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Assessment of tumor cellular microenvironment

Hepatocellular carcinoma (HCC) occurs in people with an underlying liver disease of either viral or toxic origin. It is usually preceded by cirrhosis. In the Czech Republic alcoholic liver disease is the major etiological factor. Tumor microenvironment is composed of myeloid (innate immunity) and lymphoid (adaptive immunity) lineages. Infiltrating immune cells can function to control tumor growth or to help create an immunosuppressive environment in which the tumor can thrive. The long suspected role for immune surveillance in human cancer has gained strong experimental support in the past decade. The concepts of ‘hot’ or ‘cold’ tumors refer to signs of inflammation (hot) when the tumor has already been infiltrated by T cells, which usually correlates with a response to immunotherapy. Even more gratifying, these scientific breakthroughs have also benefited clinical oncology in the context of diagnostics, prognostication, drug development and therapy.

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Students for the following Ph.D. study topics are sought in the doctoral study programme:

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T-cells as main actors in anti-tumor immunity

The long-suspected role of the importance of immunity in cancer has gained strong experimental support in the past decade. Infiltrating immune cells can function to control tumor growth or to help create an immunosuppressive environment in which the tumor can thrive. Immune surveillance by T-cells in human cancers is one of the key mechanisms of anti-cancer immunity.

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The Chaperon ERA Research Club invites you to participate in our Nerd Art Prize contest by sending us your best scientific photo or picture!

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Department of Hemato-Oncology, University Hospital Pilsen and Biomedical Center, Faculty of Medicine in Pilsen presents on May 3, 2018 from 13:00 at Seminar room (SO 01. 2.21), Biomedical Center, alej Svobody 1655/76, Plzeň 323 00 lectures from leading scientist from Imperial College London.

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Biomedical Center, Faculty of Medicine in Pilsen, Charles University, is seeking students for the following Ph.D. study topics in the doctoral study programme of Experimental Surgery:

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Team of Laboratory of Cancer Treatment and Tissue Regeneration participates on research of GECCO (The Genetics and Epidemiology of Colorecal Cancer Consortium) in Seattle, USA.

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Recently, we published a review article entitled “A Double Edged Sword role of Interleukin-22 in Wound Healing and Tissue Regeneration” in prestigious journal ‘Frontiers in Immunology’. Frontiers in Immunology is the official Journal of the International Union of Immunological Societies (IUIS). It is a leading journal in its field, publishing rigorously peer-reviewed research across basic, translational and clinical immunology.

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26th annual prizes of the French embassy of the Czech Republic for young czech scientists in postgraduate studying programs were announced this year. These were given in seven categories according to the scientific discipline of the nominees. Two students of our faculty were awarded the Albert Schweitzer prize for medical research. Student Jachym Rosendorf, M.D. was awarded a 3rd place prize for his research „Experimental use of nanofibrous materials for prevention of intestinal anastomotic leakage“ and Richard Palek, M.D. was awarded a 2nd place prize for his work on „Perfusion decellularization of whole liver - first step in new organ development“. Both of them are students of Assoc. Prof. Vaclav Liska, M.D., PhD, who is an Albert Schweitzer prize awardee himself for the year 2000. The students worked on their projects under his supervision at the Laboratory of Cancer Treatment and Tissue Regeneration of the Biomedical Center. The awarding Ceremony was held on 2nd July in the facility of the French Institute in Prague in presence of the French ambassador Roland Galharague. The opening speech is annually given by a chemistry nobelist Jean-Marie Lehn, who was able to participate only electronically this year due to the epidemiological situation. The financial award is accompanied by a month internship in a research facility in France for the first and the second prize awardees sponsored by the Pierre-Fabre Medicament company. We congratulate the awardees.

MUDr. Jan Brůha, Ph.D.

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Pavel Vodicka, M.D., PhD and Alena Opattova, PhD, from Laboratory of Cancer Treatment and Tissue Regeneration Bimedical Center in Pilsen and Institute of Experimental Medicine of the Czech Academy of Sciences, Prague are coauthors of two scientific articles published in in Nature Protocols (IF 11.360).

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Oncological and surgical treatment of malignant focal processes of the liver reaches its limits in cases where the amount of affected parenchyma is too large or where the hilar structures are involved – stages at which a complete removal of the tumor tissue equals a total loss of the organ. In such patients, restoration of the liver function by means of conventional liver transplantation is generally out of the question, as it requires the administration of drugs to suppress the immune system’s response. Since the immune system fights not only pathogens but also cancerous cells, immunosuppression can lead to a rapid recurrence of the disease originating from the remnants of the malignant cells left in the body. The hope for a change lies in tissue engineering research, which promises to create an artificial replacement organ using the patient's own cells, thereby reducing the need for immunosuppression [Liska2019]. Our Laboratory of Cancer Treatment and Tissue Regeneration, headed by Professor Václav Liška, located at the Biomedical Center of the Faculty of Medicine in Pilsen, is engaged in such research.

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 Liver scaffold in the final stage of preparation

An important step in our approach to the production of an artificial organ is the preparation of an inanimate skeleton of the liver (scaffold), which is obtained from the liver of a domestic pig and is intended for subsequent colonization by living cells. To evaluate the quality of this scaffold, it is necessary to distinguish the areas of the liver lobules and their surroundings (septa). To follow the quality assessment methodology described in [Moulisova2020], it has hitherto been necessary to manually label parts of the scaffold samples in histological slides stained with hematoxylin and eosin. In cooperation with colleagues from the Department of Cybernetics of the Faculty of Applied Sciences at the University of West Bohemia in Pilsen and Universitätsklinikum Jena, we designed an algorithm that produces the label automatically. The algorithm, which is based on convolutional neural networks, was published (https://doi.org/10.3390/s20247063) in the Sensors journal (Q1, IF=3.275).

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Hematoxylin-and-eosin-stained liver scaffold

Compared to classical methods of computer vision, convolutional neural networks usually offer better results, but require a considerable amount of training data. Therefore, we designed a two-phase training procedure. In the first phase, we use the methods of classical computer vision for semi-automatic segmentation using texture features. In this phase, we use training datasets where less than 5% of the image area is annotated. The output data are then used in the second phase for training a neural network. The architecture of the neural network is inspired by the U-Net network. After the training, full segmentation is produced automatically.

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Two-phase training procedure

Automatic histological image processing allows extensive skeletal quality measurements to be made. An important benefit of this method is the repeatability of measurements and their independence from the human factor, once the network is trained. In the follow-up research, our team is going to integrate the proposed method into a freely available application, which will make it possible to compare the results of laboratories from all over the world.

 

M. Jiřík, I. Gruber, V. Moulisová, V. Liška et al.

 

 

References

 

[Liska2019]

 Liška V, Moulisová V, Pálek R, Rosendorf J, Červenková L, Bolek L, Třeška V. Repopulation of decellularized pig scaffolds: Promising approach for liver tissue engineering. Rozhl Chir. 2019 Fall;98(10):388-393. English. PMID: 31842567.

[Moulisova2020]

Moulisová V, Jiřík M, Schindler C, et al. Novel morphological multi-scale evaluation system for quality assessment of decellularized liver scaffolds. Journal of Tissue Engineering. January 2020. doi:10.1177/2041731420921121.

[Jirik2020]

 Jirik, M.; Gruber, I.; Moulisova, V.; Schindler, C.; Cervenkova, L.; Palek, R.; Rosendorf, J.; Arlt, J.; Bolek, L.; Dejmek, J.; Dahmen, U.; Zelezny, M.; Liska, V. Semantic Segmentation of Intralobular and Extralobular Tissue from Liver Scaffold H&E Images. Sensors 2020, 20, 7063.

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Teams from the Laboratory of Cancer treatment and tissue regeneration of the Biomedical Center in Pilsen and from the Department of nonwovens and nanofibrous materials of the Technical University in Liberec cooperate on development of nanofibrous materials for healing support of intestinal anastomoses for several years.

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Members of the Laboratory of Pharmacogenomics (K. Šeborová, P. Souček and R. Václavíková) and the Laboratory of Cancer Treatment and Tissue Regeneration (P. Vodička) in cooperation with prof. L. Rob from the University Hospital Kralovske Vinohrady recently published a review article in Cancers (IF 6.1, Q1 in Oncology).

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The Czech Transplantation Society announced the winner of the Best scientific publication of the year 2020. The prize was awarded to RNDr. Vladimira Moulisova, PhD who is the first author of the original research paper “Novel morphological multi-scale evaluation system for quality assessment of decellularized liver scaffolds”.

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CHROMOSOMAL ABERRATION IN HEALTHY PERSONS

Blood white cells of healthy individuals may contain non-recurrent, random chromosomal aberrations (CAs), which disappear with cell turnover as they provide no growth advantage. These include chromatid breaks, fragmented or missing parts of chromosomes and fusions resulting in dicentric and ring chromosomes. These nonspecific CAs have been used in monitoring of occupational populations exposed to potential carcinogenic chemicals and radiation.

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Contact

Charles University
Faculty of Medicine in Pilsen
Biomedical Center

alej Svobody 1655/76
323 00 Plzeň – Severní Předměstí

T: +420 377 593 810
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