DNA repair in blood cells was observed to be suboptimal in cancer patients at diagnosis, including colorectal cancer (CRC). To explore the causality of this phenomenon, we studied the dynamics of DNA repair from diagnosis to 1 yr follow-up, and with respect to CRC treatment. Systemic CRC therapy is targeted to DNA damage induction and DNA repair is thus of interest. CRC patients were blood-sampled three times in 6-mo intervals, starting at the diagnosis, and compared to healthy controls. DNA repair was characterized by mRNA levels of 40 repair genes, by capacity of nucleotide excision repair (NER), and by levels of DNA strand breaks (SBs). NER and base excision repair genes were significantly under-expressed (P < 0.016) in patients at diagnosis compared to controls, in accordance with reduced NER function (P = 0.008) and increased SBs (P = 0.015). Six months later, there was an increase of NER capacity, but not of gene expression levels, in treated patients only. A year from diagnosis, gene expression profiles and NER capacity were significantly modified in all patients and were no longer different from those measured in controls. All patients were free of relapse at the last sampling, so we were unable to clarify the impact of DNA repair parameters on treatment response. However, we identified a panel of blood DNA repair-related markers discerning acute stage of the disease from the remission period. In conclusion, our results support a model in which DNA repair is altered as a result of cancer.

• MeSH
• antitumorózní látky terapeutické užití   MeSH
• kolon účinky léků   metabolismus   MeSH
• kolorektální nádory krev   farmakoterapie   genetika   MeSH
• lidé středního věku MeSH
• lidé MeSH
• následné studie MeSH
• oprava DNA * účinky léků   MeSH
• regulace genové exprese u nádorů účinky léků   MeSH
• rektum účinky léků   metabolismus   MeSH
• senioři MeSH
• studie případů a kontrol MeSH
• zlomy DNA účinky léků   MeSH
• Check Tag
• lidé středního věku MeSH
• lidé MeSH
• mužské pohlaví MeSH
• senioři MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH

Colorectal cancer (CRC) is one of the main causes of death of neoplasia. Demand for predictive and prognostic markers to reverse this trend is increasing. Long non-coding RNA HOTAIR (Homeobox Transcript Antisense Intergenic RNA) overexpression in tumors was previously associated with poor prognosis and higher mortality in different carcinomas. We analyzed HOTAIR expression levels in tumor and blood of incident sporadic CRC patients in relation to their overall survival with the aim to evaluate surrogate prognostic marker for CRC. Tissue donor group consisted of 73 CRC patients sampled for tumor and normal tissue. Blood donor group was represented by 84 CRC patients compared with 40 healthy controls. Patients were characterized for tumor-node-metastasis stage, tumor grade, microsatellite instability and tumor penetration by stromal cells. HOTAIR levels were assessed by real-time quantitative PCR. CRC patients had higher HOTAIR expression in blood than healthy controls (P = 0.0001), whereas there was no difference in HOTAIR levels between tumor and adjacent mucosa of CRC patients. HOTAIR levels positively correlated between blood and tumor (R = 0.43, P = 0.03). High HOTAIR levels in tumors were associated with higher mortality of patients [Cox's proportional hazard, hazard ratio = 4.4, 95% confidence interval: 1.0-19.2, P = 0.046]. The hazard ratio was even higher when blood HOTAIR levels were taken into account (hazard ratio = 5.9, 95% confidence interval: 1.3-26.1, P = 0.019). Upregulated HOTAIR relative expression in primary tumors and in blood of CRC patients is associated with unfavorable prognosis. Our data suggest that HOTAIR blood levels may serve as potential surrogate prognostic marker in sporadic CRC.

• MeSH
• dospělí MeSH
• kolon metabolismus   MeSH
• kolorektální nádory krev   genetika   mortalita   MeSH
• kvantitativní polymerázová řetězová reakce MeSH
• lidé středního věku MeSH
• lidé MeSH
• messenger RNA genetika   MeSH
• míra přežití MeSH
• nádorové biomarkery krev   genetika   MeSH
• následné studie MeSH
• polymerázová řetězová reakce s reverzní transkripcí MeSH
• prognóza MeSH
• rektum metabolismus   MeSH
• RNA dlouhá nekódující krev   genetika   MeSH
• senioři nad 80 let MeSH
• senioři MeSH
• staging nádorů MeSH
• studie případů a kontrol MeSH
• stupeň nádoru MeSH
• Check Tag
• dospělí MeSH
• lidé středního věku MeSH
• lidé MeSH
• mužské pohlaví MeSH
• senioři nad 80 let MeSH
• senioři MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH
• srovnávací studie MeSH

Worldwide, colorectal cancer (CRC) is the third most common cancer, with the highest mortality rates occurring in Central Europe. The use of chemotherapy to treat CRC is limited by the inter-individual variability in drug response and the development of cancer cell resistance. ATP-binding cassette (ABC) transporters play a crucial role in the development of resistance by the efflux of anticancer agents outside of cancer cells. The aim of this study was to explore transcript levels of all human ABCs in tumours and non-neoplastic control tissues from CRC patients collected before the first line of treatment by 5-fluorouracil (5-FU)-containing regimen. The prognostic potential of ABCs was evaluated by the correlation of transcript levels with clinical factors. Relations between transcript levels of ABCs in tumours and chemotherapy efficacy were also addressed. The transcript profile of all known human ABCs was assessed using real-time polymerase chain reaction with a relative standard curve. The majority of the studied ABCs were down-regulated or unchanged between tumours and control tissues. ABCA12, ABCA13, ABCB6, ABCC1, ABCC2 and ABCE1 were up-regulated in tumours versus control tissues. Transcript levels of ABCA12, ABCC7 and ABCC8 increased in direction from colon to rectum. Additionally, transcript levels of ABCB9, ABCB11, ABCG5 and ABCG8 followed the reverse significant trend, i.e. a decrease in direction from colon to rectum. The transcript level of ABCC10 in tumours correlated with the grade (P = 0.01). Transcript levels of ABCC6, ABCC11, ABCF1 and ABCF2 were significantly lower in non-responders to palliative chemotherapy in comparison with responders. The disease-free interval of patients treated by adjuvant chemotherapy was significantly shorter in patients with low transcript levels of ABCA7, ABCA13, ABCB4, ABCC11 and ABCD4. In conclusion, ABCC11 may be a promising candidate marker for a validation study on 5-FU therapy outcome.

• MeSH
• ABC transportéry genetika   MeSH
• adjuvantní chemoterapie MeSH
• antitumorózní látky terapeutické užití   MeSH
• kolon metabolismus   MeSH
• kolorektální nádory farmakoterapie   genetika   mortalita   MeSH
• kvantitativní polymerázová řetězová reakce MeSH
• lidé středního věku MeSH
• lidé MeSH
• messenger RNA genetika   MeSH
• metastázy nádorů MeSH
• míra přežití MeSH
• pilotní projekty MeSH
• polymerázová řetězová reakce s reverzní transkripcí MeSH
• prognóza MeSH
• progrese nemoci MeSH
• regulace genové exprese u nádorů MeSH
• rektum metabolismus   MeSH
• senioři MeSH
• studie případů a kontrol MeSH
• Check Tag
• lidé středního věku MeSH
• lidé MeSH
• mužské pohlaví MeSH
• senioři MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH

PURPOSE: Increased levels of vitamin D may protect against colorectal cancer (CRC) development and recurrence. Accumulating epidemiologic evidence suggests these effects may be partly mediated by genetic variants of the vitamin D receptor (VDR) proposed to be associated with altered risk of CRC. We wished to determine if common VDR polymorphisms affected CRC risk in the Czech Republic, a homogenous European population with a high CRC incidence rate. METHODS: Frequencies of the common VDR gene polymorphisms rs2238136, rs1544410 (BsmI), rs7975232 (ApaI), and rs731236 (TaqI) were determined using allele-specific PCR in a case control analysis of a series of 754 CRC patients and 627 patients without malignant disease recruited from centers throughout the Czech Republic. Unconditional logistic regression was used to calculate odds ratios and 95% confidence intervals for the association between these variants and risk of CRC. RESULTS: None of the four polymorphisms tested had any significant effect on CRC risk. No significant differences were observed in susceptibility when the population was stratified by anatomical sub-site, sex, BMI, smoking, alcohol, or presence of polyps. CONCLUSIONS: We conclude that common variation in the VDR gene had little effect on its own on predisposition to sporadic CRC in the Czech population.

• MeSH
• DNA genetika   MeSH
• dospělí MeSH
• kolon metabolismus   MeSH
• kolorektální nádory genetika   MeSH
• lidé středního věku MeSH
• lidé MeSH
• polymerázová řetězová reakce MeSH
• polymorfismus genetický genetika   MeSH
• prognóza MeSH
• receptory kalcitriolu genetika   MeSH
• rektum metabolismus   MeSH
• rizikové faktory MeSH
• senioři nad 80 let MeSH
• senioři MeSH
• studie případů a kontrol MeSH
• vitamin D metabolismus   MeSH
• Check Tag
• dospělí MeSH
• lidé středního věku MeSH
• lidé MeSH
• mužské pohlaví MeSH
• senioři nad 80 let MeSH
• senioři MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH
• srovnávací studie MeSH
• Geografické názvy
• Česká republika MeSH

Dysregulation of innate and adaptive intestinal immune responses to bacterial microbiota is supposed to be involved in pathogenetic mechanisms of inflammatory bowel diseases (IBDs). We investigated expression of Toll-like receptor 2 (TLR2), TLR4, and their transmembrane coreceptor CD14 in biopsy samples from patients with IBD and in non-inflamed gut mucosa from controls. Small intestine and colon samples were obtained by colonoscopy from patients with Crohn's disease (CD), ulcerative colitis (UC), and controls. Immunohistochemical analysis of cryostat sections using polyclonal and monoclonal antibodies specific for TLR2, TLR4, and CD14 showed a significant increase in TLR2 expression in the terminal ileum of patients with inactive and active UC against controls. Significant upregulation of TLR4 expression relative to controls was found in the terminal ileum and rectum of UC patients in remission and in the terminal ileum of CD patients with active disease. CD14 expression was upregulated in the terminal ileum of CD patients in remission and with active disease, in the cecum of UC patients in remission and with active disease, and in rectum of UC patients with active disease. Hence, dysregulation of TLR2, TLR4, and CD14 expression in different parts of the intestinal mucosa may be crucial in IBD pathogenesis.

• MeSH
• antigeny CD14 biosyntéza   MeSH
• biopsie MeSH
• cékum metabolismus   patologie   MeSH
• Crohnova nemoc metabolismus   patologie   MeSH
• financování organizované MeSH
• ileum metabolismus   patologie   MeSH
• imunohistochemie MeSH
• lidé MeSH
• rektum metabolismus   patologie   MeSH
• střevní sliznice metabolismus   patologie   MeSH
• toll-like receptor 2 biosyntéza   MeSH
• toll-like receptor 4 biosyntéza   MeSH
• ulcerózní kolitida metabolismus   patologie   MeSH
• Check Tag
• lidé MeSH

The panel of six lectins was used for demonstration of glycosylative changes in the hyperplastic, adenomatous and carcinomatous mucosa of large bowel. The obtained results were rather heterogeneous with regard to lectin binding capacity in the single cases but they proved a certain uniformity of changes inside every tested group. These changes cohered with decrease of capability dysplastic and neoplastic cells to produce of normal goblets and with loss of cell polarity. Possible causes of these alterations are discussed.

• MeSH
• glykosylace MeSH
• histocytochemie MeSH
• kolon metabolismus   patologie   MeSH
• lidé MeSH
• nádory tračníku metabolismus   patologie   MeSH
• receptory mitogenů metabolismus   MeSH
• rektum metabolismus   patologie   MeSH
• střevní sliznice metabolismus   patologie   MeSH
• Check Tag
• lidé MeSH
• Publikační typ
• časopisecké články MeSH

• MeSH
• Aspirin metabolismus   MeSH
• čípky MeSH
• emulze MeSH
• farmaceutické pomocné látky farmakologie   MeSH
• fenobarbital metabolismus   MeSH
• hexobarbital metabolismus   MeSH
• intestinální absorpce MeSH
• kyseliny aminohippurové metabolismus   MeSH
• kyseliny aminosalicylové metabolismus   MeSH
• léčivé přípravky metabolismus   MeSH
• lipidy MeSH
• peniciliny metabolismus   MeSH
• rektum metabolismus   MeSH
• rozpouštědla MeSH
• rozpustnost MeSH
• sodík metabolismus   MeSH
• sulfisomidin metabolismus   MeSH
• thiopental metabolismus   MeSH
• tolbutamid metabolismus   MeSH
• voda MeSH