Jump to ContentJump to Main Navigation
Show Summary Details
More options …

Journal of Veterinary Research

formerly Bulletin of the Veterinary Institute in Pulawy

4 Issues per year


IMPACT FACTOR Bull Vet Inst Pulawy 2016: 0.462

CiteScore 2016: 0.46

SCImago Journal Rank (SJR) 2015: 0.230
Source Normalized Impact per Paper (SNIP) 2015: 0.383

Open Access
Online
ISSN
2450-8608
See all formats and pricing
More options …

In vitro drug sensitivity in canine lymphoma

Aleksandra Pawlak / Bożena Obmińska-Mrukowicz / Iwona Zbyryt
  • Laboratory of Flow Cytometry, Faculty of Veterinary Medicine, Wroclaw University of Environmental and Life Sciences, 50-366 Wroclaw, Poland
  • Other articles by this author:
  • De Gruyter OnlineGoogle Scholar
/ Andrzej Rapak
  • Laboratory of Tumor Molecular Immunobiology, Ludwik Hirszfeld Institute of Immunology and Experimental Therapy, 53-114 Wroclaw, Poland
  • Other articles by this author:
  • De Gruyter OnlineGoogle Scholar
Published Online: 2016-04-29 | DOI: https://doi.org/10.1515/jvetres-2016-0009

Abstract

Introduction: Due to the high heterogeneity of canine lymphoma, the aim of the present study was to test in vitro the chemosensitivity of canine high-grade primary lymphoma cells to various cytostatic drugs commonly used to treat dogs: 4-HO-cyclophosphamide, doxorubicin, dexamethasone, prednisolone, vincristine, etoposide, chlorambucil, lomustine, and cytosine arabinoside. Material and Methods: To determine the cell viability and drug ability to induce apoptosis two different tests were used: an MTT assay and annexin V/propidium iodide staining. Results: Both in vitro tests were found to be useful tools. Significant differences in the sensitivity, depending on the drug type, between B-, T- and mixed/null-type lymphoma cells were found for the majority of the tested drugs. B-type cells were the most sensitive in vitro, whereas T-type cells seemed to be the most resistant. Doxorubicin, chlorambucil, etoposide, and vincristine most strongly reduced the cell viability and induced apoptosis. Conclusion: In vitro assays, such as the MTT test and especially the annexin V/PI assay, may be useful tools for predicting a response to the treatment of high-grade lymphoma in dogs or improving the treatment outcomes in individual animals.

Keywords: canine lymphoma; cytostatic drugs; chemosensitivity; MTT test; apoptosis

References

  • 1. Den Boer M.L., Harms D.O., Pieters R., Kazemier K.M., Gobel U., Körholz D., Graubner U., Haas R.J., Jorch N., Spaar H.J., Kaspers G.J., Kamps W.A., Van der Does-Van den Berg A., Van Wering E.R., Veerman A.J., Janka-Schaub G.E.: Patient stratification based on prednisolone-vincristineasparaginase resistance profiles in children with acute lymphoblastic leukemia. J Clin Oncol 2003, 21, 262-3268.Google Scholar

  • 2. Escherich G., Tröger A., Göbel U., Graubner U., Pekrun A., Jorch N., Kaspers G., Zimmermann M., zur Stadt U., Kazemier K., Pieters R., Den Boer M.L., Horstmann M., Janka G.E.: The long-term impact of in vitro drug sensitivity on risk stratification and treatment outcome in acute lymphoblastic leukemia of childhood (CoALL 06-97). Haematologica 2011, 96, 854-862.Google Scholar

  • 3. Fedele C., Tothill R.W., McArthur G.A.: Navigating the challenge of tumor heterogeneity in cancer therapy. Cancer Discov 2014, 4,146-148.CrossrefWeb of ScienceGoogle Scholar

  • 4. Gaurnier-Hausser A., Patel R., Baldwin A.S., May M.J., Mason N.J.: NEMO-binding domain peptide inhibits constitutive NF-kappaB activity and reduces tumor burden in a canine model of relapsed, refractory diffuse large B-cell lymphoma. Clin Cancer Res 2011, 17, 4661-4671.CrossrefGoogle Scholar

  • 5. Hatok J., Babusikova E., Matakova T., Mistuna D., Dobrota D., Racay P.: In vitro assays for the evaluation of drug resistance in tumor cells. Clin Exp Med 2009, 9, 1-7.Web of ScienceCrossrefGoogle Scholar

  • 6. Ito D., Frantz A.M., Modiano J.F.: Canine lymphoma as a comparative model for human non-Hodgkin lymphoma: recent progress and applications. Vet Immunol Immunopathol 2014, 24, 16.Web of ScienceGoogle Scholar

  • 7. Ito D., Frantz A.M., Williams C., Thomas R., Burnett R.C., Avery A.C., Modiano J.F.: CD40 ligand is necessary and sufficient to support primary diffuse large B-cell lymphoma cells in culture: a tool for in vitro preclinical studies with primary B-cell malignancies. Leuk Lymphoma 2012, 53, 1390-1398.CrossrefWeb of ScienceGoogle Scholar

  • 8. Kaspers G.J., Pieters R., Van Zantwijk C.H., De Laat P.A., De Waal F.C., Van Wering E.R., Veerman A.J.: In vitro drug sensitivity of normal peripheral blood lymphocytes and childhood leukaemic cells from bone marrow and peripheral blood. Br J Cancer 1991, 64, 469-474.CrossrefGoogle Scholar

  • 9. Kitada S., Andersen J., Akar S., Zapata J.M., Takayama S., Krajewski S., Wang H.G., Zhang X., Bullrich F., Croce C.M., Rai K., Hines J., Reed J.C.: Expression of apoptosis-regulating proteins in chronic lymphocytic leukemia: correlations with in vitro and in vivo chemoresponses. Blood 1998, 91, 3379-3389.Google Scholar

  • 10. Marconato L.: The staging and treatment of multicentric highgrade lymphoma in dogs: a review of recent developments and future prospects. Vet J 2011, 188, 34-38.Google Scholar

  • 11. Marconato L., Gelain M.E., Comazzi S.: The dog as a possible animal model for human non-Hodgkin lymphoma: a review. Hematol Oncol 2013, 31, 1-9.CrossrefWeb of ScienceGoogle Scholar

  • 12. Matsuda A., Tanaka A., Muto S., Ohmori K., Furusaka T., Jung K., Karasawa K., Okamoto N., Oida K., Itai A., Matsuda H.: A novel NF-kappaB inhibitor improves glucocorticoid sensitivity of canine neoplastic lymphoid cells by up-regulating expression of glucocorticoid receptors. Res Vet Sci 2010, 89, 378-382.CrossrefGoogle Scholar

  • 13. Mosmann T.: Rapid colorimetric assay for cellular growth and survival: application to proliferation and cytotoxicity assays. J Immunol Methods 1983, 65, 55-63.CrossrefGoogle Scholar

  • 14. Pawlak A., Rapak A., Drynda A., Poradowski D., Zbyryt I., Dzimira S., Suchański J., Obmińska-Mrukowicz B.: Immunophenotypic characterization of canine malignant lymphoma: a retrospective study of cases diagnosed in Poland Lower Silesia, over the period 2011-2013. Vet Comp Oncol 2014 doi: 10.1111/vco.12112.CrossrefWeb of ScienceGoogle Scholar

  • 15. Pawlak A., Rapak A., Zbyryt I., Obminska-Mrukowicz B.: The effect of common antineoplastic agents on induction of apoptosis in canine lymphoma and leukemia cell lines. In Vivo 2014, 28, 843-850.Google Scholar

  • 16. Pieters R., Huismans D.R., Loonen A.H., Hählen K., van der Does-van den Berg A., van Wering E.R., Veerman A.J.: Relation of cellular drug resistance to long-term clinical outcome in childhood acute lymphoblastic leukaemia. Lancet 1991, 338, 399-403.Google Scholar

  • 17. Price G.S., Page R.L., Fischer B.M., Levine J.F., Gerig T.M.: Efficacy and toxicity of doxorubicin/cyclophosphamide maintenance therapy in dogs with multicentric lymphosarcoma. J Vet Intern Med 1991, 5, 259-262.CrossrefGoogle Scholar

  • 18. Seiser E.L., Thomas R., Richards K.L., Kelley M.K., Moore P., Suter S.E., Breen M.: Reading between the lines: molecular characterization of five widely used canine lymphoid tumour cell lines. Vet Comp Oncol 2013, 11, 30-50.CrossrefWeb of ScienceGoogle Scholar

  • 19. Styczynski, J., Wysocki M.: Is the in vitro drug resistance profile the strongest prognostic factor in childhood acute lymphoblastic leukemia? J Clin Oncol 2004, 5, 963-964.CrossrefGoogle Scholar

  • 20. Vaughan A., Johnson J.L., Williams L.E.: Impact of chemotherapeutic dose intensity and hematologic toxicity on first remission duration in dogs with lymphoma treated with a chemoradiotherapy protocol. J Vet Intern Med 2007, 21, 1332-1339.CrossrefWeb of ScienceGoogle Scholar

  • 21. Zandvliet M., Teske E., Schrickx J.A.: Multi-drug resistance in a canine lymphoid cell line due to increased P-glycoprotein expression, a potential model for drug-resistant canine lymphoma. Toxicol In Vitro 2014, 28, 1498-1506.CrossrefWeb of ScienceGoogle Scholar

About the article

Received: 2015-10-31

Accepted: 2016-03-10

Published Online: 2016-04-29

Published in Print: 2016-03-01


Citation Information: Journal of Veterinary Research, Volume 60, Issue 1, Pages 55–61, ISSN (Online) 2450-8608, DOI: https://doi.org/10.1515/jvetres-2016-0009.

Export Citation

© 2016. This work is licensed under the Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 License. BY-NC-ND 4.0

Citing Articles

Here you can find all Crossref-listed publications in which this article is cited. If you would like to receive automatic email messages as soon as this article is cited in other publications, simply activate the “Citation Alert” on the top of this page.

[1]
Aleksandra Pawlak, Witold Gładkowski, Marcelina Mazur, Marta Henklewska, Bożena Obmińska-Mrukowicz, and Andrzej Rapak
Chemico-Biological Interactions, 2017, Volume 261, Page 18

Comments (0)

Please log in or register to comment.
Log in