Centre of Radiotherapy, Department of Radiobiology and Diagnostic Onco-Cytogenetics
Where to find us
Building 11., First floor, Phone: 224-8779; 224-8600/(ext) 1381, 1379, 1373, 1590.
Dr. Zsolt Jurányi MD, Ph.D., Head of Department
Dr. Gyöngyi Farkas Ph.D., biologist, Deputy Head of Dept.
Dr. Zsuzsa S. Kocsis Ph.D., chemist
Dr. Gyöngyvér Orsolya Sándor, Ph.D., biologist
Mr. Gábor Székely, biologist
Ms. Krisztina Kiss, technician
Ms. Nagyezsda Vass, special assistant in clinical genetics
Mr. Martin Fodor, assistant
Changes in immune cell subpopulations during complex therapy of TNBC patients (predictive biomarkers of immunotherapy)
Predictors of immunotherapy outcomes are needed to spare non-responding patients from the side effects and healthcare system from the cost of unnecessary therapies. Peripheral blood biomarkers are already suggested, and they would be advantageous as easily accessible and reproducible. Furthermore, new targets for immunotherapy are in clinical trials including NK cells. On the other hand, the advance of immunotherapy is possibly limited by the previous or parallel treatment modalities (for example radiotherapy) killing the targeted immune cells. However, it is already described, that not all immune cell populations are depleted as a result of radiation or chemotherapy.
Therefore, we have been recruiting triple-negative breast cancer (TNBC) (from September 2021) and have been collecting blood samples before the start of therapy and after each type of therapy: post-chemotherapy, post-surgery, post-possible radiation therapy, post-capecitabine chemotherapy, and three months after completing all treatments. We have been analyzing more than seventy cell populations including T cell and NK cell subpopulations in six fluorescent panels.
RILA assay in cervix tumor patients
The radiation-induced lymphocyte Apoptosis (RILA) method is a clinically tested tool for determining individual radiosensitivity. According to one of the hypotheses, the irradiated cells can go to senescence or die with apoptosis. The literature suggests, that the fibroblast senescence due to the irradiation causes most of the side effects, therefore, more apoptotic cells indicates less senescence and side effects. In this study, apoptotic CD8+ and CD4+ lymphocytes after 8 Gy irradiation are measured by staining with propidium iodide and using a flow cytometer. This is a high-throughput, fast and cheap new method in radiobiology. We have been testing possibilities to shorten and simplify the assay. The highest number of cervix tumor patients of worldwide RILA studies are already recruited.
Circulating endothelial cells as biomarkers of glioblastoma progression
Glioblastoma patients had to undergo frequent MRI scans to asses possible progression, which is inconvenient for the patient and expensive for the healthcare system. Blood based biomarkers, as suggested circulating endothelial and endothelial progenitor cells would be easier available and cheaper. We have been recruiting glioblastoma patients before radiotherapy with temozolomide treatment and recurrent glioblastoma patients before anti-VEGF treatment, as well as patients with long-lasting benefit from VEGF therapy.
Comparison of prostate radiotherapy techniques regarding lymphocyte damage
Approximately half of tumor patients are treated using different radiotherapy techniques. However, the biological doses of the current radiotherapeutic techniques are not compared thoroughly. The biological dose describes the reaction of cells to the absorbed radiation dose. As the biological dose is mostly quantified by the damage of lymphocytes (micronucleus assay, Comet-assay, chromosomal aberration assay), it also describes the condition of the immune cells. As immunotherapy is given to more and more patients, the damage to the targeted lymphocytes can be an important factor in the success rate. However, there is scarce information about how long it takes for the damaged cells to get eliminated. We recruited localized prostate cancer patients (N=224), who can receive radiotherapy with four techniques in our institute. The chromosomal aberration (CA) is also suggested to predict radiotherapeutic side effects, for which there is no method in clinical practice. We have been testing this hypothesis by comparing chromosomal aberrations and graded urogenital and gastrointestinal radiation toxicities. We have been comparing the four types of radiotherapy (teletherapy with conventional LINAC or Cyberknife machine, high or low dose rate brachytherapy) regarding the biological dose and side effects.
Cytogenetic screening of medical radiation workers (medical doctors, physicists, technicians and isotope and laboratory staff)
Cytogenetic analyses are performed as systematic examinations that are advised biennially for every person who works with cytostatic drugs or with ionizing radiation in our Institute.
Based on chromosome aberration values, the radiation dose absorbed by the body can be estimated. Structural changes (aberrations) in chromosomes also significantly increase the risk of cancer. The analysis of chromosomal aberrations is, therefore, a precautionary step that allows us to start preventive interventions to reduce risk (to control and decrease the chemical and radiation exposure, change of job).
Promoting the differential diagnosis of certain haematological diseases (such as Fanconi anaemia)
Fanconi anemia is a genetic disorder and the symptoms are resemble to other diseases causing aplastic anemia. Treatment of aplastic anemia is primarily bone marrow transplantation. However, conditioning treatment of patients with Fanconi anemia requires great caution, because they may respond to high doses of alkylating chemotherapy or whole-body radiation with hypersensitivity due to congenital repair deficiency. Therefore, to reduce the need of FANC genetic testing, and accelerate accurate diagnosis and the early recognition of these disorders and allowing for appropriate therapy planning we apply chromosomal aberration tests. In vitro chromosomal fragility due to mitomycin-C and mutagen sensitivity with bleomycin test are higher in Fanconi anemia patients than in other aplastic anemia patients.
In vitro research activity
Hydrogen sulphide (H2S) and radioresistance
The two-thirds of radiation-induced DNA damage of the radiotherapy of tumors occurs through the mediation of reactive oxygen species (ROS). In our research, we studied what impact of the ROS eliminating pathways have on the cellular radioresistance, which is one of the main obstacles of successful radiotherapy. This study is performed with the collaboration of Molecular Immunology and Toxicology Department. Colony forming assays, glutathione and ROS assays, cell cycle phase assays, qPCR methods, etc. are applied.
Measurement of biological dose of CT scans in adaptive radiotherapy
Cone Beam Computed Tomography (CBCT) is routinely used in radiotherapy to localize target volume. The aim of our study is to determine the biological effects of CBCT dose added to subsequent therapeutic dose by using in vitro chromosome dosimetry. (Joint work with radiation physicists.)
Publications (MTMT links)
Zsolt Jurányi MD, Ph.D.
Sarolta Gundy MD, Ph.D. Emeritus Head of Department
Dr. Zsuzsa S. Kocsis Ph.D.
Dr. Gyöngyi Farkas Ph.D.
Dr. Gyöngyvér Orsolya Sándor Ph.D.
Mr. Gábor Székely