Januario E. Castro, M.D.

  1. Hematologist / Oncologist

出版物

  1. Kansu E, Ward D, Sanchez AP, Cunard R, Hayran M, Huseyin B, Vaughan M, Ku G, Curtin P, Mulroney C, Costello C, Castro JE, Wieduwilt M, Corringham S, Ihasz-Davis A, Nelson C, Ball ED. Extracorporeal photopheresis for the treatment of chronic graft versus host disease. Hematology. 2022 Dec; 27 (1):785-794
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  2. Iqbal M, Bansal R, Yassine F, Gandhi S, Rosenthal A, Moustafa MA, Li Z, Craver EC, Mohty R, Murthy H, Ayala E, Tun H, Munoz J, Castro J, Lin Y, Kharfan-Dabaja MA. Impact of rituximab and corticosteroids on late cytopenias post chimeric antigen receptor T-cell therapy. Transplant Cell Ther. 2022 Jul 13 Epub 2022 July 13
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  3. Melody M, Gandhi S, Saunders H, Abdel-Rahman Z, Hastings J, Lengerke Diaz P, Gannon N, Truong T, Hathcock M, Khurana A, Johnston P, Ansell S, Bennani N, Paludo J, Bisneto JV, Wang Y, Rosenthal A, Foran J, Ayala E, Murthy HS, Roy V, Castro JE, Lin Y, Kharfan-Dabaja MA. Incidence of thrombosis in relapsed/refractory B-cell lymphoma treated with axicabtagene ciloleucel: Mayo Clinic experience. Leuk Lymphoma. 2022 Jun; 63 (6):1363-1368 Epub 2022 Feb 03
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  4. Kumar D, Kashyap MK, Yu Z, Spaanderman I, Villa R, Kipps TJ, La Clair JJ, Burkart MD, Castro JE. Modulation of RNA splicing associated with Wnt signaling pathway using FD-895 and pladienolide B. Aging (Albany NY). 2022 Mar 1; 14 (5):2081-2100 Epub 2022 Mar 01
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  5. Castro JE, Lengerke-Diaz PA, Velez Lujan J, Choi MY, Moreno-Cortes EF, Forero JV, Garcia-Robledo JE, Jacobs C, McCarthy C, Heinen A, Amaya-Chanaga CI, Kipps TJ. Ibrutinib plus Obinutuzumab as Frontline Therapy for Chronic Lymphocytic Leukemia Is Associated with a Lower Rate of Infusion-Related Reactions and with Sustained Remissions after Ibrutinib Discontinuation: A Single-Arm, Open-Label, Phase 1b/2 Clinical Trial NCT0231576. Adv Hematol. 2022; 2022:4450824 Epub 2022 Jan 22
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  6. Locke FL, Miklos DB, Jacobson CA, Perales MA, Kersten MJ, Oluwole OO, Ghobadi A, Rapoport AP, McGuirk J, Pagel JM, Munoz J, Farooq U, van Meerten T, Reagan PM, Sureda A, Flinn IW, Vandenberghe P, Song KW, Dickinson M, Minnema MC, Riedell PA, Leslie LA, Chaganti S, Yang Y, Filosto S, Shah J, Schupp M, To C, Cheng P, Gordon LI, Westin JR, All ZUMA-7 Investigators and Contributing Kite Members. Axicabtagene Ciloleucel as Second-Line Therapy for Large B-Cell Lymphoma. N Engl J Med. 2021 Dec 11 [Epub ahead of print]
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  7. Forero-Forero JV, Lengerke-Diaz PA, Moreno-Cortes E, Melody M, Rahman ZA, Rosenthal AC, Kharfan-Dabaja MA, Castro JE. Predictors and management of relapse to Axicabtagene Ciloleucel in patients with aggressive B-cell lymphoma. Hematol Oncol Stem Cell Ther. 2021 Sep 20 Epub 2021 Sept 20
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  8. Shah BD, Bishop MR, Oluwole OO, Logan AC, Baer MR, Donnellan WB, O'Dwyer KM, Holmes H, Arellano ML, Ghobadi A, Pagel JM, Lin Y, Cassaday RD, Park J, Abedi M, Castro JE, DeAngelo DJ, Malone AK, Mawad R, Schiller GJ, Rossi JM, Bot A, Shen T, Goyal L, Jain RK, Vezan R, Wierda WG. KTE-X19 anti-CD19 CAR T-cell therapy in adult relapsed/refractory acute lymphoblastic leukemia: ZUMA-3 phase 1 results. Blood. 2021 Jul 8; 138 (1):11-22
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  9. Melody M, Gandhi S, Rahman ZA, Lengerke-Diaz P, Gannon N, Rosenthal A, Truong T, Novo M, Brandes E, Lange G, Estby B, Johnston P, Ansell S, Bennani NN, Paludo J, Bisneto JV, Ayala E, Tun HW, Murthy HS, Roy V, Foran J, Castro J, Lin Y, Kharfan-Dabaja MA. Impact of hypoalbuminemia on the prognosis of relapsed/refractory B-cell lymphoma treated with axicabtagene ciloleucel. Eur J Haematol. 2021 Jul; 107 (1):48-53 Epub 2021 Apr 15
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  10. Melody M, Rahman ZA, Saunders H, Diaz PL, Gannon N, Rosenthal A, Ayala E, Tun HW, Murthy H, Roy V, Foran J, Castro JE, Guru P, Kharfan-Dabaja MA. C-reactive protein and ferritin levels and length of intensive care unit stay in patients with B-cell lymphomas treated with axicabtagene ciloleucel. Hematol Oncol Stem Cell Ther. 2021 Jun; 14 (2):141-146 Epub 2020 Oct 13
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  11. Moreno-Cortes E, Forero-Forero JV, Lengerke-Diaz PA, Castro JE. Chimeric antigen receptor T cell therapy in oncology - Pipeline at a glance: Analysis of the ClinicalTrials.gov database. Crit Rev Oncol Hematol. 2021 Mar; 159:103239 Epub 2021 Jan 23
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  12. Ulep TH, Zenhausern R, Gonzales A, Knoff DS, Lengerke Diaz PA, Castro JE, Yoon JY. Smartphone based on-chip fluorescence imaging and capillary flow velocity measurement for detecting ROR1+ cancer cells from buffy coat blood samples on dual-layer paper microfluidic chip. Biosens Bioelectron. 2020 Apr 1; 153:112042 Epub 2020 Jan 22
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  13. Lujan JV, Lengerke-Diaz PA, Jacobs C, Moreno-Cortes EF, Ramirez-Segura CA, Choi MY, McCarthy C, Heinen A, Kipps TJ, Castro JE. Ibrutinib reduces obinutuzumab infusion-related reactions in patients with chronic lymphocytic leukemia and is associated with changes in plasma cytokine levels. Haematologica 2020 Jan; 105 (1):e22-e25 Epub 2019 May 02
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  14. Choi MY, Widhopf GF 2nd, Ghia EM, Kidwell RL, Hasan MK, Yu J, Rassenti LZ, Chen L, Chen Y, Pittman E, Pu M, Messer K, Prussak CE, Castro JE, Jamieson C, Kipps TJ. Phase I Trial: Cirmtuzumab Inhibits ROR1 Signaling and Stemness Signatures in Patients with Chronic Lymphocytic Leukemia. Cell Stem Cell. 2018 Jun 1; 22 (6):951-959.e3
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  15. Winston DJ, Mullane KM, Cornely OA, Boeckh MJ, Brown JW, Pergam SA, Trociukas I, Zak P, Craig MD, Papanicolaou GA, Velez JD, Panse J, Hurtado K, Fernsler DA, Stek JE, Pang L, Su SC, Zhao Y, Chan ISF, Kaplan SS, Parrino J, Lee I, Popmihajlov Z, Annunziato PW, Arvin A, V212 Protocol 001 Trial Team. Inactivated varicella zoster vaccine in autologous haemopoietic stem-cell transplant recipients: an international, multicentre, randomised, double-blind, placebo-controlled trial. Lancet. 2018 May 26; 391 (10135):2116-2127 Epub 2018 May 24
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  16. Neelapu SS, Locke FL, Bartlett NL, Lekakis LJ, Miklos DB, Jacobson CA, Braunschweig I, Oluwole OO, Siddiqi T, Lin Y, Timmerman JM, Stiff PJ, Friedberg JW, Flinn IW, Goy A, Hill BT, Smith MR, Deol A, Farooq U, McSweeney P, Munoz J, Avivi I, Castro JE, Westin JR, Chavez JC, Ghobadi A, Komanduri KV, Levy R, Jacobsen ED, Witzig TE, Reagan P, Bot A, Rossi J, Navale L, Jiang Y, Aycock J, Elias M, Chang D, Wiezorek J, Go WY. Axicabtagene Ciloleucel CAR T-Cell Therapy in Refractory Large B-Cell Lymphoma. N Engl J Med. 2017 Dec 28; 377 (26):2531-2544 Epub 2017 Dec 10
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  17. Leon B, Kashyap MK, Chan WC, Krug KA, Castro JE, La Clair JJ, Burkart MD. A Challenging Pie to Splice: Drugging the Spliceosome. Angew Chem Int Ed Engl. 2017 Sep 25; 56 (40):12052-12063 Epub 2017 Aug 15
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  18. Kashyap MK, Amaya-Chanaga CI, Kumar D, Simmons B, Huser N, Gu Y, Hallin M, Lindquist K, Yafawi R, Choi MY, Amine AA, Rassenti LZ, Zhang C, Liu SH, Smeal T, Fantin VR, Kipps TJ, Pernasetti F, Castro JE. Targeting the CXCR4 pathway using a novel anti-CXCR4 IgG1 antibody (PF-06747143) in chronic lymphocytic leukemia. J Hematol Oncol. 2017 May 19; 10 (1):112
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  19. León B, Kashyap MK, Chan WC, Krug KA, Castro JE, La Clair JJ, Burkart MD. Das Spliceosom als Angriffspunkt für Pharmaka. Angewandte Chemie. 2017; 129(40):12218-30.
  20. Barile E, Marconi GD, De SK, Baggio C, Gambini L, Salem AF, Kashyap MK, Castro JE, Kipps TJ, Pellecchia M. hBfl-1/hNOXA Interaction Studies Provide New Insights on the Role of Bfl-1 in Cancer Cell Resistance and for the Design of Novel Anticancer Agents. ACS Chem Biol. 2017 Feb 17; 12 (2):444-455 Epub 2016 Dec 27
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  21. Kharfan-Dabaja MA, Kumar A, Hamadani M, Stilgenbauer S, Ghia P, Anasetti C, Dreger P, Montserrat E, Perales MA, Alyea EP, Awan FT, Ayala E, Barrientos JC, Brown JR, Castro JE, Furman RR, Gribben J, Hill BT, Mohty M, Moreno C, O'Brien S, Pavletic SZ, Pinilla-Ibarz J, Reddy NM, Sorror M, Bredeson C, Carpenter P, Savani BN. Clinical Practice Recommendations for Use of Allogeneic Hematopoietic Cell Transplantation in Chronic Lymphocytic Leukemia on Behalf of the Guidelines Committee of the American Society for Blood and Marrow Transplantation. Biol Blood Marrow Transplant. 2016 Dec; 22 (12):2117-2125 Epub 2016 Sept 19
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  22. Kumar D, Kashyap MK, La Clair JJ, Villa R, Spaanderman I, Chien S, Rassenti LZ, Kipps TJ, Burkart MD, Castro JE. Selectivity in Small Molecule Splicing Modulation. ACS Chem Biol. 2016 Oct 21; 11 (10):2716-2723 Epub 2016 Aug 08
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  23. Dhar S, La Clair JJ, Leon B, Hammons JC, Yu Z, Kashyap MK, Castro JE, Burkart MD. A Carbohydrate-Derived Splice Modulator. J Am Chem Soc. 2016 Apr 20; 138 (15):5063-8 Epub 2016 Apr 08
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  24. Castro JE, Kipps TJ. Adoptive cellular therapy for chronic lymphocytic leukemia and B cell malignancies. CARs and more. Best Pract Res Clin Haematol. 2016 Mar; 29 (1):15-29 Epub 2016 Aug 20
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  25. Kashyap MK, Kumar D, Jones H, Amaya-Chanaga CI, Choi MY, Melo-Cardenas J, Ale-Ali A, Kuhne MR, Sabbatini P, Cohen LJ, Shelat SG, Rassenti LZ, Kipps TJ, Cardarelli PM, Castro JE. Ulocuplumab (BMS-936564 / MDX1338): a fully human anti-CXCR4 antibody induces cell death in chronic lymphocytic leukemia mediated through a reactive oxygen species-dependent pathway. Oncotarget. 2016 Jan 19; 7 (3):2809-22
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  26. Alvarnas JC, Brown PA, Aoun P, Ballen KK, Barta SK, Borate U, Boyer MW, Burke PW, Cassaday R, Castro JE, Coccia PF, Coutre SE, Damon LE, DeAngelo DJ, Douer D, Frankfurt O, Greer JP, Johnson RA, Kantarjian HM, Klisovic RB, Kupfer G, Litzow M, Liu A, Rao AV, Shah B, Uy GL, Wang ES, Zelenetz AD, Gregory K, Smith C. Acute Lymphoblastic Leukemia, Version 2.2015. J Natl Compr Canc Netw. 2015 Oct; 13 (10):1240-79
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  27. Kashyap MK, Kumar D, Villa R, La Clair JJ, Benner C, Sasik R, Jones H, Ghia EM, Rassenti LZ, Kipps TJ, Burkart MD, Castro JE. Targeting the spliceosome in chronic lymphocytic leukemia with the macrolides FD-895 and pladienolide-B. Haematologica. 2015 Jul; 100 (7):945-54 Epub 2015 Apr 10
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  28. Urquiza M, Melo-Cardenas J, Aguillon R, Kipps TJ, Castro JE. Intratumoral injection of Ad-ISF35 (Chimeric CD154) breaks tolerance and induces lymphoma tumor regression. Hum Gene Ther. 2015 Jan; 26 (1):14-25
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  29. James DF, Werner L, Brown JR, Wierda WG, Barrientos JC, Castro JE, Greaves A, Johnson AJ, Rassenti LZ, Rai KR, Neuberg D, Kipps TJ. Lenalidomide and rituximab for the initial treatment of patients with chronic lymphocytic leukemia: a multicenter clinical-translational study from the chronic lymphocytic leukemia research consortium. J Clin Oncol. 2014 Jul 1; 32 (19):2067-73 Epub 2014 May 27
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  30. Stout EP, Choi MY, Castro JE, Molinski TF. Potent fluorinated agelastatin analogues for chronic lymphocytic leukemia: design, synthesis, and pharmacokinetic studies. J Med Chem. 2014 Jun 26; 57 (12):5085-93 Epub 2014 June 10
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  31. Saif MW, Takimoto C, Mita M, Banerji U, Lamanna N, Castro J, O'Brien S, Stogard C, Von Hoff D. A phase 1, dose-escalation, pharmacokinetic and pharmacodynamic study of BIIB021 administered orally in patients with advanced solid tumors. Clin Cancer Res. 2014 Jan 15; 20 (2):445-55 Epub 2013 Oct 04
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  32. Castro JE, Choi MY, Carvajal T, Almahasnah E, Chang J, James DF, Kipps TJ. Ofatumumab and high-dose methylprednisolone for the treatment of patients with relapsed or refractory chronic lymphocytic leukemia. Blood Cancer J. 2014; 4:e258. Epub 2014 Nov 14.
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  33. Villa R, Kashyap MK, Kumar D, Kipps TJ, Castro JE, La Clair JJ, Burkart MD. Stabilized cyclopropane analogs of the splicing inhibitor FD-895. J Med Chem. 2013 Sep 12; 56 (17):6576-82 Epub 2013 Aug 21
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  34. Castro JE, Diaz-Perez JA, Barajas-Gamboa JS, Horton JM, Weidner N, Kipps TJ. Chronic lymphocytic leukemia associated with immunotactoid glomerulopathy: a case report of successful treatment with high-dose methylprednisolone in combination with rituximab followed by alemtuzumab. Leuk Lymphoma 2012 Sep; 53 (9):1835-8 Epub 2012 Mar 13
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  35. Castro JE, Melo-Cardenas J, Urquiza M, Barajas-Gamboa JS, Pakbaz RS, Kipps TJ. Gene immunotherapy of chronic lymphocytic leukemia: a phase I study of intranodally injected adenovirus expressing a chimeric CD154 molecule. Cancer Res. 2012 Jun 15; 72 (12):2937-48 Epub 2012 Apr 13
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  36. Melo-Cardenas J, Urquiza M, Kipps TJ, Castro JE. Intratumoral delivery of CD154 homolog (Ad-ISF35) induces tumor regression: analysis of vector biodistribution, persistence and gene expression. Cancer Gene Ther. 2012 May; 19 (5):336-44 Epub 2012 Mar 09
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  37. Holman PR, Costello C, deMagalhaes-Silverman M, Corringham S, Castro J, Ball ED. Idiotype immunization following high-dose therapy and autologous stem cell transplantation for non-Hodgkin lymphoma. Biol Blood Marrow Transplant. 2012 Feb; 18 (2):257-64 Epub 2011 July 04
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  38. Lu D, Choi MY, Yu J, Castro JE, Kipps TJ, Carson DA. Salinomycin inhibits Wnt signaling and selectively induces apoptosis in chronic lymphocytic leukemia cells. Proc Natl Acad Sci U S A. 2011 Aug 9; 108 (32):13253-7 Epub 2011 July 25
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  39. Wierda WG, Castro JE, Aguillon R, Sampath D, Jalayer A, McMannis J, Prussak CE, Keating M, Kipps TJ. A phase I study of immune gene therapy for patients with CLL using a membrane-stable, humanized CD154. Leukemia. 2010 Nov; 24 (11):1893-900 Epub 2010 Sept 30
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  40. Byrd JC, Kipps TJ, Flinn IW, Castro J, Lin TS, Wierda W, Heerema N, Woodworth J, Hughes S, Tangri S, Harris S, Wynne D, Molina A, Leigh B, O'Brien S. Phase 1/2 study of lumiliximab combined with fludarabine, cyclophosphamide, and rituximab in patients with relapsed or refractory chronic lymphocytic leukemia. Blood. 2010 Jan 21; 115 (3):489-95 Epub 2009 Oct 20
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  41. Jung AS, Holman PR, Castro JE, Carrier EK, Bashey A, Lane TA, Nelson CL, Pu M, Messer K, Corringham SM, Ball ED. Autologous hematopoietic stem cell transplantation as an intensive consolidation therapy for adult patients in remission from acute myelogenous leukemia. Biol Blood Marrow Transplant. 2009 Oct; 15 (10):1306-13 Epub 2009 Aug 03
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  42. Castro JE, James DF, Sandoval-Sus JD, Jain S, Bole J, Rassenti L, Kipps TJ. Rituximab in combination with high-dose methylprednisolone for the treatment of chronic lymphocytic leukemia. Leukemia. 2009 Oct; 23 (10):1779-89 Epub 2009 Aug 20
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  43. Castro JE, Sandoval-Sus JD, Bole J, Rassenti L, Kipps TJ. Rituximab in combination with high-dose methylprednisolone for the treatment of fludarabine refractory high-risk chronic lymphocytic leukemia. Leukemia. 2008 Nov; 22 (11):2048-53 Epub 2008 Aug 28
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  44. Fukuda T, Chen L, Endo T, Tang L, Lu D, Castro JE, Widhopf GF 2nd, Rassenti LZ, Cantwell MJ, Prussak CE, Carson DA, Kipps TJ. Antisera induced by infusions of autologous Ad-CD154-leukemia B cells identify ROR1 as an oncofetal antigen and receptor for Wnt5a. Proc Natl Acad Sci U S A. 2008 Feb 26; 105 (8):3047-52 Epub 2008 Feb 19
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  45. Castro JE, Sandoval JDS. Terapia biológica en cáncer: nuevos tiempos con una visión optimista. MedUNAB. 2008; 11(2):73-5.
  46. Bashey A, Donohue M, Liu L, Medina B, Corringham S, Ihasz A, Carrier E, Castro JE, Holman PR, Xu R, Law P, Ball ED, Lane TA. Peripheral blood progenitor cell mobilization with intermediate-dose cyclophosphamide, sequential granulocyte-macrophage-colony-stimulating factor and granulocyte-colony-stimulating factor, and scheduled commencement of leukapheresis in 225 patients undergoing autologous transplantation. Transfusion. 2007 Nov; 47 (11):2153-60
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  47. Dicker F, Kater AP, Prada CE, Fukuda T, Castro JE, Sun G, Wang JY, Kipps TJ. CD154 induces p73 to overcome the resistance to apoptosis of chronic lymphocytic leukemia cells lacking functional p53. Blood. 2006 Nov 15; 108 (10):3450-7 Epub 2006 June 01
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  48. Husain Z, Almeciga I, Delgado JC, Clavijo OP, Castro JE, Belalcazar V, Pinto C, Zuniga J, Romero V, Yunis EJ. Increased FasL expression correlates with apoptotic changes in granulocytes cultured with oxidized clozapine. Toxicol Appl Pharmacol. 2006 Aug 1; 214 (3):326-34 Epub 2006 Feb 28
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  49. Castro JE, Prada CE, Aguillon RA, Kitada S, Fukuda T, Motta M, Wu C, Dicker F, Sun G, Wang JY, Carson DA, Reed JC, Kipps TJ. Thymidine-phosphorothioate oligonucleotides induce activation and apoptosis of CLL cells independently of CpG motifs or BCL-2 gene interference. Leukemia. 2006 Apr; 20 (4):680-8
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  50. Bashey A, Liu L, Ihasz A, Medina B, Corringham S, Keese K, Carrier E, Castro JE, Holman P, Lane TA, Hassidim K, Ball ED. Non-anthracycline based remission induction therapy for newly diagnosed patients with acute myeloid leukemia aged 60 or older. Leuk Res. 2006 Apr; 30 (4):503-6 Epub 2005 Nov 21
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  51. Castro JE, Prada CE, Loria O, Kamal A, Chen L, Burrows FJ, Kipps TJ. ZAP-70 is a novel conditional heat shock protein 90 (Hsp90) client: inhibition of Hsp90 leads to ZAP-70 degradation, apoptosis, and impaired signaling in chronic lymphocytic leukemia. Blood. 2005 Oct 1; 106 (7):2506-12 Epub 2005 June 21
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  52. Mackus WJ, Kater AP, Grummels A, Evers LM, Hooijbrink B, Kramer MH, Castro JE, Kipps TJ, van Lier RA, van Oers MH, Eldering E. Chronic lymphocytic leukemia cells display p53-dependent drug-induced Puma upregulation. Leukemia. 2005 Mar; 19 (3):427-34
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  53. Lane TA, Bashey A, Carrier E, Holman P, Castro J, Mullen M, Ward DM, Ada O, Ball ED. Improving the efficiency of PBPC collection by pre-apheresis peripheral blood and mid-apheresis product measurements of CD34 cells. Cytotherapy. 2004; 6 (4):318-27
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  54. Wu CC, Castro JE, Motta M, Cottam HB, Kyburz D, Kipps TJ, Corr M, Carson DA. Selection of oligonucleotide aptamers with enhanced uptake and activation of human leukemia B cells. Hum Gene Ther. 2003 Jun 10; 14 (9):849-60
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  55. Castro JE, Ball ED. Development of allogeneic hematopoietic stem cell transplantation (HSCT). Cancer Treat Res. 2002; 110:1-37
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  56. Listman JA, Wang Y, Castro JE, Rimm IJ, Finn PW, Perkins DL. Detection of rare apoptotic T cells in vivo. Cytometry. 1998 Nov 1; 33 (3):340-7
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  57. Castro JE, Listman JA, Jacobson BA, Wang Y, Lopez PA, Ju S, Finn PW, Perkins DL. Fas modulation of apoptosis during negative selection of thymocytes. Immunity. 1996 Dec; 5 (6):617-27
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  58. Delgado J, Castro J, Landazábal G, Matiz E. Nesidioblastosis en adultos: Presentación de dos casos. Revista Colombiana de Cirugía. 1994; 9:196-200.
  59. Gamarra G, Balaguera H, Corzo D, Figueroa C, Castro JE, Delgado JC, González H, Díaz LA, Serrano MP. Tratamiento de la hipertensión arterial esencial con dieta rica en potasio. Acta Médica Colombiana. 1994; 19(1):15-23.
  60. Saavedra CH, Castro JE. Primary brain neoplasm: current concepts and case presentation. Medicas Universidad Industrial de Santander. 1991; 5(4):191-97.
  61. Corzo D, Castro J. Aspectos moleculares y usos terapéuticos del Sistema Interferón. Medicas Universidad Industrial de Santander. 1990; 3:182-91.
  62. González H, Castro J, Delgado J. SIDA Perinatal. Revisión del tema y Presentación de casos en Santander. Medical Universidad Industrial de Santander. 1990; 4:159-69.
  63. Castro JE. Anemia: do we know far enough? Medicas Universidad Industrial de Santander. 1989; 3(3):120-3.
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