Expression of multidrug resistance membrane transporter (Pgp) and p53 protein in canine mammary tumours

The aim of this study was to determine the expression rate of P-glycoprotein (Pgp), a multidrug resistance marker and the p53 tumour-suppressor protein in canine mammary tumours. A total of 30 tumours were examined in parallel to patient history. The tumours were allotted to four groups: tubulopapillar carcinomas, complex carcinomas, benign tumours, and other malignant tumours. A monoclonal mouse antibody (C494) was used for the immunohistochemical evaluation of Pgp and a polyclonal rabbit antibody for p53. We found that the intact ductal epithelium and connective tissue showed pronounced Pgp expression. The most intensive staining was detected in tubulopapillar carcinomas for both Pgp and p53. The expression rate of Pgp and p53 differed significantly between tubulopapillar carcinoma and complex carcinoma, and between tubulopapillar carcinoma and benign mammary tumour, respectively. The expressions of Pgp and p53 highly correlated statistically; therefore, both can determine malignancy in a similar manner. In the case of tubulopapillar carcinomas, more relapsed tumours occurred than in relation to complex carcinomas and other malignant tumours. Pgp expression rate was proportional to the probability of the tumour becoming recidivant postoperatively, as well. These results suggest that routine evaluation of Pgp expression in canine mammary tumours may be prognostically helpful

Understanding Parental Attitudes toward Vaccination: Comparative Assessment of a New Tool and Its Trial on a Representative Sample in Hungary

Background: Last year’s epidemic experience proved that measurement of vaccine hesitancy is undeniably important. Existing methods for measuring this propensity are still either too specific, concerning a single vaccine, or only describe the general attitude towards vaccination. When a specific, but previously unknown infection and vaccine (such as SARS-CoV2) appear, these limitations are meaningful. Methods: Based on a method used to identify social prejudice, we created a new tool to assess vaccine hesitancy assessment and to study parental attitudes toward existing and non-existing (‘Piresian’) vaccines. After validating it with traditional tools for the measurement of vaccine hesitancy, we used the new tool for the demographic characterisation of different vaccine hesitant parent groups in Hungary. The data collected in 2017 on 430 parents, sorted by type of settlement and by geographic region, are representative of Hungarian households with children aged 0 to 18 years. Results: Our results show that attitudes towards a non-existing (‘Piresian’) vaccine have strong correlations with those towards existing vaccines (p < 0.001). No gender differences in vaccine hesitancy were found using either method. Notably, rejection was significantly higher among parents with low educational levels. Conclusion: The Piresian measurement of vaccine hesitancy offers a simple way to detect vaccine-hesitant groups, reliably quantitating vaccine hesitancy as measured for real vaccinations

Evaluation of Pgp (MDR1) immunohistochemistry in canine lymphoma – prognostic and clinical aspects

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

Tyrosine kinase inhibitors in veterinary oncology Literature review

SUMMARY Tyrosine kinases are critical regulators of normal cell signalling, because they control several key processes. Tyrosine kinases are specific signalling molecules playing an essential role in cell growth, survival, migration and differentiation. Their receptors are located on the cell surface, delivering signals to the nuc leus through a phosphorylation cascade. Receptor tyrosine kinases are those tyrosine kinases expressed on the cell surface that are stimulated by binding of growth factors. Tyrosine kinases are also of paramount importance in angiog enesis, and thus, in the development of tumor vascularisation. The emergence of abnormal signalling pathways due to the dysregulation of receptor tyrosine kinases is a known feature in several tumour types, and is regarded as a nega tive prognostic factor, as it alters tumor growth, proliferation and metastatic potential. Inhibition of tyrosine kinases is very important in human oncology, and it is likely that many more tyrosine kinase inhibitors will become available in the near future; and their biological activity will be enhanced as combination regimens with standard treatment modalities are explored. The use of kinase inhibitors in dogs and cats is relatively recent. There are now 2 small molecule inhibitors approved for use in veterinary medicine: Palladia (toceranib) and Masi vet/Kinavet (masitinib). Their use is approved in mast cell tumours of dogs by the Federal Drug Administration (USA). Gleevec (imatinib) is human tyrosine kinase inhibitor used in the treatment of multiple human cancers (for example chronic myelogenous leukaemia and GIST), but has been successfully used in dogs and cats as well. The authors review the current knowledge on the biology of tyrosine kinase dysfunction in human and animal cancers, and the application of specific tyrosine kinase inhibitors to veterinary cancer patients

Removal of frontal meningioma by bilateral transfrontal approach in dog - Case study

SUMMARY Background: Meningeoma is a common intracranial tumour type in dogs and cats. Epilepsy and obtunded mental state are the most common clinical signs of frontal meningiomas. Frontal lobe and olfactory bulb are the most typical place of meningioma in dogs. Many surgical procedures have been described about the removal of meningioma which depends on the placement of the tumour. Bilateral transfrontal approach is recommended in case when the meningioma locates at the frontal lobe. Followed by the tumour resection chemotherapy and/or radiotherapy are recommended.Materials and Methods, Results and Discussion: A 10-year-old Hungarian Vizsla was referred for examination to FeliCaVet Vet Clinic due to seizures and obtunded mental state. Neurological examination did not show any severe abnormalities except moderate obtundation. Preoperative examination, included blood and urine tests, abdominal- and heart ultrasound, chest radiography, were normal. Magnetic resonance imaging (MRI) examination of the head revealed a 15×20 mm T2W hyperintense lesion in the right frontal lobe with “dural sign” and perilesional oedema. Bilateral transfrontal approach was performed to remove the right olfactory bulb, the neoplastic lesion and a small affected part of the right frontal lobe. After the surgery two seizures were observed during the 2 days of hospitalization. Levetiracetam was started to eliminate the postoperative seizure activity. 1 week later the first control MRI examination showed that the right olfactory bulb was completely removed together with the majority of the tumorous tissue and a small part from frontal lobe. 2 months after the surgery a second follow-up MRI examination was performed which revealed the same result as the first MRI. From the second day of the surgery the dog is fine and all the previously noted clinical signs have disappeared. 3 weeks after the surgery chemotherapy was started with hydroxyurea which is currently still ongoing

Tyrosine kinase expression analyses in canine mammary gland tumours – A pilot study

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