OBJECTIVE: Evaluation of importance of serum levels of basic fibroblast growth factor (bFGF) in patients with ovarian cancer, patients with border-line ovarian tumor, patients with benign ovarian cyst and women with normal ovarian tissue. DESIGN: Prospective clinical study. SETTING: Department of Gynecology and Obstetrics, Charles University, Faculty of Medicine in Hradec Kralove and University Hospital Hradec Kralove. METHODS: Measurement of serum levels of bFGF by ELISA using reagents of company R&D Systems prior to treatment in a total of 74 consecutive coming women. RESULTS: Serum level of bFGF from peripheral blood before treatment was significantly higher (p < 0.05) in patients with newly diagnosed ovarian cancer (n = 22), Med = 10.35 pg/ml (1.2-46.2 pg/ml) compared to patients with a border-line ovarian tumor (n = 9), Med = 5.4 pg/ml (1.6-6.8 pg/ml), patients with benign ovarian cyst (n = 24), Med = 5.2 pg/ml (0.1-67.2 pg/ml), and to women with normal ovarian tissue (n = 19) Med = 4.3 pg/ml (0.9-13.4 pg/ml). There isnt strong linear correlation (Spearmans rank correlation coefficient = 0.208791) between the serum level of bFGF and CA125 collected from peripheral blood before primary surgery or neoadjuvant chemotherapy in a group of patients with ovarian cancer (n = 14). We have not found significance correlation between age and serum levels of bFGF in patients with ovarian cancer, with border-line ovarian tumor, with benign ovarian cyst and in women with normal ovarian tissue. CONCLUSION: Serum levels of bFGF in patients with ovarian cancer are significantly higher than in patients with a border-line ovarian tumor, with benign ovarian cyst and in women with normal ovarian tissue regardless of age of patients.

• Klíčová slova
• angiogenesis, basic fibroblast growth factor (bFGF), basic fibroblast growth factor (bFGF) angiogenesis., ovarian cancer,
• MeSH
• fibroblastové růstové faktory krev   MeSH
• lidé MeSH
• nádory vaječníků krev   patologie   MeSH
• ovariální cysty krev   patologie   MeSH
• prospektivní studie MeSH
• Check Tag
• lidé MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH
• Názvy látek
• fibroblastové růstové faktory MeSH

The human fibroblast growth factor (FGF) family contains 22 proteins that regulate a plethora of physiological processes in both developing and adult organism. The mutations in the FGF genes were not known to play role in human disease until the year 2000, when mutations in FGF23 were found to cause hypophosphatemic rickets. Nine years later, seven FGFs have been associated with human disorders. These include FGF3 in Michel aplasia; FGF8 in cleft lip/palate and in hypogonadotropic hypogonadism; FGF9 in carcinoma; FGF10 in the lacrimal/salivary glands aplasia, and lacrimo-auriculo-dento-digital syndrome; FGF14 in spinocerebellar ataxia; FGF20 in Parkinson disease; and FGF23 in tumoral calcinosis and hypophosphatemic rickets. The heterogeneity in the functional consequences of FGF mutations, the modes of inheritance, pattern of involved tissues/organs, and effects in different developmental stages provide fascinating insights into the physiology of the FGF signaling system. We review the current knowledge about the molecular pathology of the FGF family.

• MeSH
• fibroblastové růstové faktory genetika   metabolismus   MeSH
• fibroblastový růstový faktor 23 MeSH
• hypogonadismus genetika   metabolismus   MeSH
• karcinom genetika   metabolismus   MeSH
• lidé MeSH
• mnohočetné abnormality genetika   MeSH
• mutace * MeSH
• rozštěp rtu genetika   metabolismus   MeSH
• Check Tag
• lidé MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH
• přehledy MeSH
• Research Support, N.I.H., Extramural MeSH
• Názvy látek
• FGF23 protein, human MeSH Prohlížeč
• fibroblastové růstové faktory MeSH
• fibroblastový růstový faktor 23 MeSH

Fibroblast growth factors (FGFs) serve numerous regulatory functions in complex organisms, and their corresponding therapeutic potential is of growing interest to academics and industrial researchers alike. However, applications of these proteins are limited due to their low stability. Here we tackle this problem using a generalizable computer-assisted protein engineering strategy to create a unique modified FGF2 with nine mutations displaying unprecedented stability and uncompromised biological function. The data from the characterization of stabilized FGF2 showed a remarkable prediction potential of in silico methods and provided insight into the unfolding mechanism of the protein. The molecule holds a considerable promise for stem cell research and medical or pharmaceutical applications.

• Klíčová slova
• computational design, embryonic stem cells, fibroblast growth factor, focused directed evolution, protein engineering, protein stability,
• MeSH
• bodová mutace MeSH
• design s pomocí počítače * MeSH
• embryonální kmenové buňky cytologie   metabolismus   MeSH
• fibroblastový růstový faktor 2 chemie   genetika   metabolismus   MeSH
• lidé MeSH
• počítačová simulace MeSH
• proteinové inženýrství * MeSH
• řízená evoluce molekul MeSH
• sbalování proteinů MeSH
• sekvence aminokyselin MeSH
• stabilita proteinů * MeSH
• zvířata MeSH
• Check Tag
• lidé MeSH
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH
• Názvy látek
• fibroblastový růstový faktor 2 MeSH

BACKGROUND: Fibroblast growth factor 23 (FGF23), a potent regulator of phosphate and vitamin D metabolism, is a new biomarker of kidney, bone and cardiovascular disorders. The aim of this study was to assess the biological variation of intact fibroblast growth factor 23 (iFGF23). METHODS: The within-subject (CVI) and between-subject (CVG) biological variations were assessed in 14 healthy volunteers in a six-week protocol (seven samples). Imprecision (CVA) was assessed by duplicate measurements and the EP15-A2 protocol. Intact FGF23 was measured using a fully automated chemiluminescent assay (Liaison XL, DiaSorin S.p.A., Saluggia, Italy). Two methods with different sensitivities to non-Gaussian distribution were used to estimate the CVI, SD ANOVA and CV ANOVA methods. We calculated the index of individuality (II) and reference change values. RESULTS: Depending on the statistical method used, the CVI and CVA were 14.2 and 3.7% (SD ANOVA) or 12.5 and 3.9% (CV ANOVA), respectively. The corresponding reference change values were 40.5 and 36.4%, respectively. The CVG was 13.4% (SD ANOVA was the only option), and the total imprecision (EP15-A2) was less than 7%. CONCLUSIONS: The measurement of iFGF23 demonstrated a CVA less than 4% during the experimental estimation of biological variation. The total imprecision was less than 7% in the EP15-A2 experiment. The CVI values of iFGF23 in healthy persons were 14.2 (SD ANOVA) and 12.5% (CV ANOVA), respectively. The CVG was 13.4%, and the resulting index of individuality was 1.06. The reference change value was less than 41%. The availability of this automated assay for iFGF23 with well-characterized biological variation data delivers opportunities for improved availability and application of this assay clinically.

• Klíčová slova
• Fibroblast growth factor 23, biological variation, reference change value,
• MeSH
• analýza rozptylu MeSH
• automatizace MeSH
• dospělí MeSH
• fibroblastové růstové faktory analýza   MeSH
• fibroblastový růstový faktor 23 MeSH
• lidé středního věku MeSH
• lidé MeSH
• luminiscenční měření normy   MeSH
• mladý dospělý MeSH
• referenční hodnoty MeSH
• zdraví dobrovolníci pro lékařské studie MeSH
• Check Tag
• dospělí MeSH
• lidé středního věku MeSH
• lidé MeSH
• mladý dospělý MeSH
• mužské pohlaví MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH
• Názvy látek
• FGF23 protein, human MeSH Prohlížeč
• fibroblastové růstové faktory MeSH
• fibroblastový růstový faktor 23 MeSH

Vertebrate primary cilium is a Hedgehog signaling center but the extent of its involvement in other signaling systems is less well understood. This report delineates a mechanism by which fibroblast growth factor (FGF) controls primary cilia. Employing proteomic approaches to characterize proteins associated with the FGF-receptor, FGFR3, we identified the serine/threonine kinase intestinal cell kinase (ICK) as an FGFR interactor. ICK is involved in ciliogenesis and participates in control of ciliary length. FGF signaling partially abolished ICK's kinase activity, through FGFR-mediated ICK phosphorylation at conserved residue Tyr15, which interfered with optimal ATP binding. Activation of the FGF signaling pathway affected both primary cilia length and function in a manner consistent with cilia effects caused by inhibition of ICK activity. Moreover, knockdown and knockout of ICK rescued the FGF-mediated effect on cilia. We provide conclusive evidence that FGF signaling controls cilia via interaction with ICK.

• Klíčová slova
• FGFR, ICK, cilia length, fibroblast growth factor, intestinal cell kinase,
• MeSH
• buňky NIH 3T3 MeSH
• cilie metabolismus   MeSH
• CRISPR-Cas systémy MeSH
• fibroblastové růstové faktory metabolismus   MeSH
• fosforylace MeSH
• HEK293 buňky MeSH
• interakční proteinové domény a motivy MeSH
• lidé MeSH
• modely u zvířat MeSH
• myši knockoutované MeSH
• myši MeSH
• protein-serin-threoninkinasy genetika   metabolismus   MeSH
• proteiny hedgehog metabolismus   MeSH
• proteomika MeSH
• receptor fibroblastových růstových faktorů, typ 1 metabolismus   MeSH
• receptor fibroblastových růstových faktorů, typ 3 genetika   metabolismus   MeSH
• receptor fibroblastových růstových faktorů, typ 4 metabolismus   MeSH
• receptory fibroblastových růstových faktorů genetika   metabolismus   MeSH
• signální transdukce MeSH
• simulace molekulového dockingu MeSH
• zvířata MeSH
• Check Tag
• lidé MeSH
• myši MeSH
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH
• Research Support, N.I.H., Extramural MeSH
• Názvy látek
• CILK1 protein, human MeSH Prohlížeč
• Cilk1 protein, mouse MeSH Prohlížeč
• FGFR1 protein, human MeSH Prohlížeč
• FGFR3 protein, human MeSH Prohlížeč
• FGFR4 protein, human MeSH Prohlížeč
• fibroblastové růstové faktory MeSH
• protein-serin-threoninkinasy MeSH
• proteiny hedgehog MeSH
• receptor fibroblastových růstových faktorů, typ 1 MeSH
• receptor fibroblastových růstových faktorů, typ 3 MeSH
• receptor fibroblastových růstových faktorů, typ 4 MeSH
• receptory fibroblastových růstových faktorů MeSH

PURPOSE OF REVIEW: Fibroblast growth factor receptor (FGFR) signalling, especially induced by FGFR3, is a crucial factor in the pathogenesis of urothelial carcinoma and was therefore extensively studied over the last decades. In this review, we summarize the most relevant findings of the past two years. RECENT FINDINGS: Recent studies support the concept that FGFR3 mediates a pathway of urothelial carcinogenesis associated with low malignant potential. FGFR3 may represent a highly accurate biomarker for diagnosis and prediction of recurrence, progression or therapy response. The pan FGFR-inhibitor erdafitinib was recently approved for urothelial carcinoma, whereas several other FGFR-targeted drugs are currently undergoing clinical trials. SUMMARY: Numerous recent studies focus on the role of FGFR3 in different urothelial carcinoma subtypes and its potential clinical application as noninvasive biomarker, as well as therapeutic target.

• MeSH
• chinoxaliny terapeutické užití   MeSH
• inhibitory proteinkinas terapeutické užití   MeSH
• karcinom z přechodných buněk farmakoterapie   patologie   MeSH
• lidé MeSH
• lokální recidiva nádoru MeSH
• nádory močového měchýře farmakoterapie   patologie   MeSH
• protinádorové látky terapeutické užití   MeSH
• pyrazoly terapeutické užití   MeSH
• receptor fibroblastových růstových faktorů, typ 3 MeSH
• receptory fibroblastových růstových faktorů antagonisté a inhibitory   terapeutické užití   MeSH
• urologické nádory farmakoterapie   MeSH
• výsledek terapie MeSH
• Check Tag
• lidé MeSH
• Publikační typ
• časopisecké články MeSH
• přehledy MeSH
• Názvy látek
• chinoxaliny MeSH
• erdafitinib MeSH Prohlížeč
• inhibitory proteinkinas MeSH
• protinádorové látky MeSH
• pyrazoly MeSH
• receptor fibroblastových růstových faktorů, typ 3 MeSH
• receptory fibroblastových růstových faktorů MeSH

The FGF system is the most complex of all receptor tyrosine kinase signaling networks with 18 FGF ligands and four FGFRs that deliver morphogenic signals to pattern most embryonic structures. Even when a single FGFR is expressed in the tissue, different FGFs can trigger dramatically different biological responses via this receptor. Here we show both quantitative and qualitative differences in the signaling of one of the FGF receptors, FGFR1c, in response to different FGFs. We provide an overview of the recent discovery that FGFs engage in biased signaling via FGFR1c. We discuss the concept of ligand bias, which represents qualitative differences in signaling as it is a measure of differential ligand preferences for different downstream responses. We show how FGF ligand bias manifests in functional data in cultured chondrocyte cells. We argue that FGF-ligand bias contributes substantially to FGF-driven developmental processes, along with known differences in FGF expression levels, FGF-FGFR binding coefficients and differences in FGF stability in vivo.

• Klíčová slova
• Bias, FGF, FGFR, Signaling,
• MeSH
• chondrocyty metabolismus   MeSH
• fibroblastové růstové faktory * metabolismus   MeSH
• lidé MeSH
• ligandy MeSH
• receptor fibroblastových růstových faktorů, typ 1 * metabolismus   MeSH
• receptory fibroblastových růstových faktorů * metabolismus   MeSH
• signální transdukce * MeSH
• zvířata MeSH
• Check Tag
• lidé MeSH
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH
• přehledy MeSH
• Názvy látek
• fibroblastové růstové faktory * MeSH
• ligandy MeSH
• receptor fibroblastových růstových faktorů, typ 1 * MeSH
• receptory fibroblastových růstových faktorů * MeSH

Cancer stem cells are cancer cells that originate from the transformation of normal stem cells. The most important property of any stem cell is the ability to self-renew. Through this property, there are striking parallels between normal stem cells and cancer stem cells. Both cell types share various markers of "stemness". In particular, normal stem cells and cancer stem cells utilize similar molecular mechanisms to drive self-renewal, and similar signaling pathways may induce their differentiation. The fibroblast growth factor 2 (FGF-2) pathway is one of the most significant regulators of human embryonic stem cell (hESC) self-renewal and cancer cell tumorigenesis. Here we summarize recent data on the effects of FGF-2 and its receptors on hESCs and leukemic stem/progenitor cells. Also, we discuss the similarities of these findings with stem cell renewal and differentiation phenotypes.

• MeSH
• embryo savčí cytologie   metabolismus   MeSH
• fibroblastové růstové faktory metabolismus   MeSH
• hematologické nádory metabolismus   patologie   MeSH
• kmenové buňky metabolismus   MeSH
• kultivované buňky MeSH
• lidé MeSH
• signální transdukce * MeSH
• Check Tag
• lidé MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH
• přehledy MeSH
• Názvy látek
• fibroblastové růstové faktory MeSH

Basic fibroblast growth factor (bFGF) is a member of the fibroblast growth factor family that possess broad mitogenic and cell survival activities and is involved in a variety of biological processes. We investigated possible genetic polymorphism in the promoter and 5' flanking region of the bFGF gene. Polymorphism was analysed by means of heteroduplex analysis, fragments with altered mobility were sequenced. Three novel substitutions (-553T/A, -834T/A and -921C/G) were identified in the promoter region. Allele frequencies in a sample of healthy Caucasian subjects (n=126) were determined by polymerase chain reactions followed by restriction analyses with specific endonucleases. The frequencies of the mutated alleles (-553A, -834A and -921G) were 0.04, 0.05 and 0.14, respectively. Newly identified variants in the bFGF gene promoter appear to be common polymorphisms in the Czech population.

• MeSH
• 5' přiléhající oblast DNA MeSH
• bodová mutace MeSH
• fibroblastový růstový faktor 2 genetika   MeSH
• genetická variace * MeSH
• lidé středního věku MeSH
• lidé MeSH
• promotorové oblasti (genetika) * MeSH
• senioři MeSH
• Check Tag
• lidé středního věku MeSH
• lidé MeSH
• mužské pohlaví MeSH
• senioři MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH
• Názvy látek
• fibroblastový růstový faktor 2 MeSH

Human embryonic stem cells (hESCs) are pluripotent stem cells with long-lasting capacity to self-renew and differentiate into various cell types of endodermal, ectodermal or mesodermal origin. Unlike mouse ESCs (mESCs), which can be maintained in an undifferentiated state simply by adding leukemia inhibitory factor (LIF) into the culture medium, hESCs are notorious for the sustained willingness to differentiate and not yet clearly defined signaling pathways that are crucial for their "stemness". Presently, our knowledge involves only limited number of growth factor signaling pathways that appear to be biologically relevant for stem cell functions in vitro. These include BMP, TGFbeta, Wnt, and FGF signaling pathway. The purpose of this review is to summarize recent data on the expression of FGFs and their receptors in hESCs, and critically evaluate the potential effects of FGF signals for their undifferentiated growth and/or differentiation in context with our current understanding of FGF/FGFR biology.

• MeSH
• biologické modely MeSH
• buněčná diferenciace fyziologie   MeSH
• embryo savčí cytologie   fyziologie   MeSH
• fibroblastový růstový faktor 2 * genetika   metabolismus   fyziologie   MeSH
• kmenové buňky cytologie   fyziologie   MeSH
• lidé MeSH
• receptory fibroblastových růstových faktorů * genetika   metabolismus   fyziologie   MeSH
• signální transdukce fyziologie   MeSH
• Check Tag
• lidé MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH
• přehledy MeSH
• Názvy látek
• fibroblastový růstový faktor 2 * MeSH
• receptory fibroblastových růstových faktorů * MeSH