The aim of this study was to compare the serum levels of the anti-angiogenic factor endostatin (S-endostatin) as a potential marker of vasculogenesis after autologous cell therapy (ACT) versus percutaneous transluminal angioplasty (PTA) in diabetic patients with critical limb ischemia (CLI). A total of 25 diabetic patients with CLI treated in our foot clinic during the period 2008-2014 with ACT generating potential vasculogenesis were consecutively included in the study; 14 diabetic patients with CLI who underwent PTA during the same period were included in a control group in which no vasculogenesis had occurred. S-endostatin was measured before revascularization and at 1, 3, and 6 months after the procedure. The effect of ACT and PTA on tissue ischemia was confirmed by transcutaneous oxygen pressure (TcPO2) measurement at the same intervals. While S-endostatin levels increased significantly at 1 and 3 months after ACT (both P < 0.001), no significant change of S-endostatin after PTA was observed. Elevation of S-endostatin levels significantly correlated with an increase in TcPO2 at 1 month after ACT ( r = 0.557; P < 0.001). Our study showed that endostatin might be a potential marker of vasculogenesis because of its significant increase after ACT in diabetic patients with CLI in contrast to those undergoing PTA. This increase may be a sign of a protective feedback mechanism of this anti-angiogenic factor.

• Klíčová slova
• angiogenic factors, autologous cell therapy, critical limb ischemia, endostatin,
• MeSH
• angioplastika * MeSH
• antigeny CD34 analýza   MeSH
• autologní transplantace MeSH
• buněčná a tkáňová terapie MeSH
• diabetes mellitus 2. typu krev   komplikace   MeSH
• diabetická noha krev   terapie   MeSH
• endostatiny krev   MeSH
• fyziologická neovaskularizace MeSH
• ischemie krev   terapie   MeSH
• kmenové buňky cytologie   MeSH
• končetiny krevní zásobení   MeSH
• lidé středního věku MeSH
• lidé MeSH
• onemocnění periferních cév terapie   MeSH
• senioři MeSH
• transplantace kmenových buněk * MeSH
• výsledek terapie 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
• antigeny CD34 MeSH
• endostatiny MeSH

INTRODUCTION: Multiple myeloma (MM) is still incurable due to resistance against various therapies. Thus, the identification of biomarkers predicting progression is urgently needed. Here, we evaluated four biomarkers in bone marrow and peripheral blood of MM patients for their prognostic significance. MATERIALS & METHODS: Bone marrow- and peripheral blood plasma levels of FLT3-L, soluble TIE2, endostatin, and osteoactivin were determined in patients with monoclonal gammopathy of undetermined significance (MGUS, n = 14/n = 4), patients with newly diagnosed MM (NDMM, n = 42/n = 31) and patients with relapsed/refractory MM (RRMM, n = 27/n = 16) by sandwich ELISA. RESULTS: Median FLT3-L expression increased from MGUS (58.77 pg/ml in bone marrow; 80.40 pg/ml in peripheral blood) to NDMM (63.15 pg/ml in bone marrow; 85.05 pg/ml in peripheral blood) and was maximal in RRMM (122 pg/ml in bone marrow; 160.47 pg/ml in peripheral blood; NDMM vs. RRMM p<0.001). A cut-off value of FLT3-L >92 pg/ml in bone marrow and >121 pg/ml in peripheral blood was associated with relapse or refractoriness in MM patients. FLT3-L was found to be a high predictive marker for discrimination between NDMM and RRMM as well in bone marrow as in peripheral blood (AUC 0.75 in bone marrow; vs 0.84 in peripheral blood). CONCLUSION: High levels of FLT3-L in bone marrow and peripheral blood of MM patients identify patients with progressive disease and are associated with relapse or refractoriness in MM patients. FLT3-L could be useful as a marker to identify RRMM patients and should be evaluated as target for future therapies.

• MeSH
• diferenciální diagnóza MeSH
• dospělí MeSH
• ELISA MeSH
• endostatiny metabolismus   MeSH
• kostní dřeň metabolismus   MeSH
• lidé středního věku MeSH
• lidé MeSH
• membránové glykoproteiny metabolismus   MeSH
• membránové proteiny metabolismus   MeSH
• mnohočetný myelom metabolismus   MeSH
• nádorové biomarkery metabolismus   MeSH
• prognóza MeSH
• receptor TIE-2 metabolismus   MeSH
• recidiva MeSH
• ROC křivka MeSH
• senioři nad 80 let MeSH
• senioři 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
• Názvy látek
• endostatiny MeSH
• flt3 ligand protein MeSH Prohlížeč
• GPNMB protein, human MeSH Prohlížeč
• membránové glykoproteiny MeSH
• membránové proteiny MeSH
• nádorové biomarkery MeSH
• receptor TIE-2 MeSH

The release of proangiogenic cytokines into the circulation after stem cell (SC) therapy and compensatory increase of angiogenesis inhibitors may reflect local vasculogenesis but also can increase the risk of side effects. The aim of our study was to evaluate serum levels of angiogenic cytokines with regard to the assessment of local and systemic vasculogenesis in diabetic patients with no-option critical limb ischemia (NO-CLI). Twenty-five diabetic patients with NO-CLI treated with SCs isolated from bone marrow or stimulated peripheral blood were included in the study. Serum levels of proangiogenic cytokines (VEGF, bFGF, Ang-1, PDGF-AA, and PDGF-BB) and an antiangiogenic cytokine (endostatin) were assessed 6 months after cell treatment, compared to baseline values, and correlated with the number of injected CD34(+) cells. The clinical effect of SC therapy (assessed by changes in TcPO2) and potential systemic vasculogenesis (assessed by eye fundus examination) were evaluated after 6 months. Serum levels of angiogenic inhibitor endostatin increased significantly after 1 and 3 months (p = 0.0003), but no significant increase in serum levels of proangiogenic cytokines was observed. A significant correlation between number of injected CD34(+) cells and serum levels of endostatin was observed (r = 0.41, p < 0.05); however, proangiogenic cytokines did not correlate with CD34(+) cells. No correlation between increase in TcPO2 after treatment and serum levels of any of the angiogenic cytokines were seen, and no signs of systemic vasculogenesis in the retina were observed after 6 months. Despite the significant increase in the levels of the angiogenic inhibitor endostatin following SC treatment, there was no risk of systemic vasculogenesis after SC therapy as documented by serum levels of proangiogenic cytokines or changes in the retina.

• MeSH
• antigeny CD34 metabolismus   MeSH
• autologní transplantace MeSH
• cytokiny krev   MeSH
• diabetes mellitus krev   terapie   MeSH
• endostatiny krev   MeSH
• fyziologická neovaskularizace * MeSH
• ischemie krev   komplikace   terapie   MeSH
• kyslík metabolismus   MeSH
• lidé středního věku MeSH
• lidé MeSH
• parciální tlak MeSH
• senioři MeSH
• transplantace kmenových buněk * 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
• antigeny CD34 MeSH
• cytokiny MeSH
• endostatiny MeSH
• kyslík MeSH

We investigated whether a genetic modification of BCR-ABL-transformed mouse cells that resulted in endostatin (ES) production altered their oncogenic potential. Mouse B210 cells, which express p210bcr-abl fusion protein and induce leukemia-like disease and extremely rarely solid tumors after intravenous (i.v.) administration, were used. The cells were transfected with a plasmid carrying genes for mouse ES and resistance to blasticidine. Transduced cells were isolated in media supplemented with blasticidine. Production of ES was determined by Western blotting. For further tests, two clones were selected, and their pathogenicity after i.v. inoculation was tested. Compared with the parental B210 cells, the capability of both gene-modified cell clones to induce lethal leukemia was reduced. However, mice that did not succumb to leukemia subsequently developed solid tumors. They were composed of poorly differentiated cells with irregular nuclei and roughly granular chromatin and were well vascularized. FISH revealed the presence of the BCR-ABL fusion gene both in tumors and spleens. Immunohistological investigation of the tumors demonstrated the production of ES in vivo and the cell lines derived from the tumors produced detectable amounts of ES, this demonstrating that the formation of solid tumors was not associated with the loss or silencing of the ES gene.

• MeSH
• bcr-abl fúzní proteiny genetika   metabolismus   MeSH
• endostatiny metabolismus   farmakologie   MeSH
• endoteliální buňky pupečníkové žíly (lidské) účinky léků   fyziologie   MeSH
• Kaplanův-Meierův odhad MeSH
• kultivační média speciální farmakologie   MeSH
• MHC antigeny I. třídy metabolismus   MeSH
• myši inbrední BALB C MeSH
• myši MeSH
• nádorová transformace buněk MeSH
• proliferace buněk MeSH
• transformované buněčné linie metabolismus   patologie   transplantace   MeSH
• transplantace nádorů MeSH
• zvířata MeSH
• Check Tag
• myši MeSH
• ženské pohlaví MeSH
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH
• Názvy látek
• bcr-abl fúzní proteiny MeSH
• endostatiny MeSH
• kultivační média speciální MeSH
• MHC antigeny I. třídy MeSH

Two mouse HPV16-transformed cell lines, viz. MK16 cells, which induce metastasizing tumors, and TC-1 cells, which induce non-metastasizing tumors were transduced with the gene for mouse endostatin. Two clones constitutively expressing endostatin were isolated from each of them. They were denoted ME3 and ME9, and TE2 and TE5, respectively. When inoculated into mice, ME3 cells were non-oncogenic. Nearly all mice inoculated with ME9 cells developed tumors, but considerably later than did the parental MK16 cells and metastasis formation was strongly reduced in these animals. On the other hand, TE2 and TE5 cells displayed oncogenic potential similar to that of the parental cells. To provide more information on these different effects of endostatin production, cell lysates of all six lines studied were tested for the content of 25 factors known to be involved in angiogenesis. The parental MK16 cells differed from the parental TC-1 cells and also from all endostatin producing sublines by a markedly higher production of interleukin 1alpha (IL-1alpha) and, to a lesser extent, by a higher production of several other factors tested. Additional experiments indicated that the suppression of the production of IL-1alpha by the parental MK16 caused by endostatin was due to an autocrine mechanism.

• MeSH
• autokrinní signalizace MeSH
• časové faktory MeSH
• endostatiny genetika   metabolismus   MeSH
• endoteliální buňky metabolismus   MeSH
• geny ras * MeSH
• interleukin-1alfa metabolismus   MeSH
• interleukin-2 genetika   metabolismus   MeSH
• kultivační média speciální metabolismus   MeSH
• myši inbrední C57BL MeSH
• myši MeSH
• nádorová transformace buněk * MeSH
• nádory plic genetika   imunologie   metabolismus   prevence a kontrola   sekundární   virologie   MeSH
• onkogenní proteiny virové genetika   MeSH
• Papillomavirus E7 - proteiny MeSH
• proliferace buněk MeSH
• represorové proteiny genetika   MeSH
• transdukce genetická MeSH
• transformované buněčné linie MeSH
• virová transformace buněk * MeSH
• zvířata MeSH
• Check Tag
• myši MeSH
• ženské pohlaví MeSH
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH
• Názvy látek
• E6 protein, Human papillomavirus type 16 MeSH Prohlížeč
• endostatiny MeSH
• interleukin-1alfa MeSH
• interleukin-2 MeSH
• kultivační média speciální MeSH
• oncogene protein E7, Human papillomavirus type 16 MeSH Prohlížeč
• onkogenní proteiny virové MeSH
• Papillomavirus E7 - proteiny MeSH
• represorové proteiny MeSH

The aim of the study was to determine whether VEGF, TPS, TK or Endostatin determination in tissue cytosol may have some additional value in distinguishing among different types of thyroid lesions. These markers were chosen as representatives of the 2 main pathways (angiogenesis and proliferation) involved in thyroid diseases. VEGF is the most potent angiogenic promoter and Endostatin plays an opposing role. Thymidine kinase (TK) is a marker of DNA synthesis and TPS, cytokeratin 18 fragments, is a marker of the rate of proliferation. We determined qualitatively all four markers in tissue extracts: cytosol from 157 tissue specimens (93 goitre, 12 Hashimoto's thyroiditis, 39 adenomas and 13 carcinomas). In 6 cases we were able to compare both normal and pathological tissue samples from a single patient. Statistically significant differences were found in the measured markers, but outliers were present in all groups. This fact does not permit their use in differential diagnosis. The highest levels of all markers were reached in adenomas, being higher than in carcinomas, probably explained by the higher overall metabolic rate in adenomas.

• MeSH
• cytosol metabolismus   MeSH
• endostatiny metabolismus   MeSH
• lidé MeSH
• nemoci štítné žlázy metabolismus   MeSH
• štítná žláza metabolismus   MeSH
• thymidinkináza metabolismus   MeSH
• vaskulární endoteliální růstový faktor A metabolismus   MeSH
• Check Tag
• lidé MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH
• Názvy látek
• endostatiny MeSH
• thymidinkináza MeSH
• vaskulární endoteliální růstový faktor A MeSH