Összes szerző

Sáfrány Géza

az alábbi absztraktok szerzői között szerepel:

Balázs Katalin
Acute and long-lasting immunological changes in prostate cancer patients treated with three different radiotherapy protocols

Aug 29 - kedd

15:30 – 17:00

I. Poszterszekció

P01

Acute and long-lasting immunological changes in prostate cancer patients treated with three different radiotherapy protocols

Katalin Balázs^1,2, Zsolt Jurányi³, Zsuzsa Kocsis S³, Géza Sáfrány¹, Katalin Lumniczky¹

¹ National Public Health Center, Budapest, Hungary

² Doctoral School of Pathological Sciences, Semmelweis University, Budapest, Hungary

³ National Institute of Oncology, Budapest, Hungary

Radiotherapy can modify systemic immune responses of cancer patients. However, little is known about how long these alterations persist in patients successfully cured of cancer. We investigated how prostate cancer and radiotherapy impact the innate and adaptive immune system of cancer patients treated with various radiotherapy protocols in order to mark potential immune-related biomarkers for patient follow-up.

Blood samples were collected from 63 patients treated with three different type of radiotherapy protocols (LDR brachytherapy: n=21; HDR brachytherapy: n=22; LINAC-based teletherapy: n=20 patients) before and at 7 time points after the therapy up to 36 months. Phenotypical changes in peripheral blood mononuclear cells were analysed by multicolor flow cytometry.

Natural killer (NK) cells were among the most strongly altered in all prostate cancer patients. LDR therapy induced very moderate changes within the NK subpopulation, however teletherapy caused a strong and persistent shift toward immature NK cells. The proportion of non-senescent and senescent CD4+ and CD8+ T cells changed very similarly in HDR and teletherapy groups; the balance shifted strongly to the senescent populations during the follow-up. We further investigated the amount of PSA-containing macrophages which level increased several folds in cancer patients before therapy compared to control and found positive correlation between the plasma PSA level and the level of circulating PSA+ macrophages before therapy.

Our studies demonstrate that prostate cancer patients show long-lasting immunological changes. Furthermore different radiotherapy protocols lead to different long-term immune alterations highlighting the importance of deposition kinetics of ionizing radiation energy in modulating systemic immune responses.

This work was supported by a Hungarian research grant funded by the National Research, Development, and Innovation Office (NKFI-124879).

Győryné Galgand Kinga
Effect of ionizing radiation on the behaviour of miRNA binding proteins

Aug 29 - kedd

15:30 – 17:00

I. Poszterszekció

P09

Effect of ionizing radiation on the behaviour of miRNA binding proteins

Kinga Győryné Galgand¹, Ilona Barbara Csordás¹, Rita Hargitai¹, Eszter Szarka¹, Katalin Lumniczky¹, Géza Sáfrány¹

¹ National Public Health Center, Department of Radiobiology and Radiohygiene, Unit of Radiation Medicine, 1097 Budapest, Hungary

RNA-binding proteins play an important role in the regulation of miRNAs and affect a number of intracellular processes (e.g. DNA repair). miRNA binding proteins may also affect the regulation of intercellular communication by shaping the content of EVs, which are key players in the transmission of information between cells and are also responsible for mediating the ionizing radiation-induced bystander effect [1-4].

We investigated the effects of ionizing radiation on miRNA-binding proteins. Our aims are to analize the behaviour of proteins that influence the composition of the miRNA content of EVs after exposure and to explore their role in mediating the bystander effect.

We studied the behaviour of miRNA binding proteins in mouse bone marrow cells, which are highly sensitive to ionizing radiation. The experiments were performed in a control (0 Gy) and two X-ray irradiated groups (0.1 Gy and 3 Gy) 24 hours after exposure. Changes in the expression level of miRNA binding proteins were examined by Real-Time PCR, and intracellular protein levels by Western blot. we compared the results to the post-irradiation data of miRNAs detected by them and also present in EVs.

The results show significant differences in the expression levels of 4 out of 17 proteins tested after 3 Gy irradiation. Based on a combined interpretation of the results and the miRNA measurement data, it can be concluded that the abundance of certain proteins and the EV abundance of their bound miRNAs show a similar trend upon exposure to radiation. According to this information, it can be concluded that certain miRNA binding proteins are able to modulate the miRNA composition of extracellular vesicles in response to radiation, and thus are likely to play an important role in the bystander effect.

References

1. Han, X., et al., Single-cell mechanistic studies of radiation-mediated bystander effects. Front Immunol, 2022. 13: p. 849341.

2. Kis, D., et al., The effect of ionising radiation on the phenotype of bone marrow-derived extracellular vesicles.Br J Radiol, 2020. 93(1115): p. 20200319.

3. Kis, D., et al., Extracellular Vesicles Derived from Bone Marrow in an Early Stage of Ionizing Radiation Damage Are Able to Induce Bystander Responses in the Bone Marrow. Cells, 2022. 11(1).

4. Fabbiano, F., et al., RNA packaging into extracellular vesicles: An orchestra of RNA-binding proteins? J Extracell Vesicles, 2020. 10(2): p. e12043.

Lumniczky Katalin
Bone marrow-derived extracellular vesicles influence radiation-induced leukemogenesis

Aug 29 - kedd

14:40 – 15:00

Orvosi biofizika és sugárbiológia

E16

Bone marrow-derived extracellular vesicles influence radiation-induced leukemogenesis

Rita Hargitai, Tünde Szatmári, Ilona Csordás, Dávid Kis, Enikő Kis, Géza Sáfrány and Katalin Lumniczky

National Public Health Centre, Department of Radiobiology and Radiohygiene, Unit of Radiation Medicine, Budapest, Hungary

Haematological malignancies are considered the main long-term consequences of bone marrow (BM) irradiation. Ionizing radiation (IR) damages the stem and progenitor cells and alters signalling between the stem cell compartment and the BM stroma. The main objective of our work was to investigate extracellular vesicles (EVs)-mediated IR effects on leukaemogenesis after irradiation and to study possible underlying mechanisms using an in vivo murine model. Leukaemia incidence was followed in the CBA mouse model either irradiated or treated with EVs isolated from the BM supernatant of irradiated mice or subjected to both irradiation and EV treatment. Compared to spontaneous acute myeloid leukaemia (AML) incidence (below 1%), high dose (3 Gy) irradiation increased the incidence to 19%. EV treatment resulted in 4.5-6% leukaemia incidence with no significant difference between mice treated with EVs isolated from irradiated or non-irradiated animals. The combination of irradiation and EV treatment had an additive effect. Myeloid leukemias had two distinct phenotypes: a classical myeloblastic phenotype with a quick deterioration of the health status of the mice and increased bone marrow infiltration with myeloid blasts and a myelomonocytic phenotype with a slow clinical progression. EV treatment had a significant impact on leukaemia phenotype significantly increasing the frequency of the aggressive type myeloblastic leukemia. Lymphoid malignancies were also noted after irradiation and their incidence increased with the dose, though treatment of mice with EVs did not increase the incidence of this disease. In conclusion we showed that EVs influenced both the incidence and the phenotype of radiation-induced myeloid leukaemias but not of lymphoid ones. Our results also highlight the role of intercellular signalling mechanisms in radiation-induced leukemogenesis.

Funding: Euratom research and training programme 2014-2018, grant agreement No 662287 (CONCERT)