Projects / Programmes
Pathology and Molecular Genetics
January 1, 2014
- December 31, 2019
| Code |
Science |
Field |
Subfield |
| 3.04.00 |
Medical sciences |
Oncology |
|
| 3.01.00 |
Medical sciences |
Microbiology and immunology |
|
| Code |
Science |
Field |
| B000 |
Biomedical sciences |
|
| Code |
Science |
Field |
| 3.02 |
Medical and Health Sciences |
Clinical medicine |
| 3.01 |
Medical and Health Sciences |
Basic medicine |
Researchers (59)
Organisations (1)
Abstract
The research on squamous intraepithelial lesions (SIL) and invasive squamous cell carcinoma of the head and neck (SCCHN) will focus on the preparation of a uniform classification of SIL with the aid of the results of an international study. In the part of the research of human papilloma virus (HPV) and the development of SSC, we will examine the role of low-risk HPV in this process and the role of high risk HPV in the occurrence of the variant of SCC, verrucous carcinoma (VC). Possible changes in the signaling pathway PI3K/Akt/mTOR in the occurrence of HPV-pos. SCC and HPV-neg. SCC will contribute to new understandings of the carcinogenesis of SCCHN.
On tissue samples of the uterine cervix (UC) we will analyse the predictive significance of p16 for progression to cervical intraepithelial neoplasia (CIN) and of podoplanin for discovering early stromal invasive SCC. We will analyse the predictive significance of DNA ploidy for prostate cancer in patients with low risk of disease progression.
Mutations and epigenetic events influence the development of different diseases, which we will determine in our molecular-genetic research using some of the new technologies as next generation sequencing, high-resolution comparative genome hybridization, microarrays, methylation-specific HRM, quantitative RT-PCR. We will analyse diseases including Leber syndrome, gynecomastia with pseudoangiomatous stromal hyperplasia and stromal giant cells in association with neurofibromatosis type 1, amyotrophic lateral sclerosis, malignant glioma, melanocytic lesions, and colorectal carcinoma. Multilevel approach enabling to analyse changes in DNA, mRNA, ncRNA and epigenetic status will be used. With this approach it will be possible to discover new disease-related changes, which were missed in the past due to the limitations of used technologies. Some of these new findings might be promising biomarkers as well as diagnostic and therapeutic targets.
Our research of immune and non-immune diseases of the kidneys and blood vessels will be continued in close collaboration among pathology, laboratory and clinical medicine enabling the direct transfer of scientific results into diagnostics and patient treatment. Among systemic and diseases restricted to the kidneys, which have in common impairment of humoral immune response, particular stress will be given to identifying factors that affect the variable course of frequent IgA nephropathy (IgAN), to studying monoclonal immunoglobulin deposition diseases and to assessing the coexisting immunopathogenesis in patients with anti-GBM antibodies. Electron microscopic results in correlation with the histopathology and clinical course will be to the fore, especially in the continuation of research related to kidney injury in phospholipidosis. We plan to supplement our original findings on hantavirus nephropathy in the acute phase of the disease with results on the histopathology of the still entirely unsearched chronic phase of the disease.
Significance for science
The international study with trial introduction of a uniform classification of SIL HN, with the cooperation of experts from 4 countries, will have particular importance. With the possible adoption of diagnostic criteria our proposal could be an important basis for a uniform classification of SIL in future editions of the book WHO Head and Neck Tumours. The results of the research connected with HPV6/11 in the carcinogenesis of SCC, with HPV infection in the occurrence of VC in various organs and the comparison of changes in the signalling pathway PI3K/Akt/mTOR in the occurrence of SCC with HPV-pos. SCC and HPV-neg. SCC will significantly contribute to knowledge of carcinogenesis in connection with HPV infection. Understanding the role of HPV in the development of various tumours will also assist in the selection of populations for vaccination.
Expression of p16 is important for evaluating various grades of CIN, which can consequentially affect the share of high grade CIN in screening programmes of early discovery of cervical cancer. Changes in the expression of podoplanin in early stromal carcinoma invasion will markedly contribute to more reliable histopathological assessment of SCC DNA ploidy is an additional predictive factor in prostate cancer.
New genomic technologies have significantly accelerated the discovery of coding and non-coding changes and the complexity of the processes that lead to the disease condition (e.g. the discovery of the Notch 1 gene in connection with squamous cell carcinoma of the head and neck). We expect altered expression of lncRNA in relation to different glioma grades and differentiation. We expect altered miRNA expression in relation to received oncotherapy and survival of patients with malignant glioma. Similarly we expect to detect in all examined disease states due to our multilevel approach and the use of combination of different methods changes in DNA, RNA, and epigenetics, which will contribute to the understanding of relations at the level of genome, transcription and regulation, of the correlations between the diseases and their molecular basis, and of the improvement of diagnosis, prognosis and treatment
The scientific achievements of our research can be expected to contribute to clarifying the occurrence and development of specific immune and non-immune diseases of the kidneys and blood vessels, improving disease recognition, monitoring the natural disease course and the effects of treatment. Very precise research and identifying undesirable, still very inadequately identified side effects of chloroquine treatment in kidney tissues of patients for whom, on the basis of ever more numerous publications in the literature, it has a beneficial effect in the treatment of rheumatic diseases, is particularly important.
Significance for the country
Through our research of SIL HN, we have become one of the leading centres in this field both at home and abroad. We expect that our study will contribute to the uniformity of SIL assessment and the possibility of comparison of individual forms of treatment. The research on the link of HPV infection and the development of SCCHN will provide a clearer picture of this health problem in Slovenia since we do not have detailed data on how large a part of SCCHN is connected with high risk HPV infection; treatment of HPV-pos. and HPV-neg. SCC differ significantly.
Histopathological diagnosis of CIN and UC SCC influences the incidence of precancerous changes and cancer of the UC. The study on p16 and podoplanin will contribute to national recommendations for assessing these changes. Determining DNA ploidy will contribute to individual planning of the treatment of patients with prostate cancer with low or medium risk of disease recurrence.
The proposed molecular genetic research will make possible to introduce new methods and diagnostic approaches in Slovenia. Patients with Leber syndrome and amyotrophic lateral sclerosis have not yet been explored in the Slovenian population. The genetic factors influencing the treatment of malignant gliomas also have not been identified. We expect to discover new genomic changes, also rare duplication and deletions, which might be specific for a certain disease. In case of ncRNA we expect new lncRNA and miRNA as potential biomarkers, which may contribute to earlier and more reliable diagnosis, prognosis of disease and more targeted treatment. In the future, all these may contribute to prevention and early diagnosis of disease, improving patient’ survival and reducing the treatment costs.
Research of the pathology of immune and non-immune diseases of the kidneys and blood vessels in the context of interdisciplinary cooperation contributes to the advancement and maintenance of a high level of diagnostics and treatment of patients in Slovenia. It speeds up the introduction of new methods in practice and enables development in accordance with internationally established standards of excellence. Patients with severe, clinically otherwise hard to recognise kidney diseases have direct benefit, since objective exact biopsy diagnosis is often the main support to clinicians in the choice of the most appropriate treatment. Because of adverse side effects, contemporary forms of treatment in nephrology can be risky; some are expensive but effective if the start of treatment is timely and based on clearly defined reliable biopsy diagnosis.
The scientific achievements of our research contribute to the quality of education at undergraduate and postgraduate levels. In addition, the publications of our researchers in prominent international journals and invited lectures at international congresses contribute to Slovenia's reputation in the world.
Most important scientific results
Annual report
2014,
2015,
final report
Most important socioeconomically and culturally relevant results
Annual report
2014,
2015,
final report
