Recently we have demonstrated that recombinant human erythropoietin (EPO) protects neurosensory hair cells in the organotypic culture of the organ of Corti by reducing apoptosis and necrosis. In the present study, we tested the hypothesis that EPO may be involved in reparative angiogenesis. We analyzed in parallel the endogenous erythropoietin (Epo) mRNA expression and that of Epo receptor (Epor) and of genes associated with angiogenesis in the organ of Corti, the modiolus and the stria vascularis using real time reverse transcription polymerase chain reaction and microarray. We compared the expression levels of freshly prepared tissue (control) and tissue cultured for 24 h under normoxia or hypoxia. The basal expression of Epo- and Epor mRNA in controls of all regions was very low. However, after 24 h in culture, a 20-100 fold increase of these two transcripts was measured. In culture, the vascular endothelial growth factor and the Cxcr4 (the receptor for the stromal cell-derived factor-1, Sdf-1) mRNA levels, were found to be increased and the Sdf-1 mRNA level to be decreased. Changes in mRNA expression occurred in all pathways activated in non-erythroid cells by the application of EPO (phosphoinositide 3-kinase/serine-threonine protein kinase B, Janus-type protein tyrosine kinase 2/signal transducer and activator of transcription 3, and the mitogen activated protein kinase). These data suggest that the neuroprotective effect of EPO may include at least two molecular events, the decrease of hair cell death rate and the induction of angiogenic genes.

• MeSH
• chemokin CXCL12 genetika   metabolismus   MeSH
• erythropoetin metabolismus   MeSH
• hypoxie buňky MeSH
• krysa rodu Rattus MeSH
• látky indukující angiogenezi metabolismus   MeSH
• messenger RNA metabolismus   MeSH
• novorozená zvířata MeSH
• orgánové kultury - kultivační techniky MeSH
• počet buněk MeSH
• polymerázová řetězová reakce s reverzní transkripcí MeSH
• potkani Wistar MeSH
• receptory CXCR4 genetika   metabolismus   MeSH
• receptory erythropoetinu genetika   metabolismus   MeSH
• sekvenční analýza hybridizací s uspořádaným souborem oligonukleotidů MeSH
• vaskulární endoteliální růstový faktor A genetika   metabolismus   MeSH
• viabilita buněk MeSH
• vláskové buňky MeSH
• vnitřní ucho cytologie   zranění   metabolismus   MeSH
• zvířata MeSH
• Check Tag
• krysa rodu Rattus MeSH
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH
• Názvy látek
• chemokin CXCL12 MeSH
• Cxcr4 protein, rat MeSH Prohlížeč
• erythropoetin MeSH
• látky indukující angiogenezi MeSH
• messenger RNA MeSH
• receptory CXCR4 MeSH
• receptory erythropoetinu MeSH
• vaskulární endoteliální růstový faktor A MeSH

Angiogenesis plays a significant role in the pathogenesis of multiple myeloma (MM). We have measured concentrations of angiogenesis activators, including vascular endothelial growth factor (VEGF), basic fibroblast growth factor, and hepatocyte growth factor (HGF), and inhibitors, including endostatin, thrombospondin-1 (TSP-1), and angiostatin in the peripheral and bone marrow blood of MM patients at diagnosis and after high-dose chemotherapy. We have analyzed 96 patients with secretory MM. Serial measurements of angiogenesis factors/inhibitors were analyzed in the plasma by subgroups based on the best treatment response. Concentrations of angiogenic factors were determined in the peripheral blood and bone marrow plasma. There were significant decreases of VEGF and HGF levels and a significant increase in TSP-1 concentrations in the bone marrow plasma of patients who achieved complete or very good partial response in contrast to those who had partial or no response. VEGF and HGF levels decrease but those of TSP-1 increase after successful treatment for MM, indicating a reduction in the rate of angiogenesis.

• MeSH
• angiostatiny krev   MeSH
• antitumorózní látky aplikace a dávkování   terapeutické užití   MeSH
• dospělí MeSH
• hepatocytární růstový faktor krev   MeSH
• lidé středního věku MeSH
• lidé MeSH
• mnohočetný myelom krev   diagnóza   farmakoterapie   MeSH
• protokoly antitumorózní kombinované chemoterapie terapeutické užití   MeSH
• senioři MeSH
• thrombospondin 1 krev   MeSH
• vaskulární endoteliální růstový faktor A krev   MeSH
• výsledek terapie MeSH
• Check Tag
• dospělí MeSH
• lidé středního věku MeSH
• lidé MeSH
• mužské pohlaví MeSH
• senioři MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH
• Názvy látek
• angiostatiny MeSH
• antitumorózní látky MeSH
• hepatocytární růstový faktor MeSH
• thrombospondin 1 MeSH
• vaskulární endoteliální růstový faktor A MeSH

INTRODUCTION: This study aimed to identify whether microbial invasion of the amniotic cavity and/or intra-amniotic inflammation in women with late preterm prelabor rupture of membranes (PPROM) was associated with changes in concentrations of soluble fms-like tyrosine kinase-1 (sFlt-1), placental growth factor (PlGF) and its ratio in maternal serum, and whether placental features consistent with maternal vascular malperfusion further affect their concentrations. MATERIAL AND METHODS: This historical study included 154 women with singleton pregnancies complicated by PPROM between gestational ages 34+0 and 36+6 weeks. Transabdominal amniocentesis was performed as part of standard clinical management to evaluate the intra-amniotic environment. Women were categorized into two subgroups based on the presence of microorganisms and/or their nucleic acids in amniotic fluid (determined by culturing and molecular biology method) and intra-amniotic inflammation (by amniotic fluid interleukin-6 concentration evaluation): (1) those with the presence of microorganisms and/or inflammation (at least one present) and (2) those with negative amniotic fluid for infection/inflammation (absence of both). Concentrations of sFlt-1 and PlGF were assessed using the Elecsys® sFlt-1 and Elecsys® PlGF immunoassays and converted into multiples of medians. RESULTS: Women with the presence of microorganisms and/or inflammation in amniotic fluid had lower serum concentrations of sFlt-1 and sFlt-1/PlGF ratios and higher concentrations of PlGF compared with those with negative amniotic fluid. (sFlt-1: presence: median 1.0 multiples of the median (MoM), vs negative: median: 1.5 MoM, P = 0.003; PlGF: presence: median 0.7 MoM, vs negative: median 0.4 MoM, P = 0.02; sFlt-1/PlGF: presence: median 8.9 vs negative 25.0, P = 0.001). Higher serum concentrations of sFlt-1 and sFlt-1/PlGF ratios as well as lower concentrations of PlGF were found in the subsets of women with maternal vascular malperfusion than in those without maternal vascular malperfusion. CONCLUSIONS: Among women experiencing late PPROM, angiogenic imbalance in maternal serum is primarily observed in those without both microbial invasion of the amniotic cavity and intra-amniotic inflammation. Additionally, there is an association between angiogenic imbalance and the presence of maternal vascular malperfusion.

• Klíčová slova
• amniotic fluid, angiogenic factors, inflammation, microorganism, preterm delivery,
• MeSH
• amniocentéza MeSH
• biologické markery krev   MeSH
• chorioamnionitida krev   MeSH
• dospělí MeSH
• gestační stáří MeSH
• lidé MeSH
• placentární růstový faktor * krev   MeSH
• plodová voda * mikrobiologie   metabolismus   MeSH
• předčasný odtok plodové vody * krev   MeSH
• receptor 1 pro vaskulární endoteliální růstový faktor * krev   MeSH
• těhotenství MeSH
• Check Tag
• dospělí MeSH
• lidé MeSH
• těhotenství MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH
• Názvy látek
• FLT1 protein, human MeSH Prohlížeč
• PGF protein, human MeSH Prohlížeč

Arthrospira platensis, a blue-green alga, is a popular nutraceutical substance having potent antioxidant properties with potential anti-carcinogenic activities. The aim of our study was to assess the possible anti-angiogenic effects of A platensis in an experimental model of pancreatic cancer. The effects of an A platensis extract were investigated on human pancreatic cancer cells (PA-TU-8902) and immortalized endothelial-like cells (Ea.hy926). PA-TU-8902 pancreatic tumours xenografted to athymic mice were also examined. In vitro migration and invasiveness assays were performed on the tested cells. Multiple angiogenic factors and signalling pathways were analysed in the epithelial, endothelial and cancer cells, and tumour tissue. The A platensis extract exerted inhibitory effects on both migration and invasion of pancreatic cancer as well as endothelial-like cells. Tumours of mice treated with A platensis exhibited much lesser degrees of vascularization as measured by CD31 immunostaining (P = .004). Surprisingly, the VEGF-A mRNA and protein expressions were up-regulated in pancreatic cancer cells. A platensis inhibited ERK activation upstream of Raf and suppressed the expression of ERK-regulated proteins. Treatment of pancreatic cancer with A platensis was associated with suppressive effects on migration and invasiveness with various anti-angiogenic features, which might account for the anticancer effects of this blue-green alga.

• Klíčová slova
• Arthrospira platensis, angiogenesis, anticancer effects, carcinogenesis, pancreatic cancer,
• MeSH
• antioxidancia farmakologie   MeSH
• antitumorózní látky farmakologie   MeSH
• endoteliální buňky účinky léků   MeSH
• inhibitory angiogeneze farmakologie   MeSH
• lidé MeSH
• myši nahé MeSH
• myši MeSH
• nádorové buněčné linie MeSH
• nádory slinivky břišní farmakoterapie   MeSH
• patologická angiogeneze farmakoterapie   MeSH
• pohyb buněk účinky léků   MeSH
• signální transdukce účinky léků   MeSH
• Spirulina chemie   MeSH
• upregulace účinky léků   MeSH
• zvířata MeSH
• Check Tag
• lidé MeSH
• myši MeSH
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH
• Názvy látek
• antioxidancia MeSH
• antitumorózní látky MeSH
• inhibitory angiogeneze MeSH

OBJECTIVE: Angiogenic growth factors bFGF and VEGF ensure vascularisation of the growing tumor tissue. We decided to investigate their peripheral serum concentrations in patients with thyroid gland adenoma and papillary carcinoma and with parathyroid adenoma. We wanted to find the possible serum marker of these tumor diseases. METHODS: 28 patients with thyroid gland tumor (14x adenoma, 14x papillary carcinoma) and 12 patients with parathyroid gland adenoma. Growth factors serum levels were measured by ELISA method. RESULTS: We found significantly higher serum levels of bFGF in both groups of patients with thyroid adenoma (4.93 +/- 3.42 ng/ml) and papillary carcinoma (5.69 +/- 5.58 ng/ml) compared to the healthy population (1.47 +/- 1.77 ng/ml). There were no significant differences of VEGF serum levels between all examined groups of patients (adenoma 213 +/- 197, papillary carcinoma 210 +/- 179, healthy 227 +/- 231 pg/ml). We found significantly higher serum levels of bFGF in patients with parathyroid gland adenoma (7.59 +/- 9.12 ng/ml) compared to those in healthy people (1.47 +/- 1.77 ng/ml). CONCLUSIONS: Higher bFGF serum concentrations in patients with thyroid and parathyroid tumors are in accordance with their immunohistochemical tissue levels described in the literature. Not so in VEGF. bFGF may be a serum marker of thyroid and parathyroid neoplasms.

• MeSH
• adenom krev   MeSH
• biologické markery MeSH
• fibroblastový růstový faktor 2 krev   MeSH
• lidé MeSH
• nádorové biomarkery MeSH
• nádory příštítného tělíska krev   MeSH
• nádory štítné žlázy krev   MeSH
• papilární karcinom krev   MeSH
• patologická angiogeneze krev   MeSH
• vaskulární endoteliální růstový faktor A krev   MeSH
• Check Tag
• lidé MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH
• Názvy látek
• biologické markery MeSH
• fibroblastový růstový faktor 2 MeSH
• nádorové biomarkery MeSH
• vaskulární endoteliální růstový faktor A MeSH

PURPOSE: The aim of this study was to investigate whether there is any association between the levels of the angiogenic growth factors and the vascular oxygen saturation in eyes with diabetic retinopathy. METHODS: The study was designed as a prospective trial. The cohort consisted of 29 diabetic patients with scheduled vitreous procedures (intravitreal injection or pars plana vitrectomy). The control group included 30 patients scheduled for macular surgery (macular hole or epiretinal membrane). Nine patients (four from the diabetic maculopathy [DM] group and five from the control group) were excluded from the study because of unsuccessful vitreous samples. Retinal oximetry was performed several hours before the vitreous procedure was performed, and vitreous samples were obtained during the procedure. The concentrations of VEGF, Serpin F1/pigment epithelium-derived factor (PEDF), and placental growth factor (PlGF) were measured by ELISA. RESULTS: A negative correlation between level of VEGF and arteriovenous (AV) saturation difference was determined in the DM group (Pearson correlation coefficient r = -0.607; two-tailed test, P = 0.002). Also a negative correlation between level of PlGF and AV saturation difference was determined in the DM group (Pearson correlation coefficient r = -0.521; two-tailed test, P = 0.011) A positive correlation between PlGF level and the vein saturation was not statistically significant (Pearson correlation coefficient r = 0.325; two-tailed test, P = 0.130). We did not find any correlation between vitreous level of PEDF and vascular saturation within the DM group. CONCLUSIONS: Our findings in diabetic patients suggests a correlation between the intravitreal level of proangiogenic factors and the AV difference measured by retinal oximetry.

• MeSH
• diabetes mellitus * MeSH
• diabetická retinopatie * MeSH
• lidé MeSH
• placentární růstový faktor MeSH
• prospektivní studie MeSH
• retina MeSH
• retinální cévy MeSH
• saturace kyslíkem MeSH
• vaskulární endoteliální růstový faktor A MeSH
• Check Tag
• lidé MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH
• Názvy látek
• placentární růstový faktor MeSH
• vaskulární endoteliální růstový faktor A MeSH

Generally, patients with renal cell carcinoma (RCC) are viewed as potential candidates for antiangiogenic targeted therapy. Tubulocystic RCC (TCRC) is a recently described entity which may behave aggressively, and the rationale for antiangiogenic therapy in this group of renal tumors has yet to be determined. Seven TCRCs and five non-tumor tissue samples from seven patients were subjected to relative expression analysis of mRNA levels of 16 genes involved in three angiogenic signal pathways: (1) VHL/HIF, (2) RTK/mitogen-activated protein kinase (MAPK), and (3) PI3K/Akt/mTOR. Two of them, pathways (2) and (3), are often targeted by antiangiogenic agents. We also determined the mutation and methylation status of the VHL gene. Finally, the levels of vascular endothelial growth factor A (VEGFA), HIF-1α, HIF-2α proteins, and phosphorylated mTOR protein were also determined. The comparison of tumor and control samples revealed no changes of mRNA levels of the following genes: VHL, HIF-1α, HIF-2α, PTEN, Akt2, Akt3, mTOR, VEGFA, KDR, HRas, C-Jun, EGFR, and FGF2. Significantly elevated mRNA level of TP53 was found, while the mRNA levels of FLT1 and C-FOS were reduced in tumor samples. No mutations or methylation in the VHL gene were found. Changes in levels of studied proteins VEGFA, HIF-1α, HIF-2α, and increased phosphorylation of mTOR protein were not found. Three studied angiogenic pathways (VHL/HIF, RTK/MAPK, and PI3K/Akt/mTOR) seem not to be upregulated in TCRC samples, so there appears to be no rationale for a general recommendation of antiangiogenic targeted therapeutic protocols for patients with these tumors.

• MeSH
• cílená molekulární terapie metody   MeSH
• dospělí MeSH
• faktor 1 indukovatelný hypoxií - podjednotka alfa metabolismus   MeSH
• fosforylace MeSH
• inhibitory angiogeneze farmakologie   terapeutické užití   MeSH
• karcinom z renálních buněk krevní zásobení   farmakoterapie   metabolismus   MeSH
• lidé středního věku MeSH
• lidé MeSH
• nádorový supresorový protein VHL metabolismus   MeSH
• nádory ledvin krevní zásobení   farmakoterapie   metabolismus   MeSH
• patologická angiogeneze farmakoterapie   genetika   MeSH
• senioři MeSH
• signální transdukce účinky léků   genetika   MeSH
• TOR serin-threoninkinasy metabolismus   MeSH
• transkripční faktory bHLH metabolismus   MeSH
• vaskulární endoteliální růstový faktor A metabolismus   MeSH
• výsledek terapie MeSH
• Check Tag
• dospělí MeSH
• lidé středního věku MeSH
• lidé MeSH
• mužské pohlaví MeSH
• senioři MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH
• kazuistiky MeSH
• práce podpořená grantem MeSH
• Názvy látek
• endothelial PAS domain-containing protein 1 MeSH Prohlížeč
• faktor 1 indukovatelný hypoxií - podjednotka alfa MeSH
• HIF1A protein, human MeSH Prohlížeč
• inhibitory angiogeneze MeSH
• MTOR protein, human MeSH Prohlížeč
• nádorový supresorový protein VHL MeSH
• TOR serin-threoninkinasy MeSH
• transkripční faktory bHLH MeSH
• vaskulární endoteliální růstový faktor A MeSH
• VEGFA protein, human MeSH Prohlížeč
• VHL protein, human MeSH Prohlížeč

Neo-angiogenesis represents an important factor for the delivery of oxygen and nutrients to a growing tumour, and is considered to be one of the main pathodiagnostic features of glioblastomas (GBM). Anti-angiogenic therapy by vascular endothelial growth factor (VEGF) blocking agents has been shown to lead to morphological vascular normalisation resulting in a reduction of contrast enhancement as seen by magnetic resonance imaging (MRI). Yet the functional consequences of this normalisation and its potential for improved delivery of cytotoxic agents to the tumour are not known. The presented study aimed at determining the early physiologic changes following bevacizumab treatment. A time series of perfusion MRI and hypoxia positron emission tomography (PET) scans were acquired during the first week of treatment, in two human GBM xenograft models treated with either high or low doses of bevacizumab. We show that vascular morphology was normalised over the time period investigated, but vascular function was not improved, resulting in poor tumoural blood flow and increased hypoxia.

• Klíčová slova
• Angiogenesis, VEGF, bevacizumab, glioblastoma, hypoxia, perfusion,
• MeSH
• bevacizumab farmakologie   MeSH
• glioblastom patologie   MeSH
• inhibitory angiogeneze farmakologie   MeSH
• lidé MeSH
• myši nahé MeSH
• nádory mozku patologie   MeSH
• patologická angiogeneze patologie   MeSH
• xenogenní modely - testy antitumorózní aktivity MeSH
• zvířata MeSH
• Check Tag
• lidé MeSH
• mužské pohlaví MeSH
• ženské pohlaví MeSH
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH
• Názvy látek
• bevacizumab MeSH
• inhibitory angiogeneze MeSH

Using the protein array method we determined the serum levels of a number of angiogenic factors. We identified serum levels of angiogenin, PDGF and MCP-1 (CCL2 chemokine) in serum of 32 patients with RCC, and 14 healthy volunteers by means of antibody array analysis. The patients were divided into three groups according to their disease stages (I+II, III, and IV). We found significant differences between the controls and patients with RCC both pre-operatively and post-operatively in angiogenin, PDGF and MCP-1 serum levels. The increase in angiogenin, PDGF and MCP-1 lasted in patients with RCC stages I-III even without metastases eight weeks post-operatively. The patients with stage IV RCC showed disturbed production of PDGF and MCP-1. Protein array analysis is a powerful tool for the identification of large numbers of trace proteins. Multiplex antibody array is able to provide data more precisely reflecting the nature of pathological processes.

• MeSH
• chemokin CCL2 krev   MeSH
• čipová analýza proteinů * MeSH
• destičkový růstový faktor metabolismus   MeSH
• karcinom z renálních buněk krev   patologie   chirurgie   MeSH
• lidé středního věku MeSH
• lidé MeSH
• pankreatická ribonukleasa krev   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
• angiogenin MeSH Prohlížeč
• chemokin CCL2 MeSH
• destičkový růstový faktor MeSH
• pankreatická ribonukleasa MeSH

Melanoma is one of the most aggressive cancers which has very low response rate and survival rate. Melanoma cells are known to be inherently resistant to the chemotherapy which results in poor outcomes and even failure of the therapy. For this reason, a better understanding of underlying mechanism of melanoma pathogenesis and resistance is required, so that more efficient and novel therapeutic strategies can be developed. Survivin is a protein which is overexpressed in melanoma cells and is known to impart resistance to them against apoptosis. Also, melanoma cells overexpress Vascular Endothelial Growth Factor (VEGF) and basic Fibroblast Growth Factor (bFGF) angiogenic growth factors which lead to aggressive angiogenesis in melanoma cells thereby making the treatment more challenging. This hypothesis presents a combinatorial approach against melanoma where an anti-survivin agent and an anti-angiogenic agent are combined with a chemotherapeutic drug and loaded in surface functionalized liposomes in order to target specific mechanisms of melanoma, thus overcoming its resistance. Thus, the study aims to overcome the resistance of melanoma cells by developing a wise combination of drugs and achieve a higher response rate in resistant melanoma model, which is usually not achieved with the existing treatment modalities.

• MeSH
• antigeny CD44 metabolismus   MeSH
• antitumorózní látky chemie   MeSH
• dakarbazin terapeutické užití   MeSH
• fibroblastový růstový faktor 2 metabolismus   MeSH
• inhibitory angiogeneze chemie   MeSH
• inhibitory apoptózy chemie   MeSH
• lidé MeSH
• liposomy chemie   MeSH
• melanom metabolismus   terapie   MeSH
• nádory kůže terapie   MeSH
• nanočástice chemie   MeSH
• patologická angiogeneze MeSH
• proliferace buněk MeSH
• survivin MeSH
• teoretické modely MeSH
• vaskulární endoteliální růstový faktor A metabolismus   MeSH
• Check Tag
• lidé MeSH
• mužské pohlaví MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH
• Názvy látek
• antigeny CD44 MeSH
• antitumorózní látky MeSH
• BIRC5 protein, human MeSH Prohlížeč
• CD44 protein, human MeSH Prohlížeč
• dakarbazin MeSH
• fibroblastový růstový faktor 2 MeSH
• inhibitory angiogeneze MeSH
• inhibitory apoptózy MeSH
• liposomy MeSH
• survivin MeSH
• vaskulární endoteliální růstový faktor A MeSH