So the project was conducted in cooperation between the Hanover Medical School and the Department of Gastroenterology and the Vassil Stefanik Precopationnial National University Department of Biochemistry and Biotechnology in Ivana-Frankivsk within the scope of the DID Leonhard Euler program. The project was resulted in the publication

in oncoimmunology and about this I would like to tell you today. So first of all I would like to give a short introduction about the primary liver cancer, and the primary liver cancer is the sixth most commonly diagnosed cancer in the world and the third most leading cause of cancer

deaths worldwide. Hepatocellular carcinoma is the main type of the liver cancer, and the risk factors of the HCC, it's hepatitis B and C, after toxins, genetic factors,

gender, alcohol abuse, smoking and of course the obesity, diabetes and also non-alcoholic fatty liver disease. So Western diet is enriched with a lot of alpha-dicarbonyl compounds, for example, glyoxide and methylglyoxide which can later give rise to the advanced glycation end

products. Both of them, H and alpha-dicarbonyl compounds, they are very toxic for our body and later they can interact with the receptor for advanced glycation end products and later on

leads to the oxidative events, inflammation, proliferation and oncogenesis. So they take place in the development of healthy liver to non-alcoholic fatty liver disease, fibrosis, cirrhosis and hepatocellular carcinoma. So therefore, the aims of our study was to

investigate the biochemical and immunological parameters of the liver inflammation, characterize the role of AIDS, rage, signaling in the precancerous and cancerous liver disease and compare the results obtained in our murina models with the human and FLD and HCC. So with this I would like to introduce our animal models which we

established during this project. So we had two precancerous liver diseases and one cancerous liver disease. So first was an FLD mouse model, so fatty liver. We had animals which were exposed to the high fat diet during the 14 weeks and you can see here the liver

of the FLD animals. Next model was oncogen-induced senescence, was induced by oncogens and the last model, liver cancer, was also induced by the oncogen syndrome, it will be in the P19, AFM animals and you can see here the tumor nodules in the liver.

So here shortly just about our results. So we found that high fat diet provoked a liver injury in the mice that further increased in the hepatocellular carcinoma. Mice with an FLD and

HCC show increase in alpha-dicarbonyl compounds in the liver in the FLD and HCC. On the next step we also checked the immune system in the murina livers using flow cytometry and we could see that the receptor for advanced glycation and products

are strongly increased in T cells and NK cells in the HCC livers. And as well we checked for the inhibitory markers, for example for the PD-1 and we also could see that rage-positive lymphocytes demonstrated a significant upregulation of PD-1 in HCC livers.

So also we compare our results with the human samples from the NAFLD, NASH and HCC patients and we can see a significant increase of the serum alpha-dicarbonyls in the NAFLD and

HCC patients and healthy donors and also we checked also the liver tissue where we can see the elevated level of alpha-dicarbonyls. So with this I would summarize this and we can tell that the increase of alpha-dicarbonyl compounds and also the rage receptor on NK cells and

CD8-positive T cells can be a biomarker and potentially can be targeted during the therapy for HCC and NAFLD. So as I told this was in the scope of DED

Leonard Euler program and after this cooperation between the Hannover Medical School and Ivana Frankirsk University gave rise to another project which also supported by DED as well as DED doctoral program in Germany and the DED summer school in 2019.

So with this I would tell my acknowledgement to the team at the Hannover Medical School, to the AGIESA and also to the department of biochemistry biotechnology in Ivana Frankirsk as well as to our collaborators at the M-HAHA and the Tanopi National University. Thank you so much.