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The Team that Just Wouldn't Quit and a New Paradigm in Cancer Drug Discovery.

Shepard HM.

Cell. 2019 Sep 19;179(1):27-32. doi: 10.1016/j.cell.2019.08.028. Epub 2019 Sep 10.


Biomarker-Driven Drug Discovery in Cancer-Trastuzumab Development: 2019 Lasker-DeBakey Clinical Medical Research Award.

Shepard HM.

JAMA. 2019 Sep 10. doi: 10.1001/jama.2019.13963. [Epub ahead of print] No abstract available.


Parallel Accumulation of Tumor Hyaluronan, Collagen, and Other Drivers of Tumor Progression.

Li X, Shepard HM, Cowell JA, Zhao C, Osgood RJ, Rosengren S, Blouw B, Garrovillo SA, Pagel MD, Whatcott CJ, Han H, Von Hoff DD, Taverna DM, LaBarre MJ, Maneval DC, Thompson CB.

Clin Cancer Res. 2018 Oct 1;24(19):4798-4807. doi: 10.1158/1078-0432.CCR-17-3284. Epub 2018 Jul 3.


KIAA1199 expression and hyaluronan degradation colocalize in multiple sclerosis lesions.

Marella M, Jadin L, Keller GA, Sugarman BJ, Frost GI, Shepard HM.

Glycobiology. 2018 Dec 1;28(12):958-967. doi: 10.1093/glycob/cwy064.


Phase 1 trials of PEGylated recombinant human hyaluronidase PH20 in patients with advanced solid tumours.

Infante JR, Korn RL, Rosen LS, LoRusso P, Dychter SS, Zhu J, Maneval DC, Jiang P, Shepard HM, Frost G, Von Hoff DD, Borad MJ, Ramanathan RK.

Br J Cancer. 2018 Jan;118(2):e3. doi: 10.1038/bjc.2017.438.


Phase 1 trials of PEGylated recombinant human hyaluronidase PH20 in patients with advanced solid tumours.

Infante JR, Korn RL, Rosen LS, LoRusso P, Dychter SS, Zhu J, Maneval DC, Jiang P, Shepard HM, Frost G, Von Hoff DD, Borad MJ, Ramanathan RK.

Br J Cancer. 2018 Jan;118(2):153-161. doi: 10.1038/bjc.2017.327. Epub 2017 Sep 26. Erratum in: Br J Cancer. 2018 Jan;118(2):e3.


Developments in therapy with monoclonal antibodies and related proteins.

Shepard HM, Phillips GL, D Thanos C, Feldmann M.

Clin Med (Lond). 2017 Jun;17(3):220-232. doi: 10.7861/clinmedicine.17-3-220. Review.


PH20 is not expressed in murine CNS and oligodendrocyte precursor cells.

Marella M, Ouyang J, Zombeck J, Zhao C, Huang L, Connor RJ, Phan KB, Jorge MC, Printz MA, Paladini RD, Gelb AB, Huang Z, Frost GI, Sugarman BJ, Steinman L, Wei G, Shepard HM, Maneval DC, Lapinskas PJ.

Ann Clin Transl Neurol. 2017 Feb 23;4(3):191-211. doi: 10.1002/acn3.393. eCollection 2017 Mar.


Phase Ib Study of PEGylated Recombinant Human Hyaluronidase and Gemcitabine in Patients with Advanced Pancreatic Cancer.

Hingorani SR, Harris WP, Beck JT, Berdov BA, Wagner SA, Pshevlotsky EM, Tjulandin SA, Gladkov OA, Holcombe RF, Korn R, Raghunand N, Dychter S, Jiang P, Shepard HM, Devoe CE.

Clin Cancer Res. 2016 Jun 15;22(12):2848-54. doi: 10.1158/1078-0432.CCR-15-2010. Epub 2016 Jan 26.


Breaching the Castle Walls: Hyaluronan Depletion as a Therapeutic Approach to Cancer Therapy.

Shepard HM.

Front Oncol. 2015 Aug 28;5:192. doi: 10.3389/fonc.2015.00192. eCollection 2015. Review.


Desmoplasia in Primary Tumors and Metastatic Lesions of Pancreatic Cancer.

Whatcott CJ, Diep CH, Jiang P, Watanabe A, LoBello J, Sima C, Hostetter G, Shepard HM, Von Hoff DD, Han H.

Clin Cancer Res. 2015 Aug 1;21(15):3561-8. doi: 10.1158/1078-0432.CCR-14-1051. Epub 2015 Feb 18.


Tumor-associated hyaluronan limits efficacy of monoclonal antibody therapy.

Singha NC, Nekoroski T, Zhao C, Symons R, Jiang P, Frost GI, Huang Z, Shepard HM.

Mol Cancer Ther. 2015 Feb;14(2):523-32. doi: 10.1158/1535-7163.MCT-14-0580. Epub 2014 Dec 15.


Accumulation of extracellular hyaluronan by hyaluronan synthase 3 promotes tumor growth and modulates the pancreatic cancer microenvironment.

Kultti A, Zhao C, Singha NC, Zimmerman S, Osgood RJ, Symons R, Jiang P, Li X, Thompson CB, Infante JR, Jacobetz MA, Tuveson DA, Frost GI, Shepard HM, Huang Z.

Biomed Res Int. 2014;2014:817613. doi: 10.1155/2014/817613. Epub 2014 Jul 24.


Response to Chauhan et Al.: interstitial pressure and vascular collapse in pancreas cancer-fluids and solids, measurement and meaning.

DelGiorno KE, Carlson MA, Osgood R, Provenzano PP, Brockenbough JS, Thompson CB, Shepard HM, Frost GI, Potter JD, Hingorani SR.

Cancer Cell. 2014 Jul 14;26(1):16-7. doi: 10.1016/j.ccr.2014.06.004. No abstract available.


Characterization of a novel recombinant hyaluronan binding protein for tissue hyaluronan detection.

Jadin L, Huang L, Wei G, Zhao Q, Gelb AB, Frost GI, Jiang P, Shepard HM.

J Histochem Cytochem. 2014 Sep;62(9):672-83. doi: 10.1369/0022155414540176. Epub 2014 Jun 2.


Recombinant human hyaluronidase PH20 does not stimulate an acute inflammatory response and inhibits lipopolysaccharide-induced neutrophil recruitment in the air pouch model of inflammation.

Huang Z, Zhao C, Chen Y, Cowell JA, Wei G, Kultti A, Huang L, Thompson CB, Rosengren S, Frost GI, Shepard HM.

J Immunol. 2014 Jun 1;192(11):5285-95. doi: 10.4049/jimmunol.1303060. Epub 2014 Apr 28.


Mutations in the catalytic domain of human matrix metalloproteinase-1 (MMP-1) that allow for regulated activity through the use of Ca2+.

Paladini RD, Wei G, Kundu A, Zhao Q, Bookbinder LH, Keller GA, Shepard HM, Frost GI.

J Biol Chem. 2013 Mar 1;288(9):6629-39. doi: 10.1074/jbc.M112.364729. Epub 2013 Jan 15.


Effective targeting of the tumor microenvironment for cancer therapy.

Jiang P, Li X, Thompson CB, Huang Z, Araiza F, Osgood R, Wei G, Feldmann M, Frost GI, Shepard HM.

Anticancer Res. 2012 Apr;32(4):1203-12.


Hyaluronan impairs vascular function and drug delivery in a mouse model of pancreatic cancer.

Jacobetz MA, Chan DS, Neesse A, Bapiro TE, Cook N, Frese KK, Feig C, Nakagawa T, Caldwell ME, Zecchini HI, Lolkema MP, Jiang P, Kultti A, Thompson CB, Maneval DC, Jodrell DI, Frost GI, Shepard HM, Skepper JN, Tuveson DA.

Gut. 2013 Jan;62(1):112-20. doi: 10.1136/gutjnl-2012-302529. Epub 2012 Mar 30.


Therapeutic targeting of hyaluronan in the tumor stroma.

Kultti A, Li X, Jiang P, Thompson CB, Frost GI, Shepard HM.

Cancers (Basel). 2012 Sep 6;4(3):873-903. doi: 10.3390/cancers4030873.


Human epidermal growth factor receptor bispecific ligand trap RB200: abrogation of collagen-induced arthritis in combination with tumour necrosis factor blockade.

Gompels LL, Malik NM, Madden L, Jin P, Feldmann M, Shepard HM, Paleolog EM.

Arthritis Res Ther. 2011;13(5):R161. doi: 10.1186/ar3480. Epub 2011 Oct 7.


Enzymatic depletion of tumor hyaluronan induces antitumor responses in preclinical animal models.

Thompson CB, Shepard HM, O'Connor PM, Kadhim S, Jiang P, Osgood RJ, Bookbinder LH, Li X, Sugarman BJ, Connor RJ, Nadjsombati S, Frost GI.

Mol Cancer Ther. 2010 Nov;9(11):3052-64. doi: 10.1158/1535-7163.MCT-10-0470. Epub 2010 Oct 26.


A pan-HER approach for cancer therapy: background, current status and future development.

Huang Z, Brdlik C, Jin P, Shepard HM.

Expert Opin Biol Ther. 2009 Jan;9(1):97-110. doi: 10.1517/14712590802630427 . Review.


Rational optimization of a bispecific ligand trap targeting EGF receptor family ligands.

Jin P, Zhang J, Beryt M, Turin L, Brdlik C, Feng Y, Bai X, Liu J, Jorgensen B, Shepard HM.

Mol Med. 2009 Jan-Feb;15(1-2):11-20. doi: 10.2119/molmed.2008.00103. Epub 2008 Nov 17.


Signal integration: a framework for understanding the efficacy of therapeutics targeting the human EGFR family.

Shepard HM, Brdlik CM, Schreiber H.

J Clin Invest. 2008 Nov;118(11):3574-81. doi: 10.1172/JCI36049. Review.


Human epidermal growth factor receptor (HER-1:HER-3) Fc-mediated heterodimer has broad antiproliferative activity in vitro and in human tumor xenografts.

Sarup J, Jin P, Turin L, Bai X, Beryt M, Brdlik C, Higaki JN, Jorgensen B, Lau FW, Lindley P, Liu J, Ni I, Rozzelle J, Kumari R, Watson SA, Zhang J, Shepard HM.

Mol Cancer Ther. 2008 Oct;7(10):3223-36. doi: 10.1158/1535-7163.MCT-07-2151.


Antagonism of the human epidermal growth factor receptor family controls disease severity in murine collagen-induced arthritis.

Sumariwalla PF, Jin P, Zhang J, Ni I, Crawford D, Shepard HM, Paleolog EM, Feldmann M.

Arthritis Rheum. 2008 Oct;58(10):3071-80. doi: 10.1002/art.23885.


Novel splice variants derived from the receptor tyrosine kinase superfamily are potential therapeutics for rheumatoid arthritis.

Jin P, Zhang J, Sumariwalla PF, Ni I, Jorgensen B, Crawford D, Phillips S, Feldmann M, Shepard HM, Paleolog EM.

Arthritis Res Ther. 2008;10(4):R73. doi: 10.1186/ar2447. Epub 2008 Jul 1.



Shepard HM, Jin P, Slamon DJ, Pirot Z, Maneval DC.

Handb Exp Pharmacol. 2008;(181):183-219. Review.


A recombinant human enzyme for enhanced interstitial transport of therapeutics.

Bookbinder LH, Hofer A, Haller MF, Zepeda ML, Keller GA, Lim JE, Edgington TS, Shepard HM, Patton JS, Frost GI.

J Control Release. 2006 Aug 28;114(2):230-41. Epub 2006 Jun 7.


Inhibition of cell growth by NB1011 requires high thymidylate synthase levels and correlates with p53, p21, bax, and GADD45 induction.

Neuteboom ST, Karjian PL, Boyer CR, Beryt M, Pegram M, Wahl GM, Shepard HM.

Mol Cancer Ther. 2002 Apr;1(6):377-84.


NB2001, a novel antibacterial agent with broad-spectrum activity and enhanced potency against beta-lactamase-producing strains.

Li Q, Lee JY, Castillo R, Hixon MS, Pujol C, Doppalapudi VR, Shepard HM, Wahl GM, Lobl TJ, Chan MF.

Antimicrob Agents Chemother. 2002 May;46(5):1262-8.


A novel approach to thymidylate synthase as a target for cancer chemotherapy.

Li Q, Boyer C, Lee JY, Shepard HM.

Mol Pharmacol. 2001 Mar;59(3):446-52.


Enzyme-catalyzed therapeutic agent (ECTA) design: activation of the antitumor ECTA compound NB1011 by thymidylate synthase.

Lackey DB, Groziak MP, Sergeeva M, Beryt M, Boyer C, Stroud RM, Sayre P, Park JW, Johnston P, Slamon D, Shepard HM, Pegram M.

Biochem Pharmacol. 2001 Jan 15;61(2):179-89.


p53 gene therapy in a rat model of hepatocellular carcinoma: intra-arterial delivery of a recombinant adenovirus.

Anderson SC, Johnson DE, Harris MP, Engler H, Hancock W, Huang WM, Wills KN, Gregory RJ, Sutjipto S, Wen SF, Lofgren S, Shepard HM, Maneval DC.

Clin Cancer Res. 1998 Jul;4(7):1649-59.


Enhancement of adenovirus-mediated gene transfer to human bone marrow cells.

Watanabe T, Kelsey L, Ageitos A, Kuszynski C, Ino K, Heimann DG, Varney MT, Shepard HM, Vaillancourt MT, Maneval DC, Talmadge JE.

Leuk Lymphoma. 1998 May;29(5-6):439-51.


p53-mediated accumulation of hypophosphorylated pRb after the G1 restriction point fails to halt cell cycle progression.

Linke SP, Harris MP, Neugebauer SE, Clarkin KC, Shepard HM, Maneval DC, Wahl GM.

Oncogene. 1997 Jul 17;15(3):337-45.


Adenovirus-mediated p53 gene transfer suppresses growth of human glioblastoma cells in vitro and in vivo.

Köck H, Harris MP, Anderson SC, Machemer T, Hancock W, Sutjipto S, Wills KN, Gregory RJ, Shepard HM, Westphal M, Maneval DC.

Int J Cancer. 1996 Sep 17;67(6):808-15.


Gene transfer into human bone marrow hematopoietic cells mediated by adenovirus vectors.

Watanabe T, Kuszynski C, Ino K, Heimann DG, Shepard HM, Yasui Y, Maneval DC, Talmadge JE.

Blood. 1996 Jun 15;87(12):5032-9.


186Re-labeled antibodies to p185HER2 as HER2-targeted radioimmunopharmaceutical agents: comparison of physical and biological characteristics with 125I and 131I-labeled counterparts.

Kotts CE, Su FM, Leddy C, Dodd T, Scates S, Shalaby MR, Wirth CM, Giltinan D, Schroff RW, Fritzberg AR, Shepard HM, Slamon DJ, Hutchins BM.

Cancer Biother Radiopharm. 1996 Apr;11(2):133-44.


Adenovirus-mediated p53 gene transfer inhibits growth of human tumor cells expressing mutant p53 protein.

Harris MP, Sutjipto S, Wills KN, Hancock W, Cornell D, Johnson DE, Gregory RJ, Shepard HM, Maneval DC.

Cancer Gene Ther. 1996 Mar-Apr;3(2):121-30.


Purification of a type 5 recombinant adenovirus encoding human p53 by column chromatography.

Huyghe BG, Liu X, Sutjipto S, Sugarman BJ, Horn MT, Shepard HM, Scandella CJ, Shabram P.

Hum Gene Ther. 1995 Nov;6(11):1403-16.


Recombinant human retinoblastoma protein inhibits cancer cell growth.

Pagliaro LC, Antelman D, Johnson DE, Machemer T, McCulloch EA, Freireich EJ, Stass SA, Shepard HM, Maneval D, Gutterman JU.

Cell Growth Differ. 1995 Jun;6(6):673-80.


Inhibition of tumor cell proliferation in vitro and in vivo by exogenous p110RB, the retinoblastoma tumor suppressor protein.

Antelman D, Machemer T, Huyghe BG, Shepard HM, Maneval D, Johnson DE.

Oncogene. 1995 Feb 16;10(4):697-704.


Retinoblastoma protein monoclonal antibodies with novel characteristics.

Wen SF, Nodelman M, Nared-Hood K, Duncan J, Geradts J, Shepard HM.

J Immunol Methods. 1994 Mar 10;169(2):231-40.


Inhibition of human lung cancer cell line growth by an anti-p185HER2 antibody.

Kern JA, Torney L, Weiner D, Gazdar A, Shepard HM, Fendly B.

Am J Respir Cell Mol Biol. 1993 Oct;9(4):448-54.


Differential responses of human tumor cell lines to anti-p185HER2 monoclonal antibodies.

Lewis GD, Figari I, Fendly B, Wong WL, Carter P, Gorman C, Shepard HM.

Cancer Immunol Immunother. 1993 Sep;37(4):255-63.


c-erbB-2 oncoprotein in screen-detected breast carcinoma: an immunohistological study.

Soomro S, Taylor P, Shepard HM, Feldmann M, Sinnett HD, Shousha S.

Int J Cancer. 1993 Aug 19;55(1):63-5. Erratum in: Int J Cancer 1994 Feb 1;56(3):462.


Loss in expression of the retinoblastoma gene product in human gliomas is associated with advanced disease.

Hamel W, Westphal M, Shepard HM.

J Neurooncol. 1993 May;16(2):159-65.


Estrogen-dependent, tamoxifen-resistant tumorigenic growth of MCF-7 cells transfected with HER2/neu.

Benz CC, Scott GK, Sarup JC, Johnson RM, Tripathy D, Coronado E, Shepard HM, Osborne CK.

Breast Cancer Res Treat. 1992;24(2):85-95.


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