IGFBP-3
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- MeSH
- dospělí MeSH
- elektroforéza metody MeSH
- hypopituitarismus enzymologie patologie terapie MeSH
- lidé MeSH
- proteasy analýza MeSH
- radioimunoanalýza metody MeSH
- růstový hormon aplikace a dávkování nedostatek MeSH
- vazba proteinů MeSH
- Check Tag
- dospělí MeSH
- lidé MeSH
- mužské pohlaví MeSH
- ženské pohlaví MeSH
Závěrečná zpráva o řešení grantu Interní grantové agentury MZ ČR
75, 41 l. : tab., grafy ; 32 cm
Analýzy a evaluace nových biochemických testů k posouzení metabolických funkcí hepatocytů u pacientů v transplantačním programu (např. lidocainový test, IGFBP-3, aminokyseliny). Analýza a evaluace nových biochemických testů k posouzení renálních funkcí upacientů v transplantačním programu (např. cystatin C, aminokyseliny). Analýzy a evaluace stanovení imunosupresiv (např. mykofenolát Mofetil), analýza a evaluace testů vhodných k monitorování jejich nefrotoxicity a hepatotoxicity. Analýzy a evaluace nových biochemických testů k posouzení akutní rejekce po transplantaci orgánů (např. neopterin, plazmatická DNA).; Analysis and evaluation of the novel biochemical parametres for determination of hepatocytes metabolic function in transplant patients (lidocaine test, IGFBP-3, aminoacids). Analysis and evaluation of the novel biochemical parametres for determination kidney function in transplant patients (cystatin C, aminoacids). Evaluating of immunosuppresive drugs (mycophenolate mofetil). Analysis and evaluation of the tests available for monitoring nefrotoxicity and hepatotoxicity of these drugs. Evaluating of determination of the novel biochemical parametres for determination acute rejection after organ transplantation (neopterin, plasma DNA).
- MeSH
- cystatiny MeSH
- hepatocyty metabolismus MeSH
- IGFBP-3 MeSH
- imunosupresivní léčba MeSH
- játra imunologie MeSH
- ledviny imunologie MeSH
- lidokain MeSH
- transplantační imunologie MeSH
- Konspekt
- Patologie. Klinická medicína
- NLK Obory
- transplantologie
- biochemie
- hepatologie
- nefrologie
- NLK Publikační typ
- závěrečné zprávy o řešení grantu IGA MZ ČR
BACKGROUND: Major depressive disorder (MDD) is a main public health concern worldwide. Despite extensive investigations, the exact mechanisms responsible for MDD have not been identified. Epidermal growth factor (EGF) and insulin growth factor binding protein-3 (IGFBP-3) are involved in brain function. Tumour suppressor protein p53 is widely involved in neuronal death in response to different forms of acute insults and neurological disorders. The present study focuses on the possible associations of the single-nucleotide polymorphisms (SNP) of EGF A61G (rs4444903), IGFBP-3 C32G (rs2854746) and TP53 G72C (rs1042522) genes with MDD risk in the Slovak population. METHODS: The present case-control association study was carried out in 111 confirmed MDD patients and 207 healthy subjects. Genotyping was performed by polymerase chain reaction-restriction fragment length polymorphism methods. RESULTS: Logistic regression analysis showed no association between SNPs of selected genes and MDD risk in the Slovak population. However, the stratification of individuals by gender revealed that males carrying IGFBP-3 G alleles (G32G or GG) had marginally increased risk for developing MDD as compared to CC homozygous males (p=0.09). In women, inverse association was observed between SNP rs1042522 and MDD risk (p=0.04 for recessive model). CONCLUSION: Our results suggest the protective effect of minor allele 72C of TP53 gene towards MDD. The disruption of mechanisms involved in cell survival and death regulation may be involved in pathophysiology of MDD.
- MeSH
- alely MeSH
- depresivní porucha unipolární genetika MeSH
- dospělí MeSH
- epidermální růstový faktor genetika MeSH
- genetická predispozice k nemoci MeSH
- genotyp MeSH
- geny p53 genetika MeSH
- IGFBP-3 genetika MeSH
- jednonukleotidový polymorfismus * MeSH
- lidé středního věku MeSH
- lidé MeSH
- polymerázová řetězová reakce MeSH
- polymorfismus délky restrikčních fragmentů MeSH
- senioři nad 80 let MeSH
- senioři MeSH
- studie případů a kontrol MeSH
- Check Tag
- dospělí MeSH
- lidé středního věku MeSH
- lidé MeSH
- mužské pohlaví MeSH
- senioři nad 80 let MeSH
- senioři MeSH
- ženské pohlaví MeSH
- Publikační typ
- časopisecké články MeSH
- Geografické názvy
- Slovenská republika epidemiologie MeSH
We constructed recombinant vaccinia viruses (VACVs) coexpressing the insulin-like growth factor-binding protein-3 (IGFBP-3) gene and the fusion gene encoding the SigE7Lamp antigen. The expression of the IGFBP-3 transgene was regulated either by the early H5 promoter or by the synthetic early/late (E/L) promoter. We have shown that IGFBP-3 expression regulated by the H5 promoter yielded higher amount of IGFBP-3 protein when compared with the E/L promoter. The immunization with P13-SigE7Lamp-H5-IGFBP-3 virus was more effective in inhibiting the growth of TC-1 tumors in mice and elicited higher T-cell response against VACV-encoded antigen than the P13-SigE7Lamp-TK(-) control virus. We found that high-level production of IGFBP-3 enhanced virus replication both in vitro and in vivo, resulting in more profound antigen stimulation. Production of IGFBP-3 was associated with a higher adsorption rate of P13-SigE7Lamp-H5-IGFBP-3 to CV-1 cells when compared with P13-SigE7Lamp-TK(-). Intracellular mature virions (IMVs) of the IGFBP-3-expressing virus P13-SigE7Lamp-H5-IGFBP-3 have two structural differences: they incorporate the IGFBP-3 protein and they have elevated phosphatidylserine (PS) exposure on outer membrane that could result in increased uptake of IMVs by macropinocytosis. The IMV PS content was measured by flow cytometry using microbeads covered with immobilized purified VACV virions.
- MeSH
- antigeny virové imunologie MeSH
- IGFBP-3 genetika imunologie MeSH
- imunizace metody MeSH
- lidský papilomavirus 16 genetika imunologie MeSH
- myši inbrední C57BL MeSH
- myši MeSH
- Papillomavirus E7 - proteiny genetika imunologie MeSH
- promotorové oblasti (genetika) MeSH
- replikace viru imunologie MeSH
- T-lymfocyty imunologie MeSH
- tvorba protilátek MeSH
- vakcinace metody MeSH
- virové vakcíny imunologie farmakologie MeSH
- virus vakcinie genetika imunologie MeSH
- zvířata MeSH
- Check Tag
- myši MeSH
- ženské pohlaví MeSH
- zvířata MeSH
- Publikační typ
- časopisecké články MeSH
- práce podpořená grantem MeSH
BACKGROUND/AIM: Head and neck squamous cell carcinoma (HNSCC) includes tumors of various anatomical sites sharing multifactorial etiopathogenesis and generally dismal response to conventional treatment. The objective of this study was to determine the clinical significance of serum levels of insulin-like growth factor-1 (IGF-1) and insulin-like growth factor-binding protein-3 (IGFBP-3) in HNSCC. PATIENTS AND METHODS: A total of 46 patients, with histologically-confirmed diagnosis of HNSCC (21 oropharyngeal, 21 laryngeal, and 4 hypopharyngeal cancers) were enrolled in this study. IGF-1 and IGFBP-3 serum levels were measured by an immunoradiometric assay using commercial kits. The adjustment of serum levels at 60 years of age was performed. RESULTS: Significant differences were found in IGF-1 serum concentrations between patients with p16 positive and p16 negative HNSCC (p=0.0062), with higher IGF-1 levels in p16 positive tumors, between low-grade and high-grade cancers (p=0.0323) only in larynx, with elevated IGF-1 concentrations associated with high-grade and between recurrent and non-recurrent HNSCC (p=0.0354), with lower IGF-1 levels in recurrent tumors. CONCLUSION: The conflicting results of this study may reflect some abnormality of IGF axis regulation in HNSCC, as well as the influence of other etiological factors (e.g. smoking, HPV infection).
- MeSH
- IGFBP-3 krev MeSH
- imunohistochemie MeSH
- imunoradiometrická analýza MeSH
- inhibitor p16 cyklin-dependentní kinasy analýza MeSH
- insulinu podobný růstový faktor I analýza MeSH
- lidé středního věku MeSH
- lidé MeSH
- lokální recidiva nádoru MeSH
- nádorové biomarkery analýza krev MeSH
- nádory hlavy a krku krev chemie patologie MeSH
- prediktivní hodnota testů MeSH
- senioři nad 80 let MeSH
- senioři MeSH
- spinocelulární karcinom krev chemie patologie MeSH
- stupeň nádoru MeSH
- Check Tag
- lidé středního věku MeSH
- lidé MeSH
- mužské pohlaví MeSH
- senioři nad 80 let MeSH
- senioři MeSH
- ženské pohlaví MeSH
- Publikační typ
- časopisecké články MeSH
- srovnávací studie MeSH
The acceptance of animal products is increasingly associated with standardized animal welfare, which relates to appropriate animal husbandry from birth to slaughter. In particular, shipment to the slaughterhouse is considered as a critical process exposing the animals to a number of, in part severe, stressors. New biomarkers may be useful for the assessment of animal welfare. The IGF-system has been assessed in a commercial pig transport in conjunction with established markers of stress response. Furthermore, the effect of repeated restraint as an experimental model for repeated acute stress was investigated. During shipment from farm to slaughterhouse, plasma concentrations of IGFBP-3 and IGFBP-2 were significantly reduced (p < 0.01). After shipment, the plasma concentrations of IGFBP-5, glucocorticoids and IL-2 increased but decreased after lairage (p < 0.05) whereas IGF-1 decreased after shipment (p < 0.01). Repeated acute stress increased concentrations of IGFBP-3 and IGF-1 in exsanguination blood (p < 0.05). Differential IGF- signatures can indicate altered endocrine or metabolic control and thus contain complex animal-related information. The somatotropic axis may be of particular interest when established biomarkers such as cortisol, glucose, or lactate cannot be used for the assessment of animal stress or welfare.
- MeSH
- biologické markery krev MeSH
- časové faktory MeSH
- chov zvířat MeSH
- doprava MeSH
- fyziologický stres * MeSH
- glukokortikoidy krev MeSH
- IGFBP-3 krev MeSH
- insulinu podobný růstový faktor I analýza MeSH
- interleukin-2 krev MeSH
- jatka * MeSH
- pohoda zvířat MeSH
- prasata MeSH
- protein 2 vázající insulinu podobné růstové faktory krev MeSH
- protein 5 vázající insulinu podobné růstové faktory krev MeSH
- psychický stres prevence a kontrola MeSH
- zvířata MeSH
- Check Tag
- zvířata MeSH
- Publikační typ
- časopisecké články MeSH
- práce podpořená grantem MeSH
INTRODUCTION: We evaluate the predictive and prognostic value of insulin-like growth factor-I (IGF-1), IGF binding protein-2 (IGFBP-2) and -3 (IGFBP-3) in patients treated with radical nephroureterectomy (RNU) for upper tract urothelial carcinoma (UTUC). METHODS: This is a retrospective analysis of a multi-institutional database comprising 753 patients who underwent RNU for UTUC and had a preoperative plasma available. Logistic and Cox regression analyses were performed. The discriminative ability and clinical utility of the models was calculated using the lasso regression test, area under receiver operating characteristics curves, C-index, and decision curve analysis (DCA). RESULTS: Lower preoperative plasma levels of IGFBP-2 and -3 independently correlated with increased risks of lymph node metastasis, pT3/4 disease, nonorgan confined disease, and worse recurrence-free survival (RFS), cancer-specific survival (CSS), and overall survival (OS) (all P ≤ .004). The addition of both IGFBP-2 and -3 to a postoperative multivariable model, that included standard clinicopathologic characteristics, improved the model's concordance index by 10%, 9%, and 8% for RFS, CSS, and OS, respectively. On DCA, addition of both IGFBP-2 and -3 to base models improved their performance for RFS, CSS, and OS by a statistically and clinically significant margin. Plasma IGF-1 was not associated with any of outcomes. CONCLUSIONS: We confirmed that a lower plasma levels of IGFBP-2 and -3 both are independent and clinically significant predictors of adverse pathological features and survival outcomes in UTUC patients treated with RNU. These findings might help guide the clinical decision-making regarding perioperative systemic therapy and follow-up scheduling.
- MeSH
- hodnocení rizik metody MeSH
- IGFBP-3 krev MeSH
- insulinu podobný růstový faktor I * metabolismus MeSH
- karcinom z přechodných buněk chirurgie krev patologie mortalita MeSH
- lidé středního věku MeSH
- lidé MeSH
- nádorové biomarkery krev MeSH
- nefroureterektomie * metody MeSH
- peptidy podobné insulinu MeSH
- předoperační období MeSH
- prognóza MeSH
- protein 2 vázající insulinu podobné růstové faktory * krev MeSH
- retrospektivní studie MeSH
- senioři MeSH
- urologické nádory chirurgie krev patologie mortalita MeSH
- Check Tag
- lidé středního věku MeSH
- lidé MeSH
- mužské pohlaví MeSH
- senioři MeSH
- ženské pohlaví MeSH
- Publikační typ
- časopisecké články MeSH
- multicentrická studie MeSH
Ghrelin was originally isolated from the rat stomach and significant amounts were found also in the kidney. Present study was designed to examine changes in ghrelin levels in renal failure and their relationship to the GH/IGF-I axis. Fourty patients with mild-to-severe CRF (19 men, 21 women, aged 62.5 +/- 2.2 years, BMI 27.57 +/- 0.73 kg/m(2)) and 34 healthy control subjects (17 men, 17 women, aged 60 +/- 2.6 years, BMI 27.55 +/- 0.79 kg/m(2)) were included in the study. Total ghrelin levels were significantly increased in patients with chronic renal failure (CRF) (p < 0.0001). Total ghrelin in CRF correlated positively with active ghrelin (p < 0.001), GH (p < 0.05), IGF-I (p < 0.05), free IGF-I (p = 0.0001), IGFBP-3 (p < 0.01), IGFBP-2 and -6 (p < 0.05). Active ghrelin in CRF correlated positively with IGF-I (p < 0.001), free-IGF-I (p < 0.005), IGFBP-2 (p < 0.05) and IGFBP-3 (p < 0.05). However, most of the correlation were markedly reduced and the significance disappeared after adjustment for different creatinine levels. Hemodialysis in patients with end stage renal disease (ESRD) resulted in a significant reduction of plasma total and active ghrelin (p < 0.01 and p < 0.001 respectively). In conclusion we demonstrated elevated plasma levels of total ghrelin in CRF, and a reduction of total and active ghrelin after a single course of hemodialysis in ESRD. The elevation of ghrelin levels could be caused by impaired clearance and/or metabolism of ghrelin in the kidney. We did not prove clearly significant relationship between ghrelin serum levels and parameters of GH/IGF-I axis in study subjects.
- MeSH
- časové faktory MeSH
- chronické selhání ledvin krev metabolismus MeSH
- dialýza ledvin MeSH
- financování organizované MeSH
- ghrelin MeSH
- IGFBP-3 metabolismus MeSH
- index tělesné hmotnosti MeSH
- insulinu podobný růstový faktor I metabolismus MeSH
- kreatin krev MeSH
- ledviny metabolismus MeSH
- leptinové receptory MeSH
- lidé středního věku MeSH
- lidé MeSH
- peptidové hormony chemie krev metabolismus MeSH
- protein 2 vázající insulinu podobné růstové faktory metabolismus MeSH
- receptory buněčného povrchu chemie MeSH
- renální insuficience krev MeSH
- růstový hormon metabolismus MeSH
- statistické modely MeSH
- studie případů a kontrol MeSH
- zvířata MeSH
- Check Tag
- lidé středního věku MeSH
- lidé MeSH
- mužské pohlaví MeSH
- ženské pohlaví MeSH
- zvířata MeSH