Projects / Programmes
Pathology and Molecular Genetics
January 1, 2004
- December 31, 2008
| Code |
Science |
Field |
Subfield |
| 3.01.00 |
Medical sciences |
Microbiology and immunology |
|
| 3.04.00 |
Medical sciences |
Oncology |
|
Researchers (55)
Organisations (1)
Significance for science
Important and internationally recognized achievements of our research team contributed to the understanding of immune mechanisms of tissue injury and inflammation in the kidney and vasculature in different diseases. The members of the team presented their original achievements in the papers published in prestigious journals, cited by the SCI. In one of the largest studies of 358 patients, we demonstrated the relationship between the distribution and the intensity of the glomerular sudendothelial deposits on one side and forms of active lupus nephritis on the other side. Our studies on isolated glomeruli drew attention to the significance of apoptosis and activation of the proinflammatory genes in the pathogenesis of lupus nephritis. They also confirmed the significant role of apoptosis in the early myocardial infarction. We proposed the hypothesis that the absence of the inflammatory changes in the renal arterioles and arteries in comparison with glomeruli might be attributed to the non-fenestrated endothelial cells in these vessels preventing direct contact of immune deposits with the plasma proteins, from which by activation inflammatory mediators are released. The largest study of the clinico-pathologic correlation in C1q nephropathy published so far showed the pathogenetic heterogeneity of the disease. The disease can namely manifest clinically and histopathologically as immune complex glomerulonephritis and vasculitis, resp., or as a noninflammatory podocytopathy presented with nephrotic syndrome and minimal changes or focal segmental glomerulosclerosis. In the study of hantavirus nephropathy, our electron microscopical analysis confirmed that the small vessels of the outer kidney medulla are the main target. It appears that the endotheliotropic hantaviruses are not cytopathogenic and vascular injury results from the interaction of numerous cytokines released during the infection. Significant is also our contribution in the international research group, which elaborated detailed diagnostic criteria for still enigmatic Balkan endemic nephropathy. The international recognition of the original standpoints on classification of precancerous lesions of the larynx and oral cavity (the Ljubljana classification) has been a major success for our research team. Additional criteria for histological evaluation of these lesions were based on immunohistochemical and molecular-genetic analyses (telomerase reactivation, stromal changes and the role of survivin and FHIT gene in the process of squamous cell carcinoma development, and new insights of the apoptosis) as well as on a 25-year follow-up study of patients at different stages of squamous intraepithelial lesions with malignant alteration of 1.1% of cases with the low-risk lesions and of 9.5% of the high risk lesions. Our results have become internationally recognized and the members of our research group were invited authors of some chapters of five scientific books on the head and neck tumors. Our research work, therefore, significantly contributed to reveal new mechanisms in the development of squamous intraepithelial lesions in the head and neck region, as well as to new diagnostic and prognostic factors. In our molecular genetic investigations, we drew attention on some important and unique correlations between genotype and phenotype in several hereditary based syndromes. These data are currently being collected also by The Human Variome Projects, which is the global community's effort to collect, keep and make accessible information on genetic variations affecting human health. Within the research collaboration with The Interdisciplinary Study Group on Gene Environment Interaction and Breast Cancer (GENICA), we found several potential biomarkers for colorectal cancer and breast cancer. A study on breast cancer patients suggested that the TC21 promotor polymorphism was significantly associated with tamoxifen treatment and outcome.
Significance for the country
The introduction of modern technologies, new classifications of renal and vascular diseases, regular clinico-pathological collaborating and the archived research experiences significantly contribute to the higher level of pretentious and complicated biopsy diagnostics. Detailed qualitative and quantitative evaluation of immune and non-immune forms and grades of tissue changes in biopsy samples enables clinicians to make the most appropriate decision for the therapeutic approach and with rebiopsies in the most objective way to follow the effect of therapy and course of the disease. The results of our research of the head and neck carcinogenesis enable earlier diagnostics and more successful treatment of squamous intaepithelial lesions in the head and neck region and thus significantly contribute to improve the state of health of inhabitants of Slovenia, particularly of those with high risk factors (smokers and drinkers). Molecular genetic investigations included some hereditary syndromes as well as cancer, which have not yet been investigated in Slovenian population. We developed an efficient molecular genetic approach for screening of several hereditary diseases in Slovenian population e.g.; multiple endocrine neoplasia MEN-2, Alport syndrome and benign familial hemathuria, Darier disease and Creutzfeld Jakob disease. Furthermore, we showed some important associations with genes in complex diseases such as Chron disease, lung cancer, colorectal cancer and breast cancer. This approach enables us to perform a population screening and identification of novel families with this syndrome that is also associated with early detection and treatment of the disease. We found in hereditary diseases several new and for Slovenian population specific mutations. Through these studies we also developed new methodological approaches for efficient and relatively cost-effective detection of variations in disease genes including capillary electrophoresis-single stranded conformation polymorphism (CE-SSCP), DHPLC methodology and construction of DNA microarray. In additon, our research work importantly influences the under- and postgraduate education of biomedical students and doctors.
Most important scientific results
Final report,
complete report on dLib.si
Most important socioeconomically and culturally relevant results
Final report,
complete report on dLib.si
