Nilotinib, Kronik Miyeloid Lösemi Hücrelerinde JAK/STAT Yolu ve Sitokin Ağı Üzerinden Terapötik Bir Yaklaşım Uygular
Öz
Amaç: Kronik miyeloid lösemi (KML), çeşitli sinyal yollarının aktivasyonuna ve lösemik fenotipin sonucuna yol açan yapıcı bir tirozin kinaz (TK) aktivitesi gösterir. JAK/STAT yolundan aktive edilmiş STAT5A ve STAT5B, bir sitokin ağı tarafından teşvik edilen lösemik hücrelerin büyümesini, çoğalmasını, farklılaşmasını ve hayatta kalmasını indükler. İkinci nesil tirozin kinaz inhibitörü nilotinib, bu onkojenik TK aktivitesini inhibe etme avantajına sahip olduğundan; terapötik yaklaşımının altında yatan mekanizmayı ve yolun gelecekteki moleküler hedeflerini analiz ederek apoptozu nasıl indüklediğini araştırmayı amaçladık.
Yöntem: Nilotinib tedavileri ile hücre canlılığı ve proliferasyon deneyleri, apoptotik analiz, STAT5A&5B mRNA transkriptlerinin ekspresyonel düzenlemeleri, protein ekspresyon seviyeleri ve ayrıca sitokinlerin ekspresyonel değerlendirmeleri, in vitro olarak CML model K562 hücrelerinde belirlendi.
Sonuç: Nilotinib tedavisi, zamana ve doza bağlı bir şekilde lösemik hücre proliferasyonunu ve sağkalımını azaltarak terapötik bir yaklaşımı değerlendirdi; lösemik hücre apoptozunu indüklemek, STAT5A&5B mRNA'yı aşağı regüle etmek ve protein ekspresyon seviyelerini düzenlemek ve sitokin ekspresyon ağını düzenlemek.
Çözüm: Nilotinib aracılı terapötikler, JAK/STAT yolu üyeleri STAT5A ve STAT5B'nin hedeflenmesine bağlı olabilir, ayrıca; sitokin ağının düzenlenmesi, lösemi patogenezinde K562 hücrelerinin nilotinibe duyarlılığı ve tepkisi için başka bir altta yatan mekanizma olabilir.
Anahtar Kelimeler
: Nilotinib Kronik Miyeloid Lösemi JAK/STAT Yolu Sitokinler Apoptoz. Nilotinib Chronic Myeloid Leukemia JAK/STAT Pathway Cytokines Apoptosis.
Kaynakça
- Gardellini A, Guidotti F, Zancanella M, Maino E, Steffanoni S, Turrini M. Lichen planopilaris-like eruption in chronic myeloid leukemia patient during treatment with nilotinib as second-line therapy. J Oncol Pharm Pract,2022; 28(4):969-971.
- Iqbal N, Iqbal N. Imatinib: a breakthrough of targeted therapy in cancer. Chemother Res Pract, 2014;2014: 357027.
- Wei L, Yang Y, Gupta P, Wang A, Zhao M, Zhao Y et al. A Small Molecule Inhibitor, OGP46, Is Effective against Imatinib-Resistant BCR-ABL Mutations via the BCR-ABL/JAK-STAT Pathway. Mol Ther Oncolytics 2020;18: 137-148.
- Du Z, Lovly CM. Mechanisms of receptor tyrosine kinase activation in cancer. Mol Cancer,2018; 17(1): 58.
- Xin P, Xu X, Deng C, Liu S, Wang Y, Zhou X et al. The role of JAK/STAT signaling pathway and its inhibitors in diseases. Int Immunopharmacol, 2020;80: 106210.
- Sanchez-Correa B, Bergua JM, Campos C, Gayoso I, Arcos MJ, Bañas H et al. (2013). Cytokine profiles in acute myeloid leukemia patients at diagnosis: Survival is inversely correlated with IL-6 and directly correlated with IL-10 levels. Cytokine,2013; 61(3): 885-91.
- Xu X, Ye Y, Wang X, Lu B, Guo Z, Wu S.JMJD3-regulated expression of IL-6 is involved in the proliferation and chemosensitivity of acute myeloid leukemia cells. Biol Chem,2021; 402(7): 815-24.
- Nieborowska-Skorska M, Hoser G, Kossey P, Wasik MA, Skorski T. (2002). Complementary functions of the antiapoptotic protein A1 and serine/threonine kinase pim-1 in the BCR/ABL-mediated leukemogenesis. Blood 2002;(20 ;99(12): 4531-9.
- Hennighausen L, Robinson GW. Interpretation of cytokine signaling through the transcription factors STAT5A and STAT5B. Genes Dev.2008; 15;22(6):711-21.
- Ghoreschi K, Laurence A, O'Shea JJ. Janus kinases in immune cell signaling. Immunol Rev, 2009;228(1): 273-87.
- Bousoik E., Montazeri Aliabadi H. “Do We Know Jack” About JAK? A Closer Look at JAK/STAT Signaling Pathway. Front. Oncol. 2018;8:287
- Sanpaolo ER, Rotondo C, Cici D, Corrado A, Cantatore FP. JAK/STAT pathway and molecular mechanism in bone remodeling. Mol Biol Rep 2020; 47(11): 9087-9096.
- Dorritie KA, McCubrey JA, Johnson DE. STAT transcription factors in hematopoiesis and leukemogenesis: opportunities for therapeutic intervention. Leukemia 2014; 28(2):248-57.
- Na YJ, Yu ES, Kim DS, Lee DH, Oh SC, Choi CW. Metformin enhances the cytotoxic effect of nilotinib and overcomes nilotinib resistance in chronic myeloid leukemia cells. Korean J Intern Med, 2021;36(1):S196- s206.
- Hegedus C, Ozvegy-Laczka C, Apáti A, Magócsi M, Német K, Orfi L et al. Interaction of nilotinib, dasatinib and bosutinib with ABCB1 and ABCG2: implications for altered anti-cancer effects and pharmacological properties. Br J Pharmacol, 2009; 158(4):1153-64.
- Zhang BS, Chen YP, LV JL, Yang Y. Comparison of the Efficacy of Nilotinib and Imatinib in the Treatment of Chronic Myeloid Leukemia. J Coll Physicians Surg Pak 2019;29(7):631-34.
- Gallipoli P, Cook A, Rhodes S, Hopcroft L, Wheaton H, Whetton AD, et al. JAK2/STAT5 inhibition by nilotinib with ruxolitinib contributes to the elimination of CML CD34+ cells in vitro and in vivo. Blood. 2014;124:1492– 1501
- Holyoake TL, Vetrie D. The chronic myeloid leukemia stem cell: stemming the tide of persistence. Blood, 2017;129(12):1595-1606.
- Seif F, Khoshmirsafa M, Aazami H, Mohsenzadegan M, Sedighi G, Bahar M. The role of the JAK-STAT signaling pathway and its regulators in the fate of T helper cells. Cell Commun Signal 2017;15(1): 23.
- Wieczorek A, Uharek L. Management of Chronic Myeloid Leukemia Patients Resistant to Tyrosine Kinase Inhibitors Treatment. Biomark Insights 2015;10(3): p. 49-54.
- Maurer B, Kollmann S, Pickem J, Kovacic AH, Sexl V et al. STAT5A and STAT5B-Twins with Different Personalities in Hematopoiesis and Leukemia. Cancers (Basel), 2019;11(11):1726
- Schaller-Schönitz M,Barzan D, Williamson A, Griffiths JR, Dallmann I, Battmer K et al. BCR-ABL affects STAT5A and STAT5B differentially. PLoS One 2014;9(5): e97243.
- Verhoeven Y, Tilborghs S, Jacobs J, Waele JD, Quatannens D, Deben C et al. The potential and controversy of targeting STAT family members in cancer. Semin Cancer Biol 2020;60: 41-56.
- Wang Y, Cai D, Brendel C, Barett C, Erben P, Manley PW et al. Adaptive secretion of granulocytemacrophage colony-stimulating factor (GM-CSF) mediates imatinib and nilotinib resistance in BCR/ABL+ progenitors via JAK-2/STAT-5 pathway activation. Blood 2007;109(5): 2147-55.
- Baśkiewicz-Masiuk M, Machaliński B. The role of the STAT5 proteins in the proliferation and apoptosis of the CML and AML cells. Eur J Haematol 2004;72(6): 420-9.
- Ekiz HA, Can G, Gunduz U, Baran Y. Nilotinib significantly induces apoptosis in imatinib-resistant K562 cells with wild-type BCR-ABL, as effectively as in parental sensitive counterparts. Hematology,2010; 15(1): 33-8.
- Kantarjian H, Giles F, Wunderle L, Bhalla K, O’Brien S, Wassman B et al. Nilotinib in imatinib-resistant CML and Philadelphia chromosome-positive ALL. N Engl J Med, 2006;354(24): 2542-51.
- Kim JW, Roh JW, Park NH, Song YS, Kang SB, Lee HP. Interferon, alpha 17 (IFNA17) Ile184Arg polymorphism and cervical cancer risk. Cancer Letters, 2003;189(2): 183-8.
- Singh MK, Mobeen A, Chandra A, Joshi S, Ramachandran S. A meta-analysis of comorbidities in COVID-19: Which diseases increase the susceptibility of SARS-CoV-2 infection Comput Biol Med, 2021; 130: 104219.
- Ahluwalia P, Ahluwalia M, Mondal AK, Sahajpal N, Kota V, Rojiani MV et al . Immunogenomic Gene Signature of Cell-Death Associated Genes with Prognostic Implications in Lung Cancer. Cancers, 2021;13(1):155
- Guerenne L, Beurlet S, Said M, Gorombei P, Pogam CL, Guidez F et al. Journal of Hematology & Oncology 2016;9:5
- Ge Q, P Cong, Y Ji. Serous IFNA3 predicts unfavorable prognosis in lung cancer via abnormal activation of AKT signaling. IUBMB Life,2019; 71(11): 1806-14.
- https://www.genome.gov/Funded-Programs-Projects/Computational-Genomics-and-Data-ScienceProgram/The-Alliance
- Tagliabue M, Maffini F, Fumagalli C, Gandini S, Lepanto D, Corso F et al. A role for the immune system in advanced laryngeal cancer. Sci Rep, 2020;10(1): 18327.
- Nievergall E, Reynolds J, Kok CH, Watkins DB, Biondo M, Busfield SJ, et al. (2016). TGF‑α and IL‑6 plasma levels selectively identify CML patients who fail to achieve an early molecular response or progress in the first year of therapy. Leukemia 30:1263‑72
- Lokau J, Schoeder V, Haybaeck J, Garbers C. (2019). Jak-Stat Signaling Induced by Interleukin-6 Family Cytokines in Hepatocellular Carcinoma. Cancers (Basel) 11(11): 1704.
- Sharma K, Singh U, Madhukar R, Shukla J, Gupta V, Narayan G et al.(2020). Interleukin 6 and disease transformation in chronic myeloid leukemia: A Northeast Indian population study. J Cancer Res Ther, 6(1): 30-3.
- Manore SG, Doheny DL, Wong GL, Lo H-W. (2022). IL-6/JAK/STAT3 Signaling in Breast Cancer Metastasis: Biology and Treatment. Front. Oncol. 12:866014
- Johnson D, O'Keefe R, Grandis J. (2018). Targeting the IL-6/JAK/STAT3 signaling axis in cancer. Nat Rev Clin Oncol 15: 234–248
- Long SF, Chen GA, Fang MS. (2015). Levels of interleukin-16 in peripheral blood of 52 patients with multiple myeloma and its clinical significance. Int J Clin Exp Med, 8(12): 22520-4.
- Kuett A, Rieger C, Perathoner D, Herold T, Wagner M, Sironi S et al. (2015). IL-8 as a mediator in the microenvironment-leukemia network in acute myeloid leukemia. Scientific Reports 17(5):18411.
- Risnik D, Podaza E, Almejun MB, Colado A, Elias EE, Bezares RF et al.(2017). Revisiting the role of interleukin-8 in chronic lymphocytic leukemia. Scientific Reports 7(1): 15714
- Hantschel O, Gstoettenbauer A, Colinge J, Kaupe I, Bilban M, Burkard TR et al. (2008). The chemokine interleukin-8 and the surface activation protein CD69 are markers for Bcr-Abl activity in chronic myeloid leukemia. Molecular Oncology 2(3):272-81
- Wilson KC, Center DM, Cruikshank WW. (2004). The Effect of Interleukin-16 and its Precursor on T Lymphocyte Activation and Growth, Growth Factors 22(2):97-104,
- de Souza VH, de Alencar JB, Tiyo BT, Alves HV, Vendramini ECL, Sell AM et al. (2020). Association of functional IL16 polymorphisms with cancer and cardiovascular disease: a meta-analysis. Oncotarget. 8:11(36):3405-17
- Richmond J, Tuzova M, Cruikshank W, Center D. (2014). Regulation of Cellular Processes by Interleukin-16 in Homeostasis and Cancer. Journal of Cellular Physiology 229:139–47
- Fountain JW, Karayiorgou M, Taruscio D, Graw SL, Buckler AJ, Ward DC et al. (1992). Genetic and physical map of the interferon region on chromosome 9p. Genomics 14(1): 105-12.
- Ambjørn M, Ejlerskov P, Liu Y, Lees M, Jäättelä M, Issazadeh-Navikas S. (2013). IFNB1/interferon-β-induced autophagy in MCF-7 breast cancer cells counteracts its proapoptotic function. Autophagy, 9(3):287-302.
Nilotinib Exerts a Therapeutic Approach via JAK/STAT Pathway and Cytokine Network in Chronic Myeloid Leukemia Cells
Öz
Aim: Chronic myeloid leukemia (CML) displays a constitutive tyrosine kinase (TK) activity which in turn leads to the activation of various signaling pathways and the outcome of leukemic phenotype. Activated STAT5A and STAT5B from JAK/STAT pathway induce cell growth, proliferation, differentiation, and survival of leukemic cells which are promoted by a cytokine network. Since the second-generation tyrosine kinase inhibitor nilotinib has the advantage of inhibiting this oncogenic TK activity; we aimed to investigate the underlying mechanism of its therapeutic approach and how it induced apoptosis via analyzing the forthcoming molecular targets of the pathway.
Methods: By Nilotinib treatments, cell viability and proliferation assays, apoptotic analysis, expressional regulations of STAT5A&5B mRNA transcripts, protein expression levels, and also cytokines’ expressional assessments were determined in CML model K562 cells, in vitro.
Results: Nilotinib treatment in a time and dose-dependent manner assessed a therapeutic approach by decreasing leukemic cell proliferation and survival; inducing leukemic cell apoptosis, down-regulating STAT5A&5B mRNA, and protein expression levels, and regulating cytokine expressional network.
Conclusion: Nilotinib-mediated therapeutics could be dependent on targeting JAK/STAT pathway members STAT5A and STAT5B, besides; regulating the cytokine network might be another underlying mechanism for sensitization and response of K562 cells to nilotinib in leukemia pathogenesis.
Anahtar Kelimeler
Nilotinib Chronic Myeloid Leukemia JAK/STAT Pathway Cytokines Apoptosis.
Kaynakça
- Gardellini A, Guidotti F, Zancanella M, Maino E, Steffanoni S, Turrini M. Lichen planopilaris-like eruption in chronic myeloid leukemia patient during treatment with nilotinib as second-line therapy. J Oncol Pharm Pract,2022; 28(4):969-971.
- Iqbal N, Iqbal N. Imatinib: a breakthrough of targeted therapy in cancer. Chemother Res Pract, 2014;2014: 357027.
- Wei L, Yang Y, Gupta P, Wang A, Zhao M, Zhao Y et al. A Small Molecule Inhibitor, OGP46, Is Effective against Imatinib-Resistant BCR-ABL Mutations via the BCR-ABL/JAK-STAT Pathway. Mol Ther Oncolytics 2020;18: 137-148.
- Du Z, Lovly CM. Mechanisms of receptor tyrosine kinase activation in cancer. Mol Cancer,2018; 17(1): 58.
- Xin P, Xu X, Deng C, Liu S, Wang Y, Zhou X et al. The role of JAK/STAT signaling pathway and its inhibitors in diseases. Int Immunopharmacol, 2020;80: 106210.
- Sanchez-Correa B, Bergua JM, Campos C, Gayoso I, Arcos MJ, Bañas H et al. (2013). Cytokine profiles in acute myeloid leukemia patients at diagnosis: Survival is inversely correlated with IL-6 and directly correlated with IL-10 levels. Cytokine,2013; 61(3): 885-91.
- Xu X, Ye Y, Wang X, Lu B, Guo Z, Wu S.JMJD3-regulated expression of IL-6 is involved in the proliferation and chemosensitivity of acute myeloid leukemia cells. Biol Chem,2021; 402(7): 815-24.
- Nieborowska-Skorska M, Hoser G, Kossey P, Wasik MA, Skorski T. (2002). Complementary functions of the antiapoptotic protein A1 and serine/threonine kinase pim-1 in the BCR/ABL-mediated leukemogenesis. Blood 2002;(20 ;99(12): 4531-9.
- Hennighausen L, Robinson GW. Interpretation of cytokine signaling through the transcription factors STAT5A and STAT5B. Genes Dev.2008; 15;22(6):711-21.
- Ghoreschi K, Laurence A, O'Shea JJ. Janus kinases in immune cell signaling. Immunol Rev, 2009;228(1): 273-87.
- Bousoik E., Montazeri Aliabadi H. “Do We Know Jack” About JAK? A Closer Look at JAK/STAT Signaling Pathway. Front. Oncol. 2018;8:287
- Sanpaolo ER, Rotondo C, Cici D, Corrado A, Cantatore FP. JAK/STAT pathway and molecular mechanism in bone remodeling. Mol Biol Rep 2020; 47(11): 9087-9096.
- Dorritie KA, McCubrey JA, Johnson DE. STAT transcription factors in hematopoiesis and leukemogenesis: opportunities for therapeutic intervention. Leukemia 2014; 28(2):248-57.
- Na YJ, Yu ES, Kim DS, Lee DH, Oh SC, Choi CW. Metformin enhances the cytotoxic effect of nilotinib and overcomes nilotinib resistance in chronic myeloid leukemia cells. Korean J Intern Med, 2021;36(1):S196- s206.
- Hegedus C, Ozvegy-Laczka C, Apáti A, Magócsi M, Német K, Orfi L et al. Interaction of nilotinib, dasatinib and bosutinib with ABCB1 and ABCG2: implications for altered anti-cancer effects and pharmacological properties. Br J Pharmacol, 2009; 158(4):1153-64.
- Zhang BS, Chen YP, LV JL, Yang Y. Comparison of the Efficacy of Nilotinib and Imatinib in the Treatment of Chronic Myeloid Leukemia. J Coll Physicians Surg Pak 2019;29(7):631-34.
- Gallipoli P, Cook A, Rhodes S, Hopcroft L, Wheaton H, Whetton AD, et al. JAK2/STAT5 inhibition by nilotinib with ruxolitinib contributes to the elimination of CML CD34+ cells in vitro and in vivo. Blood. 2014;124:1492– 1501
- Holyoake TL, Vetrie D. The chronic myeloid leukemia stem cell: stemming the tide of persistence. Blood, 2017;129(12):1595-1606.
- Seif F, Khoshmirsafa M, Aazami H, Mohsenzadegan M, Sedighi G, Bahar M. The role of the JAK-STAT signaling pathway and its regulators in the fate of T helper cells. Cell Commun Signal 2017;15(1): 23.
- Wieczorek A, Uharek L. Management of Chronic Myeloid Leukemia Patients Resistant to Tyrosine Kinase Inhibitors Treatment. Biomark Insights 2015;10(3): p. 49-54.
- Maurer B, Kollmann S, Pickem J, Kovacic AH, Sexl V et al. STAT5A and STAT5B-Twins with Different Personalities in Hematopoiesis and Leukemia. Cancers (Basel), 2019;11(11):1726
- Schaller-Schönitz M,Barzan D, Williamson A, Griffiths JR, Dallmann I, Battmer K et al. BCR-ABL affects STAT5A and STAT5B differentially. PLoS One 2014;9(5): e97243.
- Verhoeven Y, Tilborghs S, Jacobs J, Waele JD, Quatannens D, Deben C et al. The potential and controversy of targeting STAT family members in cancer. Semin Cancer Biol 2020;60: 41-56.
- Wang Y, Cai D, Brendel C, Barett C, Erben P, Manley PW et al. Adaptive secretion of granulocytemacrophage colony-stimulating factor (GM-CSF) mediates imatinib and nilotinib resistance in BCR/ABL+ progenitors via JAK-2/STAT-5 pathway activation. Blood 2007;109(5): 2147-55.
- Baśkiewicz-Masiuk M, Machaliński B. The role of the STAT5 proteins in the proliferation and apoptosis of the CML and AML cells. Eur J Haematol 2004;72(6): 420-9.
- Ekiz HA, Can G, Gunduz U, Baran Y. Nilotinib significantly induces apoptosis in imatinib-resistant K562 cells with wild-type BCR-ABL, as effectively as in parental sensitive counterparts. Hematology,2010; 15(1): 33-8.
- Kantarjian H, Giles F, Wunderle L, Bhalla K, O’Brien S, Wassman B et al. Nilotinib in imatinib-resistant CML and Philadelphia chromosome-positive ALL. N Engl J Med, 2006;354(24): 2542-51.
- Kim JW, Roh JW, Park NH, Song YS, Kang SB, Lee HP. Interferon, alpha 17 (IFNA17) Ile184Arg polymorphism and cervical cancer risk. Cancer Letters, 2003;189(2): 183-8.
- Singh MK, Mobeen A, Chandra A, Joshi S, Ramachandran S. A meta-analysis of comorbidities in COVID-19: Which diseases increase the susceptibility of SARS-CoV-2 infection Comput Biol Med, 2021; 130: 104219.
- Ahluwalia P, Ahluwalia M, Mondal AK, Sahajpal N, Kota V, Rojiani MV et al . Immunogenomic Gene Signature of Cell-Death Associated Genes with Prognostic Implications in Lung Cancer. Cancers, 2021;13(1):155
- Guerenne L, Beurlet S, Said M, Gorombei P, Pogam CL, Guidez F et al. Journal of Hematology & Oncology 2016;9:5
- Ge Q, P Cong, Y Ji. Serous IFNA3 predicts unfavorable prognosis in lung cancer via abnormal activation of AKT signaling. IUBMB Life,2019; 71(11): 1806-14.
- https://www.genome.gov/Funded-Programs-Projects/Computational-Genomics-and-Data-ScienceProgram/The-Alliance
- Tagliabue M, Maffini F, Fumagalli C, Gandini S, Lepanto D, Corso F et al. A role for the immune system in advanced laryngeal cancer. Sci Rep, 2020;10(1): 18327.
- Nievergall E, Reynolds J, Kok CH, Watkins DB, Biondo M, Busfield SJ, et al. (2016). TGF‑α and IL‑6 plasma levels selectively identify CML patients who fail to achieve an early molecular response or progress in the first year of therapy. Leukemia 30:1263‑72
- Lokau J, Schoeder V, Haybaeck J, Garbers C. (2019). Jak-Stat Signaling Induced by Interleukin-6 Family Cytokines in Hepatocellular Carcinoma. Cancers (Basel) 11(11): 1704.
- Sharma K, Singh U, Madhukar R, Shukla J, Gupta V, Narayan G et al.(2020). Interleukin 6 and disease transformation in chronic myeloid leukemia: A Northeast Indian population study. J Cancer Res Ther, 6(1): 30-3.
- Manore SG, Doheny DL, Wong GL, Lo H-W. (2022). IL-6/JAK/STAT3 Signaling in Breast Cancer Metastasis: Biology and Treatment. Front. Oncol. 12:866014
- Johnson D, O'Keefe R, Grandis J. (2018). Targeting the IL-6/JAK/STAT3 signaling axis in cancer. Nat Rev Clin Oncol 15: 234–248
- Long SF, Chen GA, Fang MS. (2015). Levels of interleukin-16 in peripheral blood of 52 patients with multiple myeloma and its clinical significance. Int J Clin Exp Med, 8(12): 22520-4.
- Kuett A, Rieger C, Perathoner D, Herold T, Wagner M, Sironi S et al. (2015). IL-8 as a mediator in the microenvironment-leukemia network in acute myeloid leukemia. Scientific Reports 17(5):18411.
- Risnik D, Podaza E, Almejun MB, Colado A, Elias EE, Bezares RF et al.(2017). Revisiting the role of interleukin-8 in chronic lymphocytic leukemia. Scientific Reports 7(1): 15714
- Hantschel O, Gstoettenbauer A, Colinge J, Kaupe I, Bilban M, Burkard TR et al. (2008). The chemokine interleukin-8 and the surface activation protein CD69 are markers for Bcr-Abl activity in chronic myeloid leukemia. Molecular Oncology 2(3):272-81
- Wilson KC, Center DM, Cruikshank WW. (2004). The Effect of Interleukin-16 and its Precursor on T Lymphocyte Activation and Growth, Growth Factors 22(2):97-104,
- de Souza VH, de Alencar JB, Tiyo BT, Alves HV, Vendramini ECL, Sell AM et al. (2020). Association of functional IL16 polymorphisms with cancer and cardiovascular disease: a meta-analysis. Oncotarget. 8:11(36):3405-17
- Richmond J, Tuzova M, Cruikshank W, Center D. (2014). Regulation of Cellular Processes by Interleukin-16 in Homeostasis and Cancer. Journal of Cellular Physiology 229:139–47
- Fountain JW, Karayiorgou M, Taruscio D, Graw SL, Buckler AJ, Ward DC et al. (1992). Genetic and physical map of the interferon region on chromosome 9p. Genomics 14(1): 105-12.
- Ambjørn M, Ejlerskov P, Liu Y, Lees M, Jäättelä M, Issazadeh-Navikas S. (2013). IFNB1/interferon-β-induced autophagy in MCF-7 breast cancer cells counteracts its proapoptotic function. Autophagy, 9(3):287-302.
Ayrıntılar
| Birincil Dil | İngilizce |
|---|---|
| Konular | Sağlık Kurumları Yönetimi |
| Bölüm | Araştırma Makaleleri |
| Yazarlar | |
| Yayımlanma Tarihi | 19 Mart 2024 |
| Gönderilme Tarihi | 7 Aralık 2022 |
| Yayımlandığı Sayı | Yıl 2024Cilt: 63 Sayı: 1 |
