Keywords
Last Name

Susan R. Doctrow, PhD

TitleResearch Associate Professor
InstitutionBoston University School of Medicine
DepartmentMedicine
DivisionPulmonary, Allergy, Sleep & Critical Care Medicine
Address72 E. Concord St Housman (R)
Boston MA 02118
Phone(617) 638-4866
ORCID ORCID Icon0000-0003-0628-9960
 Research Expertise & Professional Interests
Research interests include:

-Development & study of synthetic metal-based “mito-protective” superoxide dismutase/catalase (SOD/cat) mimetics.

-SOD/cat mimetics as potential mitigators of radiation injury and combined injury, for example, in a radiological accident or terrorism scenario.

-Broader interest in the role of mitochondrial oxidative injury in neurodegenerative and certain other pathological processes.

Over a number of years, beginning at the small pharmaceutical company Eukarion, we developed and have studied synthetic “mito-protective” superoxide dismutase/catalase (SOD/cat) mimetics as potential therapeutic agents for pathologies in which reactive oxygen species (ROS) and reactive nitrogen species (RNS) are implicated. We have focussed on two classes of compounds: (1) Salen manganese complexes that catalytically scavenge ROS and RNS and protect tissues in many experimental models for injury, disease, and degeneration. Examples of these compounds include the “classic” mimetics EUK-8 and EUK-134, the more lipophilic analog EUK-189, and the more biologically-stable cyclic analog EUK-207. All are active in vivo when administered by injection and infusion and, in some cases, topically. (2) Low molecular weight porphyrin manganese complexes, for example EUK-451, with oral bioavailability and anti-apoptotic activity.

In recent years, we’ve had a particular interest in SOD/cat mimetics as potential mitigators of delayed radiation injury. Our lab has conducted this work as part of two BioShield funded, NIAID administered multi-institution “Centers for Medical Countermeasures Against Radiation (CMCR)”. Our CMCRs have studied novel agents for their ability to mitigate delayed injury to kidney, lung, CNS, GI and skin in scenarios relevant to radiological terrorism. Delayed injury to these organ systems is expected to occur weeks, months or years after radiation exposure in survivors of the initial exposure. Such tissue damage is hypothesized to result from chronic oxidative stress through such mechanisms as “proinflammatory” cascades and/or mitochondrial dysfunction. Mitigating effects of SOD/cat mimetics support this hypothesis, and our ongoing research is aimed at elucidating this further. With Dr. John Moulder’s laboratory (Medical College of WI, MCW), we’ve found that EUK-207, initiated weeks after radiation, mitigates chronic renal injury induced by total body irradiation in rats. (This is of potential relevance not only to addressing consequences of radiological accidents or terrorism but also to long-term kidney damage seen in cancer patients undergoing bone marrow transplantation.) Other collaborating CMCR laboratories observe substantial radiation mitigating effects of EUK-207 in the lung (e.g. Mahmood et al., 2011) and brain. More complex scenarios involve “combined injury”, for example radiation and trauma. With collaborators in the labs of Dr Zela Lazarova (MCW) and Dr. Moulder, we’ve found that systemic EUK-207 given beginning 48 hrs after radiation, improves both skin inflammation and wound healing, including angiogenesis, in a rat combined injury (radiation/wounding) model (Doctrow, Lopez et al., 2012). Such data, along with their preservation of microvasculature in irradiated lung (Gao et al., 2012) and inhibition of radiation induced capillary endothelial cell apoptosis (Vorotnikova et al., 2010) suggest that SOD/cat mimetics mitigate injury, at least in part, at the level of the microvascular endothelial cell.

More broadly, we have had a longstanding interest in the role of oxidative stress in neurodegenerative and other disease models, based on the effectiveness, including “structure-activity relationships”, of SOD/cat mimetics. One key target for these compounds is the mitochondrion, an organelle whose dysfunction is strongly implicated in certain neurodegenerative and other chronic disorders. Mice lacking the mitochondrial form of SOD (sod2-/- mice) suffer severe, lethal pathologies due to mitochondrial oxidative injury. With Dr. Simon Melov’s laboratory (Buck Institute), we’ve found that salen Mn complexes, especially the more lipophilic EUK-189, protect the brain and peripheral organs, extending lifespan about 3-fold (Melov et al., 2001; Doctrow et al., 2005). Of all agents, synthetic and natural products, that have been tested so far, EUK-189 continues to be the most “mito-protective” agent in this model, with EUK-207 showing similar activity (Doctrow, Liesa et al., 2012). Studies by Drs. Marc Liesa and Ivan Luptak and colleagues in the labs of Drs Orian Shirihai and Bill Colucci at BUMC have shown that EUK-207 prevents mitochondrial injury in a model for heart ischemia/reperfusion, including in a mouse strain (ABCme -/+) with a mitochondrial impairment (Liesa et al, 2011). (This research was a collaboration through the Mitochondria ARC in the Evans Center for Interdisciplinary Biomedical Research.) Salen Mn complexes also prevent delayed radiation-induced mitochondrial injury, for example in rat astrocytes (Rosenthal et al., 2011). Besides “mito-protection” another likely site of intervention of these SOD/cat mimetics is through suppression of ROS-associated “proinflammatory” transcriptional pathways. For example, they suppress activation of NF kappa B and AP-1 while protecting tissues such as the brain and liver in certain in vivo injury models. Such effects have implications not only in disease and injury, but also in age-associated degeneration. Several years ago, work with Dr. Gordon Lithgow’s lab (Buck Institute) showed that EUK-8 and EUK-134 increased lifespan of c elegans, wild type as well as a strain with a mitochondrial dysfunction (mev-1) (Melov et al., 2000). Other studies with Dr. Michel Baudry’s lab (USC) showed that in aged mice, chronically infused EUK-189 or EUK-207 improved cognitive function in behavioral models, while suppressing numerous biochemical indicators of oxidative stress in the brain (Liu et al., 2003; Clausen et al., 2010). We continue to explore, with our key collaborators, how modulation of mitochondrial function and certain ROS- and RNS-dependent signaling pathways can mediate the effects of SOD/cat mimetics in complex models for injury, aging, and disease. With Pulmonary Center colleagues, we have begun to study asthma, a very complex disorder in which both chronic inflammation and mitochondrial dysfunction have been implicated. In collaboration with Drs. Bill Cruikshank and Marty Joyce-Brady, we are studying the impact of synthetic mito-protective SOD/catalase mimetics, alone or in combination with anti-inflammatory or other experimental therapeutic strategies, in asthma models.

 Self-Described Keywords
  • medicinal inorganic chemistry
  • oxidative stress and disease
  • Biologically active metal complexes
  • Biotechnology
  • Drug development
 Publications
Publications listed below are automatically derived from MEDLINE/PubMed and other sources, which might result in incorrect or missing publications. Faculty can login to make corrections and additions.
List All   |   Timeline
  1. Raber J, Davis MJ, Pfankuch T, Rosenthal R, Doctrow SR, Moulder JE. Mitigating effect of EUK-207 on radiation-induced cognitive impairments. Behav Brain Res. 2017 Mar 01; 320:457-463. PMID: 27789343.
    View in: PubMed
  2. Mahmood J, Jelveh S, Zaidi A, Doctrow SR, Medhora M, Hill RP. Targeting the Renin-angiotensin system combined with an antioxidant is highly effective in mitigating radiation-induced lung damage. Int J Radiat Oncol Biol Phys. 2014 Jul 15; 89(4):722-8. PMID: 24867538.
    View in: PubMed
  3. Kash JC, Xiao Y, Davis AS, Walters KA, Chertow DS, Easterbrook JD, Dunfee RL, Sandouk A, Jagger BW, Schwartzman LM, Kuestner RE, Wehr NB, Huffman K, Rosenthal RA, Ozinsky A, Levine RL, Doctrow SR, Taubenberger JK. Treatment with the reactive oxygen species scavenger EUK-207 reduces lung damage and increases survival during 1918 influenza virus infection in mice. Free Radic Biol Med. 2014 Feb; 67:235-47. PMID: 24140866.
    View in: PubMed
  4. Jelveh S, Kaspler P, Bhogal N, Mahmood J, Lindsay PE, Okunieff P, Doctrow SR, Bristow RG, Hill RP. Investigations of antioxidant-mediated protection and mitigation of radiation-induced DNA damage and lipid peroxidation in murine skin. Int J Radiat Biol. 2013 Aug; 89(8):618-27. PMID: 23484491.
    View in: PubMed
  5. Mahmood J, Jelveh S, Zaidi A, Doctrow SR, Hill RP. Mitigation of radiation-induced lung injury with EUK-207 and genistein: effects in adolescent rats. Radiat Res. 2013 Feb; 179(2):125-34. PMID: 23237541.
    View in: PubMed
  6. Doctrow SR, Lopez A, Schock AM, Duncan NE, Jourdan MM, Olasz EB, Moulder JE, Fish BL, Mäder M, Lazar J, Lazarova Z. A synthetic superoxide dismutase/catalase mimetic EUK-207 mitigates radiation dermatitis and promotes wound healing in irradiated rat skin. J Invest Dermatol. 2013 Apr; 133(4):1088-96. PMID: 23190879.
    View in: PubMed
  7. Villasana LE, Rosenthal RA, Doctrow SR, Pfankuch T, Zuloaga DG, Garfinkel AM, Raber J. Effects of alpha-lipoic acid on associative and spatial memory of sham-irradiated and 56Fe-irradiated C57BL/6J male mice. Pharmacol Biochem Behav. 2013 Jan; 103(3):487-93. PMID: 23051895.
    View in: PubMed
  8. Gao F, Fish BL, Szabo A, Doctrow SR, Kma L, Molthen RC, Moulder JE, Jacobs ER, Medhora M. Short-term treatment with a SOD/catalase mimetic, EUK-207, mitigates pneumonitis and fibrosis after single-dose total-body or whole-thoracic irradiation. Radiat Res. 2012 Nov; 178(5):468-80. PMID: 23020094.
    View in: PubMed
  9. Doctrow, S.R., Liesa, M., Melov, S., Shirihai, O.S., and Tofilon, P.J. Current Inorg. Chem. (in press). Salen Mn complexes are superoxide dismutase and catalase mimetics that protect the mitochondria. 2012.
  10. Joyce-Brady, M., Cruikshank, W., and Doctrow, S.R. . Antioxidant strategies in the treatment of bronchial asthma. Bronchial Asthma (in press). InTech. 2012.
  11. Mahmood J, Jelveh S, Calveley V, Zaidi A, Doctrow SR, Hill RP. Mitigation of lung injury after accidental exposure to radiation. Radiat Res. 2011 Dec; 176(6):770-80. PMID: 22013884.
    View in: PubMed
  12. Liesa M, Luptak I, Qin F, Hyde BB, Sahin E, Siwik DA, Zhu Z, Pimentel DR, Xu XJ, Ruderman NB, Huffman KD, Doctrow SR, Richey L, Colucci WS, Shirihai OS. Mitochondrial transporter ATP binding cassette mitochondrial erythroid is a novel gene required for cardiac recovery after ischemia/reperfusion. Circulation. 2011 Aug 16; 124(7):806-13. PMID: 21788586.
    View in: PubMed
  13. Mahmood J, Jelveh S, Calveley V, Zaidi A, Doctrow SR, Hill RP. Mitigation of radiation-induced lung injury by genistein and EUK-207. Int J Radiat Biol. 2011 Aug; 87(8):889-901. PMID: 21675818.
    View in: PubMed
  14. Rosenthal RA, Fish B, Hill RP, Huffman KD, Lazarova Z, Mahmood J, Medhora M, Molthen R, Moulder JE, Sonis ST, Tofilon PJ, Doctrow SR. Salen Mn complexes mitigate radiation injury in normal tissues. Anticancer Agents Med Chem. 2011 May 1; 11(4):359-72. PMID: 21453241.
    View in: PubMed
  15. Rosenthal RA, Doctrow SR, Callaway WB. Superoxide dismutase mimics. Antioxid Redox Signal. 2011 Mar 15; 14(6):1173; author reply 1174-6. PMID: 21110789.
    View in: PubMed
  16. Vorotnikova E, Rosenthal RA, Tries M, Doctrow SR, Braunhut SJ. Novel synthetic SOD/catalase mimetics can mitigate capillary endothelial cell apoptosis caused by ionizing radiation. Radiat Res. 2010 Jun; 173(6):748-59. PMID: 20518654.
    View in: PubMed
  17. Rosenthal RA, Huffman KD, Fisette LW, Damphousse CA, Callaway WB, Malfroy B, Doctrow SR. Orally available Mn porphyrins with superoxide dismutase and catalase activities. J Biol Inorg Chem. 2009 Aug; 14(6):979-91. PMID: 19504132.
    View in: PubMed
  18. Clausen A, Doctrow S, Baudry M. Prevention of cognitive deficits and brain oxidative stress with superoxide dismutase/catalase mimetics in aged mice. Neurobiol Aging. 2010 Mar; 31(3):425-33. PMID: 18571288.
    View in: PubMed
  19. Brazier MW, Doctrow SR, Masters CL, Collins SJ. A manganese-superoxide dismutase/catalase mimetic extends survival in a mouse model of human prion disease. Free Radic Biol Med. 2008 Jul 15; 45(2):184-92. PMID: 18455516.
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  20. Srinivasan V, Doctrow S, Singh VK, Whitnall MH. Evaluation of EUK-189, a synthetic superoxide dismutase/catalase mimetic as a radiation countermeasure. Immunopharmacol Immunotoxicol. 2008; 30(2):271-90. PMID: 18569084.
    View in: PubMed
  21. Peng J, Peng L, Stevenson FF, Doctrow SR, Andersen JK. Iron and paraquat as synergistic environmental risk factors in sporadic Parkinson's disease accelerate age-related neurodegeneration. J Neurosci. 2007 Jun 27; 27(26):6914-22. PMID: 17596439.
    View in: PubMed
  22. Limoli CL, Giedzinski E, Baure J, Doctrow SR, Rola R, Fike JR. Using superoxide dismutase/catalase mimetics to manipulate the redox environment of neural precursor cells. Radiat Prot Dosimetry. 2006; 122(1-4):228-36. PMID: 17166877.
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  23. Zhang HJ, Doctrow SR, Oberley LW, Kregel KC. Chronic antioxidant enzyme mimetic treatment differentially modulates hyperthermia-induced liver HSP70 expression with aging. J Appl Physiol (1985). 2006 Apr; 100(4):1385-91. PMID: 16254069.
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  24. Peng J, Stevenson FF, Doctrow SR, Andersen JK. Superoxide dismutase/catalase mimetics are neuroprotective against selective paraquat-mediated dopaminergic neuron death in the substantial nigra: implications for Parkinson disease. J Biol Chem. 2005 Aug 12; 280(32):29194-8. PMID: 15946937.
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  25. Melov S, Wolf N, Strozyk D, Doctrow SR, Bush AI. Mice transgenic for Alzheimer disease beta-amyloid develop lens cataracts that are rescued by antioxidant treatment. Free Radic Biol Med. 2005 Jan 15; 38(2):258-61. PMID: 15607908.
    View in: PubMed
  26. Doctrow, S.R., Baudry, M., Huffman, K., Malfroy, B., and Melov, S. . Salen-manganese complexes: multifunctional catalytic antioxidants protective in models for neurodegenerative diseases of aging. Medicinal Inorganic Chemistry (J. Sessler, S. R. Doctrow, T. McMurry, and S. Lippard, eds). ACS and Oxford University Press. 2005; 319-347.
  27. J. Sessler, S. R. Doctrow, T. McMurry, and S. Lippard (editors). Medicinal Inorganic Chemistry. American Chemical Society Symposium Series. ACS and Oxford University Press. 2005; 453 pages.
  28. Zhang HJ, Doctrow SR, Xu L, Oberley LW, Beecher B, Morrison J, Oberley TD, Kregel KC. Redox modulation of the liver with chronic antioxidant enzyme mimetic treatment prevents age-related oxidative damage associated with environmental stress. FASEB J. 2004 Oct; 18(13):1547-9. PMID: 15319374.
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  29. Friedman JS, Lopez MF, Fleming MD, Rivera A, Martin FM, Welsh ML, Boyd A, Doctrow SR, Burakoff SJ. SOD2-deficiency anemia: protein oxidation and altered protein expression reveal targets of damage, stress response, and antioxidant responsiveness. Blood. 2004 Oct 15; 104(8):2565-73. PMID: 15205258.
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  30. Browne SE, Roberts LJ, Dennery PA, Doctrow SR, Beal MF, Barlow C, Levine RL. Treatment with a catalytic antioxidant corrects the neurobehavioral defect in ataxia-telangiectasia mice. Free Radic Biol Med. 2004 Apr 1; 36(7):938-42. PMID: 15019978.
    View in: PubMed
  31. Hinerfeld D, Traini MD, Weinberger RP, Cochran B, Doctrow SR, Harry J, Melov S. Endogenous mitochondrial oxidative stress: neurodegeneration, proteomic analysis, specific respiratory chain defects, and efficacious antioxidant therapy in superoxide dismutase 2 null mice. J Neurochem. 2004 Feb; 88(3):657-67. PMID: 14720215.
    View in: PubMed
  32. Liu R, Liu IY, Bi X, Thompson RF, Doctrow SR, Malfroy B, Baudry M. Reversal of age-related learning deficits and brain oxidative stress in mice with superoxide dismutase/catalase mimetics. Proc Natl Acad Sci U S A. 2003 Jul 8; 100(14):8526-31. PMID: 12815103.
    View in: PubMed
  33. Liu R, Liu W, Doctrow SR, Baudry M. Iron toxicity in organotypic cultures of hippocampal slices: role of reactive oxygen species. J Neurochem. 2003 Apr; 85(2):492-502. PMID: 12675926.
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  34. Doctrow, S.R., Adinolfi, C., Baudry, M., Huffman, K., Malfroy, B., Marcus, C.B., Melov, S., Pong, K., Rong, Y., Smart, J., and Tocco, G. . Salen manganese complexes, combined superoxide dismutase/catalase mimetics, demonstrate potential for treating neurodegenerative and other age-associated diseases. Critical Reviews in Oxidative Stress and Aging: Advances in Basic Science, Diagnostics, and Intervention. (H. Rodriguez and R. Cutler, eds.). World Scientific Publishing Company. 2003; Chptr 71(Vol I):1324-43.
  35. Doctrow SR, Huffman K, Marcus CB, Tocco G, Malfroy E, Adinolfi CA, Kruk H, Baker K, Lazarowych N, Mascarenhas J, Malfroy B. Salen-manganese complexes as catalytic scavengers of hydrogen peroxide and cytoprotective agents: structure-activity relationship studies. J Med Chem. 2002 Sep 26; 45(20):4549-58. PMID: 12238934.
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  36. Pong K, Rong Y, Doctrow SR, Baudry M. Attenuation of zinc-induced intracellular dysfunction and neurotoxicity by a synthetic superoxide dismutase/catalase mimetic, in cultured cortical neurons. Brain Res. 2002 Sep 20; 950(1-2):218-30. PMID: 12231247.
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  37. Melov S, Doctrow SR, Schneider JA, Haberson J, Patel M, Coskun PE, Huffman K, Wallace DC, Malfroy B. Lifespan extension and rescue of spongiform encephalopathy in superoxide dismutase 2 nullizygous mice treated with superoxide dismutase-catalase mimetics. J Neurosci. 2001 Nov 1; 21(21):8348-53. PMID: 11606622.
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  38. Pong K, Doctrow SR, Huffman K, Adinolfi CA, Baudry M. Attenuation of staurosporine-induced apoptosis, oxidative stress, and mitochondrial dysfunction by synthetic superoxide dismutase and catalase mimetics, in cultured cortical neurons. Exp Neurol. 2001 Sep; 171(1):84-97. PMID: 11520123.
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  39. Giblin GM, Box PC, Campbell IB, Hancock AP, Roomans S, Mills GI, Molloy C, Tranter GE, Walker AL, Doctrow SR, Huffman K, Malfroy B. 6,6'-Bis(2-hydroxyphenyl)-2,2'-bipyridine manganese(III) complexes: a novel series of superoxide dismutase and catalase mimetics. Bioorg Med Chem Lett. 2001 Jun 4; 11(11):1367-70. PMID: 11378356.
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  40. Jung C, Rong Y, Doctrow S, Baudry M, Malfroy B, Xu Z. Synthetic superoxide dismutase/catalase mimetics reduce oxidative stress and prolong survival in a mouse amyotrophic lateral sclerosis model. Neurosci Lett. 2001 May 25; 304(3):157-60. PMID: 11343826.
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  41. Anderson I, Adinolfi C, Doctrow S, Huffman K, Joy KA, Malfroy B, Soden P, Rupniak HT, Barnes JC. Oxidative signalling and inflammatory pathways in Alzheimer's disease. Biochem Soc Symp. 2001; (67):141-9. PMID: 11447830.
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  42. Pong K, Doctrow SR, Baudry M. Prevention of 1-methyl-4-phenylpyridinium- and 6-hydroxydopamine-induced nitration of tyrosine hydroxylase and neurotoxicity by EUK-134, a superoxide dismutase and catalase mimetic, in cultured dopaminergic neurons. Brain Res. 2000 Oct 27; 881(2):182-9. PMID: 11036157.
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  43. Melov S, Ravenscroft J, Malik S, Gill MS, Walker DW, Clayton PE, Wallace DC, Malfroy B, Doctrow SR, Lithgow GJ. Extension of life-span with superoxide dismutase/catalase mimetics. Science. 2000 Sep 1; 289(5484):1567-9. PMID: 10968795.
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  44. Rupniak HT, Joy KA, Atkin C, Brown G, Barnes JC, Doctrow SR, Malfroy B, Wong T, Anderson IK, Molloy CR, Mills GI, Soden P. Oxidative neuropathology and putative chemical entities for Alzheimer's disease: neuroprotective effects of salen-manganese catalytic anti-oxidants. Neurotox Res. 2000; 2(2-3):167-78. PMID: 16787839.
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  45. Rong Y, Doctrow SR, Tocco G, Baudry M. EUK-134, a synthetic superoxide dismutase and catalase mimetic, prevents oxidative stress and attenuates kainate-induced neuropathology. Proc Natl Acad Sci U S A. 1999 Aug 17; 96(17):9897-902. PMID: 10449791.
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  46. Gerol M, Curry L, McCarroll L, Doctrow S, RayChaudhury A. Growth regulation of cultured endothelial cells by inflammatory cytokines: mitogenic, anti-proliferative and cytotoxic effects. Comp Biochem Physiol C Pharmacol Toxicol Endocrinol. 1998 Oct; 120(3):397-404. PMID: 9827056.
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  47. Baker K, Marcus CB, Huffman K, Kruk H, Malfroy B, Doctrow SR. Synthetic combined superoxide dismutase/catalase mimetics are protective as a delayed treatment in a rat stroke model: a key role for reactive oxygen species in ischemic brain injury. J Pharmacol Exp Ther. 1998 Jan; 284(1):215-21. PMID: 9435181.
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  48. Gonzalez PK, Doctrow SR, Malfroy B, Fink MP. Role of oxidant stress and iron delocalization in acidosis-induced intestinal epithelial hyperpermeability. Shock. 1997 Aug; 8(2):108-14. PMID: 9261900.
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  49. Malfroy B, Doctrow SR, Orr PL, Tocco G, Fedoseyeva EV, Benichou G. Prevention and suppression of autoimmune encephalomyelitis by EUK-8, a synthetic catalytic scavenger of oxygen-reactive metabolites. Cell Immunol. 1997 Apr 10; 177(1):62-8. PMID: 9140096.
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  50. Cruikshank WW, Doctrow SR, Falvo MS, Huffman K, Maciaszek J, Viglianti G, Raina J, Kornfeld H, Malfroy B. A lipidated anti-Tat antibody enters living cells and blocks HIV-1 viral replication. J Acquir Immune Defic Syndr Hum Retrovirol. 1997 Mar 1; 14(3):193-203. PMID: 9117450.
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  51. Doctrow SR, Huffman K, Marcus CB, Musleh W, Bruce A, Baudry M, Malfroy B. Salen-manganese complexes: combined superoxide dismutase/catalase mimics with broad pharmacological efficacy. Adv Pharmacol. 1997; 38:247-69. PMID: 8895812.
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  52. Doctrow SR, Huffman K, Marcus CB, Musleh W, Bruce A, Baudry M, Malfroy B. “Salen manganese complexes: combined superoxide dismutase/catalase mimics with broad pharmacological efficacy”. in Antioxidants in Disease Mechanisms and Therapeutic Strategies (H. Sies, ed.). Advances in Pharmacology. 1997; 38:247-269.
  53. Jordan T, Walus L, Velickovic A, Last T, Doctrow S, Liu H. A competitive chemiluminescent enzyme-linked immunosorbent assay for the determination of RMP-7 in human blood. J Pharm Biomed Anal. 1996 Sep; 14(12):1653-62. PMID: 8887712.
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  54. Gonzalez PK, Zhuang J, Doctrow SR, Malfroy B, Benson PF, Menconi MJ, Fink MP. Role of oxidant stress in the adult respiratory distress syndrome: evaluation of a novel antioxidant strategy in a porcine model of endotoxin-induced acute lung injury. Shock. 1996; 6 Suppl 1:S23-6. PMID: 8828094.
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  55. Gonzalez PK, Zhuang J, Doctrow SR, Malfroy B, Benson PF, Menconi MJ, Fink MP. EUK-8, a synthetic superoxide dismutase and catalase mimetic, ameliorates acute lung injury in endotoxemic swine. J Pharmacol Exp Ther. 1995 Nov; 275(2):798-806. PMID: 7473169.
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  56. Doctrow SR, Abelleira SM, Curry LA, Heller-Harrison R, Kozarich JW, Malfroy B, McCarroll LA, Morgan KG, Morrow AR, Musso GF, et al. The bradykinin analog RMP-7 increases intracellular free calcium levels in rat brain microvascular endothelial cells. J Pharmacol Exp Ther. 1994 Oct; 271(1):229-37. PMID: 7965719.
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  57. Höckel M, Schlenger K, Doctrow S, Kissel T, Vaupel P. Therapeutic angiogenesis. Arch Surg. 1993 Apr; 128(4):423-9. PMID: 7681277.
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  58. Trippel SB, Wroblewski J, Makower AM, Whelan MC, Schoenfeld D, Doctrow SR. Regulation of growth-plate chondrocytes by insulin-like growth-factor I and basic fibroblast growth factor. J Bone Joint Surg Am. 1993 Feb; 75(2):177-89. PMID: 8423178.
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  59. Friden PM, Walus LR, Watson P, Doctrow SR, Kozarich JW, Bäckman C, Bergman H, Hoffer B, Bloom F, Granholm AC. Blood-brain barrier penetration and in vivo activity of an NGF conjugate. Science. 1993 Jan 15; 259(5093):373-7. PMID: 8420006.
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  60. Trippel SB, Whelan MC, Klagsbrun M, Doctrow SR. Interaction of basic fibroblast growth factor with bovine growth plate chondrocytes. J Orthop Res. 1992 Sep; 10(5):638-46. PMID: 1323648.
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  61. Watson PM, Anderson JM, Vanltallie CM, Doctrow SR. The tight-junction-specific protein ZO-1 is a component of the human and rat blood-brain barriers. Neurosci Lett. 1991 Aug 5; 129(1):6-10. PMID: 1922971.
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  62. Kurokawa M, Doctrow SR, Klagsbrun M. Neutralizing antibodies inhibit the binding of basic fibroblast growth factor to its receptor but not to heparin. J Biol Chem. 1989 May 5; 264(13):7686-91. PMID: 2540201.
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  63. Ravid K, Rosenthal RA, Doctrow SR, Lowenstein JM. 28 kDa adenosine-binding proteins of brain and other tissues. Biochem J. 1989 Mar 15; 258(3):653-61. PMID: 2730563.
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  64. Bashkin P, Doctrow S, Klagsbrun M, Svahn CM, Folkman J, Vlodavsky I. Basic fibroblast growth factor binds to subendothelial extracellular matrix and is released by heparitinase and heparin-like molecules. Biochemistry. 1989 Feb 21; 28(4):1737-43. PMID: 2541764.
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  65. Doctrow, S.R. and Kulakowski, E.C. Angiogenesis modulators -- new drugs for controlling blood vessel growth?. Drug News and Perspectives. 1989; 2:74-81.
  66. Doctrow SR, Lowenstein JM. Inhibition of phosphatidylinositol kinase in vascular smooth muscle membranes by adenosine and related compounds. Biochem Pharmacol. 1987 Jul 15; 36(14):2255-62. PMID: 3038119.
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  67. Doctrow SR, Folkman J. Protein kinase C activators suppress stimulation of capillary endothelial cell growth by angiogenic endothelial mitogens. J Cell Biol. 1987 Mar; 104(3):679-87. PMID: 3469205.
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  68. Doctrow SR, Lowenstein JM. Adenosine and 5'-chloro-5'-deoxyadenosine inhibit the phosphorylation of phosphatidylinositol and myosin light chain in calf aorta smooth muscle. J Biol Chem. 1985 Mar 25; 260(6):3469-76. PMID: 3919023.
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