Molecular Mechanisms Involved in the Antitumor Activity of Isolated Lectins from Marine Organisms: A Systematic Review

Author(s): Hugo Jefferson Ferreira, Evandro Moreira de Almeida, Wildson Max Barbosa da Silva, Edson Holanda Teixeira, Luiz Gonzaga do Nascimento Neto*

Journal Name: Current Drug Targets

Volume 21 , Issue 6 , 2020

  Journal Home
Translate in Chinese
Become EABM
Become Reviewer

Graphical Abstract:


Abstract:

Introduction: Tumor cells may present several molecular alterations that favor their malignancy, among which there is the expression of tumor-related antigens, such as truncated T-glycans, Thomsen-nouvelle, sialyl-Lewis X and sialyl Tn, which may help in the diagnosis and treatment using specific target molecules. Lectins are ubiquitous proteins capable of interacting with specific carbohydrates. Lectins isolated from marine organisms have important characteristics such as low immunogenicity and can bind to complex glycans compared to plant lectins.

Objective: This work evaluated, through a systematic review, the molecular mechanisms of antitumor activity of lectins isolated from marine organisms. Methodology: The Pubmed, Lilacs, Science Direct, Wiley and Scopus databases were reviewed using the descriptors: marine lectin and cancer. Articles in English, published between January 2008 and December 2018, which proposed the molecular mechanisms of anticancer activity of lectins from marine organisms were eligible for the study.

Results: 17 articles were eligible. The lectins showed promising performance against cancer cells, presenting specific cytotoxicity for some types of malignant cells. The articles presented several lectins specific to different carbohydrates, modulating: pro and anti-apoptotic proteins, transcription factor E2F-1, via mitogen-activated protein kinase. In addition, exogenous lectin expression in cancer cells has been shown to be a promising way to treat cancer.

Conclusion: This review showed the various studies that described the molecular mechanisms caused by marine lectins with antineoplastic potential. This knowledge is relevant for the development and use of the next generations of lectins isolated from marine organisms, supporting their potential in cancer treatment.

Keywords: Cancer, marine lectin, antineoplastic, natural product, molecular mechanisms, marine organisms.

[2]
Knoll, L.J.; Hogan, D.A.; Leong, J.M.; Heitman, J.; Condit, R.C. Pearls collections: What we can learn about infectious disease and cancer. PLoS Pathog., 2018, 14(3)e1006915 [http://dx.doi.org/10.1371/journal.ppat.1006915]. [PMID: 29596508].
[3]
Shen, L.; Shi, Q.; Wang, W. Double agents: genes with both oncogenic and tumor-suppressor functions. Oncogenesis, 2018, 7(3), 25. [http://dx.doi.org/10.1038/s41389-018-0034-x]. [PMID: 29540752].
[4]
Siegel, R.L.; Miller, K.D.; Jemal, A. Cancer statistics, 2018. CA Cancer J. Clin., 2018, 68(1), 7-30. [http://dx.doi.org/10.3322/caac.21442]. [PMID: 29313949].
[5]
Rayan, A.; Raiyn, J.; Falah, M. Nature is the best source of anticancer drugs: Indexing natural products for their anticancer bioactivity. PLoS One, 2017, 12(11)e0187925 [http://dx.doi.org/10.1371/journal.pone.0187925]. [PMID: 29121120].
[6]
Chen, Z.; He, A.; Liu, Y.; Huang, W.; Cai, Z. Recent development on synthetic biological devices treating bladder cancer. Synth Syst Biotechnol, 2016, 1(4), 216-220. [http://dx.doi.org/10.1016/j.synbio.2016.08.001]. [PMID: 29062946].
[7]
Burstein, H.J.; Krilov, L.; Aragon-Ching, J.B. Clinical Cancer Advances 2017: Annual Report on Progress Against Cancer From the American Society of Clinical Oncology. J. Clin. Oncol., 2017, 35(12), 1341-1367. [http://dx.doi.org/10.1200/JCO.2016.71.5292]. [PMID: 28148207].
[8]
Zhang, Z.; Wuhrer, M.; Holst, S. Serum sialylation changes in cancer. Glycoconj. J., 2018, 35(2), 139-160. [http://dx.doi.org/10.1007/s10719-018-9820-0]. [PMID: 29680984].
[9]
Guo, B.J.; Bian, Z.X.; Qiu, H.C.; Wang, Y.T.; Wang, Y. Biological and clinical implications of herbal medicine and natural products for the treatment of inflammatory bowel disease. Ann. N. Y. Acad. Sci., 2017, 1401(1), 37-48. [http://dx.doi.org/10.1111/nyas.13414]. [PMID: 28891095].
[10]
Atanasov, A.G.; Yeung, A.W.K.; Banach, M.; Banach, M.P.T. Natural products for targeted therapy in precision medicine. Biotechnol. Adv., 2018, 36(6), 1559-1562. [http://dx.doi.org/10.1016/j.biotechadv.2018.08.003]. [PMID: 30081176].
[11]
Arrieta, J.M.; Arnaud-Haond, S.; Duarte, C.M. What lies underneath: conserving the oceans’ genetic resources. Proc. Natl. Acad. Sci. USA, 2010, 107(43), 18318-18324. [http://dx.doi.org/10.1073/pnas.0911897107]. [PMID: 20837523].
[12]
Blunt, J.W.; Copp, B.R.; Keyzers, R.A.; Munro, M.H.; Prinsep, M.R. Marine natural products. Nat. Prod. Rep., 2012, 29(2), 144-222. [http://dx.doi.org/10.1039/C2NP00090C]. [PMID: 22193773].
[13]
Sharon, N.; Lis, H. History of lectins: from hemagglutinins to biological recognition molecules. Glycobiology, 2004, 14(11), 53R-62R. [http://dx.doi.org/10.1093/glycob/cwh122]. [PMID: 15229195].
[14]
Lagarda-Diaz, I.; Guzman-Partida, A.M.; Vazquez-Moreno, L. Vazquez- moreno l. Legume lectins: Proteins with diverse applications. Int. J. Mol. Sci., 2017, 18(6), 1-18. [http://dx.doi.org/10.3390/ijms18061242]. [PMID: 28604616].
[15]
Coelho, L.C.B.B.; Silva, P.M.S.; Lima, V.L.M. Lectins, interconnecting proteins with biotechnological/pharmacological and therapeutic applications; Hindawi Evidence-Based Complementary and Alternative Medicine, 2017. [http://dx.doi.org/10.1155/2017/1594074]
[16]
Yau, T.; Dan, X.; Ng, C.C.; Ng, T.B.; Ng, T.B. Lectins with potential for anti-cancer therapy. Molecules, 2015, 20(3), 3791-3810. [http://dx.doi.org/10.3390/molecules20033791]. [PMID: 25730388].
[17]
Shi, Z.; Li, W.W.; Tang, Y.; Cheng, L.J.; Review, A. A Novel Molecular Model of Plant Lectin-Induced Programmed Cell Death in Cancer. Biol. Pharm. Bull., 2017, 40(10), 1625-1629. [http://dx.doi.org/10.1248/bpb.b17-00363]. [PMID: 28768938].
[18]
Poiroux, G.; Barre, A.; van Damme, E.J.M.; Benoist, H.; Rougé, P. Plant lectins targeting o-glycans at the cell surface as tools for cancer diagnosis, prognosis and therapy. Int. J. Mol. Sci., 2017, 18(6)E1232 [http://dx.doi.org/10.3390/ijms18061232]. [PMID: 28598369].
[19]
Gardères, J.; Bourguet-Kondracki, M.L.; Hamer, B.; Batel, R.; Schröder, H.C.; Müller, W.E. Porifera lectins: diversity, physiological roles and biotechnological potential. Mar. Drugs, 2015, 13(8), 5059-5101. [http://dx.doi.org/10.3390/md13085059]. [PMID: 26262628].
[20]
Chernikov, O.V.; Molchanova, V.I.; Chikalovets, I.V.; Kondrashina, A.S.; Li, W.; Lukyanov, P.A. Lectins of marine hydrobionts. Biochemistry (Mosc.), 2013, 78(7), 760-770. [http://dx.doi.org/10.1134/S0006297913070080]. [PMID: 24010839].
[21]
Evandro, F.F.; Tzi, B.N. Antitumor Potential and other Emerging Medicinal Properties of Natural Compounds; Springer Dordrecht Heidelberg New York London, 2013.
[22]
Pati, D.; Lorusso, L.N.; Lorusso, L.N.; Arch, M.S. How to write a systematic review of the literature. HERD, 2018, 11(1), 15-30. [http://dx.doi.org/10.1177/1937586717747384]. [PMID: 29283007].
[23]
McHugh, M.L. Interrater reliability: the kappa statistic. Biochem. Med. (Zagreb), 2012, 22(3), 276-282. [http://dx.doi.org/10.11613/BM.2012.031]. [PMID: 23092060].
[24]
Schneider, K.; Schwarz, M.; Burkholder, I. “ToxRTool”, a new tool to assess the reliability of toxicological data. Toxicol. Lett., 2009, 189(2), 138-144. [http://dx.doi.org/10.1016/j.toxlet.2009.05.013]. [PMID: 19477248].
[25]
Galluzzi, L.; Vitale, I.; Aaronson, S.A. Molecular mechanisms of cell death: recommendations of the Nomenclature Committee on Cell Death 2018. Cell Death Differ., 2018, 25(3), 486-541. [http://dx.doi.org/10.1038/s41418-017-0012-4]. [PMID: 29362479].
[26]
Rabelo, L.; Monteiro, N.; Serquiz, R. A lactose-binding lectin from the marine sponge Cinachyrella apion (Cal) induces cell death in human cervical adenocarcinoma cells. Mar. Drugs, 2012, 10(4), 727-743. [http://dx.doi.org/10.3390/md10040727]. [PMID: 22690140].
[27]
Chaves, R.P.; Roberta, S.; Gonzaga, N.L.; Carneiro, R.F.; Luis, A. Structural characterization of two isolectins from the marine red alga Solieria filiformis (Kützing) PW Gabrielson and their anticancer effect on MCF-7 breast cancer cells; Int J Biol Macromol. Elsevier B.V., 2017.
[28]
Baig, S; Seevasant, I; Mohamad, J; Mukheem, A; Huri, HZ; Kamarul, T T. Potential of apoptotic pathway-targeted cancer therapeutic research: Where do we stand? Cell Death Dis 2016; 7e2058
[http://dx.doi.org/10.1038/cddis.2015.275] [PMID: 26775709]
[29]
Hasan, I.; Ozeki, Y. Histochemical localization of N- acetylhexosamine-binding lectin HOL-18 in Halichondria okadai (Japanese black sponge), and its antimicrobial and cytotoxic anticancer effects. Int. J. Biol. Macromol., 2018. [PMID: 30496858].
[30]
Kovbasnjuk, O; Mourtazina, R; Baibakov, B; Wang, T; Elowsky, C; Choti, MA The glycosphingolipid globotriaosylceramide in the metastatic transformation of colon cancer., 2005, 1(14), 1-16.
[http://dx.doi.org/10.1073/pnas.0506474102]
[31]
Stimmer, L; Dehay, S; Nemati, F; Massonnet, G; Richon, S; Decaudin, D Human breast cancer and lymph node metastases express Gb3 and can be targeted by STxB- vectorized chemotherapeutic compounds. 2014; 1-11.
[32]
Desselle, A.; Chaumette, T.; Gaugler, M. Anti- gb3 monoclonal antibody inhibits angiogenesis and tumor development. PlosOne. 2012;7(11):1–14. 12. Curr. Drug Targets, 2019, 0(0) [FERREIRA, HJ. et al.].
[33]
Geyer, P.E.; Maak, M.; Nitsche, U.; Perl, M.; Novotny, A.; Slotta-huspenina, J. Gastric Adenocarcinomas Express the Glycosphingolipid Gb 3 / CD77. Targeting of Gastric Cancer Cells with Shiga Toxin B-Subunit, 2016, 15(May), 1008-1018.
[34]
Liao, J.H.; Chien, C.T.; Wu, H.Y. A multivalent marine lectin from Crenomytilus grayanus possesses anti- cancer activity through recognizing globotriose Gb3. J. Am. Chem. Soc., 2016, 138(14), 4787-4795. [http://dx.doi.org/10.1021/jacs.6b00111]. [PMID: 27010847].
[35]
Chernikov, A.O.; Kuzmich, A.; Molchanova, V.; Hua, K. Lectin CGL from the sea mussel Crenomytilus grayanus induces Burkitt’s lymphoma cells death via interaction with surface glycan; Int J Biol Macromol. Elsevier B.V., 2017.
[36]
Morales, J.; Li, L.; Fattah, F.J. Review of poly (ADP-ribose) polymerase (PARP) mechanisms of action and rationale for targeting in cancer and other diseases. Crit. Rev. Eukaryot. Gene Expr., 2014, 24(1), 15-28. [http://dx.doi.org/10.1615/CritRevEukaryotGeneExpr.2013006875]. [PMID: 24579667].
[37]
Agarwal, A; Mahfouz, RZ; Sharma, RK; Sarkar, O; Mangrola, D; Mathur, PP . Potential biological role of poly (ADP-ribose) polymerase (PARP) in male gametes 2009; 20: 1-20.
[38]
Fujii, Y.; Dohmae, N.; Takio, K.; Kawsar, S.M.A.; Matsumoto, R.; Hasan, I. A Lectin from the Mussel Mytilus galloprovincialis Has a Highly Novel Primary Structure and Induces Glycan-mediated Cytotoxicity of Globotriaosylceramide-expressing Lymphoma Cells. J. Biol. Chem., 2012, 287(53), 44772-44783.
[39]
Terada, D.; Kawai, F.; Noguchi, H.; Unzai, S.; Hasan, I.; Fujii, Y. Crystal structure of MytiLec, a galactose-binding lectin from the mussel Mytilus galloprovincialis with cytotoxicity against certain cancer cell types; Nature Publishing Group, 2016, pp. 1-11.
[40]
Omokawa, Y.; Miyazaki, T.; Walde, P. In vitro and in vivo anti-tumor effects of novel Span 80 vesicles containing immobilized Eucheuma serra agglutinin. Int. J. Pharm., 2010, 389(1-2), 157-167. [http://dx.doi.org/10.1016/j.ijpharm.2010.01.033]. [PMID: 20100554].
[41]
Anam, C.; Chasanah, E.; Perdhana, B.P. Cytotoxicity of Crude Lectins from Red Macroalgae from the Southern Coast of Java Island, Gunung Kidul Regency, Yogyakarta, Cytotoxicity of Crude Lectins from Red Macroalgae from the Southern Coast of Java Island, Gunung Kidul Regency Yogyakarta Indonesia IOP Conf Series: Materials Science and Engineering,
[42]
Nascimento, K.S.; Cunha, A.I.; Nascimento, K.S.; Cavada, B.S.; Azevedo, A.M.; Aires-Barros, M.R. An overview of lectins purification strategies. J. Mol. Recognit., 2012, 25(11), 527-541. [http://dx.doi.org/10.1002/jmr.2200]. [PMID: 23108612].
[43]
Sugawara, S.; Im, C.; Kawano, T.; Tatsuta, T. Catfish rhamnose-binding lectin induces G 0 / 1 cell cycle arrest in Burkitt’ s lymphoma cells via membrane surface Gb3. Glycoconj. J., 2016. [PMID: 27796613].
[44]
García-Reyes, B.; Kretz, A.L.; Ruff, J.P. The Emerging Role of Cyclin-Dependent Kinases (CDKs) in Pancreatic Ductal Adenocarcinoma. Int. J. Mol. Sci., 2018, 19(10), 3219. [http://dx.doi.org/10.3390/ijms19103219]. [PMID: 30340359].
[45]
García-Gutiérrez, L.; Delgado, M.D.; León, J. MYC Oncogene Contributions to Release of Cell Cycle Brakes. Genes (Basel), 2019, 10(3), 244. [http://dx.doi.org/10.3390/genes10030244]. [PMID: 30909496].
[46]
Coqueret, O. New roles for p21 and p27 cell-cycle inhibitors: a function for each cell compartment? Trends Cell Biol., 2003, 13(2), 65-70. [http://dx.doi.org/10.1016/S0962-8924(02)00043-0]. [PMID: 12559756].
[47]
Goitre, L. The Ras Superfamily of Small GTPases: The Unlocked Secrets.Ras Signaling Methods in Molecular Biology (Methods and Protocols); Totowa, NJ Humana Press, 2014, p. 1120. [http://dx.doi.org/10.1007/978-1-62703-791-4_1]
[48]
Yue, J Integrator orchestrates RAS / ERK1 / 2 signaling transcriptional programs 2017; 1809-20
[49]
Turk, V; Stoka, V; Vasiljeva, O; Renko, M; Sun, T; Turk, B. Biochimica et Biophysica Acta Cysteine cathepsins: From structure, function and regulation to new frontiers ☆ 2012; 1824: 68-88.
[50]
Queiroz, AFS; Silva, RA; Moura, RM; Dreyfuss, JL; Ana, EJP; Ivarne, CSS Growth inhibitory activity of a novel lectin from Cliona varians against K562 human erythroleukemia cells., 2009, 1023-33.
[http://dx.doi.org//10.1007/s00280-008-0825-4]
[51]
Chen, Q; Kang, J; Fu, C The independence of and associations among apoptosis, autophagy, and necrosis. Signal Transduct Target Ther. Springer US 2017; 2018 [Internet].,
[http://dx.doi.org/10.1038/s41392-018-0018-5] [PMID: 29967689]
[52]
Neto, LGN; Cabral, MG; Carneiro, RF et al. Halilectin-3, a lectin from the marine sponge Haliclona caerulea, induces apoptosis and autophagy in human breast cancer MCF7 cells through a caspase-9 and LC3 pathway. 2018; 18(4): 521-8
[53]
Yu, L.; Chen, Y.; Tooze, S.A. Autophagy pathway: Cellular and molecular mechanisms. Autophagy, 2018, 14(2), 207-215. [http://dx.doi.org/10.1080/15548627.2017.1378838]. [PMID: 28933638].
[54]
Kang, R.; Zeh, H.J.; Lotze, M.T.; Tang, D. The Beclin 1 network regulates autophagy and apoptosis. Cell Death Differ., 2011, 18(4), 571-580. [http://dx.doi.org/10.1038/cdd.2010.191]. [PMID: 21311563].
[55]
Chude, C.I.; Amaravadi, R.K. Targeting autophagy in cancer: Update on clinical trials and novel inhibitors. Int. J. Mol. Sci., 2017, 18(6)E1279 [http://dx.doi.org/10.3390/ijms18061279]. [PMID: 28621712].
[56]
Pierzyńska-Mach, A.; Janowski, P.A.; Dobrucki, J.W. Evaluation of acridine orange, LysoTracker Red, and quinacrine as fluorescent probes for long-term tracking of acidic vesicles. Cytometry A, 2014, 85(8), 729-737. [http://dx.doi.org/10.1002/cyto.a.22495]. [PMID: 24953340].
[57]
Wu, L.; Yang, X.; Duan, X.; Cui, L.; Li, G. Exogenous expression of marine lectins DlFBL and SpRBL induces cancer cell apoptosis possibly through PRMT5-E2F-1 pathway. Sci. Rep., 2014, 4, 4505. [http://dx.doi.org/10.1038/srep04505]. [PMID: 24675921].
[58]
Tait, S.W.G.; Green, D.R. Caspase-independent cell death: leaving the set without the final cut. Oncogene, 2008, 27(50), 6452-6461. [http://dx.doi.org/10.1038/onc.2008.311]. [PMID: 18955972].
[59]
Vuillier, C. E2F1 interacts with BCL‐xL and regulates its subcellular localization dynamics to trigger cell death. EMBO Rep., 2017, •••, 44046. [PMID: 29233828].
[60]
Zheng, S.; Moehlenbrink, J.; Lu, Y.C. Arginine methylation-dependent reader-writer interplay governs growth control by E2F-1. Mol. Cell, 2013, 52(1), 37-51. [http://dx.doi.org/10.1016/j.molcel.2013.08.039]. [PMID: 24076217].
[61]
Li, G.; Gao, Y.; Cui, L.; Wu, L.; Yang, X.; Chen, J. Anguilla japonica lectin 1 delivery through adenovirus vector induces apoptotic cancer cell death through interaction with PRMT5. J. Gene Med., 2016, 18(4-6), 65-74. [http://dx.doi.org/10.1002/jgm.2878]. [PMID: 26990556].
[62]
Burotto, M.; Chiou, V.L.; Lee, J.M.; Kohn, E.C. The MAPK pathway across different malignancies: a new perspective. Cancer, 2014, 120(22), 3446-3456. [http://dx.doi.org/10.1002/cncr.28864]. [PMID: 24948110].
[63]
Lake, D.; Corrêa, S.A.L.; Müller, J. Negative feedback regulation of the ERK1/2 MAPK pathway. Cell. Mol. Life Sci., 2016, 73(23), 4397-4413. [http://dx.doi.org/10.1007/s00018-016-2297-8]. [PMID: 27342992].
[64]
Arkun, Y.; Yasemi, M. Dynamics and control of the ERK signaling pathway: Sensitivity, bistability, and oscillations. PLoS One, 2018, 13(4)e0195513 [http://dx.doi.org/10.1371/journal.pone.0195513]. [PMID: 29630631].
[65]
Ryan, M.B.; Der, C.J.; Wang-Gillam, A.; Cox, A.D. Targeting RAS-mutant cancers: is ERK the key? Trends Cancer, 2015, 1(3), 183-198. [http://dx.doi.org/10.1016/j.trecan.2015.10.001]. [PMID: 26858988].
[66]
Liu, F.; Yang, X.; Geng, M.; Huang, M. Targeting ERK, an Achilles’ Heel of the MAPK pathway, in cancer therapy. Acta Pharm. Sin. B, 2018, 8(4), 552-562. [http://dx.doi.org/10.1016/j.apsb.2018.01.008]. [PMID: 30109180].
[67]
Yu, Q.; Wu, M.; Sheng, L.; Li, Q.; Xie, F. Therapeutic effects of targeting RAS-ERK signaling in giant congenital melanocytic nevi. Am. J. Transl. Res., 2018, 10(4), 1184-1194. [PMID: 29736211].
[68]
Bahrami, A; Hassanian, SM Targeting RAS signaling pathway as a potential therapeutic target in the treatment of colorectal cancer. J. Cell. Physiol., 2018, 233(3), 2058-2066. [http://dx.doi.org/10.1002/jcp.25890]. [PMID: 28262927].
[69]
García-Gómez, R.; Bustelo, X.R.; Crespo, P. Protein-Protein Interactions: Emerging Oncotargets in the RAS-ERK Pathway. Trends Cancer, 2018, 4(9), 616-633. [http://dx.doi.org/10.1016/j.trecan.2018.07.002]. [PMID: 30149880].
[70]
Li, G.; Zhao, Z.; Wu, B. Ulva pertusa lectin 1 delivery through adenovirus vector affects multiple signaling pathways in cancer cells. Glycoconj. J., 2017, 34(4), 489-498. [http://dx.doi.org/10.1007/s10719-017-9767-6]. [PMID: 28349379].
[71]
Pasquier, E; Kavallaris, M. Critical Review Microtubules: A Dynamic Target in Cancer Therapy., 2008, 60, 165-71.
[72]
Ganguly, A.; Cabral, F. New insights into mechanisms of resistance to microtubule inhibitors. Biochim. Biophys. Acta, 2011, 1816(2), 164-171. [PMID: 21741453].
[73]
Yang, X.; Wu, L.; Duan, X.; Cui, L.; Luo, J.; Li, G. Adenovirus Carrying Gene Encoding Haliotis discus Sialic Acid Binding Lectin Induces Cancer Cell Apoptosis; MDPI, 2014, pp. 3994-4004. [http://dx.doi.org/10.3390/md12073994]
[74]
Rodrigues, E.; Macauley, M.S. Hypersialylation in cancer: Modulation of inflammation and therapeutic opportunities. Cancers (Basel), 2018, 10(6), 1-19. [http://dx.doi.org/10.3390/cancers10060207]. [PMID: 29912148].
[75]
Pinho, S.S.; Reis, C.A. Glycosylation in cancer: mechanisms and clinical implications. Nat. Rev. Cancer, 2015, 15(9), 540-555. [http://dx.doi.org/10.1038/nrc3982]. [PMID: 26289314].
[76]
Boligan, K.F.; Mesa, C.; Fernandez, L.E.; von Gunten, S. Cancer intelligence acquired (CIA): tumor glycosylation and sialylation codes dismantling antitumor defense. Cell. Mol. Life Sci., 2015, 72(7), 1231-1248. [http://dx.doi.org/10.1007/s00018-014-1799-5]. [PMID: 25487607].
[77]
Pearce, O.M.T.; Läubli, H. Sialic acids in cancer biology and immunity. Glycobiology, 2016, 26(2), 111-128. [http://dx.doi.org/10.1093/glycob/cwv097]. [PMID: 26518624].


Rights & PermissionsPrintExport Cite as

Article Details

VOLUME: 21
ISSUE: 6
Year: 2020
Page: [616 - 625]
Pages: 10
DOI: 10.2174/1389450120666191122113850
Price: $65

Article Metrics

PDF: 12
HTML: 3
EPUB: 1
PRC: 1