One-tier organisational structure of Czech joint-stock companies and British public limited companies

1 One-tier organisational structure of Czech joint-stock companies and British public limited companies Abstract This thesis deals with selected issues of one-tier board structure of a joint-stock company in the Czech and British legislation. The emphasis is placed on the position and regulation of the Board of directors, its members, shareholders, and their mutual relationship. Not only has the present legal regulation been monitored, but also its historical roots, which significantly influenced the evolution of the institute and its present form. The first chapter deals with corporate governance. It includes all aspects and theories, which as a whole have completed the position of a shareholder as well as a joint-stock company itself. Moreover, diffuse and concentrated ownership is explained, as well as separation of ownership of the company from its management, and the related "principal"-"agent" problem. Also, the basic characteristics of Anglo-Saxon and continental approach to the law have been reflected. The second chapter describes and clarifies the essence and the form of one-tier board structure as it is regulated in the UK. A remarkable element of British company law is the extent to which the company's internal affairs are left to its shareholders through the company's articles of association....1 Monistická organizační struktura akciové společnosti v české a anglické úpravě Abstrakt Tato práce se zabývá vybranou problematikou monistické struktury akciové společnosti v české a britské úpravě. Akcent je kladen na postavení a úpravu rady ředitelů (správní radu), jejích členů, akcionářů a jejich vzájemných vztahů. Sledována není jen presentní právní úprava ale rovněž její historické kořeny, které významně ovlivnily evoluci institutu i jeho nynější podobu První kapitola pojednává o dobré správě a řízení společnosti se všemi, pro tuto práci relevantními aspekty a teoriemi, které ve svém souhrnu dotvořily postavení akcionáře i samotné akciové společnosti tak, jak je známe dnes. Je vysvětlena podstata difuzního a koncentrovaného vlastnictví ve společnosti, oddělení vlastnictví společnosti od jejího řízení a s tím související problém "pána" a "správce." Pozornost je rovněž věnována základní charakteristice anglosaského a kontinentálního přístupu k právu. Kapitola druhá popisuje a objasňuje podstatu a podobu monistického systému akciové společnosti tak, jak je zakotvena v právním řádu Velké Británie. Pozoruhodným prvkem britského práva obchodních společností je rozsah, v jakém je ponechána úprava vnitřních záležitostí společnosti na jejích akcionářích, skrze stanovy společnosti. Převážná většina právní...Department of Business LawKatedra obchodního právaPrávnická fakultaFaculty of La

Role of genetic variation in ABC transporters in breast cancer prognosis and therapy response

Breast cancer is the most common cancer in women in the world. The role of germline genetic variability in ATP-binding cassette (ABC) transporters in cancer chemoresistance and prognosis still needs to be elucidated. We used next-generation sequencing to assess associations of germline variants in coding and regulatory sequences of all human ABC genes with response of the patients to the neoadjuvant cytotoxic chemotherapy and disease-free survival (n = 105). A total of 43 prioritized variants associating with response or survival in the above testing phase were then analyzed by allelic discrimination in the large validation set (n = 802). Variants in ABCA4, ABCA9, ABCA12, ABCB5, ABCC5, ABCC8, ABCC11, and ABCD4 associated with response and variants in ABCA7, ABCA13, ABCC4, and ABCG8 with survival of the patients. No association passed a false discovery rate test, however, the rs17822931 (Gly180Arg) in ABCC11, associating with response, and the synonymous rs17548783 in ABCA13 (survival) have a strong support in the literature and are, thus, interesting for further research. Although replicated associations have not reached robust statistical significance, the role of ABC transporters in breast cancer should not be ruled out. Future research and careful validation of findings will be essential for assessment of genetic variation which was not in the focus of this study, e.g., non-coding sequences, copy numbers, and structural variations together with somatic mutations. © 2020 by the authors. Licensee MDPI, Basel, Switzerland.Czech Medical Council [17-28470A]; Czech Ministry of Education, Youth and SportsMinistry of Education, Youth & Sports - Czech Republic [CZ.02.1.01/0.0/0.0/16_013/0001634]; Grant Agency of Charles University [UNCE/MED/006]; Grant Agency of the Czech RepublicGrant Agency of the Czech Republic [19-03063S

Use of germline genetic variability for prediction of chemoresistance and prognosis of breast cancer patients

The aim of our study was to set up a panel for targeted sequencing of chemoresistance genes and the main transcription factors driving their expression and to evaluate their predictive and prognostic value in breast cancer patients. Coding and regulatory regions of 509 genes, selected from PharmGKB and Phenopedia, were sequenced using massive parallel sequencing in blood DNA from 105 breast cancer patients in the testing phase. In total, 18,245 variants were identified of which 2565 were novel variants (without rs number in dbSNP build 150) in the testing phase. Variants with major allele frequency over 0.05 were further prioritized for validation phase based on a newly developed decision tree. Using emerging in silico tools and pharmacogenomic databases for functional predictions and associations with response to cytotoxic therapy or disease-free survival of patients, 55 putative variants were identified and used for validation in 805 patients with clinical follow up using KASP™ technology. In conclusion, associations of rs2227291, rs2293194, and rs4376673 (located in ATP7A, KCNAB1, and DFFB genes, respectively) with response to neoadjuvant cytotoxic therapy and rs1801160 in DPYD with disease-free survival of patients treated with cytotoxic drugs were validated and should be further functionally characterized. © 2018 by the authors. Licensee MDPI, Basel, Switzerland.Czech Medical Council [15-25618A]; Charles University [GAUK 1776218

Role of genetic variation in cytochromes P450 in breast cancer prognosis and therapy response

Breast cancer is the most frequent cancer in the female population worldwide. The role of germline genetic variability in cytochromes P450 (CYP) in breast cancer prognosis and individualized therapy awaits detailed elucidation. In the present study, we used the next-generation sequencing to assess associations of germline variants in the coding and regulatory sequences of all human CYP genes with response of the patients to the neoadjuvant cytotoxic chemotherapy and disease-free survival (n = 105). A total of 22 prioritized variants associating with a response or survival in the above evaluation phase were then analyzed by allelic discrimination in the large confirmation set (n = 802). Associations of variants in CYP1B1, CYP4F12, CYP4X1, and TBXAS1 with the response to the neoadjuvant cytotoxic chemotherapy were replicated by the confirmation phase. However, just association of variant rs17102977 in CYP4X1 passed the correction for multiple testing and can be considered clinically and statistically validated. Replicated associations for variants in CYP4X1, CYP24A1, and CYP26B1 with disease-free survival of all patients or patients stratified to subgroups according to therapy type have not passed a false discovery rate test. Although statistically not confirmed by the present study, the role of CYP genes in breast cancer prognosis should not be ruled out. In conclusion, the present study brings replicated association of variant rs17102977 in CYP4X1 with the response of patients to the neoadjuvant cytotoxic chemotherapy and warrants further research of genetic variation CYPs in breast cancer.Czech Medical Council [NV19-08-00113]; Czech Ministry of Education, Youth and Sports, INTER-EXCELLENCE LTA-USA grant [19032]; Charles University Research Fund [Q39]NV19-08-00113; Univerzita Karlova v Praze, UK; Ministerstvo Školství, Mládeže a Tělovýchovy, MŠMT: 1903

The role of cytochromes P450 and aldo-keto reductases in prognosis of breast carcinoma patients

Metabolism of anticancer drugs affects their antitumor effects. This study has investigated the associations of gene expression of enzymes metabolizing anticancer drugs with therapy response and survival of breast carcinoma patients.Gene expression of 13 aldo-keto reductases (AKRs), carbonyl reductase 1, and 10 cytochromes P450 (CYPs) was assessed using quantitative real-time polymerase chain reaction in tumors and paired adjacent nonneoplastic tissues from 68 posttreatment breast carcinoma patients. Eleven candidate genes were then evaluated in an independent series of 50 pretreatment patients. Protein expression of the most significant genes was confirmed by immunoblotting.AKR1A1 was significantly overexpressed and AKR1C1-4, KCNAB1, CYP2C19, CYP3A4, and CYP3A5 downregulated in tumors compared with control nonneoplastic tissues after correction for multiple testing. Significant association of CYP2B6 transcript levels in tumors with expression of hormonal receptors was found in the posttreatment set and replicated in the pretreatment set of patients. Significantly higher intratumoral levels of AKR1C1, AKR1C2, or CYP2W1 were found in responders to neoadjuvant chemotherapy compared with nonresponders. Patients with high AKR7A3 or CYP2B6 levels in the pretreatment set had significantly longer disease-free survival than patients with low levels. Protein products of AKR1C1, AKR1C2, AKR7A3, CYP3A4, and carbonyl reductase (CBR1) were found in tumors and those of AKR1C1, AKR7A3, and CBR1 correlated with their transcript levels. Small interfering RNA-directed knockdown of AKR1C2 or vector-mediated upregulation of CYP3A4 in MDA-MB-231 model cell line had no effect on cell proliferation after paclitaxel treatment in vitro.Prognostic and predictive roles of drug-metabolizing enzymes strikingly differ between posttreatment and pretreatment breast carcinoma patients. Mechanisms of action of AKR1C2, AKR7A3, CYP2B6, CYP3A4, and CBR1 should continue to be further followed in breast carcinoma patients and models.13-25222J, GACR, Czech Science FoundationCzech Science Foundation [13-25222J]; Internal Grant Agency of the Czech Ministry of Health [NT/14055-3

Metabolism, transport and anticancer effect of classical and novel taxanes

L I I I I I I I I t CONCLUSIONS The dissertation thesis contributes to detail knowledge of the metabolism, transport and anticancer effects of classical taxanes (paclitaxel and docetaxel) as well as their novel synthetic analogs (SB-T-1103, SB-1'-1214 and SB-T-1216). The r]lost rmportanl reslrlts concerning studies on these anticancet drugs are srultnarized as iollorvs: o Detail metabolisrrr oť paclitaxel and docetaxel rvas estimated in human. rat. pig arrd minipig liver microsomes. The metabolism of docetaxel rvas the same i:r all four tested species. Drug rvas metabolized mainly to hydroxydocetaxel and two minor h1'droxyoxazol.idinones A and B. Despite various simiiarities between human and pig netabolism of paclitaxel, the profile oť paclitaxel metabolites in the studied species r'u.as different and main hunan metabolite óo.oHP renrains uniquelv human one' The other new metabolites of paclitaxel w.ere revealed. speciíicall1 di-oHP in ra1s and a new. hydroxypaclitaxel in rats. pigs and minipigs. q,here thrs metabolite is the main metabolic pathway oť paciitaxel. The major enzymes responsible for oxidative metaboiism of paclitaxei are CYP2CB and CYP3A4 in humans and CYP3Ai/2 in rats. Docelaxel is oxidatively metabolized by GYP3A famil"v in humans as rvell as in rats. The oxidation metabolism of classical...Department of BiochemistryKatedra biochemieFaculty of SciencePřírodovědecká fakult

One-tier organisational structure of Czech joint-stock companies and British public limited companies

1 One-tier organisational structure of Czech joint-stock companies and British public limited companies Abstract This thesis deals with selected issues of one-tier board structure of a joint-stock company in the Czech and British legislation. The emphasis is placed on the position and regulation of the Board of directors, its members, shareholders, and their mutual relationship. Not only has the present legal regulation been monitored, but also its historical roots, which significantly influenced the evolution of the institute and its present form. The first chapter deals with corporate governance. It includes all aspects and theories, which as a whole have completed the position of a shareholder as well as a joint-stock company itself. Moreover, diffuse and concentrated ownership is explained, as well as separation of ownership of the company from its management, and the related "principal"-"agent" problem. Also, the basic characteristics of Anglo-Saxon and continental approach to the law have been reflected. The second chapter describes and clarifies the essence and the form of one-tier board structure as it is regulated in the UK. A remarkable element of British company law is the extent to which the company's internal affairs are left to its shareholders through the company's articles of association...

Analýza vývoje nákladů na úpravu hnědého uhlí

Import 19/04/2006Prezenční výpůjčkaVŠB - Technická univerzita Ostrava. Fakulta hornicko-geologická. Institut ekonomiky a systémů řízení (545