View More View Less
  • 1 Veterinary Haematology and Oncology Centre, Bolgárkertész u. 31, H-1148 Budapest, Hungary
  • | 2 University of Veterinary Medicine, Budapest, Hungary
Open access

Messenger RNA levels of oncogenic tyrosine kinases were determined in canine mammary tumours using real-time RT-PCR. The following tyrosine kinases and vascular endothelial growth factors (VEGF) were examined in malignant and healthy mammary tissues of 13 dogs: VEGFR1, VEGFR2, EGFR, ErbB2, PDGFR1, c-KIT and c-MET. Expression levels of all these factors were significantly higher in tumour samples than in normal mammary tissues taken from the same animal. Higher grading was associated with higher VEGFR1 levels. Grade III tumours showed significantly higher VEGF, c-MET and c-KIT mRNA expression, while Grade I tumours with lower malignancy showed significantly higher PDGFR1 and EGFR expression than tumours classified as Grade II or III. The increased presence of VEGF, VEGFR1, c-KIT and c-MET is a negative prognostic factor as these signal transduction molecules contribute to increased tumour malignancy. The presented data provide evidence, for the first time, for the existence of a complex overexpression and dysregulation of VEGF and several oncogenic tyrosine kinases such as VEGR1, PDGFR1, c-KIT and c-MET in canine mammary tumours. Therefore, canine mammary tumours may be potential targets for tyrosine kinase inhibitor therapy.

  • Al-Dissi, A. N., Haines, D. M., Singh, B. and Kidney, B. A. (2010): Immunohistochemical expression of vascular endothelial growth factor and vascular endothelial growth factor receptor-2 in canine simple mammary gland adenocarcinomas. Can. Vet. J. 51, 11091114.

    • Search Google Scholar
    • Export Citation
  • Bergman, P. J. (2000): Multidrug resistance. In: Kirk, R. W. (ed.) Current Veterinary Therapy XIII. W. B. Saunders Co., Philadelphia. pp. 479482.

    • Search Google Scholar
    • Export Citation
  • Bhargava, R., Gerald, W. L., Li, A. R., Pan, Q., Lal, P., Ladanyi, M. and Chen, B. (2005): EGFR gene amplification in breast cancer: correlation with epidermal growth factor receptor mRNA and protein expression and HER-2 status and absence of EGFR-activating mutations. Mod. Pathol. 18, 10271033.

    • Search Google Scholar
    • Export Citation
  • Carvalho, I., Milanezi, F., Martins, A., Reis, R. M. and Schmitt, F. (2005): Overexpression of platelet-derived growth factor receptor α in breast cancer is associated with tumour progression. Breast Cancer Res. 7, R788. DOI: 10.1186/bcr1304.

    • Search Google Scholar
    • Export Citation
  • Cassali, G. D., Lavalle, G. E., De Nardi, A. B., Ferreira, E., Bertagnolli, A. C., Estrela-Lima, A. et al. (2011): Consensus for the diagnosis, prognosis and treatment of canine mammary tumors. Braz. J. Vet. Pathol. 4, 153180.

    • Search Google Scholar
    • Export Citation
  • Cherrington, J. M., Strawn, L. M. and Shawver, L. K. (2008): New paradigms for the treatment of cancer: the role of anti-angiogenesis agents. Adv. Cancer Res. 79, 138.

    • Search Google Scholar
    • Export Citation
  • Clemente, M., Sánchez-Archidona, A. R., Sardón, D., Díez, L., Martín-Ruiz, A., Caceres, S., Sassi, F., Dolores Pérez-Alenza, M., Illera, J. C., Dunner, S. and Peña, L. (2013): Different role of COX-2 and angiogenesis in canine inflammatory and non-inflammatory mammary cancer. Vet. J. 197, 427432.

    • Search Google Scholar
    • Export Citation
  • De Giorgio, U. and Verweij, J. (2005): Imatinib and gastrointestinal stromal tumors: Where do we go from here? Mol. Cancer Ther. 4, 495501.

    • Search Google Scholar
    • Export Citation
  • Dickinson, P. J., Roberts, B. N., Higgins, R. J., Leutenegger, C. M., Bollen, A. W., Kass, P. H. and LeCouteur, R. A. (2006): Expression of receptor tyrosine kinases VEGFR-1 (FLT-1), VEGFR-2 (KDR), EGFR-1, PDGFRalpha and c-Met in canine primary brain tumours. Vet. Comp. Onc. 4, 132140.

    • Search Google Scholar
    • Export Citation
  • Downing, S., Chien, M. B., Kass, P. H., Moore, P. E. and London, C. A. (2002): Prevalence and importance of internal tandem duplications in exons 11 and 12 of c-kit in mast cell tumors of dogs. Am. J. Vet. Res. 63, 17181723.

    • Search Google Scholar
    • Export Citation
  • Dubreuil, P., Letard, S., Ciufolini, M., Gros, L., Humbert, M., Castéran, N., Borge, L., Hajem, B., Lermet, A., Sippl, W., Voisset, E., Arock, M., Auclair, C., Leventhal, P. S., Mansfield, C. D., Moussy, A. and Hermine, O. (2009): Masitinib (AB1010), a potent and selective tyrosine kinase inhibitor targeting KIT. PLoS One 4, e7258.

    • Search Google Scholar
    • Export Citation
  • Frost, D., Lasota, J. and Miettinen, M. (2003): Gastrointestinal stromal tumors and leiomyomas in the dog: a histopathologic, immunohistochemical, and molecular genetic study of 50 cases. Vet. Pathol. 40, 4254.

    • Search Google Scholar
    • Export Citation
  • Galli, S. J., Zsebo, K. M. and Geissler, E. N. (1994): The kit ligand, stem cell factor. Adv. Immunol. 55, 195.

  • Goldman, J. M. and Melo, J. V. (2003): Chronic myeloid leukemia – advances in biology and new approaches to treatment. N. Engl. J. Med. 349, 14511464.

    • Search Google Scholar
    • Export Citation
  • Hahn, K. A., Ogilvie, G., Rusk, T., Devauchelle, P., Leblanc, A., Legendre, A., Powers, B., Leventhal, P. S., Kinet, J. P., Palmerini, F., Dubreuil, P., Moussy, A. and Hermine, O. (2008): Masitinib is safe and effective for the treatment of canine mast cell tumors. J. Vet. Int. Med. 22, 13011309.

    • Search Google Scholar
    • Export Citation
  • Ho-Yen, C. M., Jones, J. L. and Kermorgant, S. (2015): The clinical and functional significance of c-Met in breast cancer: a review. Breast Cancer Res. 17, 52.

    • Search Google Scholar
    • Export Citation
  • Hsu, W. L., Huang, H. M., Liao, J. W., Wong, M. L. and Chang, S. C. (2007): Increased survival in dogs with malignant mammary tumours overexpressing HER-2 protein and detection of a silent single nucleotide polymorphism in the canine HER-2 gene. Vet. J. 180, 116123.

    • Search Google Scholar
    • Export Citation
  • Kubo, K., Matsuyama, S., Katayama, K., Tsutsumi, C., Yonezawa, K., Shimada, T., Kotani, T., Sakuma, S., Ohashi, F. and Takamori, Y. (1998): Frequent expression of the c-kit protooncogene in canine malignant mammary tumor. J. Vet. Med. Sci. 60, 13351340.

    • Search Google Scholar
    • Export Citation
  • Lemmon, M. A. and Schlessinger, J. (2010): Cell signaling by receptor tyrosine kinases. Cell 141, 11171134.

  • Liu, J., Liu, X., Feng, X., Liu, J., Lv, S., Zhang, W. and Niu, Y. (2015): C-kit overexpression correlates with KIT gene copy numbers increases in phyllodes tumors of the breast. Breast Cancer Res. Treat. 149, 395401.

    • Search Google Scholar
    • Export Citation
  • London, C. A. (2013): Molecular/targeted therapy of cancer, Section B. Signal transduction and cancer. In: Withrow, S., Vail, D. and Page, R. (eds) Withrow and MacEwen’s Small Animal Clinical Oncology, 5th edition. W. B. Saunders Co., Philadelphia. pp. 221229.

    • Search Google Scholar
    • Export Citation
  • London, C. A., Malpas, P. B., Wood-Follis, S. L., Boucher, J. F., Rusk, A. W., Rosenberg, M. P., Henry, C. J., Mitchener, K. L., Klein, M. K., Hintermeister, J. G., Bergman, P. J., Couto, G. C., Mauldin, G. N. and Michels, G. M. (2009): Multi-center, placebo-controlled, double- blind, randomized study of oral toceranib phosphate (SU11654), a receptor tyrosine kinase inhibitor, for the treatment of dogs with recurrent (either local or distant) mast cell tumor following surgical excision. Clin. Cancer Res. 15, 38563865.

    • Search Google Scholar
    • Export Citation
  • Masuda, H., Zhang, D., Bartholomeusz, C., Doihara, H., Hortobagyi, G. N. and Ueno, N. T. (2012): Role of epidermal growth factor receptor in breast cancer. Breast Cancer Res. Treat. 136, 10.1007/s10549-012-2289-9.

    • Search Google Scholar
    • Export Citation
  • Merlo, D. F., Rossi, L., Pellegrino, C., Ceppi, M., Cardellino, U., Capurro, C., Ratto, A., Sambucco, P. L., Sestito, V., Tanara, G. and Bocchini, V. (2008): Cancer incidence in pet dogs: Findings of the animal tumor registry of Genoa, Italy. J. Vet. Int. Med. 22, 976984.

    • Search Google Scholar
    • Export Citation
  • Millanta, F., Silvestri, G., Vaselli, C., Citi, S., Pisani, G., Lorenzi, D. and Poli, A. (2006): The role of vascular endothelial growth factor and its receptor Flk-1/KDR in promoting tumour angiogenesis in feline and canine mammary carcinomas: a preliminary study of autocrine and paracrine loops. Res. Vet. Sci. 81, 350357.

    • Search Google Scholar
    • Export Citation
  • Patruno, R., Marech, I., Zizzo, N., Ammendola, M., Nardulli, P., Gadaleta, C., Introna, M., Capriuolo, G., Rubini, R. A., Ribatti, D., Gadaleta, C. D. and Ranieri, G. (2014): C-Kit expression, angiogenesis, and grading in canine mast cell tumour: A unique model to study c-Kit driven human malignancies. Biomed. Res. Intern. 12, 2014:730246. Epub 2014 May 12.

    • Search Google Scholar
    • Export Citation
  • Restucci, B., Borzacchiello, G., Maiolino, P., Martano, M., Paciello, O. and Papparella, S. (2004): Expression of vascular endothelial growth factor receptor Flk-1 in canine mammary tumours. J. Comp. Pathol. 130, 99104.

    • Search Google Scholar
    • Export Citation
  • Slamon, D. J., Godolphin, W., Jones, L. A., Holt, J. A., Wong, S. G., Keith, D. E., Levin, W. J., Stuart, S. G., Udove, J., Ullrich, A. and Press, F. (1989): Studies of the HER-2/neu protooncogene in human breast and ovarian cancer. Science 244, 707712.

    • Search Google Scholar
    • Export Citation
  • Stellrecht, C. M. and Gandhi, V. (2009): MET receptor tyrosine kinase as a therapeutic anticancer target. Cancer Lett. 280, 114.

  • Stommel, J. M., Kimmelman, A. C., Ying, H., Nabioullin, R., Ponugoti, A. H., Wiedemeyer, R., Stegh, A. H., Bradner, J. E., Ligon, K. L., Brennan, C., Chin, L. and DePinho, R. A. (2007): Coactivation of receptor tyrosine kinases affects the response of tumor cells to targeted therapies. Science 318, 287290.

    • Search Google Scholar
    • Export Citation
  • Tan, M. and Yu, D. (2007): Molecular mechanisms of ErbB2-mediated breast cancer chemoresistance. Adv. Exp. Med. Biol. 608, 119129.

  • Xu, A. M. and Huang, P. H. (2010): Receptor tyrosine kinase coactivation networks in cancer. Cancer Res. 10, 38573860.

Author information is available in PDF.
Please, download the file from HERE.

The manuscript preparation instructions is available in PDF.
Please, download the file from HERE.

Senior editors

Editor-in-Chief: Mária BENKŐ

Managing Editor: András SZÉKELY

Editorial Board

  • Béla DÉNES (National Food Chain Safety Office, Budapest Hungary)
  • Edit ESZTERBAUER (Veterinary Medical Research Institute, Budapest, Hungary)
  • Hedvig FÉBEL (National Agricultural Innovation Centre, Herceghalom, Hungary)
  • László FODOR (University of Veterinary Medicine, Budapest, Hungary)
  • Balázs HARRACH (Veterinary Medical Research Institute, Budapest, Hungary)
  • Peter MASSÁNYI (Slovak University of Agriculture in Nitra, Nitra, Slovak Republic)
  • Béla NAGY (Veterinary Medical Research Institute, Budapest, Hungary)
  • Tibor NÉMETH (University of Veterinary Medicine, Budapest, Hungary)
  • Zsuzsanna NEOGRÁDY (University of Veterinary Medicine, Budapest, Hungary)
  • Alessandra PELAGALLI (University of Naples Federico II, Naples, Italy)
  • Kurt PFISTER (Ludwig-Maximilians-University of Munich, Munich, Germany)
  • László SOLTI (University of Veterinary Medicine, Budapest, Hungary)
  • József SZABÓ (University of Veterinary Medicine, Budapest, Hungary)
  • Péter VAJDOVICH (University of Veterinary Medicine, Budapest, Hungary)
  • János VARGA (University of Veterinary Medicine, Budapest, Hungary)
  • Štefan VILČEK (University of Veterinary Medicine in Kosice, Kosice, Slovak Republic)
  • Károly VÖRÖS (University of Veterinary Medicine, Budapest, Hungary)
  • Herbert WEISSENBÖCK (University of Veterinary Medicine, Vienna, Austria)
  • Attila ZSARNOVSZKY (Szent István University, Gödöllő, Hungary)

ACTA VETERINARIA HUNGARICA
Institute for Veterinary Medical Research
Centre for Agricultural Research
Hungarian Academy of Sciences
P.O. Box 18, H-1581 Budapest, Hungary
Phone: (36 1) 467 4081 (ed.-in-chief) or (36 1) 213 9793 (editor) Fax: (36 1) 467 4076 (ed.-in-chief) or (36 1) 213 9793

Indexing and Abstracting Services:

  • Biological Abstracts
  • BIOSIS Previews
  • CAB Abstracts
  • Chemical Abstracts
  • Current Contents: Agriculture, Biology and Environmental Sciences
  • Elsevier Science Navigator
  • Focus On: Veterinary Science and Medicine
  • Global Health
  • Index Medicus
  • Index Veterinarius
  • Medline
  • Science Citation Index
  • Science Citation Index Expanded (SciSearch)
  • SCOPUS
  • The ISI Alerting Services
  • Zoological Abstracts

 

2020  
Total Cites 987
WoS
Journal
Impact Factor
0,955
Rank by Veterinary Sciences 101/146 (Q3)
Impact Factor  
Impact Factor 0,920
without
Journal Self Cites
5 Year 1,164
Impact Factor
Journal  0,57
Citation Indicator  
Rank by Journal  Veterinary Sciences 93/166 (Q3)
Citation Indicator   
Citable 49
Items
Total 49
Articles
Total 0
Reviews
Scimago 33
H-index
Scimago 0,395
Journal Rank
Scimago Veterinary (miscellaneous) Q2
Quartile Score  
Scopus 355/217=1,6
Scite Score  
Scopus General Veterinary 73/183 (Q2)
Scite Score Rank  
Scopus 0,565
SNIP  
Days from  145
submission  
to acceptance  
Days from  150
acceptance  
to publication  
Acceptance 19%
Rate

 

2019  
Total Cites
WoS
798
Impact Factor 0,991
Impact Factor
without
Journal Self Cites
0,897
5 Year
Impact Factor
1,092
Immediacy
Index
0,119
Citable
Items
59
Total
Articles
59
Total
Reviews
0
Cited
Half-Life
9,1
Citing
Half-Life
9,2
Eigenfactor
Score
0,00080
Article Influence
Score
0,253
% Articles
in
Citable Items
100,00
Normalized
Eigenfactor
0,09791
Average
IF
Percentile
42,606
Scimago
H-index
32
Scimago
Journal Rank
0,372
Scopus
Scite Score
335/213=1,6
Scopus
Scite Score Rank
General Veterinary 62/178 (Q2)
Scopus
SNIP
0,634
Acceptance
Rate
18%

 

Acta Veterinaria Hungarica
Publication Model Hybrid
Submission Fee none
Article Processing Charge 1100 EUR/article
Printed Color Illustrations 40 EUR (or 10 000 HUF) + VAT / piece
Regional discounts on country of the funding agency World Bank Lower-middle-income economies: 50%
World Bank Low-income economies: 100%
Further Discounts Editorial Board / Advisory Board members: 50%
Corresponding authors, affiliated to an EISZ member institution subscribing to the journal package of Akadémiai Kiadó: 100%
Subscription fee 2021 Online subsscription: 696 EUR / 872 USD
Print + online subscription: 804 EUR / 1004 USD
Subscription fee 2022 Online subsscription: 710 EUR / 892 USD
Print + online subscription: 824 EUR / 1028 USD
Subscription Information Online subscribers are entitled access to all back issues published by Akadémiai Kiadó for each title for the duration of the subscription, as well as Online First content for the subscribed content.
Purchase per Title Individual articles are sold on the displayed price.

Acta Veterinaria Hungarica
Language English
Size A4
Year of
Foundation
1951
Publication
Programme
2020 Volume 68
Volumes
per Year
1
Issues
per Year
4
Founder Magyar Tudományos Akadémia
Founder's
Address
H-1051 Budapest, Hungary, Széchenyi István tér 9.
Publisher Akadémiai Kiadó
Publisher's
Address
H-1117 Budapest, Hungary 1516 Budapest, PO Box 245.
Responsible
Publisher
Chief Executive Officer, Akadémiai Kiadó
ISSN 0236-6290 (Print)
ISSN 1588-2705 (Online)

Monthly Content Usage

Abstract Views Full Text Views PDF Downloads
Jun 2021 0 17 24
Jul 2021 0 14 19
Aug 2021 0 39 4
Sep 2021 0 7 14
Oct 2021 0 14 21
Nov 2021 0 6 17
Dec 2021 0 1 2