Stepan Balatka

Charles University

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Alžběta Spálenková

National Institute of Public Health

Pavel Souček

National Institute of Public Health

KŠ

Karolína Šeborová

Charles University

ÁS

Árpád Szabó

Charles University

Martin Oliverius

Charles University

R. Václavíková

National Institute of Public Health

Tereza Tesařová

National Institute of Public Health

Tomas Sychra

Charles University

Marie Ehrlichová

Charles University

Jaroslav Truksa

Czech Academy of Sciences, Institute of Biotechnology

Cooperative Institutions

Charles University

National Institute of Public Health

University Hospital Kralovske Vinohrady

Czech Academy of Sciences

State University of New York

Czech Academy of Sciences, Institute of Biotechnology

Czech Academy of Sciences, Institute of Molecular Genetics

Institute of Clinical and Experimental Medicine

Centrum kardiovaskulární a transplantační chirurgie

Stony Brook University

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An Experimental Immunodeficient Mouse Model of Human Pancreatic Carcinoma for the Study of Optimal Therapeutic Regimens

HPB (2023)

Martin Oliverius Tomas Sychra R. Václavíková Árpád Szabó Alžběta Spálenková

Pancreatic carcinoma

10.1016/j.hpb.2023.07.567

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EP037/#733 The effect of 7-ketocholesterol on breast carcinoma cell lines treated with tamoxifen in vitro

E-Posters (2022)

Alžběta Spálenková Marie Ehrlichová Karolína Šeborová Radka Václavíková Stepan Balatka

Objectives

Oxysterols are oxidative derivatives of cholesterol that play many roles in human physiology and pathology, including cancer. For example, oxysterols modulate cell proliferation, apoptosis, or migration. This study aimed to analyze the role of important oxysterol, 7-ketocholesterol (7-KC), in response of breast carcinoma cell line models to treatment with tamoxifen.

Methods

Two estrogen receptor (ER) positive (MCF-7 and T47D) and one ER-negative (BT-20) breast carcinoma cell lines were employed. Cell lines were co-incubated with tamoxifen and 7-KC at different concentration ratios, and the viability of cells, proliferation, cell cycle, caspase activity, and gene expression changes were evaluated. Next, the ability of 7-KC to stimulate cell migration and invasivity was tested.

Results

7-KC slightly increased the IC₅₀ value of tamoxifen in the MCF7 cell line, but decreased it in the BT-20 cell line. No significant difference was observed for T47D cells. In line with these data, caspase 3/7 activity was enhanced by 7-KC in BT-20 cells, but not in any ER-positive cell line. Gene expression analysis showed upregulation of tamoxifen metabolizing genes, e.g. CYP1A1 and CYP1B1 in MCF-7 while downregulation in BT-20 cells. Finally, we found that the presence of 7-KC potentiates cellular migration and invasivity.

Conclusions

7-KC seems to modulate the response of breast carcinoma cells to tamoxifen according to ER status in vitro, making it an interesting candidate for future studies. The study was supported by projects INTER-ACTION no. LTAUSA19032 and AZV no. NU20–09–00174.

Oxysterol

Viability assay

Breast carcinoma

10.1136/ijgc-2022-igcs.128

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Introducing in vivo pancreatic cancer models for the study of new therapeutic regimens

Perspectives in Surgery (2022)

T Sychra R. Václavíková Árpád Szabó Alžběta Spálenková Karolína Šeborová

Introduction: Pancreatic cancer is a severe oncological disease with an ever-increasing incidence and a high rate of morbidity and mortality. Therapeutic options are limited and the five-year overall survival rate is 7–20%, depending on the possibility of surgical resection and the earliness of detection. Most patients with this diagnosis die due to the resistance of tumour cells and their microenvironment to the used treatment regimes. Methods: In our study, we focused on the implementation of two in vivo models, which are the cell-line derived xenograft (CDX) and the patient-derived xenograft (PDX). These two models differ significantly from each other methodologically, technically, financially, but also in their achieved results. Results: In a pilot study, we managed to successfully implement the CDX model with a very aggressive and resistant PaCa-44 line of pancreatic cancer in a total of 30 NU/NU strain mice. Furthermore, we created three PDX models with various subtypes of pancreatic cancer from patients operated at the University Hospital Kralovske Vinohrady, Department of General Surgery. These tumours were re-transplanted into subsequent generations of 23 individuals of NOD/SCID strain and 47 NU/NU strain mice. The established CDX and PDX models are then used to compare conventional and experimental chemotherapy regimens. Conclusion: The next steps will be to evaluate the effects of treatment regimens by using imaging and molecular genetic methods and to optimise the entire process for further use in precise personalised medicine for patients with pancreatic cancer. The upcoming goal is to create a library of PDX models of the most common pancreatic ductal adenocarcinoma and other rare subtypes of pancreatic cancer

10.33699/pis.2022.101.12.584-592

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Third-generation taxanes SB-T-121605 and SB-T-121606 are effective in pancreatic ductal adenocarcinoma

iScience (2024)

Tomas Sychra Alžběta Spálenková Stepan Balatka Radka Václavíková Karolína Šeborová

Pancreatic cancer is a severe malignancy with increasing incidence and high mortality due to late diagnosis and low sensitivity to treatments. Search for the most appropriate drugs and therapeutic regimens is the most promising way to improve the treatment outcomes of the patients. This study aimed to compare (1)

Pancreatic carcinoma

10.1016/j.isci.2024.109044

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Citations (1)