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Published in: Journal of Neuro-Oncology 3/2016

01-02-2016 | Laboratory Investigation

Antitumor action of temozolomide, ritonavir and aprepitant against human glioma cells

Authors: Richard E. Kast, Susana Ramiro, Sandra Lladó, Salvador Toro, Rafael Coveñas, Miguel Muñoz

Published in: Journal of Neuro-Oncology | Issue 3/2016

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Abstract

In the effort to find better treatments for glioblastoma we tested several currently marketed non-chemotherapy drugs for their ability to enhance the standard cytotoxic drug currently used to treat glioblastoma- temozolomide. We tested four antiviral drugs- acyclovir, cidofovir, maraviroc, ritonavir, and an anti-emetic, aprepitant. We found no cytotoxicity of cidofovir and discussed possible reasons for discrepancy from previous findings of others. We also found no cytotoxicity from acyclovir or maraviroc also in contradistinction to predictions. Cytotoxicity to glioma cell line GAMG for temozolomide alone was 14 %, aprepitant alone 7 %, ritonavir alone 14 %, while temozolomide + aprepitant was 19 %, temozolomide + ritonavir 34 %, ritonavir + aprepitant 64 %, and all three, temozolomide + ritonavir + aprepitant 78 %. We conclude that a remarkable synergy exists between aprepitant and ritonavir. Given the long clinical experience with these two well-tolerated drugs in treating non-cancer conditions, and the current median survival of glioblastoma of 2 years, a trial is warranted of adding these two simple drugs to current standard treatment with temozolomide.
Literature
2.
go back to reference Alifieris C, Trafalis DT (2015) Glioblastoma multiforme: pathogenesis and treatment. Pharmacol Ther 152:63–82PubMedCrossRef Alifieris C, Trafalis DT (2015) Glioblastoma multiforme: pathogenesis and treatment. Pharmacol Ther 152:63–82PubMedCrossRef
3.
go back to reference Aapro M, Carides A, Rapoport BL, Schmoll HJ, Zhang L, Warr D (2015) Aprepitant and fosaprepitant: a 10-year review of efficacy and safety. Oncologist 20(4):450–458PubMedCrossRef Aapro M, Carides A, Rapoport BL, Schmoll HJ, Zhang L, Warr D (2015) Aprepitant and fosaprepitant: a 10-year review of efficacy and safety. Oncologist 20(4):450–458PubMedCrossRef
4.
go back to reference Aapro MS, Schmoll HJ, Jahn F, Carides AD, Webb RT (2013) Review of the efficacy of aprepitant for the prevention of chemotherapy-induced nausea and vomiting in a range of tumor types. Cancer Treat Rev 39(1):113–117PubMedCrossRef Aapro MS, Schmoll HJ, Jahn F, Carides AD, Webb RT (2013) Review of the efficacy of aprepitant for the prevention of chemotherapy-induced nausea and vomiting in a range of tumor types. Cancer Treat Rev 39(1):113–117PubMedCrossRef
5.
go back to reference Coveñas R, Muñoz M (2014) Cancer progression and substance P. Histol Histopathol 29(7):881–890PubMed Coveñas R, Muñoz M (2014) Cancer progression and substance P. Histol Histopathol 29(7):881–890PubMed
6.
go back to reference Kast RE (2009) 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 11(7):408–410PubMedCrossRef Kast RE (2009) 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 11(7):408–410PubMedCrossRef
7.
go back to reference Kast RE, Karpel-Massler G, Halatsch ME (2014) CUSP9* treatment protocol for recurrent glioblastoma: aprepitant, artesunate, auranofin, captopril, celecoxib, disulfiram, itraconazole, ritonavir, sertraline augmenting continuous low dose temozolomide. Oncotarget 5(18):8052–8082PubMedPubMedCentralCrossRef Kast RE, Karpel-Massler G, Halatsch ME (2014) CUSP9* treatment protocol for recurrent glioblastoma: aprepitant, artesunate, auranofin, captopril, celecoxib, disulfiram, itraconazole, ritonavir, sertraline augmenting continuous low dose temozolomide. Oncotarget 5(18):8052–8082PubMedPubMedCentralCrossRef
8.
go back to reference Kast RE, Boockvar JA, Bruning A, Cappello F, Chang WW, Cvek B, Dou QP, Dueñas-González A, Efferth T, Focosi D, Ghaffari SH, Karpel-Massler G, Ketola K, Khoshnevisan A, Keizman D, Magne N, Marosi C, McDonald K, Muñoz M, Paranjpe A, Pourgholami MH, Sardi I, Sella A, Srivenugopal KS, Tuccori M, Wang W, Wirtz CR, Halatsch ME (2013) 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 4(4):502–530PubMedPubMedCentralCrossRef Kast RE, Boockvar JA, Bruning A, Cappello F, Chang WW, Cvek B, Dou QP, Dueñas-González A, Efferth T, Focosi D, Ghaffari SH, Karpel-Massler G, Ketola K, Khoshnevisan A, Keizman D, Magne N, Marosi C, McDonald K, Muñoz M, Paranjpe A, Pourgholami MH, Sardi I, Sella A, Srivenugopal KS, Tuccori M, Wang W, Wirtz CR, Halatsch ME (2013) 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 4(4):502–530PubMedPubMedCentralCrossRef
9.
go back to reference Palma C, Bigioni M, Irrissuto C, Nardelli F, Maggi CA, Manzini S (2000) Anti-tumour activity of tachykinin NK1 receptor antagonists on human glioma U373 MG xenograft. Br J Cancer 82(2):480–487PubMedPubMedCentralCrossRef Palma C, Bigioni M, Irrissuto C, Nardelli F, Maggi CA, Manzini S (2000) Anti-tumour activity of tachykinin NK1 receptor antagonists on human glioma U373 MG xenograft. Br J Cancer 82(2):480–487PubMedPubMedCentralCrossRef
10.
go back to reference Muñoz M, Rosso M (2010) The NK-1 receptor antagonist aprepitant as a broad spectrum antitumor drug. Invest New Drugs 28(2):187–193PubMedCrossRef Muñoz M, Rosso M (2010) The NK-1 receptor antagonist aprepitant as a broad spectrum antitumor drug. Invest New Drugs 28(2):187–193PubMedCrossRef
11.
go back to reference De Clercq E (2003) Clinical potential of the acyclic nucleoside phosphonates cidofovir, adefovir, and tenofovir in treatment of DNA virus and retrovirus infections. Clin Microbiol Rev 16(4):569–596PubMedPubMedCentralCrossRef De Clercq E (2003) Clinical potential of the acyclic nucleoside phosphonates cidofovir, adefovir, and tenofovir in treatment of DNA virus and retrovirus infections. Clin Microbiol Rev 16(4):569–596PubMedPubMedCentralCrossRef
12.
go back to reference Van Pachterbeke C, Bucella D, Rozenberg S, Manigart Y, Gilles C, Larsimont D, Vanden Houte K, Reynders M, Snoeck R, Bossens M (2009) Topical treatment of CIN 2 + by cidofovir: results of a phase II, double-blind, prospective, placebo-controlled study. Gynecol Oncol 115(1):69–74PubMedCrossRef Van Pachterbeke C, Bucella D, Rozenberg S, Manigart Y, Gilles C, Larsimont D, Vanden Houte K, Reynders M, Snoeck R, Bossens M (2009) Topical treatment of CIN 2 + by cidofovir: results of a phase II, double-blind, prospective, placebo-controlled study. Gynecol Oncol 115(1):69–74PubMedCrossRef
13.
go back to reference Moyo TK, Richards KL, Damania B (2010) Use of cidofovir for the treatment of HIV-negative human herpes virus-8-associated primary effusion lymphoma. Clin Adv Hematol Oncol 8(5):372–374PubMedPubMedCentral Moyo TK, Richards KL, Damania B (2010) Use of cidofovir for the treatment of HIV-negative human herpes virus-8-associated primary effusion lymphoma. Clin Adv Hematol Oncol 8(5):372–374PubMedPubMedCentral
14.
go back to reference De Schutter T, Andrei G, Topalis D, Naesens L, Snoeck R (2013) Cidofovir selectivity is based on the different response of normal and cancer cells to DNA damage. BMC Med Genomics 6:18PubMedPubMedCentralCrossRef De Schutter T, Andrei G, Topalis D, Naesens L, Snoeck R (2013) Cidofovir selectivity is based on the different response of normal and cancer cells to DNA damage. BMC Med Genomics 6:18PubMedPubMedCentralCrossRef
15.
go back to reference Hadaczek P, Ozawa T, Soroceanu L, Yoshida Y, Matlaf L, Singer E, Fiallos E, James CD, Cobbs CS (2013) Cidofovir: a novel antitumor agent for glioblastoma. Clin Cancer Res 19(23):6473–6483PubMedPubMedCentralCrossRef Hadaczek P, Ozawa T, Soroceanu L, Yoshida Y, Matlaf L, Singer E, Fiallos E, James CD, Cobbs CS (2013) Cidofovir: a novel antitumor agent for glioblastoma. Clin Cancer Res 19(23):6473–6483PubMedPubMedCentralCrossRef
16.
go back to reference Liekens S, Noppen S, Gijsbers S, Sienaert R, Ronca R, Tobia C, Presta M (2015) The broad-spectrum anti-DNA virus agent cidofovir inhibits lung metastasis of virus-independent, FGF2-driven tumors. Oncotarget 6(7):4633–4648PubMedPubMedCentralCrossRef Liekens S, Noppen S, Gijsbers S, Sienaert R, Ronca R, Tobia C, Presta M (2015) The broad-spectrum anti-DNA virus agent cidofovir inhibits lung metastasis of virus-independent, FGF2-driven tumors. Oncotarget 6(7):4633–4648PubMedPubMedCentralCrossRef
17.
go back to reference Wang F, Yang L, Shi L, Li Q, Zhang G, Wu J, Zheng J, Jiao B (2015) Nuclear translocation of fibroblast growth factor-2 (FGF2) is regulated by karyopherin-β2 and Ran GTPase in human glioblastoma cells. Oncotarget 6(25):21468–21478PubMedPubMedCentralCrossRef Wang F, Yang L, Shi L, Li Q, Zhang G, Wu J, Zheng J, Jiao B (2015) Nuclear translocation of fibroblast growth factor-2 (FGF2) is regulated by karyopherin-β2 and Ran GTPase in human glioblastoma cells. Oncotarget 6(25):21468–21478PubMedPubMedCentralCrossRef
18.
go back to reference Wu J, Feng X, Zhang B, Li J, Xu X, Liu J, Wang X, Wang J, Tong X (2014) Blocking the bFGF/STAT3 interaction through specific signaling pathways induces apoptosis in glioblastoma cells. J Neurooncol 120(1):33–41PubMedCrossRef Wu J, Feng X, Zhang B, Li J, Xu X, Liu J, Wang X, Wang J, Tong X (2014) Blocking the bFGF/STAT3 interaction through specific signaling pathways induces apoptosis in glioblastoma cells. J Neurooncol 120(1):33–41PubMedCrossRef
19.
go back to reference Ader I, Delmas C, Skuli N, Bonnet J, Schaeffer P, Bono F, Cohen-Jonathan-Moyal E, Toulas C (2014) Preclinical evidence that SSR128129E- a novel small-molecule multi-fibroblast growth factor receptor blocker- radiosensitises human glioblastoma. Eur J Cancer 50(13):2351–2359PubMedCrossRef Ader I, Delmas C, Skuli N, Bonnet J, Schaeffer P, Bono F, Cohen-Jonathan-Moyal E, Toulas C (2014) Preclinical evidence that SSR128129E- a novel small-molecule multi-fibroblast growth factor receptor blocker- radiosensitises human glioblastoma. Eur J Cancer 50(13):2351–2359PubMedCrossRef
20.
go back to reference Haley EM, Kim Y (2014) The role of basic fibroblast growth factor in glioblastoma multiforme and glioblastoma stem cells and in their in vitro culture. Cancer Lett 346(1):1–5PubMedCrossRef Haley EM, Kim Y (2014) The role of basic fibroblast growth factor in glioblastoma multiforme and glioblastoma stem cells and in their in vitro culture. Cancer Lett 346(1):1–5PubMedCrossRef
21.
go back to reference Lieberman-Blum SS, Fung HB, Bandres JC (2008) Maraviroc: a CCR5-receptor antagonist for the treatment of HIV-1 infection. Clin Ther 30(7):1228–1250PubMedCrossRef Lieberman-Blum SS, Fung HB, Bandres JC (2008) Maraviroc: a CCR5-receptor antagonist for the treatment of HIV-1 infection. Clin Ther 30(7):1228–1250PubMedCrossRef
22.
go back to reference Kast RE (2010) 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 35(6):657–663PubMedCrossRef Kast RE (2010) 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 35(6):657–663PubMedCrossRef
23.
go back to reference Rappa F, Cappello F, Halatsch ME, Scheuerle A, Kast RE (2013) Aldehyde dehydrogenase and HSP90 co-localize in human glioblastoma biopsy cells. Biochimie 95(4):782–786PubMedCrossRef Rappa F, Cappello F, Halatsch ME, Scheuerle A, Kast RE (2013) Aldehyde dehydrogenase and HSP90 co-localize in human glioblastoma biopsy cells. Biochimie 95(4):782–786PubMedCrossRef
24.
go back to reference Kast RE (2015) The role of interleukin-18 in glioblastoma pathology implies therapeutic potential of two old drugs-disulfiram and ritonavir. Chin J Cancer 34(4):161–165PubMed Kast RE (2015) The role of interleukin-18 in glioblastoma pathology implies therapeutic potential of two old drugs-disulfiram and ritonavir. Chin J Cancer 34(4):161–165PubMed
25.
go back to reference Sato A (2015) The human immunodeficiency virus protease inhibitor ritonavir is potentially active against urological malignancies. Onco Targets Ther 8:761–768PubMedPubMedCentralCrossRef Sato A (2015) The human immunodeficiency virus protease inhibitor ritonavir is potentially active against urological malignancies. Onco Targets Ther 8:761–768PubMedPubMedCentralCrossRef
26.
go back to reference Chow WA, Jiang C, Guan M (2009) Anti-HIV drugs for cancer therapeutics: back to the future? Lancet Oncol 10(1):61–71PubMedCrossRef Chow WA, Jiang C, Guan M (2009) Anti-HIV drugs for cancer therapeutics: back to the future? Lancet Oncol 10(1):61–71PubMedCrossRef
27.
go back to reference Liu R, Zhang L, Yang J, Zhang X, Mikkelsen R, Song S, Zhou H (2015) HIV protease inhibitors sensitize human head and neck squamous carcinoma cells to radiation by activating endoplasmic reticulum stress. PLoS One 10(5):e0125928PubMedPubMedCentralCrossRef Liu R, Zhang L, Yang J, Zhang X, Mikkelsen R, Song S, Zhou H (2015) HIV protease inhibitors sensitize human head and neck squamous carcinoma cells to radiation by activating endoplasmic reticulum stress. PLoS One 10(5):e0125928PubMedPubMedCentralCrossRef
28.
go back to reference Laurent N, de Bouard S, Guillamo JS, Christov C, Zini R, Jouault H, Andre P, Lotteau V, Peschanski M (2004) Effects of the proteasome inhibitor ritonavir on glioma growth in vitro and in vivo. Mol Cancer Ther 3(2):129–136PubMed Laurent N, de Bouard S, Guillamo JS, Christov C, Zini R, Jouault H, Andre P, Lotteau V, Peschanski M (2004) Effects of the proteasome inhibitor ritonavir on glioma growth in vitro and in vivo. Mol Cancer Ther 3(2):129–136PubMed
29.
go back to reference Bruening A, Jueckstock J (2015) Misfolded proteins: from little villains to little helpers in the fight against cancer. Front Oncol 5:47 Bruening A, Jueckstock J (2015) Misfolded proteins: from little villains to little helpers in the fight against cancer. Front Oncol 5:47
30.
go back to reference Weiss M, Kost B, Renner-Mueller I, Wolf E, Mylonas I, Bruening A (2015) Efavirenz causes oxidative stress, endoplasmic reticulum stress, and autophagy in endothelial cells. Cardiovasc Toxicol. doi:10.1007/s12012-015-9314-2 Weiss M, Kost B, Renner-Mueller I, Wolf E, Mylonas I, Bruening A (2015) Efavirenz causes oxidative stress, endoplasmic reticulum stress, and autophagy in endothelial cells. Cardiovasc Toxicol. doi:10.​1007/​s12012-015-9314-2
31.
go back to reference 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 (2007) 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 13(17):5183–5194PubMedCrossRef 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 (2007) 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 13(17):5183–5194PubMedCrossRef
32.
go back to reference Muñoz M, Coveñas R (2013) Involvement of substance P and the NK-1 receptor in cancer progression. Peptides 48:1–9PubMedCrossRef Muñoz M, Coveñas R (2013) Involvement of substance P and the NK-1 receptor in cancer progression. Peptides 48:1–9PubMedCrossRef
33.
go back to reference Muñoz M, Rosso M, Pérez A, Coveñas R, Rosso R, Zamarriego C, Piruat JI (2005) The NK1 receptor is involved in the antitumoural action of L-733,060 and in the mitogenic action of substance P on neuroblastoma and glioma cell lines. Neuropeptides 39(4):427–432PubMedCrossRef Muñoz M, Rosso M, Pérez A, Coveñas R, Rosso R, Zamarriego C, Piruat JI (2005) The NK1 receptor is involved in the antitumoural action of L-733,060 and in the mitogenic action of substance P on neuroblastoma and glioma cell lines. Neuropeptides 39(4):427–432PubMedCrossRef
34.
go back to reference Nakajima Y, Tsuchida K, Negishi M, Ito S, Nakanishi S (1992) Direct linkage of three tachykinin receptors to stimulation of both phosphatidylinositol hydrolysis and cAMP cascades in transfected Chinese hamster ovary cells. J Biol Chem 267(4):2437–2442PubMed Nakajima Y, Tsuchida K, Negishi M, Ito S, Nakanishi S (1992) Direct linkage of three tachykinin receptors to stimulation of both phosphatidylinositol hydrolysis and cAMP cascades in transfected Chinese hamster ovary cells. J Biol Chem 267(4):2437–2442PubMed
35.
go back to reference Takeda Y, Blount P, Sachais BS, Hershey AD, Raddatz R, Krause JE (1992) Ligand binding kinetics of substance P and neurokinin A receptors stably expressed in Chinese hamster ovary cells and evidence for differential stimulation of inositol 1, 4, 5-triphosphate and cyclic AMP second messenger responses. J Neurochem 59(2):740–745PubMedCrossRef Takeda Y, Blount P, Sachais BS, Hershey AD, Raddatz R, Krause JE (1992) Ligand binding kinetics of substance P and neurokinin A receptors stably expressed in Chinese hamster ovary cells and evidence for differential stimulation of inositol 1, 4, 5-triphosphate and cyclic AMP second messenger responses. J Neurochem 59(2):740–745PubMedCrossRef
36.
go back to reference Akazawa T, Kwatra SG, Goldsmith LE, Richardson MD, Cox EA, Sampson JH, Kwatra MM (2009) A constitutively active form of neurokinin 1 receptor and neurokinin 1 receptor-mediated apoptosis in glioblastomas. J Neurochem 109(4):1079–1086PubMedPubMedCentralCrossRef Akazawa T, Kwatra SG, Goldsmith LE, Richardson MD, Cox EA, Sampson JH, Kwatra MM (2009) A constitutively active form of neurokinin 1 receptor and neurokinin 1 receptor-mediated apoptosis in glioblastomas. J Neurochem 109(4):1079–1086PubMedPubMedCentralCrossRef
37.
go back to reference Dalva-Aydemir S, Bajpai R, Martinez M, Adekola KU, Kandela I, Wei C, Singhal S, Koblinski JE, Raje NS, Rosen ST, Shanmugam M (2015) Targeting the metabolic plasticity of multiple myeloma with FDA-approved ritonavir and metformin. Clin Cancer Res 21(5):1161–1171PubMedCrossRef Dalva-Aydemir S, Bajpai R, Martinez M, Adekola KU, Kandela I, Wei C, Singhal S, Koblinski JE, Raje NS, Rosen ST, Shanmugam M (2015) Targeting the metabolic plasticity of multiple myeloma with FDA-approved ritonavir and metformin. Clin Cancer Res 21(5):1161–1171PubMedCrossRef
38.
go back to reference Batchu RB, Gruzdyn OV, Bryant CS, Qazi AM, Kumar S, Chamala S, Kung ST, Sanka RS, Puttagunta US, Weaver DW, Gruber SA (2014) Ritonavir-mediated induction of apoptosis in pancreatic cancer occurs via the RB/E2F-1 and AKT pathways. Pharmaceuticals (Basel) 7(1):46–57CrossRef Batchu RB, Gruzdyn OV, Bryant CS, Qazi AM, Kumar S, Chamala S, Kung ST, Sanka RS, Puttagunta US, Weaver DW, Gruber SA (2014) Ritonavir-mediated induction of apoptosis in pancreatic cancer occurs via the RB/E2F-1 and AKT pathways. Pharmaceuticals (Basel) 7(1):46–57CrossRef
39.
go back to reference Kraus M, Mueller-Ide H, Rueckrich T, Bader J, Overkleeft H, Driessen C (2014) Ritonavir, nelfinavir, saquinavir and lopinavir induce proteotoxic stress in acute myeloid leukemia cells and sensitize them for proteasome inhibitor treatment at low micromolar drug concentrations. Leuk Res 38(3):383–392PubMedCrossRef Kraus M, Mueller-Ide H, Rueckrich T, Bader J, Overkleeft H, Driessen C (2014) Ritonavir, nelfinavir, saquinavir and lopinavir induce proteotoxic stress in acute myeloid leukemia cells and sensitize them for proteasome inhibitor treatment at low micromolar drug concentrations. Leuk Res 38(3):383–392PubMedCrossRef
40.
go back to reference Manak MM, Moshkoff DA, Nguyen LT, Meshki J, Tebas P, Tuluc F, Douglas SD (2010) Anti-HIV-1 activity of the neurokinin-1 receptor antagonist aprepitant and synergistic interactions with other antiretrovirals. AIDS 24(18):2789–2796PubMedPubMedCentralCrossRef Manak MM, Moshkoff DA, Nguyen LT, Meshki J, Tebas P, Tuluc F, Douglas SD (2010) Anti-HIV-1 activity of the neurokinin-1 receptor antagonist aprepitant and synergistic interactions with other antiretrovirals. AIDS 24(18):2789–2796PubMedPubMedCentralCrossRef
41.
go back to reference Muñoz M, Coveñas R (2013) Safety of neurokinin-1 receptor antagonists. Expert Opin Drug Saf 12(5):673–685PubMedCrossRef Muñoz M, Coveñas R (2013) Safety of neurokinin-1 receptor antagonists. Expert Opin Drug Saf 12(5):673–685PubMedCrossRef
42.
go back to reference Kramer MS, Cutler N, Feighner J, Shrivastava R, Carman J, Sramek JJ, Reines SA, Liu G, Snavely D, Wyatt-knowles E, Halle JJ, Mills SG, MacCoss M, Swain CJ, Harrison T, Hill RG, Hefti F, Scolnick EM, Cascieri MA, Chicchi GG, Sadowski S, Williams AR, Hewson L, Smith D, Carlsson EJ, Hargreaves RJ, Rupniak NM (1998) Distinct mechanism for antidepressant activity by blockade of central substance P receptors. Science 281(5383):1640–1645PubMedCrossRef Kramer MS, Cutler N, Feighner J, Shrivastava R, Carman J, Sramek JJ, Reines SA, Liu G, Snavely D, Wyatt-knowles E, Halle JJ, Mills SG, MacCoss M, Swain CJ, Harrison T, Hill RG, Hefti F, Scolnick EM, Cascieri MA, Chicchi GG, Sadowski S, Williams AR, Hewson L, Smith D, Carlsson EJ, Hargreaves RJ, Rupniak NM (1998) Distinct mechanism for antidepressant activity by blockade of central substance P receptors. Science 281(5383):1640–1645PubMedCrossRef
43.
go back to reference Harford-Wright E, Lewis KM, Ghabriel MN, Vink R (2014) Treatment with the NK1 antagonist emend reduces blood brain barrier dysfunction and edema formation in an experimental model of brain tumors. PLoS ONE 9(5):e97002PubMedPubMedCentralCrossRef Harford-Wright E, Lewis KM, Ghabriel MN, Vink R (2014) Treatment with the NK1 antagonist emend reduces blood brain barrier dysfunction and edema formation in an experimental model of brain tumors. PLoS ONE 9(5):e97002PubMedPubMedCentralCrossRef
44.
go back to reference Endo T, Saijo T, Haneda E, Maeda J, Tokunaga M, Zhang MR, Kannami A, Asai H, Suzuki M, Suhara T, Higuchi M (2015) Quantification of central substance P receptor occupancy by aprepitant using small animal positron emission tomography. Int J Neuropsychopharmacol 18(2):pyu030PubMedCentralCrossRef Endo T, Saijo T, Haneda E, Maeda J, Tokunaga M, Zhang MR, Kannami A, Asai H, Suzuki M, Suhara T, Higuchi M (2015) Quantification of central substance P receptor occupancy by aprepitant using small animal positron emission tomography. Int J Neuropsychopharmacol 18(2):pyu030PubMedCentralCrossRef
45.
go back to reference Bergström M, Hargreaves RJ, Burns HD, Goldberg MR, Sciberras D, Reines SA, Petty KJ, Ogren M, Antoni G, Långström B, Eskola O, Scheinin M, Solin O, Majumdar AK, Constanzer ML, Battisti WP, Bradstreet TE, Gargano C, Hietala J (2004) Human positron emission tomography studies of brain neurokinin 1 receptor occupancy by aprepitant. Biol Psychiatry 55(10):1007–1012PubMedCrossRef Bergström M, Hargreaves RJ, Burns HD, Goldberg MR, Sciberras D, Reines SA, Petty KJ, Ogren M, Antoni G, Långström B, Eskola O, Scheinin M, Solin O, Majumdar AK, Constanzer ML, Battisti WP, Bradstreet TE, Gargano C, Hietala J (2004) Human positron emission tomography studies of brain neurokinin 1 receptor occupancy by aprepitant. Biol Psychiatry 55(10):1007–1012PubMedCrossRef
46.
go back to reference Anthonypillai C, Sanderson RN, Gibbs JE, Thomas SA (2004) The distribution of the HIV protease inhibitor, ritonavir, to the brain, cerebrospinal fluid, and choroid plexuses of the guinea pig. J Pharmacol ExpTher 308(3):912–920CrossRef Anthonypillai C, Sanderson RN, Gibbs JE, Thomas SA (2004) The distribution of the HIV protease inhibitor, ritonavir, to the brain, cerebrospinal fluid, and choroid plexuses of the guinea pig. J Pharmacol ExpTher 308(3):912–920CrossRef
Metadata
Title
Antitumor action of temozolomide, ritonavir and aprepitant against human glioma cells
Authors
Richard E. Kast
Susana Ramiro
Sandra Lladó
Salvador Toro
Rafael Coveñas
Miguel Muñoz
Publication date
01-02-2016
Publisher
Springer US
Published in
Journal of Neuro-Oncology / Issue 3/2016
Print ISSN: 0167-594X
Electronic ISSN: 1573-7373
DOI
https://doi.org/10.1007/s11060-015-1996-6

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