Gene Expression Signature Analysis Identifies Vorinostat as a Candidate Therapy for Gastric Cancer

Gastric cancer continues to be one of the deadliest cancers in the world and therefore identification of new drugs targeting this type of cancer is thus of significant importance. The purpose of this study was to identify and validate a therapeutic agent which might improve the outcomes for gastric cancer patients in the future. manifested a reversed pattern.We showed that analysis of gene expression signature may represent an emerging approach to discover therapeutic agents for gastric cancer, such as vorinostat. The observation of altered gene expression after vorinostat treatment may provide the clue to identify the molecular mechanism of vorinostat and those patients likely to benefit from vorinostat treatment

Association Between TAS2R38 Gene Polymorphisms and Colorectal Cancer Risk: A Case-Control Study in Two Independent Populations of Caucasian Origin

Molecular sensing in the lingual mucosa and in the gastro-intestinal tract play a role in the detection of ingested harmful drugs and toxins. Therefore, genetic polymorphisms affecting the capability of initiating these responses may be critical for the subsequent efficiency of avoiding and/or eliminating possible threats to the organism. By using a tagging approach in the region of Taste Receptor 2R38 (TAS2R38) gene, we investigated all the common genetic variation of this gene region in relation to colorectal cancer risk with a case-control study in a German population (709 controls and 602 cases) and in a Czech population (623 controls and 601 cases). We found that there were no significant associations between individual SNPs of the TAS2R38 gene and colorectal cancer in the Czech or in the German population, nor in the joint analysis. However, when we analyzed the diplotypes and the phenotypes we found that the non-taster group had an increased risk of colorectal cancer in comparison to the taster group. This association was borderline significant in the Czech population, (OR = 1.28, 95% CI 0.99–1.67; Pvalue = 0.058) and statistically significant in the German population (OR = 1.36, 95% CI 1.06–1.75; Pvalue = 0.016) and in the joint analysis (OR = 1.34, 95% CI 1.12–1.61; Pvalue = 0.001). In conclusion, we found a suggestive association between the human bitter tasting phenotype and the risk of CRC in two different populations of Caucasian origin

A Functional NQO1 609C>T Polymorphism and Risk of Gastrointestinal Cancers: A Meta-Analysis

Background: The functional polymorphism (rs1800566) in the NQO1 gene, a 609C.T substitution, leading to proline-toserine amino-acid and enzyme activity changes, has been implicated in cancer risk, but individually published studies showed inconclusive results. Methodology/Principal Findings: We performed a meta-analysis of 20 publications with a total of 5,491 cases and 5,917 controls, mainly on gastrointestinal (GI) cancers. We summarized the data on the association between the NQO1 609C.T polymorphism and risk of GI cancers and performed subgroup analyses by ethnicity, cancer site, and study quality. We found that the variant CT heterozygous and CT/TT genotypes of the NQO1 609 C.T polymorphism were associated with a modestly increased risk of GI cancers (CT vs. CC: OR = 1.10, 95 % CI = 1.01 – 1.19, P heterogeneity = 0.27, I 2 = 0.15; CT/TT vs. CC: OR = 1.11, 95%CI = 1.02 – 1.20, Pheterogeneity = 0.14; I 2 = 0.27). Following further stratified analyses, the increased risk was only observed in subgroups of Caucasians, colorectal cancer in Caucasians, and high quality studies. Conclusions: This meta-analysis suggests that the NQO1 609T allele is a low-penetrance risk factor for GI cancers. Although the effect on GI cancers may be modified by ethnicity and cancer sites, small sample seizes of the subgroup analyse

Stable or improved neurological manifestations during miglustat therapy in patients from the international disease registry for Niemann-Pick disease type C: an observational cohort study

Background: Niemann-Pick disease type C (NP-C) is a rare neurovisceral disease characterised by progressive neurological degeneration, where the rate of neurological disease progression varies depending on age at neurological onset. We report longitudinal data on functional disease progression and safety observations in patients in the international NPC Registry who received continuous treatment with miglustat. Methods: The NPC Registry is a prospective observational cohort of NP-C patients. Enrolled patients who received ≥1 year of continuous miglustat therapy (for ≥90 % of the observation period, with no single treatment interruption >28 days) were included in this analysis. Disability was measured using a scale rating the four domains, ambulation, manipulation, language and swallowing from 0 (normal) to 1 (worst). Neurological disease progression was analysed in all patients based on: 1) annual progression rates between enrolment and last follow up, and; 2) categorical analysis with patients categorised as 'improved/stable' if ≥3/4 domain scores were lower/unchanged, and as 'progressed' if <3 scores were lower/unchanged between enrolment and last follow-up visit. Results: In total, 283 patients were enrolled from 28 centers in 13 European countries, Canada and Australia between September 2009 and October 2013; 92 patients received continuous miglustat therapy. The mean (SD) miglustat exposure during the observation period (enrolment to last follow-up) was 2.0 (0.7) years. Among 84 evaluable patients, 9 (11 %) had early-infantile (<2 years), 27 (32 %) had late-infantile (2 to <6 years), 30 (36 %) had juvenile (6 to <15 years) and 18 (21 %) had adolescent/adult (≥15 years) onset of neurological manifestations. The mean (95%CI) composite disability score among all patients was 0.37 (0.32,0.42) at enrolment and 0.44 (0.38,0.50) at last follow-up visit, and the mean annual progression rate was 0.038 (0.018,0.059). Progression of composite disability scores appeared highest among patients with neurological onset during infancy or childhood and lowest in those with adolescent/adult-onset. Overall, 59/86 evaluable patients (69 %) were categorized as improved/stable and the proportion of improved/stable patients increased with age at neurological onset. Safety findings were consistent with previous data. Conclusions: Disability status was improved/stable in the majority of patients who received continuous miglustat therapy for an average period of 2 years

Hard coal and brown coal mining in the Czech Republic

Zasoby węgla w Republice Czeskiej są ocenione na 10 mld ton – w tym 37% węgla kamiennego, 60% węgla brunatnego i 3% lignitu. Węgiel kamienny jest wydobywany w północnych Morawach, w 2017 roku produkcja wyniosła 5,5 mln ton. Węgiel brunatny jest eksploatowany głównie w północno-zachodnich Czechach, produkcja węgla brunatnego wyniosła w 2017 roku 38,1 mln ton. Znaczne ilości węgla kamiennego są eksportowane do Słowacji, Austrii, Niemiec i Węgier Zgodnie z polityką energetyczną państwa węgiel pozostanie głównym źródłem energii w kraju w przyszłości, pomimo zwiększonego wykorzystania energii jądrowej i gazu ziemnego. Rząd oczekuje, że w 2030 r. energia z węgla będzie stanowić 30,5% produkowanej energii. W Republice Czeskiej działa pięć przedsiębiorstw węglowych: OKD, a.s., jedyny producent węgla kamiennego oraz cztery firmy wydobywcze węgla brunatnego Severočeské Doly a.s., których właścicielem jest ČEZ, największy producent węgla brunatnego, Vršanská uhelná a.s., z zasobami węgla do 2055 roku, Severní energetická a.s. z największymi rezerwami węgla brunatnego w Republice Czeskiej i Sokolovska uhelná a.s., najmniejsza spółka górnicza wydobywającą węgiel brunatny. OKD eksploatuje węgiel kamienny w dwu kopalniach Kopalnia Důlní závod 1 – Ruch ČSA, Ruch Lazy, Ruch Darkov oraz Kopalnia Důlní závod 2 (Ruch Sever, Ruch Jih). A artykule przedstawiono również proekologiczne rozwiązanie zagospodarowania hałd odpadów po wzbogacaniu węgla – zakład wzbogacania odpadów weglowych z hałdy Hermanice.Coal reserves in the Czech Republic are estimated to be 10 billion tons – hard coal about 37%, brown coal about 60% and lignite 3%. Hard coal is produced in Northern Moravia. In 2017 the production of hard coal was 5.5 million tons. Brown coal is mined in North-Western Bohemia − the production of brown coal in 2017 was 38.1 million tons. Significant quantities of hard coal are exported to: Slovakia, Austria, Germany and Hungary. In accordance with the National Energy Policy, coal will remain the main source of energy in the country in the future, despite the increased use of nuclear energy and natural gas. The government expects that in 2030 energy from coal will account for 30.5% of energy produced. There are five coal companies in the Czech Republic: OKD, a.s., the only hard coal producer and four brown coal mining companies: Severočeské Doly a.s., owned by ČEZ, the largest producer of brown coal, Vršanská uhelná a.s., with coal resources until 2055, Severní energetická a.s. with the largest brown coal reserves in the Czech Republic and Sokolovska uhelná a.s., the smallest mining company extracting lignite. OKD operates coal in two mines Kopalnia Důlní závod 1 – (consists of three mines: ČSA Mine, Lazy Mine, Darkov Mine) and Mine Důlní závod 2 (ttwo mines Sever, Jih). The article also presents a pro-ecological solution for the management of waste heaps after coal enrichment – a plant for the enrichment of coal waste from the Hermanice heap

Energia aktywacji odpadów rzepaku

Thermal analysis describes the changes of physical and chemical properties of materials depending on increasing temperature. Thermogravimetric analysis of rape residue sample has been carried in inert atmosphere. The samples were heated over a range of temperatures that includes the entire range of pyrolysis with three different heating rates of 5, 10 and 15°C min-1. Thermogravimetric (TG) curves were obtained from experimental data. The results obtained from thermal decomposition process indicate that there are main stages such as dehydration, active and passive pyrolysis. The first region from 50°C is related to the extraction of moisture and adsorbed water in samples. The main pyrolysis process proceeds in a range from approximately 250 to 450°C. The activation energy values as a function of the extent of conversion for the pyrolysis process of rape residue have been calculated by means of the Flynn– Wall–Ozawa method. The activation energy for the pyrolysis of rape residue was 99–189 kJ.mol-1 in the conversion range of 0.2–0.8. The average activation energy calculated by this method was 142 kJ.mol-1.Analiza termiczna wykazała zmiany właściwości fizycznych oraz chemicznych materiałów w zależności od wzrostu temperatury. Analizę termograwimetryczną próbek odpadów rzepaku przeprowadzono w atmosferze gazów obojętnych. Próbki były podgrzane w różnym zakresie temperatur, który zawierał cały zakres pirolizy z trzema różnymi prędkościami ogrzewania wynoszącymi 5, 10 oraz 15°C min-1. Krzywe termograwimetru (TG) otrzymano z danych eksperymentalnych. Wyniki uzyskane z termicznej dekompozycji wskazują na istnienie głównych faz takich jak dehydratacja, aktywna i pasywna piroliza. Pierwszy proces zachodzi w okolicy 50°C, występuje wtedy parowanie wilgoci i wody z próbek. Główny proces pirolizy zachodzi w zakresie od ok. 250°C do 450°C. Wartości energii aktywacji jako przedłużenie właściwości konwersji procesu pirolizy resztek rzepy zostały obliczone metodą Flynn-Wall-Ozawa. Energia aktywacji dla pirolizy odpadów rzepaku wyniosła 99–189 kJ.mol-1 w zakresie konwersji od 0,2–0,8. Średnia energia aktywacji obliczona tą metodą wyniosła 142 kJ.mol-1