S L Gerson

Summary

Affiliation: Case Western Reserve University
Country: USA

Publications

  1. ncbi request reprint Leukocyte O6-alkylguanine-DNA alkyltransferase from human donors is uniformly sensitive to O6-benzylguanine
    S L Gerson
    Division of Hematology Oncology and the Ireland Cancer Center at Case Western Reserve University and University Hospital of Cleveland, Ohio 44106, USA
    Clin Cancer Res 5:521-4. 1999
  2. ncbi request reprint Clinical relevance of MGMT in the treatment of cancer
    Stanton L Gerson
    Division of Hematology Oncology and Comprehensive Cancer Center, University Hospitals of Cleveland, Case Western Reserve University School of Medicine, Cleveland, OH 44106 4937, USA
    J Clin Oncol 20:2388-99. 2002
  3. ncbi request reprint Transgenic expression of human MGMT blocks the hypersensitivity of PMS2-deficient mice to low dose MNU thymic lymphomagenesis
    X Qin
    Division of Hematology Oncology and the Ireland Cancer Center, Case Western Reserve University, Cleveland, OH 44106 4937, USA
    Carcinogenesis 20:1667-73. 1999
  4. ncbi request reprint Sequential tumor biopsies in early phase clinical trials of anticancer agents for pharmacodynamic evaluation
    A Dowlati
    Division of Hematology Oncology, Department of Medicine, Ireland Cancer Center at University Hospitals of Cleveland, 11100 Euclid Avenue, Cleveland, OH 44106, USA
    Clin Cancer Res 7:2971-6. 2001
  5. ncbi request reprint Overexpression of human O6-alkylguanine DNA alkyltransferase (AGT) prevents MNU induced lymphomas in heterozygous p53 deficient mice
    J S Reese
    Division of Hematology Oncology, University Hospitals of Cleveland, Cleveland, Ohio, OH 44106, USA
    Oncogene 20:5258-63. 2001
  6. ncbi request reprint Randomized cross-over trial of progenitor-cell mobilization: high-dose cyclophosphamide plus granulocyte colony-stimulating factor (G-CSF) versus granulocyte-macrophage colony-stimulating factor plus G-CSF
    O N Koc
    Department of Medicine, Case Western Reserve University, Cleveland, Ohio, USA
    J Clin Oncol 18:1824-30. 2000
  7. ncbi request reprint Human long-term culture initiating cells are sensitive to benzylguanine and 1,3-bis(2-chloroethyl)-1-nitrosourea and protected after mutant (G156A) methylguanine methyltransferase gene transfer
    O N Koc
    Division of Hematology Oncology, Case Western Reserve University University Hospitals Ireland Cancer Center, Cleveland, Ohio 44106, USA
    Cancer Gene Ther 6:340-8. 1999
  8. ncbi request reprint MMTV promoter hypomethylation is linked to spontaneous and MNU associated c-neu expression and mammary carcinogenesis in MMTV c-neu transgenic mice
    H Zhou
    Division of Hematology Oncology and Comprehensive Cancer Center, Case Western Reserve University, Cleveland, OH 44106 4937, USA
    Oncogene 20:6009-17. 2001
  9. ncbi request reprint Base excision repair as a therapeutic target in colon cancer
    Lili Liu
    Division of Hematology and Oncology, Department of Medicine, Case Western Reserve University, Cleveland, Ohio 44106, USA
    Clin Cancer Res 8:2985-91. 2002
  10. ncbi request reprint Heterozygous DNA mismatch repair gene PMS2-knockout mice are susceptible to intestinal tumor induction with N-methyl-N-nitrosourea
    X Qin
    Division of Hematology Oncology and Ireland Cancer Center, University Hospitals of Cleveland and Case Western Reserve University, Cleveland, OH 44106 4937, USA
    Carcinogenesis 21:833-8. 2000

Collaborators

Detail Information

Publications69

  1. ncbi request reprint Leukocyte O6-alkylguanine-DNA alkyltransferase from human donors is uniformly sensitive to O6-benzylguanine
    S L Gerson
    Division of Hematology Oncology and the Ireland Cancer Center at Case Western Reserve University and University Hospital of Cleveland, Ohio 44106, USA
    Clin Cancer Res 5:521-4. 1999
    ....
  2. ncbi request reprint Clinical relevance of MGMT in the treatment of cancer
    Stanton L Gerson
    Division of Hematology Oncology and Comprehensive Cancer Center, University Hospitals of Cleveland, Case Western Reserve University School of Medicine, Cleveland, OH 44106 4937, USA
    J Clin Oncol 20:2388-99. 2002
    ..MGMT remains a paradigm for development of new agents that modulate known mechanisms of drug resistance in cancer cells and raise the spectra of combinatorial therapies that encompass known drug resistance mechanisms...
  3. ncbi request reprint Transgenic expression of human MGMT blocks the hypersensitivity of PMS2-deficient mice to low dose MNU thymic lymphomagenesis
    X Qin
    Division of Hematology Oncology and the Ireland Cancer Center, Case Western Reserve University, Cleveland, OH 44106 4937, USA
    Carcinogenesis 20:1667-73. 1999
    ....
  4. ncbi request reprint Sequential tumor biopsies in early phase clinical trials of anticancer agents for pharmacodynamic evaluation
    A Dowlati
    Division of Hematology Oncology, Department of Medicine, Ireland Cancer Center at University Hospitals of Cleveland, 11100 Euclid Avenue, Cleveland, OH 44106, USA
    Clin Cancer Res 7:2971-6. 2001
    ..A major obstacle to target-based (often cytostatic) drug development has been obtaining relevant tumor tissue during clinical trials of these novel agents for laboratory analysis of the putative marker of drug effect...
  5. ncbi request reprint Overexpression of human O6-alkylguanine DNA alkyltransferase (AGT) prevents MNU induced lymphomas in heterozygous p53 deficient mice
    J S Reese
    Division of Hematology Oncology, University Hospitals of Cleveland, Cleveland, Ohio, OH 44106, USA
    Oncogene 20:5258-63. 2001
    ..These data demonstrate that unrepaired O6mG lesions act cooperatively with the reduced p53 dose and lead to lymphomagenesis in p53+/- mice, but AGT overexpression and rapid removal of O6mG adducts is protective...
  6. ncbi request reprint Randomized cross-over trial of progenitor-cell mobilization: high-dose cyclophosphamide plus granulocyte colony-stimulating factor (G-CSF) versus granulocyte-macrophage colony-stimulating factor plus G-CSF
    O N Koc
    Department of Medicine, Case Western Reserve University, Cleveland, Ohio, USA
    J Clin Oncol 18:1824-30. 2000
    ....
  7. ncbi request reprint Human long-term culture initiating cells are sensitive to benzylguanine and 1,3-bis(2-chloroethyl)-1-nitrosourea and protected after mutant (G156A) methylguanine methyltransferase gene transfer
    O N Koc
    Division of Hematology Oncology, Case Western Reserve University University Hospitals Ireland Cancer Center, Cleveland, Ohio 44106, USA
    Cancer Gene Ther 6:340-8. 1999
    ....
  8. ncbi request reprint MMTV promoter hypomethylation is linked to spontaneous and MNU associated c-neu expression and mammary carcinogenesis in MMTV c-neu transgenic mice
    H Zhou
    Division of Hematology Oncology and Comprehensive Cancer Center, Case Western Reserve University, Cleveland, OH 44106 4937, USA
    Oncogene 20:6009-17. 2001
    ..Expression of transgenic c-neu from the demethylated MMTV promoter appears to be an early event that allows outgrowth of mammary epithelium predisposed to malignant transformation...
  9. ncbi request reprint Base excision repair as a therapeutic target in colon cancer
    Lili Liu
    Division of Hematology and Oncology, Department of Medicine, Case Western Reserve University, Cleveland, Ohio 44106, USA
    Clin Cancer Res 8:2985-91. 2002
    ..DNA BER may be a useful pharmacological target through which tumor cells can be sensitized to alkylating therapeutic agents...
  10. ncbi request reprint Heterozygous DNA mismatch repair gene PMS2-knockout mice are susceptible to intestinal tumor induction with N-methyl-N-nitrosourea
    X Qin
    Division of Hematology Oncology and Ireland Cancer Center, University Hospitals of Cleveland and Case Western Reserve University, Cleveland, OH 44106 4937, USA
    Carcinogenesis 21:833-8. 2000
    ..Organ-specific factors might influence MMR- mediated resistance to methylating agents. Heterozygous PMS2 knockout mice may be used as a promising animal model for intestinal tumorigenesis studies involving environmental carcinogens...
  11. ncbi request reprint Differential degradation rates of inactivated alkyltransferase in blood mononuclear cells and tumors of patients after treatment with O(6)-benzylguanine
    L Liu
    Division of Hematology and Oncology, Department of Medicine, University Hospitals of Cleveland and Case Western Reserve University, 10900 Euclid Avenue, Cleveland, OH 44106-4937, USA
    Clin Cancer Res 7:2318-24. 2001
    ....
  12. pmc Removal of uracil by uracil DNA glycosylase limits pemetrexed cytotoxicity: overriding the limit with methoxyamine to inhibit base excision repair
    A D Bulgar
    Department of Medicine, Division of Hematology Oncology, Case Western Reserve University, Cleveland, OH, USA
    Cell Death Dis 3:e252. 2012
    ..Thus, targeting BER-based therapy exhibits more selective cytotoxicity on cancer cells through a synthetic lethal mechanism...
  13. pmc Applied molecular evolution of O6-benzylguanine-resistant DNA alkyltransferases in human hematopoietic cells
    B M Davis
    Division of Hematology/Oncology, Molecular Virology Training Program, and the Comprehensive Cancer Center at Case Western Reserve University and University Hospitals of Cleveland, Cleveland, OH 44106-4937, USA
    Proc Natl Acad Sci U S A 98:4950-4. 2001
    ..Of these, one was recovered significantly more frequently than the others. Upon further analysis, this mutant displayed a level of BG resistance in human hematopoietic cells greater than that of any previously reported mutant...
  14. ncbi request reprint Rapid hematopoietic recovery after coinfusion of autologous-blood stem cells and culture-expanded marrow mesenchymal stem cells in advanced breast cancer patients receiving high-dose chemotherapy
    O N Koc
    Departments of Medicine and Biology, Case Western Reserve University, Cleveland, OH 44106, USA
    J Clin Oncol 18:307-16. 2000
    ....
  15. ncbi request reprint Temozolomide: the effect of once- and twice-a-day dosing on tumor tissue levels of the DNA repair protein O(6)-alkylguanine-DNA-alkyltransferase
    T P Spiro
    Hematology Oncology Division, Department of Medicine, Case Western Reserve University and University Hospitals of Cleveland, Cleveland, OH 44106, USA
    Clin Cancer Res 7:2309-17. 2001
    ..Drug combinations or schedules designed to maximally deplete tumor AGT might improve TMZ efficacy...
  16. ncbi request reprint MGMT expression in murine bone marrow is a major determinant of animal survival after alkylating agent exposure
    J S Reese
    Division of Hematology/Oncology, Case Western Reserve University and University Hospitals, Ireland Cancer Center, Cleveland, OH 44106, USA
    J Hematother Stem Cell Res 10:115-23. 2001
    ..Thus, DNA repair involving AGT in hematopoietic cells is required for normal host survival following exposure to methylating and chloroethylating agents...
  17. ncbi request reprint Time-dependent effect of non-Hodgkin's lymphoma grade on disease-free survival of relapsed/refractory patients treated with high-dose chemotherapy plus autotransplantation
    P Fu
    Department of Epidemiology and Biostatistics, Case Comprehensive Cancer Center, Cleveland, Ohio 44106, United States
    Contemp Clin Trials 29:157-64. 2008
    ..65). The time-dependent effect of lymphoma grade on disease-free survival suggests the need for early (within first year) incorporation of novel therapeutic approaches in management of patients with indolent NHL undergoing autotransplant...
  18. ncbi request reprint High-dose carmustine, etoposide, and cisplatin for autologous stem cell transplantation with or without involved-field radiation for relapsed/refractory lymphoma: an effective regimen with low morbidity and mortality
    Punit D Wadhwa
    Department of Medicine, Comprehensive Cancer Center of the University Hospitals of Cleveland Case Western Reserve University, Cleveland, Ohio 44106, USA
    Biol Blood Marrow Transplant 11:13-22. 2005
    ..BEP with or without IFR is a highly effective and well-tolerated regimen in the relapsed/refractory lymphoma setting. It has low morbidity and transplant-related mortality and a low incidence (3%) of posttransplantation malignancy...
  19. ncbi request reprint Myeloablation is not required to select and maintain expression of the drug-resistance gene, mutant MGMT, in primary and secondary recipients
    Janice E Bowman
    Division of Hematology Oncology and the Comprehensive Cancer Center, University Hospitals of Cleveland and Case Western Reserve University School of Medicine, 10900 Euclid Avenue, BRB 3 West, Cleveland, Ohio 44106 4937, USA
    Mol Ther 8:42-50. 2003
    ..Thus, MFG mutant MGMT vectors transduce repopulating hematopoietic stem cells that may be used both for chemotherapeutic drug resistance and to enrich for second therapeutic genes...
  20. ncbi request reprint Systemic deficits in transporter for antigen presentation (TAP)-1 or proteasome subunit LMP2 have little or no effect on tumor incidence
    A K Johnsen
    Department of Pathology, Case Western Reserve University, Cleveland, OH, USA
    Int J Cancer 91:366-72. 2001
    ....
  21. ncbi request reprint Retroviral transduction and expression of the human alkyltransferase cDNA provides nitrosourea resistance to hematopoietic cells
    J A Allay
    Department of Medicine, Case Western Reserve University School of Medicine, Cleveland, Ohio 44106 4937, USA
    Blood 85:3342-51. 1995
    ..Overexpression of the alkyltransferase protein may protect hematopoietic progenitors from nitrosourea-induced myelosuppression...
  22. ncbi request reprint Allogeneic mesenchymal stem cell infusion for treatment of metachromatic leukodystrophy (MLD) and Hurler syndrome (MPS-IH)
    O N Koc
    Division of Hematology Oncology, Department of Medicine at Case Western Reserve University and University Hospitals of Cleveland, Cleveland, OH 44106, USA
    Bone Marrow Transplant 30:215-22. 2002
    ..We conclude that donor allogeneic MSC infusion is safe and may be associated with reversal of disease pathophysiology in some tissues. The role of MSCs in the management of Hurler syndrome and MLD should be further evaluated...
  23. ncbi request reprint Pharmacokinetics of O6-benzylguanine (NSC637037) and its metabolite, 8-oxo-O6-benzylguanine
    Kou Yi Tserng
    Louis Stokes Cleveland Department of Veterans Affairs Medical Center, Departments of Nutrition, Medicine, Mathematics, and Pharmacology, Case Western Reserve University, Ireland Cancer Center, University Hospitals of Cleveland, Cleveland, Ohio, USA
    J Clin Pharmacol 43:881-93. 2003
    ..This effect is not altered by coadministration of BCNU. The urinary excretion of drug and metabolites is minimal...
  24. ncbi request reprint Bone marrow-derived mesenchymal stem cells remain host-derived despite successful hematopoietic engraftment after allogeneic transplantation in patients with lysosomal and peroxisomal storage diseases
    O N Koc
    Department of Medicine, University of Hospitals of Cleveland, OH, USA
    Exp Hematol 27:1675-81. 1999
    ..Whether culture expanded normal MSCs can be successfully transplanted into patients with storage diseases and provide therapeutic benefit needs to be determined...
  25. ncbi request reprint DeltaMGMT-transduced bone marrow infusion increases tolerance to O6-benzylguanine and 1,3-bis(2-chloroethyl)-1-nitrosourea and allows intensive therapy of 1,3-bis(2-chloroethyl)-1-nitrosourea-resistant human colon cancer xenografts
    O N Koc
    Division of Hematology Oncology and the Ireland Cancer Center of University Hospitals of Cleveland and Case Western Reserve University, OH 44106, USA
    Hum Gene Ther 10:1021-30. 1999
    ....
  26. ncbi request reprint Hematopoietic engraftment and survival in adult recipients of umbilical-cord blood from unrelated donors
    M J Laughlin
    Department of Medicine, Ireland Cancer Center at University Hospitals of Cleveland and Case Western Reserve University, OH 44106 5065, USA
    N Engl J Med 344:1815-22. 2001
    ..We studied the use of transplantation of umbilical-cord blood to restore hematopoiesis in adults...
  27. ncbi request reprint A phase I and pharmacodynamic study of fludarabine, carboplatin, and topotecan in patients with relapsed, refractory, or high-risk acute leukemia
    Brenda W Cooper
    Department of Medicine, University Hospitals of Cleveland, Ireland Cancer Center, Case Western Reserve University, Cleveland, Ohio 44109, USA
    Clin Cancer Res 10:6830-9. 2004
    ..A novel regimen designed to maximize antileukemia activity of carboplatin through inhibiting repair of platinum-DNA adducts was conducted in poor prognosis, acute leukemia patients...
  28. ncbi request reprint Blockage of abasic site repair enhances antitumor efficacy of 1,3-bis-(2-chloroethyl)-1-nitrosourea in colon tumor xenografts
    Lili Liu
    Division of Hematology and Oncology, Department of Medicine, Case Western Reserve University, Cleveland, OH 44106, USA
    Mol Cancer Ther 2:1061-6. 2003
    ..Thus, targeting BER with MX is a promising strategy to improve the antitumor activity of BCNU and perhaps other DNA-damaging agents...
  29. ncbi request reprint Combined treatment with temozolomide and methoxyamine: blocking apurininc/pyrimidinic site repair coupled with targeting topoisomerase IIalpha
    Ling Yan
    Department of Medicine, Division of Hematology Oncology, Case Comprehensive Cancer Center, Case Western Reserve University, Cleveland, Ohio 44106, USA
    Clin Cancer Res 13:1532-9. 2007
    ..When located within topoisomerase IIalpha (topo II) cleavage sites in DNA, MX-AP sites act as dual lethal targets, not only functionally disrupting the base excision repair (BER) pathway but also potentially poisoning topo II...
  30. ncbi request reprint O6-benzylguanine and BCNU in multiple myeloma: a phase II trial
    Eric D Batts
    Developmental Therapeutics Program, CASE Comprehensive Cancer Center and the Division of Hematology Oncology, Case Western Reserve University, Cleveland, OH 44106, USA
    Cancer Chemother Pharmacol 60:415-21. 2007
    ..The objective of this study was to determine the safety and efficacy of depletion of MGMT activity in plasma cells using O6-benzylguanine (O6-BG) with BCNU in patients with multiple myeloma...
  31. ncbi request reprint Phase I and correlative study of combination bryostatin 1 and vincristine in relapsed B-cell malignancies
    Afshin Dowlati
    Developmental Therapeutics Program and the Division of Hematology Oncology, Department of Medicine, Case Western Reserve University School of Medicine and University Hospitals of Cleveland, Cleveland, Ohio 44106, USA
    Clin Cancer Res 9:5929-35. 2003
    ..Preclinical in vitro and in vivo studies demonstrate synergistic activity and increased tumor apoptosis in B-cell malignancies when a prolonged infusion of bryostatin 1 is followed by vincristine...
  32. ncbi request reprint Therapeutic impact of methoxyamine: blocking repair of abasic sites in the base excision repair pathway
    Lili Liu
    Division of Hematology and Oncology, Department of Medicine, Case Western Reserve University, Cleveland, OH 44106, USA
    Curr Opin Investig Drugs 5:623-7. 2004
    ..This review will establish the premise that targeting abasic sites formed during BER will disrupt this pathway and enhance the therapeutic efficacy of alkylating agents...
  33. ncbi request reprint Chemotherapy-induced O(6)-benzylguanine-resistant alkyltransferase mutations in mismatch-deficient colon cancer
    Lili Liu
    Division of Hematology and Oncology, Department of Medicine, Case Western Reserve University, 10900 Euclid Avenue, Cleveland, OH 44106 4937, USA
    Cancer Res 62:3070-6. 2002
    ..These results suggest that K165 AGT mutants arising in MMR-deficient tumor cells after treatment with chemotherapeutic agents are both resistant to BG-inactivation and are active in the repair of alkylated DNA adducts...
  34. ncbi request reprint A phase I and pharmacodynamic study of sequential topotecan and etoposide in patients with relapsed or refractory acute myelogenous and lymphoblastic leukemia
    Brenda W Cooper
    Department of Medicine, University Hospitals of Cleveland, Cleveland, OH 44106, USA
    Leuk Res 27:35-44. 2003
    ..The predicted up-regulation of topoisomerase II activity by topoisomerase I inhibition was not observed at this dose and schedule and may provide insight into the modest anti-leukemia activity of the regimen...
  35. pmc Hematologic effects of linezolid: summary of clinical experience
    Stanton L Gerson
    Division of Hematology Oncology and Ireland Cancer Center, Case Western Reserve University, University Hospitals of Cleveland, 10900 Euclid Avenue, Cleveland, OH 44106 4937, USA
    Antimicrob Agents Chemother 46:2723-6. 2002
    ..Hematologic abnormalities were consistent with mild, reversible, duration-dependent myelosuppression. Appropriate monitoring is warranted with linezolid use...
  36. pmc Prospective study of one- vs two-unit umbilical cord blood transplantation following reduced intensity conditioning in adults with hematological malignancies
    T L Kindwall-Keller
    Department of Medicine, Case Comprehensive Cancer Center, Case Western Reserve University, Cleveland, OH, USA
    Bone Marrow Transplant 47:924-33. 2012
    ..Taken together, one-unit UCB transplantation with a threshold cell dose 2.5 × 10(7)/kg recipient weight after RIC is a viable option for adults, although infusion of two units confers a lower relapse incidence...
  37. ncbi request reprint Hematopoietic stem cell gene therapy: progress toward therapeutic targets
    J L Vollweiler
    Division of Hematology Oncology, Comprehensive Cancer Center at University Hospitals of Cleveland, Case Western Reserve University School of Medicine, USA
    Bone Marrow Transplant 32:1-7. 2003
    ..The therapeutic potential of hematopoietic stem cell gene therapy, particularly given recent advances in stem cell plasticity, remains an exceptionally exciting area of clinical research...
  38. ncbi request reprint Mice defective in the DNA mismatch gene PMS2 are hypersensitive to MNU induced thymic lymphoma and are partially protected by transgenic expression of human MGMT
    X Qin
    Division of Hematology Oncology, Case Western Reserve University, Cleveland, Ohio, OH 44106 4937, USA
    Oncogene 18:4394-400. 1999
    ..These data suggest that PMS2 defective lymphomas may arise by the concerted action of environmental and perhaps endogenous methylation of DNA coupled to genomic instability...
  39. pmc Phase I trial of fludarabine, bortezomib and rituximab for relapsed and refractory indolent and mantle cell non-Hodgkin lymphoma
    Paul M Barr
    Department of Medicine, University Hospitals Case Medical Center, Cleveland, OH 44106, USA
    Br J Haematol 147:89-96. 2009
    ..Cumulative myelosuppression and neuropathy was observed. The combination of fludarabine, bortezomib, and rituximab appears to be an active regimen with manageable toxicity for relapsed NHL...
  40. ncbi request reprint MGMT: its role in cancer aetiology and cancer therapeutics
    Stanton L Gerson
    Case Comprehensive Cancer Center, University Hospitals of Cleveland and Case Western Reserve University, 10900 Euclid Ave, Cleveland, Ohio 44106, USA
    Nat Rev Cancer 4:296-307. 2004
  41. doi request reprint Direct detection and quantification of abasic sites for in vivo studies of DNA damage and repair
    Yanming Wang
    Division of Radiopharmaceutical Science, Case Center for Imaging Research, Department of Radiology, Case Western Reserve University, Cleveland, OH 44122, USA
    Nucl Med Biol 36:975-83. 2009
    ....
  42. ncbi request reprint Differential sensitivity of human and mouse alkyltransferase to O6-benzylguanine using a transgenic model
    L Liu
    Division of Hematology and Oncology, Department of Medicine, Case Western Reserve University School of Medicine, Cleveland, Ohio 44106 4937
    Cancer Res 56:1880-5. 1996
    ..This may influence the therapeutic index of O6-bG-BCNU combinations observed in human tumor xenograft-bearing mice...
  43. ncbi request reprint Pre-mobilization therapy blood CD34+ cell count predicts the likelihood of successful hematopoietic stem cell mobilization
    P Fu
    Department of Epidemiology and Biostatistics, University Hospitals of Cleveland, Cleveland, OH 44106, USA
    Bone Marrow Transplant 38:189-96. 2006
    ..Prospectively identifying individuals at risk for mobilization failure would allow for improved treatment planning, resource utilization and time saving...
  44. ncbi request reprint Repopulating defect of mismatch repair-deficient hematopoietic stem cells
    Jane S Reese
    BRB 3, 10900 Euclid Ave, Cleveland, OH 44106, USA
    Blood 102:1626-33. 2003
    ..Thus, mismatch repair deficiency is associated with a hematopoietic repopulation defect and stem cell exhaustion because of accumulation of genomic instability...
  45. ncbi request reprint Cancer gene therapy: scientific basis
    Punit D Wadhwa
    Division of Hematology Oncology and Comprehensive Cancer Center, University Hospitals of Cleveland and Case Western Reserve University, Cleveland, Ohio 44106 4937, USA
    Annu Rev Med 53:437-52. 2002
    ..Although no cures can consistently be expected from today's cancer gene therapy, the rapid progress may imply that such cures are a few short years away...
  46. pmc In vivo selection of MGMT(P140K) lentivirus-transduced human NOD/SCID repopulating cells without pretransplant irradiation conditioning
    Steven P Zielske
    Molecular Virology Program, Case Western Reserve University, Cleveland, Ohio 44106, USA
    J Clin Invest 112:1561-70. 2003
    ..To our knowledge, these results provide the first evidence of potent in vivo selection of MGMT(P140K) lentivirus-transduced human SRCs following BG/BCNU treatment...
  47. ncbi request reprint SarCNU mediates selection of P140K methylguanine-DNA-methyltransferase transduced human CD34(+) cells in vitro
    Steven P Zielske
    Molecular Virology Program, Division of Hematology Oncology and Comprehensive Cancer Center, Case Western Reserve University and University Hospitals of Cleveland, Cleveland, OH 44106, USA
    Blood Cells Mol Dis 31:48-50. 2003
    ..The IC(90) was increased sixfold by P140K MGMT transduction. These results suggest that SarCNU may be a suitable agent for in vivo selection strategies...
  48. ncbi request reprint Drug selection of mutant methylguanine methyltransferase from different oncoretroviral backbones results in multilineage hematopoietic transgene expression in primary and secondary recipients
    Brian M Davis
    Division of Hematology Oncology and the Comprehensive Cancer Center at Case Western Reserve University and University Hospitals of Cleveland, Cleveland, OH 44106 4937, USA
    J Hematother Stem Cell Res 12:375-87. 2003
    ..Regardless of the vector backbone used, multiorgan expression was observed without evidence of gene silencing. These data help establish mutant, BG-resistant MGMT as a potent selection gene for stem cell selection in vivo...
  49. ncbi request reprint Limited lentiviral transgene expression with increasing copy number in an MGMT selection model: lack of copy number selection by drug treatment
    Steven P Zielske
    Division of Hematology Oncology, Case Comprehensive Cancer Center and Center for Stem Cell and Regenerative Medicine, Case School of Medicine, Case Western Reserve University and University Hospitals of Cleveland, Cleveland, OH 44106, USA
    Mol Ther 9:923-31. 2004
    ..Thus drug selection would not be expected to increase the risk of oncogenesis due to exaggerated selection in favor of high-copy-number vector integration...
  50. ncbi request reprint An unusual case of autoimmune hemolytic anemia with reticulocytopenia, erythroid dysplasia, and an IgG2 autoanti-U
    G R Roush
    Department of Pathology, Case Western Reserve University, Cleveland, Ohio, USA
    Transfusion 36:575-80. 1996
    ..Early treatment with U- blood, in addition to steroids, may be beneficial...
  51. ncbi request reprint Measurement of anti-cancer agent methoxyamine in plasma by tandem mass spectrometry with on-line sample extraction
    Shuming Yang
    Department of Chemistry, Cleveland State University, Cleveland, OH 44115 2406, USA
    J Chromatogr B Analyt Technol Biomed Life Sci 795:295-307. 2003
    ..This method has been used to analyze the plasma levels of methoxyamine in samples obtained from male CD1 mice after bolus intraperitoneal injection of 2, 5 and 20mg methoxyamine hydrochloride (CH3ONH2.HCl) per kilogram mouse...
  52. ncbi request reprint Targeted modulation of MGMT: clinical implications
    Lili Liu
    Department of Medicine, Division of Hematology Oncology, Case Comprehensive Cancer Center, Case Western Reserve University, Cleveland, Ohio, USA
    Clin Cancer Res 12:328-31. 2006
    ..Because of its role in cancer etiology and chemotherapy resistance, MGMT is of particular interest. In this article, the clinical effect of MGMT expression and targeted modulation of MGMT will be summarized...
  53. ncbi request reprint DNA repair defects in stem cell function and aging
    Youngji Park
    Division of Hematology and Oncology, University Hospitals of Cleveland, Case Western Reserve University, Cleveland, Ohio 44106 4937, USA
    Annu Rev Med 56:495-508. 2005
    ..This discovery raises the possibility of a link between aging and stem cell dysfunction. In this review, we provide evidence for a link between DNA repair systems and the maintenance and longevity of stem cells...
  54. ncbi request reprint Lentiviral transduction of P140K MGMT into human CD34(+) hematopoietic progenitors at low multiplicity of infection confers significant resistance to BG/BCNU and allows selection in vitro
    Steven P Zielske
    Molecular Virology Program, Division of Hematology Oncology and Comprehensive Cancer Center, Case Western Reserve University and University Hospitals of Cleveland, Cleveland, Ohio 44106, USA
    Mol Ther 5:381-7. 2002
    ..Because drug selection will enrich for transduced progenitors, high MOI can be avoided, improving the safety profile of lentiviral gene transfer...
  55. ncbi request reprint Cytokines, including stem cell factor alone, enhance lentiviral transduction in nondividing human LTCIC and NOD/SCID repopulating cells
    Steven P Zielske
    Molecular Virology Program, Division of Hematology Oncology, and Comprehensive Cancer Center, Case Western Reserve University and University Hospitals of Cleveland, Cleveland, Ohio 44106, USA
    Mol Ther 7:325-33. 2003
    ..These data suggest that cytokines enhance lentiviral transduction of HSC, without requiring cell division, and maintain the stem cell phenotype. SCF stimulation alone was sufficient for high level transduction...
  56. pmc The role of DNA damage repair in aging of adult stem cells
    Jonathan Kenyon
    Case Western Reserve University and the Ireland Cancer Center, University Hospitals Case Medical Center, Cleveland, OH 44106, USA
    Nucleic Acids Res 35:7557-65. 2007
    ..Human diseases and animal models of loss of DNA repair provide longitudinal analysis of DNA repair processes in stem cell populations and may provide links to the physiology of aging...
  57. doi request reprint Bone marrow-derived cells exhibiting lung epithelial cell characteristics are enriched in vivo using methylguanine DNA methyltransferase-mediated drug resistance
    Jane S Reese
    Case Comprehensive Cancer Center, Case Western Reserve University, 11100 Euclid Avenue, Cleveland, Ohio 44106, USA
    Stem Cells 26:675-81. 2008
    ..These results suggest that expression of MGMT could enhance the capacity of bone marrow-derived cells to repopulate lung epithelium, and when used in combination with a gene of interest, MGMT could have therapeutic applications...
  58. ncbi request reprint Telomerase inhibition and telomere erosion: a two-pronged strategy in cancer therapy
    Fred O Odago
    Division of Hematology Oncology, Comprehensive Cancer Center, Case Western Reserve University and University Hospitals of Cleveland, 10900 Euclid Avenue, BRB 3 West, Cleveland, OH 44106 4937, USA
    Trends Pharmacol Sci 24:328-31. 2003
  59. doi request reprint Identification of 6-benzylthioinosine as a myeloid leukemia differentiation-inducing compound
    David N Wald
    Department of Pathology, Case Western Reserve School of Medicine, Cleveland, Ohio 44106, USA
    Cancer Res 68:4369-76. 2008
    ..Besides in vitro activity, 6BT also shows the ability to impair HL-60 and MV4-11 tumor growth in nude mice. 6BT is a promising new monocytic differentiation agent with apparent leukemic cell-specific activity...
  60. doi request reprint Phase I trial of VNP40101M (Cloretazine) in children with recurrent brain tumors: a pediatric brain tumor consortium study
    Sridharan Gururangan
    The Preston Robert Tisch Brain Tumor Center, Duke University Medical Center, Durham, North Carolina 27710, USA
    Clin Cancer Res 14:1124-30. 2008
    ..VNP40101M (Cloretazine), a novel DNA alkylating agent, was evaluated in a phase I study in children with recurrent brain tumors...
  61. ncbi request reprint Phase II trial of the O6-alkylguanine DNA alkyltransferase inhibitor O6-benzylguanine and 1,3-bis(2-chloroethyl)-1-nitrosourea in advanced melanoma
    Thomas F Gajewski
    Department of Medicine, University of Chicago, IL 60637, USA
    Clin Cancer Res 11:7861-5. 2005
    ..We postulated that the addition of O(6) benzylguanine (O(6)BG), a potent inactivator of AGT, would improve the clinical response to BCNU in melanoma...
  62. ncbi request reprint N-benzoylstaurosporine (PKC412) inhibits Akt kinase inducing apoptosis in multiple myeloma cells
    Nizar J Bahlis
    University of Calgary, Department of Medicine, Division of Hematology and Hematological Malignancies, Calgary, Alberta, Canada
    Leuk Lymphoma 46:899-908. 2005
    ..PKC412 is an appropriate candidate for novel treatment protocols for multiple myeloma...
  63. ncbi request reprint A randomized phase I and pharmacological trial of sequences of 1,3-bis(2-chloroethyl)-1-nitrosourea and temozolomide in patients with advanced solid neoplasms
    Lisa A Hammond
    Cancer Therapy and Research Center, University of San Antonio Health Science Center at San Antonio, San Antonio, Texas, USA
    Clin Cancer Res 10:1645-56. 2004
    ....
  64. ncbi request reprint A bicistronic SIN-lentiviral vector containing G156A MGMT allows selection and metabolic correction of hematopoietic protoporphyric cell lines
    Emmanuel Richard
    INSERM E0217, Universite Victor Segalen Bordeaux 2, France
    J Gene Med 5:737-47. 2003
    ..To overcome a preconditioning regimen, a selective growth advantage has to be conferred to the corrected cells...
  65. pmc Long-term-infected telomerase-immortalized endothelial cells: a model for Kaposi's sarcoma-associated herpesvirus latency in vitro and in vivo
    Feng Qi An
    Department of Molecular Genetics and Microbiology, University of Florida, Shands Cancer Center, Gainesville, FL 32610 0232, USA
    J Virol 80:4833-46. 2006
    ..KSHV-infected LTCs represent the first xenograft model for KS and should be of use to study KS pathogenesis and for the validation of anti-KS drug candidates...
  66. ncbi request reprint Differential competitive resistance to methylating versus chloroethylating agents among five O6-alkylguanine DNA alkyltransferases in human hematopoietic cells
    Aparecida Maria Fontes
    Division of Hematology Oncology and Comprehensive Cancer Center, Case Western Reserve University and University Hospitals of Cleveland, OH 44106 4955, USA
    Mol Cancer Ther 5:121-8. 2006
    ..The optimal mutant MGMT useful as a drug resistance gene may depend on whether a methylating or chloroethylating agent is used for drug selection...
  67. doi request reprint Bioluminescence imaging of hematopoietic stem cell repopulation in murine models
    Yuan Lin
    Department of Medicine, Division of Hematology Oncology, Case Western Reserve University, Cleveland, OH
    Methods Mol Biol 430:295-306. 2008
    ..Xenogen IVIS200 imaging system is used to record the process, and other similar imaging systems can also be used for this process...
  68. ncbi request reprint Adult bone marrow stem cells for cell and gene therapies: implications for greater use
    Christopher B Ballas
    Division of Hematology Oncology, Comprehensive Cancer Center at University Hospitals of Cleveland and Case Western Reserve University, Ohio, USA
    J Cell Biochem Suppl 38:20-8. 2002
    ..Recent information indicates HSCs, MSCs, and other cells in general may have more universal differentiation abilities than previously thought...
  69. ncbi request reprint Randomised comparison of two B-cell purging protocols for patients with B-cell non-Hodgkin lymphoma: in vivo purging with rituximab versus ex vivo purging with CliniMACS CD34 cell enrichment device
    Willem J van Heeckeren
    Department of Medicine, Case Western Reserve University and University Hospitals of Cleveland, OH, USA
    Br J Haematol 132:42-55. 2006
    ..Further studies are needed to determine whether rituximab purging is more effective than the use of unpurged autografts...