Diffüz Büyük B-hücreli Lenfoma Patogenezinde Tümör-kökenli Ekzozomların Fonksiyonal Önemi

Vildan CANER (Pamukkale Üniversitesi, Tıp Fakültesi, Tıbbi Genetik Anabilim Dalı, Denizli, Türkiye)
GÖKHAN OZAN ÇETİN, (Pamukkale Üniversitesi, Tıp Fakültesi, Dahili Tıp Bilimleri Bölümü, Tıbbi Genetik Anabilim Dalı, Denizli, Türkiye)
Sibel HACIOĞLU KABUKÇU, (Pamukkale Üniversitesi, Tıp Fakültesi, Hematoloji Anabilim Dalı, Denizli, Türkiye)
Emre TEPELİ, (Pamukkale Üniversitesi, Tıp Fakültesi, Tıbbi Biyoloji Anabilim Dalı, Denizli, Türkiye)
GÜLSEREN BAĞCI, (Boş)
Nilay Şen TÜRK (Pamukkale Üniversitesi, Tıp Fakültesi, Patoloji Anabilim Dalı, Denizli, Türkiye)
1 3

Proje Grubu: SBAG Sayfa Sayısı: 75 Proje No: 114S442 Proje Bitiş Tarihi: 01.03.2018 Metin Dili: Türkçe İndeks Tarihi: 19-03-2020

Diffüz Büyük B-hücreli Lenfoma Patogenezinde Tümör-kökenli Ekzozomların Fonksiyonal Önemi

Öz:
DBBHL hastalarının ve saglıklı bireylerin eksozom özelliklerini karsılastırdıgımız arastırmamızda, ayrıca DBBHL hücre hatlarıyla normal B-hücreleri arasındaki eksozomal etkilesim degerlendirildi. DBBHL hastalarında plazma eksozom konsantrasyonu anlamlı derecede yüksekti. DBBHL hastalarının eksozomlarında 33 adet mIRNA?nın ekspresyonunda anlamlı degisim gözlendi. Normal B-hücrelerinin DBBHL-kökenli eksozomları etkin biçimde internalize ettikleri belirlendi. Farklı lenfoma-kökenli eksozomların B-hücrelerinde farklı miRNA ekspresyon profline neden oldukları gözlendi. Bafilomisin ilavesinin, lenfoma hücrelerini RCHOP tedavisine karsı daha duyarlı hale getirdikleri belirlendi. Anahtar Kelimeler: Diffüz Büyük B-hücreli lenfoma, eksozom, miRNA, B-hücresi, Bafilomisin A1, R-CHOP tedavi
Anahtar Kelime: R-CHOP tedavi Bafilomisin A1 B-hücresi miRNA eksozom Diffüz Büyük B-hücreli lenfoma

Konular: Genel ve Dahili Tıp Onkoloji Genetik ve Kalıtım
Erişim Türü: Erişime Açık
  • Agarwal, V. Bell, G. W. Nam, J. W. and Bartel, D. P. 2015. “Predicting effective microRNA target sites in mammalian mRNAs”, eLife, 4, 10.
  • Caner V, Baris IB, Cetin GO, Tepeli E, Turk NS, Zencir S, Sari I, Hacioglu S, Bagci G. Anultracentrifugation- based protocol for exosome isolation in diffuse large B-cell lymphoma. ISEV 2016, 4-7 May, Rotterdam, Hollanda.
  • Ageberg, M. Rydström, K. Lindén, O. Linderoth, J. Jerkeman, M. Drott, K. 2011. “Inhibition of geranylgeranylation mediates sensitivity to CHOP-induced cell death of DLBCL cell lines”, Experimental Cell Research, 317(8), 1179-91.
  • Caner V, Baris IB, Cetin GO, Tepeli E, Turk NS, Zencir S, Sari I, Hacioglu S, Bagci G. Diffüz Büyük B-Hücreli Lenfoma Hastalarının Plazma Eksozom Konsantrasyonlarının Klinik Evre Ile Iliskisi. XII. Tıbbi Genetik Kongresi, 5-9 Ekim 2016, Çesme, Izmir.
  • Ageberg, M. Rydström, K. Lindén, O. Linderoth, J. Jerkeman, M. Drott, K. 2011. “Inhibition of geranylgeranylation mediates sensitivity to CHOP-induced cell death of DLBCL cell lines”, Experimental Cell Research, 317(8), 1179-91, (2011).
  • Alencar, A. J. Malumbres, R. Kozloski, G. A. Advani, R. Talreja, N. Chinichian, S. Briones, J. Natkunam, Y. Sehn, L. H. Gascoyne, R. D. Tibshirani, R. Lossos, I. S. 2011. “MicroRNAs are independent predictors of outcome in diffuse large B-cell lymphoma patients treated with RCHOP”, Clinical Cancer Research, 17(12), 4125–41.
  • Alexander, M. Hu, R. Runtsch, M. C. Kagele, D. A. Mosbruger, T. L. Tolmachova, T. Seabra, M. C. Round, J. L. Ward, D. M. O'Connell, R. M. 2015. “Exosome-delivered microRNAs modulate the inflammatory response to endotoxin”, Nature Communications,18(6), 7321.
  • Baccarini, A. Chauhan, H. Gardner, T. J. Jayaprakash, A. D. Sachidanandam, R. Brown, B. D. 2011. “Kinetic analysis reveals the fate of a microRNA following target regulation in mammalian cells”, Current Biology, 21, 369–376.
  • Ben-Dov, I. Z. Whalen, V. M. Goilav, B. Max, K. E. Tuschl, T. 2016. “Cell and Microvesicle Urine microRNA Deep Sequencing Profiles from Healthy Individuals: Observations with Potential Impact on Biomarker Studies”, PLoS One,11, e0147249.
  • Bennit, H. R. F. Amber, G. Oppegard, L. J. Chi, D. P. Khan, S. Wall, N. R. 2017. “Uptake of lymphoma-derived exosomes by peripheral blood leukocytes”, Blood and Lymphatic Cancer: Targets and Therapy, 79-23.
  • Bracken, C. P. Scott, H. S. Goodall, G. J. 2016. “A network-biology perspective of microRNA function and dysfunction in cancer”, Nature Review Genetics, 17, 719–32.
  • Caby, M. P. Lankar, D. Vincendeau-Scherrer, C. Raposo, G. Bonnerot, C. 2005. “Exosomal like vesicles are present in human blood plasma”, International Immunology, 17(7), 879-87.
  • Cech, T. R. Steitz J. A. 2014. “The noncoding RNA revolution- trashing old rules to forge new ones”, Cell, 157, 77–94.
  • Cha, D. J. Franklin, J. L. Dou, Y. Liu, Q. Higginbotham, J. N. Demory Beckler, M. Weaver, A. M. Vickers, K. Prasad, N. Levy, S. Zhang, B. Coffey, R. J. Patton, J. G. 2015. “KRASdependent sorting of miRNA to exosomes”, eLife. 1(4), e07197.
  • Clague, M. J. Urbé, S. Aniento, F. Gruenberg, J. 1994. “Vacuolar ATPase activity is required for endosomal carrier vesicle formation”, Journal of Biological Chemistry, 269(1), 21-4.
  • Cooks, T. Pateras, I.S. Jenkins, L. M. Patel, K. M. Robles, AI. Morris, J. Forshew, T. Appella, E. Gorgoulis, V. G. Harris, C. C. 2018. “Mutant p53 cancers reprogram macrophages to tumor supporting macrophages via exosomal miR-1246”, Nature Communicate, 22,9(1), 771
  • De Tute, R. M. Barrans, S. Rawstron, A. C. Johnson, P. W. M. Davies, A. J. Jack, A. 2013. “Patients With DLBCL Commonly Have B-Cell Lymphopenia and Circulating Clonal B-Cell Populations With a Phenotype Concordant With The Underlying Tumour”, Blood, 122(21), 3013.
  • Desantes, V. Ilaria, C. Luca, B. Lucia, D. M. Sergio, M. Ivana, C. Maurizio, D. Angelo, V. Maria, A. F. 2015. “MicroRNA profile in bone marrow fibroblasts from patients with multiple myeloma”, EHA Learning Center, 12, 100347.
  • Di Modica, M. Regondi, V. Sandri, M. Iorio, M. V. Zanetti, A. Tagliabue, E. Casalini, P. Triulzi, T. 2017. “Breast cancer-secreted miR-939 downregulates VE-cadherin and destroys the barrier function of endothelial monolayers”, Cancer Letters, 1(384), 94-100.
  • Duffy, A. Le, J. Sausville, E. Emadi, A. 2015. “Autophagy modulation: a target for cancer treatment development”, Cancer Chemotherapy Pharmacology, 75(3), 439-447.
  • Dunleavy, K. Pittaluga, S. Czuczman, M. S. Dave, S. S. Wright, G. Grant, N. Shovlin, M. Jaffe, E. S. Janik, J. E. Staudt, L. M. Wilson, W. H. 2009. “Differential efficacy of bortezomib plus chemotherapy within molecular subtypes of diffuse large B-cell lymphoma” Blood, 113(24), 6069–6076.
  • Eitan, E. Green, J. Bodogai, M. Mode, N. A. Bæk, R. Jørgensen, M. M. Freeman, D. W. Witwer, K. W. Zonderman, A. B. Biragyn, A. Mattson, M. P. Noren Hooten, N. Evans, M. K. 2017. “Age Related Changes in Plasma Extracellular Vesicle Characteristics and Internalization by Leukocytes”, Scientific Reports, 7(1), 1342.
  • Etheridge, A. Lee, I. Hood, L. Galas, D. Wang, K. 2011. “Extracellular microRNA: A new source of biomarkers”, Mutation Research, 717(1-2), 85–90.
  • Fang, C. Zhu, D. -X. Dong, H. -J. Zhou, Z. -J. Wang, Y. -H. Liu, L. Fan, L. Miao, K.-R. Liu, P. Xu, W. et al. 2012, “Serum microRNAs are promising novel biomarkers for diffuse large B cell lymphoma”, Annals of Hematology, 91, 553–559.
  • Fehlmann, T. Ludwig, N. Backes, C. Meese, E. Keller, A. 2016. “Distribution of microRNA biomarker candidates in solid tissues and body fluids”, RNA Biology, 13, 1084–88.
  • Ferrero, G. Cordero, F. Tarallo, S. Arigoni, M. Riccardo, F. Gallo, G. Ronco, G. Allasia, M. Kulkarni, N. Matullo, G. Vineis, P. Calogero, R. A. Pardini, B. Naccarati, A. 2017. “Small noncoding RNA profiling in human biofluids and surrogate tissues from healthy individuals: description of the diverse and most represented species”, Oncotarget, 14,9(3), 3097-3111.
  • Fotinos-Ioannis, D. D. Anastasia, K. Andrew, Y. Kristen, R. Stephen, B. Alicia, H. Malcolm, B. 2016. “Correlation of exosome concentrations in the plasma of lung cancer patients with disease stage”, Journal of Clinical Oncology, 34.
  • Freedman, J. E. Gerstein, M. Mick, E. Rozowsky, J. Levy, D. Kitchen, R. Das, S. Shah, R. Danielson, K. Beaulieu, L. Navarro, F. C. Wang, Y. Galeev, T. R. et al. 2016. “Diverse human extracellular RNAs are widely detected in human plasma”, Nature Communicate, 7, 11106.
  • Galindo-Hernandez, O. Villegas-Comonfort, S. Candanedo, F. et al. 2013. “Elevated concentration of microvesicles isolated from peripheral blood in breast cancer patients”, Archives of Medical Research, 44(3), 208–214,
  • Garzon, R. Marcucci, G. Croce, C. M. 2010. “Targeting microRNAs in cancer: rationale, strategies and challenges”, Nature Reviews Drug Discovery, 9(10), 775-89.
  • Gould, S. J. Raposo, G. 2013. “As we wait: coping with an imperfect nomenclature for extracellular vesicles”, Journal of Extracellular Vesicles, 15, 2.
  • Hans, C. P. Weisenburger D. D. Greiner, T. C. Gascoyne, R. D. Delabie, J. Ott, G. Muller- Hermelink, H. K. Campo, E. Braziel, R. M. Jaffe, E. S. Pan, Z. Farinha, P. Smith L. M. Falini, B. Banham, A. H. Rosenwald, A. Staudt, L. M. Connors, J. M. Armitage, J. O. Chan, W. C. 2004. “Confirmation of the molecular classification of diffuse large B-cell lymphoma by immunohistochemistry using a tissue microarray”, Blood, 103(1), 275-82.
  • Hans, C. P. Weisenburger, D. D. Greiner, T. C. Gascoyne, R. D. Delabie, J. Ott, G. Muller- Hermelink, H. K. Campo, E. Braziel, R. M. Jaffe, E. S. Pan, Z. Farinha, P. Smith, L. M. Falini, B. Banham, A. H. Rosenwald, A. Staudt, L. M. Connors, J. M. Armitage, J. O. Chan, W. C. 2004. “Confirmation of the molecular classification of diffuse large B-cell lymphoma by immunohistochemistry using a tissue microarray”, Blood, 103(1), 275-82
  • Hans, C. P. Weisenburger, D. D. Greiner, T. C. Gascoyne, R. D. Delabie, J. Ott, G. Muller- Hermelink, H. K. Campo, E. Braziel, R. M. Jaffe, E. S. Pan, Z. Farinha, P. Smith, L. M. Falini B. Banham A. H. Rosenwald, A. Staudt, L. M. Connors, J. M. Armitage, J. O. Chan, W. C. 2004. “Confirmation of the molecular classification of diffuse large B-cell lymphoma by immunohistochemistry using a tissue microarray”, Blood, 103(1), 275-82.
  • Hazan-Halevy, I. Rosenblum, D. Weinstein, S. Bairey, O. Raanani, P. Peer, D. 2015. “Cellspecific uptake of mantle cell lymphoma-derived exosomes by malignant and non-malignant B-lymphocytes”, Cancer Letters, 364(1), 59–69.
  • He, M. Crow, J. Roth, M. Zeng, Y. Godwin, A. K. 2014. “Integrated immunoisolation and protein analysis of circulating exosomes using microfluidic technology”, Lab on a Chip, 7,14(19), 3773- 80.
  • Hessvik, N. P. Phuyal, S. Brech, A. Sandvig, K. Llorente, A. 2012. “Profiling of microRNAs in exosomes released from PC-3 prostate cancer cells”, Biochimica et Biophysica Acta, 1819(11- 12), 1154-63.
  • Hruštincová, A. Votavová, H. Dostálová, Merkerová, M. 2015. “Circulating MicroRNAs: Methodological Aspects in Detection of These Biomarkers”, Folia Biologica (Praha) 61(6), 203- 18.
  • Huang, S. Lu, W. Ge, D. Meng, N. Li, Y. Su, L. Zhang, S. Zhang, Y. Zhao, B. Miao, J. 2015. “A new microRNA signal pathway regulated by long noncoding RNA TGFB2-OT1 in autophagy and inflammation of vascular endothelial cells”, Autophagy, 11(12), 2172-83.
  • Iqbal, J. Shen, Y. Huang, X. Liu, Y. Wake, L. Liu, C. Deffenbacher, K. Lachel, C.M. Wang, C. Rohr, J. et al. 2015. “Global microRNA expression profiling uncovers molecular markers for classification and prognosis in aggressive B-cell lymphoma”, Blood, 125, 1137–1145.
  • Ivashchenko, A. Berillo, O. Pyrkova, A. Niyazova, R. Atambayeva, S. 2014. “MiR-3960 binding sites with mRNA of human genes”, Bioinformation, 22,10(7), 423-7.
  • Jaiswal, R. Luk, F. Gong, J. Mathys J. M. Grau, G. E. Bebawy, M. 2012. “Microparticle conferred microRNA profiles - implications in the transfer and dominance of cancer traits”, Molecular Cancer, 11(1), 37.
  • Jones, K. Nourse, J. P. Colm, K. Bhatnagar, A. Gandhi, M. K. 2013, “Plasma microRNA are disease response biomarkers in classical hodgkin lymphoma”, Clinical Cancer Research, 20, 253–264.
  • Jørgensen, M. Bæk, R. Pedersen, S. Søndergaard, E. K. Kristensen, S. R. Varming, K. 2013. “Extracellular Vesicle (EV) Array: microarray capturing of exosomes and other extracellular vesicles for multiplexed phenotyping”, Journal of Extracellular Vesicles, 18, 2.
  • Kawaguchi, T. Miyazawa, K. Moriya, S. Ohtomo, T. Che, X. F. Naito, M. Itoh, M. Tomoda, A. 2011. “Combined treatment with bortezomib plus bafilomycin A1 enhances the cytocidal effect and induces endoplasmic reticulum stress in U266 myeloma cells: crosstalk among proteasome, autophagy-lysosome and ER stres”, International Journal of Oncology, 38(3), 643-54.
  • Keller, S. Sanderson, M. P. Stoeck, A. and Altevogt, P. 2006. “Exosomes: From biogenesis and secretion to biological function”, Immunology Letters, 107(2), 102-08.
  • Khare, D. Goldschmidt, N. Bardugo, A. Gur-Wahnon, D. Ben-Dov, I. Z. Avni B. 2017. “Plasma microRNA profiling: Exploring better biomarkers for lymphoma surveillance”, PLoS One, 13,12(11), e0187722.
  • Klionsky, D. J. Elazar, Z. Seglen, P. O. Rubinsztein, D. C. 2008 “Does bafilomycin A1 block the fusion of autophagosomes with lysosomes”, Autophagy. 4(7), 849–850.
  • Koppers-Lalic, D. Hackenberg, M. Bijnsdorp, IV. van Eijndhoven, M. A. J. Sadek, P. Sie, D. Zini, N. Middeldorp, J. M. Ylstra, B. de Menezes, R. X. Würdinger, T. Meijer, G. A. Pegtel, D. M. 2014. “Nontemplated nucleotide additions distinguish the small RNA composition in cells from exosomes”, Cell Reports, 25,8(6), 1649-1658.
  • Kowal, J. Arras, G. Colombo, M. Jouve, M. Morath, J. P. Primdal-Bengtson, B. Dingli, F. Loew, D. Tkach, M. Théry, C. 2016. “Proteomic comparison defines novel markers to characterize heterogeneous populations of extracellular vesicle subtypes”, Proceedings of National Academy Sciences United States of America, 113(8), 968-77.
  • Kowal, J. Tkach, M. Théry, C. 2014. “Biogenesis and secretion of exosomes”, Current Opinion in Cell Biology, 29, 116-25.
  • Kwak, P. B. Iwasaki, S. Tomari, Y. 2010. “The microRNA pathway and cancer”, Cancer Sciences, 101(11), 2309-15.
  • Lacroix, R. Judicone, C. Mooberry, M. Boucekine, M. Key, N. S. Dignat-George, F. 2013. “The ISTH SSC Workshop. Standardization of pre-analytical variables in plasma microparticle determination: results of the International Society on Thrombosis and Haemostasis SSC Collaborative workshop”, Journal of Thrombosis and Haemostasis.
  • Lacroix, R. Judicone, C. Mooberry, M. Boucekine, M. Key, N. S. Dignat-George, F. 2013. “The ISTH SSC Workshop. “Standardization of pre-analytical variables in plasma microparticle determination: results of the International Society on Thrombosis and Haemostasis SSC Collaborative workshop”, Journal of Thrombosis and Haemostasis.
  • Lasser, C. Eldh, M. Lötvall, J. 2012. “Isolation and Characterization of RNA-Containing Exosomes”, Journal of Visualized Experiments, (59), 3037.
  • Lawrie, C. H. Gal, S. Dunlop, H. M. Pushkaran, B. Liggins, A. P. Pulford, K. Banham, A. H. Pezzella, F. Boultwood, J. Wainscoat, J. S. Hatton, C. S. Harris, A. L. 2008. “Detection of elevated levels of tumour-associated microRNAs in serum of patients with diffuse large B-cell lymphoma”, British Journal of Haematology, 141(5), 672-5.
  • Lawrie, C. H. Gal, S. Dunlop, H. M. Pushkaran, B. Liggins, A.P. Pulford, K. Banham, A. H. Pezzella, F. Boultwood, J. Wainscoat, J. S. et al. 2008. “Detection of elevated levels of tumourassociated micrornas in serum of patients with diffuse large B-cell lymphoma”, British Journal of Haematology, 141, 672–675.
  • Lawrie, C. H. Gal, S., Dunlop, H. M. Pushkaran, B. Liggins, A. P. Pulford, K. Banham, A. H. Pezzella, F. Boultwood, J., Wainscoat, J. S. et al. 2008. “Detection of elevated levels of tumourassociated micrornas in serum of patients with diffuse large B-cell lymphoma”, British Journal of Haematology, 141, 672–675.
  • Le, M. Fernandez-Palomo, C. McNeill, F. E. Seymour, C. B. Rainbow, A. J. Mothersill, C. E. 2017. “Exosomes are released by bystander cells exposed to radiation-induced biophoton signals: Reconciling the mechanisms mediating the bystander effect”, PLoS One, 9,12(3), e0173685.
  • Lenz, G. Wright, G. W. Emre, N. C. Kohlhammer, H. Dave, S. S. Davis, R. E. Carty, S. Lam, L. T. Shaffer, A. L. Xiao, W. Powell, J. Rosenwald, A. Ott, G. Muller-Hermelink, H. K. Gascoyne, R. D. Connors, J. M. Campo, E. Jaffe, E. S. Delabie, J. Smeland, E. B. Rimsza, L. M. Fisher, R. I. Weisenburger, D. D. Chan, W. C. Staudt, L. M. 2008. “Molecular subtypes of diffuse large B-cell lymphoma arise by distinct genetic pathways”, Proceedings of the National Academy of Sciences of the USA, 105(36), 13520–13525.
  • Lespagnol, A. et al. 2008. “Exosome secretion, including the DNA damage-induced p53- dependent secretory pathway, is severely compromised in TSAP6/Steap3-null mice”, Cell Death & Differentiation, 15, 1723–1733.
  • Li, H. Huang, S. Guo, C. Guan, H. Xiong, C. 2012. “Cell-free seminal mRNA and microRNA exist in different forms”, PLoS One, 7(4), e34566.
  • Lobb, R. J. Becker, M. Wen, S. W. Wong, C. S. Wiegmans, A. P. Leimgruber, A. Möller, A. “Optimized exosome isolation protocol for cell culture supernatant and human plasma”, Journal of Extracellular Vesicles, 17(4), 27031.
  • Lötvall, J, Hill, A. F. Hochberg, F. Buzás, E. Di Vizio, D. Gardiner, C. Gho, Y. S. Kurochkin IV, Mathivanan, S. Quesenberry, P. Sahoo, S. Tahara, H. Wauben, M. H. Witwer, K. W. Théry, C. 2014. “Minimal experimental requirements for definition of extracellular vesicles and their functions: a position statement from the International Society for Extracellular Vesicles”, Journal Extracellular Vesicles, 22, 3.
  • Ludwig, N. Leidinger, P. Becker, K. Backes, C. Fehlmann, T. Pallasch, C. Rheinheimer, S. Meder, B. Stähler, C. Meese, E. Keller, A. 2016. “Distribution of miRNA expression across human tissues”, Nucleic Acids Reserch, 5,44(8), 3865-77.
  • Malumbres, R. Sarosiek, K. A. Cubedo, E. Ruiz, J. W. Jiang, X. Gascoyne, R. D. Tibshirani, R. Lossos, I. S. 2009. “Differentiation stage-specific expression of microRNAs in B lymphocytes and diffuse large B-cell lymphomas”, Blood, 113(6), 3754-3764.
  • Margue, C. Reinsbach, S. Philippidou, D. Beaume, N. Walters, C. Schneider, J. G. Nashan, D. Behrmann, I. Kreis, S. 2015. “Comparison of a healthy miRNome with melanoma patient miRNomes: are microRNAs suitable serum biomarkers for cancer”, Oncotarget, 6, 12110–27.
  • Mateescu, B. Kowal, E. J. van Balkom, B. W. Bartel, S. Bhattacharyya, S. N. Buzás, E. Buck, A. H. de Candia, P. Chow, F. W. Das, S. Driedonks, T. A. Fernández-Messina, L. Haderk, F. Hill, A. F. Jones, J. C. Van Keuren-Jensen, K. R. Lai, C. P. Lässer, C. Liegro, I. D. Lunavat, T. R. Lorenowicz, M. J. Maas, S. L. Mäger, I. Mittelbrunn, M. Momma, S. Mukherjee, K. Nawaz, M. Pegtel, D. M. Pfaffl, M. W. Schiffelers, R. M. Tahara, H. Théry, C. Tosar, J. P. Wauben, M. H. Witwer, K. W. Nolte-'t Hoen, E. N. 2017. “Obstacles and opportunities in the functional analysis of extracellular vesicle RNA - an ISEV position paper”, Journal of Extracellular Vesicles, 7,6(1).
  • Mathivanan, S. Ji, H. Simpson, R. J. 2010. “Exosomes: extracellular organelles important in intercellular communication” Journal of Proteomics, 73(10), 1907-20.
  • Matsuzaki, J. Ochiya, T. 2017. “Circulating microRNAs and extracellular vesicles as potential cancer biomarkers: a systematic review”, International Journal of Clinical Oncology, 22(3), 413-420.
  • McCready, J, Sims, J. D. Chan, D. Jay, D. G. 2010. “Secretion of extracellular hsp90alpha via exosomes increases cancer cell motility: a role for plasminogen activation”, BMC Cancer, 16(10), 294.
  • McDonald, M. K. Capasso, K. E. Ajit, S. K. 2013. “Purification and microRNA profiling of exosomes derived from blood and culture media”, Journal of Visualized Experiment, 14(76), e50294.
  • McDonald, M. K. Capasso, K. E. Ajit, S. K. 2013. “Purification and microRNA profiling of exosomes derived from blood and culture media”, Journal of Visualized Experiments, (76), e50294.
  • Monique, A. J. van Eijndhoven, J. Zijlstra, M. Nils, J. Groenewegen, Esther, E. E. Drees, Stuart, van Niele, S. Rubina, B. Danijela, K. L. Hans van der, V. Libregts, S. Marca, H. M. W., Renee, X. de M. Jan, R. T. Van, W., Rienk, N. Lydia, V. Anke, van den B. Daphne de, J. and D. Michiel, P. 2016, “Plasma vesicle miRNAs for therapy response monitoring in Hodgkin lymphoma patients”, JCI Insight, 17,1(19), e89631.
  • Morimura, T. Fujita, K. Akita, M. Nagashima, M. Satomi, A. 2008. “The proton pump inhibitor inhibits cell growth and induces apoptosis in human hepatoblastoma”, Pediatric Surgery International, 24,1087–1094.
  • Moshiri, F. Salvi, A. Gramantieri, L. Sangiovanni, A. Guerriero, P. De Petro, G. Bassi, C. Lupini, L. Sattari, A. Cheung, D. Veneziano, D. Nigita, G. Shankaraiah, R. C. Portolani, N. Carcoforo, P. Fornari, F. Bolondi, L. Frassoldati, A. Sabbioni, S. Colombo, M. Croce, C. M. Negrini, M. 2018. “Circulating miR-106b-3p, miR-101-3p and miR-1246 as diagnostic biomarkers of hepatocellular carcinoma”, Oncotarget, 27,9(20), 15350-15364.
  • Mulcahy, L. A. Pink R. C. Carter, D. R. F. 2014. “Routes and mechanisms of extracellular vesicle uptake”, Journal of Extracellular Vesicles, 3, 10.
  • Muller, L. Hong, C. S. Stolz, D. B. Watkins, S. C. Whiteside, T.L. 2014. “Isolation of biologicallyactive exosomes from human plasma”, Journal of Immunology Methods, 411, 55-65.
  • Muringampurath-John, D. Jaye, D. L. Flowers, C. R. Saxe, D. Chen, Z. Lechowicz, M. J. Weisenburger, D. D. Bast, M. Arellano, M. L. Bernal-Mizrachi, L. Heffner, L. T. McLemore, M. Kaufman, J. L. Winton, E. F. Lonial, S. Armitage, J. O. Khoury, H. J. 2012, “Characteristics and outcomes of diffuse large B-cell lymphoma presenting in leukaemic phase”. British Journal of Haematology, 158(5), 608-14.
  • Pashaei, E. Pashaei, E. Ahmady, M. Ozen, M. Aydin, N. 2017. “Meta-analysis of miRNA expression profiles for prostate cancer recurrence following radical prostatectomy”, PLoS One, 26,12(6), e0179543.
  • Peinado, H. Alečković, M. Lavotshkin, S. Matei, I. Costa-Silva, B. Moreno-Bueno, G. Hergueta- Redondo, M. Williams, C. García-Santos, G. Ghajar, C. Nitadori-Hoshino, A. Hoffman, C. Badal, K. Garcia, B. A. Callahan, M. K. Yuan, J. Martins, V. R. Skog, J. Kaplan, R. N. Brady, M. S. Wolchok, J. D. Chapman, P. B. Kang, Y. Bromberg, J. Lyden, D. 2012. “Melanoma exosomes educate bone marrow progenitor cells toward a pro-metastatic phenotype through MET., Nature Medicine, 18(6), 883-91.
  • Rabinowits, G. Gerçel-Taylor, C. Day, J. M. Taylor, D. D. Kloecker, G. H. 2009. “Exosomal microRNA: a diagnostic marker for lung cancer”, Clinical Lung Cancer,10(1), 42-6.
  • Raposo, G. Stoorvogel, W. 2013. “Extracellular vesicles: exosomes, microvesicles, and friends”, Journal of Cell Biology, 200(4), 373-83.
  • Redmann, M. Benavides, G. A. Berryhill, T. F. Wani, W. Y. Ouyang, X. Johnson, M. S. Ravi, S. Barnes, S. Darley-Usmar, V. M. Zhang, J. 2017. “Inhibition of autophagy with bafilomycin and chloroquine decreases mitochondrial quality and bioenergetic function in primary neurons”, Redox Biology, 11, 73-81.
  • Redmann, M. Benavides, G. A. Berryhill, T. F. Wani, W. Y. Ouyang, X. Johnson, M. S. Ravi, S. Barnes, S. Darley-Usmar, V. M. Zhang, J. 2017. “Inhibition of autophagy with bafilomycin and chloroquine decreases mitochondrial quality and bioenergetic function in primary neurons”, Redox Biology, 11, 73-81.
  • Reza, A. M. M. T. Choi, Y. J. Yuan, Y. G. Das, J. Yasuda, H. Kim, J. H. 2017. “MicroRNA-7641 is a regulator of ribosomal proteins and a promising targeting factor to improve the efficacy of cancer therapy”, Scientific Reports, 21,7(1), 8365.
  • Roccaro, A. M. Sacco, A. Maiso, P. Azab, A. K. Tai, Y. T. Reagan, M. Azab, F. Flores, L. M. Campigotto, F. Weller, E. Anderson, K. C. Scadden, D. T. Ghobrial, I. M. 2013. “BM mesenchymal stromal cell-derived exosomes facilitate multiple myeloma progression”, Journal of Clinical Investigation 123(4),1542-55.
  • Ronquist, K. G. Sanchez, C. Dubois, L. Chioureas, D. Fonseca, P. Larsson, A. Ullén, A. Yachnin, J. Ronquist G. & Panaretakis, T 2016. “Energy-requiring uptake of prostasomes and PC3 cell-derived exosomes into non-malignant and malignant cells”, Journal of Extracellular Vesicles, 7(5), 29877.
  • Saddoughi, S. A. Garrett-Mayer, E. Chaudhary, U. O'Brien, P.E. Afrin, L. B. Day, T. A. Gillespie, M. B. Sharma, A. K. Wilhoit, C. S. Bostick, R. et al. 2011. “Results of a phase II trial of gemcitabine plus doxorubicin in patients with recurrent head and neck cancers: serum C(1)(8)-ceramide as a novel biomarker for monitoring response”, Clinical Cancer Research, 17, 6097-105.
  • Scholer, N. Langer, C. Dohner, H. Buske, C. Kuchenbauer, F. 2010. “Serum microRNAs as a novel class of biomarkers: A comprehensive review of the literatüre” Experimental Hematology, 38(12), 1126–1130.
  • Sentelle, R. D. Senkal, C. E. Jiang, W. Ponnusamy, S. Gencer, S. Selvam, S. P. Ramshesh, V. K. Peterson, Y. K. Lemasters, J. J. Szulc, Z. M. et al. 2012. “Ceramide targets autophagosomes to mitochondria and induces lethal mitophagy”, Nature Chemical Biology, 8, 831-8.
  • Shelke, G. V. Lässer, C. Gho, Y. S. Lötvall, J. 2014. “Importance of exosome depletion protocols to eliminate functional and RNA-containing extracellular vesicles from fetal bovine serum”, Journal of Extracellular Vesicles 30, 3.
  • Shelke, G. V. Lässer, C. Gho, Y. S. Lötvall, J. 2014. “Importance of exosome depletion protocols to eliminate functional and RNA-containing extracellular vesicles from fetal bovine serum”, Journal Extracellular Vesicles.
  • Swerdlow, S. H. Campo, E. Harris, N. L. Jaffe, E. S. Pileri, S. A. Stein, H. Thiele, J. Vardimanet, J. W. 2008. “WHO classification of tumours of haematopoietic and lymphoid tissues”, IARC, Lyon.
  • Szajnik, M. Derbis, M. Lach, M. Patalas, P. Michalak, M. Drzewiecka, H. Szpurek, D. Nowakowski, A. Spaczynski, M. Baranowski, W. Whiteside, T. L. 2013. “Exosomes in Plasma of Patients with Ovarian Carcinoma: Potential Biomarkers of Tumor Progression and Response to Therapy”, Gynecology Obstetrics (Sunnyvale), 29(4), 3.
  • Szczepanski, M. J. Szajnik, M. Welsh, A. Whiteside, T. L. Boyiadzis, M. 2011. “Blast-derived microvesicles in sera from patients with acute myeloid leukemia suppress natural killer cell function via membrane-associated transforming growth factor-beta1”, Haematologica, 96(9), 1302-9.
  • Tang, M. Jiang, L. Lin, Y. Wu, X. Wang, K. He, Q. Wang, X. Li, W. 2017. “Platelet microparticlemediated transfer of miR-939 to epithelial ovarian cancer cells promotes epithelial to mesenchymal transition”, Oncotarget, 27,8(57), 97464-97475.
  • Taylor, D. D. Gercel-Taylor, C. 2008. “MicroRNA signatures of tumor-derived exosomes as diagnostic biomarkers of ovarian cancer”, Gynecologic Oncology, 110(1),13-21.
  • Théry, C. Amigorena, S. Raposo, G. Clayton, A. 2006. “Isolation and characterization of exosomes from cell culture supernatants and biological fluids”, Current Protocol Cell Biology, 3(3), 22.
  • Tiansuo, Z. He, R. Xiuchao, W. Pengfei, L. Fan, Y. Wenna, J. Yang, L. Jing, L. John, G. G. Li, J. Jihui, H. 2015. “Rituximab-induced HMGB1 release is associated with inhibition of STAT3 activity in human diffuse large B-cell lymphoma”, Oncotarget, 6(29), 27816–27831.
  • Trivedi, M. Talekar, M. Shah. P. Ouyang, Q. Amiji, M. 2016. “Modification of tumor cell exosome content by transfection with wt-p53 and microRNA-125b expressing plasmid DNA and its effect on macrophage polarization”, Oncogenesis. 8,5(8), e250.
  • van der Goot, F. G. and Gruenberg, J. 2006. “Intra-endosomal membrane traffic”, Trends in Cell Biology, 16(10), 514-21.
  • Van Deurs, B. Holm, P. K. & Sandvig, K. 1996. “Inhibition of the vacuolar H(+)-ATPase with bafilomycin reduces delivery of internalized molecules from mature multivesicular endosomes to lysosomes in HEp-2 cells”, European Journal of Cell Biology, 69, 343–350.
  • van Deurs, B. Holm, P. K. Sandvig, K. 1996. “Inhibition of the vacuolar H(+)-ATPase with bafilomycin reduces delivery of internalized molecules from mature multivesicular endosomes to lysosomes in HEp-2 cells” European Journal of Cell Biology, 69(4), 343-50.
  • van Schooneveld, E. Wouters, M. C. Van der Auwera, I, et al. 2012. “Expression profiling of cancerous and normal breast tissues identifies microRNAs that are differentially expressed in serum from patients with (metastatic) breast cancer and healthy volunteers”, Breast Cancer Research, 14(1), R34.
  • Vickers, K. C. Palmisano, B. T. Shoucri, B. M. Shamburek, R. D. Remaley, A. T. 2011. “MicroRNAs are transported in plasma and delivered to recipient cells by high-density lipoproteins”, Nature Cell Biology, 13(4), 423-433.
  • Wang, B. Shen, Z. L. Gao, Z. D. Zhao, G. Wang, C. Y. Yang, Y. Zhang, J. Z. Yan, Y. C. Shen, C. Jiang, K. W. Ye, Y. J. Wang, S. 2015. “MiR-194, commonly repressed in colorectal cancer, suppresses tumor growth by regulating the MAP4K4/c-Jun/MDM2 signaling pathway”, Cell Cycle, 14(7), 1046-58.
  • Wang, K. Yuan, Y. Cho, J. H. McClarty, S. Baxter, D. Galas, D. J. 2012. “Comparing the MicroRNA Spectrum between Serum and Plasma”, PLoS One, 7(7), e41561.
  • Weber, J. A. Baxter, D. H. Zhang, S. Huang, D. Y. Huang, K. H. Lee, M. J. Galas, D. J. Wang, K. 2010. “The microRNA spectrum in 12 body fluids” Clinical Chemistry, 56(11), 1733–1741.
  • Whiteside, T. L. 2016. “Tumor-derived exosomes and their role in cancer progression”, Advance in Clinical Chemistry. 74, 103–141.
  • Willms, E. Johansson, H. J. Mäger, I. Lee, Y. Blomberg, K. E. Sadik, M. Alaarg, A. Smith, C. I. Lehtiö, J. El Andaloussi, S. Wood, M. J. Vader, P. 2016. “Cells release subpopulations of exosomes with distinct molecular and biological properties”, Scientific Reports, 2(6), 22519.
  • Witwer, K. W. Buzás, E. I. Bemis, L. T. Bora, A. Lässer, C. Lötvall, J. Nolte-'t Hoen, E. N. Piper, M. G. Sivaraman, S. Skog, J. Théry, C. Wauben, M. H. Hochberg, F. 2013. “Standardization of sample collection, isolation and analysis methods in extracellular vesicle research”, Journal of Extracellular Vesicles.
  • Witwer, K. W. Buzás, E. I. Bemis, L. T. Bora, A. Lässer, C. Lötvall, J. Nolte-'t Hoen, E. N. Piper, M. G. Sivaraman, S. Skog, J. Théry, C. Wauben, M. H. Hochberg, F. 2013. “Standardization of sample collection, isolation and analysis methods in extracellular vesicle research”, Journal of Extracellular Vesicles, 2.
  • Witwer, K. W. Soekmadji, C. Hill, A. F. Wauben, M. H. Buzás, E. Di Vizio, D. Falcon-Perez, J. M. Gardiner, C. Hochberg, F. Kurochkin IV, Lötvall, J. Mathivanan, S. Nieuwland, R. Sahoo, S. Tahara, H. Torrecilhas, A. C. Weaver, A. M. Yin, H. Zheng, L. Gho, Y. S. Quesenberry, P. Théry, C. 2017. “Updating the MISEV minimal requirements for extracellular vesicle studies: building bridges to reproducibility”, Journal of Extracellular Vesicles, 15,6(1), 1396823.
  • Xiao, C. Calado, D. P. Galler, G. Thai, T. H. Patterson, H.C. Wang, J. Rajewsky, N. Bender, T. P. Rajewsky, K. 2007. “Mir-150 controls B cell differentiation by targeting the transcription factor c-Myb”, Cell, 131, 146–159.
  • Xiaodong, L. Lufang, C. Yuanyuan, C. Qixiang, S. Wenxin, Q. 2015. “Bafilomycin A1 inhibits the growth and metastatic potential of the BEL-7402 liver cancer and HO-8910 ovarian cancer cell lines and induces alterations in their microRNA expression”, Experimental and Therapeutic Medicine, 10(5), 1829–1834.
  • Yan, S. Han, B. Gao, S. Wang, X. Wang, Z. Wang, F. Zhang, J. Xu, D. Sun, B. 2017. “Exosome-encapsulated microRNAs as circulating biomarkers for colorectal cancer”, Oncotarget,16,8(36), 60149-60158.
  • Yeh, Y. Y. Ozer, H. G. Lehman, A. M. Maddocks, K. Yu, L, Johnson, A.J. Byrd, J. C. 2015. “Characterization of CLL exosomes reveals a distinct microRNA signature and enhanced secretion by activation of BCR signaling”, Blood. 125(21), 3297-305.
  • Yuan, N. Song, L. Zhang, S. Lin, W. Cao, Y. Xu, F. Fang, Y. Wang, Z. Zhang, H. Li, X. Wang, Z. Cai, J. Wang, J. Zhang, Y. Mao, X. Zhao, W. Hu, S. Chen, S. Wang, J. 2015. “Bafilomycin A1 targets both autophagy and apoptosis pathways in pediatric B-cell acute lymphoblastic leukemia”, Haematologica, 100(3), 345-56.
  • Yuan, N. Song, L. Zhang, S. Lin, W. Cao, Y. Xu, F. Fang, Y. Wang, Z. Zhang, H. Li, X. Wang, Z. Cai, J. Wang, J. Zhang, Y. Mao, X. Zhao, W. Hu, S. Chen, S. Wang, J. 2015. “Bafilomycin A1 targets both autophagy and apoptosis pathways in pediatric B-cell acute lymphoblastic leukemia”, Haematologica, 100(3), 345-56.
  • Yuan, N. Song, L. Zhang, S. Lin, W. Cao, Y. Xu, F. Fang, Y. Wang, Z. Zhang, H. Li, X. Wang, Z. Cai, J. Wang, J. Zhang, Y. Mao, X. Zhao, W. Hu, S. Chen, S. Wang, J. 2015. “Bafilomycin A1 targets both autophagy and apoptosis pathways in pediatric B-cell acute lymphoblastic leukemia”, Haematologica, 100(3), 345-56.
  • Yuan, T. Huang, X. Woodcock, M. Du, M. Dittmar, R. Wang, Y. Tsai, S. Kohli, M. Boardman, L. Patel, T. Wang, L. 2016. “Plasma extracellular RNA profiles in healthy and cancer patients”, Scientific Reports, 6, 19413.
  • Zhang, J. X. Xu, Y. Gao, Y. Chen, C. Zheng, Z. S. Yun, M. Weng, H.W. Xie, D. Ye, S. 2017. “Decreased expression of miR-939 contributes to chemoresistance and metastasis of gastric cancer via dysregulation of SLC34A2 and Raf/MEK/ERK pathway”, Molecular Cancer, 23,16(1), 18.
  • Zhang, Y. Liu, D. Chen, X. et al. 2010. “Secreted monocytic miR-150 enhances targeted endothelial cell migration”, Molecular Cell, 39(1), 133-144,
  • Zhao, T. Ren, H. Wang, X. Liu, P. Yan, F. Jiang, W. Li, Y. Li, J. Gribben, J. G. Jia, L. Hao, J. 2015. “Rituximab-induced HMGB1 release is associated with inhibition of STAT3 activity in human diffuse large B-cell lymphoma”, Oncotarget, 6(29), 27816-31.
  • Zhua, H. Guarigliab, S. Yua, R. Y. L. Lia, W. Branchoa, D. Peinadoc, H. Lydenc, D. Salzerd, J. Bennette, C. Chowa, C. W. 2013. “Mutation of SIMPLE in Charcot–Marie–Tooth 1C alters production of exosomes”, Molecular Biology of the Cell, 24(11), 1619-37.
APA CANER V, ÇETİN G, HACIOĞLU KABUKÇU S, TEPELİ E, bağcı g, ŞEN TÜRK N (2018). Diffüz Büyük B-hücreli Lenfoma Patogenezinde Tümör-kökenli Ekzozomların Fonksiyonal Önemi. , 1 - 75.
Chicago CANER Vildan,ÇETİN GÖKHAN OZAN,HACIOĞLU KABUKÇU Sibel,TEPELİ Emre,bağcı gülseren,ŞEN TÜRK Nilay Diffüz Büyük B-hücreli Lenfoma Patogenezinde Tümör-kökenli Ekzozomların Fonksiyonal Önemi. (2018): 1 - 75.
MLA CANER Vildan,ÇETİN GÖKHAN OZAN,HACIOĞLU KABUKÇU Sibel,TEPELİ Emre,bağcı gülseren,ŞEN TÜRK Nilay Diffüz Büyük B-hücreli Lenfoma Patogenezinde Tümör-kökenli Ekzozomların Fonksiyonal Önemi. , 2018, ss.1 - 75.
AMA CANER V,ÇETİN G,HACIOĞLU KABUKÇU S,TEPELİ E,bağcı g,ŞEN TÜRK N Diffüz Büyük B-hücreli Lenfoma Patogenezinde Tümör-kökenli Ekzozomların Fonksiyonal Önemi. . 2018; 1 - 75.
Vancouver CANER V,ÇETİN G,HACIOĞLU KABUKÇU S,TEPELİ E,bağcı g,ŞEN TÜRK N Diffüz Büyük B-hücreli Lenfoma Patogenezinde Tümör-kökenli Ekzozomların Fonksiyonal Önemi. . 2018; 1 - 75.
IEEE CANER V,ÇETİN G,HACIOĞLU KABUKÇU S,TEPELİ E,bağcı g,ŞEN TÜRK N "Diffüz Büyük B-hücreli Lenfoma Patogenezinde Tümör-kökenli Ekzozomların Fonksiyonal Önemi." , ss.1 - 75, 2018.
ISNAD CANER, Vildan vd. "Diffüz Büyük B-hücreli Lenfoma Patogenezinde Tümör-kökenli Ekzozomların Fonksiyonal Önemi". (2018), 1-75.
APA CANER V, ÇETİN G, HACIOĞLU KABUKÇU S, TEPELİ E, bağcı g, ŞEN TÜRK N (2018). Diffüz Büyük B-hücreli Lenfoma Patogenezinde Tümör-kökenli Ekzozomların Fonksiyonal Önemi. , 1 - 75.
Chicago CANER Vildan,ÇETİN GÖKHAN OZAN,HACIOĞLU KABUKÇU Sibel,TEPELİ Emre,bağcı gülseren,ŞEN TÜRK Nilay Diffüz Büyük B-hücreli Lenfoma Patogenezinde Tümör-kökenli Ekzozomların Fonksiyonal Önemi. (2018): 1 - 75.
MLA CANER Vildan,ÇETİN GÖKHAN OZAN,HACIOĞLU KABUKÇU Sibel,TEPELİ Emre,bağcı gülseren,ŞEN TÜRK Nilay Diffüz Büyük B-hücreli Lenfoma Patogenezinde Tümör-kökenli Ekzozomların Fonksiyonal Önemi. , 2018, ss.1 - 75.
AMA CANER V,ÇETİN G,HACIOĞLU KABUKÇU S,TEPELİ E,bağcı g,ŞEN TÜRK N Diffüz Büyük B-hücreli Lenfoma Patogenezinde Tümör-kökenli Ekzozomların Fonksiyonal Önemi. . 2018; 1 - 75.
Vancouver CANER V,ÇETİN G,HACIOĞLU KABUKÇU S,TEPELİ E,bağcı g,ŞEN TÜRK N Diffüz Büyük B-hücreli Lenfoma Patogenezinde Tümör-kökenli Ekzozomların Fonksiyonal Önemi. . 2018; 1 - 75.
IEEE CANER V,ÇETİN G,HACIOĞLU KABUKÇU S,TEPELİ E,bağcı g,ŞEN TÜRK N "Diffüz Büyük B-hücreli Lenfoma Patogenezinde Tümör-kökenli Ekzozomların Fonksiyonal Önemi." , ss.1 - 75, 2018.
ISNAD CANER, Vildan vd. "Diffüz Büyük B-hücreli Lenfoma Patogenezinde Tümör-kökenli Ekzozomların Fonksiyonal Önemi". (2018), 1-75.
Sayfa Oluşturulma Tarihi
24-04-2024 1:42

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