Aim of the tender is to examine multidrug resistance (MDR). We plan to perform examinations during treatment of canine lymphoma, mammary gland tumour, mastocytoma, sarcoma, immune mediated hemolytic anemia, thrombocytopenia, cardiomyopathy and endocardosis. We start the work by clinical, radiological, haematological and histological examinations. Laboratory evaluations are aiming to determine MDR causing transporter proteins (P-glycoprotein, multidrug resistance associated protein1).
Quantity of MDR-proteins and coding mRNA will be determined by immunohistochemical, western blot and PCR analytical methods in neoplastic, myocardiac and spelinc tissues, and in cells separated from these, moreover in cells separated from blood. Flow cytometric and scyntigraphical analyses will be used to evaluate the function of MDR-proteins.
We plan to evaluate whether quantity, quality and function of MDR-proteins correlate the clinical manifestation of MDR. We then get a picture about which protein is responsible for the development of MDR. We get information about the pathophysiology of MDR from the degree of the expression of coding genes and proteins till the clinical manifestation.
This project will contribute a deeper recognition of the examined diseases, determination of the prognosis and selection of adequate therapy.
This research will help graduate students in preparing their diploma work and PhD students in preparing their thesis. We expect to evaluate our works at international congresses.
Results of our research will be published in diploma works, scientific congresses and papers. Rrealization is guaranteed by the participant research institutes.
Infrastructural background is available, utilization of the instruments will be improved by the project.
We are planning to examine those factors that can be used as prognostic markers in various canine neoplastic diseases (haemopoietic, mammary gland, skin tumours and tumours of the inner organs). In this topic we are developing new methods to examine staging, and proliferation markers (AgNOR, PCNA, Ki67 etc.). We are planning to examine the development of therapy resistance: expression of the genes, and proteins influencing it, such as P-glycoprotein and mrp1, moreover the function of these and the clinical manifestation of therapy resistance. We are planning to adapt and examine efficacy of various novel methods for anticancer therapy (primarily photodinamic therapy), too.