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Developmental Therapeutics Program (DTP)
Last Updated: 07/23/15

TPB Publications

Davis M, Li J, Knight E, Eldridge SR, Daniels KK, Bushel PR. Toxicogenomics profiling of bone marrow from rats treated with topotecan in combination with oxaliplatin: a mechanistic strategy to inform combination toxicity. Front. Genet. 2015, 6 (14).

This paper represents the first in a series of papers derived from a significant collaboration between the NCI and the NIEHS Bioinformatics group. The data presented demonstrated the potential for early mRNA patterns derived from target organs of toxicity to inform toxicological risk and molecular mechanisms for agents given in combination. It provided a path forward for inclusion of a genomic-based high content screens to be used in early exploration of risk for enhanced toxicities with combination therapy.

Eldridge S, Guo L, Mussio J, Furniss M, Hamre J 3rd, Davis M. Examining the protective role of ErbB2 modulation in human-induced pluripotent stem cell-derived cardiomyocytes. Toxicol Sci. 2014, 141(2): 547-59.

This paper is the first in a series of detailed, functional characterization of pathways know to be key contributors to cardiac myocyte viability and responses to injury within the context of the whole heart in iPSC derived cardiac myocytes in culture. The expanding use of these cells for toxicology evaluation will require exploration of signaling pathways that can be translated to whole organ responses. This paper is a contribution to that body of literature.

Eldridge SR, Covey J, Morris J, Fang B, Horn TL, Elsass KE, Hamre JR 3rd, McCormick DL, Davis MA. Characterization of acute biliary hyperplasia in Fisher 344 rats administered the indole-3-carbinol analog, NSC-743380. Toxicol. Appl. Pharmacol. 2014, 281(3):303-9.

Biliary hyperplasia represents an unmanageable and non-monitorable adverse effect in clinical settings. The model described in this paper model provided an opportunity for investigators to use a short-duration study design to explore biomarkers of biliary hyperplasia. Requests from groups who wanted to use NSC-743380 in additional studies or as a positive control resulted from this publication.

Turteltaub KW, Davis MA, Burns-Naas LA, Lawton MP, Clark AM, Reynolds JA. Identification and elucidation of the biology of adverse events: the challenges of safety assessment and translational medicine. Clin Cancer Res. 2011, 17(21):6641-5.

The significance of this paper is linked to subsequent discussion and research direction for the Regan-Udall Foundation that was kicked off by this paper. This publication was the product of the work of all of the Authors as equal contributors (except JA Reynolds who did most of the editing).

Additional published research and technical reports

Davis, M., Eldridge, S., and Louden, C. (2013). Biomarkers: Discovery, Qualification and Application. In Handbook of Toxicologic Pathology, Third Edition (W. Haschek and C. Rousseaux, eds.), Elsevier Inc.

Muzzio M, Hua S-C, Holleran JL, Parise RA, Eiseman JL,  Yellow-Duke AE, Covey JM, Glaze ER, Engelke K, Egorin MJ, McCormick DL, Beumer JH (2015).  Plasma pharmacokinetics of the indenoisoquinoline topoisomerase I inhibitor, NSC 743400, in rats and dogs.  Cancer Chemother Pharmacol. (2015) 75: 1015-1023

Schweikart KM, Eldridge SR, Safgren SL, Parman T, Reid JM, Ames MM, Goetz MP and Davis MA. Comparative Uterotrophic Effects of Endoxifen and Tamoxifen in Ovariectomized Sprague-Dawley Rats, Toxicol. Pathol. 2014, 42 (8): 1188-1196

Shelburne N, Adhikari B, Brell J, Davis M, Desvigne-Nickens P, Freedman A, Minasian L, Force T, Remick SC. Cancer treatment-related cardiotoxicity: current state of knowledge and future research priorities. J Natl Cancer Inst. 2014, 106(9)

Davis M, Bunin DI, Samuelsson SJ, Altera KP, Kinders RJ, Lawrence SM, Ji J, Ames MM, Buhrow SA, Walden C, Reid JM, Rausch LL, Parman T. Characterization of Batracylin-induced Renal and Bladder Toxicity in Rats. Toxicol Pathol. 2014 Published online before print October 1, 2014, doi: 10.1177/0192623314548766

Behrsing HP, Furniss MJ, Davis M, Tomaszewski JE, Parchment RE. In Vitro Exposure of Precision-Cut Lung Slices to 2-(4-Amino-3-Methylphenyl)-5-Fluorobenzothiazole Lysylamide Dihydrochloride (NSC 710305, Phortress) Increases Inflammatory Cytokine Content and Tissue Damage. Toxicol. Sci. 2013, 131(2):470-9.

Schweikart K, Guo L, Shuler, Z, Abrams R, Chiao ET, Kolaja, KL and Davis M. The effects of jaspamide on human cardiomyocyte function and cardiac ion channel activity. Toxicology in Vitro. 2013:27 (2); 745-751.

Park SR, Davis M, Doroshow JH and Kummar S. Safety and feasibility of targeted agent combinations in solid tumours. Nature Reviews Clinical Oncology 2013, 10; 154-168

Davis, Myrtle, Boekelheide Kim, Boverhof Darrell R., Eichenbaum Gary, Hartung Thomas, Holsapple Michael P., Jones Thomas W., Richard Ann M., Watkins Paul B. The new revolution in toxicology: The good, the bad, and the ugly. Ann N Y Acad Sci 2013,1278(1):11-24.

Kaur G, Behrsing H, Parchment RE, Davis Millin M, Teicher BA. Analyses of the combination of 6-MP and dasatinib in cell culture. Int J Oncol. 2013, 43(1):13-22.

Mahfouz R, Jankowska A, Ebrahem Q, Gu X, Visconte V, Tabarroki A, Terse P, Covey J, Chan K, LingY, Engelke KJ, Sekeres MA, Tiu R, Maciejewski J, Radivoyevitch T, Saunthararajah Y (2013). Increased CDA expression/activity in males contributes to decreased cytidine analogue half-life and likely contributes to worse outcomes with 5-azacytidine or decitabine therapy. Clin Cancer Res.19(4):938-48

Parise RA, Anyang BN, Eiseman JL, Egorin MJ, Covey JM, Beumer JH. Formation of active products of benzaldehyde dimethane sulfonate (NSC 281612, DMS612) in human blood and plasma and their activity against renal cell carcinoma lines. Cancer Chemother. Pharmacol. 2012:1-11.

Rayburn E, Wang W, Li M, Zhang X, Xu H, Li H, Qin J-, Jia L, Covey J, Lee M, Zhang R. Preclinical pharmacology of novel indolecarboxamide ML-970, an investigative anticancer agent. Cancer Chemother Pharmacol 2012;69(6):1423-31.

Lavelle D, Vaitkus K, Ling Y, Ruiz MA, Mahfouz R, Ng KP, Negrotto S, Smith N, Terse P, Engelke KJ, Covey J, Chan KK, DeSimone J, Saunthararajah Y. (2012) Effects of tetrahydrouridine on pharmacokinetics and pharmacodynamics of oral decitabine. Blood;119(5):1240-7.

Elena Y Dobrikova, Christian Goetz, Robert W Walters, Sarah K Lawson, James O Peggins, Karen Muszynski, Sheryl Ruppel, Karyol Poole, Steven L Giardina, Eric M Vela, James E Estep, and Matthias Gromeier (2012). Attenuation of Neurovirulence, Biodistribution, and Shedding of a Poliovirus: Rhinovirus Chimera after Intrathalamic Inoculation in M. Fascicularis. Journal of Virology. J. Virol., 86(5):2750.

Beumer JH, Eiseman JL, Gilbert JA, Holleran JL, Yellow-Duke AE, Clausen DM, D'Argenio DZ, Ames MM, Hershberger PA, Parise RA, Bai L, Covey JM, Egorin MJ (2011). Plasma pharmacokinetics and oral bioavailability of the 3,4,5,6-tetrahydrouridine (THU) prodrug, triacetyl-THU (taTHU) in mice. Cancer Chemother Pharmacol;67(2):421-30.

Rausch L, Green C, Steinmetz K, Levalley S, Catz P, Zaveri N, Schweikart K, Tomaszewski J, and Mirsalis J (2011). Preclinical pharmacokinetic, toxicological and biomarker evaluation of SR16157, a novel dual-acting steroid sulfatase inhibitor and selective estrogen receptor modulator. Cancer Chemother Pharmacol 67: 1341-52.

Holleran JL, Parise RA, Yellow-Duke AE, Egorin MJ, Eiseman JL, Covey JM, Beumer JH (2011). Liquid chromatography-tandem mass spectrometric assay for the quantitation in human plasma of the novel indenoisoquinoline topoisomerase I inhibitors, NSC 743400 and NSC 725776. J Pharm. Biomed. Anal. 52(5):714-20.

Kenneth H Kim, Michael J Ryan, James E Estep, Brock M Miniard, Thomas L Rudge, James O Peggins, Trevor L Broadt, Minghui Wang, Meredith A Preuss, Gene P Siegal, Akseli Hemminki, Raymond D Harris, Rosemarie Aurigemma, David T Curiel, and Ronald D Alvarez (2011). A new generation of serotype chimeric infectivity-enhanced conditionally replicative adenovirals: the safety profile of ad5/3-Δ24 in advance of a phase I clinical trial in ovarian cancer patients. Human Gene Therapy, 22(7), 821-828.

Pramod S Terse, Jerry D Johnson, Michael A Hawk, Glenn D Ritchie, Michael J Ryan, Daphne Y Vasconcelos, Denise A Contos, Susan P Perrine, James O Peggins, and Joseph E Tomaszewski (2011). Short-term toxicity study of ST-20 (NSC-741804) by oral gavage in Sprague-Dawley rats. Toxicologic Pathology, 39(4), 614-622.

Earlier published research and technical reports

About the Branch Chief

Myrtle Davis, DVM. Ph.D. Myrtle Davis, DVM. Ph.D. is currently the Branch Chief for Toxicology and Pharmacology in the Developmental Therapeutics Program of the Division of Cancer Diagnostics and Treat-ment of the National Cancer Institute and serves as Scientific Director of the Labor-atory of Investigative Toxicology at the Frederick National Laboratory for Cancer Research (FNLCR). More…