Authors:Zsófia Koltai, Bernadett Szabó, Judit Jakus, and Péter Vajdovich
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.
Authors:Judit Csöndes, Ibolya Fábián, Bernadett Szabó, Ákos Máthé, and Péter Vajdovich
Inflammatory markers and adrenocorticotropic hormone (ACTH) stimulation test results may help us recognise critically ill dogs with poor disease outcome. Systemic inflammatory response syndrome (SIRS) criteria, the fast version of the Acute Patient Physiologic and Laboratory Evaluation Score (APPLEfast), complete blood count, albumin and C-reactive protein (CRP) levels, baseline and stimulated cortisol levels and Δcortisol value were recorded in 50 client-owned dogs admitted to the Small Animal Hospital of the University of Veterinary Medicine Budapest with various inflammatory or neoplastic conditions. Increasing APPLEfast score was associated with a decreasing chance of survival (P = 0.0420). The Δcortisol value was significantly higher in SIRS dogs than in non-SIRS dogs (mean ± SD ΔcortisolSIRS: 342.5 ± 273.96; mean ± SD Δcortisolnon-SIRS: 175.3 ± 150.35; P = 0.0443). Elevated baseline or stimulated cortisol levels were associated with a higher chance of non-survival (P = 0.0135 and P = 0.0311, respectively). These data indicate that pathologically higher baseline and stimulated cortisol levels represent an exaggerated stress response in critically ill dogs, which is negatively associated with survival.
Authors:Péter Vajdovich, Zsófia Koltai, Valéria Dékay, Krisztina Kungl, and Andrea Harnos
Permeability glycoprotein (P-glycoprotein, Pgp) immunohistochemistry (IHC) was evaluated in dogs with multicentric lymphoma treated with cyclophosphamide– doxorubicin–vincristine–prednisolone with or without L-Asparaginase. Lymph nodes of 33 untreated dogs were immunophenotyped: Ki67% and Pgp analyses (with anti-Pgp, monoclonal mouse C494 clone) were performed. Pgp positivity rate and intensity were determined microscopically (by manual counting done by two blinded authors in two parallel specimens). The median overall survival time (OST) was 333 days and the relapse-free period (RFP) 134 days. Pgp expressions were positive in 18 out of 33 (54.5%) of tumour cells. T-cell types stained more intensively. Lower OST and RFP were found with Pgp positivity ≥ 35% (OST: 240 days, RFP: 95 days) compared to Pgp positivity < 35% (OST: 428 days, RFP: 232 days). Intensive staining was associated with a lower OST and RFP (240 and 103 days, respectively) than weak staining (428 and 221 days, respectively). Death due to adverse drug reactions was best predicted at Pgp positivity ≤ 6.5% (sensitivity/specificity: 0.55/0.81) and ≤ 123 days (sensitivity/ specificity: 0.55/0.86). Pgp evaluation by IHC can have prognostic value with a properly established Pgp% positivity cut-off value in dogs treated with Pgp substrate drugs.
Authors:Beáta Török-Nagy, Péter Vajdovich, Lajos Balogh, Julianna Thuróczy, and Béla Dénes
The goal of this study was to evaluate the suitability of a commercially available D-dimer assay as a diagnostic tool for testing dogs. This assay is an immunoturbidimetric diagnostic test, capable of determining the D-dimer levels in human plasma by using 2B9 monoclonal antibody. Plasma samples of clinically healthy (n = 20) and tumour-bearing (n = 50) dogs were measured. The tumours were grouped on the basis of histological type and aggressiveness, and then the measured D-dimer concentrations of these groups were compared to those of the control group. The differences were analysed statistically. For benign tumours, we did not find alterations in the D-dimer levels. However, in the case of malignant tumours (lymphoma, sarcoma, and carcinoma) and in the presence of metastases, significantly elevated D-dimer levels were measured. The assay proved to be suitable for measuring the D-dimer levels in plasma samples of dogs. The calculated reference range for dogs was confirmed to be between 0.06 and 0.69 µg/mL fibrinogen equivalent unit.