Článek popisuje terapeutické spektrum možností a jeho specifika u gastrointestinálního stromálního tumoru (GIST) se zaměřením na adjuvantní léčbu. V jeho úvodní části se věnuje obecným poznatkům o GIST – epidemiologii, histopatologii či symptomatologii. Vzhledem k faktu, že GIST patří mezi radiorezistentní a chemorezistentní tumory, účinnost imatinib mesylátu (Glivec®), selektivního inhibitoru tyrozinkinázových domén receptorů c-kit, PDGFRA-alfa a bcr-abl, znamenala výrazný průlom v terapii tohoto nádoru. V další části proto článek shrnuje současné poznatky o indikacích imatinibu a popisuje determinaci rizika rekurence – pro GIST dlouho nebyla vytvořena TNM klasifikace, míra rizika recidivy byla tedy stanovována na základě několika kritérií, jako je velikost tumoru, počet mitóz na 50 patologických polí při histologickém vyšetření nádoru, lokalizace a ruptura tumoru, z nichž také nová TNM klasifikace vychází. Současně článek přináší přehled zásadních klinických studií pro adjuvantní podávání imatinibu a zmiňuje se i o možnostech terapie pro pacienty s metastatickým či pokročilým onemocněním, resp. o další linii biologické léčby, sunitinibu (Sutent®)., The paper describes the spectrum of therapeutic options and its specific features in gastrointestinal stromal tumour (GIST) with a focus on adjuvant therapy. The introduction deals with general information related to GIST, i. e. epidemiology, histopathology and symptomatology. Given the fact that GIST is among radioresistant and chemoresistant tumours, the efficacy of imatinib mesylate (Glivec®), a selective tyrosine kinase inhibitor of c-kit, PDGFRA-alpha and bcr-abl, has been a significant breakthrough in the treatment of this tumour. Therefore, the paper also summarizes the current knowledge of the indications for imatinib treatment and describes the assessment of the risk of recurrence – there had been no TNM classification for GIST for a long time; therefore, the risk of recurrence was established based on several criteria, including the tumour size, the number of mitoses per 50 high-power fields on the histological examination of the tumour, and the tumour site and rupture, criteria which are also used in the new TNM classification. Additionally, the paper presents an overview of clinical trials essential for adjuvant imatinib treatment and deals with the treatment options for patients with metastatic or advanced disease as well as with another line of biological therapy, sunitinib (Sutent®)., Michaela Zezulová, Bohuslav Melichar, and Lit.: 13
We investigated the effects of telmisartan, the blocker of angiotensin II receptor 1, on the regulation of systolic blood pressure (SBP) and oxidative stress through endothelial nitric oxide (NO) release in spontaneously hypertensive rats (SHRs). SHRs randomly received placebo, oral feeding of telmisartan (5 mg/kg or 10 mg/kg) every day and Wistar-Kyoto rats (WKYs) served as normotensive control. The SBP of rat was measured before and weekly thereafter. After a total of 8-week treatment, rats were killed for experimental measurements. Parameters that subject to measurements in isolated aorta endothelial cells include: NO concentration, protein expression levels of angiotensin II receptor 1, nitrotyrosine, 8-isoprostane, SOD, PI3K, Akt, AMPK and eNOS. In addition, L-NMMA, a general inhibitor of nitric oxide synthase, was also applied to test the inhibition of NO concentration. We found that SBPs were significantly lower in telmisartan therapy group than in placebo treated hypertensive rats and WKYs (p<0.05). The NO concentration was significantly higher in telmisartan-treated group with increased activity of the PI3K/Akt pathway and activated eNOS signaling. Blockade of Akt activity reversed such effects. Activation of AMPK also contributed to the phosphorylation of eNOS. L-NMMA treatment reduced less NO concentration in SHR rats than the telmisartan co-treated groups. Oxidative stress in SHRs was also attenuated by telmisartan administration, shown by reduced formation of nitrotyrosine, 8-isoprostane, and recovered SOD protein level. Telmisartan enhanced NO release by activating the PI3K/Akt system, AMPK phosphorylation and eNOS expression, which attenuated the blood pressure and oxidative stress in SHRs., L. Xu, Y. Liu., and Obsahuje seznam literatury
Let y be observation vector in the usual linear model with expectation Aβ and covariance matrix known up to a multiplicative scalar, possibly singular. A linear statistic aTy is called invariant estimator for a parametric function ϕ=cTβ if its MSE depends on β only through ϕ. It is shown that aTy is admissible invariant for ϕ, if and only if, it is a BLUE of ϕ, in the case when ϕ is estimable with zero variance, and it is of the form kϕˆ, where k∈⟨0,1⟩ and ϕˆ is an arbitrary BLUE, otherwise. This result is used in the one- and two-way ANOVA models. Our paper is self-contained and accessible, also for non-specialists.
Christian Hartmann, Thomas Vordermeyer, Othmar Plöckinger, and Roman Töppel (eds.). Hitler, Mein Kampf: Eine kritische Edition. Munich and Berlin: Institut für Zeitgeschichte, 2016, vols 1-2, 947 + 1019 pp., ISBN 978-3-9814052-3-1. With Edith Raim, Pascal Trees, Angelika Reizle, and Martina Seewald-Mooser. Includes illustrations, maps, a list of all known translations of Mein Kampf before 1945, a list of abbreviations, a detailed bibliography in three parts (before 1932, 1933-45, after 1945), and four indexes (a biographical index and indexes of persons, places, and subjects).In the form of an essay, the author comments here on the 2016 critical edition of Hitler’s Mein Kampf (1925-26), edited by a team of historians from the Institute of Contemporary History in Munich, with additional assistance from others. He contemplates the nature and importance of this book and discusses its author and his meaning in the history of twentieth-century central Europe. He then discusses some of the ideas of Mein Kampf, and clarifi es the historical context of the work, returning to the circumstances that led to its being written and published. He also discusses some of Hitler’s fellow travellers in the Nazi movement, who were of importance for this key work. The author brings up episodes in Hitler’s life, and pays particular attention to his still unclear transformation from an apolitical soldier into a zealous antisemite and political agitator of exceptional rhetorical skill, who was able to bewitch the German people and become their Führer. The author also discusses the diffi culties that the editors of this critical edition had to struggle with, and he praises their work as utterly solid and astonishingly thorough, particularly the commentaries in the huge critical apparatus. The author concludes by discussing reactions both to the fi rst edition of Mein Kampf and to this critical edition, and he discusses various attempts to publish a Czech edition.
Cílem imunoterapie je využití imunitních mechanizmů k eliminaci nebo ke kontrole růstu maligně transformovaných buněk. Jednou z možností imunoterapie je aplikace adoptivního transferu lymfocytů T, jehož podstatou je infuze ex vivo expandovaných tumor specifických lymfocytů, které rozeznávají a ničí neoplastické buňky. Úspěšnost adoptivní T buněčné terapie se významně zlepšila pochopením základních molekulárních mechanizmů interakce imunitního systému s nádory. Slibných výsledků bylo dosaženo zejména u maligního melanomu, karcinomu ledviny a lymfatické leukemie. Adoptivní T buněčná terapie se postupně etabluje mezi nadějné imunoterapeutické postupy a rozšiřuje tak portfolio léčebných možností, i když pro svoji metodickou náročnost nenašla dosud velké rozšíření., The aim of current immunotherapeutic approaches is to harness the individual’s immune system towards a tumor tissue to eliminate or, at least, to control proliferation of the neoplastic cells. Among the cancer treatment strategies, the adoptive T cell transfer is progressively developing method that uses an ex vivo modified and expanded tumor-specific T cells as a tool to target and destroy the neoplastic tumor cells. The efficacy of the adoptive T cell therapy has significantly improved in recent years due to a better understanding of the molecular mechanisms that control the interactions of immune system and tumor cells. Promising results have already been achieved within the clinical trials in malignant melanoma, renal cancer and lymphoid leukemia. The adoptive T cell therapy is therefore gradually finding its place among the other immunotherapeutic strategies and expands the spectrum of available treatment options in cancer therapy., Kateřina Vávrová, Jiřina Bartůňková, Rudolf Horváth, and Literatura
Nedostatečnost kůry nadledvin je potenciálně život ohrožující stav. Článek pojednává o diferenciální diagnostice a limitech dynamického testování, možnostech deeskalace kortikoidní terapie a substituční terapii glukokortikoidy, mineralokortikoidy a androgeny. Zmíněny jsou nové substituční možnosti včetně nově vyvíjených., Adrenal insufficiency is a potentially life threatening condition. The paper deals with differential diagnostics and limits of dynamic testing, possibilities of de-escalation of corticosteroid therapy and substitution therapy with glucocorticoids, mineralocorticoids and androgens. New replacement possibilities are mentioned including those in development., and Filip Gabalec, Jan Čáp
The method of cellular immobilization and perfusion was applied to adipocytes. The lipolytic effect of isoprénaline, whose action is produced as a result of receptor-drug interaction, was followed. An agarose solution kept at at 37 °C was mixed 1:1 with the cell suspension. Thereafter, adipocytes were immobilized in the agarose threads. The lipolytic effect of 0.1 ml of isoprénaline (1x10~4 mol/1), that was rapidly introduced to the cell perfusion inlet in a non-recirculating system, was monitored by assessing glycerol production. The immobilized and perfused adipocytes exhibited significant lipolytic activity. After reaching the maximum effect, 0.1 ml of propranol (lxl 0-3 mol/1) that was applied to the bioreactor inlet, abolished the isoprénaline effect. The present data demonstrate the potential applicability of immobilized perfused adipocytes for various kinds of studies.
Adrenergic receptors (ARs) are the primary targets of catecholamines released from the sympathetic nerve endings during their activation. ARs play a central role in autonomic nervous system and serve as important targets of widely used drugs. Several ARs gene polymorphisms were found to be associated with cardiovascular disease in previous clinical studies. Although more precise mechanism of the polymorphisms influence on autonomic control of cardiovascular system was studied in many previous physiological studies, their results are not unequivocal. This paper reviews the results of clinical and physiological studies focused on the impact of selected common single nucleotide polymorphisms of ARs genes involved in sympathetic control on cardiovascular system and its control. In summary, many studies assessed only a very limited range of cardiovascular control related parameters providing only very limited view on the complex cardiovascular control. The overview of partially contradicting results underlines a need to examine wider range of cardiovascular measures including their reactivity under various stress conditions requiring further study. It is expected that an effect of one given polymorphism is not very prominent, but it is suggested that even subtle differences in cardiovascular control could – on a longer time scale – lead to the development of severe pathological consequences.