ADI-PEG 20

General
Glioblastoma
Hepatocellular carcinoma
Lymphomas
Melanoma
Mesothelioma
Myxofibrosarcoma
Ovarian cancer
Pancreatic cancer
Prostate cancer
Small cell lung cancer
Sarcoma
ADI-PEG 20 Antiviral

General

Arginine deprivation and argininosuccinate synthetase expression in the treatment of cancer

B. Delage, D.A. Fennell, L. Nicholson, I. McNeish, N.R. Lemoine, T. Crook, P.W. Szlosarek
International Journal of Cancer (2010), Vol. 126 pages 2762-2772
Abstract

Targeted cellular metabolism for cancer chemotherapy with recombinant arginine-degrading enzymes

M.T. Kuo, N. Savaraj, L.G. Feun
Oncotarget (2010), Vol. 1 pages 246-251
Abstract

ADI, autophagy and apoptosis: metabolic stress as a therapeutic option for prostate cancer

Kim RH, Bold RJ, Kung HJ.
Autophagy (2009), Vol. 5, Pages 567-8.
Abstract

Arginine deprivation as a targeted therapy for cancer

L. Feun, M. You, C.J. Wu, M.T. Kuo, M. Wangpaichitr, S. Spector and N. Savaraj
Current Pharmaceutical Design (2008), Vol. 14 pages 1049-1057
Abstract

Pegylated arginine deiminase: a novel anticancer enzyme agent

L. Feun and N. Savaraj
Expert Opinions on Investigational Drugs (2006), Vol. 15 pages 815-822
Abstract

Incidence and distribution of argininosuccinate synthetase deficiency in human cancers

B.J. Dillon, V.G. Prieto, S.A. Curley, C.M. Ensor, F.W. Holtsberg, J.S. Bomalaski and M.A. Clark
Cancer (2004), Vol. 100 pages 826-833
Abstract

Comparative toxicity of arginine deiminase formulated with poly(ethylene glycol) 5000 or 20,000 and the effects of arginine

J.S. Bomalaski, J.L. Ivett, M. Vegarra, F.W. Holtsberg, C.M. Ensor and M.A. Clark
Preclinica (2003), Vol. 1 pages 284-293
Abstract

Poly(ethylene glycol) (PEG) conjugated arginine deiminase: effects of PEG formulations on its pharmacological properties

F.W. Holtsberg, C.M. Ensor, M.R. Steiner, J.S. Bomalaski and M.A. Clark
Journal of Controlled Release (2002), Vol. 23 pages 259-271
Abstract

Enzymic degradation of plasma arginine using arginine deiminase inhibits nitric oxide production and protects mice from the lethal effects of tumour necrosis factor α and endotoxin

J.B. Thomas, F.W. Holtsberg, C.M. Ensor, J.S. Bomalaski and M.A. Clark
Biochemical Journal (2002), Vol. 363 pages 581-587
Abstract

Biochemical characterization of the arginine degrading enzymes arginase and arginine deiminase and their effect on nitric oxide production

B. Dillon, F. Holtsberg, C. Ensor, J. Bomalaski and M. Clark
Medical Science Monitor (2002), Vol. 8 pages BR248-253
Abstract

Pegylated arginine deiminase (ADI-SS PEG20,000mw) inhibits human melanomas and hepatocellular carcinomas in vitro and in vivo

Ensor CM, Holtsberg FW, Bomalaski JS, Clark MA.
Cancer Res (2002), Vol. 62, pages 5443-50.
Abstract

Glioblastoma

Epigenetic status of argininosuccinate synthetase and argininosuccinate lyase modulates autophagy and cell death in glioblastoma

Syed N, Langer J, Janczar K, Singh P, Lo Nigro C, Lattanzio L, Coley HM, Hatzimichael E, Bomalaski J, Szlosarek P, Awad M, O'Neil K, Roncaroli F, Crook T.
Cell Death Dis. (2013), Jan 17; 4:e458
Abstract

Hepatocellular carcinoma

Phase II Study of Pegylated Arginine Deiminase for Nonresectable and Metastatic Hepatocellular Carcinoma

E.S. Glazer, M. Piccirillo, V. Albino, R.D. Giacomo, R. Palaia, A.A. Mastro, G. Beneduce, G. Castello, V.D. Rosa, A. Petrillo, P.A. Ascierto, S.A. Curley, F. Izzo
Journal of Clinical Oncology (2010), Vol. 28 pages 2220-2226
Abstract

A randomised phase II study of pegylated arginine deiminase(ADI-PEG 20) in Asian advanced hepatocellular carcinoma patients

T-S Yang, S-N Lu, Y Chao, I-S Sheen, C-C Lin, T-E Wang, S-C Chen, J-H Wang, L-Y Liao, JA Thomson, J Wang-Peng, P-J Chenand L-T Chen
British Journal of Cancer (2010), Vol. 103 pages 954-960
Abstract

Pegylated arginine deiminase treatment of patients with unresectable hepatocellular carcinoma: results from phase I/II studies

F. Izzo, P. Marra, G. Beneduce, G. Castello, P. Vallone, V. De Rosa, F. Cremona, C.M. Ensor, F.W. Holtsberg, J.S. Bomalaski, M.A. Clark, C. Ng and S.A. Curley
Journal of Clinical Oncology (2004), Vol. 22 pages 1815-182
Abstract

Regression of hepatocellular cancer in a patient treated with arginine deiminase

S.A Curley, J.S. Bomalaski, C.M.Ensor, F.W. Holtsberg and M.A. Clark
Hepatogastroenterology (2003), Vol. 50 pages 1214-1216
Abstract

Pegylated arginine deiminase (ADI-SS PEG20,000 mw) inhibits human melanomas and hepatocellular carcinomas in vitro and in vivo

C.M. Ensor, F.W. Holtsberg, J.S. Bomalaski and M.A. Clark
Cancer Research (2002), Vol. 62 pages 5443-5450
Abstract

Lymphomas

Promoter methylation of argininosuccinate synthetase-1 sensitises lymphomas to arginine deiminase treatment, autophagy and caspase-dependent apoptosis.

Delage B, Luong P, Maharaj L, O'Riain C, Syed N, Crook T, Hatzimichael E, Papoudou-Bai A, Mitchell TJ, Whittaker SJ, Cerio R, Gribben J, Lemoine N, Bomalaski J, Li CF, Joel S, Fitgibbon J, Chen LT, Szlosarek PW.
Cell Death & Disease (2012) Jul 5;3:e342. doi: 10.1038/cddis.2012.83
Abstract

Melanoma

Evaluation of Arginine Deiminase Treatment in Melanoma Xenografts Using 18F-FLT PET

Stelter L, Fuchs S, Jungbluth AA, Ritter G, Longo VA, Zanzonico P, Raschzok N, Sauer IM, Bomalaski JS, Larson SM.
Mol. Imaging Biol (2013) DOI:10.1007/s 11307-013-0655-6
Abstract

Imaging of tumor vascularization using fluorescence molecular tomography to monitor arginine deiminase treatment in melanoma

Stelter L, Evans MJ, Jungbluth AA, Longo VA, Zanzonico P, Ritter G, Bomalaski JS, Old L, Larson SM.
Mol Imaging. (2013) Vol. 12 pages 67-73
Abstract

Arginine deprivation therapy for malignant melanoma

Yoon JK, Frankel AE, Feun LG, Ekmekcioglu S, Kim KB.
Clin Pharmacol (2013) Vol. 5 pages 11-19
Abstract

TRAIL induces autophagic protein cleavage through caspase activation in melanoma cell lines under arginine depravation.

You M, Savaraj N, Kuo MT, Wangpaichitr M, Varona-Santos J, Wu C, Nguyen DM, Feun L.
Mol Cell Biochem. (2013) Vol. 374, pages 181-90
Abstract

Novel Mechanistic Insights into Arginine Deiminase Pharmacology Suggest 18-FDG is Not Suitable to Evaluate Clinical Response in Melanoma.

Stelter L, Evans MJ, Jungbluth AA, Zanzonico P, Ritter G, Ku T, Rosenfeld E, Bomalaski JS, Old L, Larson SM.
J Nucl Med. (2012) Vol. 53, pages 281-6
Abstract

Phase I/II study of pegylated arginine deiminase (ADI-PEG 20) in patients with advanced melanoma

Patrick A. Ott & Richard D. Carvajal & Neeta Pandit-Taskar & Achim A. Jungbluth & Eric W. Hoffman & Bor-Wen Wu & John S. Bomalaski & Ralph Venhaus & Linda Pan & Lloyd J. Old & Anna C. Pavlick & Jedd D. Wolchok
Invest New Drugs (2012), DOI 10.1007/s10637-012-9862-2
Abstract

Activation of Ras/PI3K/ERK Pathway Induces c-Myc Stabilization to Upregulate Argininosuccinate Synthetase, Leading to Arginine Deiminase Resistance in Melanoma Cells

Wen-Bin Tsai, Isamu Aiba, Yan Long, Hui-Kuan Lin, Lynn Feun, Niramol Savaraj, and Macus Tien Kuo
Cancer Research(2012), Vol. 72 pages 2622-2633
Abstract

Negative argininosuccinate synthetase expression in melanoma tumours may predict clinical benefit from arginine-depleting therapy with pegylated arginine deiminase

LG Feun, A Marini, G Walker, G Elgart, F Moffat, SE Rodgers, CJWu, M You, M Wangpaichitr, MT Kuo, W Sisson, AA Jungbluth, J Bomalaski and N Savaraj
British Journal of Cancer (2012), Vol. 106 pages 1481-1485
Abstract

Induction of arginosuccinate synthetase (ASS) expression affects the antiproliferative activity of arginine deiminase (ADI) in melanoma cells.

Manca A, Sini MC, Izzo F, Ascierto PA, Tatangelo F, Botti G, Gentilcore G, Capone M, Mozzillo N, Rozzo C, Cossu A, Tanda F, Palmieri G.
Oncol Rep (2011) Vol. 25, pages 1495-1502
Abstract

The combination of ADI-PEG20 and TRAIL effectively increases cell death in melanoma cell lines.

You M, Savaraj N, Wangpaichitr M, Wu C, Kuo MT, Varona-Santos J, Nguyen DM, Feun L.
Biochem Biophys Res Commun. (2010), Vol. 394, pages 760-6.
Abstract

Arginine Deprivation, Autophagy, Apoptosis (AAA) for the Treatment of Melanoma

N. Savaraj, M. You, C. Wu, M. Wangpaichitr, M.T. Kuo and L.G. Feun
Current Molecular Medicine(2010), Vol. 10 pages 405-412
Abstract

Resistance to arginine deiminase treatment in melanoma cells is associated with induced argininosuccinate synthetase expression involving c-Myc/HIF-1α/Sp4

W-B Tsai, I. Aiba, S-y Lee, L. Feun, N. Savaraj, M.T. Kuo
Molecular Cancer Therapy(2009), Vol. 8 pages 3223-33
Abstract

The relationship of arginine deprivation, argininosuccinate synthetase and cell death in melanoma

N. Savaraj, C. Wu, M.T. Kuo, M. You, M. Wangpaichitr, C. Robles, S. Spector and L. Feun
Drug Target Insights (2007), Vol. 2 pages 119-128
Abstract

Pegylated arginine deiminase treatment of patients with metastatic melanoma: results from phase I and II studies

P.A. Ascierto, S. Scala, G. Castello, A. Daponte, E. Simeone, A. Ottaiano, G. Beneduce, V. De Rosa, F. Izzo, M.T. Melucci, C.M. Ensor, A.W. Prestayko, F.W. Holtsberg, J.S. Bomalaski, M.A. Clark, N. Savaraj, L.G. Feun and T.F. Logan
Journal of Clinical Oncology (2005), Vol. 23 pages 7660-7668
Abstract

Pegylated arginine deiminase (ADI-SS PEG20,000 mw) inhibits human melanomas and hepatocellular carcinomas in vitro and in vivo

C.M. Ensor, F.W. Holtsberg, J.S. Bomalaski and M.A. Clark
Cancer Research (2002), Vol. 62 pages 5443-5450
Abstract

Mesothelioma

Metabolic response to pegylated arginine deiminase in mesothelioma with promoter methylation of argininosuccinate synthetase

Szlosarek PW, Luong P, Phillips MM, Baccarini M, Stephen E, Szyszko T, Sheaff MT, Avril N
J Clin Oncol. (2013) Mar 1; 31(7):e111-3

In vivo loss of expression of argininosuccinate synthetase in malignant pleural mesothelioma is a biomarker for susceptibility to arginine depletion

P.W. Szlosarek, A. Klabatsa, A. Pallaska, M. Sheaff, P. Smith, T. Crook, M.J. Grimshaw, J.P. Steele, R.M. Rudd, F.R. Balkwill and D.A. Fennell
Clinical Cancer Research (2006), Vol. 12 pages 7126-7135
Abstract

Myxofibrosarcoma

ASS1 as a Novel Tumor Suppressor Gene in Myxofibrosarcoma: Aberrant loss via epigenetic DNA methylation confers aggressive phenotypes, negative prognostic impact, and therapeutic relevance

Huang HY, Wu WR, Wang YH, Wang JW, Fang FM, Tsai JW, Li SH, Hung HC, Yu SC, Lan J, Shiue YL, Hsing CH, Chen LT, Li CF
Clin Cancer Res (2013) Apr 2
Abstract

Ovarian cancer

Epigenetic silencing of argininosuccinate synthetase confers resistance to platinum-induced cell death but collateral sensitivity to arginine auxotrophy in ovarian cancer

L.J. Nicholson, P.R. Smith, L. Hiller, P.W. Szlosarek, C. Kimberley, J. Sehouli, D. Koensgen, A. Mustea, P. Schmid, T. Crook
International Journal of Cancer (2009), Vol. 125 pages 1454-1463
Abstract

Aberrant regulation of argininosuccinate synthetase by TNF-α in human epithelial ovarian cancer

P.W. Szlosarek, M.J. Grimshaw, G.D. Wilbanks, T. Hagemann, J.L. Wilson, F. Burke, G. Stamp and F.R. Balkwill
International Journal of Cancer (2007), Vol. 121 pages 6-11
Abstract

Pancreatic cancer

Pancreatic cancer cell lines deficient in argininosuccinate synthetase are sensitive to arginine deprivation by arginine deiminase

T.L. Bowles, R. Kim, J. Galante, C.M. Parsons, S. Virudachalam, H-J. Kung and R.J. Bold
International Journal of Cancer (2008), Vol. 123 pages 1950-1955
Abstract

Prostate cancer

Arginine deiminase as a novel therapy for prostate cancer induces autophagy and caspase-independent apoptosis

R.H. Kim, J.M. Coates, T.L. Bowles, G.P. McNerney, J. Sutcliffe, J.U. Jung, R. Gandour-Edwards, F.Y. Chuang, R.J. Bold, and H.J. Kung
Cancer Research (2009), Vol. 69 pages 700-708
Abstract

ADI, autophagy, and apoptosis: metabolic stress as a therapeutic option for prostate cancer

R.H. Kim, R.J. Bold, H.J. Kung
Autophagy (2009), Vol. 5 pages 567-568
Abstract

Small cell lung cancer

Arginine deiminase PEG20 inhibits growth of small cell lung cancers lacking expression of argininosuccinate synthetase

MP Kelly, AA Jungbluth, B-W Wu, J Bomalaski, LJ Old and G Ritter
British Journal of Cancer (2012), Vol. 106 pages 324-332
Abstract

Sarcoma

Reduced Argininosuccinate Synthetase Is a Predictive Biomarker for the Development of Pulmonary Metastasis in Patients with Osteosarcoma

E. Kobayashi, M. Masuda, R. Nakayama, H. Ichikawa, R. Satow, M. Shitashige, K. Honda, U. Yamaguchi, A. Shoji, N. Tochigi, H. Morioka, Y. Toyama, S. Hirohashi, A. Kawai, T. Yamada
Molecular Cancer Therapeutics (2010), Vol. 9 pages 535-44
Abstract

ADI-PEG 20 Antiviral

Pegylated arginine deiminase lowers hepatitis C viral titers and inhibits nitric oxide synthesis

F. Izzo, M. Montella, A.P. Orlando, G. Nasti, G. Beneduce, G. Castello, F. Cremona, C.M. Ensor, F.W. Holtzberg, J.S. Bomalaski, M.A. Clark, S.A. Curley, R. Orlando, F. Scordino and B.E. Korba
Journal of Gastroenterology and Hepatology (2007), Vol. 22 pages 86-91
Abstract

Suppression of human immunodeficiency virus type 1 replication by arginine deiminase of Mycoplasma arginini

M. Kubo, H. Nishitsuji, K. Kurihara, T. Hayashi, T. Masuda, M. Kannagi
Journal of General Virology (2006), Vol. 87 pages 1589-1593
Abstract

TNF-PEG 20

Tumour necrosis factor (cachectin) induces phospholipase A2 activity and synthesis of a phospholipase A2-activating protein in endothelial cells

M.A. Clark, M.J. Chen, S.T. Crooke and J.S. Bomalaski
Biochemical Journal (1988), Vol. 250 pages 125-132
Abstract

CK2 Inhibitor

Structure-based design and synthesis of novel macrocyclic pyrazolo[1,5-a][1,3,5]triazine compounds as potent inhibitors of protein kinase CK2 and their anticancer activities>

Z. Nie, C. Perretta, P. Erickson, S. Margosiak, J. Lu, A. Averill, R. Almassy and S. Chu
Bioorganic & Medicinal Chemistry Letters (2008), Vol. 18 pages 619-623
Abstract

Structure-based design, synthesis, and study of pyrazolo[1,5-a][1,3,5]triazine derivatives as potent inhibitors of protein kinase CK2

Z. Nie, C. Perretta, P. Erickson, S. Margosiak, R. Almassy, J. Lu, A. Averill, K.M. Yager and S. Chu
Bioorganic & Medicinal Chemistry Letters (2007), Vol. 17 pages 4191-4195
Abstract