Search

Start Over Creator Bendlová, Běla

3. Genetika nádorů štítné žlázy a jejich molekulárně cílená léčba

Creator:
Bendlová, Běla, Dvořáková, Šárka, Sýkorová, Vlasta, Hálková, Tereza, and Václavíková, Eliška
Format:
braille, text, and regular print
Type:
model:article, article, Text, and TEXT
Subject:
nádory štítné žlázy--genetika--chirurgie--terapie, genetické markery--genetika, mutace--genetika, papilární karcinom--genetika--terapie, folikulární papilární karcinom--genetika--terapie, protoonkogenní proteiny B-raf--diagnostické užití, protoonkogenní proteiny c-ret--diagnostické užití, translokace genetická--genetika, geny ras--genetika, transkripční faktory paired box--diagnostické užití, karcinom--genetika--terapie, medulární karcinom--genetika--terapie, genetická terapie--metody--využití, receptory vaskulárního endoteliálního růstového faktoru--antagonisté a inhibitory, raf kinázy--antagonisté a inhibitory, diagnostické techniky molekulární--metody--využití, lidé, financování organizované, inhibitory, mutace, BRAF, and RET
Language:
Czech and English
Description:
Nádory štítné žlázy jsou nejčastějšími neoplaziemi endokrinního systému. Nejvíce zastoupeným typem nádorů štítné žlázy je papilární karcinom, u kterého jsou nalézány bodové mutace genů BRAF a RAS a RET/PTC přeskupení. Nejčastějšími molekulárně-genetickými změnami u folikulárního karcinomu jsou mutace RAS a PAX8-PPARγ přeskupení. Bodové mutace v RET proto-onkogenu jsou klíčové pro vývoj medulárního karcinomu štítné žlázy, kde se u familiární formy vyskytují zárodečné mutace a u sporadické formy mutace somatické. U nejagresivnějšího anaplastického karcinomu štítné žlázy jsou detekovány mutace BRAF a RAS a dále mutace v genech TP53 a CTNNB1. Díky zjištění genetických příčin vzniku nádorů štítné žlázy začaly být tyto geny a jejich mutace zkoumány jako nadějné terapeutické cíle. Mnoho látek ukázalo protinádorový efekt v preklinických studiích. Nejslibnějšími tyrozinkinázovými inhibitory jsou Vandetanib, Sunitinib a Sorafenib, které jsou zkoumány na tkáňových kulturách, zvířecích modelech a v klinických studiích u metastatických stadií karcinomů štítné žlázy., Thyroid cancer is the most frequent neoplasm of endocrine system. The major type of thyroid tumor is papillary thyroid carcinoma, in which point mutations in the BRAF and RAS genes and RET/PTC rearrangements are found. The most frequent molecular genetic changes in follicular thyroid carcinoma are mutations in the RAS genes and PAX8-PPARγ rearrangemets. Point mutations in the RET proto-oncogene are crucial for development of medullary thyroid carcinoma, where germ-line and somatic mutations occur in familial and sporadic form, respectively. Mutations in the BRAF and RAS genes and moreover mutations in the TP53 and CTNNB1 genes are also detected in the most aggressive anaplastic thyroid carcinoma. Thanks to the finding of genetic causes of thyroid cancer, these genes and their mutations begin to be investigated as promising therapeutic targets. Many compounds show anti-tumor effect in preclinical studies. The most promising tyrosine kinase inhibitors are Vandetanib, Sunitinib and Sorafenib, which are investigated in thyroid tumor cell-lines, animal models and clinical studies on patients with metastatic stage of thyroid cancer., Běla Bendlová, Šárka Dvořáková, Vlasta Sýkorová, Tereza Hálková, Eliška Václavíková, and Literatura 22
Rights:
http://creativecommons.org/publicdomain/mark/1.0/ and policy:public

4. Insights into the physiology of C-peptide

Creator:
Vejražková, Daniela, Vaňková, Markéta, Lukášová, Petra, Včelák, Josef, and Bendlová, Běla
Format:
počítač and online zdroj
Type:
model:article and TEXT
Subject:
inzulin, diabetes mellitus, terapie, insulin, therapy, C-peptide, diabetes complications, 14, and 612
Language:
English
Description:
Current knowledge suggests a complex role of C-peptide in human physiology, but its mechanism of action is only partially understood. The effects of C-peptide appear to be variable depending on the target tissue, physiological environment, its combination with other bioactive molecules such as insulin, or depending on its concentration. It is apparent that C-peptide has therapeutic potential for the treatment of vascular and nervous damage caused by type 1 or late type 2 diabetes mellitus. The question remains whether the effect is mediated by the receptor, the existence of which is still uncertain, or whether an alternative non-receptor-mediated mechanism is responsible. The Institute of Endocrinology in Prague has been paying much attention to the issue of C-peptide and its metabolic effect since the 1980s. The RIA methodology of human C-peptide determination was introduced here and transferred to commercial production. By long-term monitoring of C-peptide oGTT-derived indices, the Institute has contributed to elucidating the pathophysiology of glucose tolerance disorders. This review summarizes the current knowledge of C-peptide physiology and highlights the contributions of the Institute of Endocrinology to this issue., Daniela Vejrazkova, Marketa Vankova, Petra Lukasova, Josef Vcelak, Bela Bendlova., and Obsahuje bibliografii
Rights:
http://creativecommons.org/publicdomain/mark/1.0/ and policy:public

5. Melanocortin pathways: suppressed and stimulated melanocortin-4 receptor (MC4R)

Creator:
Hainer, Vojtěch, Aldhoon Hainerová, Irena, Kunešová, Marie, Braunerová, Radka, Zamrazilová, Hana, and Bendlová, Běla
Format:
počítač and online zdroj
Type:
model:article and TEXT
Subject:
obezita, obesity, MC4R agonists, melanocortin-4 receptor (MC4R) function, monogenic obesity, common obesity, gene polymorphisms, 14, and 612
Language:
English
Description:
Leptin-melanocortin pathway plays an essential role in the body weight regulation. Enhanced melanocortin signaling in the hypothalamus results in both decreased food intake and increased energy expenditure. The discovery of monogenic obesities with dysfunction of melanocortin-4 receptor (MC4R) greatly contributed to understanding of energy balance regulation. This review presents phenotypical characterization and prevalence of the MC4R gene mutations. Genome-wide association studies revealed that MC4R gene is significantly related not only to monogenic obesities but also to common obesity. An interaction of variants in the MC4R gene with fat mass and obesity associated (FTO) gene significantly increases the risk for obesity, particularly in adolescence. On the other hand, about 15 % of the MC4R gene variants result in a gain of function that protects against obesity and is associated with favorable metabolic profile. Long-term attempts to activate the MC4R have recently been finalized by a discovery of setmelanotide, a novel specific MC4R agonist that is devoid of untoward cardiovascular side-effects. The employment of specific MC4R agonists may open new horizons not only in the treatment of rare monogenic obesities but also in some common obesities where stimulation of MC4R could be achieved., Vojtěch Hainer, Irena Aldhoon Hainerová, Marie Kunešová, Radka Taxová Braunerová, Hana Zamrazilová, Běla Bendlová., and Obsahuje bibliografii
Rights:
http://creativecommons.org/publicdomain/mark/1.0/ and policy:public

6. Plasma levels of adipokines in patients with Alzheimer’s disease: Where is the "breaking point" in Alzheimer’s disease pathogenesis?

Creator:
Vaňková, Markéta, Vacínová, Gabriela, Včelák, Josef, Vejražková, Daniela, Lukášová, Petra, Rusina, Robert, Holmerová, Iva, Jarolímová, Eva, Vaňková, Hana, and Bendlová, Běla
Format:
počítač and online zdroj
Type:
model:article and TEXT
Subject:
Alzheimerova choroba, leptin, Alzheimer's disease, adiponectin, adipsin, bloodbased biomarker, 14, and 612
Language:
English
Description:
Peripheral insulin resistance is associated with decreasing adiponectin and increasing leptin plasma levels, and also with cognitive decline. The effects of adipokines on brain function have been published from both animal and human studies. In particular, the influence of leptin and adiponectin on the development of Alzheimer’s disease (AD) has been extensively investigated. However, the association between adipsin and AD is as yet unknown. In 37 patients with AD and 65 controls that followed the same study protocol, we tested whether adiponectin, leptin, and adipsin could be used as biomarkers in the early stages of AD. In contrast with conclusions of cognition studies in insulin resistant states, our study found a correlation of impaired neuropsychological performance with increasing adiponectin and decreasing leptin in AD patients. Nevertheless, no significant differences between patients and controls were found. AD women had significantly increased adipsin compared to controls, and there was a positive correlation of adipsin with age and disease duration. Although adipokines do not appear to be suitable biomarkers for early AD diagnosis, they certainly play a role in the pathogenesis of AD. Further studies will be needed to explain the cause of the adipokine “breaking point” that leads to the pathogenesis of overt AD., Markéta Vaňková, Gabriela Vacínová, Josef Včelák, Daniela Vejražková, Petra Lukášová, Robert Rusina, Iva Holmerová, Eva Jarolímová, Hana Vaňková, Běla Bendlová., and Obsahuje bibliografii
Rights:
http://creativecommons.org/publicdomain/mark/1.0/ and policy:public