A conceptually new treatment approach for relapsed glioblastoma: Coordinated undermining of survival paths with nine repurposed drugs (CUSP9) by the International Initiative for Accelerated Improvement of Glioblastoma Care

Oncotarget

Volumn 4, Issue 4, 2013, Pages 502-530

  Kast, Richard E ^a   Boockvar, John A ^b   Brüning, Ansgar ^c   Cappello, Francesco ^d   Chang, Wen Wei ^e   Cvek, Boris ^f   Dou, Q Ping ^g   Duenas Gonzalez, Alfonso ^h   Efferth, Thomas ⁱ   Focosi, Daniele ^j   Ghaffari, Seyed H ^k   Karpel Massler, Georg ^l   Ketola, Kirsi ^m   Khoshnevisan, Alireza ⁿ   Keizman, Daniel ^o   Magné, Nicolas ^p   Marosi, Christine ^q   McDonald, Kerrie ^r   Muñoz, Miguel ^s   Paranjpe, Ameya ^t   Pourgholami, Mohammad H ^r   Sardi, Iacopo ^u   Sella, Avishay ^v   Srivenugopal, Kalkunte S ^t   Tuccori, Marco ^j   Wang, Weiguang ^w   Wirtz, Christian R ^l   Halatsch, Marc Eric ^l   more..

^a IIAIGC Headquarters   (United States)

^b WEILL CORNELL MEDICAL COLLEGE   (United States)

^c UNIVERSITY OF MUNICH   (Germany)

^d UNIVERSITY OF PALERMO   (Italy)

^e CHUNG SHAN MEDICAL UNIVERSITY HOSPITAL   (Taiwan)

^f PALACKÝ UNIVERSITY   (Czech Republic)

^g WAYNE STATE UNIVERSITY   (United States)

^h INSTITUTO DE INVESTIGACIONES BIOMÉDICAS   (Mexico)

ⁱ JOHANNES GUTENBERG UNIVERSITY   (Germany)

^j UNIVERSITY OF PISA   (Italy)

^k TEHRAN UNIVERSITY OF MEDICAL SCIENCES   (Iran)

^l UNIVERSITY OF ULM   (Germany)

^m UNIVERSITY OF BRITISH COLUMBIA   (Canada)

ⁿ TEHRAN UNIVERSITY OF MEDICAL SCIENCES   (Iran)

^o TEL AVIV UNIVERSITY   (Israel)

^p Cancer Institute Lucien Neuwirth   (France)

^q MEDICAL UNIVERSITY OF VIENNA   (Austria)

^r UNIVERSITY OF NEW SOUTH WALES   (Australia)

^s HOSPITAL UNIVERSITARIO VIRGEN DEL ROCÍO   (Spain)

^t TEXAS TECH UNIVERSITY HEALTH SCIENCES CENTER   (United States)

^u UNIVERSITY OF FLORENCE   (Italy)

^v ASSAF HAROFEH MEDICAL CENTER   (Israel)

^w UNIVERSITY OF WOLVERHAMPTON   (United Kingdom)

more..

Author keywords

Angiotensin; Aprepitant; Artesunate; Auranofin; Captopril; Cytokines; Disulfiram; Glioblastoma; Ketoconazole; Nelfinavir; Neurokinin; Sertraline; Temozolomide

Indexed keywords

APREPITANT; ARTESUNATE; AURANOFIN; CAPTOPRIL; CARMUSTINE; CATHEPSIN B; CISPLATIN; CYCLOPHOSPHAMIDE; DEXAMETHASONE; DIETHYLDITHIOCARBAMIC ACID; DISULFIRAM; DOCETAXEL; DOXORUBICIN; ERLOTINIB; FLUOROURACIL; GEMCITABINE; GLUCONATE COPPER; GLUCONATE ZINC; KETOCONAZOLE; NELFINAVIR; PACLITAXEL; PLACEBO; RITONAVIR; SERTRALINE; SUNITINIB; TANESPIMYCIN; TEMOZOLOMIDE; THIOREDOXIN REDUCTASE;

ADJUVANT THERAPY; ALCOHOLISM; APOPTOSIS; ARTICLE; BREAST CANCER; CANCER ADJUVANT THERAPY; CANCER INHIBITION; CELL CYCLE ARREST; CHEMOTHERAPY INDUCED NAUSEA AND VOMITING; CONGESTIVE HEART FAILURE; DEPRESSION; DRUG BIOAVAILABILITY; DRUG BLOOD LEVEL; DRUG CYTOTOXICITY; DRUG DOSE INCREASE; DRUG DOSE TITRATION; DRUG METABOLISM; DRUG POTENTIATION; DRUG SAFETY; DRUG WITHDRAWAL; GLIOBLASTOMA; GLIOMA; HIV ASSOCIATED LIPODYSTROPHY; HUMAN; HUMAN IMMUNODEFICIENCY VIRUS INFECTION; HYPERTENSION; IMMUNE DEFICIENCY; INSULIN RESISTANCE; LOW DRUG DOSE; MALARIA; MELANOMA; MENTAL DISEASE; METABOLIC DISORDER; METALLIC TASTE; METASTATIC MELANOMA; NONHUMAN; ONYCHOMYCOSIS; ORTHOSTATIC HYPOTENSION; OVERALL SURVIVAL; PHARMACODYNAMICS; PROSTATE CANCER; QT PROLONGATION; QUALITY OF LIFE; RECOMMENDED DRUG DOSE; RECURRENT CANCER; RHEUMATOID ARTHRITIS; SIDE EFFECT; TASTE; TOXIC HEPATITIS; UNSPECIFIED SIDE EFFECT;

EID: 84879165730     PISSN: None     EISSN: 19492553     Source Type: Journal    
DOI: 10.18632/oncotarget.969     Document Type: Article

References (314)

1. Stummer W, Meinel T, Ewelt C, Martus P, Jakobs O, Felsberg J, Reifenberger G. Prospective cohort study of radiotherapy with concomitant and adjuvant temozolomide chemotherapy for glioblastoma patients with no or minimal residual enhancing tumor load after surgery.J Neurooncol. 2012;108:89-97. doi: 10.1007/s11060-012-0798-3.
2. Dressmann G. Temozolomide in malignant glioma. Onco Targets Ther. 2010;3:139-46. PubMed PMID: 20856849; PMCID:PMC2939767.
3. Chinnaiyan P, Chowdhary S, Potthast L, Prabhu A, Tsai YY, Sarcar B, Kahali S, Brem S, Yu HM, Rojiani A, Murtagh R, Pan E. Phase I trial of vorinostat combined with bevacizumab and CPT-11 in recurrent glioblastoma. Neuro Oncol. 2012;14:93-100. doi: 10.1093/neuonc/nor187.
4. Conti A, Pontoriero A, Arpa D, Siragusa C, Tomasello C, Romanelli P, Cardali S, Granata F, De Renzis C, Tomasello F. Efficacy and toxicity of CyberKnife re-irradiation and "dose dense" temozolomide for recurrent gliomas. Acta Neurochir (Wien). 2012;154:203-9. doi: 10.1007/s00701-011-1184-1.
5. Desjardins A, Reardon DA, Coan A, Marcello J, Herndon JE 2nd, Bailey L, Peters KB, Friedman HS, Vredenburgh JJ. Bevacizumab and daily temozolomide for recurrent glioblastoma. Cancer. 2012;118:1302-12. doi:10.1002/ cncr.26381.
6. Franceschi E, Stupp R, van den Bent MJ, van Herpen C, Laigle Donadey F, Gorlia T, Hegi M, Lhermitte B, StraussLC, Allgeier A, Lacombe D, Brandes AA EORTC 26083 phase I/II trial of dasatinib in combination with CCNU in patients with recurrent glioblastoma. Neuro Oncol. 2012;14:1503-10. doi: 10.1093/neuonc/nos256.
7. Friday BB, Anderson SK, Buckner J, Yu C, Giannini C, Geoffroy F, Schwerkoske J, Mazurczak M, Gross H, Pajon E, Jaeckle K, Galanis E. Phase II trial of vorinostat in combination with bortezomib in recurrent glioblastoma: a north central cancer treatment group study. Neuro Oncol. 2012;14:215-21. doi:10.1093/neuonc/nor198.
8. Gil MJ, de Las Peñas R, Reynés G, Balañá C, Peréz-Segura P, García-Velasco A, Mesia C, Gallego O, Fernández-Chacón C, Martínez-García M, Herrero A, Andrés R, Benavides M, Quintanar T, Pérez-Martin X. Bevacizumab plus irinotecan in recurrent malignant glioma shows high overall survival in a multicenter retrospective pooled series of the Spanish Neuro-Oncology Research Group. Anticancer Drugs. 2012;23:659-65. doi:10.1097/ CAD.0b013e3283534d3e.
9. Gilbert MR, Kuhn J, Lamborn KR, Lieberman F, Wen PY, Mehta M, Cloughesy T, Lassman AB, Deangelis LM, Chang S, Prados M. Cilengitide in patients with recurrent glioblastoma: the results of NABTC 03-02, a phase II trial with measures of treatment delivery. J Neurooncol. 2012;106:147-53. doi: 10.1007/s11060-011-0650-1.
10. Giglio P, Dhamne M, Hess KR, Gilbert MR, Groves MD, Levin VA, Kang SL, Ictech SE, Liu V, Colman H, Conrad CA, Loghin M, de Groot J, Yung WK, Puduvalli VK. Phase 2 trial of irinotecan and thalidomide in adults with recurrent anaplastic glioma. Cancer. 2012;118:3599-606. doi: 10.1002/cncr.26663.
11. Lv S, Teugels E, Sadones J, De Brakeleer S, Duerinck J, Du Four S, Michotte A, De Grève J, Neyns B. Correlation of EGFR, IDH1 and PTEN status with the outcome of patients with recurrent glioblastoma treated in a phase II clinical trial with the EGFR-blocking monoclonal antibody cetuximab. Int J Oncol. 2012;41:1029-35. doi: 10.3892/ ijo.2012.1539.
12. Mason WP, Belanger K, Nicholas G, Vallières I, Mathieu D, Kavan P, Desjardins A, Omuro A, Reymond D. A phase II study of the Ras-MAPK signaling pathway inhibitor TLN-4601 in patients with glioblastoma at first progression. J Neurooncol. 2012;107:343-9. doi: 10.1007/s11060-011-0747-6.
13. McPherson CM, Gerena-Lewis M, Breneman JC, Warnick RE. Results of phase I study of a multi-modality treatment for newly diagnosed glioblastoma multiforme using local implantation of concurrent BCNU wafers and permanent I-125 seeds followed by fractionated radiation and temozolomide chemotherapy. J Neurooncol. 2012;108:521-5. doi: 10.1007/s11060-012-0854-z.
14. Møller S, Grunnet K, Hansen S, Schultz H, Holmberg M, Sorensen M, Poulsen HS, Lassen U. A phase II trial with bevacizumab and irinotecan for patients with primary brain tumors and progression after standard therapy. Acta Oncol.2012;51:797-804. doi: 10.3109/0284186X.2012.681063.
15. Nagane M, Nishikawa R, Narita Y, Kobayashi H, Takano S, Shinoura N, Aoki T, Sugiyama K, Kuratsu J, Muragaki Y, Sawamura Y, Matsutani M. Phase II study of single-agent bevacizumab in Japanese patients with recurrent malignant glioma. Jpn J Clin Oncol. 2012;42:887-95.
16. Oehler C, Frei K, Rushing EJ, McSheehy PM, Weber D, Allegrini PR, Weniger D, Lütolf UM, Knuth A, Yonekawa Y, Barath K, Broggini-Tenzer A, Pruschy M, Hofer S. Patupilone (epothilone B) for recurrent glioblastoma: clinical outcome and translational analysis of a singleinstitution phase I/II trial. Oncology. 2012;83:1-9. doi: 10.1159/000339152.
17. Paccapelo A, Lolli I, Fabrini MG, Silvano G, Detti B, Perrone F, Savio G, Santoni M, Bonizzoni E, Perrone T, Scoccianti S. A retrospective pooled analysis of response patterns and risk factors in recurrent malignant glioma patients receiving a nitrosourea-based chemotherapy. J Transl Med. 2012;10:90. doi:10.1186/1479-5876-10-90.
18. Rampling R, Sanson M, Gorlia T, Lacombe D, Lai C, Gharib M, Taal W, Stoffregen C, Decker R, van den Bent MJ. A phase I study of LY317615 (enzastaurin) and temozolomide in patients with gliomas (EORTC trial 26054). Neuro Oncol. 2012;14:344-50. doi: 10.1093/ neuonc/nor221.
19. Reardon DA, Conrad CA, Cloughesy T, Prados MD, Friedman HS, Aldape KD, Mischel P, Xia J, DiLea C, Huang J, Mietlowski W, Dugan M, Chen W, Yung WK. Phase I study of EE788, a novel multitarget inhibitor of ErbB- and VEGF-receptor-family tyrosine kinases, in recurrent glioblastoma patients. Cancer Chemother Pharmacol. 2012;69:1507-18. doi: 10.1007/s00280-012-1854-6.
20. Reardon DA, Desjardins A, Peters KB, Gururangan S, Sampson JH, McLendon RE, Herndon JE 2nd, Bulusu A, Threatt S, Friedman AH, Vredenburgh JJ, Friedman HS. Phase II study of carboplatin, irinotecan, and bevacizumab for bevacizumab naïve, recurrent glioblastoma. J Neurooncol. 2012;107:155-64. doi: 10.1007/s11060-011-0722-2.
21. Sorensen AG, Emblem KE, Polaskova P, Jennings D, Kim H, Ancukiewicz M, Wang M, Wen PY, Ivy P, Batchelor TT, Jain RK. Increased survival of glioblastoma patients who respond to antiangiogenic therapy with elevated blood perfusion. Cancer Res. 2012;72:402-7. doi: 10.1158/0008-5472.CAN-11-2464.
22. Stupp R, Wong ET, Kanner AA, Steinberg D, Engelhard H, Heidecke V, Kirson ED, Taillibert S, Liebermann F, Dbalý V, Ram Z, Villano JL, Rainov N, Weinberg U, Schiff D, Kunschner L, Raizer J, Honnorat J, Sloan A, Malkin M, Landolfi JC, Payer F, Mehdorn M, Weil RJ, Pannullo SC, Westphal M, Smrcka M, Chin L, Kostron H, Hofer S, Bruce J, Cosgrove R, Paleologous N, Palti Y, Gutin PH. NovoTTF-100A versus physician's choice chemotherapy in recurrent glioblastoma: a randomized phase III trial of anovel treatment modality. Eur J Cancer. 2012;48:2192-202. doi: 10.1016/j.ejca.2012.04.011.
23. White E, Bienemann A, Taylor H, Hopkins K, Cameron A, Gill S. A phase I trial of carboplatin administered by convection-enhanced delivery to patients with recurrent/ progressive glioblastoma multiforme. Contemp Clin Trials. 2012;33:320-31. doi: 10.1016/j.cct.2011.10.010.
24. Dörner L, Mustafa A, Rohr A, Mehdorn HM, Nabavi A. Growth pattern of tumor recurrence following bischloroethylnitrosourea (BCNU) wafer implantation in malignant glioma. J Clin Neurosci. 2013 Jan 10. doi:pii: S0967-5868(12)00440-7. 10.1016/j.jocn.2012.01.060. [Epub ahead of print] PubMed PMID: 23313517.
25. Kast RE. Profound blockage of CXCR4 signaling at multiple points using the synergy between plerixafor, mirtazapine, and clotrimazole as a new glioblastoma treatment adjunct. Turk Neurosurg. 2010;20:425-9. doi: 10.5137/1019-5149.JTN.3334-10.0.
26. Thirant C, Gavard J, Junier MP, Chneiweiss H. Critical multiple angiogenic factors secreted by glioblastoma stem-like cells underline the need for combinatorial antiangiogenic therapeutic strategies. Proteomics Clin Appl. 2013;7(1-2):79-90. doi: 10.1002/prca.201200102.
27. Guo J, Niu R, Huang W, Zhou M, Shi J, Zhang L, Liao H. Growth factors from tumor microenvironment possibly promote the proliferation of glioblastoma-derived stem-like cells in vitro. Pathol Oncol Res. 2012;18:1047-57. PubMed PMID: 22996727.
28. Yang L, Lin C, Wang L, Guo H, Wang X. Hypoxia and hypoxia-inducible factors in glioblastoma multiforme progression and therapeutic implications. Exp Cell Res. 2012;318:2417-26. doi: 10.1016/j.yexcr.2012.07.017.
29. Siegelin MD, Plescia J, Raskett CM, Gilbert CA, Ross AH, Altieri DC. Global targeting of subcellular heat shock protein-90 networks for therapy of glioblastoma. Mol Cancer Ther. 2010;9:1638-46. doi:10.1158/1535-7163. MCT-10-0097.
30. Eyler CE, Rich JN Looking in the miR-ror: TGF-β-mediated activation of NF-κB in glioma. J Clin Invest. 2012;122:3473-5. doi: 10.1172/JCI66058.
31. Reddy K, Damek D, Gaspar LE, Ney D, Waziri A, Lillehei K, Stuhr K, Kavanagh BD, Chen C. Phase II trial of hypofractionated IMRT with temozolomide for patients with newly diagnosed glioblastoma multiforme. Int J Radiat Oncol Biol Phys. 2012;84:655-60. doi: 10.1016/j.ijrobp.2012.01.035.
32. Rock K, McArdle O, Forde P, Dunne M, Fitzpatrick D, O'Neill B, Faul C. A clinical review of treatment outcomes in glioblastoma multiforme--the validation in a non-trial population of the results of a randomised Phase III clinical trial: has a more radical approach improved survival? Br J Radiol. 2012;85:e729-33. doi: 10.1259/bjr/83796755.
33. Kong DS, Lee JI, Kim JH, Kim ST, Kim WS, Suh YL, Dong SM, Nam DH. Phase II trial of low-dose continuous(metronomic) treatment of temozolomide for recurrent glioblastoma. Neuro Oncol. 2010;12:289-96.doi:10.1093/ neuonc/nop030.
34. Omuro A, Chan TA, Abrey LE, Khasraw M, Reiner AS, Kaley TJ, Deangelis LM, Lassman, AB, Nolan CP, Gavrilovic IT, Hormigo A, Salvant C, Heguy A, Kaufman A, Huse JT, Panageas KS, Hottinger AF, Mellinghoff I. Phase II trial of continuous low-dose temozolomide for patients with recurrent malignant glioma. Neuro Oncol. 2013;15:242-50. doi: 10.1093/neuonc/nos295.
35. Ruhlmann CH, Herrstedt J. Safety evaluation of aprepitant for the prevention of chemotherapy-induced nausea and vomiting. Expert Opin Drug Saf. 2011;10:449-62. doi: 10.1517/14740338.2011.563235.
36. Chrisp P. Aprepitant: the evidence for its place in the prevention of chemotherapy-induced nausea and vomiting Core Evid. 2007; 2: 15-30.
37. Dando TM, Perry CM. Aprepitant: a review of its use in the prevention of chemotherapy-induced nausea and vomiting. Drugs. 2004;64:777-94.
38. Navari RM. Aprepitant: a neurokinin-1 receptor antagonist for the treatment of chemotherapy-induced nausea and vomiting. Expert Rev Anticancer Ther. 2004;4:715-24. PubMed PMID: 15485308.
39. dos Santos LV, Souza FH, Brunetto AT, Sasse AD, da Silveira Nogueira Lima JP. Neurokinin-1 receptor antagonists for chemotherapy-induced nausea and vomiting: a systematic review. J Natl Cancer Inst. 2012;104:1280-92. doi: 10.1093/jnci/djs335.
40. Aapro MS, Schmoll HJ, Jahn F, Carides AD, Webb RT. Review of the efficacy of aprepitant for the prevention of chemotherapy-induced nausea and vomiting in a range of tumor types. Cancer Treat Rev. 2013;39:113-7. doi: 10.1016/j.ctrv.2012.09.002.
41. Muñoz M, González-Ortega A, Rosso M, Robles-Frias MJ, Carranza A, Salinas-Martín MV, Coveñas R. The substance P/neurokinin-1 receptor system in lung cancer: Focus on the antitumor action of neurokinin-1 receptor antagonists. Peptides. 2012;38:318-25. doi: 10.1016/j. peptides.2012.09.024.
42. Muñoz M and Rosso M. The NK-1 receptor antagonist aprepitant as a broad spectrum antitumor drug. Invest New Drugs 2010; 28:187-193.
43. Muñoz M, Rosso M, Coveñas R. The NK-1 Receptor: A New Target in Cancer Therapy. Curr Drug Target 2011;12: 909-921.
44. Muñoz M, Coveñas R. NK-1 receptor antagonists: a new generation of anticancer drugs. Mini Rev Med Chem 2012;12: 593-599.
45. Muñoz M, Rosso M, Perez A, Coveñas R, Rosso R, Zamarriego C, Piruat JI. The NK1 receptor is involved in the antitumoral action of L-733,060 and the mitogenic action of substance P on neuroblastoma and glioma cell lines. Neuropeptides 2005; 39:427-32.
46. Kast RE. Why cerebellar glioblastoma is rare and how that indicates adjunctive use of the FDA-approved anti-emetic aprepitant might retard cerebral glioblastoma growth: a new hypothesis to an old question. Clin Transl Oncol. 2009;11:408-10. PubMed PMID: 19574198.
47. Kast RE. Glioblastoma: synergy of growth promotion between CCL5 and NK-1R can be thwarted by blocking CCL5 with miraviroc, an FDA approved anti-HIV drug and blocking NK-1R with aprepitant, an FDA approved anti-nausea drug. J Clin Pharm Ther. 2010;35:657-63. doi: 10.1111/j.1365-2710.2009.01148.x.
48. Muñoz M, Martinez-Armesto J, Coveñas R. NK-1 receptor antagonists as antitumor drugs: a survey of the literature from 2000 to 2011. Expert Opin Ther Pat. 2012;22:735-46. doi: 10.1517/13543776.2012.697153.
49. Kramer MS, Cutler N, Feighner J. Distinct mechanism for antidepressant activity by blockade of central substance P receptors. Science, 1998;281:1640-5.
50. Hennig IM, Laissue JA, Horisberger U, Reubi JC. Substance-P receptors in human primary neoplasms: tumoral and vascular localization. Int J Cancer 1995;61: 786-92.
51. Castelli F, Tomasoni LR, Matteelli A. Advances in the treatment of malaria. Mediterr J Hematol Infect Dis. 2012;4:e2012064. doi: 10.4084/MJHID.2012.064.
52. Efferth T, Dunstan H, Sauerbrey A, Miyachi H, Chitambar CR. The antimalarial artesunate is also active against cancer. Int J Oncol 2001;18:767-73.
53. Efferth T, Rücker G, Falkenberg M, Manns D, Olbrich A, Fabry U, Osieka R. Detection of apoptosis in KG-1a leukemic cells treated with investigational drugs. Arzneimittelforschung. 1996;46:196-200.
54. Efferth T. Molecular pharmacology and pharmacogenomics of artemisinin and its derivatives in cancer cells. Curr Drug Targets 2006;7:407-21.
55. Efferth T, Dunstan H, Sauerbrey A, Miyachi H, Chitambar CR. The anti-malarial artesunate is also active against cancer. Int J Oncol 2001;18:767-73.
56. Efferth T, Davey M, Olbrich A, Rücker G, Gebhart E, Davey R. Activity of drugs from traditional Chinese medicine toward sensitive and MDR1- or MRP1-overexpressing multidrug-resistant human CCRF-CEM leukemia cells. Blood Cells Mol Dis 2002;28:160-8.
57. Davis TM, Binh TQ, Ilett KF, Batty KT, Phuöng HL, Chiswell GM, Phuong VD, Agus C. Penetration of dihydroartemisinin into cerebrospinal fluid after administration of intravenous artesunate in severe falciparum malaria. Antimicrob Agents Chemother. 2003;47:368-70. PubMed PMID: 12499215
58. Efferth T, Briehl MM, Tome ME. Role of antioxidant genes for the activity of artesunate against tumor cells. Int J Oncol 2003;23:1231-5.
59. Efferth T, Oesch F. Oxidative stress response of tumor cells: microarray-based comparison between artemisinins andanthracyclines. Biochem Pharmacol 2004;68:3-10.
60. Efferth T, Volm M. Glutathione-related enzymes contribute to resistance of tumor cells and low toxicity in normal organs to artesunate. In Vivo 2005;19: 225-32.
61. Aisen P. Transferrin receptor 1. Int J Biochem Cell Biol. 2004;36:2137-43. PubMed PMID: 15313461.
62. Calzolari A, Oliviero I, Deaglio S, Mariani G, Biffoni M, Sposi NM, Malavasi F, Peschle C, Testa U. Transferrin receptor 2 is frequently expressed in human cancer cell lines. Blood Cells Mol Dis. 2007;39:82-91. PubMed PMID: 17428703.
63. Kang MK, Kang SK. Tumorigenesis of chemotherapeutic drug-resistant cancer stem-like cells in brain glioma. Stem Cells Dev. 2007;16:837-47. PubMed PMID: 17999604.
64. Efferth T, Benakis A, Romero MR, Tomicic M, Rauh R, Steinbach D, Hafer R, Stamminger T, Oesch F, Kaina B, Marschall M. Enhancement of cytotoxicity of artemisinins toward cancer cells by ferrous iron. Free Radic Biol Med 2004;37: 998-1009.
65. Efferth T, Sauerbrey A, Olbrich A, Gebhart E, Rauch P, Weber HO, Hengstler JG, Halatsch ME, Volm M, Tew KD, Ross DD, Funk JO. Molecular modes of action of artesunate in tumor cell lines. Mol Pharmacol 2003;64:382-94.
66. Berdelle N, Nikolova T, Quiros S, Efferth T, Kaina B. Artesunate induces oxidative DNA damage, sustained DNA double-strand breaks, and the ATM/ATR damage response in cancer cells. Mol Cancer Ther. 2011;10:2224-33.
67. Karpel-Massler G, Westhoff MA, Kast RE, Wirtz CR, Halatsch ME. Erlotinib in glioblastoma: lost in translation? Anticancer Agents Med Chem. 2011;11:748-55. PubMed PMID: 21707495.
68. Karpel-Massler G, Wirtz CR, Halatsch ME. Drug combinations enhancing the antineoplastic effects of erlotinib in high-grade glioma. Recent Pat Anticancer Drug Discov. 2011;6:384-94. doi: 10.2174/157489211796957748.
69. Loew S, Schmidt U, Unterberg A, Halatsch ME. The epidermal growth factor receptor as a therapeutic target in glioblastoma multiforme and other malignant neoplasms. Anticancer Agents Med Chem. 2009;9:703-15. PubMed PMID: 19601750.
70. Efferth T, Ramirez T, Gebhart E, Halatsch ME. Combination treatment of glioblastoma multiforme cell lines with the anti-malarial artesunate and the epidermal growth factor receptor tyrosine kinase inhibitor OSI-774. Biochem Pharmacol 2004;67:1689-700.
71. Efferth T, Giaisi M, Merling A, Krammer PH, Li-Weber M. Artesunate induces ROS-mediated apoptosis in doxorubicin-resistant T leukemia cells. PLoS One 2007; 2: e693.
72. Reichert S, Reinboldt V, Hehlgans S, Efferth T, Rödel C, Rödel F. A radiosensitizing effect of artesunate in glioblastoma cells is associated with a diminished expression of the inhibitor of apoptosis protein survivin.Radiother Oncol. 2012;103:394-401. doi: 10.1016/j. radonc.2012.03.018.
73. Zhao Y, Jiang W, Li B, Yao Q, Dong J, Cen Y, Pan X, Li J, Zheng J, Pang X, Zhou H. Artesunate enhances radiosensitivity of human non-small cell lung cancer A549 cells via increasing NO production to induce cell cycle arrest at G2/M phase. Int Immunopharmacol. 2011;11:2039-46. doi:10.1016/j.intimp.2011.08.017.
74. Glennås A, Kvien TK, Andrup O, Clarke-Jenssen O, Karstensen B, Brodin U. Auranofin is safe and superior to placebo in elderly-onset rheumatoid arthritis. Br J Rheumatol. 1997;36:870-7. PubMed PMID: 9291856.
75. Kean WF, Hart L, Buchanan WW. Auranofin. Br J Rheumatol. 1997;36:560-72.
76. Choksi S, Lin Y, Pobezinskaya Y, Chen L, Park C, Morgan M, Li T, Jitkaew S, Cao X, Kim YS, Kim HS, Levitt P, Shih G, Birre M, Deng CX, Liu ZG. A HIF-1 target, ATIA, protects cells from apoptosis by modulating the mitochondrial thioredoxin, TRX2. Mol Cell. 2011;42:597-609. doi: 10.1016/j.molcel.2011.03.030.
77. Becker K, Gromer S, Schirmer RH, Müller S. Thioredoxin reductase as a pathophysiological factor and drug target. Eur J Biochem. 2000;267:6118-25.
78. Kemerdere R, Kacira T, Hanimoglu H, Kucur M, Tanriverdi T, Canbaz B. Tissue and Plasma Thioredoxin Reductase Expressions in Patients with Glioblastoma Multiforme. J Neurol Surg A Cent Eur Neurosurg. 2013 Mar 19. [Epub ahead of print] PMID: 23512591.
79. Powis G, Kirkpatrick DL. Thioredoxin signaling as a target for cancer therapy. Curr Opin Pharmacol. 2007;7:392-7.
80. Biaglow JE, Miller RA. The thioredoxin reductase/ thioredoxin system: novel redox targets for cancer therapy. Cancer Biol Ther. 2005;4:6-13.
81. Drechsel DA, Patel M. Respiration-dependent H2O2 removal in brain mitochondria via the thioredoxin/ peroxiredoxin system. J Biol Chem. 2010;285:27850-8. doi:10.1074/jbc.M110.101196.
82. Lopert P, Day BJ, Patel M. Thioredoxin reductase deficiency potentiates oxidative stress, mitochondrial dysfunction and cell death in dopaminergic cells. PLoS One. 2012;7:e50683. doi: 10.1371/journal.pone.0050683.
83. Wang L, Fu JN, Wang JY, Jin CJ, Ren XY, Tan Q, Li J, Yin HW, Xiong K, Wang TY, Liu XM, Zeng HH. Seleniumcontaining thioredoxin reductase inhibitor ethaselen sensitizes non-small cell lung cancer to radiotherapy. Anticancer Drugs. 2011;22:732-40. doi: 10.1097/ CAD.0b013e32834618bc.
84. Lan L, Zhao F, Wang Y, Zeng H. The mechanism of apoptosis induced by a novel thioredoxin reductase inhibitor in A549 cells: possible involvement of nuclear factorkappaB-dependent pathway. Eur J Pharmacol. 2007;555:83-92.
85. van Horssen R, Willemse M, Haeger A, Attanasio F, Güneri T, Schwab A, Stock CM, Buccione R, Fransen JA,Wieringa B. Intracellular NAD(H) levels control motility and invasion of glioma cells. Cell Mol Life Sci. 2013 Jan 10. [Epub ahead of print] PMID:23307072.
86. Madeira JM, Gibson DL, Kean WF, Klegeris A. The biological activity of auranofin: implications for novel treatment of diseases. Inflammopharmacology. 2012;20:297-306. doi: 10.1007/s10787-012-0149-1.
87. Guidi F, Landini I, Puglia M, Magherini F, Gabbiani C, Cinellu MA, Nobili S, Fiaschi T, Bini L, Mini E, Messori L, Modesti A. Proteomic analysis of ovarian cancer cell responses to cytotoxic gold compounds. Metallomics. 2012;4:307-14. doi: 10.1039/c2mt00083k.
88. Sobhakumari A, Love-Homan L, Fletcher EV, Martin SM, Parsons AD, Spitz DR, Knudson CM, Simons AL. Susceptibility of human head and neck cancer cells to combined inhibition of glutathione and thioredoxin metabolism. PLoS One. 2012;7:e48175. doi: 10.1371/ journal.pone.0048175.
89. Kenig S, Alonso MB, Mueller MM, Lah TT. Glioblastoma and endothelial cells cross-talk, mediated by SDF-1, enhances tumour invasion and endothelial proliferation by increasing expression of cathepsins B, S, and MMP-9. Cancer Lett. 2010;289:53-61. doi: 10.1016/j. canlet.2009.07.014.
90. Gole B, Durán Alonso MB, Dolenc V, Lah T. Posttranslational regulation of cathepsin B, but not of other cysteine cathepsins, contributes to increased glioblastoma cell invasiveness in vitro. Pathol Oncol Res. 2009;15:711-23.doi: 10.1007/s12253-009-9175-8.
91. Colin C, Voutsinos-Porche B, Nanni I, Fina F, Metellus P, Intagliata D, Baeza N, Bouvier C, Delfino C, Loundou A, Chinot O, Lah T, Kos J, Martin PM, Ouafik L, Figarella-Branger D. High expression of cathepsin B and plasminogen activator inhibitor type-1 are strong predictors of survival in glioblastomas. Acta Neuropathol. 2009;118:745-54. doi: 10.1007/s00401-009-0592-2.
92. Strojnik T, Kos J, Zidanik B, Golouh R, Lah T. Cathepsin B immunohistochemical staining in tumor and endothelial cells is a new prognostic factor for survival in patients with brain tumors. Clin Cancer Res. 1999;5:559-67. PubMed PMID: 10100707.
93. Lakka SS, Gondi CS, Yanamandra N, Olivero WC, Dinh DH, Gujrati M, Rao JS. Inhibition of cathepsin B and MMP-9 gene expression in glioblastoma cell line via RNA interference reduces tumor cell invasion, tumor growth and angiogenesis. Oncogene. 2004;23:4681-9.
94. Kast RE. Glioblastoma invasion, cathepsin B, and the potential for both to be inhibited by auranofin, an old anti-rheumatoid arthritis drug. Cent Eur Neurosurg. 2010;71:139-42. doi: 10.1055/s-0029-1242756.
95. Jørgensen CH, Pedersen B, Tønnesen H. The efficacy of disulfiram for the treatment of alcohol use disorder. Alcohol Clin Exp Res. 2011;35:1749-58. doi: 10.1111/j.1530-0277.2011.01523.x.
96. Johansson B. A review of the pharmacokinetics and pharmacodynamics of disulfiram and its metabolites. Acta Psychiatr Scand Suppl. 1992;369:15-26.
97. Liu P, Brown S, Goktug T, Channathodiyil P, Kannappan V, Hugnot JP, Guichet PO, Bian X, Armesilla AL, Darling JL, Wang W. Cytotoxic effect of disulfiram/copper on human glioblastoma cell lines and ALDH-positive cancerstem-like cells. Br J Cancer. 2012;107:1488-97. doi: 10.1038/bjc.2012.442.
98. Liu P, Brown S, Channathodiyil P, Kannappan V, Armesilla AL, Darling JL, Wang W. Reply: Cytotoxic effect of disulfiram/copper on human glioblastoma cell lines and ALDH-positive cancer-stem-like cells. Br J Cancer. 2013 Jan 22. doi:10.1038/bjc.2013.19. [Epub ahead of print] PubMed PMID: 23340450.
99. Xu B, Shi P, Fombon IS, Zhang Y, Huang F, Wang W, Zhou S. Disulfiram/copper complex activated JNK/c-jun pathway and sensitized cytotoxicity of doxorubicin in doxorubicin resistant leukemia HL60 cells. Blood Cells Mol Dis. 2011;47:264-9. doi: 10.1016/j.bcmd.2011.08.004.
100. Yip NC, Fombon IS, Liu P, Brown S, Kannappan V, Armesilla AL, Xu B, Cassidy J, Darling JL, Wang W. Disulfiram modulated ROS-MAPK and NFκB pathways and targeted breast cancer cells with cancer stem cell-like properties. Br J Cancer. 2011;104:1564-74. doi: 10.1038/ bjc.2011.126.
101. Guo X, Xu B, Pandey S, Goessl E, Brown J, Armesilla AL, Darling JL, Wang W. Disulfiram/copper complex inhibiting NFkappaB activity and potentiating cytotoxic effect of gemcitabine on colon and breast cancer cell lines. Cancer Lett. 2010;290:104-13. doi:10.1016/j.canlet.2009.09.002.
102. Wang W, McLeod HL, Cassidy J. Disulfiram-mediated inhibition of NF-kappaB activity enhances cytotoxicity of 5-fluorouracil in human colorectal cancer cell lines. Int J Cancer. 2003;104:504-11. PubMed PMID: 12584750.
103. Chen D, Dou QP. New uses for old copper-binding drugs: converting the pro-angiogenic copper to a specific cancer cell death inducer. Expert Opin Ther Targets. 2008;12:739-48. doi: 10.1517/14728222.12.6.739.
104. Ketola K, Kallioniemi O, Iljin K. Chemical biology drug sensitivity screen identifies sunitinib as synergistic agent with disulfiram in prostate cancer cells PLoS One. 2012; 7:e51470. doi: 10.1371/journal.pone.
105. Morrison BW, Doudican NA, Patel KR, Orlow SJ. Disulfiram induces copper-dependent stimulation of reactive oxygen species and activation of the extrinsic apoptotic pathway in melanoma. Melanoma Res. 2010;20:11-20. doi:10.1097/CMR.0b013e328334131d.
106. Wickström M, Danielsson K, Rickardson L, Gullbo J, Nygren P, Isaksson A, Larsson R, Lövborg H. Pharmacological profiling of disulfiram using human tumor cell lines and human tumor cells from patients. Biochem Pharmacol. 2007;73:25-33. PubMed PMID: 17026967.
107. Yakisich JS, Sidén A, Eneroth P, Cruz M. Disulfiram is apotent in vitro inhibitor of DNA topoisomerases. Biochem Biophys Res Commun. 2001;289:586-90. PubMed PMID: 11716515.
108. Sauna ZE, Peng XH, Nandigama K, Tekle S, Ambudkar SV. The molecular basis of the action of disulfiram as a modulator of the multidrug resistance-linked ATP binding cassette transporters MDR1 (ABCB1) and MRP1 (ABCC1). Mol Pharmacol. 2004;65:675-84. PubMed PMID: 14978246.
109. Sauna ZE, Shukla S, Ambudkar SV. Disulfiram, an old drug with new potential therapeutic uses for human cancers and fungal infections. Mol Biosyst. 2005;1:127-34. PubMed PMID: 16880974.
110. Brar SS, Grigg C, Wilson KS, Holder WD Jr, Dreau D, Austin C, Foster M, Ghio AJ, Whorton AR, Stowell GW, Whittall LB, Whittle RR, White DP, Kennedy TP. Disulfiram inhibits activating transcription factor/cyclic AMP-responsive element binding protein and human melanoma growth in a metal-dependent manner in vitro, in mice and in a patient with metastatic disease. Mol Cancer Ther. 2004;3:1049-60. PubMed PMID: 15367699.
111. Lövborg H, Oberg F, Rickardson L, Gullbo J, Nygren P, Larsson R. Inhibition of proteasome activity, nuclear factor-KappaB translocation and cell survival by the antialcoholism drug disulfiram. Int J Cancer. 2006;118:1577-80. PubMed PMID: 16206267.
112. Lin J, Haffner MC, Zhang Y, Lee BH, Brennen WN, Britton J, Kachhap SK, Shim JS, Liu JO, Nelson WG, Yegnasubramanian S, Carducci MA. Disulfiram is a DNA demethylating agent and inhibits prostate cancer cell growth. Prostate. 2011;71:333-43. doi: 10.1002/pros.21247.
113. Cvek B. Targeting malignancies with disulfiram (Antabuse): multidrug resistance, angiogenesis, and proteasome. Curr Cancer Drug Targets. 2011;11:332-7. PubMed PMID: 21247389.
114. Cvek B. Antabuse (disulfiram) as a pilot case of nonprofit drug. Int J Cancer. 2010;127:2486. doi: 10.1002/ijc.25237. PubMed PMID: 20143396.
115. Cvek B, Dvorak Z. The value of proteasome inhibition in cancer. Can the old drug, disulfiram, have a bright new future as a novel proteasome inhibitor? Drug Discov Today. 2008;13:716-22. doi: 10.1016/j.drudis.2008.05.003.
116. Cvek B, Dvorak Z. Targeting of nuclear factor-kappaB and proteasome by dithiocarbamate complexes with metals. Curr Pharm Des. 2007;13:3155-67.
117. Conticello C, Martinetti D, Adamo L, Buccheri S, Giuffrida R, Parrinello N, Lombardo L, Anastasi G, Amato G, Cavalli M, Chiarenza A, De Maria R, Giustolisi R, Gulisano M, Di Raimondo F. Disulfiram, an old drug with new potential therapeutic uses for human hematological malignancies. Int J Cancer. 2012;131:2197-203. doi: 10.1002/ijc.27482.
118. Iljin K, Ketola K, Vainio P, Halonen P, Kohonen P, Fey V, Grafström RC, Perälä M, Kallioniemi O. Highthroughput cell-based screening of 4910 known drugsand drug-like small molecules identifies disulfiram as an inhibitor of prostate cancer cell growth. Clin Cancer Res. 2009;15:6070-8. doi:10.1158/1078-0432.CCR-09-1035.
119. Cvek B, Milacic V, Taraba J, Dou QP. Ni(II), Cu(II), and Zn(II) diethyldithiocarbamate complexes show various activities against the proteasome in breast cancer cells. J Med Chem. 2008;51:6256-8. doi: 10.1021/jm8007807.
120. Cvek B. Nonprofit drugs as the salvation of the world's healthcare systems: the case of Antabuse (disulfiram). Drug Discov Today. 2012;17:409-12. doi: 10.1016/j. drudis.2011.12.010. PubMed PMID: 22192884.
121. Rasper M, Schäfer A, Piontek G, Teufel J, Brockhoff G, Ringel F, Heindl S, Zimmer C, Schlegel J. Aldehyde dehydrogenase 1 positive glioblastoma cells show brain tumor stem cell capacity. Neuro Oncol. 2010; 12(10): 1024-1033. doi: 10.1093/neuonc/noq070.
122. Rappa F, Cappello F, Halatsch ME, Scheuerle A, Kast RE. Aldehyde dehydrogenase and HSP90 co-localize in human glioblastoma biopsy cells. Biochimie 2013;95(4):782-6. doi: 10.1016/j.biochi.2012.11.007.
123. Schäfer A, Teufel J, Ringel F, Bettstetter M, Hoepner I, Rasper M, Gempt J, Koeritzer J, Schmidt-Graf F, Meyer B, Beier CP, Schlegel J. Aldehyde dehydrogenase 1A1--a new mediator of resistance to temozolomide in glioblastoma. Neuro Oncol. 2012;14:1452-64. doi: 10.1093/neuonc/ nos270.
124. Quemener V, Moulinoux JP, Martin C, Darcel F, Guegan Y, Faivre J, Quash GA. Aldehyde dehydrogenase activity in xenografted human brain tumor in nude mice. Preliminary results in human glioma biopsies. J Neurooncol. 1990;9:115-23.PubMed PMID: 2262798.
125. Benayoun L, Shaked Y. In vitro enrichment of tumorinitiating cells from human established cell lines. Curr Protoc Stem Cell Biol. 2013 Feb;Chapter 3:Unit3.7.doi: 10.1002/9780470151808.sc0307s24.
126. Hothi P, Martins TJ, Chen L, Deleyrolle L, Yoon JG, Reynolds B, Foltz G. High-throughput chemical screens identify disulfiram as an inhibitor of human glioblastoma stem cells. Oncotarget. 2012;3(10):1124-36.
127. Kast RE, Belda-Iniesta C. Suppressing glioblastoma stem cell function by aldehyde dehydrogenase inhibition with chloramphenicol or disulfiram as a new treatment adjunct: an hypothesis. Curr Stem Cell Res Ther. 2009;4(4):314-7. PubMed PMID: 19500061.
128. O'Brien A, Barber JE, Reid S, Niknejad N, Dimitroulakos J. Enhancement of cisplatin cytotoxicity by disulfiram involves activating transcription factor 3. Anticancer Res. 2012;32:2679-88. PubMed PMID: 22753726.
129. Dalla Pozza E, Donadelli M, Costanzo C, Zaniboni T, Dando I, Franchini M, Arpicco S, Scarpa A, Palmieri M. Gemcitabine response in pancreatic adenocarcinoma cells is synergistically enhanced by dithiocarbamate derivatives. Free Radic Biol Med. 201;50:926-33. doi:10.1016/j.freeradbiomed.2011.01.001.
130. Triscott J, Lee C, Hu K, Fotovati A, Berns R, Pambid M, Luk M, Kast RE, Kong E, Toyota E, Yip S, Toyota B, Dunn SE. Disulfiram, a drug widely used to control alcoholism, suppresses the self-renewal of glioblastoma and over-rides resistance to temozolomide. Oncotarget. 2012;3:1112-23. PubMed PMID: 23047041.
131. Budman DR, Calabro A. In vitro search for synergy and antagonism: evaluation of docetaxel combinations in breast cancer cell lines. Breast Cancer Res Treat. 2002;74:41-6. PubMed PMID: 12150451.
132. Moreb JS, Ucar D, Han S, Amory JK, Goldstein AS, Ostmark B, Chang LJ. The enzymatic activity of human aldehyde dehydrogenases 1A2 and 2 (ALDH1A2 and ALDH2) is detected by Aldefluor, inhibited by diethylaminobenzaldehyde and has significant effects on cell proliferation and drug resistance. Chem Biol Interact. 2012;195:52-60. doi: 10.1016/j.cbi.2011.10.007.
133. Paranjpe A, Srivenugopal KS. Degradation of NF-κB, p53 and other regulatory redox-sensitive proteins by thiolconjugating and -nitrosylating drugs in human tumor cells. Carcinogenesis. 2013 Feb 15. [Epub ahead of print] PubMed PMID: 23354308.
134. Dufour P, Lang JM, Giron C, Duclos B, Haehnel P, Jaeck D, Jung JM, Oberling F. Sodium dithiocarb as adjuvant immunotherapy for high risk breast cancer: a randomized study. Biotherapy. 1993;6:9-12.
135. Suh JJ, Pettinati HM, Kampman KM, O'Brien CP. The status of disulfiram: a half of a century later. J Clin Psychopharmacol. 2006;26:290-302.
136. Lewison EF. Spontaneous regression of breast cancer. Prog Clin Biol Res. 1977;12:47-53. PMID: 918117
137. Chen D, Cui QC, Yang H, Dou QP. Disulfiram, a clinically used anti-alcoholism drug and copper-binding agent, induces apoptotic cell death in breast cancer cultures and xenografts via inhibition of the proteasome activity. Cancer Res. 2006;66:10425-33.
138. Yu Z, Wang F, Milacic V, Li X, Cui QC, Zhang B, Yan B, Dou QP. Evaluation of copper-dependent proteasomeinhibitory and apoptosis-inducing activities of novel pyrrolidine dithiocarbamate analogues. Int J Mol Med. 2007;20:919-25. PubMed PMID: 17982703.
139. Loo TW, Bartlett MC, Clarke DM. Disulfiram metabolites permanently inactivates human multidrug resistance P-glycoprotein. Mol Pharm. 2004;1:426-33. PubMed PMID: 16028354.
140. Kaina B, Margison GP, Christmann M. Targeting O6-methylguanine-DNA methyltransferase with specific inhibitors as a strategy in cancer therapy. Cell Mol Life Sci. 2010;67:3663-3681.
141. Jiang G, Li LT, Xin Y, Zhang L, Liu YQ, Zheng JN. Strategies to improve the killing of tumors using temozolomide: targeting the DNA repair protein MGMT. Curr Med Chem. 2012;19:3886-92. PubMed PMID: 22788764.
142. Fukushima T, Takeshima H, Kataoka H. Anti-glioma therapy with temozolomide and status of the DNA-repair gene MGMT. Anticancer Res. 2009;29:4845-54. PubMed PMID: 20032445.
143. Srivenugopal KS, Paranjpe A. Potent redox-based inhibition of human MGMT for improving the efficacy of anticancer alkylating agents. Proc Amer Ass Cancer Res. 52, p.1321, 2011.
144. Niture SK, Velu CS, Bailey N, Srivenugopal KS. Human MGMT is a prime target for inactivation by oxidative stress, mediated by glutathionylation and oxidation of the active site cysteine145. Proc Amer Assoc Cancer Res. 2004;45:355, 2004.
145. Cohen KJ, Pollack IF, Zhou T, Buxton A, Holmes EJ, Burger PC, Brat DJ, Rosenblum MK, Hamilton RL, Lavey RS, Heideman RL. Temozolomide in the treatment of highgrade gliomas in children: a report from the Children's Oncology Group. Neuro Oncol. 2011;13(3):317-23. doi: 10.1093/neuonc/noq191.
146. Watanabe R, Nakasu Y, Tashiro H, Mitsuya K, Ito I, Nakasu S, Nakajima T. O6-methylguanine DNA methyltransferase expression in tumor cells predicts outcome of radiotherapy plus concomitant and adjuvant temozolomide therapy in patients with primary glioblastoma. Brain Tumor Pathol. 2011;28:127-135.
147. Quinn JA, Jiang SX, Reardon DA, Desjardins A, Vredenburgh JJ, Rich JN, Gururangan S, Friedman AH, Bigner DD, Sampson JH, McLendon RE, Herndon JE 2nd, Walker A, Friedman HS. Phase II trial of temozolomide plus o6-benzylguanine in adults with recurrent, temozolomideresistant malignant glioma. J Clin Oncol. 2009;27:1262-7. doi: 10.1200/JCO.2008.18.8417.
148. Guengerich, Fang Q, Liu L, Hachey DL, Pegg AE. O6-alkylguanine-DNA alkyltransferase: low pKa and high reactivity of cysteine 145. Biochemistry. 2003;42:10965-70. PubMed PMID: 12974631.
149. Niture SK, Velu CS, Smith QR, Bhat GJ, Srivenugopal KS. Increased expression of the MGMT repair protein mediated by cysteine prodrugs and chemopreventive natural products in human lymphocytes and tumor cell lines. Carcinogenesis 2006;28:378-389.
150. Matsuno T, Kariya R, Yano S, Morino-Koga S, Taura M, Suico MA, Shimauchi Y, Matsuyama S, Okamoto Y, Shuto T, Kai H, Okada S. Diethyldithiocarbamate induces apoptosis in HHV-8-infected primary effusion lymphoma cells via inhibition of the NF-κB pathway. Int J Oncol. 2012;40:1071-8. doi: 10.3892/ijo.2011.1313.
151. Skrott Z, Cvek B. Diethyldithiocarbamate complex with copper: the mechanism of action in cancer cells. Mini Rev Med Chem. 2012;12:1184-92. PubMed PMID: 22931589.
152. Lehmann K, Rickenbacher A, Jang JH, Oberkofler CE, Vonlanthen R, von Boehmer L, Humar B, Graf R, Gertsch P, Clavien PA. New insight into hyperthermic intraperitoneal chemotherapy: induction of oxidative stress dramatically enhanced tumor killing in in vitro andin vivo models. Ann Surg. 2012;256:730-7. doi: 10.1097/ SLA.0b013e3182737517.
153. Kast RE. Ritonavir and disulfiram may be synergistic in lowering active interleukin-18 levels in acute pancreatitis, and thereby hasten recovery. JOP. 2008;9(3):350-3. PubMed PMID: 18469453.
154. Foley K, Kast RE, Altschuler EL. Ritonavir and disulfiram have potential to inhibit caspase-1 mediated inflammation and reduce neurological sequelae after minor blast exposure. Med Hypotheses. 2009;72:150-2. doi: 10.1016/j.mehy.2008.08.024.
155. Nishikawa S, Konno M, Hamabe A, Hasegawa S, Kano Y, Ohta K, Fukusumi T, Sakai D, Kudo T, Haraguchi N, Satoh T, Takiguchi S, Mori M, Doki Y, Ishii H. Aldehyde dehydrogenase high gastric cancer stem cells are resistant to chemotherapy. Int J Oncol. 2013 Feb 22. doi: 10.3892/ ijo.2013.1837.
156. FDA.gov. accessed 3 Feb 2013. http://www. fda.gov/Food/FoodIngredientsPackaging/ GenerallyRecognizedasSafeGRAS/ GRASSubstancesSCOGSDatabase/ucm261260.htm
157. Olmo M, Podzamczer D. A review of nelfinavir for the treatment of HIV infection. Expert Opin Drug Metab Toxicol. 2006;2:285-300. PubMed PMID: 16866614.
158. Chiosis G, Dickey CA, Johnson JL. A global view of Hsp90 functions. Nat Struct Mol Biol. 2013;20:1-4. doi: 10.1038/ nsmb.2481.
159. Kast RE, Halatsch ME. Matrix metalloproteinase-2 and -9 in glioblastoma: a trio of old drugs-captopril, disulfiram and nelfinavir-are inhibitors with potential as adjunctive treatments in glioblastoma. Arch Med Res. 2012;43:243-7. doi: 10.1016/j.arcmed.2012.04.005.
160. Khaliq Y, Gallicano K, Venance S, Kravcik S, Cameron DW. Effect of ketoconazole on ritonavir and saquinavir concentrations in plasma and cerebrospinal fluid from patients infected with human immunodeficiency virus. Clin Pharmacol Ther. 2000;68:637-46.
161. Shim JS, Rao R, Beebe K, Neckers L, Han I, Nahta R, Liu JO. Selective inhibition of HER2-positive breast cancer cells by the HIV protease inhibitor nelfinavir. J Natl Cancer Inst. 2012;104:1576-90. doi: 10.1093/jnci/djs396.
162. Brüning A, Gingelmaier A, Friese K, Mylonas I. New prospects for nelfinavir in non-HIV-related diseases. Curr Mol Pharmacol. 2010;3:91-7. PubMed PMID: 20359290.
163. Brüning A, Burger P, Vogel M, Rahmeh M, Gingelmaiers A, Friese K, Lenhard M, Burges A. Nelfinavir induces the unfolded protein response in ovarian cancer cells, resulting in ER vacuolization, cell cycle retardation and apoptosis. Cancer Biol Ther. 2009;8:226-32.
164. Brüning A, Rahmeh M, Gingelmaier A, Friese K. The mitochondria-independent cytotoxic effect of nelfinavir on leukemia cells can be enhanced by sorafenib-mediated mcl-1 downregulation and mitochondrial membrane destabilization Mol Cancer. 2010; 9:19. doi: 10.1186/1476-4598-9-19.
165. Chow WA, Jiang C, Guan M. Anti-HIV drugs for cancer therapeutics: back to the future? Lancet Oncol. 2009;10:61-71. doi: 10.1016/S1470-2045(08)70334-6.
166. Brüning A, Friese K, Burges, Ioannis Mylonas I. Tamoxifen enhances the cytotoxic effects of nelfinavir in breast cancer cells. Breast Cancer Res. 2010;12: R45. doi: 10.1186/bcr2602.
167. Brüning A. Analysis of nelfinavir-induced endoplasmic reticulum stress. Methods Enzymol. 2011;491:127-42. doi: 10.1016/B978-0-12-385928-0.00008-0.
168. Pyrko P, Kardosh A, Wang W, Xiong W, Schönthal AH, Chen TC. HIV-1 protease inhibitors nelfinavir and atazanavir induce malignant glioma death by triggering endoplasmic reticulum stress. Cancer Res. 2007;67:10920-8.
169. Gills JJ, Lopiccolo J, Dennis PA. Nelfinavir, a new anticancer drug with pleiotropic effects and many paths to autophagy. Autophagy. 2008;4:107-9. PubMed PMID: 18000394.
170. Gills JJ, Lopiccolo J, Tsurutani J, Shoemaker RH, Best CJ, Abu-Asab MS, Borojerdi J, Warfel NA, Gardner ER, Danish M, Hollander MC, Kawabata S, Tsokos M, Figg WD, Steeg PS, Dennis PA. Nelfinavir, A lead HIV protease inhibitor, is a broad-spectrum, anticancer agent that induces endoplasmic reticulum stress, autophagy, and apoptosis in vitro and in vivo. Clin Cancer Res. 2007;13:5183-94. PubMed PMID: 17785575.
171. Bono C, Karlin L, Harel S, Mouly E, Labaume S, Galicier L, Apcher S, Sauvageon H,Fermand JP, Bories JC, Arnulf B. The human immunodeficiency virus-1 protease inhibitor nelfinavir impairs proteasome activity and inhibits the proliferation of multiple myeloma cells invitro and in vivo. Haematologica. 2012;97:1101-9. doi: 10.3324/ haematol.2011.049981.
172. Cruickshanks N, Shervington L, Patel R, Munje C, Thakkar D, Shervington A. Can hsp90alpha-targeted siRNA combined with TMZ be a future therapy for glioma? Cancer Invest. 2010;28:608-14. doi: 10.3109/07357901003630967.
173. Lu X, Xiao L, Wang L, Ruden DM. Hsp90 inhibitors and drug resistance in cancer: the potential benefits of combination therapies of Hsp90 inhibitors and other anticancer drugs. Biochem Pharmacol. 2012;83(8):995-1004. doi: 10.1016/j.bcp.2011.11.011.
174. Ohba S, Hirose Y, Yoshida K, Yazaki T, Kawase T. Inhibition of 90-kD heat shock protein potentiates the cytotoxicity of chemotherapeutic agents in human glioma cells. J Neurosurg. 2010;112(1):33-42. doi: 10.3171/2009.3.JNS081146.
175. Zhu H, Woolfenden S, Bronson RT, Jaffer ZM, Barluenga S, Winssinger N, Rubenstein AE, Chen R, Charest A. The novel Hsp90 inhibitor NXD30001 induces tumor regression in a genetically engineered mouse model of glioblastoma multiforme. Mol Cancer Ther. 2010;9:2618-26. doi:10.1158/1535-7163.MCT-10-0248.
176. Siegelin MD, Habel A, Gaiser T. 17-AAG sensitized malignant glioma cells to death-receptor mediated apoptosis. Neurobiol Dis. 2009;33:243-9. doi:10.1016/j. nbd.2008.10.005.
177. Premkumar DR, Arnold B, Jane EP, Pollack IF. Synergistic interaction between 17-AAG and phosphatidylinositol 3-kinase inhibition in human malignant glioma cells. Mol Carcinog. 2006;45:47-59.
178. Dungey FA, Caldecott KW, Chalmers AJ. Enhanced radiosensitization of human glioma cells by combining inhibition of poly(ADP-ribose) polymerase witinhibition of heat shock protein 90. Mol Cancer Ther. 2009;8:2243-54. doi:10.1158/1535-7163.MCT-09-0201.
179. Gaspar N, Sharp SY, Eccles SA, Gowan S, Popov S, Jones C, Pearson A, Vassal G, Workman P. Mechanistic evaluation of the novel HSP90 inhibitor NVP-AUY922 in adult and pediatric glioblastoma. Mol Cancer Ther. 2010;9:1219-33. doi:10.1158/1535-7163.MCT-09-0683.
180. Sauvageot CM, Weatherbee JL, Kesari S, Winters SE, Barnes J, Dellagatta J, Ramakrishna NR, Stiles CD, Kung AL, Kieran MW, Wen PY. Efficacy of the HSP90 inhibitor 17-AAG in human glioma cell lines and tumorigenic glioma stem cells. Neuro Oncol. 2009;11:109-21. doi: 10.1215/15228517-2008-060.
181. Tian X, Ye J, Alonso-Basanta M, Hahn SM, Koumenis C, Dorsey JF. Modulation of CCAAT/enhancer binding protein homologous protein (CHOP)-dependent DR5 expression by nelfinavir sensitizes glioblastoma multiforme cells to tumor necrosis factor-related apoptosis-inducing ligand (TRAIL). J Biol Chem. 2011;286(33):29408-16. doi:10.1074/jbc.M110.197665.
182. Nakada M, Okada Y, Yamashita J. The role of matrix metalloproteinases in glioma invasion. Front Biosci. 2003;8:e261-9.
183. Chintala SK, Tonn JC, Rao JS. Matrix metalloproteinases and their biological function in human gliomas. Int J Dev Neurosci. 1999;17:495-502.
184. Kim MS, Kwak HJ, Lee JW, Kim HJ, Park MJ, Park JB, Choi KH, Yoo H, Shin SH, Shin WS, Song ES, Lee SH. 17-Allylamino-17-demethoxygeldanamycin down-regulates hyaluronic acid-induced glioma invasion by blocking matrix metalloproteinase-9 secretion. Mol Cancer Res. 2008;6:1657-65. doi:10.1158/1541-7786.MCR-08-0034.
185. Kumar S, Bryant CS, Chamala S, Qazi A, Seward S, Pal J, Steffes CP, Weaver DW, Morris R, Malone JM, Shammas MA, Prasad M, Batchu RB. Ritonavir blocks AKT signaling, activates apoptosis and inhibits migration and invasion in ovarian cancer cells. Mol Cancer. 2009;8:26. doi: 10.1186/1476-4598-8-26.
186. Gary-Bobo G, Houssaini A, Amsellem V, Rideau D, Pacaud P, Perrin A, Brégeon J, Marcos E, Dubois-Randé JL, Sitbon O, Savale L, Adnot S. Effects of HIV protease inhibitors on progression of monocrotaline-and hypoxia-induced pulmonary hypertension in rats. Circulation. 2010;122:1937-47. doi:10.1161/CIRCULATIONAHA.110.973750.
187. Gupta AK, Cerniglia GJ, Mick R, McKenna WG, Muschel RJ. HIV protease inhibitors block Akt signaling and radiosensitize tumor cells both in vitro and in vivo. Cancer Res. 2005;65:8256-65. PubMed PMID: 16166302.
188. Gupta AK, Li B, Cerniglia GJ, Ahmed MS, Hahn SM, Maity A. The HIV protease inhibitor nelfinavir downregulates Akt phosphorylation by inhibiting proteasomal activity and inducing the unfolded protein response. Neoplasia. 2007;9:271-8.
189. Srirangam A, Mitra R, Wang M, Gorski JC, Badve S, Baldridge L, Hamilton J, Kishimoto H, Hawes J, Li L, Orschell CM, Srour EF, Blum JS, Donner D, Sledge GW, Nakshatri H, Potter DA. Effects of HIV protease inhibitor ritonavir on Akt-regulated cell proliferation in breast cancer. Clin Cancer Res. 2006;12:1883-96.
190. Xie L, Evangelidis T, Xie L, Bourne PE. Drug discovery using chemical systems biology: weak inhibition of multiple kinases may contribute to the anti-cancer effect of nelfinavir. PLoS Comput Biol. 2011;7:e1002037. doi: 10.1371/journal.pcbi.1002037.
191. Jiang Z, Pore N, Cerniglia GJ, Mick R, Georgescu MM, Bernhard EJ, Hahn SM, Gupta AK, Maity A. Phosphatase and tensin homologue deficiency in glioblastoma confers resistance to radiation and temozolomide that is reversed by the protease inhibitor nelfinavir. Cancer Res. 2007;67:4467-73.
192. Koul D. PTEN signaling pathways in glioblastoma. Cancer Biol Ther. 2008;7:1321-5.
193. McDowell KA, Riggins GJ, Gallia GL. Targeting the AKT pathway in glioblastoma. Curr Pharm Des. 2011;17:2411-20.
194. Pore N, Gupta AK, Cerniglia GJ, Jiang Z, Bernhard EJ, Evans SM, Koch CJ, Hahn SM, Maity A. Nelfinavir downregulates hypoxia-inducible factor 1alpha and VEGF expression and increases tumor oxygenation: implications for radiotherapy. Cancer Res. 2006;66:9252-9.
195. Pore N, Gupta AK, Cerniglia GJ, Maity A. HIV protease inhibitors decrease VEGF/HIF-1alpha expression and angiogenesis in glioblastoma cells. Neoplasia. 2006;8:889-95.
196. Haupt A, Joberty G, Bantscheff M, Fröhlich H, Stehr H, Schweiger MR, Fischer A, Kerick M, Boerno ST, Dahl A, Lappe M, Lehrach H, Gonzalez C, Drewes G, Lange BM. Hsp90 inhibition differentially destabilises MAP kinase and TGF-beta signalling components in cancer cells revealed by kinase-targeted chemoproteomics. BMC Cancer. 2012;12:38. doi: 10.1186/1471-2407-12-38.
197. Noh H, Kim HJ, Yu MR, Kim WY, Kim J, Ryu JH, Kwon SH, Jeon JS, Han DC, Ziyadeh F. Heat shock protein 90 inhibitor attenuates renal fibrosis through degradation of transforming growth factor-β type II receptor. Lab Invest.2012;92:1583-96. doi: 10.1038/labinvest.2012.127.
198. Shi L, Zhang Z, Fang S, Xu J, Liu J, Shen J, Fang F, Luo L, Yin Z. Heat shock protein 90 (Hsp90) regulates the stability of transforming growth factor beta-activated kinase 1 (TAK1) in interleukin-1beta-induced cell signaling. Mol Immunol. 2009;46:541-50. doi: 10.1016/j. molimm.2008.07.019.
199. Zhang K, Lu Y, Yang P, Li C, Sun H, Tao D, Liu Y, Zhang S, Ma Y. HILI inhibits TGF-β signaling by interacting with Hsp90 and promoting TβR degradation. PLoS One. 2012;7(7):e41973. doi: 10.1371/journal.pone.0041973.
200. Rengan R, Mick R, Pryma D, Rosen MA, Lin LL, Maity AM, Evans TL, Stevenson JP, Langer CJ, Kucharczuk J, Friedberg J, Prendergast S, Sharkoski T, Hahn SM. A phase I trial of the HIV protease inhibitor nelfinavir with concurrent chemoradiotherapy for unresectable stage IIIA/ IIIB non-small cell lung cancer: a report of toxicities and clinical response. J Thorac Oncol. 2012;7:709-15. doi: 10.1097/JTO.0b013e3182435aa6.
201. Walmsley S, Bernstein B, King M, Arribas J, Beall G, Ruane P, Johnson M, Johnson D, Lalonde R, Japour A, Brun S, Sun E; M98-863 Study Team. Lopinavir-ritonavir versus nelfinavir for the initial treatment of HIV infection. N Engl J Med. 2002;346:2039-46.
202. Barillari G, Iovane A, Bacigalupo I, Palladino C, Bellino S, Leone P, Monini P, Ensoli B. Ritonavir or saquinavir impairs the invasion of cervical intraepithelial neoplasia cells via a reduction of MMP expression and activity. AIDS. 2012;26:909-19.
203. McRae AL, Brady KT. Review of sertraline and its clinical applications in psychiatric disorders. Expert Opin Pharmacother. 2001;2:883-92.
204. Sheehan DV, Kamijima K. An evidence-based review of the clinical use of sertraline in mood and anxiety disorders. Int Clin Psychopharmacol. 2009;24:43-60
205. Raysi Dehcordi S, De Paulis D, Marzi S, Ricci A, Cimini A, Cifone MG, Galzio RJ. Survival prognostic factors in patients with glioblastoma: our experience. J Neurosurg Sci. 2012;56:239-45. PubMed PMID: 22854592.
206. Fox SW, Lyon D, Farace E. Symptom clusters in patients with high-grade glioma. J Nurs Scholarsh. 2007;39:61-7.
207. Rooney AG, McNamara S, Mackinnon M, Fraser M, Rampling R, Carson A, Grant R. Screening for major depressive disorder in adults with glioma using the PHQ-9: a comparison of patient versus proxy reports. J Neurooncol. 2013 Feb 24. [Epub ahead of print] PubMed PMID: 23436131.
208. Walker AJ, Grainge M, Bates TE, Card TR. Survival of glioma and colorectal cancer patients using tricyclic antidepressants post-diagnosis. Cancer Causes Control. 2012;23:1959-64. doi: 10.1007/s10552-012-0073-0.
209. Caudill JS, Brown PD, Cerhan JH, Rummans TA. Selective serotonin reuptake inhibitors, glioblastoma multiforme, and impact on toxicities and overall survival: the mayo clinic experience. Am J Clin Oncol. 2011;34:385-7. doi: 10.1097/COC.0b013e3181e8461a.
210. Tzadok S, Beery E, Israeli M, Uziel O, Lahav M, Fenig E, Gil-Ad I, Weizman A, Nordenberg J. In vitro novel combinations of psychotropics and anti-cancer modalities in U87 human glioblastoma cells. Int J Oncol. 2010;37:1043-51.
211. Reddy KK, Lefkove B, Chen LB, Govindarajan B, Carracedo A, Velasco G, Carrillo CO, Bhandarkar SS, Owens MJ, Mechta-Grigoriou F, Arbiser JL. The antidepressant sertraline downregulates Akt and has activity against melanoma cells. Pigment Cell Melanoma Res. 2008;21:451-6. doi: 10.1111/j.1755-148X.2008.00481.x.
212. Arroll B, Doughty R, Andersen V. Investigation and management of congestive heart failure. BMJ. 2010;341:c3657. doi: 10.1136/bmj.c3657.
213. Brogden RN, Todd PA, Sorkin EM. Captopril. An update of its pharmacodynamic and pharmacokinetic properties, and therapeutic use in hypertension and congestive heart failure. Drugs. 1988;36:540-600.
214. Carpentier AF, Ferrari D, Bailon O, Ursu R, Banissi C, Dubessy AL, Belin C, Levy C. Steroid-sparing effects of angiotensin-II inhibitors in glioblastoma patients. Eur J Neurol. 2012;19:1337-42. doi:10.1111/j.1468-1331.2012.03766.x.
215. Kenna HA, Poon AW, de los Angeles CP, Koran LM. Psychiatric complications of treatment with corticosteroids: review with case report. Psychiatry Clin Neurosci. 2011;65:549-60. doi: 10.1111/j.1440-1819.2011.02260.x.
216. Dubovsky AN, Arvikar S, Stern TA, Axelrod L. The neuropsychiatric complications of glucocorticoid use: steroid psychosis revisited. Psychosomatics. 2012;53:103-15. doi: 10.1016/j.psym.2011.12.007.
217. Roth P, Wick W, Weller M. Steroids in neurooncology: actions, indications, side-effects. Curr Opin Neurol. 2010;23:597-602. doi:10.1097/WCO.0b013e32833e5a5d.
218. Gustafson MP, Lin Y, New KC, Bulur PA, O'Neill BP, Gastineau DA, Dietz AB. Systemic immune suppression in glioblastoma: the interplay between CD14+HLA-DRlo/ neg monocytes, tumor factors, and dexamethasone. Neuro Oncol. 2010;12:631-44. doi: 10.1093/neuonc/noq001. Epub 2010 Feb 23.
219. Plosker GL, McTavish D. Captopril. A review of its pharmacology and therapeutic efficacy after myocardial infarction and in ischaemic heart disease. Drugs Aging. 1995;7:226-53.
220. Kleber FX, Reindl I, Wenzel M, Rodewyk P, Beil S, Kosloswki B, Doering W, Sabin GV, Hinzmann S, Winter UJ, et al. Experiences with ACE inhibitors early after acute myocardial infarction. Rationale and design of the German Multicenter Study on the Effects of Captopril on Cardiopulmonary Exercise parameters post myocardial infarction (ECCE). Herz. 1993;18 Suppl 1:424-9. PubMed PMID: 8125422.
221. Yoshiji H, Kuriyama S, Fukui H. Angiotensin-I-converting enzyme inhibitors may be an alternative anti-angiogenic strategy in the treatment of liver fibrosis and hepatocellular carcinoma. Possible role of vascular endothelial growth factor. Tumour Biol 2002, 23:348-356.
222. Yasumatsu R, Nakashima T, Masuda M, Ito A, Kuratomi Y, Nakagawa T, Komune S. Effects of the angiotensin-I converting enzyme inhibitor perindopril on tumor growth and angiogenesis in head and neck squamous cell carcinoma cells. J Cancer Res Clin Oncol 2004, 130:567-573.
223. Miyajima A, Kosaka T, Asano T, Asano T, Seta K, Kawai T, Hayakawa M. Angiotensin II type I antagonist prevents pulmonary metastasis of murine renal cancer by inhibiting tumor angiogenesis. Cancer Res 2002; 62:4176-4179.
224. Hii SI, Nicol DL, Gotley DC, Thompson LC, Green MK, Jonsson JR. Captopril inhibits tumour growth in a xenograftmodel of human renal cell carcinoma. Br J Cancer 1998;77:880-883.
225. Arrieta O, Pineda-Olvera B, Guevara-Salazar P, Hernández-Pedro N, Morales-Espinosa D, Cerón-Lizarraga TL, González-De la Rosa CH, Rembao D, Segura-Pacheco B, Sotelo J. Expression of AT1 and AT2 angiotensin receptors in astrocytomas is associated with poor prognosis. Br J Cancer. 2008;99:160-6. doi: 10.1038/sj.bjc.6604431.
226. Arrieta O, Guevara P, Escobar E, García-Navarrete R, Pineda B, Sotelo J. Blockage of angiotensin II type 1 receptor decreases the synthesis of growth factors and induces apoptosis in C6 cultured cells and C6 rat glioma. Br J Cancer 2005;92:1247-1252.
227. Kosugi M, Miyajima A, Kikuchi E, Kosaka T, Horiguchi Y, Murai M. Effect of angiotensin II type 1 receptor antagonist on tumor growth and angiogenesis in a xenograft model of human bladder cancer. Hum Cell 2007;20:1-9.
228. Suganuma T, Ino K, Shibata K, Kajiyama H, Nagasaka T, Mizutani S, Kikkawa F. Functional expression of the angiotensin II type 1 receptor in human ovarian carcinoma cells and its blockade therapy resulting in suppression of tumor invasion, angio- genesis, and peritoneal dissemination. Clin Cancer Res 2005, 11:2686-2694.
229. Kosaka T, Miyajima A, Takayama E, Kikuchi E, Nakashima J, Ohigashi T, Asano T, Sakamoto M, Okita H, Murai M, Hayakawa M. Angiotensin II type 1 receptor antagonist as an angiogenic inhibitor in prostate cancer. Prostate 2007;67:41.
230. Puddefoot JR, Udeozo UK, Barker S, Vinson GP. The role of angiotensin II in the regulation of breast cancer cell adhesion and invasion. Endocr Relat Cancer 2006, 13:895-903.
231. Neo JH, Malcontenti-Wilson C, Muralidharan V, Christophi C. Effect of ACE inhibitors and angiotensin II receptor antagonists in a mouse model of colorectal cancer liver metastases. J Gastroenterol Hepatol 2007, 22:577-584.
232. Huang W, Wu YL, Zhong J, Jiang FX, Tian XL, Yu LF. Angiotensin II type 1 receptor antagonist suppressangiogenesis and growth of gastric cancer xenografts. Dig Dis Sci 2008;53:1206-1210.
233. Juillerat-Jeanneret L, Celerier J, Chapuis Bernasconi C, Nguyen G, Wostl W, Maerki HP, Janzer RC, Corvol P, Gasc JM. Renin and angiotensinogen expression and functions in growth and apoptosis of human glioblastoma. Br J Cancer. 2004;90:1059-68.
234. Rivera E, Arrieta O, Guevara P, Duarte-Rojo A, Sotelo J. AT1 receptor is present in glioma cells; its blockage reduces the growth of rat glioma. Br J Cancer. 2001;85:1396-9.
235. Nakagawa T, Kubota T, Kabuto M, Kodera T. Captopril inhibits glioma cell invasion in vitro: involvement of matrix metalloproteinases. Anticancer Res. 1995;15(5B):1985-9. PubMed PMID: 8572589.
236. Sohn CA. Evaluation of ketoconazole. Clin Pharm. 1982;1:217-24.
237. Beetens JR, Loots W, Somers Y, Coene MC, De Clerck F. Ketoconazole inhibits the biosynthesis of leukotrienes in vitro and in vivo. Biochem Pharmacol. 1986;35:883-91. PubMed PMID: 3006695.
238. Nardone PA, Slotman GJ, Vezeridis MP. Ketoconazole: a thromboxane synthetase and 5-lipoxygenase inhibitor with antimetastatic activity in B16-F10 melanoma. J Surg Res. 1988;44:425-9. PubMed PMID: 3361885.
239. Tzanakakis GN, Krambovitis E, Tsatsakis AM, Vezeridis MP. The preventive effect of ketoconazole on experimental metastasis from a human pancreatic carcinoma may be related to its effect on prostaglandin synthesis. Int J Gastrointest Cancer. 2002;32:23-30. PubMed PMID: 12630766.
240. Lelcuk S, Huval WV, Valeri CR, Shepro D, Hechtman HB. Inhibition ofischemia-induced thromboxane synthesis in man. J Trauma. 1984;24:393-6.PubMed PMID: 6325720.
241. Tolman EL, Fuller BL. Inhibition of thromboxane synthesis in guinea pig lung and human platelets by clotrimazole and other imidazole antifungals. Biochem Pharmacol. 1983;32:3488-90. PubMed PMID: 6316985.
242. Tzanakakis GN, Agarwal KC, Vezeridis MP. Inhibition of hepatic metastasis from a human pancreatic adenocarcinoma (RWP-2) in the nude mouse by prostacyclin, forskolin, and ketoconazole. Cancer. 1990;65:446-51. PubMed PMID:2404557.
243. Williams JG, Maier RV. Ketoconazole inhibits alveolar macrophage production of inflammatory mediators involved in acute lung injury (adult respiratory distress syndrome). Surgery. 1992;112:270-7. PubMed PMID: 1322565.
244. McManus M, Serhan C, Jackson P, Strange K. Ketoconazole blocks organic osmolyte efflux independently of its effect on arachidonic acid conversion. Am J Physiol. 1994;267(1 Pt 1):C266-71.
245. Venishetty VK, Komuravelli R, Kuncha M, Sistla R, Diwan PV. Increased brain uptake of docetaxel and ketoconazole loaded folate-grafted solid lipid nanoparticles. Nanomedicine. 2013;9:111-21. doi:10.1016/j.nano.2012.03.003.
246. Yang ZH, Liu XD. P-glycoprotein-mediated efflux of phenobarbital at the blood-brain barrier evidence from transport experiments in vitro. Epilepsy Res. 2008;78:40-9. PubMed PMID: 18063342.
247. Kageyama M, Namiki H, Fukushima H, Ito Y, Shibata N, Takada K. In vivo effects of cyclosporin A and ketoconazole on the pharmacokinetics of representative substrates for P-glycoprotein and cytochrome P450 (CYP) 3A in rats. Biol Pharm Bull. 2005;28:316-22. PubMed PMID: 15684491.
248. Choo EF, Leake B, Wandel C, Imamura H, Wood AJ, Wilkinson GR, Kim RB. Pharmacological inhibition of P-glycoprotein transport enhances the distribution of HIV-1 protease inhibitors into brain and testes. Drug Metab Dispos. 2000;28:655-60. PubMed PMID: 10820137.
249. Eagling VA, Profit L, Back DJ. Inhibition of the CYP3A4-mediated metabolism and P-glycoprotein-mediated transport of the HIV-1 protease inhibitor saquinavir by grapefruit juice components. Br J Clin Pharmacol. 1999;48:543-52. PubMed PMID: 10583025; PubMed Central PMCID: PMC2014377.
250. Gupta A, Unadkat JD, Mao Q. Interactions of azole antifungal agents with the human breast cancer resistance protein (BCRP). J Pharm Sci. 2007;96:3226-35. PubMed PMID: 17518356.
251. Chien RN, Yang LJ, Lin PY, Liaw YF. Hepatic injury during ketoconazole therapy in patients with onychomycosis: a controlled cohort study. Hepatology. 1997;25:103-7.
252. Hay RJ. Risk/benefit ratio of modern antifungal therapy: focus on hepatic reactions. J Am Acad Dermatol. 1993;29:S50-4.
253. Knight TE, Shikuma CY, Knight J. Ketoconazole-induced fulminant hepatitis necessitating liver transplantation. J Am Acad Dermatol. 1991;25(2 Pt 2):398-400.
254. Figg WD, Woo S, Zhu W, Chen X, Ajiboye AS, Steinberg SM, Price DK, Wright JJ, Parnes HL, Arlen PM, Gulley JL, Dahut WL. A phase I clinical study of high dose ketoconazole plus weekly docetaxel for metastatic castration resistant prostate cancer. J Urol. 2010;183:2219-26. doi: 10.1016/j.juro.2010.02.020.
255. Kim JA, Chung YJ, Lee YS. Intracellular Ca2+ mediates lipoxygenase-induced proliferation of U-373 MG human astrocytoma cells. Arch Pharm Res. 1998;21:664-70.
256. Wang B, Yu SC, Jiang JY, Porter GW, Zhao LT, Wang Z, Tan H, Cui YH, Qian C, Ping YF, Bian XW. An inhibitor of arachidonate 5-lipoxygenase, Nordy, induces differentiation and inhibits self-renewal of glioma stem-like cells. Stem Cell Rev. 2011;7:458-70. doi: 10.1007/s12015-010-9175-9.
257. Ishii K, Zaitsu M, Yonemitsu N, Kan Y, Hamasaki Y, Matsuo M. 5-lipoxygenase pathway promotes cell proliferation in human glioma cell lines. Clin Neuropathol.2009;28:445-52.
258. Lim JY, Oh JH, Jung JR, Kim SM, Ryu CH, Kim HT, Jeun SS. MK886-induced apoptosis depends on the 5-LO expression level in human malignant glioma cells. J Neurooncol. 2010;97(3):339-46. doi: 10.1007/s11060-009-0036-9.
259. Zhang L, Zhang WP, Hu H, Wang ML, Sheng WW, Yao HT, Ding W, Chen Z, Wei EQ. Expression patterns of 5-lipoxygenase in human brain with traumatic injury and astrocytoma. Neuropathology. 2006;26(2):99-106.
260. Chio CC, Baba T, Black KL. Selective blood-tumor barrier disruption by leukotrienes. J Neurosurg. 1992;77:407-10. 261.
261. Shinonaga M, Chang CC, Kuwabara T. Relation between macrophage infiltrates and peritumoral edema. Adv Neurol. 1990;52:475-81.
262. Black KL, Hoff JT, McGillicuddy JE, Gebarski SS Increased leukotriene C4 and vasogenic edema surrounding brain tumors in humans. Ann Neurol. 1986;19:592-5.
263. Simmet T, Luck W, Winking M, Delank WK, Peskar BA. Identification and characterization of cysteinyl-leukotriene formation in tissue slices from human intracranial tumors: evidence for their biosynthesis under in vivo conditions. J Neurochem. 1990;54:2091-9.
264. Gàti I, Bergström M, Westerberg G, Csòka K, Muhr C, Carlsson J. Effects of prostaglandin and leukotriene inhibitors on the growth of human glioma spheroids. Eur J Cancer. 1990;26:802-7. PubMed PMID: 2145898.
265. Gáti I, Bergström M, Muhr C, Carlsson J. Leukotriene and 5-lipoxygenase inhibitor induced variations in thymidine uptake in a human glioma cell line cultured as monolayers or as multicellular spheroids. Anticancer Res. 1994;14(2A):453-9. PubMed PMID: 8017847.
266. Golubic M, Prayson RA, Vargo L, Bondar J, Barnett GH. Increased expression of 5-lipoxygenase in glioblastoma multiforme. Adv Exp Med Biol. 2003;525:205-8.
267. Nathoo N, Prayson RA, Bondar J, Vargo L, Arrigain S, Mascha EJ, Suh JH, Barnett GH, Golubic M. Increased expression of 5-lipoxygenase in high-grade astrocytomas. Neurosurgery. 2006;58:347-54.
268. Castelli MG, Butti G, Chiabrando C, Cozzi E, Fanelli R, Gaetani P, Silvani V, Paoletti P. Arachidonic acid metabolic profiles in human meningiomas and gliomas. J Neurooncol. 1987;5:369-75.
269. Murphy S, Welk G, Thwin SS. Stimulation of thromboxane release from primary cell cultures derived from human astrocytic glioma biopsies. Glia 1990;3:205-11. PubMed PMID: 2141596.
270. Takano S, Ishimoto H, Nakahata N, Nakanishi H. Thromboxane A2 receptor characterization in human astrocytoma cells and rabbit platelets by a new thromboxane antagonist, [3H]ONO NT-126. Res Commun Chem Pathol Pharmacol. 1999;76:155-70. PubMed PMID: 1534919.
271. Nakahata N, Matsuoka I, Ono T, Nakanishi H. Thromboxane A2 activates phospholipase C in astrocytomacells via pertussis toxin-insensitive G-protein. Eur J Pharmacol. 1989;162:407-17. PubMed PMID: 2545456.
272. McDonough W, Tran N, Giese A, Norman SA, Berens ME. Altered gene expression in human astrocytoma cells selected for migration: I.Thromboxane synthase. J Neuropathol Exp Neurol. 1998;57:449-55.
273. Schmidt NO, Ziu M, Cargioli T, Westphal M, Giese A, Black PM, Carroll RS. Inhibition of thromboxane synthase activity improves glioblastoma response to alkylation chemotherapy. Transl Oncol. 2010;3(1):43-9.
274. Schauff AK, Kim EL, Leppert J, Nadrowitz R, Wuestenberg R, Brockmann MA, Giese A. Inhibition of invasionassociated thromboxane synthase sensitizes experimental gliomas to gamma-radiation. J Neurooncol. 2009;91:241-9. doi: 10.1007/s11060-008-9708-0.
275. Yoshizato K, Zapf S, Westphal M, Berens ME, Giese A. Thromboxane synthase inhibitors induce apoptosis in migration-arrested glioma cells. Neurosurgery. 2002;50:343-54.
276. Ekambaram P, Lambiv W, Cazzolli R, Ashton AW, Honn KV. The thromboxane synthase and receptor signaling pathway in cancer: an emerging paradigm in cancer progression and metastasis. Cancer Metastasis Rev. 2011;30:397-408. doi: 10.1007/s10555-011-9297-9.
277. Gallagher P, Malik N, Newham J, Young AH, Ferrier IN, Mackin P. Antiglucocorticoid treatments for mood disorders. Cochrane Database Syst Rev. 2008;(1):CD005168. doi:10.1002/14651858.CD005168. pub2.
278. Reist C, Wu JC, Lilja Y, Mukherjee J, Gripeos D, Constantinescu C, Raggi MA, Mercolini L, Ozdemir V. Ketoconazole-associated preferential increase in dopamine D2 receptor occupancy in striatum compared to pituitary in vivo: role for drug transporters? J Clin Psychopharmacol. 2012;32:110-3. doi:10.1097/JCP.0b013e3182408fc8.
279. FDA.gov http://www.fda.gov/Drugs/DrugSafety/drugSafetyInformationforPatientsandProviders/ucm111085. htm
280. Sanchez RI, Wang RW, Newton DJ, Bakhtiar R, Lu P, Chiu SH, Evans DC, Huskey SE. Cytochrome P450 3A4 is the major enzyme involved in the metabolism of the substance P receptor antagonist aprepitant. Drug Metab Dispos. 2004;32(11):1287-92.
281. EMENDTM SPC, (accessed January, 2012) http://www.accessdata.fda.gov/drugsatfda_docs/label/2009/021549s016lbl.pdf
282. Granfors MT, Wang JS, Kajosaari LI, Laitila J, Neuvonen PJ, Backman JT. Differential inhibition of cytochrome P450 3A4, 3A5 and 3A7 by five human immunodeficiency virus (HIV) protease inhibitors in vitro. Basic Clin Pharmacol Toxicol. 2006;98:79-85.
283. Piscitelli SC, Gallicano KD. Interactions among drugs for HIV and opportunistic infections. N Engl J Med. 2001;344:984-96.
284. van Agtmael MA, Eggelte TA, van Boxtel CJ. Artemisinin drugs in the treatment of malaria: from medicinal herb to registered medication. Trends Pharmacol Sci. 1999;20:199-205.PubMed PMID: 10354615.
285. Coartem product information. Novartis at http://www.coartem.com/coartem-riamet.htm
286. Velayudham LS, Farrell GC. Drug-induced cholestasis. Expert Opin Drug Saf. 2003;2:287-304.
287. Bruno R, Sacchi P, Maiocchi L, Zocchetti C, Filice G. Hepatotoxicity and nelfinavir: a meta-analysis. Clin Gastroenterol Hepatol. 2005;3:482-8.
288. Sarganas G, Orzechowski HD, Klimpel A, Thomae M, Kauffmann W, Herbst H, Bronder E, Garbe E. Severe sustained cholestatic hepatitis following temozolomide in a patient with glioblastoma multiforme: case study and review of data from the FDA adverse event reporting system. Neuro Oncol. 2012;14:541-6. doi: 10.1093/neuonc/ nos056.
289. Rolling T, Schmiedel S, Wichmann D, Wittkopf D, Burchard GD, Cramer JP. Post-treatment haemolysis in severe imported malaria after intravenous artesunate: case report of three patients with hyperparasitaemia.Malar J. 2012;11:169. doi: 10.1186/1475-2875-11-169.
290. Liu C, Liu Z, Li M, Li X, Wong YS, Ngai SM, Zheng W, Zhang Y, Chen T. Enhancement of auranofin-induced apoptosis in MCF-7 human breast cells by selenocystine, a synergistic inhibitor of thioredoxin reductase. PLoS One. 2013;8(1):e53945. doi: 10.1371/journal.pone.0053945.
291. Schuh E, Pflüger C, Citta A, Folda A, Rigobello MP, Bindoli A, Casini A, Mohr F. Gold(I) carbene complexes causing thioredoxin 1 and thioredoxin 2 oxidation as potential anticancer agents. J Med Chem. 2012;55:5518-28. doi:10.1021/jm300428v.
292. Cho HJ, Lee TS, Park JB, Park KK, Choe JY, Sin DI, Park YY, Moon YS, Lee KG, Yeo JH, Han SM, Cho YS, Choi MR, Park NG, Lee YS, Chang YC. Disulfiram suppresses invasive ability of osteosarcoma cells via the inhibition of MMP-2 and MMP-9 expression. J Biochem Mol Biol. 2007;40:1069-76. PMID: 18047805.
293. Shian SG, Kao YR, Wu FY, Wu CW. Inhibition of invasion and angiogenesis by zinc-chelating agent disulfiram. Mol Pharmacol. 2003;64:1076-84. PubMed PMID: 14573756.
294. Newman B, Liu Y, Lee HF, Sun D, Wang Y. HSP90 inhibitor 17-AAG selectively eradicates lymphoma stem cells. Cancer Res. 2012;72(17):4551-61. doi:10.1158/0008-5472.CAN-11-3600.
295. Sobhan PK, Seervi M, Joseph J, Chandrika BB, Varghese S, Santhoshkumar TR, Radhakrishna Pillai M. Identification of heat shock protein 90 inhibitors to sensitize drug resistant side population tumor cells using a cell based assay platform. Cancer Lett. 2012;317:78-88. doi:10.1016/j.canlet.2011.11.009.
296. Tatokoro M, Koga F, Yoshida S, Kawakami S, Fujii Y, Neckers L, Kihara K. Potential role of Hsp90 inhibitors inovercoming cisplatin resistance of bladder cancer-initiating cells. Int J Cancer. 2012;131:987-96. doi:10.1002/ijc.26475.
297. He Y, Fan J, Lin H, Yang X, Ye Y, Liang L, Zhan Z, Dong X, Sun L, Xu H. The anti-malaria agent artesunate inhibits expression of vascular endothelial growth factor and hypoxia-inducible factor-1α in human rheumatoid arthritis fibroblast-like synoviocyte. Rheumatol Int. 2011;31:53-60. doi: 10.1007/s00296-009-1218-7.
298. Kast RE, Foley KF, Focosi D. Doxorubicin cardiomyopathy via TLR-2 stimulation: potential for prevention using current anti-retroviral inhibitors such as ritonavir and nelfinavir. Hematol Oncol. 2007;25:96-7. PubMed PMID: 17351982.
299. Casini A, Messori L. Molecular mechanisms and proposed targets for selected anticancer gold compounds. Curr Top Med Chem. 2011;11:2647-60. PMID: 22039866 300.
300. Weir SJ, DeGennaro LJ, Austin CP. Repurposing approved and abandoned drugs for the treatment and prevention of cancer through public-private partnership. Cancer Res. 2012;72:1055-8. doi: 10.1158/0008-5472.CAN-11-3439.
301. Multhoff G, Radons J. Radiation, inflammation, and immune responses in cancer. Front Oncol. 2012;2:58. doi: 10.3389/fonc.2012.00058.
302. Multhoff G, Molls M, Radons J. Chronic inflammation in cancer development. Front Immunol. 2011;2:98. doi: 10.3389/fimmu.2011.00098.
303. Randle JC, Harding MW, Ku G, Schönharting M, Kurrle R. ICE/Caspase-1 inhibitors as novel anti-inflammatory drugs. Expert Opin Investig Drugs. 2001;10:1207-9.
304. Sethi G, Shanmugam MK, Ramachandran L, Kumar AP, Tergaonkar V. Multifaceted link between cancer and inflammation. Biosci Rep. 2012;32:1-15. doi: 10.1042/BSR20100136.
305. Sgambato A, Cittadini A. Inflammation and cancer: a multifaceted link. Eur Rev Med Pharmacol Sci. 2010;14:263-8.
306. Yeh WL, Lu DY, Liou HC, Fu WM. A forward loop between glioma and microglia: glioma-derived extracellular matrix-activated microglia secrete IL-18 to enhance the migration of glioma cells. J Cell Physiol. 2012;227:558-68. doi: 10.1002/jcp.22746.
307. Kaluz S, Van Meir EG. At the crossroads of cancer and inflammation: Ras rewires an HIF-driven IL-1 autocrine loop. J Mol Med (Berl). 2011;89:91-4.doi: 10.1007/s00109-010-0706-2. PubMed PMID: 21161499.
308. Wolff JE, Brown RE, Buryanek J, Pfister S, Vats TS, Rytting ME. Preliminary experience with personalized and targeted therapy for pediatric brain tumors. Pediatr Blood Cancer. 2012;59:27-33. doi: 10.1002/pbc.23402.
309. Khoshnevisan A. An overview of therapeutic approaches to brain tumor stem cells. Med J Islam Repub Iran. 2012;26:31-40. PMID: 23483074
310. Mantamadiotis T, Taraviras S. Self-renewal mechanisms in neural cancer stem cells. Front Biosci. 2011;16:598-607.
311. Phillips JJ. Novel therapeutic targets in the brain tumor microenvironment. Oncotarget. 2012;3:568-75. PMID: 22643827.
312. Hideki Yamaguchi, Tsukasa Oikawa. Membrane lipids in invadopodia and podosomes: Key structures for cancer invasion and metastasis. Oncotarget. 2010; 1: 320-328. PMC3157727
313. Wolf A, Agnihotri S, Guha A. Targeting metabolic remodeling in glioblastoma multiforme. Oncotarget. 2010; 1: 567-577. PMC3248131
314. Nogueira L, Ruiz-Ontañon P, Vazquez-Barquero A, Moris F, Fernandez-Luna JL. The NFkB pathway: a therapeutic target in glioblastoma. Oncotarget. 2011;2:646-53.