A5018683556- Genetic factors in colorectal cancer
- Colorectal Cancer Treatments and Studies
- Education, Psychology, and Social Research
- DNA Repair Mechanisms
- RNA modifications and cancer
- Telomeres, Telomerase, and Senescence
- Cancer-related molecular mechanisms research
- Pelvic and Acetabular Injuries
- BRCA gene mutations in cancer
- Epigenetics and DNA Methylation
- Colorectal and Anal Carcinomas
- MicroRNA in disease regulation
- Colorectal Cancer Screening and Detection
- Microbial Metabolites in Food Biotechnology
- Nutrition, Genetics, and Disease
- Cancer Genomics and Diagnostics
- Cancer Risks and Factors
- Glycosylation and Glycoproteins Research
- Multiple and Secondary Primary Cancers
- Cholangiocarcinoma and Gallbladder Cancer Studies
- Gut microbiota and health
- Pancreatic and Hepatic Oncology Research
- Circular RNAs in diseases
- Pectus Deformity Diagnosis and Treatment
- Congenital limb and hand anomalies
Charles University
2012-2022
General University Hospital in Prague
2012-2022
University Hospital Kralovske Vinohrady
2020-2022
Masaryk University
2015
Czech Academy of Sciences, Institute of Experimental Medicine
2012
Heidelberg University
2012
University Hospital Heidelberg
2012
University of Oslo
2012
Colorectal cancer (CRC) is one of the main causes death neoplasia. Demand for predictive and prognostic markers to reverse this trend increasing. Long non-coding RNA HOTAIR (Homeobox Transcript Antisense Intergenic RNA) overexpression in tumors was previously associated with poor prognosis higher mortality different carcinomas. We analyzed expression levels tumor blood incident sporadic CRC patients relation their overall survival aim evaluate surrogate marker CRC. Tissue donor group...
Germline mutations in checkpoint kinase 2 ( CHEK2 ), a multiple cancer‐predisposing gene, increase breast cancer (BC) risk; however, risk estimates differ substantially published studies. We analyzed germline variants 1,928 high‐risk Czech breast/ovarian (BC/OC) patients and 3,360 population‐matched controls (PMCs). For functional classification of VUS, we developed complementation assay human nontransformed RPE1‐ ‐knockout cells quantifying CHK2‐specific phosphorylation endogenous protein...
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...
There is increasing evidence indicating a role for Fusobacterium nucleatum (F. nucleatum) in colorectal cancer (CRC) development and prognosis. This study evaluated F. as prognostic biomarker, by assessing its association with post-diagnosis survival from CRC. From September 2008 to April 2012 CRC patients (n = 190) were recruited three hospitals within the Czech Republic. DNA copies measured adjacent non-malignant tumor tissues using quantitative real-time PCR. Cox Proportional Hazards (HR)...
Telomeres, repetitive DNA capping ends of eukaryotic chromosomes, are important in the maintenance genomic integrity. Perturbed telomeres common features many human malignancies, including colorectal cancer.Telomere length (TL), measured by a Monochrome Multiplex Real-Time qPCR, was investigated tumour tissues, adjacent mucosa, and blood from patients with cancer different clinicopathological its impact on patient survival. TL also limited number liver metastases, non-cancerous tissues or...
MicroRNA (miRNA) profiling represents a promising source of cancer-related biomarkers. miRNA signatures are specific for each cancer type and subgroups patients with diverse treatment sensitivity. Yet this potential has not been satisfactorily explored in rectal (RC). The aim the study was to identify signature clinical therapeutic relevance RC. Expressions 2555 were examined 20 pairs tumors matched non-malignant tissues by 3D-Gene Toray microarray. Candidate miRNAs validated an independent...
This study addresses involvement of major 5-fluorouracil (5-FU) pathway genes in the prognosis colorectal carcinoma patients. Testing set and two validation sets comprising paired tumor adjacent mucosa tissue samples from 151 patients were used for transcript profiling 15 5-FU by quantitative real-time PCR DNA methylation high resolution melting analysis. Intratumoral molecular profiles correlated with clinical data Protein levels most relevant candidate markers assessed immunoblotting....
DNA repair processes are involved in both the onset and treatment efficacy of colorectal cancer (CRC). A change a single nucleotide causing an amino acid substitution corresponding protein may alter efficiency repair, thus modifying CRC susceptibility clinical outcome. We performed candidate gene approach order to analyze association non-synonymous polymorphisms (nsSNPs) genes covering main pathways with risk outcome modifications. Our were selected according foremost genomic functional...
Aim: The aim of the present study is to address a genome-wide search for novel methylation biomarkers in rectal cancer (RC), as only scarce information on profile available. Materials & methods: We analyzed status 25 pairs RC and adjacent healthy mucosa using Illumina Human Methylation 450 BeadChip. Results: found significantly aberrant 33 genes. After validation our results by pyrosequencing, we good agreement with findings. BPIL3 HBBP1 genes resulted hypomethylated RC, whereas TIFPI2,...
According to the Vogelstein's model of colorectal carcinogenesis, genetic variations in highly penetrant genes may be involved cancer (CRC) pathogenesis. Similarly, aberrant function and/or altered expression microRNAs (miRNAs) often occur CRC. In this context, polymorphisms miRNA-binding sites (miRSNPs) affect miRNA/target gene interaction, resulting differential mRNA/protein and increased susceptibility common diseases. To explore phenomenon, we have mined 3' untranslated regions (3'UTRs)...
Abstract Protein phosphatase magnesium-dependent 1 delta (PPM1D) terminates cell response to genotoxic stress by negatively regulating the tumor suppressor p53 and other targets at chromatin. Mutations in exon 6 of PPM1D result production a highly stable, C-terminally truncated PPM1D. These gain-of-function mutations are present various human cancers but their role tumorigenesis remains unresolved. Here we show that impairs activation cycle checkpoints non-transformed RPE cells allows...
Oxidative stress, oxidative DNA damage and resulting mutations play a role in colorectal carcinogenesis. Impaired equilibrium between formation, antioxidant status, repair capacity is responsible for the accumulation of genetic genomic instability. The lesion-specific glycosylases, e.g., hOGG1 MUTYH, initiate damage. Hereditary syndromes (MUTYH-associated polyposis, NTHL1-associated tumor syndrome) with germline causing loss-of-function base excision serve as straight forward evidence on its...
Disruption of genomic integrity due to deficient DNA repair capacity and telomere shortening constitute hallmarks malignant diseases. Incomplete or double-strand breaks (DSB) is manifested by chromosomal aberrations their frequency reflects inter-individual differences response exposure mutagenic compounds. In this study, we investigated in peripheral blood lymphocytes (PBL) from newly diagnosed cancer patients, including 47 breast (BC) 44 colorectal (CRC) patients 90 matched healthy...
Cancer therapy failure is a fundamental challenge in cancer treatment. One of the most common reasons for development acquired resistance cells. DNA-damaging agents are frequently used first-line chemotherapy regimens and DNA damage response, repair pathways significantly involved mechanisms chemoresistance. MRE11, part MRN complex double-strand break (DSB) repair, connected to colorectal (CRC) patients' prognosis. Our previous results showed that single-nucleotide polymorphisms (SNPs) 3'...
Východiska: Dědičné mutace v genu CHEK2 kódujícím CHK2 proteinkinázu způsobují středně zvýšené riziko vzniku karcinomu prsu (breast cancer -BC) a dalších nádorových onemocnění.Vysoká populační variabilita mutací výskyt vzácných missense variant nejasného významu (variants of unknown clinical significance -VUS) komplikuje odhad rizika onemocnění u nosičů germinálních variant.Soubor pacientů metody: Mutační analýzu CHEK2, vč.analýzy velkých přestaveb, jsme provedli 1 526 vysoce rizikových...
Mutations in the mutL homolog 1 (MLH1) gene are frequent patients with hereditary non‑polyposis colorectal cancer (CRC). The MLH1 was screened for mutations sporadic CRC. nucleotide sequences all 19 exons of were analyzed by high resolution melting and sequenced a group 104 CRC patients, results verified replication 1,095 1,469 controls. Different profiles exon 2 observed germline DNA one patient. Sequencing patient's resulted identification heterozygous C>G variant at c.204, which an...