Deciphering cellular biological processes to clinical application: a new perspective for Tα1 treatment targeting multiple diseases

References

• Scannell JW, Blanckley A, Boldon H, et al. Diagnosing the decline in pharmaceutical R&D efficiency. Nat Rev Drug Discov. 2012;11(3):191–200.
   PubMed Web of Science ®Google Scholar
• Ashburn TT, Thor KB. Drug repositioning: identifying and developing new uses for existing drugs. Nat Rev Drug Discov. 2004;3(8):673–683.
   PubMed Web of Science ®Google Scholar
• Huang DW, Sherman BT, Lempicki RA. Bioinformatics enrichment tools: paths toward the comprehensive functional analysis of large gene lists. Nucleic Acids Res. 2009;37(1):1–13.
   PubMed Web of Science ®Google Scholar
• Pan Y, Cheng T, Wang Y, et al. Pathway analysis for drug repositioning based on public database mining. J Chem Inf Model. 2014;54:407–418.
   PubMed Web of Science ®Google Scholar
• Goldstein AL. From lab to bedside: emerging clinical applications of thymosin alpha 1. Expert Opin Biol Ther. 2009;9(5):593–608.
   PubMed Web of Science ®Google Scholar
• Garaci E, Pica F, Serafino A, et al. Thymosin α1 and cancer: action on immune effector and tumor target cells. Ann N Y Acad Sci. 2012;1269:26–33.
   PubMed Web of Science ®Google Scholar
• Matteucci C, Grelli S, Balestrieri, et al. Thymosin alpha 1 and HIV-1: recent advances and future perspectives. Fut Microbiol. 2017;12:141–155.
   PubMed Web of Science ®Google Scholar
• Camerini R, Garaci E. Historical review of thymosin α 1 in infectious diseases. Expert Opin Biol Ther. 2015;15(Suppl 1):S117–127.
   PubMedGoogle Scholar
• Garaci E, Pica F, Matteucci C, et al. Historical review on thymosin α1 in oncology: preclinical and clinical experiences. Expert Opin Biol Ther. 2015;15(Suppl 1):31–39.
   PubMed Web of Science ®Google Scholar
• Matteucci C, Minutolo A, Sinibaldi-Vallebona P, et al. Transcription profile of human lymphocytes following in vitro treatment with thymosin alpha-1. Ann N Y Acad Sci. 2010;1194:6–19.
   PubMed Web of Science ®Google Scholar
• Matteucci C, Minutolo A, Pollicita M, et al. Thymosin α 1 potentiates the release by CD8+ cells of soluble factors able to inhibit HIV-1 and human T lymphotropic virus 1 infection in vitro. Expert Opin Biol Ther. 2015;15(Suppl 1):83–100.
   Google Scholar
• Tripathi S, Pohl MO, Zhou Y, et al. Meta-and orthogonal integration of influenza “OMICs” data defines a role for UBR4 in virus budding. Cell Host Microbe. 2015;18(6):723–735.
   PubMed Web of Science ®Google Scholar
• Ashburner M, Ball CA, Blake JA, et al. Gene ontology: tool for the unification of biology. The gene ontology consortium. Nat Genet. 2000;25(1):25–29.
   PubMed Web of Science ®Google Scholar
• The Gene Ontology Consortium. Expansion of the gene ontology knowledgebase and resources. Nucleic Acids Res. 2017;45(Database issue):D331–D338.
   PubMedGoogle Scholar
• Kanehisa M, Goto S, Kyoto KEGG. Encyclopedia of genes and genomes. Nucleic Acids Res. 2000;28(1):27–30.
   PubMed Web of Science ®Google Scholar
• Huang DW, Sherman BT, Lempicki RA. Systematic and integrative analysis of large gene lists using DAVID bioinformatics resources. Nature Protocols. 2009;4(1):44–57.
   PubMed Web of Science ®Google Scholar
• Becker KG, Barnes KC, Bright TJ, et al. The genetic association database. Nat Genet. 2004;36(5):431–432.
   PubMed Web of Science ®Google Scholar
• Naylor PH, Quadrini K, Garaci E, et al. Immunopharmacology of thymosin alpha1 and cytokine synergy. Ann NY Acad Sci. 2007;1112:235–244.
   PubMed Web of Science ®Google Scholar
• Naylor PH1, Hadden JW. Preclinical studies with IRX-2 and thymosin alpha1 in combination therapy. Ann NY Acad Sci. 2010;1194:162–168.
   PubMed Web of Science ®Google Scholar
• Mastino A, Favalli C, Grelli S, et al. Combination therapy with thymosin alpha 1 potentiates the anti-tumor activity of interleukin-2 with cyclophosphamide in the treatment of the Lewis lung carcinoma in mice. Int J Cancer. 1992;50(3):493–499.
   PubMed Web of Science ®Google Scholar
• Perruccio K, Bonifazi P, Topini F, et al. Thymosin alpha1 to harness immunity to pathogens after haploidentical hematopoietic transplantation. Ann NY Acad Sci. 2010;1194:153–161.
   PubMed Web of Science ®Google Scholar
• Romani L, Bistoni F, Gaziano R, et al. Thymosin alpha 1 activates dendritic cells for antifungal Th1 resistance through toll-like receptor signaling. Blood. 2004;103(11):4232–4239.
   PubMed Web of Science ®Google Scholar
• Tatonetti NP, Liu T, Altman RB, et al. Predicting drug side-effects by chemical systems biology. Genome Biol. 2009;10(9):238.
   PubMed Web of Science ®Google Scholar
• Hotamisligil GS. Inflammation and metabolic disorders. Nature. 2006;444(7121):860–867.
   PubMed Web of Science ®Google Scholar
• Armutcu F, Coskun O, Gürel A, et al. Thymosin alpha 1 attenuates lipid peroxidation and improves fructose-induced steatohepatitis in rats. Clin Biochem. 2005;38(6):540–547.
   PubMed Web of Science ®Google Scholar
• Qiu L, Zhang C, Zhang J, et al. Intraperitoneal co-administration of thymosin alpha-1 ameliorates streptozotocin-induced pancreatic lesions and diabetes in C57BL/6 mice. Int J Mol Med. 2009;23(5):597–602.
   PubMed Web of Science ®Google Scholar
• Lodhi IJ, Semenkovich CF. Peroxisomes: a nexus for lipid metabolism and cellular signaling. Cell Metab. 2014;19(3):380–392.
   PubMed Web of Science ®Google Scholar
• Di Cara F, Sheshachalam A, Braverman NE, et al. Peroxisome-mediated metabolism is required for immune response to microbial infection. Immunity. 2017;47(1):93–106.
   PubMed Web of Science ®Google Scholar
• Lao X, Li B, Liu M, et al. A modified thymosin alpha 1 inhibits the growth of breast cancer both in vitro and in vivo: suppressment of cell proliferation, inducible cell apoptosis and enhancement of targeted anticancer effects. Apoptosis. 2015;20(10):1307–1320.
   PubMed Web of Science ®Google Scholar
• Guo Y, Chang H, Li J, et al. Thymosin alpha 1 suppresses proliferation and induces apoptosis in breast cancer cells through PTEN-mediated inhibition of PI3K/Akt/mTOR signaling pathway. Apoptosis. 2015;20:1109–1121.
   PubMed Web of Science ®Google Scholar
• Giuliani C, Napoletano G, Mastino A, et al. Thymosin-alpha1 regulates MHC class I expression in FRTL-5 cells at transcriptional level. Eur J Immunol. 2000;30(3):778–786.
   PubMed Web of Science ®Google Scholar
• Garaci E, Pica F, Sinibaldi-Vallebona P, et al. Thymosin alpha(1) in combination with cytokines and chemotherapy for the treatment of cancer. Int Immunopharmacol. 2003;3(8):1145–1150.
   PubMed Web of Science ®Google Scholar
• Ni C, Wu P, Wu X, et al. Thymosin alpha1 enhanced cytotoxicity of iNKT cells against colon cancer via upregulating CD1d expression. Cancer Lett. 2015;8(356):579–588.
   Google Scholar
• Li X, Liu X, Zhao Y, et al. Effect of thymosin α₁ on the phenotypic and functional maturation of dendritic cells from children with acute lymphoblastic leukemia. Mol Med Rep. 2015;12(4):6093–6097.
   PubMed Web of Science ®Google Scholar
• Wu X, Jia J, You H. Thymosin alpha-1 treatment in chronic hepatitis B. Expert Opin Bio Ther. 2015;15:S129–S132.
   PubMed Web of Science ®Google Scholar
• Sherman KE. Thymosin alpha 1 for treatment of hepatitis C virus: promise and proof. Ann N Y Acad Sci. 2010;1194:136–140.
   PubMed Web of Science ®Google Scholar
• Naylor PH, Mutchnick MG. Immunotherapy for hepatitis B in the direct acting antiviral era: reevaluating the thymosin α1 efficacy trials in the light of a combination therapy approach. J Viral Hepat. 2018;25(1):4–9.
   PubMed Web of Science ®Google Scholar
• Li C, Bo L, Liu Q, et al. Thymosin alpha1 based immunomodulatory therapy for sepsis: a systematic review and meta-analysis. Int J Infect Dis. 2015;33:90–96.
   PubMed Web of Science ®Google Scholar
• Liu F, Wang HM, Wang T, et al. The efficacy of thymosin α1 as immunomodulatory treatment for sepsis: a systematic review of randomized controlled trials. BMC Infect Dis. 2016;16:488.
   PubMed Web of Science ®Google Scholar
• Jia Z, Feng Z, Tian R, et al. Thymosin α1 plus routine treatment inhibit inflammatory reaction and improve the quality of life in AECOPD patients. Immunopharm Immunot. 2015;37(4):388–392.
   PubMed Web of Science ®Google Scholar
• Romani L, Bistoni F, Perruccio K, et al. Thymosin alpha1 activates dendritic cell tryptophan catabolism and establishes a regulatory environment for balance of inflammation and tolerance. Blood. 2006;108(7):2265–2274.
   PubMed Web of Science ®Google Scholar
• Romani L, Oikonomou V, Moretti S, et al. Thymosin α1 represents a potential potent single-molecule-based therapy for cystic fibrosis. Nat Med. 2017;23(5):590–600.
   PubMed Web of Science ®Google Scholar
• McCuaig S, Martin JG. How the airway smooth muscle in cystic fibrosis reacts in proinflammatory conditions: implications for airway hyper-responsiveness and asthma in cystic fibrosis. Lancet Respir Med. 2013;1(2):137–147.
   PubMed Web of Science ®Google Scholar
• Hübner CA, Jentsch TJ. Ion channel diseases. Hum Mol Genet. 2002;11(20):2435–2445.
   PubMed Web of Science ®Google Scholar
• Bagal SK, Brown AD, Cox PJ, et al. Ion channels as therapeutic targets: a drug discovery perspective. J Med Chem. 2012;56(3):593–624.
   PubMed Web of Science ®Google Scholar
• Bilbo SD, Schwarz JM. The immune system and developmental programming of brain and behavior. Front Neuroendocrinol. 2012;33(3):267–286.
   PubMed Web of Science ®Google Scholar
• Wang G, He F, Zhang Y, et al. Immunopotentiator thymosin alpha-1 promotes neurogenesis and cognition in the developing mouse via a systemic Th1 bias. Neurosci Bull. 2017;33(6):657–684.
   Web of Science ®Google Scholar
• Giacomini E, Rizzo F, Etna MP, et al. Thymosin-α1 expands deficient IL-10-producing regulatory B cell subsets in relapsing-remitting multiple sclerosis patients. Mult Scler. 2017;24(2):1–13.
   Web of Science ®Google Scholar
• Pica F, Chimenti MS, Gaziano R, et al. Serum thymosin α 1 levels in patients with chronic inflammatory autoimmune diseases. Clin Exp Immunol. 2016;186(1):39–45.
   PubMed Web of Science ®Google Scholar
• Dalakas MC, Rose JW, Paul J, et al. Increased circulation of T lymphocytes bearing surface thymosin alpha 1 in patients with myasthenia gravis: effect of thymectomy. Neurology. 1983;33(2):144–149.
   PubMed Web of Science ®Google Scholar
• Sosne G, Rimmer D, Kleinman HK, et al. Thymosin beta 4: a potential novel therapy for neurotrophic keratopathy, dry eye, and ocular surface diseases. Vitam Horm. 2016;102:277–306.
   PubMed Web of Science ®Google Scholar
• Marks ED, Kumar A. Thymosin β4: roles in development, repair, and engineering of the cardiovascular system. Vitam Horm. 2016;102:227–249.
   PubMed Web of Science ®Google Scholar
• Lee JW, Ryu YK, Ji YH, et al. Hypoxia/reoxygenation-experienced cancer cell migration and metastasis are regulated by Rap1- and Rac1-GTPase activation via the expression of thymosin beta-4. Oncotarget. 2015;6(12):9820–9833.
   PubMedGoogle Scholar
• Halder SK, Matsunaga H, Yamaguchi H, et al. Novel neuroprotective action of prothymosin α-derived peptide against retinal and brain ischemic damages. J Neurochem. 2013;125(5):713–723.
   PubMed Web of Science ®Google Scholar
• U.S. Food and Drug Administration (FDA). Novel drug approvals for 2017; [cited 2018 May 14]. Available from: https://www.fda.gov/Drugs/DevelopmentApprovalProcess/DrugInnovation/ucm537040.htm
   Google Scholar