Klaus Podar

Summary

Affiliation: Harvard University
Country: USA

Publications

  1. pmc The small-molecule VEGF receptor inhibitor pazopanib (GW786034B) targets both tumor and endothelial cells in multiple myeloma
    Klaus Podar
    Department of Medical Oncology, Dana Farber Cancer Institute, Harvard Medical School, Boston, MA 02115, USA
    Proc Natl Acad Sci U S A 103:19478-83. 2006
  2. ncbi request reprint Targeting mitochondria to overcome conventional and bortezomib/proteasome inhibitor PS-341 resistance in multiple myeloma (MM) cells
    Dharminder Chauhan
    Dana Farber Cancer Institute, 44 Binney St, Boston, MA 02215, USA
    Blood 104:2458-66. 2004
  3. pmc CS1 promotes multiple myeloma cell adhesion, clonogenic growth, and tumorigenicity via c-maf-mediated interactions with bone marrow stromal cells
    Yu Tzu Tai
    LeBow Institute for Myeloma Therapeutics and Jerome Lipper Multiple Myeloma Center, Department of Medical Oncology, Dana Farber Cancer Institute, Boston, MA 02115, USA
    Blood 113:4309-18. 2009
  4. ncbi request reprint Molecular characterization of PS-341 (bortezomib) resistance: implications for overcoming resistance using lysophosphatidic acid acyltransferase (LPAAT)-beta inhibitors
    Teru Hideshima
    Jerome Lipper Multiple Myeloma Center, Department of Medical Oncology, Dana Farber Cancer Institute and Harvard Medical School, 44 Binney Street, Boston, MA 02115, USA
    Oncogene 24:3121-9. 2005
  5. pmc Targeting MEK induces myeloma-cell cytotoxicity and inhibits osteoclastogenesis
    Yu Tzu Tai
    The Jerome Lipper Multiple Myeloma Center, Department of Medical Oncology, Dana Farber Cancer Institute, Boston, MA 02115, USA
    Blood 110:1656-63. 2007
  6. ncbi request reprint Identification of genes regulated by 2-methoxyestradiol (2ME2) in multiple myeloma cells using oligonucleotide arrays
    Dharminder Chauhan
    The Jerome Lipper Multiple Myeloma Center, The Department of Medical Oncology, Cancer Biology, Boston Veteran Affairs Healthcare System, Boston, MA, USA
    Blood 101:3606-14. 2003
  7. ncbi request reprint The bortezomib/proteasome inhibitor PS-341 and triterpenoid CDDO-Im induce synergistic anti-multiple myeloma (MM) activity and overcome bortezomib resistance
    Dharminder Chauhan
    Jerome Lipper Multiple Myeloma Center, Department of Medical Oncology, Dana Farber Cancer Institute, Harvard Medical School, Boston, MA 02215, USA
    Blood 103:3158-66. 2004
  8. pmc Honokiol overcomes conventional drug resistance in human multiple myeloma by induction of caspase-dependent and -independent apoptosis
    Kenji Ishitsuka
    Department of Medical Oncology, Dana Farber Cancer Institute, 44 Binney St, Boston, MA 02115, USA
    Blood 106:1794-800. 2005
  9. pmc Functional interaction of plasmacytoid dendritic cells with multiple myeloma cells: a therapeutic target
    Dharminder Chauhan
    The LeBow Institute for Myeloma Therapeutics and Jerome Lipper Center for Myeloma Research, Department of Medical Oncology, Dana Farber Cancer Institute, Harvard Medical School, Boston, MA 02115, USA
    Cancer Cell 16:309-23. 2009
  10. ncbi request reprint BIRB 796 enhances cytotoxicity triggered by bortezomib, heat shock protein (Hsp) 90 inhibitor, and dexamethasone via inhibition of p38 mitogen-activated protein kinase/Hsp27 pathway in multiple myeloma cell lines and inhibits paracrine tumour growth
    Hiroshi Yasui
    Jerome Lipper Multiple Myeloma Center, Dana Farber Cancer Institute and Harvard Medical School, Boston, MA 02115, USA
    Br J Haematol 136:414-23. 2007

Detail Information

Publications78

  1. pmc The small-molecule VEGF receptor inhibitor pazopanib (GW786034B) targets both tumor and endothelial cells in multiple myeloma
    Klaus Podar
    Department of Medical Oncology, Dana Farber Cancer Institute, Harvard Medical School, Boston, MA 02115, USA
    Proc Natl Acad Sci U S A 103:19478-83. 2006
    ....
  2. ncbi request reprint Targeting mitochondria to overcome conventional and bortezomib/proteasome inhibitor PS-341 resistance in multiple myeloma (MM) cells
    Dharminder Chauhan
    Dana Farber Cancer Institute, 44 Binney St, Boston, MA 02215, USA
    Blood 104:2458-66. 2004
    ..Together, these preclinical studies suggest that combining bortezomib with PK may enhance its clinical efficacy, reduce attendant toxicity, and overcome conventional and bortezomib resistance in patients with relapsed refractory MM...
  3. pmc CS1 promotes multiple myeloma cell adhesion, clonogenic growth, and tumorigenicity via c-maf-mediated interactions with bone marrow stromal cells
    Yu Tzu Tai
    LeBow Institute for Myeloma Therapeutics and Jerome Lipper Multiple Myeloma Center, Department of Medical Oncology, Dana Farber Cancer Institute, Boston, MA 02115, USA
    Blood 113:4309-18. 2009
    ..These studies provide direct evidence of the role of CS1 in myeloma pathogenesis, define molecular mechanisms regulating its effects, and further support novel therapies targeting CS1 in MM...
  4. ncbi request reprint Molecular characterization of PS-341 (bortezomib) resistance: implications for overcoming resistance using lysophosphatidic acid acyltransferase (LPAAT)-beta inhibitors
    Teru Hideshima
    Jerome Lipper Multiple Myeloma Center, Department of Medical Oncology, Dana Farber Cancer Institute and Harvard Medical School, 44 Binney Street, Boston, MA 02115, USA
    Oncogene 24:3121-9. 2005
    ..Our studies therefore demonstrate that LPAAT-beta inhibitor CT-32615 triggers necrosis, even in PS-341-resistant DHL-4 cells, providing the framework for its evaluation to overcome clinical PS-341 resistance and improve patient outcome...
  5. pmc Targeting MEK induces myeloma-cell cytotoxicity and inhibits osteoclastogenesis
    Yu Tzu Tai
    The Jerome Lipper Multiple Myeloma Center, Department of Medical Oncology, Dana Farber Cancer Institute, Boston, MA 02115, USA
    Blood 110:1656-63. 2007
    ..Taken together, these results show that AZD6244 targets both MM cells and OCs in the BM microenvironment, providing the preclinical framework for clinical trials to improve patient outcome in MM...
  6. ncbi request reprint Identification of genes regulated by 2-methoxyestradiol (2ME2) in multiple myeloma cells using oligonucleotide arrays
    Dharminder Chauhan
    The Jerome Lipper Multiple Myeloma Center, The Department of Medical Oncology, Cancer Biology, Boston Veteran Affairs Healthcare System, Boston, MA, USA
    Blood 101:3606-14. 2003
    ..These studies may therefore allow improved therapeutic use of 2ME2, based upon targeting genes that regulate MM cell growth and survival...
  7. ncbi request reprint The bortezomib/proteasome inhibitor PS-341 and triterpenoid CDDO-Im induce synergistic anti-multiple myeloma (MM) activity and overcome bortezomib resistance
    Dharminder Chauhan
    Jerome Lipper Multiple Myeloma Center, Department of Medical Oncology, Dana Farber Cancer Institute, Harvard Medical School, Boston, MA 02215, USA
    Blood 103:3158-66. 2004
    ..Together, these findings provide the framework for clinical evaluation of CDDO-Im, either alone or in combination with bortezomib, to overcome drug resistance and improve patient outcome in MM...
  8. pmc Honokiol overcomes conventional drug resistance in human multiple myeloma by induction of caspase-dependent and -independent apoptosis
    Kenji Ishitsuka
    Department of Medical Oncology, Dana Farber Cancer Institute, 44 Binney St, Boston, MA 02115, USA
    Blood 106:1794-800. 2005
    ..Taken together, our results provide the preclinical rationale for clinical protocols of HNK to improve patient outcome in MM...
  9. pmc Functional interaction of plasmacytoid dendritic cells with multiple myeloma cells: a therapeutic target
    Dharminder Chauhan
    The LeBow Institute for Myeloma Therapeutics and Jerome Lipper Center for Myeloma Research, Department of Medical Oncology, Dana Farber Cancer Institute, Harvard Medical School, Boston, MA 02115, USA
    Cancer Cell 16:309-23. 2009
    ..Our study therefore validates targeting pDC-MM interactions as a therapeutic strategy to overcome drug resistance in MM...
  10. ncbi request reprint BIRB 796 enhances cytotoxicity triggered by bortezomib, heat shock protein (Hsp) 90 inhibitor, and dexamethasone via inhibition of p38 mitogen-activated protein kinase/Hsp27 pathway in multiple myeloma cell lines and inhibits paracrine tumour growth
    Hiroshi Yasui
    Jerome Lipper Multiple Myeloma Center, Dana Farber Cancer Institute and Harvard Medical School, Boston, MA 02115, USA
    Br J Haematol 136:414-23. 2007
    ....
  11. ncbi request reprint The biological sequelae of stromal cell-derived factor-1alpha in multiple myeloma
    Teru Hideshima
    Jerome Lipper Multiple Myeloma Center, Dana Farber Cancer Institute, and Harvard Medical School, Boston, Massachusetts 02115, USA
    Mol Cancer Ther 1:539-44. 2002
    ....
  12. ncbi request reprint A novel orally active proteasome inhibitor induces apoptosis in multiple myeloma cells with mechanisms distinct from Bortezomib
    Dharminder Chauhan
    The Jerome Lipper Multiple Myeloma Center, Department of Medical Oncology, Dana Farber Cancer Institute, Harvard Medical School, Boston, Massachusetts 02115, USA
    Cancer Cell 8:407-19. 2005
    ..Combining NPI-0052 and Bortezomib induces synergistic anti-MM activity. Our study therefore provides the rationale for clinical protocols evaluating NPI-0052, alone and together with Bortezomib, to improve patient outcome in MM...
  13. ncbi request reprint Transforming growth factor beta receptor I kinase inhibitor down-regulates cytokine secretion and multiple myeloma cell growth in the bone marrow microenvironment
    Toshiaki Hayashi
    Jerome Lipper Multiple Myeloma Center, Department of Medical Oncology, Dana Farber Cancer Institute, Boston, Massachusetts 02115, USA
    Clin Cancer Res 10:7540-6. 2004
    ....
  14. ncbi request reprint A novel carbohydrate-based therapeutic GCS-100 overcomes bortezomib resistance and enhances dexamethasone-induced apoptosis in multiple myeloma cells
    Dharminder Chauhan
    The Jerome Lipper Multiple Myeloma Center, Department of Medical Oncology, Dana Farber Cancer Institute, Harvard Medical School, Boston, Massachusetts 02115, USA
    Cancer Res 65:8350-8. 2005
    ....
  15. pmc Bortezomib induces canonical nuclear factor-kappaB activation in multiple myeloma cells
    Teru Hideshima
    Jerome Lipper Multiple Myeloma Center, Department of Medical Oncology, Dana Farber Cancer Institute, Boston, MA 02115, USA
    Blood 114:1046-52. 2009
    ..Moreover, IKKbeta inhibitors enhanced bortezomib-induced cytotoxicity. Our studies therefore suggest that bortezomib-induced cytotoxicity cannot be fully attributed to inhibition of canonical NF-kappaB activity in MM cells...
  16. ncbi request reprint MLN120B, a novel IkappaB kinase beta inhibitor, blocks multiple myeloma cell growth in vitro and in vivo
    Teru Hideshima
    Jerome Lipper Multiple Myeloma Center, Dana Farber Cancer Institute and Harvard Medical School, 44 Binney Street, Boston, MA 02115, USA
    Clin Cancer Res 12:5887-94. 2006
    ..The purpose of this study is to delineate the biological significance of IkappaB kinase (IKK) beta inhibition in multiple myeloma cells in the context of bone marrow stromal cells (BMSC) using a novel IKKbeta inhibitor MLN120B...
  17. ncbi request reprint Proteasomal degradation of topoisomerase I is preceded by c-Jun NH2-terminal kinase activation, Fas up-regulation, and poly(ADP-ribose) polymerase cleavage in SN38-mediated cytotoxicity against multiple myeloma
    Laurence Catley
    Department of Medical Oncology, Dana Farber Cancer Institute, Harvard Medical School, Boston, Massachusetts 02215, USA
    Cancer Res 64:8746-53. 2004
    ..These findings have clinical significance, because identification of downstream apoptotic signaling after topoisomerase I inhibition will both elucidate mechanisms of resistance and optimize future combination chemotherapy against MM...
  18. ncbi request reprint Caveolin-1 is required for vascular endothelial growth factor-triggered multiple myeloma cell migration and is targeted by bortezomib
    Klaus Podar
    Department of Medical Oncology, Jerome Lipper Multiple Myeloma Center, Dana Farber Cancer Institute, Harvard Medical School, Boston, Massachusetts, USA
    Cancer Res 64:7500-6. 2004
    ....
  19. ncbi request reprint FTY720 induces apoptosis in multiple myeloma cells and overcomes drug resistance
    Hiroshi Yasui
    Jerome Lipper Multiple Myeloma Center, Department of Medical Oncology, Dana Farber Cancer Institute, Harvard Medical School, Boston, Massachusetts 02115, USA
    Cancer Res 65:7478-84. 2005
    ..These results suggest that FTY720 overcomes drug resistance in multiple myeloma cells and provide the rationale for its clinical evaluation to improve patient outcome in multiple myeloma...
  20. pmc Janus kinase inhibitor INCB20 has antiproliferative and apoptotic effects on human myeloma cells in vitro and in vivo
    Renate Burger
    Jerome Lipper Multiple Myeloma Center, Department of Medical Oncology, Dana Farber Cancer Institute, Harvard Medical School, 44 Binney Street, Boston, MA 02115, USA
    Mol Cancer Ther 8:26-35. 2009
    ....
  21. pmc SDX-101, the R-enantiomer of etodolac, induces cytotoxicity, overcomes drug resistance, and enhances the activity of dexamethasone in multiple myeloma
    Hiroshi Yasui
    Jerome Lipper Multiple Myeloma Center, Department of Medical Oncology, Dana Farber Cancer Institute, Mayer 557, 44 Binney St, Boston, MA 02115, USA
    Blood 106:706-12. 2005
    ..Our data, therefore, indicate that R-etodolac circumvents drug resistance in MM cells at clinically relevant concentrations, targets Mcl-1, and can be synergistically combined with Dex...
  22. ncbi request reprint Antitumor activity of lysophosphatidic acid acyltransferase-beta inhibitors, a novel class of agents, in multiple myeloma
    Teru Hideshima
    Jerome Lipper Multiple Myeloma Center, Department of Medical Oncology, Dana Farber Cancer Institute and Harvard Medical School, Boston, Massachusetts 02115, USA
    Cancer Res 63:8428-36. 2003
    ..Our data therefore demonstrate for the first time that inhibiting LPAAT-beta induces cytotoxicity in MM cells in the bone marrow milieu, providing the framework for clinical trials of these novel agents in MM...
  23. ncbi request reprint Novel inosine monophosphate dehydrogenase inhibitor VX-944 induces apoptosis in multiple myeloma cells primarily via caspase-independent AIF/Endo G pathway
    Kenji Ishitsuka
    Jerome Lipper Multiple Myeloma Center, Department of Medical Oncology, Dana Farber Cancer Institute and Harvard Medical School, Boston, MA 02115, USA
    Oncogene 24:5888-96. 2005
    ....
  24. pmc Combination of proteasome inhibitors bortezomib and NPI-0052 trigger in vivo synergistic cytotoxicity in multiple myeloma
    Dharminder Chauhan
    The LeBow Institute for Myeloma Therapeutics and Jerome Lipper Center for Myeloma Research, Department of Medical Oncology, Dana Farber Cancer Institute, Boston, MA 02115, USA
    Blood 111:1654-64. 2008
    ..Taken together, our study provides the preclinical rationale for clinical protocols evaluating bortezomib together with NPI-0052 to improve patient outcome in MM...
  25. pmc Targeting mitochondrial factor Smac/DIABLO as therapy for multiple myeloma (MM)
    Dharminder Chauhan
    The Jerome Lipper Multiple Myeloma Center, Department of Medical Oncology, Dana Farber Cancer Institute, Harvard Medical School, Boston, MA 02115, USA
    Blood 109:1220-7. 2007
    ..Our study therefore provides the rationale for clinical protocols evaluating LBW242, alone and together with other anti-MM agents, to improve patient outcome in MM...
  26. ncbi request reprint Inhibition of Akt induces significant downregulation of survivin and cytotoxicity in human multiple myeloma cells
    Teru Hideshima
    Jerome Lipper Multiple Myeloma Center, Department of Medical Oncology, Dana Farber Cancer Institute and Harvard Medical School, Boston, MA 02115, USA
    Br J Haematol 138:783-91. 2007
    ..These preclinical studies provide the framework for clinical trials of bortezomib with Perifosine to improve patient outcome in MM...
  27. ncbi request reprint Insulin-like growth factor-1 induces adhesion and migration in human multiple myeloma cells via activation of beta1-integrin and phosphatidylinositol 3'-kinase/AKT signaling
    Yu Tzu Tai
    The Jerome Lipper Multiple Myeloma Center, Department of Medical Oncology, Dana Farber Cancer Institute, Boston, MA 02115, USA
    Cancer Res 63:5850-8. 2003
    ..Moreover, they define the functional association of IGF-IR and beta1 integrin in mediating MM cell homing, providing the preclinical rationale for novel treatment strategies targeting IGF-I/IGF-IR in MM...
  28. ncbi request reprint GW654652, the pan-inhibitor of VEGF receptors, blocks the growth and migration of multiple myeloma cells in the bone marrow microenvironment
    Klaus Podar
    Department of Medical Oncology, Jerome Lipper Multiple Myeloma Center, Harvard Medical School, Boston, MA 02115, USA
    Blood 103:3474-9. 2004
    ....
  29. ncbi request reprint Mechanisms by which SGN-40, a humanized anti-CD40 antibody, induces cytotoxicity in human multiple myeloma cells: clinical implications
    Yu Tzu Tai
    The Jerome Lipper Multiple Myeloma Center, Department of Medical Oncology, Dana Farber Cancer Institute, Harvard Medical School, Boston, Massachusetts, USA
    Cancer Res 64:2846-52. 2004
    ..1S cells and patient MM cells. Taken together, these results provide the preclinical rationale for the evaluation of SGN-40 as a potential new therapy to improve patient outcome in MM...
  30. ncbi request reprint CD40 induces human multiple myeloma cell migration via phosphatidylinositol 3-kinase/AKT/NF-kappa B signaling
    Yu Tzu Tai
    Jerome Lipper Multiple Myeloma Center, Department of Adult Oncology, Dana Farber Cancer Institute, Harvard Medical School, Boston, MA 02115, USA
    Blood 101:2762-9. 2003
    ....
  31. pmc Targeting PKC in multiple myeloma: in vitro and in vivo effects of the novel, orally available small-molecule inhibitor enzastaurin (LY317615.HCl)
    Klaus Podar
    Department of Medical Oncology, Dana Farber Cancer Institute, Harvard Medical School, Boston, MA 02115, USA
    Blood 109:1669-77. 2007
    ....
  32. ncbi request reprint Role of B-cell-activating factor in adhesion and growth of human multiple myeloma cells in the bone marrow microenvironment
    Yu Tzu Tai
    The Jerome Lipper Multiple Myeloma Center, Department of Medical Oncology, Dana Farber Cancer Institute, Harvard Medical School, 44 Binney Street, Boston, MA 02115, USA
    Cancer Res 66:6675-82. 2006
    ....
  33. ncbi request reprint Up-regulation of c-Jun inhibits proliferation and induces apoptosis via caspase-triggered c-Abl cleavage in human multiple myeloma
    Klaus Podar
    Jerome Lipper Multiple Myeloma Center, Medical Oncology, Dana Farber Cancer Institute, Harvard Medical School, 44 Binney Street, Boston, MA 02115, USA
    Cancer Res 67:1680-8. 2007
    ..Finally, our data suggest that this mechanism may not only be restricted to MM but may also be important in a broad range of malignancies including erythroleukemia and solid tumors...
  34. pmc Targeting PKC: a novel role for beta-catenin in ER stress and apoptotic signaling
    Marc S Raab
    LeBow Institute for Myeloma Therapeutics and Jerome Lipper Multiple Myeloma Center, Dana Farber Cancer Institute, Harvard Medical School, Boston, MA 02115, USA
    Blood 113:1513-21. 2009
    ..Moreover, we identify p73 as a potential novel therapeutic target in MM. Based on these and previous data, enzastaurin is currently under clinical investigation in a variety of hematologic malignancies, including MM...
  35. pmc Blockade of the MEK/ERK signalling cascade by AS703026, a novel selective MEK1/2 inhibitor, induces pleiotropic anti-myeloma activity in vitro and in vivo
    Kihyun Kim
    Department of Medical Oncology, The LeBow Institute for Myeloma Therapeutics and Jerome Lipper Multiple Myeloma Center, Dana Farber Cancer Institute, Harvard Medical School, Boston, MA 02115, USA
    Br J Haematol 149:537-49. 2010
    ..Our results therefore support clinical evaluation of AS703026, alone or in combination with other anti-MM agents, to improve patient outcome...
  36. ncbi request reprint JNK-dependent release of mitochondrial protein, Smac, during apoptosis in multiple myeloma (MM) cells
    Dharminder Chauhan
    Jerome Lipper Multiple Myeloma Center, Department of Medical Oncology, Dana Farber Cancer Institute, Harvard Medical School, Boston, Massachusetts 02115, USA
    J Biol Chem 278:17593-6. 2003
    ..These findings demonstrate that activation of JNK is an obligatory event for the release of Smac during stress-induced apoptosis in MM cells...
  37. ncbi request reprint Hsp27 inhibits release of mitochondrial protein Smac in multiple myeloma cells and confers dexamethasone resistance
    Dharminder Chauhan
    Jerome Lipper Multiple Myeloma Center, Medical Oncology, Dana Farber Cancer Institute, Harvard Medical School, Boston, MA 02215, USA
    Blood 102:3379-86. 2003
    ..Moreover, AS-Hsp27 overcomes interleukin-6 (IL-6)-mediated protection against Dex-induced apoptosis. These data demonstrate that Hsp27 inhibits the release of Smac, and thereby confers Dex resistance in MM cells...
  38. ncbi request reprint Combination of the mTOR inhibitor rapamycin and CC-5013 has synergistic activity in multiple myeloma
    Noopur Raje
    Jerome Lipper Multiple Myeloma Center, Dana Farber Cancer Institute, VA Boston Healthcare System and Harvard Medical School, Boston, MA 02115, USA
    Blood 104:4188-93. 2004
    ..These studies, therefore, provide the framework for clinical evaluation of mTOR inhibitors combined with IMiDs to improve patient outcome in MM...
  39. ncbi request reprint Human anti-CD40 antagonist antibody triggers significant antitumor activity against human multiple myeloma
    Yu Tzu Tai
    Jerome Lipper Multiple Myeloma Center, Department of Medical Oncology, Dana Farber Cancer Institute, Harvard Medical School, Boston, Massachusetts 02115, USA
    Cancer Res 65:5898-906. 2005
    ..These results provide the preclinical rationale for clinical trials of CHIR-12.12 to improve patient outcome in multiple myeloma...
  40. ncbi request reprint Activation of the PI3K/mTOR pathway by BCR-ABL contributes to increased production of reactive oxygen species
    Jeong H Kim
    Department of Medical Oncology, Dana Farber Cancer Institute, 44 Binney St, Boston, MA 02115, USA
    Blood 105:1717-23. 2005
    ..Finally, these results hint at novel targets for drug development that may aid traditional therapy...
  41. ncbi request reprint Proteasome inhibitor PS-341 abrogates IL-6 triggered signaling cascades via caspase-dependent downregulation of gp130 in multiple myeloma
    Teru Hideshima
    Department of Adult Oncology, Dana Farber Cancer Institute and Harvard Medical School, Jerome Lipper Multiple Myeloma Center, 44 Binney Street, Boston, MA 02155, USA
    Oncogene 22:8386-93. 2003
    ..Importantly, this effect on cytokine-induced gp130 signaling cascades may account, at least in part, for the remarkable preclinical sensitivity and clinical responses achieved in MM with PS-341 treatment...
  42. ncbi request reprint Patupilone (epothilone B) inhibits growth and survival of multiple myeloma cells in vitro and in vivo
    Boris Lin
    Jerome Lipper Multiple Myeloma Center, Department of Adult Oncology, Dana Farber Cancer Institute, Boston, MA 02115, USA
    Blood 105:350-7. 2005
    ..Taken together, these preclinical findings suggest that patupilone may be a safe and effective drug in the treatment of MM, providing the framework for clinical studies to improve patient outcome in MM...
  43. ncbi request reprint Molecular mechanisms whereby immunomodulatory drugs activate natural killer cells: clinical application
    Toshiaki Hayashi
    Department of Medical Oncology, Jerome Lipper Multiple Myeloma Center, Dana Farber Cancer Institute, and Department of Medicine, Harvard Medical School, Boston, MA 02115, USA
    Br J Haematol 128:192-203. 2005
    ..These studies defined the mechanisms whereby IMiDs trigger NK cell-mediated tumour-cell lysis, further supporting their therapeutic use in MM...
  44. ncbi request reprint Blockade of Hsp27 overcomes Bortezomib/proteasome inhibitor PS-341 resistance in lymphoma cells
    Dharminder Chauhan
    The Jerome Lipper Multiple Myeloma Center, Department of Medical Oncology, Dana Farber Cancer Institute, Harvard Medical School, Boston, MA 02115, USA
    Cancer Res 63:6174-7. 2003
    ..These findings provide the first evidence that Hsp27 confers PS-341 resistance...
  45. ncbi request reprint Superoxide-dependent and -independent mitochondrial signaling during apoptosis in multiple myeloma cells
    Dharminder Chauhan
    Department of Medical Oncology, The Jerome Lipper Multiple Myeloma Center, Dana Farber Cancer Institute, Harvard Medical School, Boston, MA 02115, USA
    Oncogene 22:6296-300. 2003
    ....
  46. pmc MLN3897, a novel CCR1 inhibitor, impairs osteoclastogenesis and inhibits the interaction of multiple myeloma cells and osteoclasts
    Sonia Vallet
    Jerome Lipper Multiple Myeloma Disease Center, Dana Farber Cancer Institute, Harvard Medical School, Boston, MA, USA
    Blood 110:3744-52. 2007
    ..Our results therefore show novel biologic sequelae of CCL3 and its inhibition in both osteoclastogenesis and MM cell growth, providing the preclinical rationale for clinical trials of MLN3897 to treat OBD in MM...
  47. doi request reprint Targeting angiogenesis via a c-Myc/hypoxia-inducible factor-1alpha-dependent pathway in multiple myeloma
    Jing Zhang
    Department of Medical Oncology, LeBow Institute for Myeloma Therapeutics, Boston, MA 02115, USA
    Cancer Res 69:5082-90. 2009
    ..Our data, therefore, identify Hif-1alpha as a novel molecular target in MM and add another facet to anti-MM drug activity...
  48. ncbi request reprint Critical role for hematopoietic cell kinase (Hck)-mediated phosphorylation of Gab1 and Gab2 docking proteins in interleukin 6-induced proliferation and survival of multiple myeloma cells
    Klaus Podar
    Department of Medical Oncology, Jerome Lipper Multiple Myeloma Center, Dana Farber Cancer Institute, 44 Binney Street, Boston, MA 02115, USA
    J Biol Chem 279:21658-65. 2004
    ....
  49. ncbi request reprint Combination therapy with interleukin-6 receptor superantagonist Sant7 and dexamethasone induces antitumor effects in a novel SCID-hu In vivo model of human multiple myeloma
    Pierfrancesco Tassone
    Jerome Lipper Multiple Myeloma Center, Dana Farber Cancer Institute and VA Boston Healthcare System, Harvard Medical School, Boston, Massachusetts 02115, USA
    Clin Cancer Res 11:4251-8. 2005
    ....
  50. ncbi request reprint The vascular endothelial growth factor receptor tyrosine kinase inhibitor PTK787/ZK222584 inhibits growth and migration of multiple myeloma cells in the bone marrow microenvironment
    Boris Lin
    Jerome Lipper Multiple Myeloma Center, Department of Adult Oncology, Dana Farber Cancer Institute, Boston, Massachusetts 02115, USA
    Cancer Res 62:5019-26. 2002
    ..The demonstrated anti-MM activity of PTK787, coupled with its antiangiogenic effects, provides the framework for clinical trials of this agent to overcome drug resistance and improve outcome in MM...
  51. ncbi request reprint Gene expression analysis of B-lymphoma cells resistant and sensitive to bortezomib
    Reshma Shringarpure
    Department of Medical Oncology, Dana Farber Cancer Institute, Boston, MA 02115, USA
    Br J Haematol 134:145-56. 2006
    ....
  52. ncbi request reprint Immunomodulatory drug lenalidomide (CC-5013, IMiD3) augments anti-CD40 SGN-40-induced cytotoxicity in human multiple myeloma: clinical implications
    Yu Tzu Tai
    Jerome Lipper Multiple Myeloma Center, Department of Medical Oncology, Dana Farber Cancer Institute, Harvard Medical School, Boston, MA 02115, USA
    Cancer Res 65:11712-20. 2005
    ....
  53. pmc Biologic sequelae of I{kappa}B kinase (IKK) inhibition in multiple myeloma: therapeutic implications
    Teru Hideshima
    Jerome Lipper Multiple Myeloma Center, Department of Medical Oncology, Dana Farber Cancer Institute, Boston, MA 02115, USA
    Blood 113:5228-36. 2009
    ..Combination therapy targeting these kinases therefore represents a promising treatment strategy in MM...
  54. pmc Perifosine, an oral bioactive novel alkylphospholipid, inhibits Akt and induces in vitro and in vivo cytotoxicity in human multiple myeloma cells
    Teru Hideshima
    Jerome Lipper Multiple Myeloma Center, Department of Medical Oncology, Dana Farber Cancer Institute, Mayer 557, 44 Binney Street, Boston, MA 02115, USA
    Blood 107:4053-62. 2006
    ..Taken together, our data provide the rationale for clinical trials of perifosine to improve patient outcome in MM...
  55. ncbi request reprint 2-Methoxyestradiol overcomes drug resistance in multiple myeloma cells
    Dharminder Chauhan
    Department of Adult Oncology, Dana Farber Cancer Institute, Harvard Medical School, 44 Binney Street, Boston, MA 02215, USA
    Blood 100:2187-94. 2002
    ..They provide a framework for the use of 2ME2, either alone or in combination with Dex, to overcome drug resistance and to improve outcome in MM...
  56. ncbi request reprint Molecular mechanisms mediating antimyeloma activity of proteasome inhibitor PS-341
    Teru Hideshima
    Jerome Lipper Multiple Myeloma Center, Dana Farber Cancer Institute and Harvard Medical School, Boston, MA 02115, USA
    Blood 101:1530-4. 2003
    ..Inhibition of JNK activity abrogates PS-341-induced MM cell death. These studies identify molecular targets of PS-341 and provide the rationale for the development of second-generation, more targeted therapies...
  57. ncbi request reprint p38 MAPK inhibition enhances PS-341 (bortezomib)-induced cytotoxicity against multiple myeloma cells
    Teru Hideshima
    Jerome Lipper Multiple Myeloma Center, Department of Medical Oncology, Dana Farber Cancer Institute and Harvard Medical School, Mayer 557, 44 Binney Street, Boston, MA 02115, USA
    Oncogene 23:8766-76. 2004
    ..These studies therefore provide the framework for clinical trials of SCIO-469 to enhance sensitivity and overcome resistance to PS-341, thereby improving patient outcome in MM...
  58. ncbi request reprint beta-lapachone, a novel plant product, overcomes drug resistance in human multiple myeloma cells
    Deepak Gupta
    Jerome Lipper Myeloma Center, Department of Adult Oncology, Dana Farber Cancer Institute, Boston, MA 02115, USA
    Exp Hematol 30:711-20. 2002
    ..1S); MM cell lines resistant to dexamethasone (MM.1R), melphalan (RPMI8226/LR5), doxorubicin (RPMI8226/DOX40), and mitoxantrone (RPMI8226/ MR20); and MM cells from patients (MM1-MM4)...
  59. doi request reprint The selective adhesion molecule inhibitor Natalizumab decreases multiple myeloma cell growth in the bone marrow microenvironment: therapeutic implications
    Klaus Podar
    Department of Medical Oncology, LeBow Institute for Myeloma Therapeutics, Boston, MA 02115, USA
    Br J Haematol 155:438-48. 2011
    ..Our data therefore provide the rationale for the clinical evaluation of Natalizumab, preferably in combination with novel agents (e.g. bortezomib) to enhance MM cytotoxicity and improve patient outcome...
  60. ncbi request reprint VEGF induces Mcl-1 up-regulation and protects multiple myeloma cells against apoptosis
    Steven Le Gouill
    Jerome Lipper Multiple Myeloma Center Department of Medical Oncology, Dana Farber Cancer Institute, Harvard Medical School, Boston, MA 02215, USA
    Blood 104:2886-92. 2004
    ..Our studies therefore demonstrate that VEGF-induced MM cell proliferation and survival are mediated via Mcl-1, providing the preclinical framework for novel therapeutics targeting Mcl-1 and/or VEGF to improve patient outcome in MM...
  61. ncbi request reprint Essential role of caveolae in interleukin-6- and insulin-like growth factor I-triggered Akt-1-mediated survival of multiple myeloma cells
    Klaus Podar
    Jerome Lipper Multiple Myeloma Center, Department of Medical Oncology, Dana Farber Cancer Institute, Harvard Medical School, Boston, Massachusetts 02115, USA
    J Biol Chem 278:5794-801. 2003
    ..Taken together, this study identifies caveolin-1 and other structural membrane components as potential new therapeutic targets in multiple myeloma...
  62. pmc Anti-CS1 humanized monoclonal antibody HuLuc63 inhibits myeloma cell adhesion and induces antibody-dependent cellular cytotoxicity in the bone marrow milieu
    Yu Tzu Tai
    Department of Medical Oncology, Jerome Lipper Multiple Myeloma Center, Dana Farber Cancer Institute, Harvard Medical School, Boston, MA 02115, USA
    Blood 112:1329-37. 2008
    ..These results thus define the functional significance of CS1 in MM and provide the preclinical rationale for testing HuLuc63 in clinical trials, either alone or in combination...
  63. ncbi request reprint Identification of genes regulated by dexamethasone in multiple myeloma cells using oligonucleotide arrays
    Dharminder Chauhan
    The Jerome Lipper Multiple Myeloma Center, Department of Adult Oncology, Dana Farber Cancer Institute, Harvard Medical School, Boston, Massachusetts, MA 02115, USA
    Oncogene 21:1346-58. 2002
    ..These studies may therefore allow improved therapeutic uses of Dex, based upon targeting genes that regulate MM cell growth and survival...
  64. pmc The Jak2V617F oncogene associated with myeloproliferative diseases requires a functional FERM domain for transformation and for expression of the Myc and Pim proto-oncogenes
    Gerlinde Wernig
    Department of Medicine, Brigham and Women s Hospital and Harvard Medical School, Boston, MA 02115, USA
    Blood 111:3751-9. 2008
    ..Overall, our results suggest that constitutive activation of Jak2 requires an intact FERM domain for a transforming phenotype, and is necessary for activation of the major target of Jak2, STAT5...
  65. doi request reprint Multiple myeloma
    Marc S Raab
    LeBow Institute for Myeloma Therapeutics and Jerome Lipper Center for Multiple Myeloma Research, Dana Farber Cancer Institute, Harvard Medical School, Boston, MA 02115, USA
    Lancet 374:324-39. 2009
    ..This treatment framework promises to improve outcome not only for patients with multiple myeloma, but also with other haematological malignancies and solid tumours...
  66. ncbi request reprint Vascular endothelial growth factor-induced migration of multiple myeloma cells is associated with beta 1 integrin- and phosphatidylinositol 3-kinase-dependent PKC alpha activation
    Klaus Podar
    Jerome Lipper Multiple Myeloma Research Center Dana Farber Cancer Institute and the Department of Medicine, Harvard Medical School, Boston, Massachusetts 02115, USA
    J Biol Chem 277:7875-81. 2002
    ..Time-lapse phase contrast video microscopy (TLVM) studies confirm the importance of these signaling components in VEGF-triggered MM cell migration on fibronectin...
  67. ncbi request reprint Critical role for Gab2 in transformation by BCR/ABL
    Martin Sattler
    Dana Farber Cancer Institute, Department of Adult Oncology, Harvard Medical School, 44 Binney Street, Boston, Massachusetts 02115, USA
    Cancer Cell 1:479-92. 2002
    ..Our results identify Gab2 and its associated proteins as key determinants of the lineage and severity of BCR/ABL transformation...
  68. ncbi request reprint Translocation of Ku86/Ku70 to the multiple myeloma cell membrane: functional implications
    Yu Tzu Tai
    The Jerome Lipper Multiple Myeloma Center, Department of Adult Oncology, Dana Farber Cancer Institute, Boston, MA 02115, USA
    Exp Hematol 30:212-20. 2002
    ..We here define the mechanism and functional significance of CD40-induced Ku translocation from the cytoplasm to the cell membrane in MM cells vs normal B cells...
  69. ncbi request reprint A novel small molecule met inhibitor induces apoptosis in cells transformed by the oncogenic TPR-MET tyrosine kinase
    Martin Sattler
    Department of Medical Oncology, Dana Farber Cancer Institute, Boston, Massachusetts 02115, USA
    Cancer Res 63:5462-9. 2003
    ..The characterization of SU11274 as an effective inhibitor of Met tyrosine kinase activity illustrates the potential of targeting for Met therapeutic use in cancers associated with activated forms of this kinase...
  70. pmc Effects of PKC412, nilotinib, and imatinib against GIST-associated PDGFRA mutants with differential imatinib sensitivity
    Ellen Weisberg
    Department of Medical Oncology, Dana Farber Cancer Institute, Boston, Massachusetts 02115, USA
    Gastroenterology 131:1734-42. 2006
    ..In this study, we compare the effects of 3 tyrosine kinase inhibitors, PKC412 and nilotinib, and imatinib, on 2 GIST-related PDGFRA mutants, V561D and D842V, which possess differential sensitivity to imatinib...
  71. ncbi request reprint CD40 activation induces p53-dependent vascular endothelial growth factor secretion in human multiple myeloma cells
    Yu Tzu Tai
    Department of Adult Oncology, Jerome Lipper Multiple Myeloma Center, Dana Farber Cancer Institute, Harvard Medical School, Boston, MA 02115, USA
    Blood 99:1419-27. 2002
    ..These studies demonstrate that CD40 induces VEGF secretion and MM cell migration, suggesting a role for CD40 in regulating MM homing and angiogenesis...
  72. ncbi request reprint The malignant clone and the bone-marrow environment
    Klaus Podar
    Department of Medical Oncology, Jerome Lipper Multiple Myeloma Center, Dana Farber Cancer Institute, Harvard Medical School, 44 Binney Street, Boston, MA 02115, USA
    Best Pract Res Clin Haematol 20:597-612. 2007
    ....
  73. ncbi request reprint The therapeutic role of targeting protein kinase C in solid and hematologic malignancies
    Klaus Podar
    Dana Farber Cancer Institute, Department of Medical Oncology, Jerome Lipper Multiple Myeloma Center, 44 Binney Street, Boston, MA 02115, USA
    Expert Opin Investig Drugs 16:1693-707. 2007
    ..Therefore, it is necessary to further dissect the relative contribution of PKC isozymes in the development and progression of specific tumors in order to identify therapeutic opportunities, using either PKC inhibitors or PKC activators...
  74. ncbi request reprint Blockade of ubiquitin-conjugating enzyme CDC34 enhances anti-myeloma activity of Bortezomib/Proteasome inhibitor PS-341
    Dharminder Chauhan
    Department of Medical Oncology, Harvard Medical School, The Jerome Lipper Multiple Myeloma Center, Dana Farber Cancer Institute, 44 Binney Street, Boston, MA 02115, USA
    Oncogene 23:3597-602. 2004
    ....
  75. ncbi request reprint Inhibition of VEGF signaling pathways in multiple myeloma and other malignancies
    Klaus Podar
    Department of Medical Oncology, Dana Farber Cancer Institute, Harvard Medical School, Boston, Massachusetts 02115, USA
    Cell Cycle 6:538-42. 2007
    ..Our own and others' work suggest that VEGF-inhibitors e.g., the small molecule VEGF receptor inhibitor pazopanib, may also improve patient outcome in MM...
  76. ncbi request reprint Targeting signalling pathways for the treatment of multiple myeloma
    Klaus Podar
    Department of Medical Oncology, Jerome Lipper Multiple Myeloma Center, Dana Farber Cancer Institute, Harvard Medical School, 44 Binney Street, Boston, MA 02115, USA
    Expert Opin Ther Targets 9:359-81. 2005
    ..Close collaboration between basic researchers and clinicians will be required to further improve our knowledge of MM pathophysiologically in order to translate advances from the bench to the bedside and improve patient outcome...
  77. ncbi request reprint FQPD, a novel immunomodulatory drug, has significant in vitro activity in multiple myeloma
    Shaji Kumar
    Division of Hematology, Mayo Clinic, Rochester, MN, USA
    Br J Haematol 132:698-704. 2006
    ..Our studies therefore demonstrated in vitro anti-MM activity of FQPD and provide the rationale for its in vivo evaluation in animal models and derived clinical trials...
  78. ncbi request reprint Targeting the vascular endothelial growth factor pathway in the treatment of multiple myeloma
    Klaus Podar
    Dana Farber Cancer Institute, Department of Medical Oncology, Jerome Lipper Multiple Myeloma Center, Boston, MA 02115, USA
    Expert Rev Anticancer Ther 7:551-66. 2007
    ..Important contributing effectors are tumor cell-stroma cell and cell-extracellular matrix contacts, the bone marrow vasculature, and a variety of cytokines and growth factors in the bone marrow milieu...