EHRLİCH ASSİT TÜMÖR (EAT) MODELİ

Neoplastik hastalıkların deneysel hayvan modelleri, insanlarda görülen kanser türlerinin etiyolojik ve patofizyolojik süreçlerini anlamak ve preklinik çalışmalarda etkili tedavilerin geliştirilebilmesi için oldukça önemlidir. Onkolojik süreçlerin değerlendirilmesinde in vitro modeller sıklıkla kullanılmasına rağmen, uygulanan ajana karşı metabolizma cevabında yaşanan eksiklikler hayvan modellerinin kullanımını vazgeçilmez kılmaktadır. Ehrlich Assit Tümörü (EAT) en yaygın deneysel kanser modellerinden biridir. EAT farklılaşmamış bir karsinom olup orjinal olarak hiperdiploiddir. EAT yüksek transplante olma yeteneğine, hızlı çoğalma, daha kısa yaşam süresi, % 100 malignansiye sahiptir. Tümör hücresi içeren assit sıvısı intraperitoneal olarak enjekte edilir ise sıvı form, deri altına enjekte edilirse solid form elde edilir. EAT hücreleri farelerin peritoneal boşluğunda süspansiyon içinde büyür ve in vitro olarak sentetik yüzeylere yapışmazlar. EAT farklılaşmamış olmaları ve hızlı büyüme oranına sahip olmaları nedeniyle kemoterapiye en duyarlı insan tümörlerine benzer. Bu derlemede kanser yönetimi ile ilişkili birçok çalışmada kullanılan EAT modelinin önemi ve bu modelle ilgili son gelişmeler hakkında bilgi verilecektir.

EHRLİCH ASCİTES TUMOR MODEL

Experimental animal models of the neoplastic diseases are important to understand etiological and pathophysiological processes of cancer types and to develop more effective treatments in preclinical evaluation. Even if, in vitro models are also widely used to study different oncological processes, the response deficiencies of metabolism in case of applied agents cause the cessation of the using animal models. Ehrlich ascites carcinoma (EAC) is one of the commonest experimental tumor models. EAC is referred to as an undifferentiated hyperdiploid, has high transplantable capability, rapid proliferation, shorter life span, and 100% malignancy. If ascites fluid that contains the tumor cell is injected intraperitoneally, the ascitic form is obtained, but if it is injected subcutaneously, a solid form is obtained. EAC cells grow in suspension in the peritoneal cavity of mice and they do not adhere to the synthetic surface in vitro. EAC resembles human tumors which are the most sensitive to chemotherapy due to the fact that they are undifferentiated and that they have a rapid growth rate. This review highlights the importance and some recent advances of EAC model that was used in a lot of researches related to cancer management.

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  • 1. Yıldırım E. Deneysel kanser çalışmalarında kinetik özellikler ve tümör modelleri. Acta Oncologica Turcica 2006; 39:63-71.
  • 2. Eijan AM, Lodillinsky C, Sandes EO. Animal models for basic and preclinical research in bladder cancer. In: Canda AE (eds), Bladder Cancer- From Basic Science to Robotic Surgery. Intech Publisher, Croatia 2012; pp 383-404.
  • 3. Koşan M, Mungan A. Deney hayvanında mesane kanseri modelleri. Üroonkoloji Bülteni 2015; 14:29-32.
  • 4. Zeybek Ü. Kanser araştırmaları ve deneysel modeller. Deneysel Tıp Araştırma Enstitüsü Dergisi 2002; 2:1-12.
  • 5. Ozaslan M, Karagöz ID, Kalender MEI, et al. In vivo Antitumoral effect of Plantago major L. extract on Balb/C mouse with Ehrlich Ascites Tumor. The American Journal of Chinese Medicine 2007; 35:841-851.
  • 6. Karayel İ. Ehrlich Asit Tümörü İmplante Edilen Deneklerde Oksidan Stresin İncelenmesi. Yüksek Lisans Tezi. Gazi Üniversitesi Sağlık Bilimleri Enstitüsü, Ankara 2009; ss 3-8.
  • 7. Yuspa SH, Poirier MC. Chemical carcinogenesis: from animal models to molecular models in one decade. Adv Cancer Research 1988; 50:25-70.
  • 8. Beydogan AB, Bolkent S. The effects of silibin administration for different time periods on mouse liver with Ehrlich ascites carcinoma. Pharmacol Rep 2015; 68:543-549.
  • 9. Bahr HI, Toraih EA, Mohammed EA, et al. Chemopreventive effect of leflunomide against Ehrlich's solid tumor grown in mice: Effect on EGF and EGFR expression and tumor proliferation. Life Sci 2015; 141:193-201.
  • 10. Corbett TH, Polin L, Roberts BJ, et al. Transplantable Syngeneic Rodent Tumors. In: Teicher BA (eds), Tumor Models in Cancer Research. Humana Press, New Jersey 2002; pp 41- 71.
  • 11. Giovanella B. Xenotransplantation of Human Cell Cultures in Nude Mice. In: Teicher BA (eds), Tumor Models in Cancer Research. Humana Press, New Jersey 2002; pp 93-97.
  • 12. Ehrlich P, Apolant H. Beobachtungen Über Maligne Mäusentumoren. Wiener Klinische Wochenschrift 1905; 28:871-874.
  • 13. Ozaslan M, Karagöz ID, Kılıç İH, Güldür ME. Ehrlich ascites carcinoma. African Journal of Biotechnology 2011; 10: 2375-2378.
  • 14. Lazebnik YA, Medvedeva DN, Zenin VV. Reversible G2 block in the cell cycle of ehrlich ascites carcinoma cells. Experimental Cell Research 1991; 195:247-254.
  • 15. Loewenthal H, Jahn G. Übertragung-Suersuche mit carcinomatöser mause-asciteslussigleit und ihr verhalten gegen physikalische und chemische einwirkungen. Z Krebsforsch Journal 1932; 37:439-447.
  • 16. Lettre R, Paweletz N, Werner D, Granzow C. Sublines of the Ehrlich-Lettre Mouse Ascites Tumor. A New Tool for Experimental Cell Research 1972; 59: 59-63.
  • 17. Lennartz KJ, Maurer W, Eder M. Autoradiographic Analysis of the Cell Cycle of Ascites Tumors (Mouse) of Various Chromosome Stemlines and Different Origin. Z Krebsforsch 1968; 71:267-282.
  • 18. Burns ER. Initation of DNA Synthesis in Ehrlich Ascites Tumor Cells in Their Plateau Phase of Growth. The Journal of Cancer Research 1968; 28:1191-96.
  • 19. Kaleoğlu Ö, Dişli N. Ehrlich-Lettre Assit Tümörü. DÜ Tıp Fakültesi Mecmuası 1977; 401:978-984.
  • 20. Klein G. Comparative studies of mouse tumors with respect to their capacity for growth as "ascites tumors" and their average nucleic acid content per cell. Experimental Cell Research 1951; 2:518-573.
  • 21. Abdel-Aziz AK, Shouman S, El-Demerdash E, Elgendy M, Abdel-Naim AB. Chloroquine synergizes sunitinib cytotoxicity via modulating autophagic, apoptotic and angiogenic machineries. Chem Biol Interact 2014; 217:28-40.
  • 22. Gomes Nde M, Rezende Cde M, Fontes SP, Hovell AM, Landgraf RG, Matheus ME, Pinto Ada C, Fernandes PD. Antineoplasic activity of Copaifera multijuga oil and fractions against ascitic and solid Ehrlich tumor. J Ethnopharmacol 2008;119:179- 84.
  • 23. Patel MS, Antala BV, Dowerah E, Senthilkumar R, Lahkar M. Antitumor activity of Pogostemon benghalensis Linn. on ehrlich ascites carcinoma tumor bearing mice. J Cancer Res Ther 2014;10:1071-1075.
  • 24. Altun S, Özalpan A. Interactive regeneration of Liver and Growth of Ehrlich Ascites Tumour in Mice. Biologia Bratislava 2004; 59:375-382.
  • 25. Song Z, Varani J, Goldstein IJ. Differences in cell surface carbohydrates and in laminin and fibronectin synthesis between adherent and nonadherent ehrlich ascites tumor cells. International Journal of Cancer1993; 55:1029-1035.
  • 26. Tannock IF. A Comparison of cell proliferation parameters in solid and ascites ehrlich tumors. Cancer Research 1969; 29: 1527-1534.
  • 27. Altun S. Normal, tümöral ve rejeneratif büyümeler arasındaki kinetik ilişkiler. Traditional Journal Biology Tübitak 1996; 20:153-173.
  • 28. Grune T, Siems W, Uhlig R, Jakstadt M. adenine metabolism of ehrlich mouse ascites cells in proliferating and resting phases of tumor growth. Biochemical Int 1992; 26: 199-209.
  • 29. Szıkla K, Pokorny E, Hullan L, Holczinger L. Variations of thymidine kinase activity and DNA content in ehrlich and l121o ascites tumor cells during tumor growth. Cancer Biochemistry Biophysics 1981; 5:259-264.
  • 30. Segur JA, Ruiz-Bellido MA, Arenas M, et al. Ehrlich ascites tumor cells expressing anti-sense glutaminase rna lose their capacity to evade the mouse immune system. International Journal of Cancer 2001; 91:379-384.
  • 31. Senger DR, Gali SJ, Dvorak MA, et al. tumor cells secrete a vascular permeability factor that promotes accumulation of ascites fluid. Science 1983; 219:983-985.
  • 32. Siems W, Schmidt H, Werner A, Uerlings I, David H, Gerber G. Changes in the Nucleotid Metabolism of Ehrlich Ascites Tumor Cells During Their Growth In vivo. Cellular and Molecular Biology 1989; 35:255-262.
  • 33. Siems WG, Grune T, Schmidt H, Tikhonov YV, Pimenov MA. Purine nucleotide levels in host tissues of ehrlich ascites tumor bearing mice in different growth phases of the tumor. Cancer Research 1993; 53:5143-5147.
  • 34. Schmidt H, Siems W, Müler M, Dumdey R, Rapoport SM. ATP Producing and Consuming Processes of Ehrlich Mouse Ascites Tumor Cells in Proliferating and Resting Phases. Exp Cell Res 1991; 194:122-127.
  • 35. Schwendel A, Siems WG, Grune T, Holzhütter GH. Transitions of hepatic purine metabolism of ehrlich ascites tumor bearing mice in different phases of tumor growth. Biochem Mol Biol Int 1994; 34: 457-463.
  • 36. Skog S, He Q, Tribukait B. Lack of correlation between thymidine kinase activity and changes of dna synthesis with tumour age: an ın vivo study in ehrlich ascites tumour. Cell Tissue Kinetics 1990; 23:603-617.
  • 37. Lobo C, Ruiz-Bellido MA, Aledo JC, et al. Inhibition of glutaminase expression by antisense mrna decreases growth and tumourigenicity of tumour cells. Biochemical Journal 2000; 348: 257-261. 38. Balint Z, Holczinger L. Changes in Lipoprotein Lipase Activity (LPLA) in Tumor Cells and Tissues in Mice Bearing Ehrlich Ascites Tumor. Bull Cancer 1984;71:412-418.
  • 39. Bulan, Ö. Ehrlich Ascites Tümör Hücrelerinde Yaş- lanma ile Hücre Kinetigi Arasındaki İlişkiler. Yüksek Lisans Tezi, İstanbul Üniversitesi Fen Bilimleri Enstitüsü, İstanbul 1990; ss 1-25.
  • 40. Kın, T. The Effects of Carcinostatic Agents on the Cell Cycle of Ehrlich Ascites Carcinoma Cells. Nagoya Journal of Medicine Science 1971; 33:307- 314.
  • 41. Ergül L. Ehrlıch Asit Tümörlerinin Sitogenetik Açıdan İncelenmesi. Yüksek Lisans Tezi, Gaziantep Üniversitesi Fen Bilimleri Enstitüsü, Gaziantep 2011; ss36-55
  • 42. Burns ER. On the Failure of Self-Inhibition of Growth in Tumors. Growth 1969; 33, 24-48.
  • 43. Burns ER, Soloff BL. Further Studies on the Recurrent Growth of the Ehrlich Ascites Tumor. The Anatomical Record 1970; 166: 285.
  • 44. Batista AP, da Silva TG, Teixeira AA, et al. Melatonin effect on the ultrastructure of Ehrlich ascites tumor cells, lifetime and histopathology in Swiss mice. Life Sci 2013; 93:882-8.
  • 45. Ourique F, Kviecinski MR, Felipe KB, et al. DNA damage and inhibition of akt pathway in mcf-7 cells and ehrlich tumor in mice treated with 1,4- naphthoquinones in combination with ascorbate. Oxid Med Cell Longev 2015; 2015:495305.
  • 46. Joseph MM, Aravind SR, George SK, et al. Antitumor activity of galactoxyloglucan-gold nanoparticles against murine ascites and solid carcinoma. Colloids Surf B Biointerfaces 2014; 116:219-27.
  • 47. Patra S, Muthuraman MS, Prabhu AR, Priyadharshini RR, Parthiban S. Evaluation of antitumor and antioxidant activity of Sargassum tenerrimum against Ehrlich ascites carcinoma in mice. Asian Pac J Cancer Prev 2015; 16:915-21.
  • 48. Agrawal SS, Saraswati S, Mathur R, Pandey M. Cytotoxic and antitumor effects of brucine on