Telomeric sequences, the structures comprised of hexanucleotide repeats and associated proteins, play a pivotal role in chromosome end protection and preservation of genomic stability. Herein we address telomere length (TL) dynamics in primary colorectal cancer (CRC) tumour tissues and corresponding liver metastases. TL was measured by multiplex monochrome real-time qPCR in paired samples of primary tumours and liver metastases along with non-cancerous reference tissues obtained from 51 patients diagnosed with metastatic CRC. Telomere shortening was observed in the majority of primary tumour tissues compared to non-cancerous mucosa (84.1%, p < 0.0001). Tumours located within the proximal colon had shorter TL than those in the rectum (p < 0.05). TL in liver metastases was not significantly different from that in primary tumours (p = 0.41). TL in metastatic tissue was shorter in the patients diagnosed with metachronous liver metastases than in those diagnosed with synchronous liver metastases (p = 0.03). The metastatic liver lesions size correlated with the TL in metastases (p < 0.05). Following the neoadjuvant treatment, the patients with rectal cancer had shortened telomeres in tumour tissue than prior to the therapy (p = 0.01). Patients with a TL ratio between tumour tissue and the adjacent non-cancerous mucosa of ≥ 0.387 were associated with increased overall survival (p = 0.01). This study provides insights into TL dynamics during progression of the disease. The results show TL differences in metastatic lesions and may help in clinical practice to predict the patient's prognosis.
Long chain 3-hydroxyacyl-CoA dehydrogenase deficiency (LCHADD/MTPD) and medium chain acyl-CoA dehydrogenase deficiency (MCADD) were included in the expanded neonatal screening program (ENBS) in Czechia in 2009, allowing for the presymptomatic diagnosis and nutritional management of these patients. The aim of our study was to assess the nationwide impact of ENBS on clinical outcome. This retrospective study analysed acute events and chronic complications and their severity in pre-ENBS and post-ENBS cohorts. In total, 28 children (12 before, 16 after ENBS) were diagnosed with LCHADD/MTPD (incidence 0.8/100,000 before and 1.2/100,000 after ENBS). In the subgroup detected by ENBS, a significantly longer interval from birth to first acute encephalopathy was observed. In addition, improvement in neuropathy and cardiomyopathy (although statistically non-significant) was demonstrated in the post-ENBS subgroup. In the MCADD cohort, we included 69 patients (15 before, 54 after ENBS). The estimated incidence rose from 0.7/100,000 before to 4.3/100,000 after ENBS. We confirmed a significant decrease in the number of episodes of acute encephalopathy and lower proportion of intellectual disability after ENBS (p < 0.0001). The genotype-phenotype correlations suggest a new association between homozygosity for the c.1528C > G variant and more severe heart involvement in LCHADD patients.
- MeSH
- 3-hydroxyacyl-CoA-dehydrogenasy nedostatek MeSH
- acyl-CoA-dehydrogenasa nedostatek MeSH
- dítě MeSH
- hodnocení výsledků zdravotní péče MeSH
- incidence MeSH
- kardiomyopatie diagnóza dietoterapie epidemiologie MeSH
- karnitin analogy a deriváty krev MeSH
- kojenec MeSH
- lidé MeSH
- mitochondriální myopatie diagnóza dietoterapie epidemiologie MeSH
- mitochondriální trifunkční protein nedostatek MeSH
- nemoci nervového systému diagnóza dietoterapie epidemiologie MeSH
- novorozenec MeSH
- novorozenecký screening metody MeSH
- předškolní dítě MeSH
- retrospektivní studie MeSH
- rhabdomyolýza diagnóza dietoterapie epidemiologie MeSH
- stupeň závažnosti nemoci MeSH
- vrozené poruchy metabolismu tuků diagnóza dietoterapie epidemiologie MeSH
- vrozené poruchy metabolismu diagnóza MeSH
- Check Tag
- dítě MeSH
- kojenec MeSH
- lidé MeSH
- mužské pohlaví MeSH
- novorozenec MeSH
- předškolní dítě MeSH
- ženské pohlaví MeSH
- Publikační typ
- časopisecké články MeSH
- Geografické názvy
- Česká republika MeSH
An interlaboratory study in 12 laboratories was performed to prove the validation of the ELISA method developed for the quantitative determination of mustard protein in foods. The ELISA kit used for this study is based on rabbit polyclonal antibody. This kit did not produce any false-positive results or cross-reactivity with in-house validation for a broad range of food matrixes with no detectable mustard protein. All participants obtained the Mustard ELISA kit with standard operational procedures, a list of samples, samples, and a protocol for recording test results. The study included 15 food samples and two spiked samples. Seven food matrix samples of zero mustard content and four samples with mustard declared as an ingredient showed mustard protein content lower than that of the first standard (0.42 mg/kg). Four samples with mustard declared as an ingredient revealed mustard protein content above 12.5 mg/kg (the highest standard). The statistical tests (Cochran, Dixon, and Mandel) and analysis of variance were used to evaluate the interlaboratory study results. Repeatability and reproducibility limits, as well as an LOQ (1.8 mg mustard proteins/kg) and LOD (0.5 mg mustard proteins/kg), for the kit were calculated.
An interlaboratory study was performed in eight laboratories to validate an ELISA method developed for quantitative determination of casein in foods. The ELISA kit used is based on rabbit polyclonal antibodies. The kit is quite specific; no false-positive results or cross-reactivities were obtained for a broad range of food matrixes with zero content of milk proteins. All participants in the study received the casein kit, which included a standard operating procedure, a list of the samples, the samples, and a protocol for recording test results. The study included nine food samples: wheat flour, buckwheat flour, instant potato purée with milk, instant coffee with sugar and cream, a mixture for fancy bread, salami, liver paté, chocolate muesli with nuts, and a mixture for gluten-free bread. Three food samples with zero content of milk proteins showed a casein content lower than the lowest casein standard (1.0 mg CAS/kg) in most laboratories and measurements (64%). In 98% of the cases, the casein content was lower than the estimated LOQ. Two food samples with no dairy ingredient declared on the ingredient list contained casein levels higher than the second casein standard (3.0 mg CAS/kg) and the third standard (10.0 mg CAS/kg), respectively. Four food samples containing milk as an ingredient tested positive, and three showed casein contents higher than the highest standard (30.0 mg CAS/kg). The statistical tests (Cochran, Dixon) and analysis of variance were used for evaluation of the interlaboratory study results. Repeatability and reproducibility limits as well as LOQ (1.8 mg CAS/kg) and LOD (0.5 mg CAS/kg) for the kit were calculated from the results of the interlaboratory study.
- MeSH
- alergeny analýza MeSH
- analýza potravin metody MeSH
- ELISA metody MeSH
- kalibrace MeSH
- kaseiny analýza MeSH
- králíci MeSH
- mléčné bílkoviny chemie MeSH
- mléčné výrobky analýza MeSH
- potraviny MeSH
- referenční standardy MeSH
- reprodukovatelnost výsledků MeSH
- zkřížené reakce MeSH
- zvířata MeSH
- Check Tag
- králíci MeSH
- zvířata MeSH
- Publikační typ
- časopisecké články MeSH
- práce podpořená grantem MeSH
An interlaboratory study was conducted in 11 laboratories to validate an ELISA method developed for the quantitative determination of egg white proteins (EWPs) in foods. The ELISA kit used for this study is based on sheep polyclonal antibody. It does not produce any false-positive results or cross-reactivity in a broad food matrix range with zero EWP content. All participants obtained the Egg ELISA Kit-native with standard operational procedure and the list of samples, as well as the samples and a protocol for recording test results. The study included 10 food samples. Four samples of food matrix with zero EWP content showed EWP content lower than the first standard (EWP content 0.5 mg/kg). One sample of food matrix with zero EWP content revealed EWP content higher than standard 3 (1.5 mg EWP/kg). Five food samples containing EWP as an ingredient tested positive and one negative. The statistical tests (Cochran, Dixon, and Mandel) and analysis of variance were used to evaluate the interlaboratory study results. Repeatability and reproducibility limits, as well as LOQ (1.4 mg EWP/kg) and LOD (0.43 mg EWP/kg), were calculated for the kit.
- MeSH
- alergeny analýza MeSH
- analýza potravin MeSH
- ELISA MeSH
- Evropská unie MeSH
- indikátory a reagencie MeSH
- kalibrace MeSH
- reagenční diagnostické soupravy MeSH
- referenční standardy MeSH
- reprodukovatelnost výsledků MeSH
- teplota MeSH
- vaječné proteiny analýza MeSH
- zkřížené reakce MeSH
- Publikační typ
- časopisecké články MeSH
- práce podpořená grantem MeSH
- validační studie MeSH
Nové protinádorové léky využívají znalostí molekulárních mechanizmů malignit pro cílený zásah potlačující patologický proces. Cílem zásahu jsou jednak receptory růstových faktorů, jejich ligandy a molekuly z navazujících signalizačních drah, jednak deacetylázy histonů a dalších molekul transkripčního aparátu. V prvé skupině jde o protilátky proti receptorům a především o „malé molekuly“ inhibující jejich funkci. Naproti tomu inhibitory histonových deacetyláz jsou chemicky heterogenní skupina látek, které udržováním vysoké míry acetylace cílových molekul zajišťují přepis genů různých antionkogenně působících molekul. Řada látek z obou skupin prošla úspěšně preklinickými nebo i klinickými testy, některé preparáty, zvláště z kategorie protilátek, již zásadním způsobem proměnily léčbu konkrétních malignit. Cílem tohoto článku je podat přehlednou informaci alespoň o nejvýznamnějších látkách z těchto nově nastupujících skupin protinádorových léčiv. Je popisován obecný mechanizmus účinku u každé skupiny, dosažená úroveň preklinického a klinického testování, chemie a případně konkrétní molekulární interakce v maligní buňce.
New anti-cancer medicines take advantage of knowledge of molecular mechanisms of malignities for aimed intervention suppressing the pathological process. The targets of the intervention are on the one hand receptors of growth factors, their ligands and molecules from connected signal paths and, on the other hand, deacetylases of histones and further molecules of the transcription apparatus. The first group comprises antibodies against receptors and mainly “small molecules” inhibiting their function. In contrast, inhibitors of histone deacetylases are a chemically heterogeneous group of substances providing the transcription of genes of different molecules exerting anti-oncogenic action by maintaining a high level of the acetylation of target molecules. A number of substances from both groups successfully passed preclinical or also clinical tests and certain products, particularly antibodies, already principally affected the treatment of particular malignities. The purpose of the present article is to offer a review of at least most important substances from these recently occurring groups of anti-cancer medicines. A general mechanism of effects, achieved level of preclinical and clinical testing, chemistry and possibly particular molecular interactions in the malignant cells are described with each group.
- MeSH
- biologická terapie metody využití MeSH
- farmakoterapie metody MeSH
- hepatocytární růstový faktor terapeutické užití MeSH
- histondeacetylasy farmakologie terapeutické užití MeSH
- inhibitory histondeacetylas MeSH
- lidé MeSH
- nádory farmakoterapie terapie MeSH
- p21 aktivované kinasy antagonisté a inhibitory farmakologie terapeutické užití MeSH
- Check Tag
- lidé MeSH
- MeSH
- Evropská unie MeSH
- lidé MeSH
- zaměstnání pro postižené organizace a řízení pracovní síly trendy MeSH
- Check Tag
- lidé MeSH
- Publikační typ
- recenze MeSH
