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Our Science – Keefer Website

Larry K. Keefer, Ph.D.

Selected Publications

1)  Wink DA, Kasprzak KS, Maragos CM, Elespuru RK, Misra M, Dunams TM, Cebula TA, Koch WH, Andrews AW, Allen JS.
DNA deaminating ability and genotoxicity of nitric oxide and its progenitors.
Science. 254: 1001-3, 1991.
2)  Maragos CM, Morley D, Wink DA, Dunams TM, Saavedra JE, Hoffman A, Bove AA, Isaac L, Hrabie JA, Keefer LK.
Complexes of .NO with nucleophiles as agents for the controlled biological release of nitric oxide. Vasorelaxant effects.
J. Med. Chem. 34: 3242-7, 1991.
3)  Hrabie JA, Klose JR, Wink DA, Keefer LK.
New nitric oxide-releasing zwitterions derived from polyamines.
Journal of Organic Chemistry. 58: 1472-1476, 1993.
4)  Saavedra JE, Billiar TR, Williams DL, Kim YM, Watkins SC, Keefer LK.
Targeting nitric oxide (NO) delivery in vivo. Design of a liver-selective NO donor prodrug that blocks tumor necrosis factor-alpha-induced apoptosis and toxicity in the liver.
J. Med. Chem. 40: 1947-54, 1997.
5)  Keefer LK, Roller PP.
N-nitrosation by nitrite ion in neutral and basic medium.
Science. 181: 1245-7, 1973.
6)  Biswas D, Hrabie JA, Saavedra JE, Cao Z, Keefer LK, Ivanic J, Holland RJ.
Aminolysis of an N-Diazeniumdiolated Amidine as an Approach to Diazeniumdiolated Ammonia.
J. Org. Chem. [Epub ahead of print], 2014.
7)  Kaczmarek MZ, Holland RJ, Lavanier SA, Troxler JA, Fesenkova VI, Hanson CA, Cmarik JL, Saavedra JE, Keefer LK, Ruscetti SK.
Mechanism of action for the cytotoxic effects of the nitric oxide prodrug JS-K in murine erythroleukemia cells.
Leuk. Res. 38: 377-82, 2014.
8)  Maciag AE, Holland RJ, Kim Y, Kumari V, Luthers CE, Sehareen WS, Biswas D, Morris NL, Ji X, Anderson LM, Saavedra JE, Keefer LK.
Nitric Oxide (NO) Releasing Poly ADP-ribose Polymerase 1 (PARP-1) Inhibitors Targeted to Glutathione S-Transferase P1-Overexpressing Cancer Cells.
J. Med. Chem. 57: 2292-302, 2014.
9)  Wang YN, Collins J, Holland RJ, Keefer LK, Ivanic J.
Decoding nitric oxide release rates of amine-based diazeniumdiolates.
J Phys Chem A. 117: 6671-7, 2013.
10)  Weidensteiner C, Reichardt W, Shami PJ, Saavedra JE, Keefer LK, Baumer B, Werres A, Jasinski R, Osterberg N, Weyerbrock A.
Effects of the nitric oxide donor JS-K on the blood-tumor barrier and on orthotopic U87 rat gliomas assessed by MRI.
Nitric Oxide. 30C: 17-25, 2013.
11)  Holland RJ, Paulisch R, Cao Z, Keefer LK, Saavedra JE, Donzelli S.
Enzymatic generation of the NO/HNO-releasing IPA/NO anion at controlled rates in physiological media using ß-galactosidase.
Nitric Oxide. 35: 131-6, 2013.
12)  Fuhrman BJ, Pfeiffer RM, Wu AH, Xu X, Keefer LK, Veenstra TD, Ziegler RG.
Green tea intake is associated with urinary estrogen profiles in Japanese-American women.
Nutr J. 12: 25, 2013.
13)  Maciag AE, Holland RJ, Robert Cheng YS, Rodriguez LG, Saavedra JE, Anderson LM, Keefer LK.
Nitric oxide-releasing prodrug triggers cancer cell death through deregulation of cellular redox balance.
Redox Biol. 1: 115-24, 2013.
14)  Holland RJ, Maciag AE, Kumar V, Shi L, Saavedra JE, Prud'homme RK, Chakrapani H, Keefer LK.
Cross-Linking Protein Glutathionylation Mediated by O(2)-Arylated Bis-Diazeniumdiolate 'Double JS-K'.
Chem. Res. Toxicol. 25: 2670-7, 2012.
15)  Nandurdikar RS, Maciag AE, Cao Z, Keefer LK, Saavedra JE.
Diazeniumdiolated carbamates: a novel class of nitric oxide donors.
Bioorg. Med. Chem. 20: 2025-9, 2012.
16)  Fuhrman BJ, Schairer C, Gail MH, Boyd-Morin J, Xu X, Sue LY, Buys SS, Isaacs C, Keefer LK, Veenstra TD, Berg CD, Hoover RN, Ziegler RG.
Estrogen metabolism and risk of breast cancer in postmenopausal women.
J. Natl. Cancer Inst. 104: 326-39, 2012.
17)  Kogias E, Osterberg N, Baumer B, Psarras N, Koentges C, Papazoglou A, Saavedra JE, Keefer LK, Weyerbrock A.
Growth-inhibitory and chemosensitizing effects of the glutathione-S-transferase-Ï€-activated nitric oxide donor PABA/NO in malignant gliomas.
Int. J. Cancer. 130: 1184-94, 2012.
18)  Weyerbrock A, Osterberg N, Psarras N, Baumer B, Kogias E, Werres A, Bette S, Saavedra JE, Keefer LK, Papazoglou A.
JS-K, a glutathione S-transferase-activated nitric oxide donor with antineoplastic activity in malignant gliomas.
Neurosurgery. 70: 497-510; discussion 510, 2012.
19)  Biswas D, Cao Z, Keefer LK, Saavedra JE.
Nitrous oxide as a primary product in base-mediated beta-elimination reactions of diazeniumdiolated benzylamine derivatives.
Chem Commun (Camb). 48: 5931-5933, 2012.
20)  Biswas D, Holland RJ, Deschamps JR, Cao Z, Keefer LK, Saavedra JE.
O2-Functionalized Methylamine Diazeniumdiolates: Evidence for E<->Z Equilibration in an Acyclic System.
J. Org. Chem. 77: 10804-10, 2012.
21)  Eisenbrand G, Gates KS, Hecht SS, Janzowski C, Keefer LK, Marnett LJ, Tannenbaum SR.
Richard Loeppky (1937-2012).
Chem. Res. Toxicol. 25: 1155-6, 2012.
22)  Nandurdikar RS, Maciag AE, Holland RJ, Cao Z, Shami PJ, Anderson LM, Keefer LK, Saavedra JE.
Structural modifications modulate stability of glutathione-activated arylated diazeniumdiolate prodrugs.
Bioorg. Med. Chem. 20: 3094-9, 2012.
23)  Hogg ME, Vavra AK, Banerjee MN, Martinez J, Jiang Q, Keefer LK, Chambon P, Kibbe MR.
The role of estrogen receptor alpha and beta in regulating vascular smooth muscle cell proliferation is based on sex.
J. Surg. Res. 173: e1-10, 2012.
24)  Maciag AE, Holland RJ, Saavedra JE, Chakrapani H, Shami PJ, Keefer LK.
Thiol Modification By Pharmacologically Active Agents of the Diazeniumdiolate Class.
For Immunopathol Dis Therap. 3: 91-95, 2012.
25)  Eliassen AH, Spiegelman D, Xu X, Keefer LK, Veenstra TD, Barbieri RL, Willett WC, Hankinson SE, Ziegler RG.
Urinary estrogens and estrogen metabolites and subsequent risk of breast cancer among premenopausal women.
Cancer Res. 72: 696-706, 2012.
26)  Maciag AE, Nandurdikar RS, Hong SY, Chakrapani H, Diwan B, Morris NL, Shami PJ, Shiao YH, Anderson LM, Keefer LK, Saavedra JE.
Activation of the c-Jun N-terminal Kinase/Activating Transcription Factor 3 (ATF3) Pathway Characterizes Effective Arylated Diazeniumdiolate-Based Nitric Oxide-Releasing Anticancer Prodrugs.
J. Med. Chem. 54: 7751-8, 2011.
27)  Weyerbrock A, Walbridge S, Saavedra JE, Keefer LK, Oldfield EH.
Differential effects of nitric oxide on blood-brain barrier integrity and cerebral blood flow in intracerebral C6 gliomas.
Neuro-oncology. 13: 203-11, 2011.
28)  Hogg ME, Varu VN, Vavra AK, Popowich DA, Banerjee MN, Martinez J, Jiang Q, Saavedra JE, Keefer LK, Kibbe MR.
Effect of nitric oxide on neointimal hyperplasia based on sex and hormone status.
Free Radic. Biol. Med. 50: 1065-74, 2011.
29)  Keefer LK.
Fifty years of diazeniumdiolate research. From laboratory curiosity to broad-spectrum biomedical advances.
ACS Chem. Biol. 6: 1147-55, 2011.
30)  Salmon DJ, Torres de Holding CL, Thomas L, Peterson KV, Goodman GP, Saavedra JE, Srinivasan A, Davies KM, Keefer LK, Miranda KM.
HNO and NO Release from a Primary Amine-Based Diazeniumdiolate As a Function of pH.
Inorg Chem. 50: 3262-70, 2011.
31)  Vavra AK, Havelka GE, Martinez J, Lee VR, Fu B, Jiang Q, Keefer LK, Kibbe MR.
Insights into the effect of nitric oxide and its metabolites nitrite and nitrate at inhibiting neointimal hyperplasia.
Nitric Oxide. 25: 22-30, 2011.
32)  McMurtry V, Saavedra JE, Nieves-Alicea R, Simeone AM, Keefer LK, Tari AM.
JS-K, a nitric oxide-releasing prodrug, induces breast cancer cell death while sparing normal mammary epithelial cells.
Int. J. Oncol. 38: 963-71, 2011.
33)  Qu W, Cheng L, Dill AL, Saavedra JE, Hong SY, Keefer LK, Waalkes MP.
Nitric oxide donor, V-PROLI/NO, provides protection against arsenical induced toxicity in rat liver cells: requirement for Cyp1a1.
Chem. Biol. Interact. 193: 88-96, 2011.
34)  Qu W, Cheng L, Dill A, Saavedra J, Hong S, Keefer L, Waalkes M.
Nitric oxide donor, V-PROLI/NO, provides protection against arsenical induced toxicity in rat liver cells: requirement for Cyp1a1.
Chem. Biol. Interact. 193: 88-96, 2011.
35)  Tsihlis ND, Oustwani CS, Vavra AK, Jiang Q, Keefer LK, Kibbe MR.
Nitric Oxide Inhibits Vascular Smooth Muscle Cell Proliferation and Neointimal Hyperplasia by Increasing the Ubiquitination and Degradation of UbcH10.
Cell Biochem. Biophys. 60: 89-97, 2011.
36)  Nandurdikar RS, Keefer LK, Saavedra JE.
Novel protection-deprotection strategies in diazeniumdiolate chemistry: synthesis of V-IPA/NO.
Chem. Commun. (Camb.). 47: 6710-2, 2011.
37)  Serrano MC, Vavra AK, Jen M, Hogg ME, Murar J, Martinez J, Keefer LK, Ameer GA, Kibbe MR.
Poly(diol-co-citrate)s as Novel Elastomeric Perivascular Wraps for the Reduction of Neointimal Hyperplasia.
Macromol Biosci. 11: 700-9, 2011.
38)  Maciag AE, Chakrapani H, Saavedra JE, Morris NL, Holland RJ, Kosak KM, Shami PJ, Anderson LM, Keefer LK.
The nitric oxide prodrug JS-K is effective against non-small-cell lung cancer cells in vitro and in vivo: involvement of reactive oxygen species.
J. Pharmacol. Exp. Ther. 336: 313-20, 2011.
39)  Oladeinde OA, Hong SY, Holland RJ, Maciag AE, Keefer LK, Saavedra JE, Nandurdikar RS.
"Click" reaction in conjunction with diazeniudiolate chemistry: Developing high-load nitric oxide donors.
Org. Lett. 12: 4256-9, 2010.
40)  Ziegler RG, Faupel-Badger JM, Sue LY, Fuhrman BJ, Falk RT, Boyd-Morin J, Henderson MK, Hoover RN, Veenstra TD, Keefer LK, Xu X.
A new approach to measuring estrogen exposure and metabolism in epidemiologic studies.
J. Steroid Biochem. Mol. Biol. 121: 538-45, 2010.
41)  Velazquez CA, Lynn GM, Kumar V, Keefer LK, Malhotra SV.
Arylation of sensitive 1-(pyrrolidin-1-yl)-diazen-1-ium-diolate in ionic liquids.
Synth. Commun. 40: 1322-32, 2010.
42)  Keefer LK.
Broad-spectrum anti-cancer activity of O2-arylated diazeniumdiolates.
Forum on Immunopathol. Dis. Ther. 1: 205-218, 2010.
43)  Chattopadhyay M, Velazquez CA, Pruski A, Nia KV, Abdellatif KR, Keefer LK, Kashfi K.
Comparison between 3-Nitrooxyphenyl acetylsalicylate (NO-ASA) and O2-(acetylsalicyloxymethyl)-1-(pyrrolidin-1-yl)diazen-1-ium-1,2-diolate (NONO-ASA) as safe anti-inflammatory, analgesic, antipyretic, antioxidant prodrugs.
J. Pharmacol. Exp. Ther. 335: 443-50, 2010.
44)  Faupel-Badger JM, Fuhrman BJ, Xu X, Falk RT, Keefer LK, Veenstra TD, Hoover RN, Ziegler RG.
Comparison of liquid chromatography-tandem mass spectrometry, RIA, and ELISA methods for measurement of urinary estrogens.
Cancer Epidemiol. Biomarkers Prev. 19: 292-300, 2010.
45)  Andrei D, Salmon DJ, Donzelli S, Wahab A, Klose JR, Citro ML, Saavedra JE, Wink DA, Miranda KM, Keefer LK.
Dual mechanisms of HNO generation by a nitroxyl prodrug of the diazeniumdiolate (NONOate) class.
J. Am. Chem. Soc. 132: 16526-32, 2010.
46)  Nandurdikar RS, Maciag AE, Hong SY, Chakrapani H, Citro ML, Keefer LK, Saavedra JE.
Glycosylated PROLI/NO derivatives as nitric oxide prodrugs.
Org. Lett. 12: 56-9, 2010.
47)  Varu VN, Ahanchi SS, Hogg ME, Bhikhapurwala HA, Chen A, Popowich DA, Vavra AK, Martinez J, Jiang Q, Saavedra JE, Hrabie JA, Keefer LK, Kibbe MR.
Insulin enhances the effect of nitric oxide at inhibiting neointimal hyperplasia in a rat model of type 1 diabetes.
Am. J. Physiol. Heart Circ. Physiol. 299: H772-9, 2010.
48)  Tsihlis ND, Murar J, Kapadia MR, Ahanchi SS, Oustwani CS, Saavedra JE, Keefer LK, Kibbe MR.
Isopropylamine NONOate (IPA/NO) moderates neointimal hyperplasia following vascular injury.
J. Vasc. Surg. 51: 1248-59, 2010.
49)  Kiziltepe T, Anderson KC, Kutok JL, Jia L, Boucher KM, Saavedra JE, Keefer LK, Shami PJ.
JS-K has potent anti-angiogenic activity in vitro and inhibits tumour angiogenesis in a multiple myeloma model in vivo.
J. Pharm. Pharmacol. 62: 145-51, 2010.
50)  Kiziltepe T, Anderson KC, Kutok JL, Jia L, Boucher KM, Saavedra JE, Keefer LK, Shami PJ.
JS-K has potent anti-angiogenic activity in vitro and inhibits tumour angiogenesis in a multiple myeloma model in vivo.
J. Pharm. Pharmacol. 62: 145-51, 2010.
51)  Nath N, Chattopadhyay M, Pospishil L, Cieciura LZ, Goswami S, Kodela R, Saavedra JE, Keefer LK, Kashfi K.
JS-K, a nitric oxide-releasing prodrug, modulates ß-catenin/TCF signaling in leukemic Jurkat cells: evidence of an S-nitrosylated mechanism.
Biochem. Pharmacol. 80: 1641-9, 2010.
52)  Weiss JM, Ridnour LA, Back T, Hussain SP, He P, Maciag AE, Keefer LK, Murphy WJ, Harris CC, Wink DA, Wiltrout RH.
Macrophage-dependent nitric oxide expression regulates tumor cell detachment and metastasis after IL-2/anti-CD40 immunotherapy.
J. Exp. Med. 207: 2455-67, 2010.
53)  Biswas D, Deschamps JR, Keefer LK, Hrabie JA.
Nitrogen-bound diazeniumdiolated amidines.
Chem. Commun. (Camb.). 46: 5799-801, 2010.
54)  Fuhrman BJ, Xu X, Falk RT, Hankinson SE, Veenstra TD, Keefer LK, Ziegler RG.
Stability of 15 estrogens and estrogen metabolites in urine samples under processing and storage conditions typically used in epidemiologic studies.
Int. J. Biol. Markers. 25: 185-94, 2010.
55)  Kumar V, Hong SY, Maciag AE, Saavedra JE, Adamson DH, Prud'homme RK, Keefer LK, Chakrapani H.
Stabilization of the nitric oxide (NO) prodrugs and anticancer leads, PABA/NO and Double JS-K, through incorporation into PEG-protected nanoparticles.
Mol. Pharm. 7: 291-8, 2010.
56)  Reynolds MM, Saavedra JE, Showalter BM, Valdez CA, Shanklin AP, Oh BK, Keefer LK, Meyerhoff ME.
Tailored Synthesis of Nitric Oxide-Releasing Polyurethanes Using O-Protected Diazeniumdiolated Chain Extenders.
J Mater Chem. 20: 3107-2114, 2010.
57)  Reynolds MM, Saavedra JE, Showalter BM, Valdez CA, Shanklin AP, Oh BK, Keefer LK, Meyerhoff ME.
Tailored synthesis of nitric oxide-releasing polyurethanes using O-protected diazeniumdiolated chain extenders.
J. Mater. Chem. 20: 3107-14, 2010.
58)  Hong SY, Borchert GL, Maciag AE, Nandurdikar RS, Saavedra JE, Keefer LK, Phang JM, Chakrapani H.
The Nitric Oxide Prodrug V-PROLI/NO Inhibits Cellular Uptake of Proline.
ACS medicinal chemistry letters. 1: 386-389, 2010.
59)  Hong SY, Nandurdikar RS, Keefer LK, Saavedra JE, Chakrapani H.
An improved synthesis of V-PROLI/NO, a cytochrome P450-activated nitric oxide prodrug.
Tetrahedron Lett. 50: 4545-8, 2009.
60)  Liu J, Malavya S, Wang X, Saavedra JE, Keefer LK, Tokar E, Qu W, Waalkes MP, Shami PJ.
Gene expression profiling for nitric oxide prodrug JS-K to kill HL-60 myeloid leukemia cells.
Genomics. 94: 32-8, 2009.
61)  Hong SY, Saavedra JE, Keefer LK, Chakrapani H.
Improved synthesis of V-PYRRO/NO, a liver-selective nitric oxide prodrug, and analogues.
Tetrahedron Lett. 50: 2069-71, 2009.
62)  Shami PJ, Maciag AE, Eddington JK, Udupi V, Kosak KM, Saavedra JE, Keefer LK.
JS-K, an arylating nitric oxide (NO) donor, has synergistic anti-leukemic activity with cytarabine (ARA-C).
Leuk. Res. 33: 1525-9, 2009.
63)  Kitagaki J, Yang Y, Saavedra JE, Colburn NH, Keefer LK, Perantoni AO.
Nitric oxide prodrug JS-K inhibits ubiquitin E1 and kills tumor cells retaining wild-type p53.
Oncogene. 28: 619-24, 2009.
64)  Bohle DS, Keefer LK, Saavedra JE.
Primary amine diazeniumdiolate ions of structure [RNN(O)NOR']- as ambident nucleophiles.
Tetrahedron Lett. 50: 5917-19, 2009.
65)  Fuhrman BJ, Pfeiffer R, Xu X, Wu AH, Korde L, Gail MH, Keefer LK, Veenstra TD, Hoover RN, Ziegler RG.
Soy intake is associated with increased 2-hydroxylation and decreased 16alpha-hydroxylation of estrogens in Asian-American women.
Cancer Epidemiol. Biomarkers Prev. 18: 2751-60, 2009.
66)  Rai G, Sayed AA, Lea WA, Luecke HF, Chakrapani H, Prast-Nielsen S, Jadhav A, Leister W, Shen M, Inglese J, Austin CP, Keefer L, Arnér ES, Simeonov A, Maloney DJ, Williams DL, Thomas CJ.
Structure mechanism insights and the role of nitric oxide donation guide the development of oxadiazole-2-oxides as therapeutic agents against schistosomiasis.
J. Med. Chem. 52: 6474-83, 2009.
67)  Nandurdikar RS, Maciag AE, Citro ML, Shami PJ, Keefer LK, Saavedra JE, Chakrapani H.
Synthesis and evaluation of piperazine and homopiperazine analogues of JS-K, an anti-cancer lead compound.
Bioorg. Med. Chem. Lett. 19: 2760-2, 2009.
68)  Maciag AE, Saavedra JE, Chakrapani H.
The nitric oxide prodrug JS-K and its structural analogues as cancer therapeutic agents.
Anti-cancer Agents Med. Chem. 9: 798-803, 2009.
69)  Saavedra JE, Davies KM, Barchi, Jr. JJ, Keefer LK.
Unexpected incorporation of bromine at a non-anomeric position during the synthesis of an O2-glycosylated diazeniumdiolate.
Org. Prep. Proced. Int. 41: 143-7, 2009.
70)  Qu W, Liu J, Dill AL, Saavedra JE, Keefer LK, Waalkes MP.
V-PROLI/NO, a nitric oxide donor prodrug, protects liver cells from arsenic-induced toxicity.
Cancer Sci. 100: 382-8, 2009.
71)  Falk RT, Xu X, Keefer L, Veenstra TD, Ziegler RG.
A liquid chromatography-mass spectrometry method for the simultaneous measurement of 15 urinary estrogens and estrogen metabolites: assay reproducibility and interindividual variability.
Cancer Epidemiol. Biomarkers Prev. 17: 3411-8, 2008.
72)  Andrei D, Maciag AE, Chakrapani H, Citro ML, Keefer LK, Saavedra JE.
Aryl bis(diazeniumdiolates): potent inducers of S-glutathionylation of cellular proteins and their in vitro antiproliferative activities.
J. Med. Chem. 51: 7944-52, 2008.
73)  Pearce CG, Najjar SF, Kapadia MR, Murar J, Eng J, Lyle B, Aalami OO, Jiang Q, Hrabie JA, Saavedra JE, Keefer LK, Kibbe MR.
Beneficial effect of a short-acting NO donor for the prevention of neointimal hyperplasia.
Free Radic. Biol. Med. 44: 73-81, 2008.
74)  Chakrapani H, Maciag AE, Citro ML, Keefer LK, Saavedra JE.
Cell-permeable esters of diazeniumdiolate-based nitric oxide prodrugs.
Org. Lett. 10: 5155-8, 2008.
75)  Ahanchi SS, Varu VN, Tsihlis ND, Martinez J, Pearce CG, Kapadia MR, Jiang Q, Saavedra JE, Keefer LK, Hrabie JA, Kibbe MR.
Heightened efficacy of nitric oxide-based therapies in type II diabetes mellitus and metabolic syndrome.
Am. J. Physiol. Heart Circ. Physiol. 295: H2388-98, 2008.
76)  Valdez CA, Saavedra JE, Showalter BM, Davies KM, Wilde TC, Citro ML, Barchi, Jr JJ, Deschamps JR, Parrish D, El-Gayar S, Schleicher U, Bogdan C, Keefer LK.
Hydrolytic Reactivity Trends among Potential Prodrugs of the O(2)-Glycosylated Diazeniumdiolate Family. Targeting Nitric Oxide to Macrophages for Antileishmanial Activity. This article may be obtain for free at
J. Med. Chem. 51: 3961-70, 2008.
Full Text Article. [Journal]
77)  Kapadia MR, Chow LW, Tsihlis ND, Ahanchi SS, Eng JW, Murar JM, Martinez JM, Popowich DA, Jiang Q, Hrabie JA, Saavedra JE, Keefer LK, Hulvat JF, Stupp SI, Kibbe MR.
Nitric oxide and nanotechnology: A novel approach to inhibit neointimal hyperplasia.
J. Vasc. Surg. 47: 173-82, 2008.
78)  DeRosa F, Keefer LK, Hrabie JA.
Nitric oxide reacts with methoxide.
J. Org. Chem. 73: 1139-42, 2008.
79)  Velazquez CA, Chen QH, Citro ML, Keefer LK, Knaus EE.
Second-generation aspirin and indomethacin prodrugs possessing an O(2)-(acetoxymethyl)-1-(2-carboxypyrrolidin-1-yl)diazenium-1,2-diolate nitric oxide donor moiety: design, synthesis, biological evaluation, and nitric oxide release studies.
J. Med. Chem. 51: 1954-61, 2008.
80)  Ji X, Pal A, Kalathur R, Hu X, Gu Y, Saavedra JE, Buzard GS, Srinivasan A, Keefer LK, Singh SV.
Structure-Based Design of Anticancer Prodrug PABA/NO.
Drug Des Devel Ther. 2: 123-130, 2008.
81)  Ji X, Pal A, Kalathur R, Hu X, Gu Y, Saavedra JE, Buzard GS, Srinivasan A, Keefer LK, Singh SV.
Structure-based design of anticancer prodrug PABA/NO.
Drug Design Devel. Ther. 2: 123-130, 2008.
82)  Chakrapani H, Goodblatt MM, Udupi V, Malaviya S, Shami PJ, Keefer LK, Saavedra JE.
Synthesis and in vitro anti-leukemic activity of structural analogues of JS-K, an anti-cancer lead compound.
Bioorg. Med. Chem. Lett. 18: 950-3, 2008.
83)  Chakrapani H, Kalathur RC, Maciag AE, Citro ML, Ji X, Keefer LK, Saavedra JE.
Synthesis, mechanistic studies, and anti-proliferative activity of glutathione/glutathione S-transferase-activated nitric oxide prodrugs.
Bioorg. Med. Chem. 16: 9764-71, 2008.
84)  Chakrapani H, Wilde TC, Citro ML, Goodblatt MM, Keefer LK, Saavedra JE.
Synthesis, nitric oxide release, and anti-leukemic activity of glutathione-activated nitric oxide prodrugs: Structural analogues of PABA/NO, an anti-cancer lead compound.
Bioorg. Med. Chem. 16: 2657-64, 2008.
85)  Simeone A, McMurtry V, Nieves-Alicea R, Saavedra JE, Keefer LK, Johnson MM, Tari AM.
TIMP-2 mediates the anti-invasive effects of the nitric oxide-releasing prodrug JS-K in breast cancer cells.
Breast Cancer Res. 10: R44 (Epub ahead of print), 2008.
86)  Xu X, Keefer LK, Ziegler RG, Veenstra TD.
A liquid chromatography-mass spectrometry method for the quantitative analysis of urinary endogenous estrogen metabolites.
Nature protocols. 2: 1350-5, 2007.
87)  Tarasova NI, Loeppky RN, Byrd RA, Keefer LK.
In memoriam: Christopher J. Michejda (December 19, 1937-January 9, 2007).
Chem. Res. Toxicol. 20: 323-5, 2007.
88)  Kiziltepe T, Hideshima T, Ishitsuka K, Ocio EM, Raje N, Catley L, Li CQ, Trudel LJ, Yasui H, Vallet S, Kutok JL, Chauhan D, Mitsiades CS, Saavedra JE, Wogan GN, Keefer LK, Shami PJ, Anderson KC.
JS-K, a GST-activated nitric oxide generator, induces DNA double-strand breaks, activates DNA damage response pathways, and induces apoptosis in vitro and in vivo in human multiple myeloma cells.
Blood. 110: 709-18, 2007.
89)  Chakrapani H, Showalter BM, Citro ML, Keefer LK, Saavedra JE.
Nitric oxide prodrugs: diazeniumdiolate anions of hindered secondary amines.
Org. Lett. 9: 4551-4, 2007.
90)  DeRosa F, Kibbe MR, Najjar SF, Citro ML, Keefer LK, Hrabie JA.
Nitric oxide-releasing fabrics and other acrylonitrile-based diazeniumdiolates.
J. Am. Chem. Soc. 129: 3786-7, 2007.
91)  Velazquez CA, Praveen Rao PN, Citro ML, Keefer LK, Knaus EE.
O2-Acetoxymethyl-protected diazeniumdiolate-based NSAIDs (NONO-NSAIDs): synthesis, nitric oxide release, and biological evaluation studies.
Bioorg. Med. Chem. 15: 4767-74, 2007.
92)  Xu X, Roman JM, Issaq HJ, Keefer LK, Veenstra TD, Ziegler RG.
Quantitative measurement of endogenous estrogens and estrogen metabolites in human serum by liquid chromatography-tandem mass spectrometry.
Anal. Chem. 79: 7813-21, 2007.
93)  Qu W, Liu J, Fuquay R, Saavedra JE, Keefer LK, Waalkes MP.
The nitric oxide prodrug, V-PYRRO/NO, mitigates arsenic-induced liver cell toxicity and apoptosis.
Cancer Lett. 256: 238-45, 2007.
94)  Chakrapani H, Showalter BM, Kong L, Keefer LK, Saavedra JE.
V-PROLI/NO, a prodrug of the nitric oxide donor, PROLI/NO.
Org. Lett. 9: 3409-12, 2007.
95)  Townsend DM, Findlay VJ, Fazilev F, Ogle M, Fraser J, Saavedra JE, Ji X, Keefer LK, Tew KD.
A glutathione S-transferase pi-activated prodrug causes kinase activation concurrent with S-glutathionylation of proteins.
Mol Pharmacol. 69: 501-8, 2006.
Full Text Article. [Journal]
96)  Shami PJ, Saavedra JE, Bonifant CL, Chu J, Udupi V, Malaviya S, Carr BI, Kar S, Wang M, Jia L, Ji X, Keefer LK.
Antitumor activity of JS-K [O2-(2,4-dinitrophenyl) 1-[(4-ethoxycarbonyl)piperazin-1-yl]diazen-1-ium-1,2-diolate] and related O2-aryl diazeniumdiolates in vitro and in vivo.
J. Med. Chem. 49: 4356-66, 2006.
97)  Kong L, Saavedra JE, Buzard GS, Xu X, Hood BL, Conrads TP, Veenstra TD, Keefer LK.
Deamidation of peptides in aerobic nitric oxide solution by a nitrosative pathway.
Nitric Oxide. 14: 144-51, 2006.
98)  Waterhouse DJ, Saavedra JE, Davies KM, Citro ML, Xu X, Powell DA, Grimes GJ, Potti GK, Keefer LK.
Injectable formulation of disodium 1-[2-(carboxylato)pyrrolidin-1-yl]diazen-1-ium-1,2-diolate (PROLI/NO), an ultrafast nitric oxide donor prodrug.
J Pharm Sci. 95: 108-15, 2006.
Full Text Article. [Journal]
99)  Inami K, Nims RW, Srinivasan A, Citro ML, Saavedra JE, Cederbaum AI, Keefer LK.
Metabolism of a liver-selective nitric oxide-releasing agent, V-PYRRO/NO, by human microsomal cytochromes P450.
Nitric Oxide: Biol Chem. 14: 309-15, 2006.
100)  Reynolds MM, Hrabie JA, Oh BK, Politis JK, Citro ML, Keefer LK, Meyerhoff ME.
Nitric oxide releasing polyurethanes with covalently linked diazeniumdiolated secondary amines.
Biomacromolecules. 7: 987-94, 2006.
Full Text Article. [Journal]
101)  Saavedra JE, Srinivasan A, Buzard GS, Davies KM, Waterhouse DJ, Inami K, Wilde TC, Citro ML, Cuellar M, Deschamps JR, Parrish D, Shami PJ, Findlay VJ, Townsend DM, Tew KD, Singh S, Jia L, Ji X, Keefer LK.
PABA/NO as an anticancer lead: analogue synthesis, structure revision, solution chemistry, reactivity toward glutathione, and in vitro activity.
J Med Chem. 49: 1157-64, 2006.
Full Text Article. [Journal]
102)  Hrabie JA, Citro ML, Chmurny GN, Keefer LK.
Carbon-bound diazeniumdiolates from the reaction of nitric oxide with amidines.
J. Org. Chem. 70: 7647-53, 2005.
103)  Wang Y, Bohle DS, Bonifant CL, Chmurny GN, Collins JR, Davies KM, Deschamps J, Flippen-Anderson JL, Keefer LK, Klose JR, Saavedra JE, Waterhouse DJ, Ivanic J.
Chemistry of the diazeniumdiolates: Z to E isomerism.
J Am Chem Soc. 127: 5388-95, 2005.
104)  Miranda KM, Katori T, Torres de Holding CL, Thomas L, Ridnour LA, McLendon WJ, Cologna SM, Dutton AS, Champion HC, Mancardi D, Tocchetti CG, Saavedra JE, Keefer LK, Houk KN, Fukuto JM, Kass DA, Paolocci N, Wink DA.
Comparison of the NO and HNO donating properties of diazeniumdiolates: primary amine adducts release HNO in Vivo.
J. Med. Chem. 48: 8220-8, 2005.
105)  Showalter BM, Reynolds MM, Valdez CA, Saavedra JE, Davies KM, Klose JR, Chmurny GN, Citro ML, Barchi JJ, Merz SI, Meyerhoff ME, Keefer LK.
Diazeniumdiolate ions as leaving groups in anomeric displacement reactions: a protection-deprotection strategy for ionic diazeniumdiolates.
J. Am. Chem. Soc. 127: 14188-9, 2005.
106)  Xu X, Veenstra TD, Fox SD, Roman JM, Issaq HJ, Falk R, Saavedra JE, Keefer LK, Ziegler RG.
Measuring fifteen endogenous estrogens simultaneously in human urine by high-performance liquid chromatography-mass spectrometry.
Anal. Chem. 77: 6646-54, 2005.
107)  Keefer LK.
Nitric oxide (NO)- and nitroxyl (HNO)-generating diazeniumdiolates (NONOates): Emerging commercial opportunities.
Curr Top Med Chem. 5: 625-636, 2005.
108)  Qu W, Liu J, Fuquay R, Shimoda R, Sakurai T, Saavedra JE, Keefer LK, Waalkes MP.
The nitric oxide prodrug, V-PYRRO/NO, protects against cadmium toxicity and apoptosis at the cellular level.
Nitric Oxide. 12: 114-20, 2005.
109)  Saavedra JE, Bohle DS, Smith KN, George C, Deschamps JR, Parrish D, Ivanic J, Wang YN, Citro ML, Keefer LK.
Chemistry of the diazeniumdiolates. O- versus N-alkylation of the RNH[N(O)NO](-) ion.
J Am Chem Soc. 126: 12880-7, 2004.
110)  Xu X, Keefer LK, Waterhouse DJ, Saavedra JE, Veenstra TD, Ziegler RG.
Measuring seven endogenous ketolic estrogens simultaneously in human urine by high-performance liquid chromatography-mass spectrometry.
Anal Chem. 76: 5829-36, 2004.
111)  Liu J, Li C, Qu W, Leslie E, Bonifant CL, Buzard GS, Saavedra JE, Keefer LK, Waalkes MP.
Nitric oxide prodrugs and metallochemotherapeutics: JS-K and CB-3-100 enhance arsenic and cisplatin cytolethality by increasing cellular accumulation.
Mol Cancer Ther. 3: 709-14, 2004.
112)  Findlay VJ, Townsend DM, Saavedra JE, Buzard GS, Citro ML, Keefer LK, Ji X, Tew KD.
Tumor cell responses to a novel glutathione S-transferase-activated nitric oxide-releasing prodrug.
Mol Pharmacol. 65: 1070-9, 2004.
113)  Keefer LK.
Biomaterials. Thwarting thrombus.
Nat Mater. 2: 357-8, 2003.
114)  Shami PJ, Saavedra JE, Wang LY, Bonifant CL, Diwan BA, Singh SV, Gu Y, Fox SD, Buzard GS, Citro ML, Waterhouse DJ, Davies KM, Ji X, Keefer LK.
JS-K, a glutathione/glutathione S-transferase-activated nitric oxide donor of the diazeniumdiolate class with potent antineoplastic activity.
Mol Cancer Ther. 2: 409-17, 2003.
115)  Dhar A, Brindley JM, Stark C, Citro ML, Keefer LK, Colburn NH.
Nitric oxide does not mediate but inhibits transformation and tumor phenotype.
Mol Cancer Ther. 2: 1285-93, 2003.
116)  D'Sa RA, Wang Y, Ruane PH, Showalter BM, Saavedra JE, Davies KM, Citro ML, Booth MN, Keefer LK, Toscano JP.
Preparation and reactivity of O2-sulfonated diazeniumdiolates.
J Org Chem. 68: 656-57, 2003.
117)  Keefer LK.
Progress toward clinical application of the nitric oxide-releasing diazeniumdiolates.
Annu Rev Pharmacol Toxicol. 43: 585-607, 2003.
118)  Weyerbrock A, Walbridge S, Pluta RM, Saavedra JE, Keefer LK, Oldfield EH.
Selective opening of the blood-tumor barrier by a nitric oxide donor and long-term survival in rats with C6 gliomas.
J. Neurosurg. 99: 728-37, 2003.
119)  Liu J, Li C, Waalkes MP, Clark J, Myers P, Saavedra JE, Keefer LK.
The nitric oxide donor, V-PYRRO/NO, protects against acetaminophen-induced hepatotoxicity in mice.
Hepatology. 37: 324-33, 2003.
120)  Li C, Liu J, Saavedra JE, Keefer LK, Waalkes MP.
The nitric oxide donor, V-PYRRO/NO, protects against acetaminophen-induced nephrotoxicity in mice.
Toxicology. 189: 173-80, 2003.
121)  Arnold EV, Citro ML, Keefer LK, Hrabie JA.
A nitric oxide-releasing polydiazeniumdiolate derived from acetonitrile.
Org. Lett. 4: 1323-5, 2002.
122)  Baek SH, Hrabie JA, Keefer LK, Hou D, Fineberg N, Rhoades R, March KL.
Augmentation of intrapericardial nitric oxide level by a prolonged-release nitric oxide donor reduces luminal narrowing after porcine coronary angioplasty.
Circulation. 105: 2779-84, 2002.
123)  Hrabie JA, Keefer LK.
Chemistry of the nitric oxide-releasing diazeniumdiolate ("nitrosohydroxylamine") functional group and its oxygen-substituted derivatives.
Chem Rev. 102: 1135-54, 2002.
124)  Arnold EV, Citro ML, Saavedra EA, Davies KM, Keefer LK, Hrabie JA.
Mechanistic insight into exclusive nitric oxide recovery from a carbon-bound diazeniumdiolate.
Nitric Oxide. 7: 103-8, 2002.
125)  Saavedra JE, Keefer LK.
Nitrogen-based diazeniumdiolates. Versatile nitric oxide-releasing compounds for biomedical research and potential clinical applications.
J Chem Educ. 79: 1427-34, 2002.
126)  Liu J, Saavedra JE, Lu T, Song JG, Clark J, Waalkes MP, Keefer LK.
O(2)-Vinyl 1-(pyrrolidin-1-yl)diazen-1-ium-1,2-diolate protection against D-galactosamine/endotoxin-induced hepatotoxicity in mice: genomic analysis using microarrays.
J Pharmacol Exp Ther. 300: 18-25, 2002.
127)  Stinson SF, House T, Bramhall C, Saavedra JE, Keefer LK, Nims RW.
Plasma pharmacokinetics of a liver-selective nitric oxide-donating diazeniumdiolate in the male C57BL/6 mouse.
Xenobiotica. 32: 339-47, 2002.
128)  Fitzhugh AL, Anadu NO, Waterhouse DJ, Hrabie JA, Saavedra JE, Keefer LK.
Qualitative thin-layer and high-performance liquid chromatographic analysis of 1-substituted diazen-1-ium-1,2-diolates on aminopropyl-bonded silica gel.
Anal Biochem. 301: 97-102, 2002.
129)  Xu X, Ziegler RG, Waterhouse DJ, Saavedra JE, Keefer LK.
Stable isotope dilution high-performance liquid chromatography-electrospray ionization mass spectrometry method for endogenous 2- and 4-hydroxyestrones in human urine.
J Chromatogr B Analyt Technol Biomed Life Sci. 780: 315-30, 2002.
130)  Bivalacqua TJ, Champion HC, De Witt BJ, Saavedra JE, Hrabie JA, Keefer LK, Kadowitz PJ.
Analysis of vasodilator responses to novel nitric oxide donors in the hindquarters vascular bed of the cat.
J Cardiovasc Pharmacol. 38: 120-9, 2001.
131)  Davies KM, Wink DA, Saavedra JE, Keefer LK.
Chemistry of the diazeniumdiolates. 2. Kinetics and mechanism of dissociation to nitric oxide in aqueous solution.
J Am Chem Soc. 123: 5473-81, 2001.
132)  Srinivasan A, Kebede N, Saavedra JE, Nikolaitchik AV, Brady DA, Yourd E, Davies KM, Keefer LK, Toscano JP.
Chemistry of the diazeniumdiolates. 3. Photoreactivity.
J Am Chem Soc. 123: 5465-72, 2001.
133)  Keefer LK, Flippen-Anderson JL, George C, Shanklin AP, Dunams TM, Christodoulou D, Saavedra JE, Sagan ES, Bohle DS.
Chemistry of the diazeniumdiolates. I. Structural and spectral characteristics of the [N(O)NO]- functional group.
Nitric Oxide. 5: 377-94, 2001.
134)  De Witt BJ, Marrone JR, Kaye AD, Keefer LK, Kadowitz PJ.
Comparison of responses to novel nitric oxide donors in the feline pulmonary vascular bed.
Eur J Pharmacol. 430: 311-5, 2001.
135)  Kotamraju S, Hogg N, Joseph J, Keefer LK, Kalyanaraman B.
Inhibition of oxidized low-density lipoprotein-induced apoptosis in endothelial cells by nitric oxide. Peroxyl radical scavenging as an antiapoptotic mechanism.
J Biol Chem. 276: 17316-23, 2001.
136)  Souici AC, Fitzhugh AL, Keefer LK, Felley-Bosco E.
L-tyrosine and nitric oxide synergize to prevent cytotoxic effects of superoxide.
Toxicology. 165: 163-70, 2001.
137)  Katakai K, Liu J, Nakajima K, Keefer LK, Waalkes MP.
Nitric oxide induces metallothionein (MT) gene expression apparently by displacing zinc bound to MT.
Toxicol Lett. 119: 103-8, 2001.
138)  Liu J, Chen H, Miller DS, Saavedra JE, Keefer LK, Johnson DR, Klaassen CD, Waalkes MP.
Overexpression of glutathione S-transferase II and multidrug resistance transport proteins is associated with acquired tolerance to inorganic arsenic.
Mol Pharmacol. 60: 302-9, 2001.
139)  Noguchi CT, Gladwin M, Diwan B, Merciris P, Smith R, Yu X, Buzard G, Fitzhugh A, Keefer LK, Schechter AN, Mohandas N.
Pathophysiology of a sickle cell trait mouse model: human alpha(beta)(S) transgenes with one mouse beta-globin allele.
Blood Cells Mol Dis. 27: 971-7, 2001.
140)  Shokolenko I, Oberyszyn TM, D'Ambrosio SM, Saavedra JE, Keefer LK, LeDoux SP, Wilson GL, Robertson FM.
Protection of human keratinocyte mtDNA by low-level nitric oxide.
Nitric Oxide. 5: 555-60, 2001.
141)  Saavedra JE, Srinivasan A, Bonifant CL, Chu J, Shanklin AP, Flippen-Anderson JL, Rice WG, Turpin JA, Davies KM, Keefer LK.
The secondary amine/nitric oxide complex ion R(2)N[N(O)NO](-) as nucleophile and leaving group in S9N)Ar reactions.
J Org Chem. 66: 3090-8, 2001.
142)  Ricciardi R, Foley DP, Quarfordt SH, Saavedra JE, Keefer LK, Wheeler SM, Donohue SE, Callery MP, Meyers WC.
V-PYRRO/NO: an hepato-selective nitric oxide donor improves porcine liver hemodynamics and function after ischemia reperfusion.
Transplantation. 71: 193-8, 2001.
143)  Saavedra JE, Mooradian DL, Mowery KA, Schoenfisch MH, Citro ML, Davies KM, Meyerhoff ME, Keefer LK.
Conversion of a polysaccharide to nitric oxide-releasing form. Dual-mechanism anticoagulant activity of diazeniumdiolated heparin.
Bioorg. Med. Chem. Lett. 10: 751-3, 2000.
144)  Fitzhugh AL, Keefer LK.
Diazeniumdiolates: pro- and antioxidant applications of the "NONOates".
Free Radic. Biol. Med. 28: 1463-9, 2000.
145)  Saavedra JE, Shami PJ, Wang LY, Davies KM, Booth MN, Citro ML, Keefer LK.
Esterase-sensitive nitric oxide donors of the diazeniumdiolate family: in vitro antileukemic activity.
J. Med. Chem. 43: 261-9, 2000.
146)  Waalkes MP, Keefer LK, Diwan BA.
Induction of proliferative lesions of the uterus, testes, and liver in swiss mice given repeated injections of sodium arsenate: possible estrogenic mode of action.
Toxicol. Appl. Pharmacol. 166: 24-35, 2000.
147)  Mowery KA, Schoenfisch MH, Saavedra JE, Keefer LK, Meyerhoff ME.
Preparation and characterization of hydrophobic polymeric films that are thromboresistant via nitric oxide release.
Biomaterials. 21: 9-21, 2000.
148)  Hrabie JA, Arnold EV, Citro ML, George C, Keefer LK.
Reaction of nitric oxide at the beta-carbon of enamines. A new method of preparing compounds containing the diazeniumdiolate functional group.
J. Org. Chem. 65: 5745-51, 2000.
149)  Souici AC, Mirkovitch J, Hausel P, Keefer LK, Felley-Bosco E.
Transition mutation in codon 248 of the p53 tumor suppressor gene induced by reactive oxygen species and a nitric oxide-releasing compound.
Carcinogenesis. 21: 281-7, 2000.
150)  Hrabie JA, Saavedra JE, Roller PP, Southan GJ, Keefer LK.
Conversion of proteins to diazeniumdiolate-based nitric oxide donors.
Bioconjug. Chem. 10: 838-42, 1999.
151)  Champion HC, Bivalacqua TJ, Wang R, Kadowitz PJ, Keefer LK, Saavedra JE, Hrabie JA, Doherty PC, Hellstrom WJ.
Induction of penile erection by intracavernosal and transurethral administration of novel nitric oxide donors in the cat.
J. Urol. 161: 2013-9, 1999.
152)  Stoll HP, Carlson K, Keefer LK, Hrabie JA, March KL.
Pharmacokinetics and consistency of pericardial delivery directed to coronary arteries: direct comparison with endoluminal delivery.
Clin Cardiol. 22: I10-6, 1999.
153)  Modzelewska B, Sipowicz MA, Saavedra JE, Keefer LK, Kostrzewska A.
Involvement of K+ATP channels in nitric oxide-induced inhibition of spontaneous contractile activity of the nonpregnant human myometrium.
Biochem. Biophys. Res. Commun. 253: 653-7, 1998.
154)  Chen C, Hanson SR, Keefer LK, Saavedra JE, Davies KM, Hutsell TC, Hughes JD, Ku DN, Lumsden AB.
Boundary layer infusion of nitric oxide reduces early smooth muscle cell proliferation in the endarterectomized canine artery.
J. Surg. Res. 67: 26-32, 1997.
155)  Ou J, Carlos TM, Watkins SC, Saavedra JE, Keefer LK, Kim YM, Harbrecht BG, Billiar TR.
Differential effects of nonselective nitric oxide synthase (NOS) and selective inducible NOS inhibition on hepatic necrosis, apoptosis, ICAM-1 expression, and neutrophil accumulation during endotoxemia.
Nitric Oxide. 1: 404-16, 1997.
156)  Donovan PJ, Smith GT, Lawlor TE, Cifone MA, Murli H, Keefer LK.
Quantification of diazeniumdiolate mutagenicity in four different in vitro assays.
Nitric Oxide. 1: 158-66, 1997.
157)  Kelman DJ, Christodoulou D, Wink DA, Keefer LK, Srinivasan A, Dipple A.
Relative mutagenicities of gaseous nitrogen oxides in the supF gene of pSP189.
Carcinogenesis. 18: 1045-8, 1997.
158)  Keefer LK, Nims RW, Davies KM, Wink DA.
"NONOates" (1-substituted diazen-1-ium-1,2-diolates) as nitric oxide donors: convenient nitric oxide dosage forms.
Meth. Enzymol. 268: 281-93, 1996.
159)  Lee VM, Keefer LK, Archer MC.
An evaluation of the roles of metabolic denitrosation and alpha-hydroxylation in the hepatotoxicity of N-Nitrosodimethylamine.
Chem. Res. Toxicol. 9: 1319-24, 1996.
160)  Merchant K, Chen H, Gonzalez TC, Keefer LK, Shaw BR.
Deamination of single-stranded DNA cytosine residues in aerobic nitric oxide solution at micromolar total NO exposures.
Chem. Res. Toxicol. 9: 891-6, 1996.
161)  Keefer LK, Wink DA.
DNA damage and nitric oxide.
Adv. Exp. Med. Biol. 387: 177-85, 1996.
162)  Tamano S, Ward JM, Diwan BA, Keefer LK, Weghorst CM, Calvert RJ, Henneman JR, Ramljak D, Rice JM.
Histogenesis and the role of p53 and K-ras mutations in hepatocarcinogenesis by glyceryl trinitrate (nitroglycerin) in male F344 rats.
Carcinogenesis. 17: 2477-86, 1996.
163)  Canella KA, Diwan BA, Gorelick PL, Donovan PJ, Sipowicz MA, Kasprzak KS, Weghorst CM, Snyderwine EG, Davis CD, Keefer LK, Kyrtopoulos SA, Hecht SS, Wang M, Anderson LM, Rice JM.
Liver tumorigenesis by Helicobacter hepaticus: considerations of mechanism.
In Vivo. 10: 285-92, 1996.
164)  Saavedra JE, Southan GJ, Davies KM, Lundell A, Markou C, Hanson SR, Adrie C, Hurford WE, Zapol WM, Keefer LK.
Localizing antithrombotic and vasodilatory activity with a novel, ultrafast nitric oxide donor.
J. Med. Chem. 39: 4361-5, 1996.
165)  Kong L, Dunn GD, Keefer LK, Korthuis RJ.
Nitric oxide reduces tumor cell adhesion to isolated rat postcapillary venules.
Clin. Exp. Metastasis. 14: 335-43, 1996.
166)  Smith DJ, Chakravarthy D, Pulfer S, Simmons ML, Hrabie JA, Citro ML, Saavedra JE, Davies KM, Hutsell TC, Mooradian DL, Hanson SR, Keefer LK.
Nitric oxide-releasing polymers containing the [N(O)NO]- group.
J. Med. Chem. 39: 1148-56, 1996.
167)  Mooradian DL, Hutsell TC, Keefer LK.
Nitric oxide (NO) donor molecules: effect of NO release rate on vascular smooth muscle cell proliferation in vitro.
J. Cardiovasc. Pharmacol. 25: 674-8, 1995.
168)  Felley-Bosco E, Mirkovitch J, Ambs S, Macé K, Pfeifer A, Keefer LK, Harris CC.
Nitric oxide and ethylnitrosourea: relative mutagenicity in the p53 tumor suppressor and hypoxanthine-phosphoribosyltransferase genes.
Carcinogenesis. 16: 2069-74, 1995.
169)  Maciejewski JP, Selleri C, Sato T, Cho HJ, Keefer LK, Nathan CF, Young NS.
Nitric oxide suppression of human hematopoiesis in vitro. Contribution to inhibitory action of interferon-gamma and tumor necrosis factor-alpha.
J. Clin. Invest. 96: 1085-92, 1995.
170)  Felley-Bosco E, Ambs S, Lowenstein CJ, Keefer LK, Harris CC.
Constitutive expression of inducible nitric oxide synthase in human bronchial epithelial cells induces c-fos and stimulates the cGMP pathway.
Am. J. Respir. Cell Mol. Biol. 11: 159-64, 1994.
171)  Vanderford PA, Wong J, Chang R, Keefer LK, Soifer SJ, Fineman JR.
Diethylamine/nitric oxide (NO) adduct, an NO donor, produces potent pulmonary and systemic vasodilation in intact newborn lambs.
J. Cardiovasc. Pharmacol. 23: 113-9, 1994.
172)  Routledge MN, Wink DA, Keefer LK, Dipple A.
DNA sequence changes induced by two nitric oxide donor drugs in the supF assay.
Chem. Res. Toxicol. 7: 628-32, 1994.
173)  Liebmann J, DeLuca AM, Coffin D, Keefer LK, Venzon D, Wink DA, Mitchell JB.
In vivo radiation protection by nitric oxide modulation.
Cancer Res. 54: 3365-8, 1994.
174)  Routledge MN, Mirsky FJ, Wink DA, Keefer LK, Dipple A.
Nitrite-induced mutations in a forward mutation assay: influence of nitrite concentration and pH.
Mutat. Res. 322: 341-6, 1994.
175)  Diodati JG, Quyyumi AA, Hussain N, Keefer LK.
Complexes of nitric oxide with nucleophiles as agents for the controlled biological release of nitric oxide: antiplatelet effect.
Thromb. Haemost. 70: 654-8, 1993.
176)  Diodati JG, Quyyumi AA, Keefer LK.
Complexes of nitric oxide with nucleophiles as agents for the controlled biological release of nitric oxide: hemodynamic effect in the rabbit.
J. Cardiovasc. Pharmacol. 22: 287-92, 1993.
177)  Nims RW, Syi JL, Wink DA, Nelson VC, Thomas PE, Jones CR, Diwan BA, Keefer LK, Rice JM, Lubet RA.
Hepatic cytochrome P450 2B-type induction by ethyl/phenyl-substituted congeners of phenobarbital in the rat.
Chem. Res. Toxicol. 6: 180-7, 1993.
178)  Mitchell JB, Wink DA, DeGraff W, Gamson J, Keefer LK, Krishna MC.
Hypoxic mammalian cell radiosensitization by nitric oxide.
Cancer Res. 53: 5845-8, 1993.
179)  Morley D, Maragos CM, Zhang XY, Boignon M, Wink DA, Keefer LK.
Mechanism of vascular relaxation induced by the nitric oxide (NO)/nucleophile complexes, a new class of NO-based vasodilators.
J. Cardiovasc. Pharmacol. 21: 670-6, 1993.
180)  Maragos CM, Andrews AW, Keefer LK, Elespuru RK.
Mutagenicity of glyceryl trinitrate (nitroglycerin) in Salmonella typhimurium.
Mutat. Res. 298: 187-95, 1993.
181)  Routledge MN, Wink DA, Keefer LK, Dipple A.
Mutations induced by saturated aqueous nitric oxide in the pSP189 supF gene in human Ad293 and E. coli MBM7070 cells.
Carcinogenesis. 14: 1251-4, 1993.
182)  Maragos CM, Wang JM, Hrabie JA, Oppenheim JJ, Keefer LK.
Nitric oxide/nucleophile complexes inhibit the in vitro proliferation of A375 melanoma cells via nitric oxide release.
Cancer Res. 53: 564-8, 1993.
183)  Morley D, Keefer LK.
Nitric oxide/nucleophile complexes: a unique class of nitric oxide-based vasodilators.
J. Cardiovasc. Pharmacol. 22 Suppl 7: S3-9, 1993.
184)  Wink DA, Nims RW, Desrosiers MF, Ford PC, Keefer LK.
A kinetic investigation of intermediates formed during the Fenton reagent mediated degradation of N-nitrosodimethylamine: evidence for an oxidative pathway not involving hydroxyl radical.
Chem. Res. Toxicol. 4: 510-2, 1991.
185)  Sullivan BP, Meyer TJ, Stershic MT, Keefer LK.
Acceleration of N-nitrosation reactions by electrophiles.
IARC Sci. Publ. 370-4, 1991.
186)  von Hofe E, Schmerold I, Nims RW, Keefer LK, Reist EJ, Kleihues P.
Beta-deuteration of N-nitrosoethylmethylamine causes a shift in DNA methylation from rat liver to esophagus.
Carcinogenesis. 12: 545-9, 1991.
187)  Devor DE, Henneman JR, Keefer LK, Logsdon DL, Rice JM, Streeter AJ, Ward JM.
Carcinogenicity study of fecapentaene-12 diacetate on skin painting in SENCAR mice.
Cancer Lett. 56: 11-5, 1991.
188)  Streeter AJ, Nims RW, Sheffels PR, Keefer LK.
Denitrosation of N-nitrosodimethylamine in the rat in vivo.
Adv. Exp. Med. Biol. 283: 371-5, 1991.
189)  Streeter AJ, Nims RW, Keefer LK.
Toxicokinetic studies of N-nitrosamine carcinogenesis.
IARC Sci. Publ. 362-5, 1991.
190)  Streeter AJ, Nims RW, Sheffels PR, Hrabie JA, Ohannesian L, Heur YH, Mico BA, Keefer LK.
Deuterium isotope effect on the toxicokinetics of monomethylamine in the rat.
Drug Metab. Dispos. 18: 447-52, 1990.
191)  Streeter AJ, Nims RW, Sheffels PR, Heur YH, Yang CS, Mico BA, Gombar CT, Keefer LK.
Metabolic denitrosation of N-nitrosodimethylamine in vivo in the rat.
Cancer Res. 50: 1144-50, 1990.
192)  Keefer LK, Goff U, Stevens J, Bennett EO.
Persistence of N-nitrosodiethanolamine contamination in American metal-working lubricants.
Food Chem. Toxicol. 28: 531-4, 1990.
193)  Streeter AJ, Nims RW, Anderson LM, Heur YH, von Hofe E, Kleihues P, Nelson VC, Mico BA, Keefer LK.
Single-dose toxicokinetics of N-nitrosomethylethylamine and N-nitrosomethyl (2,2,2-trideuterioethyl)amine in the rat.
Arch. Toxicol. 64: 109-15, 1990.
194)  Keefer LK, Kroeger-Koepke MB, Ishizaki H, Michejda CJ, Saavedra JE, Hrabie JA, Yang CS, Roller PP.
Stereoselectivity in the microsomal conversion of N-nitrosodimethylamine to formaldehyde.
Chem. Res. Toxicol. 3: 540-4, 1990.
195)  Streeter AJ, Donovan PJ, Anjo T, Ohannesian L, Sheffels PR, Wu PP, Keefer LK, Andrews AW, Bradford WW, Reist EJ.
Decomposition and quality control considerations in biological work with fecapentaene preparations.
Chem. Res. Toxicol. 2: 162-8, 1989.
196)  Streeter AJ, Nims RW, Hrabie JA, Heur YH, Keefer LK.
Sex differences in the single-dose toxicokinetics of N-nitrosomethyl(2-hydroxyethyl)amine in the rat.
Cancer Res. 49: 1783-9, 1989.
197)  Heur YH, Streeter AJ, Nims RW, Keefer LK.
The Fenton degradation as a nonenzymatic model for microsomal denitrosation of N-nitrosodimethylamine.
Chem. Res. Toxicol. 2: 247-53, 1989.
198)  Lijinsky W, Kovatch RM, Keefer LK, Saavedra JE, Hansen TJ, Miller AJ, Fiddler W.
Carcinogenesis in rats by cyclic N-nitrosamines containing sulphur.
Food Chem. Toxicol. 26: 3-7, 1988.
199)  Turusov VS, Lanko NS, Parfenov YD, Gordon WP, Nelson SD, Hillery PS, Keefer LK.
Carcinogenicity of deuterium-labeled 1,2-dimethylhydrazine in mice.
Cancer Res. 48: 2162-7, 1988.
200)  Lunn G, Sansone EB, Andrews AW, Keefer LK.
Decontamination and disposal of nitrosoureas and related N-nitroso compounds.
Cancer Res. 48: 522-6, 1988.
201)  Ward JM, Anjo T, Ohannesian L, Keefer LK, Devor DE, Donovan PJ, Smith GT, Henneman JR, Streeter AJ, Konishi N.
Inactivity of fecapentaene-12 as a rodent carcinogen or tumor initiator.
Cancer Lett. 42: 49-59, 1988.
202)  Keefer LK, Anjo T, Wade D, Wang T, Yang CS.
Concurrent generation of methylamine and nitrite during denitrosation of N-nitrosodimethylamine by rat liver microsomes.
Cancer Res. 47: 447-52, 1987.
203)  Wade D, Yang CS, Metral CJ, Roman JM, Hrabie JA, Riggs CW, Anjo T, Keefer LK, Mico BA.
Deuterium isotope effect on denitrosation and demethylation of N-nitrosodimethylamine by rat liver microsomes.
Cancer Res. 47: 3373-7, 1987.
204)  Tan YZ, Keefer LK, Yang CS.
Inhibition of microsomal N-nitrosodimethylamine demethylase by diethyl ether and other anesthetics.
Biochem. Pharmacol. 36: 1973-8, 1987.
205)  Yang CS, Wade D, Anjo T, Keefer LK.
Kinetic isotope effect on the demethylation and denitrosation of N-nitrosodimethylamine in vitro.
IARC Sci. Publ. 124-8, 1987.
206)  Kleihues P, von Hofe E, Schmerold I, Keefer LK, Lijinsky W.
Organ specificity, metabolism and reaction with DNA of aliphatic nitrosomethylalkylamines.
IARC Sci. Publ. 49-54, 1987.
207)  Keefer LK, Streeter AJ, Leung LY, Perry WC, Hu HS, Baillie TA.
Pharmacokinetic and deuterium isotope effect studies on the metabolism of formaldehyde and formate to carbon dioxide in rats in vivo.
Drug Metab. Dispos. 15: 300-4, 1987.
208)  Keefer LK, Anjo T, Heur YH, Yang CS, Mico BA.
Potential for metabolic deactivation of carcinogenic N-nitrosodimethylamine in vivo.
IARC Sci. Publ. 113-6, 1987.
209)  von Hofe E, Kleihues P, Keefer LK.
Extent of DNA 2-hydroxyethylation by N-nitrosomethylethylamine and N-nitrosodiethylamine in vivo.
Carcinogenesis. 7: 1335-7, 1986.
210)  von Hofe E, Grahmann F, Keefer LK, Lijinsky W, Nelson V, Kleihues P.
Methylation versus ethylation of DNA in target and nontarget tissues of Fischer 344 rats treated with N-nitrosomethylethylamine.
Cancer Res. 46: 1038-42, 1986.
211)  Keefer LK, Garland WA, Oldfield NF, Swagzdis JE, Mico BA.
Inhibition of N-nitrosodimethylamine metabolism in rats by ether anesthesia.
Cancer Res. 45: 5457-60, 1985.
212)  Mico BA, Swagzdis JE, Hu HS, Keefer LK, Oldfield NF, Garland WA.
Low-dose in vivo pharmacokinetic and deuterium isotope effect studies of N-nitrosodimethylamine in rats.
Cancer Res. 45: 6280-5, 1985.
213)  Kroeger-Koepke MB, Michejda CJ, Roller PP, Keefer LK.
Use of 3,4-dichlorobenzenethiol as a trapping agent for alkylating intermediates during in vitro metabolism of nitrosamines.
Cancer Res. 45: 2973-5, 1985.
214)  Lunn G, Sansone EB, Andrews AW, Castegnaro M, Malaveille C, Michelon J, Brouet I, Keefer LK.
Destruction of carcinogenic and mutagenic N-nitrosamides in laboratory wastes.
IARC Sci. Publ. 387-98, 1984.
215)  Likhachev AJ, Ohshima H, Anisimov VN, Ovsyannikov AI, Keefer LK, Reist EJ.
Carcinogenesis and aging. II. Modifying effect of aging on metabolism of methyl(acetoxymethyl)nitrosamine and its interaction with DNA of various tissues in rats.
Carcinogenesis. 4: 967-73, 1983.
216)  Swann PF, Mace R, Angeles RM, Keefer LK.
Deuterium isotope effect on metabolism of N-nitrosodimethylamine in vivo in rat.
Carcinogenesis. 4: 821-5, 1983.
217)  Lunn G, Sansone EB, Keefer LK.
Notes. Reductive destruction of hydrazines as an approach to hazard control.
Environ. Sci. Technol. 17: 240-3, 1983.
218)  Loeppky RN, Hansen TJ, Keefer LK.
Reducing nitrosamine contamination in cutting fluids.
Food Chem. Toxicol. 21: 607-13, 1983.
219)  Lunn G, Sansone EB, Keefer LK.
Safe disposal of carcinogenic nitrosamines.
Carcinogenesis. 4: 315-9, 1983.
220)  Sansone EB, Lunn G, Jonas LA, Keefer LK.
Approaches to hazard control in the carcinogenesis laboratory: N-nitroso compounds.
IARC Sci. Publ. 137-49, 1982.
221)  Hansen TJ, Croisy AF, Keefer LK.
N-nitrosation of secondary amines by nitric oxide via the "Drago complex".
IARC Sci. Publ. 21-9, 1982.
222)  Keefer LK, Hansen TJ.
Primary amine use and other strategies for preventing human exposure to N nitroso compounds: application to cutting fluids.
IARC Sci. Publ. 245-56, 1982.
223)  Lunn G, Sansone EB, Keefer LK.
Reductive destruction of N-nitrosodimethylamine as an approach to hazard control in the carcinogenesis laboratory.
Food Cosmet Toxicol. 19: 493-4, 1981.
224)  Roller PP, Keefer LK, Slavin BW.
Inhibitory agents and chemical and mechanisms in the dihalomethane-mediated nitrosation of amines with solid nitrite.
IARC Sci. Publ. 119-28, 1980.
225)  Croisy AF, Fanning JC, Keefer LK, Slavin BW, Uhm SJ.
Metal complexes as promoters of N-nitrosation reactions: a progress report.
IARC Sci. Publ. 83-93, 1980.
226)  Walters CL, Hart RJ, Keefer LK, Newberne PJ.
The sequential determination of nitrite, N-nitroso compounds and nitrate and its application.
IARC Sci. Publ. 389-401, 1980.
227)  Kleihues P, Doerjer G, Keefer LK, Rice JM, Roller PP, Hodgson RM.
Correlation of DNA methylation by methyl(acetoxymethyl)nitrosamine with organ-specific carcinogenicity in rats.
Cancer Res. 39: 5136-40, 1979.
228)  Angeles RM, Keefer LK, Roller PP, Uhm SJ.
Chemical models for possible nitrosamine artifact formation in environmental analysis.
IARC Sci Publ. 109-15, 1978.
229)  Reese DH, Friedman RD, Gaffield W, Keefer LK.
Focal suppression and induction of hyperplasia by the bladder carcinogens butyl(4-hydroxybutyl)nitrosamine and buty(3-carboxypropyl)nitrosamine in organ-cultured rat bladder epithelium.
J. Natl. Cancer Inst. 60: 219-23, 1978.
230)  Love LA, Lijinsky W, Keefer LK, Garcia H.
Chronic oral administration of 1-nitrosopiperazine at high doses to MRC rats.
Z Krebsforsch Klin Onkol Cancer Res Clin Oncol. 89: 69-73, 1977.
231)  Joshi SR, Rice JM, Wenk ML, Roller PP, Keefer LK.
Selective induction of intestinal tumors in rats by methyl(acetoxymethyl)nitrosamine, an ester of the presumed reactive metabolite of dimethylnitrosamine.
J. Natl. Cancer Inst. 58: 1531-5, 1977.
232)  Keefer LK.
Promotion of N-nitrosation reactions by metal complexes.
IARC Sci Publ. 153-9, 1976.
233)  Lijinsky W, Taylor HW, Keefer LK.
Reduction of rat liver carcinogenicity of 4-nitrosomorpholine by alpha-deuterium substitution.
J. Natl. Cancer Inst. 57: 1311-3, 1976.
234)  Olah GA, Donovan DJ, Keefer LK.
Carcinogen chemistry. I. Reactions of protonated dialkylnitrosamines leading to alkylating and aminoalkylating agents of potential metabolic significance.
J. Natl. Cancer Inst. 54: 465-72, 1975.
235)  Keefer LK, Lijinsky W, Garcia H.
Deuterium isotope effect on the carcinogenicity of dimethylnitrosamine in rat liver.
J. Natl. Cancer Inst. 51: 299-302, 1973.
236)  Keefer LK, Johnson DE.
Magnesium hydroxide as a thin-layer chromatographic adsorbent. 3. Application to separations of vitamin A and related carotenoids.
J. Chromatogr. 69: 215-8, 1972.
237)  Keefer LK, Wallcave L, Loo J, Peterson RS.
Analysis of mixtures of isomeric polynuclear hydrocarbons by nuclear magnetic resonance spectrometry methylated derivatives of anthracene, benz(a)anthracene, benzo(c)phenanthrene, and pyrene.
Anal. Chem. 43: 1411-6, 1971.
238)  Keefer LK, Johnson DE.
Magnesium hydroxide as a thin-layer chromatographic adsorbent. II. A unique system for separating polynuclear azaaromatic compounds.
J. Chromatogr. 47: 20-6, 1970.
239)  Keefer LK.
Magnesium hydroxide as a thin-layer chromatographic adsorbent. A new system for the separation of polynuclear hydrocarbons.
J. Chromatogr. 31: 390-5, 1967.
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