A5023782138- Genetic factors in colorectal cancer
- Cancer Cells and Metastasis
- Wnt/β-catenin signaling in development and cancer
- Cancer Genomics and Diagnostics
- Colorectal Cancer Treatments and Studies
- RNA modifications and cancer
- Hormonal Regulation and Hypertension
- Cancer-related gene regulation
- Digestive system and related health
- Epigenetics and DNA Methylation
- Hippo pathway signaling and YAP/TAZ
- Cancer Research and Treatments
- Pancreatic function and diabetes
- DNA Repair Mechanisms
- Cancer-related molecular mechanisms research
- Heat shock proteins research
- Growth Hormone and Insulin-like Growth Factors
- Inflammatory mediators and NSAID effects
- Neutrophil, Myeloperoxidase and Oxidative Mechanisms
- Multiple and Secondary Primary Cancers
- Immunotherapy and Immune Responses
- interferon and immune responses
- Stress Responses and Cortisol
- Gastrointestinal disorders and treatments
- Cancer-related Molecular Pathways
Charles University
2009-2024
Czech Academy of Sciences, Institute of Molecular Genetics
2012-2024
University Hospital Kralovske Vinohrady
2022-2024
Czech Academy of Sciences
2009-2022
Czech Academy of Sciences, Institute of Experimental Medicine
2012-2014
Czech Academy of Sciences, Institute of Physiology
2009-2014
General University Hospital in Prague
2012
Heidelberg University
2012
University Hospital Heidelberg
2012
University of Oslo
2012
Abstract Purpose: DNA repair capacity (DRC) is a determinant not only of cancer development but also individual response to therapy. Previously, altered base and nucleotide excision (BER NER) have been described in lymphocytes patients with sporadic colorectal cancer. We, for the first time, evaluate both capacities human colon biopsies study their participation tumorigenesis. Experimental design: Seventy pairs tumor adjacent healthy tissues were analyzed BER- NER-specific DRC by comet...
The activity of the Wnt pathway undergoes complex regulation to ensure proper functioning this principal signaling mechanism during development adult tissues. may occur at several levels and includes both positive negative feedback loops. In present study we employed one such regulators, naked cuticle homolog 1 (Nkd1), follow in intestine liver neoplasia originated these organs. Using lineage tracing transgenic mice localized Nkd1 mRNA bottom parts small intestinal crypts hepatocytes...
Trophoblastic cell surface antigen 2 (TROP2) is a membrane glycoprotein overexpressed in many solid tumors with poor prognosis, including intestinal neoplasms. In our study, we show that TROP2 expressed preneoplastic lesions, and its expression maintained most colorectal cancers (CRC). High positivity correlated lymph node metastases tumor differentiation was negative prognostic factor. To investigate the role of tumors, analyzed two mouse models conditional disruption adenomatous polyposis...
Abstract The first step in the development of human colorectal cancer is aberrant activation Wnt signaling pathway. hyperactivation predominantly caused by loss-of-function mutations adenomatous polyposis coli ( APC ) gene that encodes pathway negative regulator. In order to identify genes affected Apc loss, we performed expression profiling intestinal epithelium isolated from mice harboring a conditional allele. encoding transcriptional factor msh homeobox 1 Msx 1) displayed robust...
Commensal microbiota contribute to gut homeostasis by inducing transcription of mucosal genes. Analysis the impact various on intestinal tissue provides an important insight into function this organ. We used cDNA microarrays determine gene expression signature mucosa isolated from small intestine and colon germ-free (GF) mice animals monoassociated with two E. coli strains. The results were compared data obtained in conventionally reared (CR) mice. In addition, we analyzed organoids derived...
Abstract A large proportion of colorectal carcinomas (CRC) evolve from adenomas. However, not all individuals with colonic adenomas have a risk CRC substantially higher than those the general population. The aim study was to determine differences or similarities mutation profile among low- and high-grade in situ carcinoma detailed follow up. We investigated spectrum well-known genes involved (such as APC, BRAF, EGFR, NRAS, KRAS, PIK3CA, POLE, POLD1, SMAD4, PTEN, TP53 ) large, well-defined...
Elevated levels of survivin, telomerase catalytic subunit (TERT), integrin-linked kinase (ILK), cyclooxygenase 2 (COX-2), inducible nitric oxide synthase (iNOS) and the regulatory factors c-MYB Tcf-4 are often found in human cancers including colorectal cancer (CRC) have been implicated development progression tumorigenesis. The aim this study was to determine expression these genes mouse models sporadic colitis-associated CRC. To address issues, we used qRT-PCR approach changes gene...
Inflammatory bowel diseases including long-standing ulcerative colitis (UC) have an increased risk of evolving into colorectal cancer (CRC). The overexpression some proproliferative and antiapoptotic genes, such as survivin, telomerase catalytic subunit (hTERT), integrin-linked kinase (ILK), regulatory factors c-MYB Tcf-4, has been implicated in the development progression several human malignancies CRC.In this study we analyzed expression alterations these markers proinflammatory enzymes...
Radiation and chemotherapy represent standard‐of‐care cancer treatments. However, most patients eventually experience tumour recurrence, treatment failure metastatic dissemination with fatal consequences. To elucidate the molecular mechanisms of resistance to radio‐ chemotherapy, we exposed human cell lines (HeLa, MCF‐7 DU 145) clinically relevant doses 5‐azacytidine or ionizing radiation compared transcript profiles all surviving subpopulations, including low‐adherent stem‐like cells....
Neoplastic growth is frequently associated with genomic DNA methylation that causes transcriptional silencing of tumor suppressor genes. We used a collection colorectal polyps and carcinomas in combination bioinformatics analysis large datasets to study the expression Hypermethylated cancer 1 (HIC1), gene inactivated many neoplasms. In premalignant stages, HIC1 was decreased, decrease linked specific region locus. However, carcinomas, variable and, some specimens, comparable healthy tissue....
Leucine-rich repeat-containing G-protein-coupled receptor 4 (LGR4) is produced in a broad spectrum of mouse embryonic and adult tissues its deficiency results embryonal or perinatal lethality. The LGR4 function was mainly related to potentiation canonical Wnt signaling; however, several recent studies associate with additional signaling pathways. To obtain suitable tool for studying the properties Lgr4, we generated tagged variant Lgr4 using gene targeting oocyte. modified allele expresses...
Although the effects of glucocorticoids on proliferation, differentiation and apoptosis are well known, steroid hormones have been identified to play a role in pathogenesis development various cancers, limited data available regarding relationship between local metabolism colorectal adenocarcinoma (CRC) formation. Glucocorticoid is determined by 11β-hydroxysteroid dehydrogenases type 1 2 (11HSD1, 11HSD2), which increase concentration cortisol due reduction cortisone, or decrease this...
Abstract Hypermethylated in Cancer 1 (HIC1) is an established tumor suppressor, which frequently inactivated various cancers. In colorectal carcinoma (CRC), silencing of HIC1 has been recognized as one the important events malignant progression. Strikingly, CRC patients with high expression have a worse prognosis than relatively low mRNA levels. To analyze function HIC1, we performed profiling human primary fibroblasts after downregulation by RNA interference. We show that deficiency...
Abstract Trophoblastic cell surface antigen 2 (TROP2) is a membrane glycoprotein overexpressed in many solid tumors with poor prognosis, including intestinal neoplasms. In our study, we show that TROP2 expressed preneoplastic lesions and its expression maintained most colorectal cancer (CRC). High positivity correlated lymph node metastases tumor differentiation was negative prognostic factor. To investigate the role of tumors, analyzed two mouse models conditional disruption adenomatous...