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Journal of Translational Medicine
Published in: Journal of Translational Medicine 1/2017

Open Access 01-12-2017 | Research

FTY720 inhibits mesothelioma growth in vitro and in a syngeneic mouse model

Authors: Agata Szymiczek, Sandra Pastorino, David Larson, Mika Tanji, Laura Pellegrini, Jiaming Xue, Shuangjing Li, Carlotta Giorgi, Paolo Pinton, Yasutaka Takinishi, Harvey I. Pass, Hideki Furuya, Giovanni Gaudino, Andrea Napolitano, Michele Carbone, Haining Yang

Published in: Journal of Translational Medicine | Issue 1/2017

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Abstract

Background

Malignant mesothelioma (MM) is a very aggressive type of cancer, with a dismal prognosis and inherent resistance to chemotherapeutics. Development and evaluation of new therapeutic approaches is highly needed. Immunosuppressant FTY720, approved for multiple sclerosis treatment, has recently raised attention for its anti-tumor activity in a variety of cancers. However, its therapeutic potential in MM has not been evaluated yet.

Methods

Cell viability and anchorage–independent growth were evaluated in a panel of MM cell lines and human mesothelial cells (HM) upon FTY720 treatment to assess in vitro anti-tumor efficacy. The mechanism of action of FTY720 in MM was assessed by measuring the activity of phosphatase protein 2A (PP2A)—a major target of FTY720. The binding of the endogenous inhibitor SET to PP2A in presence of FTY720 was evaluated by immunoblotting and immunoprecipitation. Signaling and activation of programmed cell death were evaluated by immunoblotting and flow cytometry. A syngeneic mouse model was used to evaluate anti-tumor efficacy and toxicity profile of FTY720 in vivo.

Results

We show that FTY720 significantly suppressed MM cell viability and anchorage–independent growth without affecting normal HM cells. FTY720 inhibited the phosphatase activity of PP2A by displacement of SET protein, which appeared overexpressed in MM, as compared to HM cells. FTY720 promoted AKT dephosphorylation and Bcl-2 degradation, leading to induction of programmed cell death, as demonstrated by caspase-3 and PARP activation, as well as by cytochrome c and AIF intracellular translocation. Moreover, FTY720 administration in vivo effectively reduced tumor burden in mice without apparent toxicity.

Conclusions

Our preclinical data indicate that FTY720 is a potentially promising therapeutic agent for MM treatment.
Appendix
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Literature
1.
Carbone M, Ly BH, Dodson RF, Pagano I, Morris PT, Dogan UA, Gazdar AF, Pass HI, Yang H. Malignant mesothelioma: facts, myths, and hypotheses. J Cell Physiol. 2012;227:44–58.CrossRefPubMedPubMedCentral
2.
Henley SJ, Larson TC, Wu M, Antao VC, Lewis M, Pinheiro GA, Eheman C. Mesothelioma incidence in 50 states and the District of Columbia, United States, 2003–2008. Int J Occup Environ Health. 2013;19:1–10.CrossRefPubMedPubMedCentral
3.
Delgermaa V, Takahashi K, Park EK, Le GV, Hara T, Sorahan T. Global mesothelioma deaths reported to the World Health Organization between 1994 and 2008. Bull World Health Organ. 2011;89(716–724):724A.
4.
Hillegass JM, Shukla A, Lathrop SA, MacPherson MB, Beuschel SL, Butnor KJ, Testa JR, Pass HI, Carbone M, Steele C, Mossman BT. Inflammation precedes the development of human malignant mesotheliomas in a SCID mouse xenograft model. Ann N Y Acad Sci. 2010;1203:7–14.CrossRefPubMedPubMedCentral
5.
Carbone M, Yang H. Molecular pathways: targeting mechanisms of asbestos and erionite carcinogenesis in mesothelioma. Clin Cancer Res. 2012;18:598–604.CrossRefPubMed
6.
Guo Z, Carbone M, Zhang X, Su D, Sun W, Lou J, Gao Z, Shao D, Chen J, Zhang G, Hu J, Chen K, Wang F, Pass HI, Yu H, Napolitano A, Yang H, Mao W. Improving the accuracy of mesothelioma diagnosis in China. J Thorac Oncol. 2016;7:59314.
7.
Mao W, Zhang X, Guo Z, Gao Z, Pass HI, Yang H, Carbone M. Association of asbestos exposure with malignant mesothelioma incidence in Eastern China. JAMA Oncol. 2016;6:2374–437.
8.
Carbone M, Kanodia S, Chao A, Miller A, Wali A, Weissman D, Adjei A, Baumann F, Boffetta P, Buck B, de Perrot M, Dogan AU, Gavett S, Gualtieri A, Hassan R, Hesdorffer M, Hirsch FR, Larson D, Mao W, Masten S, Pass HI, Peto J, Pira E, Steele I, Tsao A, Woodard GA, Yang H, Malik S. Consensus report of the 2015 Weinman International Conference on mesothelioma. J Thorac Oncol. 2016;11:1246–62.CrossRefPubMed
9.
10.
Baumann F, Buck BJ, Metcalf RV, McLaurin BT, Merkler DJ, Carbone M. The presence of asbestos in the natural environment is likely related to mesothelioma in young individuals and women from Southern Nevada. J Thorac Oncol. 2015;10:731–7.CrossRefPubMedPubMedCentral
11.
Baumann F, Ambrosi JP, Carbone M. Asbestos is not just asbestos: an unrecognised health hazard. Lancet Oncol. 2013;14:576–8.CrossRefPubMed
12.
Carbone M, Baris YI, Bertino P, Brass B, Comertpay S, Dogan AU, Gaudino G, Jube S, Kanodia S, Partridge CR, Pass HI, Rivera ZS, Steele I, Tuncer M, Way S, Yang H, Miller A. Erionite exposure in North Dakota and Turkish villages with mesothelioma. Proc Natl Acad Sci USA. 2011;108:13618–23.CrossRefPubMedPubMedCentral
13.
Carbone M, Rizzo P, Pass H. Simian virus 40: the link with human malignant mesothelioma is well established. Anticancer Res. 2000;20:875–7.PubMed
14.
Gazdar AF, Carbone M. Molecular pathogenesis of malignant mesothelioma and its relationship to simian virus 40. Clin Lung Cancer. 2003;5:177–81.CrossRefPubMed
15.
16.
Testa JR, Cheung M, Pei J, Below JE, Tan Y, Sementino E, Cox NJ, Dogan AU, Pass HI, Trusa S, Hesdorffer M, Nasu M, Powers A, Rivera Z, Comertpay S, Tanji M, Gaudino G, Yang H, Carbone M. Germline BAP1 mutations predispose to malignant mesothelioma. Nat Genet. 2011;43:1022–5.CrossRefPubMedPubMedCentral
17.
Nasu M, Emi M, Pastorino S, Tanji M, Powers A, Luk H, Baumann F, Zhang YA, Gazdar A, Kanodia S, Tiirikainen M, Flores E, Gaudino G, Becich MJ, Pass HI, Yang H, Carbone M. High incidence of somatic BAP1 alterations in sporadic malignant mesothelioma. J Thorac Oncol. 2015;10:565–76.CrossRefPubMedPubMedCentral
18.
Napolitano A, Pellegrini L, Dey A, Larson D, Tanji M, Flores EG, Kendrick B, Lapid D, Powers A, Kanodia S, Pastorino S, Pass HI, Dixit V, Yang H, Carbone M. Minimal asbestos exposure in germline BAP1 heterozygous mice is associated with deregulated inflammatory response and increased risk of mesothelioma. Oncogene. 2016;35:1996–2002.CrossRefPubMed
19.
van Zandwijk N, Clarke C, Henderson D, Musk AW, Fong K, Nowak A, Loneragan R, McCaughan B, Boyer M, Feigen M, Currow D, Schofield P, Nick Pavlakis BI, McLean J, Marshall H, Leong S, Keena V, Penman A. Guidelines for the diagnosis and treatment of malignant pleural mesothelioma. J Thorac Dis. 2013;5:E254–307.PubMedPubMedCentral
20.
Chun J, Brinkmann V. A mechanistically novel, first oral therapy for multiple sclerosis: the development of fingolimod (FTY720, Gilenya). Discov Med. 2011;12:213–28.PubMedPubMedCentral
21.
Mullershausen F, Zecri F, Cetin C, Billich A, Guerini D, Seuwen K. Persistent signaling induced by FTY720-phosphate is mediated by internalized S1P1 receptors. Nat Chem Biol. 2009;5:428–34.CrossRefPubMed
22.
Patmanathan SN, Yap LF, Murray PG, Paterson IC. The antineoplastic properties of FTY720: evidence for the repurposing of fingolimod. J Cell Mol Med. 2015;19:2329–40.CrossRefPubMedPubMedCentral
23.
Kim HS, Yoon G, Ryu JY, Cho YJ, Choi JJ, Lee YY, Kim TJ, Choi CH, Song SY, Kim BG, Bae DS, Lee JW. Sphingosine kinase 1 is a reliable prognostic factor and a novel therapeutic target for uterine cervical cancer. Oncotarget. 2015;6:26746–56.CrossRefPubMedPubMedCentral
24.
Oaks JJ, Santhanam R, Walker CJ, Roof S, Harb JG, Ferenchak G, Eisfeld AK, Van Brocklyn JR, Briesewitz R, Saddoughi SA, Nagata K, Bittman R, Caligiuri MA, Abdel-Wahab O, Levine R, Arlinghaus RB, Quintas-Cardama A, Goldman JM, Apperley J, Reid A, Milojkovic D, Ziolo MT, Marcucci G, Ogretmen B, Neviani P, Perrotti D. Antagonistic activities of the immunomodulator and PP2A-activating drug FTY720 (Fingolimod, Gilenya) in Jak2-driven hematologic malignancies. Blood. 2013;122:1923–34.CrossRefPubMedPubMedCentral
25.
Lee WJ, Yoo HS, Suh PG, Oh S, Lim JS, Lee YM. Sphingosine mediates FTY720-induced apoptosis in LLC-PK1 cells. Exp Mol Med. 2004;36:420–7.CrossRefPubMed
26.
Azuma H, Takahara S, Ichimaru N, Wang JD, Itoh Y, Otsuki Y, Morimoto J, Fukui R, Hoshiga M, Ishihara T, Nonomura N, Suzuki S, Okuyama A, Katsuoka Y. Marked prevention of tumor growth and metastasis by a novel immunosuppressive agent, FTY720, in mouse breast cancer models. Cancer Res. 2002;62:1410–9.PubMed
27.
Schmid G, Guba M, Papyan A, Ischenko I, Bruckel M, Bruns CJ, Jauch KW, Graeb C. FTY720 inhibits tumor growth and angiogenesis. Transplant Proc. 2005;37:110–1.CrossRefPubMed
28.
Chua CW, Lee DT, Ling MT, Zhou C, Man K, Ho J, Chan FL, Wang X, Wong YC. FTY720, a fungus metabolite, inhibits in vivo growth of androgen-independent prostate cancer. Int J Cancer. 2005;117:1039–48.CrossRefPubMed
29.
Gstalder C, Ader I, Cuvillier O. FTY720 (Fingolimod) inhibits HIF-1 and HIF-2 signaling, promotes vascular remodeling and chemosensitizes in renal cell carcinoma animal model. Mol Cancer Ther. 2016;15:2465–74.CrossRefPubMed
30.
Ahmed D, de Verdier PJ, Ryk C, Lunqe O, Stal P, Flygare J. FTY720 (Fingolimod) sensitizes hepatocellular carcinoma cells to sorafenib-mediated cytotoxicity. Pharmacol Res Perspect. 2015;3:e00171.CrossRefPubMedPubMedCentral
31.
Neviani P, Harb JG, Oaks JJ, Santhanam R, Walker CJ, Ellis JJ, Ferenchak G, Dorrance AM, Paisie CA, Eiring AM, Ma Y, Mao HC, Zhang B, Wunderlich M, May PC, Sun C, Saddoughi SA, Bielawski J, Blum W, Klisovic RB, Solt JA, Byrd JC, Volinia S, Cortes J, Huettner CS, Koschmieder S, Holyoake TL, Devine S, Caligiuri MA, Croce CM, Garzon R, Ogretmen B, Arlinghaus RB, Chen CS, Bittman R, Hokland P, Roy DC, Milojkovic D, Apperley J, Goldman JM, Reid A, Mulloy JC, Bhatia R, Marcucci G, Perrotti D. PP2A-activating drugs selectively eradicate TKI-resistant chronic myeloid leukemic stem cells. J Clin Invest. 2013;123:4144–57.CrossRefPubMedPubMedCentral
32.
Tonelli F, Lim KG, Loveridge C, Long J, Pitson SM, Tigyi G, Bittman R, Pyne S, Pyne NJ. FTY720 and (S)-FTY720 vinylphosphonate inhibit sphingosine kinase 1 and promote its proteasomal degradation in human pulmonary artery smooth muscle, breast cancer and androgen-independent prostate cancer cells. Cell Signal. 2010;22:1536–42.CrossRefPubMedPubMedCentral
33.
Li W, Li J, Wang Y, Zhang K, Li N, Tian Z, Ni B, Wang H, Ruan Z. Sphingosine kinase 1 is a potential therapeutic target for nasopharyngeal carcinoma. Oncotarget. 2016;7:80586–98.PubMed
34.
Zhang L, Wang H, Zhu J, Ding K, Xu J. FTY720 reduces migration and invasion of human glioblastoma cell lines via inhibiting the PI3K/AKT/mTOR/p70S6K signaling pathway. Tumour Biol. 2014;35:10707–14.CrossRefPubMed
35.
Kalari S, Moolky N, Pendyala S, Berdyshev EV, Rolle C, Kanteti R, Kanteti A, Ma W, He D, Husain AN, Kindler HL, Kanteti P, Salgia R, Natarajan V. Sphingosine kinase 1 is required for mesothelioma cell proliferation: role of histone acetylation. PLoS ONE. 2012;7:e45330.CrossRefPubMedPubMedCentral
36.
Kaku Y, Tsuchiya A, Kanno T, Nakano T, Nishizaki T. Dipalmitoleoyl-phosphatidylethanolamine induces apoptosis of NCI-H28 malignant mesothelioma cells. Anticancer Res. 2014;34:1759–64.PubMed
37.
Aceto N, Bertino P, Barbone D, Tassi G, Manzo L, Porta C, Mutti L, Gaudino G. Taurolidine and oxidative stress: a rationale for local treatment of mesothelioma. Eur Respir J. 2009;34:1399–407.CrossRefPubMed
38.
Bocchetta M, Di Resta I, Powers A, Fresco R, Tosolini A, Testa JR, Pass HI, Rizzo P, Carbone M. Human mesothelial cells are unusually susceptible to simian virus 40-mediated transformation and asbestos cocarcinogenicity. Proc Natl Acad Sci USA. 2000;97:10214–9.CrossRefPubMedPubMedCentral
39.
Pass HI, Stevens EJ, Oie H, Tsokos MG, Abati AD, Fetsch PA, Mew DJ, Pogrebniak HW, Matthews WJ. Characteristics of nine newly derived mesothelioma cell lines. Ann Thorac Surg. 1995;59:835–44.CrossRefPubMed
40.
Reale FR, Griffin TW, Compton JM, Graham S, Townes PL, Bogden A. Characterization of a human malignant mesothelioma cell line (H-MESO-1): a biphasic solid and ascitic tumor model. Cancer Res. 1987;47:3199–205.PubMed
41.
Davis MR, Manning LS, Whitaker D, Garlepp MJ, Robinson BW. Establishment of a murine model of malignant mesothelioma. Int J Cancer. 1992;52:881–6.CrossRefPubMed
42.
Pitman MR, Pham DH, Pitson SM. Isoform-selective assays for sphingosine kinase activity. Methods Mol Biol. 2012;874:21–31.CrossRefPubMed
43.
Jube S, Rivera ZS, Bianchi ME, Powers A, Wang E, Pagano I, Pass HI, Gaudino G, Carbone M, Yang H. Cancer cell secretion of the DAMP protein HMGB1 supports progression in malignant mesothelioma. Cancer Res. 2012;72:3290–301.CrossRefPubMedPubMedCentral
44.
Sanchez T, Estrada-Hernandez T, Paik JH, Wu MT, Venkataraman K, Brinkmann V, Claffey K, Hla T. Phosphorylation and action of the immunomodulator FTY720 inhibits vascular endothelial cell growth factor-induced vascular permeability. J Biol Chem. 2003;278:47281–90.CrossRefPubMed
45.
Liu Q, Alinari L, Chen CS, Yan F, Dalton JT, Lapalombella R, Zhang X, Mani R, Lin T, Byrd JC, Baiocchi RA, Muthusamy N. FTY720 shows promising in vitro and in vivo preclinical activity by downmodulating Cyclin D1 and phospho-Akt in mantle cell lymphoma. Clin Cancer Res. 2010;16:3182–92.CrossRefPubMedPubMedCentral
46.
Saddoughi SA, Gencer S, Peterson YK, Ward KE, Mukhopadhyay A, Oaks J, Bielawski J, Szulc ZM, Thomas RJ, Selvam SP, Senkal CE, Garrett-Mayer E, De Palma RM, Fedarovich D, Liu A, Habib AA, Stahelin RV, Perrotti D, Ogretmen B. Sphingosine analogue drug FTY720 targets I2PP2A/SET and mediates lung tumour suppression via activation of PP2A-RIPK1-dependent necroptosis. EMBO Mol Med. 2013;5:105–21.CrossRefPubMed
47.
Junttila MR, Puustinen P, Niemela M, Ahola R, Arnold H, Bottzauw T, Ala-aho R, Nielsen C, Ivaska J, Taya Y, Lu SL, Lin S, Chan EK, Wang XJ, Grenman R, Kast J, Kallunki T, Sears R, Kahari VM, Westermarck J. CIP2A inhibits PP2A in human malignancies. Cell. 2007;130:51–62.CrossRefPubMed
48.
Mukhopadhyay A, Saddoughi SA, Song P, Sultan I, Ponnusamy S, Senkal CE, Snook CF, Arnold HK, Sears RC, Hannun YA, Ogretmen B. Direct interaction between the inhibitor 2 and ceramide via sphingolipid-protein binding is involved in the regulation of protein phosphatase 2A activity and signaling. FASEB J. 2009;23:751–63.CrossRefPubMedPubMedCentral
49.
Li J, Song Z, Wang Y, Yin Y, Liu Y, Yuan R, Nan X. Overexpression of SphK1 enhances cell proliferation and invasion in triple-negative breast cancer via the PI3K/AKT signaling pathway. Tumour Biol. 2016;37:10587–93.CrossRefPubMed
50.
Andrabi S, Gjoerup OV, Kean JA, Roberts TM, Schaffhausen B. Protein phosphatase 2A regulates life and death decisions via Akt in a context-dependent manner. Proc Natl Acad Sci USA. 2007;104:19011–6.CrossRefPubMedPubMedCentral
51.
Pugazhenthi S, Nesterova A, Sable C, Heidenreich KA, Boxer LM, Heasley LE, Reusch JE. Akt/protein kinase B up-regulates Bcl-2 expression through cAMP-response element-binding protein. J Biol Chem. 2000;275:10761–6.CrossRefPubMed
52.
Yamaguchi H, Wang HG. The protein kinase PKB/Akt regulates cell survival and apoptosis by inhibiting Bax conformational change. Oncogene. 2001;20:7779–86.CrossRefPubMed
53.
Mezzapelle R, Rrapaj E, Gatti E, Ceriotti C, Marchis FD, Preti A, Spinelli AE, Perani L, Venturini M, Valtorta S, Moresco RM, Pecciarini L, Doglioni C, Frenquelli M, Crippa L, Recordati C, Scanziani E, de Vries H, Berns A, Frapolli R, Boldorini R, D’Incalci M, Bianchi ME, Crippa MP. Human malignant mesothelioma is recapitulated in immunocompetent BALB/c mice injected with murine AB cells. Sci Rep. 2016;6:22850.CrossRefPubMedPubMedCentral
54.
Napolitano A, Carbone M. Malignant mesothelioma: time to translate? Trends in Cancer. 2016;2:467–74.CrossRef
55.
Zalcman G, Mazieres J, Margery J, Greillier L, Audigier-Valette C, Moro-Sibilot D, Molinier O, Corre R, Monnet I, Gounant V, Riviere F, Janicot H, Gervais R, Locher C, Milleron B, Tran Q, Lebitasy MP, Morin F, Creveuil C, Parienti JJ, Scherpereel A, French Cooperative Thoracic I. Bevacizumab for newly diagnosed pleural mesothelioma in the Mesothelioma Avastin Cisplatin Pemetrexed Study (MAPS): a randomised, controlled, open-label, phase 3 trial. Lancet. 2016;387:1405–14.CrossRefPubMed
56.
57.
58.
Kroczynska B, Cutrone R, Bocchetta M, Yang H, Elmishad AG, Vacek P, Ramos-Nino M, Mossman BT, Pass HI, Carbone M. Crocidolite asbestos and SV40 are cocarcinogens in human mesothelial cells and in causing mesothelioma in hamsters. Proc Natl Acad Sci USA. 2006;103:14128–33.CrossRefPubMedPubMedCentral
59.
Carbone M. Simian virus 40 and human tumors: it is time to study mechanisms. J Cell Biochem. 1999;76:189–93.CrossRefPubMed
60.
Pitman MR, Barr RK, Gliddon BL, Magarey AM, Moretti PA, Pitson SM. A critical role for the protein phosphatase 2A B′α regulatory subunit in dephosphorylation of sphingosine kinase 1. Int J Biochem Cell Biol. 2011;43:342–7.CrossRefPubMed
61.
Barr RK, Lynn HE, Moretti PA, Khew-Goodall Y, Pitson SM. Deactivation of sphingosine kinase 1 by protein phosphatase 2A. J Biol Chem. 2008;283:34994–5002.CrossRefPubMedPubMedCentral
62.
Salas A, Ponnusamy S, Senkal CE, Meyers-Needham M, Selvam SP, Saddoughi SA, Apohan E, Sentelle RD, Smith C, Gault CR, Obeid LM, El-Shewy HM, Oaks J, Santhanam R, Marcucci G, Baran Y, Mahajan S, Fernandes D, Stuart R, Perrotti D, Ogretmen B. Sphingosine kinase-1 and sphingosine 1-phosphate receptor 2 mediate Bcr-Abl1 stability and drug resistance by modulation of protein phosphatase 2A. Blood. 2011;117:5941–52.CrossRefPubMedPubMedCentral
63.
Ingwersen J, Aktas O, Kuery P, Kieseier B, Boyko A, Hartung HP. Fingolimod in multiple sclerosis: mechanisms of action and clinical efficacy. Clin Immunol. 2012;142:15–24.CrossRefPubMed
64.
Enjeti AK, D’Crus A, Melville K, Verrills NM, Rowlings P. A systematic evaluation of the safety and toxicity of fingolimod for its potential use in the treatment of acute myeloid leukaemia. Anticancer Drugs. 2016;27:560–8.CrossRefPubMedPubMedCentral
65.
Bueno R, Stawiski EW, Goldstein LD, Durinck S, De Rienzo A, Modrusan Z, Gnad F, Nguyen TT, Jaiswal BS, Chirieac LR, Sciaranghella D, Dao N, Gustafson CE, Munir KJ, Hackney JA, Chaudhuri A, Gupta R, Guillory J, Toy K, Ha C, Chen YJ, Stinson J, Chaudhuri S, Zhang N, Wu TD, Sugarbaker DJ, de Sauvage FJ, Richards WG, Seshagiri S. Comprehensive genomic analysis of malignant pleural mesothelioma identifies recurrent mutations, gene fusions and splicing alterations. Nat Genet. 2016;48:407–16.CrossRefPubMed
66.
Ostroff RM, Mehan MR, Stewart A, Ayers D, Brody EN, Williams SA, Levin S, Black B, Harbut M, Carbone M, Goparaju C, Pass HI. Early detection of malignant pleural mesothelioma in asbestos-exposed individuals with a noninvasive proteomics-based surveillance tool. PLoS ONE. 2012;7:e46091.CrossRefPubMedPubMedCentral
67.
Napolitano A, Antoine DJ, Pellegrini L, Baumann F, Pagano I, Pastorino S, Goparaju CM, Prokrym K, Canino C, Pass HI, Carbone M, Yang H. HMGB1 and its hyperacetylated isoform are sensitive and specific serum biomarkers to detect asbestos exposure and to identify mesothelioma patients. Clin Cancer Res. 2016;22:3087–96.CrossRefPubMedPubMedCentral
68.
Francis G, Kappos L, O’Connor P, Collins W, Tang D, Mercier F, Cohen JA. Temporal profile of lymphocyte counts and relationship with infections with fingolimod therapy. Mult Scler J. 2014;20:471–80.CrossRef
69.
Omar HA, Chou CC, Berman-Booty LD, Ma Y, Hung JH, Wang D, Kogure T, Patel T, Terracciano L, Muthusamy N, Byrd JC, Kulp SK, Chen CS. Antitumor effects of OSU-2S, a nonimmunosuppressive analogue of FTY720, in hepatocellular carcinoma. Hepatology. 2011;53:1943–58.CrossRefPubMedPubMedCentral
Metadata
Title
FTY720 inhibits mesothelioma growth in vitro and in a syngeneic mouse model
Authors
Agata Szymiczek
Sandra Pastorino
David Larson
Mika Tanji
Laura Pellegrini
Jiaming Xue
Shuangjing Li
Carlotta Giorgi
Paolo Pinton
Yasutaka Takinishi
Harvey I. Pass
Hideki Furuya
Giovanni Gaudino
Andrea Napolitano
Michele Carbone
Haining Yang
Publication date
01-12-2017
Publisher
BioMed Central
Published in
Journal of Translational Medicine / Issue 1/2017
Electronic ISSN: 1479-5876
DOI
https://doi.org/10.1186/s12967-017-1158-z

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