Student’s scientific activity

EXPLAINING TRANSITION FROM STAGE II TO STAGES III AND IV COLON CANCER THROUGH ASSESSMENT OF TUMOR MICROENVIRONMENT AND ACTIONABLE SOMATIC MUTATIONS

Responsible supervisor of the SVOČ project: Andriy Trailin, MD, DSc, andriy.trailin@lfp.cuni.cz

Brief description of the Student´s scientific activity project:

More than half of new colon cancer (CC) patients in the Czech Republic presented at diagnosis with metastases in regional lymph nodes (RLNs) (stage III) and distant metastases (stage IV). Survival in CC is successively worse in stages III and IV compared with stage II. Treatment of stage II CC consists of surgical resection and then adjuvant therapy is used in patients with a high risk of recurrence. The identification of stage II CC patients in a high risk of developing RLNs or distant metastasis through the use of additional morphological and molecular risk factors is important to support clinical decision making on the follow-up and use of adjuvant therapy.

Our hypothesis posits that histopathological changes in the primary tumor and RLNs along with immune tumor microenvironment (TME) and cancer genomics will reveal specific pathways underlying the metastatic process.

We also hypothesize that the extent and characteristics of angiogenesis in the primary carcinoma-RLNs axis is a prerequisite for the metastatic spread.

We further posit that differences in the mutational patterns between primary tumor, RLNs and distant metastases may explain distinct metastatic potential of individual tumors.

We assume that the results of our study could bring new insights to the understanding of CC metastatic process and especially we could define a high-risk profile predictive of early metastasis leading to personalized selection of stage II CC patients suitable for adjuvant chemotherapy and active follow-up. A fundamentally novel tumor biological assessment of primary tumor and RLNs from the same patients will provide important data on the role of various players in the TME on patient outcome. Integrative analyses of the TME at the various steps of the metastatic cascade should highlight their relative contribution to the metastatic spread and to delineate the role of tumor and immune parameters to this process.

Students will be primarily engaged into image analysis using QuPath software.

2 students, optimal frequency is 2 times per week, however, remote work is possible.
Results will be presented on students’ scientific conference. Considering the extent and quality of scientific contribution students might be acknowledged in the paper or become co-authors.

Immune cell landscape in colorectal cancer from normal mucosa to liver metastasis

Responsible supervisor of the SVOČ project: Andriy Trailin, MD, DSc, andriy.trailin@lfp.cuni.cz

Brief description of the SVOČ project:
Most cancer deaths occur when cancer moves from the original tumor to other organs, which is frequently the liver in case of colorectal cancer (CRC). Metastatic traits of the original tumor can occur either from cell-autonomous mutational changes in the genome of cancer cells or through the exposure to signals from the tumor microenvironment. Resident and infiltrating innate and adaptive immune cells play important role in tumor microenvironment, and altogether can contribute to tumor suppression or promotion. Previous studies have focused on immune microenvironment in the primary tumor, but disregarding the liver metastasis may miss important prognostic information.  Density of CD3+ and CD8+ T-cells in primary CRC have demonstrated positive correlation with patient survival. The mechanisms of linkage and coordination of immune response between primary and metastatic tumors remains unestablished and is the focus of this project.

In the current project we use a unique collection of tissue samples from the same patients, including their normal colonic mucosa, a primary CRC sample and a sample from the liver metastasis. For some patients the liver metastases were found at diagnosis, and were collected along with the primary tumor; for other patients the metastases appeared later and matched with the primary tumor. Tissues will be subjected to extensive immunohistochemistry study followed by computer-assisted image analysis aimed at establishing location, densities and functional orientation of innate and adaptive immune cells.

By comparing the immune cell landscape between normal mucosa, primary and metastatic CRC and correlating the findings with pathological and clinical variables, the goal is to understand the role of the patient’s own immune defence in the metastatic process. We will also compare these triplet tissue sets from patients with and without distant metastases at diagnosis in order to show the distinction between immune cell landscape when metastatic process has already taken place to cases when it will take place in the future.

2 students, optimal frequency is 2 times per week, however, remote work is possible.
Results will be presented on students’ scientific conference. Considering the extent and quality of scientific contribution students might be acknowledged in the paper or become co-authors.

Clinic of Infectious Diseases and Travel Medicine. HIV Centre

Responsible supervisor of the SVOČ project: doc. MUDr. Dalibor Sedláček, CSc.
Long-term monitoring of patients’ adherence to antiretroviral treatment

Brief description of the SVOČ project:
Antiretroviral therapy (ART) together with preventive measures are the only recognized methods to control the HIV/AIDS epidemic. Patients on modern ART regimens are regularly monitored and screened at HIV centres. This allows for rapid intervention in the therapeutic regimen should HIV resistance to the drugs being administered develop. It is well known that new ART is well tolerated and has minimal AEs, therefore treatment outcomes are generally very favourable and within about 1-2 months the initial HIV viremia drops to undetectable levels. For the infected person, this means the cessation of HIV replication and restoration of the immune system. A person with an undetectable viral load (VL) is also virtually non-infectious to the environment, which of course has important epidemiological consequences. However, if patients do not adhere to the necessary recommendations (have poor adherence to treatment), then we usually encounter a slow decline in VL and an inadequate immune system response. Monitoring adherence is difficult, but there are laboratory methods that can help us to prove lack of adherence. In additionally educated patients, this often means a positive adherence to treatment and a significant improvement in treatment outcomes.

Students would process patient data and compare laboratory test results with medical records. Evaluation of the parameters monitored will give an overview of adherence. The results obtained from patients on different treatment regimens can be compared, which can help in selecting the optimal therapeutic approach for different groups of patients.

Number of students who could participate in the SVOČ project: 2-3, HIV centre pav. 2, FN Plzeň Bory. Schedule: one 2-3 hours per week

Department of histology and embryology

Responsible trainer of the project SVOČ: Mgr. Mgr. Kolinko Yaroslav Ph.D.
Quantitative analysis of microglial cells in the cerebellum during neurodegeneration

Brief description of the SVOČ project:

The project aims to count microglial cells and measure the length of their processes across various histological layers of the cerebellum in mice experiencing degeneration associated with the death of Purkinje cells. The student will gain experience in operating a scientific microscope, learn the fundamentals of quantitative histology and stereology, and acquire basic data analysis skills.
The project is planned for a student who will work for two hours a day twice a week. The findings will be presented at the Student Scientific Conference.

I. Internal Clinic, Diabetology

Responsible supervisor of the SVOČ project: MUDr. Michal Krčma, Ph.D.
Name of the SVOČ project.

Brief description of the SVOČ project:
The student will be practically involved in the measurement and evaluation of cardiovascular autonomic neuropathy in type 1 diabetic patients and from the beginning of 2024 also in an investigator-initiated clinical study comparing the accuracy of the newly developed device with the current standard VariaCardio TF5. A presentation at a Czech conference + co-authorship of a publication in a journal with IF in 2025 can be expected. The duration will exceed two semesters, participation in two follow-up years is appropriate.

Suitable for students in 4th year and above, in Czech only (communication with the patient).
One student will be attending for the time being, it would be appropriate to attend some mornings between approximately 7:30 – 11:30 am.

Oncology and Radiotherapy Clinic

Responsible supervisor of the SVOČ project: prof. MUDr. Samuel Vokurka, Ph.D.

SVOČ project titles:
Original and biosimilar pegylated granulopoiesis growth factors in clinical oncology practice since 2005 – real use, benefits, risks.
Ovarian cancer – factors influencing treatment outcomes in elderly patients, use of maintenance therapy with PARP inhibitors in daily practice (tolerance, effect), molecular markers of prognosis and effect.
Prehabilitation, physiotherapy and rehabilitation programmes in cancer patients – factors influencing participation in activities, benefits of active support for participation in the programme, monitoring the development of adequate clinical and laboratory markers.
Cancer and the economic impact on patients – change in income and expenditure, nature of new expenditure, options for addressing in real practice.
Active anti-cancer treatment or other end-of-life care management approach for cancer patients – analysis of the situation in real practice, analysis of factors, limitations and options for change.
Palliative and supportive medicine and care – assessment of quality of life or other specific characteristics in selected patient groups in relation to cancer treatment and/or palliative and supportive treatment and care intervention.
Drug interactions and their risks – status in real practice in cancer patients.

Brief description of the JRC project (common to all themes):
Anticancer treatment itself, but also supportive treatment, play crucial roles in the case of cancer patients with possible positive and negative impact on their health and quality of life. Some changes can be observed relatively soon, while others require long-term follow-up in large cohorts. The heavily represented population of elderly patients certainly deserves separate attention. Not only clinical parameters can be monitored, but also possible laboratory parameters and markers influencing the possible effect of treatment or signalling a better or worse prognosis. Cancer disease and treatment bring many changes to the patient’s life, not only in terms of their own health and fitness, but also in the socio-economic sphere. With the emerging and apparent importance of palliative medicine as an independent field, it is also very important to seek answers to the question of the adequacy of the management of active cancer treatment at the end of life in patients with advanced and virtually uncontrollable malignancies. The topics of the projects are designed in such a way that their solutions will bring practical knowledge that can be used to modify established practice.

The aim of the project: to involve students in active collaboration on individual topics and sub-tasks, the outputs of which can further contribute to the improvement of care, especially for cancer patients.

Requirements for students: interest in the chosen topic, ideally completed 3rd year of study at the Faculty of Arts, compliance with agreed deadlines for cooperation and results, ability to work with MS Excell, Word, PowerPoint, communication and organizational skills.

Project outputs: presentation of results at the SVOČ conference and possibly others, possibility of participation in publications according to the scope of cooperation.