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Review Article

The Role of Chloroquine and Hydroxychloroquine in Immune Regulation and Diseases

Author(s): Gricelis P. Martinez, Mercedes E. Zabaleta, Camilo Di Giulio, Jaime E. Charris and Michael R. Mijares*

Volume 26, Issue 35, 2020

Page: [4467 - 4485] Pages: 19

DOI: 10.2174/1381612826666200707132920

Price: $65

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Abstract

Chloroquine (CQ) and hydroxychloroquine (HCQ) are derivatives of the heterocyclic aromatic compound quinoline. These economical compounds have been used as antimalarial agents for many years. Currently, they are used as monotherapy or in conjunction with other therapies for the treatment of autoimmune diseases such as systemic lupus erythematosus (SLE), rheumatoid arthritis (RA), Sjögren's syndrome (SS) and antiphospholipid antibody syndrome (APS). Based on its effects on the modulation of the autophagy process, various clinical studies suggest that CQ and HCQ could be used in combination with other chemotherapeutics for the treatment of various types of cancer. Furthermore, the antiviral effects showed against Zika, Chikungunya, and HIV are due to the annulation of endosomal/lysosomal acidification. Recently, CQ and HCQ were approved for the U.S. Food and Drug Administration (FDA) for the treatment of infected patients with the coronavirus SARSCoV- 2, causing the disease originated in December 2019, namely COVID-2019. Several mechanisms have been proposed to explain the pharmacological effects of these drugs: 1) disruption of lysosomal and endosomal pH, 2) inhibition of protein secretion/expression, 3) inhibition of antigen presentation, 4) decrease of proinflammatory cytokines, 5) inhibition of autophagy, 6) induction of apoptosis and 7) inhibition of ion channels activation. Thus, evidence has shown that these structures are leading molecules that can be modified or combined with other therapeutic agents. In this review, we will discuss the most recent findings in the mechanisms of action of CQ and HCQ in the immune system, and the use of these antimalarial drugs on diseases.

Keywords: Chloroquine, hydroxychloroquine, cancer, autophagy, autoimmune diseases, COVID-19, coronavirus, inflammation.

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[1]
Heusch R, Leverkusen B. Ullmann’s Encyclopedia of Industrial Chemistry 2000. Available at: . https://onlinelibrary.wiley.com/d oi/book/10.1002/14356007
[2]
Manske R. The chemistry of quinolines. Chem Rev 1942; 30(1): 113-44.
[http://dx.doi.org/10.1021/cr60095a006]
[3]
Steck EA, Hallock LL, Suter CM. Quinolines; some 4-aminoquinoline derivatives. J Am Chem Soc 1948; 70(12): 4063-5.
[http://dx.doi.org/10.1021/ja01192a030] [PMID: 18105939]
[4]
Burrows JN, Duparc S, Gutteridge WE, et al. New developments in anti-malarial target candidate and product profiles. Malar J 2017; 16(1): 26.
[http://dx.doi.org/10.1186/s12936-016-1675-x] [PMID: 28086874]
[5]
Baird JK. 8-Aminoquinoline Therapy for Latent Malaria. Clin Microbiol Rev 2019; 32(4): e00011-9.
[http://dx.doi.org/10.1128/CMR.00011-19] [PMID: 31366609]
[6]
Shukla AM, Wagle Shukla A. Expanding horizons for clinical applications of chloroquine, hydroxychloroquine, and related structural analogues. Drugs Context 2019; 8: 2019-9-1.
[http://dx.doi.org/10.7573/dic.2019-9-1] [PMID: 31844421]
[7]
Andersag H, Breitner S, Jung H. Verfahren zur Darstellung von in 4-Stellung basisch substituierte Aminogruppen enthaltenden Chinolinverbindungen. German Pat. 1939; 683: 692..
[8]
Schrezenmeier E, Dörner T. Mechanisms of action of hydroxychloroquine and chloroquine: implications for rheumatology. Nat Rev Rheumatol 2020; 16(3): 155-66.
[http://dx.doi.org/10.1038/s41584-020-0372-x] [PMID: 32034323]
[9]
Golden EB, Cho HY, Hofman FM, Louie SG, Schönthal AH, Chen TC. Quinoline-based antimalarial drugs: a novel class of autophagy inhibitors. Neurosurg Focus 2015; 38(3) E12
[http://dx.doi.org/10.3171/2014.12.FOCUS14748] [PMID: 25727221]
[10]
Yeo SJ, Liu DX, Kim HS, Park H. Anti-malarial effect of novel chloroquine derivatives as agents for the treatment of malaria. Malar J 2017; 16(1): 80.
[http://dx.doi.org/10.1186/s12936-017-1725-z] [PMID: 28212631]
[11]
Sáenz FE, Mutka T, Udenze K, Oduola AM, Kyle DE. Novel 4-aminoquinoline analogs highly active against the blood and sexual stages of Plasmodium in vivo and in vitro. Antimicrob Agents Chemother 2012; 56(9): 4685-92.
[http://dx.doi.org/10.1128/AAC.01061-12] [PMID: 22710117]
[12]
Hu C, Lu L, Wan JP, Wen C. The Pharmacological Mechanisms and Therapeutic Activities of Hydroxychloroquine in Rheumatic and Related Diseases. Curr Med Chem 2017; 24(20): 2241-9.
[http://dx.doi.org/10.2174/0929867324666170316115938] [PMID: 28302011]
[13]
Rainsford KD, Parke AL, Clifford-Rashotte M, Kean WF. Therapy and pharmacological properties of hydroxychloroquine and chloroquine in treatment of systemic lupus erythematosus, rheumatoid arthritis and related diseases. Inflammopharmacology 2015; 23(5): 231-69.
[http://dx.doi.org/10.1007/s10787-015-0239-y] [PMID: 26246395]
[14]
Charris JE, Monasterios MC, Acosta ME, et al. Antimalarial antiproliferative and apoptotic activity of quinoline-chalcone and quinoline-pyrazoline hybrids. A dual action. Med Chem Res 2019; 28: 2050-66.
[http://dx.doi.org/10.1007/s00044-019-02435-0]
[15]
Ramirez H, Rodrigues JR, Mijares MR, De Sanctis JB, Jaime E. Charris. Synthesis and biological activity of 2-[2-(7-chloroquinolin-4-ylthio)-4-methylthiazol-5-yl]-N-phenylacetamide derivatives as antimalarial and cytotoxic agents. J Chem Res 2020; 44(5-6): 305-14.
[http://dx.doi.org/10.1177/1747519819899073]
[16]
Romero JA, Acosta ME, Gamboa ND, Mijares MR, De Sanctis JB, Charris JE. Optimization of antimalarial, and anticancer activities of (E)-methyl 2-(7-chloroquinolin-4-ylthio)-3-(4-hydroxyphenyl) acrylate. Bioorg Med Chem 2018; 26(4): 815-23.
[http://dx.doi.org/10.1016/j.bmc.2017.12.022] [PMID: 29398445]
[17]
Lin YC, Lin JF, Wen SI, et al. Chloroquine and hydroxychloroquine inhibit bladder cancer cell growth by targeting basal autophagy and enhancing apoptosis. Kaohsiung J Med Sci 2017; 33(5): 215-23.
[http://dx.doi.org/10.1016/j.kjms.2017.01.004] [PMID: 28433067]
[18]
Ponticelli C, Moroni G. Hydroxychloroquine in systemic lupus erythematosus (SLE). Expert Opin Drug Saf 2017; 16(3): 411-9.
[http://dx.doi.org/10.1080/14740338.2017.1269168] [PMID: 27927040]
[19]
Plantone D, Koudriavtseva T. Current and Future Use of Chloroquine and Hydroxychloroquine in Infectious, Immune, Neoplastic, and Neurological Diseases: A Mini-Review. Clin Drug Investig 2018; 38(8): 653-71.
[http://dx.doi.org/10.1007/s40261-018-0656-y] [PMID: 29737455]
[20]
Al-Bari MA. Chloroquine analogues in drug discovery: new directions of uses, mechanisms of actions and toxic manifestations from malaria to multifarious diseases. J Antimicrob Chemother 2015; 70(6): 1608-21.
[http://dx.doi.org/10.1093/jac/dkv018] [PMID: 25693996]
[21]
Pasquier B. Autophagy inhibitors. Cell Mol Life Sci 2016; 73(5): 985-1001.
[http://dx.doi.org/10.1007/s00018-015-2104-y] [PMID: 26658914]
[22]
Mindell JA. Lysosomal acidification mechanisms. Annu Rev Physiol 2012; 74: 69-86.
[http://dx.doi.org/10.1146/annurev-physiol-012110-142317] [PMID: 22335796]
[23]
Fitzgerald KA, Kagan JC. Toll-like Receptors and the Control of Immunity. Cell 2020; 180(6): 1044-66.
[http://dx.doi.org/10.1016/j.cell.2020.02.041] [PMID: 32164908]
[24]
Chen JQ, Szodoray P, Zeher M. Toll-Like Receptor Pathways in Autoimmune Diseases. Clin Rev Allergy Immunol 2016; 50(1): 1-17.
[http://dx.doi.org/10.1007/s12016-015-8473-z] [PMID: 25687121]
[25]
Frasca L, Lande R. Toll-like receptors in mediating pathogenesis in systemic sclerosis. Clin Exp Immunol 2020; 201(1): 14-24.
[http://dx.doi.org/10.1111/cei.13426] [PMID: 32048277]
[26]
Kawasaki T, Kawai T. Toll-like receptor signaling pathways. Front Immunol 2014; 5: 461.
[http://dx.doi.org/10.3389/fimmu.2014.00461] [PMID: 25309543]
[27]
Kuznik A, Bencina M, Svajger U, Jeras M, Rozman B, Jerala R. Mechanism of endosomal TLR inhibition by antimalarial drugs and imidazoquinolines. J Immunol 2011; 186(8): 4794-804.
[http://dx.doi.org/10.4049/jimmunol.1000702] [PMID: 21398612]
[28]
Lamphier M, Zheng W, Latz E, et al. Novel small molecule inhibitors of TLR7 and TLR9: mechanism of action and efficacy in vivo. Mol Pharmacol 2014; 85(3): 429-40.
[http://dx.doi.org/10.1124/mol.113.089821] [PMID: 24342772]
[29]
Clancy RM, Markham AJ, Buyon JP. Endosomal Toll-like receptors in clinically overt and silent autoimmunity. Immunol Rev 2016; 269(1): 76-84.
[http://dx.doi.org/10.1111/imr.12383] [PMID: 26683146]
[30]
Salvi V, Gianello V, Busatto S, et al. Exosome-delivered microRNAs promote IFN-α secretion by human plasmacytoid DCs via TLR7. JCI Insight 2018; 3(10): 98204.
[http://dx.doi.org/10.1172/jci.insight.98204] [PMID: 29769437]
[31]
Biermann MH, Veissi S, Maueröder C, et al. The role of dead cell clearance in the etiology and pathogenesis of systemic lupus erythematosus: dendritic cells as potential targets. Expert Rev Clin Immunol 2014; 10(9): 1151-64.
[http://dx.doi.org/10.1586/1744666X.2014.944162] [PMID: 25081199]
[32]
Farrugia M, Baron B. The Role of Toll-Like Receptors in Autoimmune Diseases through Failure of the Self-Recognition Mechanism. Int J Inflamm 2017. 20178391230
[http://dx.doi.org/10.1155/2017/8391230] [PMID: 28553556]
[33]
Thwaites R, Chamberlain G, Sacre S. Emerging role of endosomal toll-like receptors in rheumatoid arthritis. Front Immunol 2014; 5: 1.
[http://dx.doi.org/10.3389/fimmu.2014.00001] [PMID: 24474949]
[34]
Torigoe M, Sakata K, Ishii A, Iwata S, Nakayamada S, Tanaka Y. Hydroxychloroquine efficiently suppresses inflammatory responses of human class-switched memory B cells via Toll-like receptor 9 inhibition. Clin Immunol 2018; 195: 1-7.
[http://dx.doi.org/10.1016/j.clim.2018.07.003] [PMID: 29981383]
[35]
Sacre SM, Lo A, Gregory B, et al. Inhibitors of TLR8 reduce TNF production from human rheumatoid synovial membrane cultures. J Immunol 2008; 181(11): 8002-9.
[http://dx.doi.org/10.4049/jimmunol.181.11.8002] [PMID: 19017992]
[36]
Janas T, Janas MM, Sapoń K, Janas T. Mechanisms of RNA loading into exosomes. FEBS Lett 2015; 589(13): 1391-8.
[http://dx.doi.org/10.1016/j.febslet.2015.04.036] [PMID: 25937124]
[37]
Greening DW, Gopal SK, Xu R, Simpson RJ, Chen W. Exosomes and their roles in immune regulation and cancer. Semin Cell Dev Biol 2015; 40: 72-81.
[http://dx.doi.org/10.1016/j.semcdb.2015.02.009] [PMID: 25724562]
[38]
Chan BD, Wong WY, Lee MM, et al. Exosomes in Inflammation and Inflammatory Disease. Proteomics 2019; 19(8) e1800149
[http://dx.doi.org/10.1002/pmic.201800149] [PMID: 30758141]
[39]
Hough KP, Deshane JS. Exosomes in Allergic Airway Diseases. Curr Allergy Asthma Rep 2019; 19(5): 26.
[http://dx.doi.org/10.1007/s11882-019-0857-3] [PMID: 30903454]
[40]
Li Z, Wang Y, Xiao K, Xiang S, Li Z, Weng X. Emerging Role of Exosomes in the Joint Diseases. Cell Physiol Biochem 2018; 47(5): 2008-17.
[http://dx.doi.org/10.1159/000491469] [PMID: 29969758]
[41]
Hessvik NP, Llorente A. Current knowledge on exosome biogenesis and release. Cell Mol Life Sci 2018; 75(2): 193-208.
[http://dx.doi.org/10.1007/s00018-017-2595-9] [PMID: 28733901]
[42]
Mortaz E, Alipoor SD, Varahram M, et al. Exosomes in Severe Asthma: Update in Their Roles and Potential in Therapy. BioMed Res Int 2018. 20182862187
[http://dx.doi.org/10.1155/2018/2862187] [PMID: 29854739]
[43]
Selmaj I, Mycko MP, Raine CS, Selmaj KW. The role of exosomes in CNS inflammation and their involvement in multiple sclerosis. J Neuroimmunol 2017; 306: 1-10.
[http://dx.doi.org/10.1016/j.jneuroim.2017.02.002] [PMID: 28385180]
[44]
Lee JY, Park JK, Lee EY, Lee EB, Song YW. Circulating exosomes from patients with systemic lupus erythematosus induce an proinflammatory immune response. Arthritis Res Ther 2016; 18(1): 264.
[http://dx.doi.org/10.1186/s13075-016-1159-y] [PMID: 27852323]
[45]
Ye W, Tang X, Yang Z, et al. Plasma-derived exosomes contribute to inflammation via the TLR9-NF-κB pathway in chronic heart failure patients. Mol Immunol 2017; 87: 114-21.
[http://dx.doi.org/10.1016/j.molimm.2017.03.011] [PMID: 28433888]
[46]
Mobergslien A, Sioud M. Exosome-derived miRNAs and cellular miRNAs activate innate immunity. J Innate Immun 2014; 6(1): 105-10.
[http://dx.doi.org/10.1159/000351460] [PMID: 23774807]
[47]
Dong Y, Lin Y, Gao X, et al. Targeted blocking of miR328 lysosomal degradation with alkalized exosomes sensitizes the chronic leukemia cells to imatinib. Appl Microbiol Biotechnol 2019; 103(23-24): 9569-82.
[http://dx.doi.org/10.1007/s00253-019-10127-3] [PMID: 31701195]
[48]
Dikic I, Elazar Z. Mechanism and medical implications of mammalian autophagy. Nat Rev Mol Cell Biol 2018; 19(6): 349-64.
[http://dx.doi.org/10.1038/s41580-018-0003-4] [PMID: 29618831]
[49]
Nakamura S, Yoshimori T. New insights into autophagosome-lysosome fusion. J Cell Sci 2017; 130(7): 1209-16.
[http://dx.doi.org/10.1242/jcs.196352] [PMID: 28302910]
[50]
Abada A, Elazar Z. Getting ready for building: signaling and autophagosome biogenesis. EMBO Rep 2014; 15(8): 839-52.
[http://dx.doi.org/10.15252/embr.201439076] [PMID: 25027988]
[51]
Li W, Zhang L. Regulation of ATG and Autophagy Initiation. Adv Exp Med Biol 2019; 1206: 41-65.
[http://dx.doi.org/10.1007/978-981-15-0602-4_2] [PMID: 31776979]
[52]
Mizushima N, Yoshimori T, Ohsumi Y. The role of Atg proteins in autophagosome formation. Annu Rev Cell Dev Biol 2011; 27: 107-32.
[http://dx.doi.org/10.1146/annurev-cellbio-092910-154005] [PMID: 21801009]
[53]
Fenouille N, Nascimbeni AC, Botti-Millet J, Dupont N, Morel E, Codogno P. To be or not to be cell autonomous? Autophagy says both. Essays Biochem 2017; 61(6): 649-61.
[http://dx.doi.org/10.1042/EBC20170025] [PMID: 29233875]
[54]
Mizushima N. The ATG conjugation systems in autophagy. Curr Opin Cell Biol 2020; 63: 1-10.
[http://dx.doi.org/10.1016/j.ceb.2019.12.001] [PMID: 31901645]
[55]
Bednarczyk M, Zmarzły N, Grabarek B, Mazurek U, Muc-Wierzgoń M. Genes involved in the regulation of different types of autophagy and their participation in cancer pathogenesis. Oncotarget 2018; 9(76): 34413-28.
[http://dx.doi.org/10.18632/oncotarget.26126] [PMID: 30344951]
[56]
Carlsson SR, Simonsen A. Membrane dynamics in autophagosome biogenesis. J Cell Sci 2015; 128(2): 193-205.
[http://dx.doi.org/10.1242/jcs.141036] [PMID: 25568151]
[57]
Zhan L, Li J, Wei B. Autophagy therapeutics: preclinical basis and initial clinical studies. Cancer Chemother Pharmacol 2018; 82(6): 923-34.
[http://dx.doi.org/10.1007/s00280-018-3688-3] [PMID: 30225602]
[58]
Levy JMM, Towers CG, Thorburn A. Targeting autophagy in cancer. Nat Rev Cancer 2017; 17(9): 528-42.
[http://dx.doi.org/10.1038/nrc.2017.53] [PMID: 28751651]
[59]
White E, Mehnert JM, Chan CS. Autophagy, metabolism and cancer. Clin Cancer Res 2015; 21(22): 5037-46.
[http://dx.doi.org/10.1158/1078-0432.CCR-15-0490] [PMID: 26567363]
[60]
Yuan N, Song L, Lin W, et al. Autophagy collaborates with ubiquitination to downregulate oncoprotein E2A/Pbx1 in B-cell acute lymphoblastic leukemia. Blood Cancer J 2015; 5(1) e274
[http://dx.doi.org/10.1038/bcj.2014.96] [PMID: 25615280]
[61]
Liu R, Li J, Zhang T, et al. Itraconazole suppresses the growth of glioblastoma through induction of autophagy: involvement of abnormal cholesterol trafficking. Autophagy 2014; 10(7): 1241-55.
[http://dx.doi.org/10.4161/auto.28912] [PMID: 24905460]
[62]
Dong LH, Cheng S, Zheng Z, et al. Histone deacetylase inhibitor potentiated the ability of MTOR inhibitor to induce autophagic cell death in Burkitt leukemia/lymphoma. J Hematol Oncol 2013; 6: 53.
[http://dx.doi.org/10.1186/1756-8722-6-53] [PMID: 23866964]
[63]
Yuk JM, Shin DM, Song KS, et al. Bacillus calmette-guerin cell wall cytoskeleton enhances colon cancer radiosensitivity through autophagy. Autophagy 2010; 6(1): 46-60.
[http://dx.doi.org/10.4161/auto.6.1.10325] [PMID: 19901560]
[64]
Noman MZ, Janji B, Kaminska B, et al. Blocking hypoxia-induced autophagy in tumors restores cytotoxic T-cell activity and promotes regression. Cancer Res 2011; 71(18): 5976-86.
[http://dx.doi.org/10.1158/0008-5472.CAN-11-1094] [PMID: 21810913]
[65]
Perillo B, Di Donato M, Pezone A, et al. ROS in cancer therapy: the bright side of the moon. Exp Mol Med 2020; 52(2): 192-203.
[http://dx.doi.org/10.1038/s12276-020-0384-2] [PMID: 32060354]
[66]
Yang B, Chen Y, Shi J. Reactive Oxygen Species (ROS)-Based Nanomedicine. Chem Rev 2019; 119(8): 4881-985.
[http://dx.doi.org/10.1021/acs.chemrev.8b00626] [PMID: 30973011]
[67]
Yang B, Ding L, Yao H, Chen Y, Shi J. A Metal-Organic Framework (MOF) Fenton Nanoagent-Enabled Nanocatalytic Cancer Therapy in Synergy with Autophagy Inhibition. Adv Mater 2020; 32(12) e1907152
[http://dx.doi.org/10.1002/adma.201907152] [PMID: 32053261]
[68]
Maiuri MC, Zalckvar E, Kimchi A, Kroemer G. Self-eating and self-killing: crosstalk between autophagy and apoptosis. Nat Rev Mol Cell Biol 2007; 8(9): 741-52.
[http://dx.doi.org/10.1038/nrm2239] [PMID: 17717517]
[69]
Xu HD, Qin ZH. Beclin-1, Bcl-2 and autophagy. Adv Exp Med Biol 2019; 1206: 109-26.
[http://dx.doi.org/10.1007/978-981-15-0602-4_5] [PMID: 31776982]
[70]
D’Arcy MS. Cell death: a review of the major forms of apoptosis, necrosis and autophagy. Cell Biol Int 2019; 43(6): 582-92.
[http://dx.doi.org/10.1002/cbin.11137] [PMID: 30958602]
[71]
Moldoveanu T, Czabotar PE. BAX, BAK, and BOK: A Coming of Age for the BCL-2 Family Effector Proteins. Cold Spring Harb Perspect Biol 2020; 12(4) a036319
[http://dx.doi.org/10.1101/cshperspect.a036319] [PMID: 31570337]
[72]
Luo S, Rubinsztein DC. Apoptosis blocks Beclin 1-dependent autophagosome synthesis: an effect rescued by Bcl-xL. Cell Death Differ 2010; 17(2): 268-77.
[http://dx.doi.org/10.1038/cdd.2009.121] [PMID: 19713971]
[73]
Maji AK. Drug susceptibility testing methods of antimalarial agents. Trop Parasitol 2018; 8(2): 70-6.
[http://dx.doi.org/10.4103/2229-5070.248695] [PMID: 30693210]
[74]
Kim Y, Eom JI, Jeung HK, et al. Induction of cytosine arabinoside-resistant human myeloid leukemia cell death through autophagy regulation by hydroxychloroquine. Biomed Pharmacother 2015; 73: 87-96.
[http://dx.doi.org/10.1016/j.biopha.2015.05.012] [PMID: 26211587]
[75]
Li X, Han Y, Sun E. Sniping the scout: Targeting the key molecules in dendritic cell functions for treatment of autoimmune diseases. Pharmacol Res 2016; 107: 27-41.
[http://dx.doi.org/10.1016/j.phrs.2016.02.023] [PMID: 26931618]
[76]
Flórez-Grau G, Zubizarreta I, Cabezón R, Villoslada P, Benitez-Ribas D. Tolerogenic Dendritic Cells as a Promising Antigen-Specific Therapy in the Treatment of Multiple Sclerosis and Neuromyelitis Optica From Preclinical to Clinical Trials. Front Immunol 2018; 9: 1169.
[http://dx.doi.org/10.3389/fimmu.2018.01169] [PMID: 29904379]
[77]
Thome R, Bonfanti AP, Rasouli J, et al. Chloroquine-treated dendritic cells require STAT1 signaling for their tolerogenic activity. Eur J Immunol 2018; 48(7): 1228-34.
[http://dx.doi.org/10.1002/eji.201747362] [PMID: 29572810]
[78]
Guidos C, Wong M, Lee KC. A comparison of the stimulatory activities of lymphoid dendritic cells and macrophages in T proliferative responses to various antigens. J Immunol 1984; 133(3): 1179-84.
[PMID: 6235282]
[79]
Lee KC, Wong M, Spitzer D. Chloroquine as a probe for antigen processing by accessory cells. Transplantation 1982; 34(3): 150-3.
[http://dx.doi.org/10.1097/00007890-198209000-00008] [PMID: 6982546]
[80]
Lombard-Platlet S, Bertolino P, Deng H, Gerlier D, Rabourdin-Combe C. Inhibition by chloroquine of the class II major histocompatibility complex-restricted presentation of endogenous antigens varies according to the cellular origin of the antigen-presenting cells, the nature of the T-cell epitope, and the responding T cell. Immunology 1993; 80(4): 566-73.
[PMID: 7508420]
[81]
Ziegler HK, Unanue ER. Decrease in macrophage antigen catabolism caused by ammonia and chloroquine is associated with inhibition of antigen presentation to T cells. Proc Natl Acad Sci USA 1982; 79(1): 175-8.
[http://dx.doi.org/10.1073/pnas.79.1.175] [PMID: 6798568]
[82]
Accapezzato D, Visco V, Francavilla V, et al. Chloroquine enhances human CD8+ T cell responses against soluble antigens in vivo. J Exp Med 2005; 202(6): 817-28.
[http://dx.doi.org/10.1084/jem.20051106] [PMID: 16157687]
[83]
Garulli B, Stillitano MG, Barnaba V, Castrucci MR. Primary CD8+ T-cell response to soluble ovalbumin is improved by chloroquine treatment in vivo. Clin Vaccine Immunol 2008; 15(10): 1497-504.
[http://dx.doi.org/10.1128/CVI.00166-08] [PMID: 18753338]
[84]
Thomé R, Issayama LK, DiGangi R, et al. Dendritic cells treated with chloroquine modulate experimental autoimmune encephalomyelitis. Immunol Cell Biol 2014; 92(2): 124-32.
[http://dx.doi.org/10.1038/icb.2013.73] [PMID: 24217811]
[85]
Verinaud L, Issayama LK, Zanucoli F, et al. Nitric oxide plays a key role in the suppressive activity of tolerogenic dendritic cells. Cell Mol Immunol 2015; 12(3): 384-6.
[http://dx.doi.org/10.1038/cmi.2014.94] [PMID: 25308751]
[86]
Thomé R, Moraes AS, Bombeiro AL, et al. Chloroquine treatment enhances regulatory T cells and reduces the severity of experimental autoimmune encephalomyelitis. PLoS One 2013; 8(6) e65913
[http://dx.doi.org/10.1371/journal.pone.0065913] [PMID: 23799062]
[87]
Bhattacharya A, Parillon X, Zeng S, Han S, Eissa NT. Deficiency of autophagy in dendritic cells protects against experimental autoimmune encephalomyelitis. J Biol Chem 2014; 289(38): 26525-32.
[http://dx.doi.org/10.1074/jbc.M114.575860] [PMID: 25077962]
[88]
Rönnblom L, Alm GV. A pivotal role for the natural interferon alpha-producing cells (plasmacytoid dendritic cells) in the pathogenesis of lupus. J Exp Med 2001; 194(12): F59-63.
[http://dx.doi.org/10.1084/jem.194.12.f59] [PMID: 11748288]
[89]
Kadowaki N, Ho S, Antonenko S, et al. Subsets of human dendritic cell precursors express different toll-like receptors and respond to different microbial antigens. J Exp Med 2001; 194(6): 863-9.
[http://dx.doi.org/10.1084/jem.194.6.863] [PMID: 11561001]
[90]
Means TK, Latz E, Hayashi F, Murali MR, Golenbock DT, Luster AD. Human lupus autoantibody-DNA complexes activate DCs through cooperation of CD32 and TLR9. J Clin Invest 2005; 115(2): 407-17.
[http://dx.doi.org/10.1172/JCI23025] [PMID: 15668740]
[91]
Sacre K, Criswell LA, McCune JM. Hydroxychloroquine is associated with impaired interferon-alpha and tumor necrosis factor-alpha production by plasmacytoid dendritic cells in systemic lupus erythematosus. Arthritis Res Ther 2012; 14(3): R155.
[http://dx.doi.org/10.1186/ar3895] [PMID: 22734582]
[92]
Wozniacka A, Lesiak A, Narbutt J, Kobos J, Pavel S, Sysa-Jedrzejowska A. Chloroquine treatment reduces the number of cutaneous HLA-DR+ and CD1a+ cells in patients with systemic lupus erythematosus. Lupus 2007; 16(2): 89-94.
[http://dx.doi.org/10.1177/0961203306075384] [PMID: 17402364]
[93]
Siouti E, Andreakos E. The many facets of macrophages in rheumatoid arthritis. Biochem Pharmacol 2019; 165: 152-69.
[http://dx.doi.org/10.1016/j.bcp.2019.03.029] [PMID: 30910693]
[94]
Cohen EM, D’Silva K, Kreps D, Son MB, Costenbader KH. Arthritis and use of hydroxychloroquine associated with a decreased risk of macrophage activation syndrome among adult patients hospitalized with systemic lupus erythematosus. Lupus 2018; 27(7): 1065-71.
[http://dx.doi.org/10.1177/0961203318759428] [PMID: 29451069]
[95]
Fox RI. Mechanism of action of hydroxychloroquine as an antirheumatic drug. Semin Arthritis Rheum 1993; 23(2)(Suppl. 1): 82-91.
[http://dx.doi.org/10.1016/S0049-0172(10)80012-5] [PMID: 8278823]
[96]
Jeong JY, Jue DM. Chloroquine inhibits processing of tumor necrosis factor in lipopolysaccharide-stimulated RAW 264.7 macrophages. J Immunol 1997; 158(10): 4901-7.
[PMID: 9144507]
[97]
Bondeson J, Sundler R. Antimalarial drugs inhibit phospholipase A2 activation and induction of interleukin 1beta and tumor necrosis factor alpha in macrophages: implications for their mode of action in rheumatoid arthritis. Gen Pharmacol 1998; 30(3): 357-66.
[http://dx.doi.org/10.1016/S0306-3623(97)00269-3] [PMID: 9510087]
[98]
Park YC, Pae HO, Yoo JC, Choi BM, Jue DM, Chung HT. Chloroquine inhibits inducible nitric oxide synthase expression in murine peritoneal macrophages. Pharmacol Toxicol 1999; 85(4): 188-91.
[http://dx.doi.org/10.1111/j.1600-0773.1999.tb00090.x] [PMID: 10563518]
[99]
Fox RI, Kang HI. Mechanism of action of antimalarial drugs: inhibition of antigen processing and presentation. Lupus 1993; 2(Suppl. 1): S9-S12.
[http://dx.doi.org/10.1177/0961203393002001031] [PMID: 8097945]
[100]
Jang CH, Choi JH, Byun MS, Jue DM. Chloroquine inhibits production of TNF-alpha, IL-1beta and IL-6 from lipopolysaccharide-stimulated human monocytes/macrophages by different modes. Rheumatology (Oxford) 2006; 45(6): 703-10.
[http://dx.doi.org/10.1093/rheumatology/kei282] [PMID: 16418198]
[101]
Yang M, Cao L, Xie M, et al. Chloroquine inhibits HMGB1 inflammatory signaling and protects mice from lethal sepsis. Biochem Pharmacol 2013; 86(3): 410-8.
[http://dx.doi.org/10.1016/j.bcp.2013.05.013] [PMID: 23707973]
[102]
Weber SM, Levitz SM. Chloroquine antagonizes the proinflammatory cytokine response to opportunistic fungi by alkalizing the fungal phagolysosome. J Infect Dis 2001; 183(6): 935-42.
[http://dx.doi.org/10.1086/319259] [PMID: 11237811]
[103]
Karres I, Kremer JP, Dietl I, Steckholzer U, Jochum M, Ertel W. Chloroquine inhibits proinflammatory cytokine release into human whole blood. Am J Physiol 1998; 274(4): R1058-64.
[PMID: 9575969]
[104]
Ding C, Li F, Long Y, Zheng J. Chloroquine attenuates lipopolysaccharide-induced inflammatory responses through upregulation of USP25. Can J Physiol Pharmacol 2017; 95(5): 481-91.
[http://dx.doi.org/10.1139/cjpp-2016-0303] [PMID: 28134560]
[105]
Bhalekar MR, Upadhaya PG, Madgulkar AR. Fabrication and efficacy evaluation of chloroquine nanoparticles in CFA-induced arthritic rats using TNF-α ELISA. Eur J Pharm Sci 2016; 84: 1-8.
[http://dx.doi.org/10.1016/j.ejps.2016.01.009] [PMID: 26776969]
[106]
Guo C, Fu R, Wang S, et al. NLRP3 inflammasome activation contributes to the pathogenesis of rheumatoid arthritis. Clin Exp Immunol 2018; 194(2): 231-43.
[http://dx.doi.org/10.1111/cei.13167] [PMID: 30277570]
[107]
Shen HH, Yang YX, Meng X, et al. NLRP3: A promising therapeutic target for autoimmune diseases. Autoimmun Rev 2018; 17(7): 694-702.
[http://dx.doi.org/10.1016/j.autrev.2018.01.020] [PMID: 29729449]
[108]
Tang TT, Lv LL, Pan MM, et al. Hydroxychloroquine attenuates renal ischemia/reperfusion injury by inhibiting cathepsin mediated NLRP3 inflammasome activation. Cell Death Dis 2018; 9(3): 351.
[http://dx.doi.org/10.1038/s41419-018-0378-3] [PMID: 29500339]
[109]
Chen X, Wang N, Zhu Y, Lu Y, Liu X, Zheng J. The Antimalarial Chloroquine Suppresses LPS-Induced NLRP3 Inflammasome Activation and Confers Protection against Murine Endotoxic Shock. Mediators Inflamm 2017. 20176543237
[http://dx.doi.org/10.1155/2017/6543237] [PMID: 28321151]
[110]
Eugenia Schroeder M, Russo S, Costa C, et al. Pro-inflammatory Ca++-activated K+ channels are inhibited by hydroxychloroquine. Sci Rep 2017; 7(1): 1892.
[http://dx.doi.org/10.1038/s41598-017-01836-8] [PMID: 28507328]
[111]
Misra UK, Gawdi G, Pizzo SV. Chloroquine, quinine and quinidine inhibit calcium release from macrophage intracellular stores by blocking inositol 1,4,5-trisphosphate binding to its receptor. J Cell Biochem 1997; 64(2): 225-32.
[http://dx.doi.org/10.1002/(SICI)1097-4644(199702)64:2<225:AID-JCB6>3.0.CO;2-Z] [PMID: 9027583]
[112]
Kopeć-Mędrek M, Widuchowska M, Kucharz EJ. Calprotectin in rheumatic diseases: a review. Reumatologia 2016; 54(6): 306-9.
[http://dx.doi.org/10.5114/reum.2016.64907] [PMID: 28115781]
[113]
Wakiya R, Kameda T, Ueeda K, et al. Hydroxychloroquine modulates elevated expression of S100 proteins in systemic lupus erythematosus. Lupus 2019; 28(7): 826-33.
[http://dx.doi.org/10.1177/0961203319846391] [PMID: 31068068]
[114]
Riva M, Källberg E, Björk P, et al. Induction of nuclear factor-κB responses by the S100A9 protein is Toll-like receptor-4-dependent. Immunology 2012; 137(2): 172-82.
[http://dx.doi.org/10.1111/j.1365-2567.2012.03619.x] [PMID: 22804476]
[115]
Šumová B, Cerezo LA, Szczuková L, et al. Circulating S100 proteins effectively discriminate SLE patients from healthy controls: a cross-sectional study. Rheumatol Int 2019; 39(3): 469-78.
[http://dx.doi.org/10.1007/s00296-018-4190-2] [PMID: 30392117]
[116]
Ngabire D, Kim GD. Autophagy and Inflammatory Response in the Tumor Microenvironment. Int J Mol Sci 2017; 18(9): 2016.
[http://dx.doi.org/10.3390/ijms18092016] [PMID: 28930154]
[117]
De Palma M, Lewis CE. Macrophage regulation of tumor responses to anticancer therapies. Cancer Cell 2013; 23(3): 277-86.
[http://dx.doi.org/10.1016/j.ccr.2013.02.013] [PMID: 23518347]
[118]
Li R, Zhou R, Wang H, et al. Gut microbiota-stimulated cathepsin K secretion mediates TLR4-dependent M2 macrophage polarization and promotes tumor metastasis in colorectal cancer. Cell Death Differ 2019; 26(11): 2447-63.
[http://dx.doi.org/10.1038/s41418-019-0312-y] [PMID: 30850734]
[119]
Guo Y, Feng Y, Cui X, Wang Q, Pan X. Autophagy inhibition induces the repolarisation of tumour-associated macrophages and enhances chemosensitivity of laryngeal cancer cells to cisplatin in mice. Cancer Immunol Immunother 2019; 68(12): 1909-20.
[http://dx.doi.org/10.1007/s00262-019-02415-8] [PMID: 31641796]
[120]
Chen D, Xie J, Fiskesund R, et al. Chloroquine modulates antitumor immune response by resetting tumor-associated macrophages toward M1 phenotype. Nat Commun 2018; 9(1): 873.
[http://dx.doi.org/10.1038/s41467-018-03225-9] [PMID: 29491374]
[121]
Li Y, Cao F, Li M, et al. Hydroxychloroquine induced lung cancer suppression by enhancing chemo-sensitization and promoting the transition of M2-TAMs to M1-like macrophages. J Exp Clin Cancer Res 2018; 37(1): 259.
[http://dx.doi.org/10.1186/s13046-018-0938-5] [PMID: 30373678]
[122]
Amulic B, Cazalet C, Hayes GL, Metzler KD, Zychlinsky A. Neutrophil function: from mechanisms to disease. Annu Rev Immunol 2012; 30: 459-89.
[http://dx.doi.org/10.1146/annurev-immunol-020711-074942] [PMID: 22224774]
[123]
Kaplan MJ. Neutrophils in the pathogenesis and manifestations of SLE. Nat Rev Rheumatol 2011; 7(12): 691-9.
[http://dx.doi.org/10.1038/nrrheum.2011.132] [PMID: 21947176]
[124]
Labro MT, Babin-Chevaye C. Effects of amodiaquine, chloroquine, and mefloquine on human polymorphonuclear neutrophil function in vitro. Antimicrob Agents Chemother 1988; 32(8): 1124-30.
[http://dx.doi.org/10.1128/AAC.32.8.1124] [PMID: 3263835]
[125]
Hurst NP, French JK, Gorjatschko L, Betts WH. Studies on the mechanism of inhibition of chemotactic tripeptide stimulated human neutrophil polymorphonuclear leucocyte superoxide production by chloroquine and hydroxychloroquine. Ann Rheum Dis 1987; 46(10): 750-6.
[http://dx.doi.org/10.1136/ard.46.10.750] [PMID: 2825613]
[126]
Doherty NS, Dinerstein RJ, Mehdi S. Novel inhibitors of polymorphonuclear neutrophil (PMN) elastase and cathepsin G: evaluation in vitro of their potential for the treatment of inflammatory connective tissue damage. Int J Immunopharmacol 1990; 12(7): 787-95.
[http://dx.doi.org/10.1016/0192-0561(90)90043-M] [PMID: 2292460]
[127]
Jančinová V, Pažoureková S, Lucová M, et al. Selective inhibition of extracellular oxidants liberated from human neutrophils-A new mechanism potentially involved in the anti-inflammatory activity of hydroxychloroquine. Int Immunopharmacol 2015; 28(1): 175-81.
[http://dx.doi.org/10.1016/j.intimp.2015.05.048] [PMID: 26071217]
[128]
Jourde-Chiche N, Whalen E, Gondouin B, et al. Modular transcriptional repertoire analyses identify a blood neutrophil signature as a candidate biomarker for lupus nephritis. Rheumatology (Oxford) 2017; 56(3): 477-87.
[PMID: 28031441]
[129]
Nishi H, Mayadas TN. Neutrophils in lupus nephritis. Curr Opin Rheumatol 2019; 31(2): 193-200.
[http://dx.doi.org/10.1097/BOR.0000000000000577] [PMID: 30540580]
[130]
Bonegio RG, Lin JD, Beaudette-Zlatanova B, York MR, Menn-Josephy H, Yasuda K. Lupus-Associated Immune Complexes Activate Human Neutrophils in an FcγRIIA-Dependent but TLR-Independent Response. J Immunol 2019; 202(3): 675-83.
[http://dx.doi.org/10.4049/jimmunol.1800300] [PMID: 30610165]
[131]
Camicia G, de Larrañaga G. Trampas extracelulares de neutrófilos: un mecanismo de defensa con dos caras. Med Clin (Barc) 2013; 140(2): 70-5. [Neutrophil extracellular traps: a 2-faced host defense mechanism
[http://dx.doi.org/10.1016/j.medcli.2012.04.022] [PMID: 22766060]
[132]
Boone BA, Murthy P, Miller-Ocuin J, et al. Chloroquine reduces hypercoagulability in pancreatic cancer through inhibition of neutrophil extracellular traps. BMC Cancer 2018; 18(1): 678.
[http://dx.doi.org/10.1186/s12885-018-4584-2] [PMID: 29929491]
[133]
Smith CK, Vivekanandan-Giri A, Tang C, et al. Neutrophil extracellular trap-derived enzymes oxidize high-density lipoprotein: an additional proatherogenic mechanism in systemic lupus erythematosus. Arthritis Rheumatol 2014; 66(9): 2532-44.
[http://dx.doi.org/10.1002/art.38703] [PMID: 24838349]
[134]
Murthy P, Singhi AD, Ross MA, et al. Enhanced Neutrophil Extracellular Trap Formation in Acute Pancreatitis Contributes to Disease Severity and Is Reduced by Chloroquine. Front Immunol 2019; 10: 28.
[http://dx.doi.org/10.3389/fimmu.2019.00028] [PMID: 30733719]
[135]
Li R, Lin H, Ye Y, et al. Attenuation of antimalarial agent hydroxychloroquine on TNF-α-induced endothelial inflammation. Int Immunopharmacol 2018; 63: 261-9.
[http://dx.doi.org/10.1016/j.intimp.2018.08.008] [PMID: 30121047]
[136]
Wu CH, Li KJ, Yu CL, Tsai CY, Hsieh SC. Sjögren’s Syndrome Antigen B Acts as an Endogenous Danger Molecule to Induce Interleukin-8 Gene Expression in Polymorphonuclear Neutrophils. PLoS One 2015; 10(4) e0125501
[http://dx.doi.org/10.1371/journal.pone.0125501] [PMID: 25915936]
[137]
Fujita Y, Matsuoka N, Temmoku J, et al. Hydroxychloroquine inhibits IL-1β production from amyloid-stimulated human neutrophils. Arthritis Res Ther 2019; 21(1): 250.
[http://dx.doi.org/10.1186/s13075-019-2040-6] [PMID: 31775905]
[138]
Hannah CE, Moye MS, Wanat KA, Liu V. Systemic lupus erythematosus-associated neutrophilic dermatosis manifesting as an acneiform eruption and foot pain. Clin Exp Dermatol 2019; 44(7): 801-3.
[http://dx.doi.org/10.1111/ced.13900] [PMID: 30610768]
[139]
Henriet SS, Jans J, Simonetti E, et al. Chloroquine modulates the fungal immune response in phagocytic cells from patients with chronic granulomatous disease. J Infect Dis 2013; 207(12): 1932-9.
[http://dx.doi.org/10.1093/infdis/jit103] [PMID: 23482646]
[140]
Hirahara K, Nakayama T. CD4+ T-cell subsets in inflammatory diseases: beyond the Th1/Th2 paradigm. Int Immunol 2016; 28(4): 163-71.
[http://dx.doi.org/10.1093/intimm/dxw006] [PMID: 26874355]
[141]
Raphael I, Nalawade S, Eagar TN, Forsthuber TG. T cell subsets and their signature cytokines in autoimmune and inflammatory diseases. Cytokine 2015; 74(1): 5-17.
[http://dx.doi.org/10.1016/j.cyto.2014.09.011] [PMID: 25458968]
[142]
Durcan L, Petri M. Immunomodulators in SLE: Clinical evidence and immunologic actions. J Autoimmun 2016; 74: 73-84.
[http://dx.doi.org/10.1016/j.jaut.2016.06.010] [PMID: 27371107]
[143]
Kotake S, Udagawa N, Takahashi N, et al. IL-17 in synovial fluids from patients with rheumatoid arthritis is a potent stimulator of osteoclastogenesis. J Clin Invest 1999; 103(9): 1345-52.
[http://dx.doi.org/10.1172/JCI5703] [PMID: 10225978]
[144]
Koenders MI, Lubberts E, Oppers-Walgreen B, et al. Blocking of interleukin-17 during reactivation of experimental arthritis prevents joint inflammation and bone erosion by decreasing RANKL and interleukin-1. Am J Pathol 2005; 167(1): 141-9.
[http://dx.doi.org/10.1016/S0002-9440(10)62961-6] [PMID: 15972960]
[145]
Jovanovic DV, Di Battista JA, Martel-Pelletier J, et al. IL-17 stimulates the production and expression of proinflammatory cytokines, IL-beta and TNF-alpha, by human macrophages. J Immunol 1998; 160(7): 3513-21.
[PMID: 9531313]
[146]
Yang J, Yang X, Yang J, Li M. hydroxychloroquine inhibits the differentiation of Th17 cells in systemic lupus erythematosus. J Rheumatol 2018; 45(6): 818-26.
[http://dx.doi.org/10.3899/jrheum.170737] [PMID: 29545450]
[147]
van den Borne BE, Dijkmans BA, de Rooij HH, le Cessie S, Verweij CL. Chloroquine and hydroxychloroquine equally affect tumor necrosis factor-alpha, interleukin 6, and interferon-gamma production by peripheral blood mononuclear cells. J Rheumatol 1997; 24(1): 55-60.
[PMID: 9002011]
[148]
Silva JC, Mariz HA, Rocha LF Jr, et al. Hydroxychloroquine decreases Th17-related cytokines in systemic lupus erythematosus and rheumatoid arthritis patients. Clinics (São Paulo) 2013; 68(6): 766-71.
[http://dx.doi.org/10.6061/clinics/2013(06)07] [PMID: 23778483]
[149]
Goldman FD, Gilman AL, Hollenback C, Kato RM, Premack BA, Rawlings DJ. Hydroxychloroquine inhibits calcium signals in T cells: a new mechanism to explain its immunomodulatory properties. Blood 2000; 95(11): 3460-6.
[http://dx.doi.org/10.1182/blood.V95.11.3460] [PMID: 10828029]
[150]
An N, Chen Y, Wang C, et al. Chloroquine Autophagic Inhibition Rebalances Th17/Treg-Mediated Immunity and Ameliorates Systemic Lupus Erythematosus. Cell Physiol Biochem 2017; 44(1): 412-22.
[http://dx.doi.org/10.1159/000484955] [PMID: 29141242]
[151]
Wen Z, Xu L, Xu W, Xiong S. Detection of dynamic frequencies of Th17 cells and their associations with clinical parameters in patients with systemic lupus erythematosus receiving standard therapy. Clin Rheumatol 2014; 33(10): 1451-8.
[http://dx.doi.org/10.1007/s10067-014-2656-5] [PMID: 24810699]
[152]
Hofmann K, Clauder AK, Manz RA, Targeting B, Targeting B. Cells and Plasma Cells in Autoimmune Diseases. Front Immunol 2018; 9: 835.
[http://dx.doi.org/10.3389/fimmu.2018.00835] [PMID: 29740441]
[153]
Sabatino JJ Jr, Pröbstel AK, Zamvil SS. B cells in autoimmune and neurodegenerative central nervous system diseases. Nat Rev Neurosci 2019; 20(12): 728-45. [published correction appears in Nat Rev Neurosci. 2020 Jan;21(1):56
[http://dx.doi.org/10.1038/s41583-019-0233-2] [PMID: 31712781]
[154]
Bugatti S, Vitolo B, Caporali R, Montecucco C, Manzo A. B cells in rheumatoid arthritis: from pathogenic players to disease biomarkers. BioMed Res Int 2014. 2014681678
[http://dx.doi.org/10.1155/2014/681678] [PMID: 24877127]
[155]
Dörner T, Giesecke C, Lipsky PE. Mechanisms of B cell autoimmunity in SLE. Arthritis Res Ther 2011; 13(5): 243.
[http://dx.doi.org/10.1186/ar3433] [PMID: 22078750]
[156]
Musette P, Bouaziz JD. B Cell Modulation Strategies in Autoimmune Diseases: New Concepts. Front Immunol 2018; 9: 622.
[http://dx.doi.org/10.3389/fimmu.2018.00622] [PMID: 29706952]
[157]
Hamilton JA, Hsu HC, Mountz JD. Autoreactive B cells in SLE, villains or innocent bystanders? Immunol Rev 2019; 292(1): 120-38.
[http://dx.doi.org/10.1111/imr.12815] [PMID: 31631359]
[158]
Nowell J, Quaranta V. Chloroquine affects biosynthesis of Ia molecules by inhibiting dissociation of invariant (gamma) chains from alpha-beta dimers in B cells. J Exp Med 1985; 162(4): 1371-6.
[http://dx.doi.org/10.1084/jem.162.4.1371] [PMID: 3930653]
[159]
Thorens B, Vassalli P. Chloroquine and ammonium chloride prevent terminal glycosylation of immunoglobulins in plasma cells without affecting secretion. Nature 1986; 321(6070): 618-20.
[http://dx.doi.org/10.1038/321618a0] [PMID: 3086747]
[160]
Becker HJ, Kondo E, Shimabukuro-Vornhagen A, Theurich S, von Bergwelt-Baildon MS. Processing and MHC class II presentation of exogenous soluble antigen involving a proteasome-dependent cytosolic pathway in CD40-activated B cells. Eur J Haematol 2016; 97(2): 166-74.
[http://dx.doi.org/10.1111/ejh.12699] [PMID: 26561366]
[161]
Leadbetter EA, Rifkin IR, Hohlbaum AM, Beaudette BC, Shlomchik MJ, Marshak-Rothstein A. Chromatin-IgG complexes activate B cells by dual engagement of IgM and Toll-like receptors. Nature 2002; 416(6881): 603-7.
[http://dx.doi.org/10.1038/416603a] [PMID: 11948342]
[162]
Yi AK, Peckham DW, Ashman RF, Krieg AM. CpG DNA rescues B cells from apoptosis by activating NFkappaB and preventing mitochondrial membrane potential disruption via a chloroquine-sensitive pathway. Int Immunol 1999; 11(12): 2015-24.
[http://dx.doi.org/10.1093/intimm/11.12.2015] [PMID: 10590267]
[163]
Wu YF, Zhao P, Luo X, et al. Chloroquine inhibits Ca2+ permeable ion channels-mediated Ca2+ signaling in primary B lymphocytes. Cell Biosci 2017; 7: 28.
[http://dx.doi.org/10.1186/s13578-017-0155-5] [PMID: 28546857]
[164]
Cepika AM, Soldo Jureša D, Morović Vergles J, et al. Decrease in circulating DNA, IL-10 and BAFF levels in newly-diagnosed SLE patients after corticosteroid and chloroquine treatment. Cell Immunol 2012; 276(1-2): 196-203.
[http://dx.doi.org/10.1016/j.cellimm.2012.05.009] [PMID: 22703694]
[165]
Olsen NJ, Schleich MA, Karp DR. Multifaceted effects of hydroxychloroquine in human disease. Semin Arthritis Rheum 2013; 43(2): 264-72.
[http://dx.doi.org/10.1016/j.semarthrit.2013.01.001] [PMID: 23481418]
[166]
Costedoat-Chalumeau N, Dunogué B, Morel N, Le Guern V, Guettrot-Imbert G. Hydroxychloroquine: a multifaceted treatment in lupus. Presse Med 2014; 43(6 Pt 2): e167-80.
[http://dx.doi.org/10.1016/j.lpm.2014.03.007] [PMID: 24855048]
[167]
Alarcón GS, McGwin G, Bertoli AM, et al. LUMINA Study Group. Effect of hydroxychloroquine on the survival of patients with systemic lupus erythematosus: data from LUMINA, a multiethnic US cohort (LUMINA L). Ann Rheum Dis 2007; 66(9): 1168-72.
[http://dx.doi.org/10.1136/ard.2006.068676] [PMID: 17389655]
[168]
De Sanctis JB, Garmendia JV, Moreno D, et al. Pharmacological modulation of Th17. Recent Pat Inflamm Allergy Drug Discov 2009; 3(2): 149-56.
[http://dx.doi.org/10.2174/187221309788489814] [PMID: 19519592]
[169]
Gordon C, Amissah-Arthur MB, Gayed M, et al. British Society for Rheumatology Standards, Audit and Guidelines Working Group. The British Society for Rheumatology guideline for the management of systemic lupus erythematosus in adults. Rheumatology (Oxford) 2018; 57(1): e1-e45.
[http://dx.doi.org/10.1093/rheumatology/kex286] [PMID: 29029350]
[170]
Shee JC. Lupus erythematosus treated with chloroquine. Lancet 1953; 265(6778): 201-2.
[http://dx.doi.org/10.1016/S0140-6736(53)90138-X] [PMID: 13070595]
[171]
Mullins JF, Watts FL, Wilson CJ. Plaquenil in the treatment of lupus erythematosus. J Am Med Assoc 1956; 161(9): 879-81.
[http://dx.doi.org/10.1001/jama.1956.62970090020017k] [PMID: 13319032]
[172]
Fanouriakis A, Kostopoulou M, Alunno A, et al. 2019 update of the EULAR recommendations for the management of systemic lupus erythematosus. Ann Rheum Dis 2019; 78(6): 736-45.
[http://dx.doi.org/10.1136/annrheumdis-2019-215089] [PMID: 30926722]
[173]
Cavazzana I, Sala R, Bazzani C, et al. Treatment of lupus skin involvement with quinacrine and hydroxychloroquine. Lupus 2009; 18(8): 735-9.
[http://dx.doi.org/10.1177/0961203308101714] [PMID: 19502270]
[174]
Ruiz-Irastorza G, Ramos-Casals M, Brito-Zeron P, Khamashta MA. Clinical efficacy and side effects of antimalarials in systemic lupus erythematosus: a systematic review. Ann Rheum Dis 2010; 69(1): 20-8.
[http://dx.doi.org/10.1136/ard.2008.101766] [PMID: 19103632]
[175]
Wozniacka A, Lesiak A, Narbutt J, McCauliffe DP, Sysa-Jedrzejowska A. Chloroquine treatment influences proinflammatory cytokine levels in systemic lupus erythematosus patients. Lupus 2006; 15(5): 268-75.
[http://dx.doi.org/10.1191/0961203306lu2299oa] [PMID: 16761500]
[176]
Flint J, Panchal S, Hurrell A, et al. BSR and BHPR Standards, Guidelines and Audit Working Group. BSR and BHPR guideline on prescribing drugs in pregnancy and breastfeeding-Part I: standard and biologic disease modifying anti-rheumatic drugs and corticosteroids. Rheumatology (Oxford) 2016; 55(9): 1693-7.
[http://dx.doi.org/10.1093/rheumatology/kev404] [PMID: 26750124]
[177]
Abarientos C, Sperber K, Shapiro DL, Aronow WS, Chao CP, Ash JY. Hydroxychloroquine in systemic lupus erythematosus and rheumatoid arthritis and its safety in pregnancy. Expert Opin Drug Saf 2011; 10(5): 705-14.
[http://dx.doi.org/10.1517/14740338.2011.566555] [PMID: 21417950]
[178]
Melles RB, Marmor MF. The risk of toxic retinopathy in patients on long-term hydroxychloroquine therapy. JAMA Ophthalmol 2014; 132(12): 1453-60. [published correction appears in JAMA Ophthalmol. 2014;132(12):1493
[http://dx.doi.org/10.1001/jamaophthalmol.2014.3459] [PMID: 25275721]
[179]
Croia C, Bursi R, Sutera D, Petrelli F, Alunno A, Puxeddu I. One year in review 2019: pathogenesis of rheumatoid arthritis. Clin Exp Rheumatol 2019; 37(3): 347-57.
[PMID: 31111823]
[180]
Abbasi M, Mousavi MJ, Jamalzehi S, et al. Strategies toward rheumatoid arthritis therapy; the old and the new. J Cell Physiol 2019; 234(7): 10018-31.
[http://dx.doi.org/10.1002/jcp.27860] [PMID: 30536757]
[181]
Bugatti S, Bozzalla Cassione E, De Stefano L, Manzo A. Established rheumatoid arthritis. The pathogenic aspects. Best Pract Res Clin Rheumatol 2019; 33(5) 101478
[http://dx.doi.org/10.1016/j.berh.2019.101478] [PMID: 32001167]
[182]
Haydu GG. Rheumatoid arthritis therapy; a rationale and the use of chloroquine diphosphate. Am J Med Sci 1953; 225(1): 71-5.
[http://dx.doi.org/10.1097/00000441-195322510-00012] [PMID: 13007699]
[183]
Cusnir I, Dobing S, Jones N, Russell A. Antimalarial drugs alone may still have a role in rheumatoid arthritis. J Clin Rheumatol 2015; 21(4): 193-5.
[http://dx.doi.org/10.1097/RHU.0000000000000243] [PMID: 26010182]
[184]
Rempenault C, Combe B, Barnetche T, et al. Metabolic and cardiovascular benefits of hydroxychloroquine in patients with rheumatoid arthritis: a systematic review and meta-analysis. Ann Rheum Dis 2018; 77(1): 98-103.
[http://dx.doi.org/10.1136/annrheumdis-2017-211836] [PMID: 28970215]
[185]
Liu D, Li X, Zhang Y, et al. Chloroquine and hydroxychloroquine are associated with reduced cardiovascular risk: a systematic review and meta-analysis. Drug Des Devel Ther 2018; 12: 1685-95.
[http://dx.doi.org/10.2147/DDDT.S166893] [PMID: 29928112]
[186]
Rodrigues JC, Bargman JM. Antimalarial Drugs for the Prevention of Chronic Kidney Disease in Patients with Rheumatoid Arthritis: The Importance of Controlling Chronic Inflammation? Clin J Am Soc Nephrol 2018; 13(5): 679-80.
[http://dx.doi.org/10.2215/CJN.03300318] [PMID: 29661771]
[187]
Sharma TS, Wasko MC, Tang X, et al. Hydroxychloroquine use is associated with decreased incident cardiovascular events in rheumatoid arthritis patients. J Am Heart Assoc 2016; 5(1) e002867
[http://dx.doi.org/10.1161/JAHA.115.002867] [PMID: 26727968]
[188]
Doms J, Horisberger A, Ribi C. Prise en charge du syndrome des anticorps antiphospholipides chez l’adulte. Rev Med Suisse 2020; 16(689): 670-4. [Management of the antiphospholipid syndrome in adults
[PMID: 32270932]
[189]
Linnemann B. Antiphospholipid syndrome - an update. Vasa 2018; 47(6): 451-64.
[http://dx.doi.org/10.1024/0301-1526/a000723] [PMID: 30205764]
[190]
Sammaritano LR. Antiphospholipid syndrome. Best Pract Res Clin Rheumatol 2020; 34(1) 101463
[PMID: 31866276]
[191]
Radic M, Pattanaik D. Cellular and Molecular Mechanisms of Anti-Phospholipid Syndrome. Front Immunol 2018; 9: 969.
[http://dx.doi.org/10.3389/fimmu.2018.00969] [PMID: 29867951]
[192]
Mekinian A, Vicaut E, Cohen J, Bornes M, Kayem G, Fain O. [Hydroxychloroquine to obtain pregnancy without adverse obstetrical events in primary antiphospholipid syndrome: French phase II multicenter randomized trial, HYDROSAPL Gynécol Obstét Fertil Sénol 2018; 46(7-8): 598-604.
[http://dx.doi.org/10.1016/j.gofs.2018.06.008] [PMID: 30041771]
[193]
Chighizola CB, Andreoli L, Gerosa M, Tincani A, Ruffatti A, Meroni PL. The treatment of anti-phospholipid syndrome: A comprehensive clinical approach. J Autoimmun 2018; 90: 1-27.
[http://dx.doi.org/10.1016/j.jaut.2018.02.003] [PMID: 29449131]
[194]
Belizna C, Pregnolato F, Abad S, et al. HIBISCUS: Hydroxychloroquine for the secondary prevention of thrombotic and obstetrical events in primary antiphospholipid syndrome. Autoimmun Rev 2018; 17(12): 1153-68.
[http://dx.doi.org/10.1016/j.autrev.2018.05.012] [PMID: 30316994]
[195]
Belizna C. Hydroxychloroquine as an anti-thrombotic in antiphospholipid syndrome. Autoimmun Rev 2015; 14(4): 358-62.
[http://dx.doi.org/10.1016/j.autrev.2014.12.006] [PMID: 25534016]
[196]
Szymezak J, Ankri A, Fischer AM, Darnige L. Hydrox ychloroquine: une nouvelle approche thérapeutique des manifest tations thrombotiques du syndrome des antiphospholipides. Rev Med Interne 2010; 31(12): 854-7.
[http://dx.doi.org/10.1016/j.revmed.2010.08.018] [PMID: 20888088]
[197]
Achuthan S, Ahluwalia J, Shafiq N, et al. Hydroxychloroquine’s Efficacy as an Antiplatelet Agent Study in Healthy Volunteers: A Proof of Concept Study. J Cardiovasc Pharmacol Ther 2015; 20(2): 174-80.
[http://dx.doi.org/10.1177/1074248414546324] [PMID: 25125385]
[198]
Nosál’ R, Jancinová V, Danihelová E. Chloroquine: a multipotent inhibitor of human platelets in vitro. Thromb Res 2000; 98(5): 411-21.
[http://dx.doi.org/10.1016/S0049-3848(00)00200-0] [PMID: 10828481]
[199]
Mekinian A, Lazzaroni MG, Kuzenko A, et al. SNFMI and the European Forum on Antiphospholipid Antibodies. The efficacy of hydroxychloroquine for obstetrical outcome in anti-phospholipid syndrome: Data from a European multicenter retrospective study. Autoimmun Rev 2015; 14(6): 498-502.
[http://dx.doi.org/10.1016/j.autrev.2015.01.012] [PMID: 25617818]
[200]
Bowman SJ. Primary Sjogren’s syndrome. Lupus 2018; 27(1): 32-5.
[http://dx.doi.org/10.1177/0961203318801673]
[201]
Ramos-Casals M, Brito-Zerón P, Bombardieri S, et al. EULAR-Sjögren Syndrome Task Force Group. EULAR recommendations for the management of Sjögren’s syndrome with topical and systemic therapies. Ann Rheum Dis 2020; 79(1): 3-18.
[http://dx.doi.org/10.1136/annrheumdis-2019-216114] [PMID: 31672775]
[202]
Heaton JM. Antimalarials in treatment of Sjogren’s syndrome. BMJ 1959; 1(5136): 1512-3.
[http://dx.doi.org/10.1136/bmj.1.5136.1512] [PMID: 13651781]
[203]
Migkos MP, Markatseli TE, Iliou C, Voulgari PV, Drosos AA. Effect of hydroxychloroquine on the lipid profile of patients with Sjögren syndrome. J Rheumatol 2014; 41(5): 902-8.
[http://dx.doi.org/10.3899/jrheum.131156] [PMID: 24634203]
[204]
Demarchi J, Papasidero S, Medina MA, et al. Primary Sjögren’s syndrome: Extraglandular manifestations and hydroxychloroquine therapy. Clin Rheumatol 2017; 36(11): 2455-60.
[http://dx.doi.org/10.1007/s10067-017-3822-3] [PMID: 28913747]
[205]
Brito-Zerón P, Sisó-Almirall A, Bové A, Kostov BA, Ramos-Casals M. Primary Sjögren syndrome: an update on current pharmacotherapy options and future directions. Expert Opin Pharmacother 2013; 14(3): 279-89.
[http://dx.doi.org/10.1517/14656566.2013.767333] [PMID: 23346917]
[206]
Gottenberg JE, Ravaud P, Puéchal X, et al. Effects of hydroxychloroquine on symptomatic improvement in primary Sjögren syndrome: the JOQUER randomized clinical trial. JAMA 2014; 312(3): 249-58.
[http://dx.doi.org/10.1001/jama.2014.7682] [PMID: 25027140]
[207]
Wang SQ, Zhang LW, Wei P, Hua H. Is hydroxychloroquine effective in treating primary Sjogren’s syndrome: a systematic review and meta-analysis. BMC Musculoskelet Disord 2017; 18(1): 186.
[http://dx.doi.org/10.1186/s12891-017-1543-z] [PMID: 28499370]
[208]
Al-Bari MAA. Targeting endosomal acidification by chloroquine analogs as a promising strategy for the treatment of emerging viral diseases. Pharmacol Res Perspect 2017; 5(1) e00293
[http://dx.doi.org/10.1002/prp2.293] [PMID: 28596841]
[209]
Savarino A, Shytaj IL. Chloroquine and beyond: exploring anti-rheumatic drugs to reduce immune hyperactivation in HIV/AIDS. Retrovirology 2015; 12: 51.
[http://dx.doi.org/10.1186/s12977-015-0178-0] [PMID: 26084487]
[210]
Zhang YZ, Holmes EC. A Genomic Perspective on the Origin and Emergence of SARS-CoV-2. Cell 2020; 181(2): 223-7.
[http://dx.doi.org/10.1016/j.cell.2020.03.035] [PMID: 32220310]
[211]
Yuki K, Fujiogi M, Koutsogiannaki S. COVID-19 pathophysiology: A review. Clin Immunol 2020. 215108427
[http://dx.doi.org/10.1016/j.clim.2020.108427] [PMID: 32325252]
[212]
JHUoM. Corona virus resource centreCOVID in the US 2020Available at: https://coronavirus.jhu.edu/
[213]
Sparks MA, South A, Welling P, et al. Sound Science before Quick Judgement Regarding RAS Blockade in COVID-19. Clin J Am Soc Nephrol 2020.
[214]
Fung TS, Liu DX. Human Coronavirus: Host-Pathogen Interaction. Annu Rev Microbiol 2019; 73: 529-57.
[http://dx.doi.org/10.1146/annurev-micro-020518-115759] [PMID: 31226023]
[215]
Devaux CA, Rolain JM, Colson P, Raoult D. New insights on the antiviral effects of chloroquine against coronavirus: what to expect for COVID-19? Int J Antimicrob Agents 2020; 55(5) 105938
[http://dx.doi.org/10.1016/j.ijantimicag.2020.105938] [PMID: 32171740]
[216]
Vincent MJ, Bergeron E, Benjannet S, et al. Chloroquine is a potent inhibitor of SARS coronavirus infection and spread. Virol J 2005; 2: 69.
[http://dx.doi.org/10.1186/1743-422X-2-69] [PMID: 16115318]
[217]
Wang M, Cao R, Zhang L, et al. Remdesivir and chloroquine effectively inhibit the recently emerged novel coronavirus (2019-nCoV) in vitro. Cell Res 2020; 30(3): 269-71.
[http://dx.doi.org/10.1038/s41422-020-0282-0] [PMID: 32020029]
[218]
Yao X, Ye F, Zhang M, et al. In Vitro Antiviral Activity and Projection of Optimized Dosing Design of Hydroxychloroquine for the Treatment of Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2). Clin Infect Dis 2020.
[219]
Gao J, Tian Z, Yang X. Breakthrough: Chloroquine phosphate has shown apparent efficacy in treatment of COVID-19 associated pneumonia in clinical studies. Biosci Trends 2020; 14(1): 72-3.
[http://dx.doi.org/10.5582/bst.2020.01047] [PMID: 32074550]
[220]
Lenzer J. Covid-19: US gives emergency approval to hydroxychloroquine despite lack of evidence. BMJ 2020; 369: m1335.
[http://dx.doi.org/10.1136/bmj.m1335] [PMID: 32238355]
[221]
Gautret P, Lagier JC, Parola P, et al. Hydroxychloroquine and azithromycin as a treatment of COVID-19: results of an open-label non-randomized clinical trial. Int J Antimicrob Agents 2020; 56(1) 105949
[http://dx.doi.org/10.1016/j.ijantimicag.2020.105949] [PMID: 32205204]
[222]
Kupferschmidt K, Cohen J. Race to find COVID-19 treatments accelerates. Science 2020; 367(6485): 1412-3.
[http://dx.doi.org/10.1126/science.367.6485.1412] [PMID: 32217705]
[223]
Lin M, Da LT. Refolding Dynamics of gp41 from Pre-fusion to Pre-hairpin States during HIV-1 Entry. J Chem Inf Model 2020; 60(1): 162-74.
[http://dx.doi.org/10.1021/acs.jcim.9b00746] [PMID: 31845803]
[224]
Martinelli E, Cicala C, Van Ryk D, et al. HIV-1 gp120 inhibits TLR9-mediated activation and IFN-alpha secretion in plasmacytoid dendritic cells. Proc Natl Acad Sci USA 2007; 104(9): 3396-401.
[http://dx.doi.org/10.1073/pnas.0611353104] [PMID: 17360657]
[225]
Martinson JA, Montoya CJ, Usuga X, Ronquillo R, Landay AL, Desai SN. Chloroquine modulates HIV-1-induced plasmacytoid dendritic cell alpha interferon: implication for T-cell activation. Antimicrob Agents Chemother 2010; 54(2): 871-81.
[http://dx.doi.org/10.1128/AAC.01246-09] [PMID: 19949061]
[226]
Martí-Carvajal A, Ramon-Pardo P, Javelle E, et al. Interventions for treating patients with chikungunya virus infection-related rheumatic and musculoskeletal disorders: A systematic review. PLoS One 2017; 12(6) e0179028
[http://dx.doi.org/10.1371/journal.pone.0179028] [PMID: 28609439]
[227]
Hamel R, Liégeois F, Wichit S, et al. Zika virus: epidemiology, clinical features and host-virus interactions. Microbes Infect 2016; 18(7-8): 441-9.
[http://dx.doi.org/10.1016/j.micinf.2016.03.009] [PMID: 27012221]
[228]
Li C, Zhu X, Ji X, et al. Chloroquine, a FDA-approved drug, prevents zika virus infection and its associated congenital microcephaly in mice. EBioMedicine 2017; 24: 189-94.
[http://dx.doi.org/10.1016/j.ebiom.2017.09.034] [PMID: 29033372]
[229]
Peng H, Liu B, Yves TD, et al. Zika virus induces autophagy in human umbilical vein endothelial cells. Viruses 2018; 10(5): 259.
[http://dx.doi.org/10.3390/v10050259] [PMID: 29762492]
[230]
Zhang S, Yi C, Li C, et al. Chloroquine inhibits endosomal viral RNA release and autophagy-dependent viral replication and effectively prevents maternal to fetal transmission of Zika virus. Antiviral Res 2019. 169104547
[http://dx.doi.org/10.1016/j.antiviral.2019.104547] [PMID: 31251958]
[231]
Boya P, Gonzalez-Polo RA, Poncet D, et al. Mitochondrial membrane permeabilization is a critical step of lysosome-initiated apoptosis induced by hydroxychloroquine. Oncogene 2003; 22(25): 3927-36.
[http://dx.doi.org/10.1038/sj.onc.1206622] [PMID: 12813466]
[232]
Jiang PD, Zhao YL, Shi W, et al. Cell growth inhibition, G2/M cell cycle arrest, and apoptosis induced by chloroquine in human breast cancer cell line Bcap-37. Cell Physiol Biochem 2008; 22(5-6): 431-40.
[http://dx.doi.org/10.1159/000185488] [PMID: 19088425]
[233]
Jiang PD, Zhao YL, Deng XQ, et al. Antitumor and antimetastatic activities of chloroquine diphosphate in a murine model of breast cancer. Biomed Pharmacother 2010; 64(9): 609-14.
[http://dx.doi.org/10.1016/j.biopha.2010.06.004] [PMID: 20888174]
[234]
Chude CI, Amaravadi RK. Targeting Autophagy in Cancer: Update on Clinical Trials and Novel Inhibitors. Int J Mol Sci 2017; 18(6): 1279.
[http://dx.doi.org/10.3390/ijms18061279] [PMID: 28621712]
[235]
Cuomo F, Altucci L, Cobellis G. Autophagy Function and Dysfunction: Potential Drugs as Anti-Cancer Therapy. Cancers (Basel) 2019; 11(10): 1465.
[http://dx.doi.org/10.3390/cancers11101465] [PMID: 31569540]
[236]
Wang Y, Peng RQ, Li DD, et al. Chloroquine enhances the cytotoxicity of topotecan by inhibiting autophagy in lung cancer cells. Chin J Cancer 2011; 30(10): 690-700.
[http://dx.doi.org/10.5732/cjc.011.10056] [PMID: 21959046]
[237]
Xu R, Ji Z, Xu C, Zhu J. The clinical value of using chloroquine or hydroxychloroquine as autophagy inhibitors in the treatment of cancers: A systematic review and meta-analysis. Medicine (Baltimore) 2018; 97(46) e12912
[http://dx.doi.org/10.1097/MD.0000000000012912] [PMID: 30431566]
[238]
Rangwala R, Chang YC, Hu J, et al. Combined MTOR and autophagy inhibition: phase I trial of hydroxychloroquine and temsirolimus in patients with advanced solid tumors and melanoma. Autophagy 2014; 10(8): 1391-402.
[http://dx.doi.org/10.4161/auto.29119] [PMID: 24991838]
[239]
Rangwala R, Leone R, Chang YC, et al. Phase I trial of hydroxychloroquine with dose-intense temozolomide in patients with advanced solid tumors and melanoma. Autophagy 2014; 10(8): 1369-79.
[http://dx.doi.org/10.4161/auto.29118] [PMID: 24991839]
[240]
Mehnert JM, Kaveney AD, Malhotra J, et al. A phase I trial of MK-2206 and hydroxychloroquine in patients with advanced solid tumors. Cancer Chemother Pharmacol 2019; 84(4): 899-907.
[http://dx.doi.org/10.1007/s00280-019-03919-x] [PMID: 31463691]
[241]
Zeh H, Bahary N, Boone BA, et al. Randomized Phase II Preoperative Study of Autophagy Inhibition With High-Dose Hydroxychloroquine and Gemcitabine/Nab-Paclitaxel in Pancreatic Cancer Patients Clin Cancer Res 2020
[242]
Horne GA, Stobo J, Kelly C, et al. A randomised phase II trial of hydroxychloroquine and imatinib versus imatinib alone for patients with chronic myeloid leukaemia in major cytogenetic response with residual disease. Leukemia 2020; 34(7): 1775-86.
[http://dx.doi.org/10.1038/s41375-019-0700-9] [PMID: 31925317]
[243]
Haas NB, Appleman LJ, Stein M, et al. Autophagy Inhibition to Augment mTOR Inhibition: a Phase I/II Trial of Everolimus and Hydroxychloroquine in Patients with Previously Treated Renal Cell Carcinoma. Clin Cancer Res 2019; 25(7): 2080-7.
[http://dx.doi.org/10.1158/1078-0432.CCR-18-2204] [PMID: 30635337]
[244]
Biological Effects of Maintenance Usage of HCQ on PAR-4 Levels in Patients With Resected Solid Tumors ClinicalTrialsgov identifier: NCT03015324.
[245]
Vorinostat plus HCQ Versus Regorafenib in Colorectal Cancer Available at:. https://clinicaltrials.gov/ct2/show/NCT02316340
[246]
Molenaar RJ, Coelen RJS, Khurshed M, et al. Study protocol of a phase IB/II clinical trial of metformin and chloroquine in patients with IDH1-mutated or IDH2-mutated solid tumours. BMJ Open 2017; 7(6) e014961
[http://dx.doi.org/10.1136/bmjopen-2016-014961] [PMID: 28601826]
[247]
Karasic TB, O’Hara MH, Loaiza-Bonilla A, et al. Effect of Gemcitabine and nab-Paclitaxel With or Without Hydroxychloroquine on Patients With Advanced Pancreatic Cancer: A Phase 2 Randomized Clinical Trial. JAMA Oncol 2019; 5(7): 993-8.
[http://dx.doi.org/10.1001/jamaoncol.2019.0684] [PMID: 31120501]
[248]
Wang P, Burikhanov R, Jayswal R, et al. Neoadjuvant administration of hydroxychloroquine in a phase 1 clinical trial induced plasma Par-4 levels and apoptosis in diverse tumors. Genes Cancer 2018; 9(5-6): 190-7.
[PMID: 30603055]
[249]
El-Chemaly S, Taveira-Dasilva A, Goldberg HJ, et al. Sirolimus and Autophagy Inhibition in Lymphangioleiomyomatosis: Results of a Phase I Clinical Trial. Chest 2017; 151(6): 1302-10.
[http://dx.doi.org/10.1016/j.chest.2017.01.033] [PMID: 28192114]
[250]
Samaras P, Tusup M, Nguyen-Kim TDL, et al. Phase I study of a chloroquine-gemcitabine combination in patients with metastatic or unresectable pancreatic cancer. Cancer Chemother Pharmacol 2017; 80(5): 1005-12.
[http://dx.doi.org/10.1007/s00280-017-3446-y] [PMID: 28980060]
[251]
Patel S, Hurez V, Nawrocki ST, et al. Vorinostat and hydroxychloroquine improve immunity and inhibit autophagy in metastatic colorectal cancer. Oncotarget 2016; 7(37): 59087-97.
[http://dx.doi.org/10.18632/oncotarget.10824] [PMID: 27463016]
[252]
Boone BA, Bahary N, Zureikat AH, et al. Safety and Biologic Response of Pre-operative Autophagy Inhibition in Combination with Gemcitabine in Patients with Pancreatic Adenocarcinoma. Ann Surg Oncol 2015; 22(13): 4402-10.
[http://dx.doi.org/10.1245/s10434-015-4566-4] [PMID: 25905586]
[253]
Chi KH, Ko HL, Yang KL, Lee CY, Chi MS, Kao SJ. Addition of rapamycin and hydroxychloroquine to metronomic chemotherapy as a second line treatment results in high salvage rates for refractory metastatic solid tumors: a pilot safety and effectiveness analysis in a small patient cohort. Oncotarget 2015; 6(18): 16735-45.
[http://dx.doi.org/10.18632/oncotarget.3793] [PMID: 25944689]
[254]
Mahalingam D, Mita M, Sarantopoulos J, et al. Combined autophagy and HDAC inhibition: a phase I safety, tolerability, pharmacokinetic, and pharmacodynamic analysis of hydroxychloroquine in combination with the HDAC inhibitor vorinostat in patients with advanced solid tumors. Autophagy 2014; 10(8): 1403-14.
[http://dx.doi.org/10.4161/auto.29231] [PMID: 24991835]
[255]
Rosenfeld MR, Ye X, Supko JG, et al. A phase I/II trial of hydroxychloroquine in conjunction with radiation therapy and concurrent and adjuvant temozolomide in patients with newly diagnosed glioblastoma multiforme. Autophagy 2014; 10(8): 1359-68.
[http://dx.doi.org/10.4161/auto.28984] [PMID: 24991840]
[256]
Vogl DT, Stadtmauer EA, Tan KS, et al. Combined autophagy and proteasome inhibition: a phase 1 trial of hydroxychloroquine and bortezomib in patients with relapsed/refractory myeloma. Autophagy 2014; 10(8): 1380-90.
[http://dx.doi.org/10.4161/auto.29264] [PMID: 24991834]
[257]
Wolpin BM, Rubinson DA, Wang X, et al. Phase II and pharmacodynamic study of autophagy inhibition using hydroxychloroquine in patients with metastatic pancreatic adenocarcinoma. Oncologist 2014; 19(6): 637-8.
[http://dx.doi.org/10.1634/theoncologist.2014-0086] [PMID: 24821822]
[258]
Rojas-Puentes LL, Gonzalez-Pinedo M, Crismatt A, et al. Phase II randomized, double-blind, placebo-controlled study of whole-brain irradiation with concomitant chloroquine for brain metastases. Radiat Oncol 2013; 8: 209.
[http://dx.doi.org/10.1186/1748-717X-8-209] [PMID: 24010771]
[259]
Goldberg SB, Supko JG, Neal JW, et al. A phase I study of erlotinib and hydroxychloroquine in advanced non-small-cell lung cancer. J Thorac Oncol 2012; 7(10): 1602-8.
[http://dx.doi.org/10.1097/JTO.0b013e318262de4a] [PMID: 22878749]
[260]
Briceño E, Calderon A, Sotelo J. Institutional experience with chloroquine as an adjuvant to the therapy for glioblastoma multiforme. Surg Neurol 2007; 67(4): 388-91.
[http://dx.doi.org/10.1016/j.surneu.2006.08.080] [PMID: 17350410]
[261]
Sotelo J, Briceño E, López-González MA. Adding chloroquine to conventional treatment for glioblastoma multiforme: a randomized, double-blind, placebo-controlled trial. Ann Intern Med 2006; 144(5): 337-43.
[http://dx.doi.org/10.7326/0003-4819-144-5-200603070-00008] [PMID: 16520474]

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