work demonstrates both the development of new agents based on molecular mechanisms and how these agents further our understanding of the biology of apoptosis...
  5. ncbi request reprint Clioquinol - a novel copper-dependent and independent proteasome inhibitor
    A D Schimmer
    The Princess Margaret Hospital, The Ontario Cancer Institute, Toronto, ON, Canada
    Curr Cancer Drug Targets 11:325-31. 2011
    ..In addition, it discusses the human pharmacology and toxicology studies and how this information would guide a phase I clinical trial of this agent for patients with malignancy...
  6. pmc Metabolic adaptation to chronic inhibition of mitochondrial protein synthesis in acute myeloid leukemia cells
    Bozhena Jhas
    The Princess Margaret Hospital and the Ontario Cancer Institute, University Health Network, Toronto, Canada
    PLoS ONE 8:e58367. 2013
    ..Thus, we have generated cells with a reversible metabolic phenotype by chronic treatment with an inhibitor of mitochondrial protein synthesis. These cells will provide insight into cellular adaptations used to cope with metabolic stress...
  7. pmc Inhibition of SREBP1 sensitizes cells to death ligands
    Yanina Eberhard
    Princess Margaret Hospital, Ontario Cancer Institute, Toronto, ON, Canada
    Oncotarget 2:186-96. 2011
    ..Thus, inhibition of SREBP1 or its downstream target fatty acid synthase sensitizes resistant cells to death ligands...
  8. pmc Suppression of cancer progression by MGAT1 shRNA knockdown
    Reza Beheshti Zavareh
    Ontario Cancer Institute, Princess Margaret Hospital, and Department of Medical Biophysics, University of Toronto, Toronto, Ontario, Canada
    PLoS ONE 7:e43721. 2012
    ..Our results demonstrate that blocking MGAT1 is a potential target for anti-cancer therapy...
  9. pmc An evidence-based review of obatoclax mesylate in the treatment of hematological malignancies
    Carolyn A Goard
    Princess Margaret Cancer Centre, Ontario Cancer Institute, University Health Network, Toronto, ON, Canada
    Core Evid 8:15-26. 2013
    ..By understanding the molecular underpinnings of obatoclax response, along with optimal therapeutic regimens and indications, the potential of obatoclax mesylate for the treatment of hematological malignancies may be further clarified...
  10. doi request reprint A phase I study of the metal ionophore clioquinol in patients with advanced hematologic malignancies
    Aaron D Schimmer
    Princess Margaret Hospital, Ontario Cancer Institute, Toronto, Ontario, Canada
    Clin Lymphoma Myeloma Leuk 12:330-6. 2012
    ..Neuropathy and abdominal pain were dose-limiting toxicities. Minimal pharmacodynamic effects were observed, and there were no clinical responses...
  11. ncbi request reprint Male sexual function after autologous blood or marrow transplantation
    A D Schimmer
    Autologous Blood and Marrow Transplant Long Term Follow up Research Unit, The Princess Margaret Hospital, University Health Network, Toronto, Ontario, Canada
    Biol Blood Marrow Transplant 7:279-83. 2001
    ..Decreased levels of testosterone and symptoms of sexual dysfunction correlated with a diagnosis of Hodgkin's disease and may be related to the induction and salvage therapy received prior to autoBMT...
  12. doi request reprint Phase I/II trial of AEG35156 X-linked inhibitor of apoptosis protein antisense oligonucleotide combined with idarubicin and cytarabine in patients with relapsed or primary refractory acute myeloid leukemia
    Aaron D Schimmer
    Princess Margaret Hospital, Ontario Cancer Institute, Toronto, Ontario, Canada M5G 2M9
    J Clin Oncol 27:4741-6. 2009
    ..We report on a phase I/II trial of the XIAP antisense oligonucleotide AEG35156 in combination with reinduction chemotherapy...
  13. ncbi request reprint A phase I study of the pan bcl-2 family inhibitor obatoclax mesylate in patients with advanced hematologic malignancies
    Aaron D Schimmer
    Ontario Cancer Institute, Princess Margaret Hospital, Toronto, Ontario, Canada
    Clin Cancer Res 14:8295-301. 2008
    ..Therefore, we conducted a phase I clinical trial of the small-molecule pan-Bcl-2 inhibitor, obatoclax mesylate, in patients with refractory leukemia and myelodysplasia to assess its safety and define its optimal dose...
  14. ncbi request reprint Chemical biology--understanding biology and advancing therapy
    Aaron D Schimmer
    The Princess Margaret Hospital, Ontario Cancer Institute, Toronto, ON, Canada
    Clin Invest Med 31:E282-9. 2008
    ..Finally, this review discusses the opportunities to identify off-patent drugs with previously unrecognized anti-cancer activity and how the prior data on the drug would permit it to be rapidly repurposed...
  15. doi request reprint Addition of AEG35156 XIAP antisense oligonucleotide in reinduction chemotherapy does not improve remission rates in patients with primary refractory acute myeloid leukemia in a randomized phase II study
    Aaron D Schimmer
    Princess Margaret Hospital, Ontario Cancer Institute, Toronto, Canada
    Clin Lymphoma Myeloma Leuk 11:433-8. 2011
    ..We report an open-label randomized phase II trial of reinduction chemotherapy with and without the XIAP antisense oligonucleotide AEG35156 in patients with AML who did not achieve remission with initial induction chemotherapy...
  16. ncbi request reprint Novel therapies targeting the apoptosis pathway for the treatment of acute myeloid leukemia
    Aaron D Schimmer
    Ontario Cancer Institute, Princess Margaret Hospital, 610 University Ave, M5G 2M9, Toronto, ON, Canada
    Curr Treat Options Oncol 8:277-86. 2007
    ..In addition, this review will discuss how these novel therapies are being used as chemical probes to better understand the biology of the apoptosis pathway...
  17. ncbi request reprint The autologous blood and marrow transplant long-term follow-up clinic: a model of care for following and treating survivors of autotransplant
    Aaron D Schimmer
    ABMT Long term Follow up Research Unit, Princess Margaret Hospital, University of Toronto, ABMT Program, Canada
    Support Care Cancer 10:247-52. 2002
    ..In conclusion, we present an inexpensive model of care for ABMT survivors that can be extended to adult survivors of malignancy not treated by ABMT...
  18. ncbi request reprint Targeting XIAP for the treatment of malignancy
    A D Schimmer
    The Ontario Cancer Institute, Toronto, Ontario, Canada
    Cell Death Differ 13:179-88. 2006
    ..This review will discuss the progress being made in developing antisense and small-molecule XIAP inhibitors...
  19. ncbi request reprint Inhibitor of apoptosis proteins: translating basic knowledge into clinical practice
    Aaron D Schimmer
    Ontario Cancer Institute, Princess Margaret Hospital, Toronto, Ontario, Canada
    Cancer Res 64:7183-90. 2004
    ..For all of these potential clinical applications, however, the challenge remains to incorporate these findings into actual clinical practice...
  20. doi request reprint Identification of a non-phosphorylated, cell permeable, small molecule ligand for the Stat3 SH2 domain
    Brent D G Page
    Department of Chemistry, University of Toronto Mississauga, 3359 Mississauga Road, Mississauga, ON, Canada L5L 1C6
    Bioorg Med Chem Lett 21:5605-9. 2011
    ..Inhibition of Stat3 function in both breast and multiple myeloma (MM) tumor cells correlated with induced cell death (EC(50)=10 and 16 μM, respectively)...
  21. doi request reprint The antiparasitic agent ivermectin induces chloride-dependent membrane hyperpolarization and cell death in leukemia cells
    Sumaiya Sharmeen
    Princess Margaret Hospital, Ontario Cancer Institute, Toronto, ON, Canada
    Blood 116:3593-603. 2010
    ..Thus, given its known toxicology and pharmacology, ivermectin could be rapidly advanced into clinical trial for leukemia...
  22. doi request reprint Selective inhibition of histone deacetylases sensitizes malignant cells to death receptor ligands
    Tabitha E Wood
    Princess Margaret Hospital, Ontario Cancer Institute, Ontario, Canada
    Mol Cancer Ther 9:246-56. 2010
    ..Thus, we have identified a selective HDAC inhibitor and showed that selective HDAC inhibition sensitizes cells to death ligands, thereby highlighting a new mechanism to overcome resistance to death receptor ligands...
  23. doi request reprint Chelation of intracellular iron with the antifungal agent ciclopirox olamine induces cell death in leukemia and myeloma cells
    Yanina Eberhard
    Princess Margaret Hospital, Ontario Cancer Institute, Toronto, ON, Canada
    Blood 114:3064-73. 2009
    ..Thus, in summary, CPX has previously unrecognized anticancer activity at concentrations that are pharmacologically achievable. Therefore, CPX could be rapidly repurposed for the treatment of malignancies, including leukemia and myeloma...
  24. doi request reprint Effect of noncompetitive proteasome inhibition on bortezomib resistance
    Xiaoming Li
    Ontario Cancer Institute, Princess Margaret Hospital, Toronto, ON, Canada
    J Natl Cancer Inst 102:1069-82. 2010
    ..We hypothesized that proteasome inhibitors that act through a noncompetitive mechanism might overcome some forms of bortezomib resistance...
  25. pmc The ubiquitin-activating enzyme E1 as a therapeutic target for the treatment of leukemia and multiple myeloma
    G Wei Xu
    The Princess Margaret Hospital, The Ontario Cancer Institute, Toronto, ON, Canada
    Blood 115:2251-9. 2010
    ..Thus, our work highlights the E1 enzyme as a novel target for the treatment of hematologic malignancies...
  26. doi request reprint Inhibition of the sodium potassium adenosine triphosphatase pump sensitizes cancer cells to anoikis and prevents distant tumor formation
    Craig D Simpson
    Ontario Cancer Institute, Princess Margaret Hospital, Toronto, ON, Canada
    Cancer Res 69:2739-47. 2009
    ..These results suggest a potential mechanism for the observed clinical reduction in metastasis and relapse in breast cancer patients who have undergone treatments with cardiac glycosides...
  27. doi request reprint Inhibition of the sodium/potassium ATPase impairs N-glycan expression and function
    Reza Beheshti Zavareh
    Ontario Cancer Institute, Princess Margaret Hospital, Canada
    Cancer Res 68:6688-97. 2008
    ..These molecules can be used as tools to better understand the role of N-glycans in normal and malignant cells. Moreover, these results may partly explain the anticancer effect of CGs in cardiovascular patients...
  28. pmc Inhibition of mitochondrial translation as a therapeutic strategy for human acute myeloid leukemia
    Marko Skrtic
    Campbell Family Cancer Research Institute, Princess Margaret Hospital, Ontario Cancer Institute, Toronto, Ontario M5G 2M9, Canada
    Cancer Cell 20:674-88. 2011
    ....
  29. doi request reprint Potential use of cetrimonium bromide as an apoptosis-promoting anticancer agent for head and neck cancer
    Emma Ito
    Department of Medical Biophysics, University of Toronto, Ontario, Canada
    Mol Pharmacol 76:969-83. 2009
    ..Thus, using an HTS approach, CTAB was identified as a potential apoptogenic quaternary ammonium compound possessing in vitro and in vivo efficacy against HNC models...
  30. doi request reprint Cyproheptadine displays preclinical activity in myeloma and leukemia
    Xinliang Mao
    Princess Margaret Hospital, Ontario Cancer Institute, Toronto, ON, Canada
    Blood 112:760-9. 2008
    ..Because the drug is well tolerated and already approved in multiple countries for clinical use as an antihistamine and appetite stimulant, it could be moved directly into clinical trials for cancer...
  31. doi request reprint High-dose cytarabine-based consolidation shows superior results for older AML patients with intermediate risk cytogenetics in first complete remission
    Mona Hassanein
    Department of Medical Oncology and Hematology, Princess Margaret Cancer Centre, University of Toronto, Toronto, ON, Canada
    Leuk Res 37:556-60. 2013
    ..The results indicate that a high-dose cytarabine-containing consolidation regimen produces superior outcomes in AML patients age>60 years with intermediate-risk cytogenetics...
  32. doi request reprint Outcomes of adult patients with relapsed acute lymphoblastic leukemia following frontline treatment with a pediatric regimen
    Elena Liew
    Department of Medical Oncology and Hematology, Princess Margaret Hospital, University of Toronto, Toronto, ON, Canada
    Leuk Res 36:1517-20. 2012
    ..The outcome of adult ALL relapsing after treatment was therefore poor, and novel salvage strategies are needed to improve outcomes...
  33. doi request reprint Novel proteasome inhibitors to overcome bortezomib resistance
    Amy M Ruschak
    Department of Molecular Genetics, The University of Toronto, Toronto, ON, Canada
    J Natl Cancer Inst 103:1007-17. 2011
    ..We then focus on the molecular biology, chemistry, and the preclinical and clinical efficacy of novel proteasome inhibitors as strategies to inhibit this target and overcome some forms of bortezomib resistance...
  34. doi request reprint The antihelmintic flubendazole inhibits microtubule function through a mechanism distinct from Vinca alkaloids and displays preclinical activity in leukemia and myeloma
    Paul A Spagnuolo
    Princess Margaret Hospital, Ontario Cancer Institute, Toronto, ON
    Blood 115:4824-33. 2010
    ..Therefore, flubendazole is a novel microtubule inhibitor that displays preclinical activity in leukemia and myeloma...
  35. pmc Design, synthesis, and in vitro characterization of novel hybrid peptidomimetic inhibitors of STAT3 protein
    Vijay M Shahani
    Department of Chemistry, University of Toronto, Mississauga, ON, Canada
    Bioorg Med Chem 19:1823-38. 2011
    ..The effect of compounds 14aa and 14aa-OH are accompanied by a moderate loss of cell viability...
  36. doi request reprint Treatment outcomes following leukemic transformation in Philadelphia-negative myeloproliferative neoplasms
    James A Kennedy
    Department of Medicine, University Health Network, Toronto, Ontario, Canada
    Blood 121:2725-33. 2013
    ..03). Thus, induction chemotherapy followed by HCT has the potential for long-term disease control in select patients with LT preceded by a MPN...
  37. doi request reprint Treatment of Philadelphia chromosome-positive acute lymphoblastic leukaemia with imatinib combined with a paediatric-based protocol
    Santhosh Thyagu
    Department of Medical Oncology and Hematology, Princess Margaret Hospital, University of Toronto, Toronto, ON, Canada
    Br J Haematol 158:506-14. 2012
    ..The combination of imatinib with a paediatric-based regimen in adults produced high response rates, but was associated with considerable toxicity and high non-relapse mortality post-HSCT...
  38. doi request reprint A novel inhibitor of glucose uptake sensitizes cells to FAS-induced cell death
    Tabitha E Wood
    Princess Margaret Hospital, Ontario Cancer Institute, 610 University Avenue, Toronto, Ontario, Canada
    Mol Cancer Ther 7:3546-55. 2008
    ..Thus, fasentin is a novel inhibitor of glucose transport that blocks glucose uptake and highlights a new mechanism to sensitize cells to death ligands...
  39. doi request reprint A novel diquinolonium displays preclinical anti-cancer activity and induces caspase-independent cell death
    Rose Hurren
    Ontario Cancer Institute, Princess Margaret Hospital, 610 University Ave, Toronto, ON, Canada M5G 2M9
    Apoptosis 13:748-55. 2008
    ..Thus, Q(2) is a novel quinolinium with preclinical activity in malignancies such as leukemia and myeloma and warrants further investigation...
  40. pmc Re-directing an alkylating agent to mitochondria alters drug target and cell death mechanism
    Rida Mourtada
    Department of Pharmaceutical Sciences, Faculty of Pharmacy, University of Toronto, Toronto, Ontario, Canada
    PLoS ONE 8:e60253. 2013
    ..Thus, mitochondrial delivery allows the exploitation of Cbl as a promiscuous mitochondrial protein inhibitor with promising therapeutic potential...
  41. doi request reprint Feasibility of outpatient consolidation chemotherapy in older versus younger patients with acute myeloid leukemia
    Lalit Saini
    Department of Medical Oncology and Hematology, Princess Margaret Hospital, University of Toronto, Toronto, Ontario, Canada
    Am J Hematol 87:323-6. 2012
    ..We conclude that outpatient-based consolidation therapy can be safely undertaken in a substantial proportion of fit older patients with AML...
  42. doi request reprint Rerouting chlorambucil to mitochondria combats drug deactivation and resistance in cancer cells
    Sonali B Fonseca
    Department of Pharmaceutical Sciences, Faculty of Pharmacy, University of Toronto, Toronto, ON M5S1A8, Canada
    Chem Biol 18:445-53. 2011
    ..This retention of activity is observed even in cells with resistance to chlorambucil or disabled apoptotic triggering...
  43. ncbi request reprint Treatment of elderly patients with acute lymphoblastic leukaemia using a paediatric-based protocol
    Marc Poch Martell
    Department of Medical Oncology and Hematology, Princess Margaret Cancer Centre, University of Toronto, Toronto, ON, Canada
    Br J Haematol 163:458-64. 2013
    ..Survival is superior to most previously reported series in this age group, but remains worse compared to younger patients. Further improvement of the toxicity profile, particularly during induction, is required to improve outcomes...
  44. ncbi request reprint Predictors of response to reinduction chemotherapy for patients with acute myeloid leukemia who do not achieve complete remission with frontline induction chemotherapy
    Joseph M Brandwein
    Department of Medical Oncology and Hematology, Princess Margaret Hospital, University Health Network, University of Toronto, Toronto, Ontario, Canada
    Am J Hematol 83:54-8. 2008
    ..Patients achieving CR are at high risk of relapse and should be considered for allogeneic BMT or novel strategies to attempt to reduce relapse rates...
  45. doi request reprint Treatment of adults with BCR-ABL negative acute lymphoblastic leukaemia with a modified paediatric regimen
    John M Storring
    Department of Medical Oncology and Haematology, Princess Margaret Hospital, University of Toronto, Toronto, ON, Canada
    Br J Haematol 146:76-85. 2009
    ..Effective delivery of asparaginase dosing appears to be important in achieving an optimal antileukaemic effect...
  46. ncbi request reprint Outcomes of older patients (> or = 60 years) with acquired aplastic anaemia treated with immunosuppressive therapy
    Susan Y Kao
    Department of Medical Oncology and Hematology, Princess Margaret Hospital, Toronto, ON, Canada
    Br J Haematol 143:738-43. 2008
    ..Nine out of 14 evaluable patients in the attenuated IST group had durable responses to treatment, suggesting that patients not suitable for standard IST can still benefit from attenuated IST...
  47. pmc Lysosomal disruption preferentially targets acute myeloid leukemia cells and progenitors
    Mahadeo A Sukhai
    Princess Margaret Hospital the Ontario Cancer Institute, University Health Network, Toronto, Ontario, Canada
    J Clin Invest 123:315-28. 2013
    ..These results demonstrate that lysosomal disruption preferentially targets AML cells and AML progenitor cells, providing a rationale for testing lysosomal disruption as a novel therapeutic strategy for AML...
  48. doi request reprint Wnt inhibitor screen reveals iron dependence of β-catenin signaling in cancers
    Siyuan Song
    Department of Biochemistry, Donnelly Centre for Cellular and Biomolecular Research, University of Toronto, Toronto, Ontario, Canada
    Cancer Res 71:7628-39. 2011
    ..Taken together, our results reveal a critical requirement for iron in Wnt signaling and they show that iron chelation serves as an effective mechanism to inhibit Wnt signaling in humans...
  49. doi request reprint Improved survival using an intensive, pediatric-based chemotherapy regimen in adults with T-cell acute lymphoblastic leukemia
    Murtadha Al-Khabori
    Department of Medical Oncology and Hematology, Princess Margaret Hospital, University of Toronto, Toronto, ON, Canada
    Leuk Lymphoma 51:61-5. 2010
    ..non-DFCI) was the major prognostic factor influencing both RFS and OS. The results provide evidence supporting the superior efficacy of asparaginase-intensive pediatric-based regimens for adults with T-ALL...
  50. ncbi request reprint The dietary isothiocyanate sulforaphane targets pathways of apoptosis, cell cycle arrest, and oxidative stress in human pancreatic cancer cells and inhibits tumor growth in severe combined immunodeficient mice
    Nhu An Pham
    Department of Medical Biophysics, University of Toronto, Ontario, Canada
    Mol Cancer Ther 3:1239-48. 2004
    ..Our findings suggest that, in addition to the known effects on cancer prevention, sulforaphane may have activity in established pancreatic cancer...
  51. ncbi request reprint Disruption of the endoplasmic reticulum and increases in cytoplasmic calcium are early events in cell death induced by the natural triterpenoid Asiatic acid
    Debbie M Gurfinkel
    The Princess Margaret Hospital and the Ontario Cancer Institute, Rm 9 516, 610 University Ave, M5G 2M9, Toronto, ON, Canada
    Apoptosis 11:1463-71. 2006
    ..Thus, disruption of the endoplasmic reticulum and alterations in calcium homeostasis are early events in AA-induced death...
  52. ncbi request reprint Mutations in UBA3 confer resistance to the NEDD8-activating enzyme inhibitor MLN4924 in human leukemic cells
    G Wei Xu
    Ontario Cancer Institute, Princess Margaret Cancer Centre, University Health Network, Toronto, Ontario, Canada
    PLoS ONE 9:e93530. 2014
    ..Thus, our work provides insight into mechanisms of MLN4924 resistance to facilitate the development of more effective second-generation NAE inhibitors...
  53. pmc Antagonism of the Stat3-Stat3 protein dimer with salicylic acid based small molecules
    Steven Fletcher
    Department of Chemistry, University of Toronto Mississauga, Mississauga, ON L5L1C6, Canada
    ChemMedChem 6:1459-70. 2011
    ....
  54. doi request reprint Influence of FLT3-internal tandem duplication allele burden and white blood cell count on the outcome in patients with intermediate-risk karyotype acute myeloid leukemia
    Jonathan How
    Department of Medical Oncology and Hematology, Princess Margaret Hospital, University Health Network, University of Toronto, Toronto, Ontario, Canada
    Cancer 118:6110-7. 2012
    ....
  55. doi request reprint A genome wide shRNA screen identifies α/β hydrolase domain containing 4 (ABHD4) as a novel regulator of anoikis resistance
    Craig D Simpson
    Ontario Cancer Institute, Princess Margaret Hospital, Toronto, Canada
    Apoptosis 17:666-78. 2012
    ..Thus, ABHD4 is a novel genetic regulator of anoikis sensitivity...
  56. doi request reprint Anoikis resistance and tumor metastasis
    Craig D Simpson
    Ontario Cancer Institute, Princess Margaret Hospital, University of Toronto, 610 University Avenue, Toronto, Ont, Canada M5G 2M9
    Cancer Lett 272:177-85. 2008
    ....
  57. doi request reprint Predictors of outcome in adults with BCR-ABL negative acute lymphoblastic leukemia treated with a pediatric-based regimen
    Joseph M Brandwein
    Department of Medical Oncology and Hematology, Princess Margaret Cancer Centre, University of Toronto, Toronto, ON, Canada Electronic address
    Leuk Res 38:532-6. 2014
    ..Cytogenetics and phenotype were not independent predictors of OS. ..
  58. doi request reprint A 2,6,9-hetero-trisubstituted purine inhibitor exhibits potent biological effects against multiple myeloma cells
    Vijay M Shahani
    Department of Chemistry, University of Toronto, 3359 Mississauga Road North, Mississauga, ON, L5L 1C6, Canada
    Bioorg Med Chem 21:5618-28. 2013
    ..Initial screening against the kinome, prompted by the purine scaffold's history for targeting ATP binding pockets, suggests possible targeting of the JAK family kinases, as well for ABL1 (nonphosphorylated F317L) and AAK1. ..
  59. ncbi request reprint Targeting the ubiquitin E1 as a novel anti-cancer strategy
    Wei Xu
    The Princess Margaret Hospital, The Ontario Cancer Institute, Toronto, ON, M5G 2M9 Canada
    Curr Pharm Des 19:3201-9. 2013
    ..These molecules are useful tools to understand the biology of UBA1 and highlight the potential of inhibiting this target for the treatment of malignancy...
  60. doi request reprint Phosphopeptide selective coordination complexes as promising SRC homology 2 domain mimetics
    Joel A Drewry
    Department of Chemical and Physical Sciences, University of Toronto, 3359 Mississauga Road North, Mississauga, Ontario L5L 1C6, Canada
    Inorg Chem 51:8284-91. 2012
    ..Several receptors potently disrupted cancer cell viability in breast cancer, prostate cancer, and acute myeloid leukemia cell lines...
  61. ncbi request reprint Characteristics and outcomes of acute myelogenous leukemia patients with very late relapse (>5 years)
    Bruno C Medeiros
    Department of Medical Oncology, Peincess Margaret Hospital, University Health Network, Univeristy of Toronto, Toronto, Ontario, Canada
    Leuk Lymphoma 48:65-71. 2007
    ..We conclude that very late-relapse AML is a rare event, and that reinduction in these patients is associated with very high CR rates and a potential cure fraction...
  62. doi request reprint Uroporphyrinogen decarboxylase is a radiosensitizing target for head and neck cancer
    Emma Ito
    Department of Medical Biophysics, University of Toronto, Toronto, Ontario, Canada M5G 2M9
    Sci Transl Med 3:67ra7. 2011
    ..Thus, our study has revealed UROD as a potent tumor-selective sensitizer for both radiation and chemotherapy, with potential relevance to many human malignancies...
  63. pmc Crystal structure of the human ubiquitin-activating enzyme 5 (UBA5) bound to ATP: mechanistic insights into a minimalistic E1 enzyme
    John Paul Bacik
    Structural Genomics Consortium, University of Toronto, Toronto, Ontario M5G 1L7, Canada
    J Biol Chem 285:20273-80. 2010
    ..These studies reveal structural features that further our understanding of the UBA5 enzyme reaction mechanism and provide insight into the evolution of ubiquitin activation...
  64. ncbi request reprint Oral ciclopirox olamine displays biological activity in a phase I study in patients with advanced hematologic malignancies
    Mark D Minden
    Princess Margaret Cancer Centre, University Health Network, Toronto, Ontario, Canada
    Am J Hematol 89:363-8. 2014
    ..Once-daily dosing of oral ciclopirox olamine was well tolerated in patients with relapsed or refractory hematologic malignancies, and further optimization of dosing regimens is warranted in this patient population...
  65. pmc Glycogen synthase kinase-3 inhibition sensitizes pancreatic cancer cells to TRAIL-induced apoptosis
    Shadi Mamaghani
    Division of Applied Molecular Oncology, University Health Network, Toronto, Ontario, Canada
    PLoS ONE 7:e41102. 2012
    ..These results suggest that GSK-3 inhibitors might be effectively combined with TRAIL for the treatment of pancreatic cancer...
  66. pmc Targeting p53 via JNK pathway: a novel role of RITA for apoptotic signaling in multiple myeloma
    Manujendra N Saha
    Division of Molecular and Cellular Biology, Toronto General Hospital Research Institute, Toronto, Ontario, Canada
    PLoS ONE 7:e30215. 2012
    ..Our study unveils a previously undescribed mechanism of RITA-induced p53-mediated apoptosis through JNK signaling pathway and provides the rationale for combination of p53 activating drugs with JNK activators in the treatment of MM...
  67. doi request reprint A high-content chemical screen identifies ellipticine as a modulator of p53 nuclear localization
    G Wei Xu
    Ontario Cancer Institute, Princess Margaret Hospital, 610 University Ave, M5G 2M9, Toronto, ON, Canada
    Apoptosis 13:413-22. 2008
    ..Thus, a chemical biology approach has identified a molecule that shifts the localization of p53 and enhances its nuclear activity...
  68. pmc New sources of drugs for hematologic malignancies
    Mahadeo A Sukhai
    Princess Margaret Hospital, Ontario Cancer Institute, Toronto, ON, Canada
    Blood 117:6747-55. 2011
    ..Finally, the mechanisms to enhance drug repurposing through increased collaborations between academia, industry, and nonprofit charitable organizations are discussed...
  69. doi request reprint Deoxyribonucleic acid methyltransferase 3B promotes epigenetic silencing through histone 3 chromatin modifications in pituitary cells
    Xuegong Zhu
    Department of Medicine, University Health Network, The Ontario Cancer Institute, 610 University Avenue 8 327, Toronto, Ontario, Canada M5G 2M9
    J Clin Endocrinol Metab 93:3610-7. 2008
    ..Epigenetic dysregulation is implicated in pituitary neoplasia as the cause of silencing of several tumor suppressor genes. However, the upstream mediators of such events remain unknown...
  70. doi request reprint SBDS-deficiency results in specific hypersensitivity to Fas stimulation and accumulation of Fas at the plasma membrane
    Ken Ichiro Watanabe
    Cell Biology Program, Research Institute, The Hospital for Sick Children, University of Toronto, Toronto, ON, Canada
    Apoptosis 14:77-89. 2009
    ..These results suggest that SBDS loss results in abnormal accumulation of Fas at the plasma membrane, where it sensitizes the cells to stimulation by Fas ligand...
  71. doi request reprint TROSY-based NMR evidence for a novel class of 20S proteasome inhibitors
    Remco Sprangers
    Departments of Molecular Genetics, Biochemistry, and Chemistry, The University of Toronto, Toronto, Ontario M5S 1A8, Canada
    Biochemistry 47:6727-34. 2008
    ..Our data thus establish a novel class of proteasome inhibitor that functions via a mechanism distinct from binding to active sites...
  72. pmc Coordination complex SH2 domain proteomimetics: an alternative approach to disrupting oncogenic protein-protein interactions
    Joel A Drewry
    Department of Chemistry, University of Toronto, Toronto, Canada
    Chem Commun (Camb) 46:892-4. 2010
    ..As a proof-of-concept, functionalized bis-dipicolylamine (BDPA) copper(ii) complexes are shown to disrupt oncogenic Stat3-Stat3 protein complexes and elicit promising anti-tumour activity...
  73. ncbi request reprint A chemical biology screen identifies glucocorticoids that regulate c-maf expression by increasing its proteasomal degradation through up-regulation of ubiquitin
    Xinliang Mao
    Princess Margaret Hospital, Ontario Cancer Institute, Toronto, ON, Canada
    Blood 110:4047-54. 2007
    ..Thus, using a chemical biology approach, we identified a novel mechanism of action of glucocorticoids and a novel mechanism by which levels of c-maf protein are regulated by the abundance of the ubiquitin substrate...
  74. ncbi request reprint Livin/melanoma inhibitor of apoptosis protein as a potential therapeutic target for the treatment of malignancy
    Hong Chang
    Princess Margaret Hospital, Room 9 516, 610 University Avenue, Toronto, Ontario, Canada
    Mol Cancer Ther 6:24-30. 2007
    ..This review will discuss Livin as a potential therapeutic target and strategies for its inhibition, including antisense oligonucleotides, small-molecule inhibitors, and immune-mediated approaches...
  75. doi request reprint Catalase activity and arsenic sensitivity in acute leukemia
    Emma Coe
    Ontario Cancer Institute, Princess Margaret Hospital, and Department of Medical Biophysics, University of Toronto, Toronto, Canada
    Leuk Lymphoma 49:1976-81. 2008
    ..Therefore, other strategies should be explored to enhance the cytotoxicity of As2O3 in AML...
  76. doi request reprint The toxicology of Clioquinol
    Xinliang Mao
    Ontario Cancer Institute, Princess Margaret Hospital, Toronto, ON, Canada
    Toxicol Lett 182:1-6. 2008
    ..Such information will aid in the design of clinical trials of oral Clioquinol for new indications such as cancer therapy...
  77. ncbi request reprint Global profiles of gene expression induced by adrenocorticotropin in Y1 mouse adrenal cells
    Bernard P Schimmer
    Banting and Best Department of Medical Research, University of Toronto, Ontario, Canada
    Endocrinology 147:2357-67. 2006
    ..The large number of transcripts affected by ACTH anticipates a broader range of actions than previously appreciated...
  78. doi request reprint Increased efficiency for performing colony formation assays in 96-well plates: novel applications to combination therapies and high-throughput screening
    David Katz
    University of Toronto, Canada
    Biotechniques 44:ix-xiv. 2008
    ..These data indicate that the 96-well CFA can be adopted as an efficient alternative assay to the 6-well CFA in evaluating single and combination therapies in vitro, providing a possible readout that could be used on a HTS platform...
  79. ncbi request reprint Self-concept as a "BMT patient", illness intrusiveness, and engulfment in allogeneic bone marrow transplant recipients
    Heather J Beanlands
    Ryerson University, Toronto, ON, Canada
    J Psychosom Res 55:419-25. 2003
    ..Illness intrusiveness and engulfment may interact, leading affected individuals to construe themselves as highly similar to a prototypical "BMT patient"...
  80. ncbi request reprint Functional blocks in caspase activation pathways are common in leukemia and predict patient response to induction chemotherapy
    Aaron D Schimmer
    The Burnham Institute, La Jolla, California 92037, USA
    Cancer Res 63:1242-8. 2003
    ..This study supports the importance of apoptosis pathways in determining response to chemotherapy and suggests that functional defects in caspase activation are prognostic in patients with leukemia...
  81. doi request reprint Bcl-B expression in human epithelial and nonepithelial malignancies
    Maryla Krajewska
    Burnham Institute for Medical Research, La Jolla, California 92037, USA
    Clin Cancer Res 14:3011-21. 2008
    ..Bcl-B is an antiapoptotic Bcl-2 family member, which is known to change its phenotype upon binding to Nur77/TR3. The expression pattern of this protein in human malignancies has not been reported...
  82. pmc Identification of kinetin riboside as a repressor of CCND1 and CCND2 with preclinical antimyeloma activity
    Rodger E Tiedemann
    Mayo Clinic, Comprehensive Cancer Center, Division of Hematology and Oncology, Scottsdale, Arizona, USA
    J Clin Invest 118:1750-64. 2008
    ..These data support targeted repression of cyclin D genes as a therapeutic strategy for human malignancies...
  83. ncbi request reprint Small-molecule antagonists of apoptosis suppressor XIAP exhibit broad antitumor activity
    Aaron D Schimmer
    The Burnham Institute, La Jolla, CA 92037, USA
    Cancer Cell 5:25-35. 2004
    ..Active compounds also suppressed growth of established tumors in xenograft models in mice, while displaying little toxicity to normal tissues. These findings validate IAPs as targets for cancer drug discovery...
  84. pmc Small-molecule XIAP inhibitors derepress downstream effector caspases and induce apoptosis of acute myeloid leukemia cells
    Bing Z Carter
    University of Texas MD Anderson Cancer Center, Houston, TX, USA
    Blood 105:4043-50. 2005
    ..Thus, polyphenylurea-based XIAP antagonsists directly induce apoptosis of leukemia cells and AML patient samples at low micromolar concentrations through a mechanism of action distinct from conventional chemotherapeutic agents...
  85. doi request reprint Superstition but not distrust in the medical system predicts the use of complementary and alternative medicine in a group of patients with acute leukemia
    Maria Teresa Lourenco
    Leuk Lymphoma 49:339-41. 2008
  86. doi request reprint Dexamethasone increases ubiquitin transcription through an SP-1 dependent mechanism in multiple myeloma cells
    Xinliang Mao
    Leuk Res 32:1480-2. 2008
  87. ncbi request reprint Myelodysplastic syndromes: the complexity of stem-cell diseases
    Seth J Corey
    Department of Leukemia, University of Texas M D Anderson Cancer Center, 1515 Holcombe Boulevard, Houston, Texas 77030, USA
    Nat Rev Cancer 7:118-29. 2007
    ....
  88. ncbi request reprint Increased expression of apoptosis inhibitor protein XIAP contributes to anoikis resistance of circulating human prostate cancer metastasis precursor cells
    Olga Berezovskaya
    The Sidney Kimmel Cancer Center, San Diego, CA 92121, USA
    Cancer Res 65:2378-86. 2005
    ..We also provide initial preclinical data on the antimetastatic efficacy of recently discovered small-molecule antagonists of XIAP...
  89. ncbi request reprint Identification of small molecules that sensitize resistant tumor cells to tumor necrosis factor-family death receptors
    Aaron D Schimmer
    Burnham Institute for Medical Research, La Jolla, California 92037, USA
    Cancer Res 66:2367-75. 2006
    ....
  90. ncbi request reprint Bcl-2 and apoptosis in chronic lymphocytic leukemia
    Aaron D Schimmer
    The Burnham Institute, Room 6308, 10901 N Torrey Pines Road, La Jolla, CA 92037, USA
    Curr Treat Options Oncol 4:211-8. 2003
    ..In addition, we anticipate that in the next decade, rationally designed therapies targeting specific molecular defects in the malignant CLL lymphocytes will be introduced into the clinic...