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Targeting Glycolysis through Inhibition of Lactate Dehydrogenase Impairs Tumor Growth in Preclinical Models of Ewing Sarcoma.

Yeung C, Gibson AE, Issaq SH, Oshima N, Baumgart JT, Edessa LD, Rai G, Urban DJ, Johnson MS, Benavides GA, Squadrito GL, Yohe ME, Lei H, Eldridge S, Hamre J 3rd, Dowdy T, Ruiz-Rodado V, Lita A, Mendoza A, Shern JF, Larion M, Helman LJ, Stott GM, Krishna MC, Hall MD, Darley-Usmar V, Neckers LM, Heske CM.

Cancer Res. 2019 Oct 1;79(19):5060-5073. doi: 10.1158/0008-5472.CAN-19-0217. Epub 2019 Aug 20.


The mitochondrial type IB topoisomerase drives mitochondrial translation and carcinogenesis.

Baechler SA, Factor VM, Dalla Rosa I, Ravji A, Becker D, Khiati S, Miller Jenkins LM, Lang M, Sourbier C, Michaels SA, Neckers LM, Zhang HL, Spinazzola A, Huang SN, Marquardt JU, Pommier Y.

Nat Commun. 2019 Jan 8;10(1):83. doi: 10.1038/s41467-018-07922-3.


Induction of Thioredoxin-Interacting Protein by a Histone Deacetylase Inhibitor, Entinostat, Is Associated with DNA Damage and Apoptosis in Esophageal Adenocarcinoma.

Feingold PL, Surman DR, Brown K, Xu Y, McDuffie LA, Shukla V, Reardon ES, Crooks DR, Trepel JB, Lee S, Lee MJ, Gao S, Xi S, McLoughlin KC, Diggs LP, Beer DG, Nancarrow DJ, Neckers LM, Davis JL, Hoang CD, Hernandez JM, Schrump DS, Ripley RT.

Mol Cancer Ther. 2018 Sep;17(9):2013-2023. doi: 10.1158/1535-7163.MCT-17-1240. Epub 2018 Jun 22.


Targeting the Hsp40/Hsp70 Chaperone Axis as a Novel Strategy to Treat Castration-Resistant Prostate Cancer.

Moses MA, Kim YS, Rivera-Marquez GM, Oshima N, Watson MJ, Beebe KE, Wells C, Lee S, Zuehlke AD, Shao H, Bingman WE 3rd, Kumar V, Malhotra SV, Weigel NL, Gestwicki JE, Trepel JB, Neckers LM.

Cancer Res. 2018 Jul 15;78(14):4022-4035. doi: 10.1158/0008-5472.CAN-17-3728. Epub 2018 May 15.


Discovery and Optimization of Potent, Cell-Active Pyrazole-Based Inhibitors of Lactate Dehydrogenase (LDH).

Rai G, Brimacombe KR, Mott BT, Urban DJ, Hu X, Yang SM, Lee TD, Cheff DM, Kouznetsova J, Benavides GA, Pohida K, Kuenstner EJ, Luci DK, Lukacs CM, Davies DR, Dranow DM, Zhu H, Sulikowski G, Moore WJ, Stott GM, Flint AJ, Hall MD, Darley-Usmar VM, Neckers LM, Dang CV, Waterson AG, Simeonov A, Jadhav A, Maloney DJ.

J Med Chem. 2017 Nov 22;60(22):9184-9204. doi: 10.1021/acs.jmedchem.7b00941. Epub 2017 Nov 9.


Computational polypharmacology analysis of the heat shock protein 90 interactome.

Anighoro A, Stumpfe D, Heikamp K, Beebe K, Neckers LM, Bajorath J, Rastelli G.

J Chem Inf Model. 2015 Mar 23;55(3):676-86. doi: 10.1021/ci5006959. Epub 2015 Feb 23.


Solution formulation development and efficacy of MJC13 in a preclinical model of castration-resistant prostate cancer.

Liang S, Bian X, Liang D, Sivils JC, Neckers LM, Cox MB, Xie H.

Pharm Dev Technol. 2016;21(1):121-6. doi: 10.3109/10837450.2014.979946. Epub 2014 Nov 7.


Mitochondrial topoisomerase I (top1mt) is a novel limiting factor of doxorubicin cardiotoxicity.

Khiati S, Dalla Rosa I, Sourbier C, Ma X, Rao VA, Neckers LM, Zhang H, Pommier Y.

Clin Cancer Res. 2014 Sep 15;20(18):4873-81. doi: 10.1158/1078-0432.CCR-13-3373. Epub 2014 Apr 8.


Tumor-intrinsic and tumor-extrinsic factors impacting hsp90- targeted therapy.

Alarcon SV, Mollapour M, Lee MJ, Tsutsumi S, Lee S, Kim YS, Prince T, Apolo AB, Giaccone G, Xu W, Neckers LM, Trepel JB.

Curr Mol Med. 2012 Nov 1;12(9):1125-41. Review.


Amplification and high-level expression of heat shock protein 90 marks aggressive phenotypes of human epidermal growth factor receptor 2 negative breast cancer.

Cheng Q, Chang JT, Geradts J, Neckers LM, Haystead T, Spector NL, Lyerly HK.

Breast Cancer Res. 2012 Apr 17;14(2):R62.


Charged linker sequence modulates eukaryotic heat shock protein 90 (Hsp90) chaperone activity.

Tsutsumi S, Mollapour M, Prodromou C, Lee CT, Panaretou B, Yoshida S, Mayer MP, Neckers LM.

Proc Natl Acad Sci U S A. 2012 Feb 21;109(8):2937-42. doi: 10.1073/pnas.1114414109. Epub 2012 Feb 6.


Targeting the regulation of androgen receptor signaling by the heat shock protein 90 cochaperone FKBP52 in prostate cancer cells.

De Leon JT, Iwai A, Feau C, Garcia Y, Balsiger HA, Storer CL, Suro RM, Garza KM, Lee S, Kim YS, Chen Y, Ning YM, Riggs DL, Fletterick RJ, Guy RK, Trepel JB, Neckers LM, Cox MB.

Proc Natl Acad Sci U S A. 2011 Jul 19;108(29):11878-83. doi: 10.1073/pnas.1105160108. Epub 2011 Jul 5.


STA-9090, a small-molecule Hsp90 inhibitor for the potential treatment of cancer.

Wang Y, Trepel JB, Neckers LM, Giaccone G.

Curr Opin Investig Drugs. 2010 Dec;11(12):1466-76. Review.


Heat shock protein 90 inhibitor 17-dimethylaminoethylamino-17-demethoxygeldanamycin enhances EphA2+ tumor cell recognition by specific CD8+ T cells.

Kawabe M, Mandic M, Taylor JL, Vasquez CA, Wesa AK, Neckers LM, Storkus WJ.

Cancer Res. 2009 Sep 1;69(17):6995-7003. doi: 10.1158/0008-5472.CAN-08-4511. Epub 2009 Aug 18.


Low dose geldanamycin inhibits hepatocyte growth factor and hypoxia-stimulated invasion of cancer cells.

Koga F, Tsutsumi S, Neckers LM.

Cell Cycle. 2007 Jun 1;6(11):1393-402. Epub 2007 Jun 13.


Measuring ubiquitin conjugation in cells.

Mimnaugh EG, Neckers LM.

Methods Mol Biol. 2005;301:223-41.


Expression of the insulin-like growth factor I receptor and urokinase plasminogen activator in breast cancer is associated with poor survival: potential for intervention with 17-allylamino geldanamycin.

Nielsen TO, Andrews HN, Cheang M, Kucab JE, Hsu FD, Ragaz J, Gilks CB, Makretsov N, Bajdik CD, Brookes C, Neckers LM, Evdokimova V, Huntsman DG, Dunn SE.

Cancer Res. 2004 Jan 1;64(1):286-91.


Geldanamycin and 17-allylamino-17-demethoxygeldanamycin potentiate the in vitro and in vivo radiation response of cervical tumor cells via the heat shock protein 90-mediated intracellular signaling and cytotoxicity.

Bisht KS, Bradbury CM, Mattson D, Kaushal A, Sowers A, Markovina S, Ortiz KL, Sieck LK, Isaacs JS, Brechbiel MW, Mitchell JB, Neckers LM, Gius D.

Cancer Res. 2003 Dec 15;63(24):8984-95.


Hsp90 regulates a von Hippel Lindau-independent hypoxia-inducible factor-1 alpha-degradative pathway.

Isaacs JS, Jung YJ, Mimnaugh EG, Martinez A, Cuttitta F, Neckers LM.

J Biol Chem. 2002 Aug 16;277(33):29936-44. Epub 2002 Jun 6.


Immunoblotting methods for the study of protein ubiquitination.

Mimnaugh EG, Neckers LM.

Methods Mol Biol. 2002;194:179-203. No abstract available.


Hsp90, not Grp94, regulates the intracellular trafficking and stability of nascent ErbB2.

Xu W, Mimnaugh EG, Kim JS, Trepel JB, Neckers LM.

Cell Stress Chaperones. 2002 Jan;7(1):91-6.


Stereospecific antitumor activity of radicicol oxime derivatives.

Soga S, Sharma SV, Shiotsu Y, Shimizu M, Tahara H, Yamaguchi K, Ikuina Y, Murakata C, Tamaoki T, Kurebayashi J, Schulte TW, Neckers LM, Akinaga S.

Cancer Chemother Pharmacol. 2001 Dec;48(6):435-45.


The Hsp90 inhibitor geldanamycin selectively sensitizes Bcr-Abl-expressing leukemia cells to cytotoxic chemotherapy.

Blagosklonny MV, Fojo T, Bhalla KN, Kim JS, Trepel JB, Figg WD, Rivera Y, Neckers LM.

Leukemia. 2001 Oct;15(10):1537-43.


Can the heat shock protein 90 inhibitor geldanamycin be designed to specifically inhibit HER-2 tyrosine kinase?

Neckers LM.

Drug Resist Updat. 2000 Aug;3(4):203-205. No abstract available.


Requirement for HDM2 activity in the rapid degradation of p53 in neuroblastoma.

Isaacs JS, Saito S, Neckers LM.

J Biol Chem. 2001 May 25;276(21):18497-506. Epub 2001 Feb 26.


Regulation of BRCA1 by protein degradation.

Blagosklonny MV, An WG, Melillo G, Nguyen P, Trepel JB, Neckers LM.

Oncogene. 1999 Nov 11;18(47):6460-8.


Interaction of radicicol with members of the heat shock protein 90 family of molecular chaperones.

Schulte TW, Akinaga S, Murakata T, Agatsuma T, Sugimoto S, Nakano H, Lee YS, Simen BB, Argon Y, Felts S, Toft DO, Neckers LM, Sharma SV.

Mol Endocrinol. 1999 Sep;13(9):1435-48.


KF25706, a novel oxime derivative of radicicol, exhibits in vivo antitumor activity via selective depletion of Hsp90 binding signaling molecules.

Soga S, Neckers LM, Schulte TW, Shiotsu Y, Akasaka K, Narumi H, Agatsuma T, Ikuina Y, Murakata C, Tamaoki T, Akinaga S.

Cancer Res. 1999 Jun 15;59(12):2931-8.


aHIF: the missing link between HIF-1 and VHL?

Neckers LM.

J Natl Cancer Inst. 1999 Jan 20;91(2):106-7. No abstract available.


Antibiotic radicicol binds to the N-terminal domain of Hsp90 and shares important biologic activities with geldanamycin.

Schulte TW, Akinaga S, Soga S, Sullivan W, Stensgard B, Toft D, Neckers LM.

Cell Stress Chaperones. 1998 Jun;3(2):100-8.


Oligodeoxynucleotide inhibitors of function: mRNA and protein interactions.

Neckers LM.

Cancer J Sci Am. 1998 May;4 Suppl 1:S35-42. Review. No abstract available.


Non-antisense oligonucleotide approaches for experimental treatment of glioblastoma.

Neckers LM, Kanekal M, Connell Y.

Antisense Nucleic Acid Drug Dev. 1998 Apr;8(2):177-9. Review. No abstract available.


Stabilization of wild-type p53 by hypoxia-inducible factor 1alpha.

An WG, Kanekal M, Simon MC, Maltepe E, Blagosklonny MV, Neckers LM.

Nature. 1998 Mar 26;392(6674):405-8.


In vivo degradation of N-myc in neuroblastoma cells is mediated by the 26S proteasome.

Bonvini P, Nguyen P, Trepel J, Neckers LM.

Oncogene. 1998 Mar 5;16(9):1131-9.


Geldanamycin-induced destabilization of Raf-1 involves the proteasome.

Schulte TW, An WG, Neckers LM.

Biochem Biophys Res Commun. 1997 Oct 29;239(3):655-9.


The amino-terminal domain of heat shock protein 90 (hsp90) that binds geldanamycin is an ATP/ADP switch domain that regulates hsp90 conformation.

Grenert JP, Sullivan WP, Fadden P, Haystead TA, Clark J, Mimnaugh E, Krutzsch H, Ochel HJ, Schulte TW, Sausville E, Neckers LM, Toft DO.

J Biol Chem. 1997 Sep 19;272(38):23843-50.


Expression of PAX3 in Ewing's sarcoma family of tumors.

Schulte TW, Toretsky JA, Ress E, Helman L, Neckers LM.

Biochem Mol Med. 1997 Apr;60(2):121-6.


Destabilization of Raf-1 by geldanamycin leads to disruption of the Raf-1-MEK-mitogen-activated protein kinase signalling pathway.

Schulte TW, Blagosklonny MV, Romanova L, Mushinski JF, Monia BP, Johnston JF, Nguyen P, Trepel J, Neckers LM.

Mol Cell Biol. 1996 Oct;16(10):5839-45.


Taxol-induced apoptosis and phosphorylation of Bcl-2 protein involves c-Raf-1 and represents a novel c-Raf-1 signal transduction pathway.

Blagosklonny MV, Schulte T, Nguyen P, Trepel J, Neckers LM.

Cancer Res. 1996 Apr 15;56(8):1851-4.


bcl-2 protein downregulation is not required for differentiation of multidrug resistant HL60 leukemia cells.

Blagosklonny MV, Alvarez M, Fojo A, Neckers LM.

Leuk Res. 1996 Feb;20(2):101-7.


Antisense efficacy : site-restricted in vivo and ex vivo models.

Neckers LM, Geselowitz D, Chavany C, Whitesell L, Bergan R.

Methods Mol Med. 1996;1:47-56. doi: 10.1385/0-89603-305-8:47.


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