BACKGROUND: The current obstructive sleep apnea (OSA) diagnostic uses polysomnography or limited polygraphy and requires specialized personnel and technical equipment. Glycoprotein biomarkers and microRNAs are being explored as a possible new method for screening. We aimed to evaluate whether certain biomarkers and microRNA, previously identified as related to OSA, could be influenced by factors such as gender, age, and obesity level in patients with OSA. METHODS: In this retrospective analytical study, patients with moderate to severe OSA (n = 130) were compared with the control group. Serum levels of selected biomarkers and microRNA were taken from both groups. The group of OSA patients was then stratified by gender, obesity level, and age to see the possible influence of those variables on biomarker levels. RESULTS: Levels of all studied biomarkers - C-reactive protein (CRP), high-sensitivity troponin I (hsTnI), pentraxin-3 (PTX-3), and microRNA-499 were significantly higher in patients with OSA compared to the control group. In the OSA group only hsTnI showed a statistically significant relationship with gender. Levels of CRP and hsTnI showed a significant dependence on the level of obesity. Dependency on age was proven for hsTnI. CRP, PTX-3, and microRNA-499 did not have any statistically significant relationship with age. CONCLUSION: We found that serum levels of pentraxin-3 and microRNA-499 in patients with moderate to severe obstructive sleep apnoea are independent of gender, obesity, and age. CRP was affected by the level of obesity and hsTnI was influenced by all 3 variables. We consider these findings important for further research of OSA biomarkers.
- MeSH
- biologické markery * krev MeSH
- C-reaktivní protein * analýza metabolismus MeSH
- dospělí MeSH
- glykoproteiny krev genetika MeSH
- lidé středního věku MeSH
- lidé MeSH
- mikro RNA * krev MeSH
- obezita * krev genetika MeSH
- obstrukční spánková apnoe * krev genetika MeSH
- retrospektivní studie MeSH
- senioři MeSH
- sérový amyloidový protein metabolismus analýza genetika MeSH
- sexuální faktory MeSH
- troponin I krev MeSH
- věkové faktory MeSH
- Check Tag
- dospělí MeSH
- lidé středního věku MeSH
- lidé MeSH
- mužské pohlaví MeSH
- senioři MeSH
- ženské pohlaví MeSH
- Publikační typ
- časopisecké články MeSH
Východiska: Glykosylace je posttranslační modifikace, která je zapojena do mnoha biologických procesů a významně zasahuje i do dějů spojených s nádorovou progresí. Změny glykanových struktur na povrchu nádorových buněk způsobené alterujícími hladinami exprese glykosyltransferáz a glykosidáz ovlivňují proliferaci, adhezi, migraci i buněčnou signalizaci. Přítomnost neobvyklých glykanových struktur a glykokonjugátů v sérech byla popsána u mnohých onkologických onemocnění a řada glykoproteinů byla schválena Úřadem pro kontrolu potravin a léčiv v USA jako nádorové biomarkery pro klinická vyšetření. V současnosti se pozornost při hledání nových glykomarkerů zaměřuje na detekci proteinů s aberantní glykosylací nebo zvýšenou koncentrací v sérech nebo exozomech, a to z důvodu jejich aktivní sekrece nebo uvolňování z nádorových buněk do extracelulárního prostoru. Cíl: Cílem článku bylo popsat strukturu glykanů, glykoproteinů i glykokonjugátů a přiblížit jejich funkci ve vývoji a progresi nádorů. Dalším cílem bylo čtenáře seznámit s vybranými klinicky schválenými glykoproteiny využívanými k diagnostice onkologických onemocnění (AFP, PSA, CA 125, HE4). Pozornost byla zaměřena na změny v glykanové struktuře uvedených proteinů, jejich funkce, koncentrace v sérech a jejich využití v klinice a diagnostice onkologických onemocnění.
Background: Glycosylation is a posttranslational modification that is involved in many biological processes and significantly affects the processes associated with tumour progression. Changes in glycan structures on the surface of tumour cells caused by altering levels of glycosyltransferase and glycosidase expression affect proliferation, adhesion, migration and cellular signalling. The presence of aberrant glycan structures and glycoconjugates in the sera of oncological patients has been reported in many cancers. Consequently, many glycoproteins have been approved by the U.S. Food and Drug Administration as tumour biomarkers for clinical investigations. At present, attention is focused on the search for new glycomarkers that are decorated by aberrant glycosylation or are overexpressed in the serum or exosomes due to their active secretion or release from tumour cells to the extracellular space. Purpose: The aim of this article has been to review the structure of glycans, glycoproteins and other glycoconjugates and to give more details about their functions in the development and progression of tumours. Another aim was to familiarise the reader with selected clinically approved glycoproteins used to diagnose oncological diseases (AFP, PSA, CA 125, HE4). Attention was paid to changes in the glycan structure of these proteins, their function, serum concentrations and clinical use in the diagnostics of cancer.
Glykomika se zabývá detekcí a charakterizací glykanů přítomných v biologických vzorcích. Je známo, že glykanové struktury dodávají biomolekulám vysoký stupeň strukturní diverzity a tím i mnohostranné biologické funkce, jako jsou buněčné rozpoznávání, adheze nebo zapojení v buněčných signálních drahách. Významně se také účastní onkogeneze, např. ve fázích invaze, metastazování a angiogeneze. Analýza glykanových struktur přítomných v nádorových tkáních nebo tělních tekutinách pacientů je tedy slibným nástrojem pro hledání potenciálních nádorových biomarkerů nezbytných pro časnou diagnostiku nádorových onemocnění. V předložené práci je popsán proces glykosylace a vznik N a O glykanů, současně jsou zmíněny příklady glykanového profilování u rakoviny slinivky břišní, prostaty a vaječníku.
Glycomics is concerned with detection and characterization of glycans present in biological samples. It is well‑known that glycan structures impart high degree of structural diversity to biomolecules and thus add wide‑ranging biological functions, such as cellular recognition, adhesion or involvement in cellular signaling pathways. They substantially participate in oncogenesis, e. g. in phases of invasion, metastasis and angiogenesis. Therefore, analysis of glycan structures in tumor tissues or body liquids is a promising tool for searching for potential tumor biomarkers essential for an early diagnosis of the neoplastic disease. The presented review describes the process of glycosylation and the origination of N and O glycans, presenting examples of glycan profiling in pancreatic, prostate and ovarian cancer. Key words: glycomics – tumor biomarker – pancreatic cancer – prostate cancer – ovarian cancer This study was supported by IGA MH CR NT/13794-4/2012, by the European Regional Development Fund and the State Budget of the Czech Republic (RECAMO, CZ.1.05/2.1.00/03.0101), MEYS – NPS I – LO1413, by MH CZ – DRO (MMCI, 00209805) and by BBMRI_CZ (LM2010004). The authors declare they have no potential conflicts of interest concerning drugs, products, or services used in the study. The Editorial Board declares that the manuscript met the ICMJE “uniform requirements” for biomedical papers. Submitted: 10. 4. 2015 Accepted: 25. 6. 2015
- MeSH
- fukosa metabolismus MeSH
- glykomika * MeSH
- glykoproteiny krev metabolismus MeSH
- glykosylace * MeSH
- lidé MeSH
- nádorové biomarkery * krev metabolismus MeSH
- nádory prostaty krev metabolismus MeSH
- nádory slinivky břišní krev metabolismus MeSH
- nádory vaječníků krev metabolismus MeSH
- Check Tag
- lidé MeSH
- Publikační typ
- práce podpořená grantem MeSH
In recent years the plasma proteomes of several different myelodysplastic syndrome (MDS) subgroups have been investigated and compared with those of healthy donors. However, the resulting data do not facilitate a direct and statistical comparison of the changes among the different MDS subgroups that would be useful for the selection and proposal of diagnostic biomarker candidates. The aim of this work was to identify plasma protein biomarker candidates for different MDS subgroups by reanalyzing the proteomic data of four MDS subgroups: refractory cytopenia with multilineage dysplasia (RCMD), refractory anemia or refractory anemia with ringed sideroblasts (RA-RARS), refractory anemia with excess blasts subtype 1 (RAEB-1), and refractory anemia with excess blasts subtype 2 (RAEB-2). Reanalysis of a total of 47 MDS patients revealed biomarker candidates, with alpha-2-HS-glycoprotein and leucine-rich alpha-2-glycoprotein as the most promising candidates.
- MeSH
- biologické markery krev MeSH
- dospělí MeSH
- fetuin A metabolismus MeSH
- glykoproteiny krev MeSH
- lidé středního věku MeSH
- lidé MeSH
- myelodysplastické syndromy krev MeSH
- senioři MeSH
- Check Tag
- dospělí MeSH
- lidé středního věku MeSH
- lidé MeSH
- mužské pohlaví MeSH
- senioři MeSH
- ženské pohlaví MeSH
- Publikační typ
- časopisecké články MeSH
- práce podpořená grantem MeSH
- srovnávací studie MeSH
Chronic liver diseases are a serious health problem worldwide. One of the frequently reported glycan alterations in liver disease is aberrant fucosylation, which was suggested as a marker for noninvasive serologic monitoring. We present a case study that compares site specific glycoforms of four proteins including haptoglobin, complement factor H, kininogen-1, and hemopexin isolated from the same patient. Our exoglycosidase-assisted LC-MS/MS analysis confirms the high degree of fucosylation of some of the proteins but shows that microheterogeneity is protein- and site-specific. MSn analysis of permethylated detached glycans confirms the presence of LeY glycoforms on haptoglobin, which cannot be detected in hemopexin or complement factor H; all three proteins carry Lewis and H epitopes. Core fucosylation is detectable in only trace amounts in haptoglobin but with confidence on hemopexin and complement factor H, where core fucosylation of the bi-antennary glycans on select glycopeptides reaches 15-20% intensity. These protein-specific differences in fucosylation, observed in proteins isolated from the same patient source, suggest that factors other than up-regulation of enzymatic activity regulate the microheterogeneity of glycoforms. This has implications for selection of candidate proteins for disease monitoring and suggests that site-specific glycoforms have structural determinants, which could lead to functional consequences for specific subsets of proteins or their domains.
- MeSH
- glykoproteiny krev sekrece MeSH
- glykosylace MeSH
- hepatitida C krev MeSH
- jaterní cirhóza krev virologie MeSH
- játra sekrece MeSH
- konformace sacharidů MeSH
- lidé středního věku MeSH
- lidé MeSH
- molekulární sekvence - údaje MeSH
- posttranslační úpravy proteinů * MeSH
- sacharidové sekvence MeSH
- sekvence aminokyselin MeSH
- Check Tag
- lidé středního věku MeSH
- lidé MeSH
- mužské pohlaví MeSH
- Publikační typ
- časopisecké články MeSH
- práce podpořená grantem MeSH
- Research Support, N.I.H., Extramural MeSH
BACKGROUND: Rituximab and alemtuzumab, mAbs used in recent years to treat CLL, are directed against antigens CD20 and CD52. CD20 is not highly expressed by CLL tumor cells, and rituximab does not have significant effectiveness in CLL unless combined with chemotherapy. Alemtuzumab targets CD52, which is much more highly expressed, and is currently the most effective agent used alone for CLL. Variability in expression of both antigens among these patients might be related to different individual therapeutic responses to mAb therapy. PATIENTS AND METHODS: A total 95 patients diagnosed with CLL and/or SLL were divided into 4 groups: (1) untreated; (2) in complete or partial remission; (3) disease in progression; and (4) diagnosed with SLL. Flow cytometry of peripheral blood cells included gating of the CD5(+)CD19(+) tumor population, within which mean fluorescence intensity of fluorescein isothiocyanate (FITC) conjugated with anti-CD20 or anti-CD52 antibody was measured. The resulting expression of the 2 antigens was deduced from the calibration curve using Quantum FITC particles. RESULTS: Expression of CD20 showed no significant differences among the 4 groups of patients. However, significantly greater expression of surface antigen CD52 was recorded in patient group 2 in complete or partial remission (P < .001). CONCLUSION: The residual population of CLL cells after therapy is characterized by increased surface detection of CD52. Although the exact cause of this phenomenon is unknown, our results provide a basis to consider the potential for CLL consolidation therapy using alemtuzumab.
- MeSH
- antigeny nádorové krev MeSH
- CD antigeny krev MeSH
- chronická lymfatická leukemie krev farmakoterapie MeSH
- cílená molekulární terapie MeSH
- dospělí MeSH
- fluorescein-5-isothiokyanát analýza MeSH
- fluorescenční barviva analýza MeSH
- fluorometrie metody MeSH
- glykoproteiny krev MeSH
- humanizované monoklonální protilátky terapeutické užití MeSH
- indukce remise MeSH
- kalibrace MeSH
- lidé středního věku MeSH
- lidé MeSH
- lymfocyty chemie MeSH
- protokoly protinádorové kombinované chemoterapie terapeutické užití MeSH
- průtoková cytometrie metody MeSH
- reziduální nádor MeSH
- senioři nad 80 let MeSH
- senioři MeSH
- výběr pacientů 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
- práce podpořená grantem MeSH
The presence of sialylated structures in tick organs was observed previously using lectin staining. Recently, we demonstrated the presence of sialylated N-glycans using mass spectrometry in tick salivary glands and the gut. However, we proposed a host (blood) origin for these glycans and mapped the transport of sialylated molecules from the gut to the salivary glands. In this report, we performed quantitation of whole sialic acid and of metabolically incorporated sialic acid (N-azido neuraminic acid) in Ixodes ricinus tick samples. We show that the majority of sialylated molecules in the adult tick originate in the host (blood) and are not synthesized by the tick. Similar results were observed for tick cell cultures. The almost complete absence of tick sialylated molecules and the specific transport and localization of host structures into the tick salivary glands and the saliva raises many questions on the role of these molecules in the physiology and, specifically, the blood-feeding of ticks.
- MeSH
- buněčné linie MeSH
- glykoproteiny krev metabolismus MeSH
- interakce hostitele a parazita * MeSH
- klíště metabolismus fyziologie MeSH
- kyselina N-acetylneuraminová metabolismus MeSH
- sliny metabolismus MeSH
- zvířata MeSH
- Check Tag
- ženské pohlaví MeSH
- zvířata MeSH
- Publikační typ
- časopisecké články MeSH
- práce podpořená grantem MeSH
BACKGROUND: Participation of protein polymorphism is often considered in the pathogenesis of various diseases. Aberrant protein glycosylation has been recognized to play major roles in human disorders, including neurodegenerative diseases. OBJECTIVE: The aim of the study was to examine possible involvement of protein genetic variants and degree of glycosylation of some serum glycoproteins in the manifestation of neurodegenerative disorders in a Czech population sample. METHODS: Apolipoprotein (Apo) E and three main serum markers of glycosylation defects (transferrin, Tf, alpha1-antitrypsin, aAT and ApoCIII) in patients with Alzheimer's dementia (AD), Parkinson's disease (PD) and vascular dementia (n=62, 139 and 44, respectively) were analyzed by isoelectric focusing. Children with serious neurological symptoms (n=55) and three age-matched control groups (n=45, 45 and 42) were examined for comparison. RESULTS: Of the supposedly pathognomonic protein variants Tf C2, aAT ZM and ApoE e4 only the latter was detected with higher frequency in AD patients; significant synergy of the C2/e4 allelic combination was not confirmed. The most prominent finding among PD adults was an increased appearance of Tf C2 allele and significant mean hypoglycosylation of ApoCIII, besides a C2/e4 positive correlation in PD seniors. Laboratory signs of Tf hypoglycosylation and a pattern of Tf/ApoCIII hyperglycosylation have been occasionally found.
- MeSH
- alely MeSH
- alfa-1-antitrypsin krev genetika MeSH
- Alzheimerova nemoc krev genetika MeSH
- apolipoprotein C-III krev genetika MeSH
- apolipoproteiny E krev genetika MeSH
- dítě MeSH
- dospělí MeSH
- frekvence genu MeSH
- glykoproteiny krev genetika MeSH
- glykosylace MeSH
- isoelektrická fokusace MeSH
- lidé středního věku MeSH
- lidé MeSH
- neurodegenerativní nemoci krev epidemiologie genetika MeSH
- Parkinsonova nemoc krev genetika MeSH
- senioři MeSH
- sexuální faktory MeSH
- stárnutí fyziologie MeSH
- transferin genetika metabolismus MeSH
- vaskulární demence krev genetika MeSH
- věkové faktory MeSH
- Check Tag
- dítě MeSH
- dospělí MeSH
- lidé středního věku MeSH
- lidé MeSH
- mužské pohlaví MeSH
- senioři MeSH
- ženské pohlaví MeSH
- Publikační typ
- časopisecké články MeSH
- práce podpořená grantem MeSH
- Geografické názvy
- Česká republika MeSH
CD34 is the most frequently used marker for the selection of cells for bone marrow (BM) transplantation. The use of CD133 as an alternative marker is an open research topic. The goal of this study was to evaluate the proliferation and differentiation potential for hematopoiesis (short and long term) of CD133+ and CD34+ populations from bone marrow and mobilized peripheral blood. Eight cell populations were compared: CD34+ and CD133+ cells from both the BM (CML Ph-, CML Ph+, and healthy volunteers) and mobilized peripheral blood cells. Multicolor flow cytometry and cultivation experiments were used to measure expression and differentiation of the individual populations. It was observed that the CD133+ BM population showed higher cell expansion. Another finding is that during a 6-day cultivation with 5(6)-carboxyfluorescein diacetate N-succinimidyl ester (CFSE), more cells remained in division D0 (non-dividing cells). There was a higher percentage of CD38- cells observed on the CD133+ BM population. It was also observed that the studied populations contained very similar but not the same pools of progenitors: erythroid, lymphoid, and myeloid. This was confirmed by CFU-GM and CFU-E experiments. The VEGFR antigen was used to monitor subpopulations of endothelial sinusoidal progenitors. The CD133+ BM population contained significantly more VEGFR+ cells. Our findings suggest that the CD133+ population from the BM shows better proliferation activity and a higher distribution of primitive progenitors than any other studied population.
- MeSH
- antigeny CD34 krev imunologie MeSH
- biologické markery metabolismus MeSH
- buněčná diferenciace imunologie MeSH
- buněčný rodokmen MeSH
- buňky kostní dřeně cytologie fyziologie MeSH
- CD antigeny krev imunologie MeSH
- glykoproteiny krev imunologie MeSH
- hematopoetické kmenové buňky cytologie fyziologie MeSH
- krevní buňky cytologie fyziologie MeSH
- kultivované buňky MeSH
- lidé MeSH
- peptidy krev imunologie MeSH
- proliferace buněk MeSH
- separace buněk MeSH
- vaskulární endoteliální růstový faktor A metabolismus MeSH
- Check Tag
- lidé MeSH
- Publikační typ
- časopisecké články MeSH
- práce podpořená grantem MeSH
Our objective was to study the kinetics of circulating endothelial cells (EC) and endothelial precursor cells (EPC) in hematological patients during chemotherapy and autologous stem cell transplantion (ASCT). Eighteen newly diagnosed patients and 17 patients undergoing ASCT were studied and compared to healthy controls. ECs were evaluated as CD146+CD31+Lin- cells, while EPCs were evaluated as CD34+CD133+Lin-, or CD34+VEGFR2+Lin- cells, or CFU-En colony forming units. Numbers of these cells were evaluated before and after treatment, and, in patients treated with ASCT, during mobilization of hematopoietic progenitors. Both newly diagnosed patients and patients before ASCT had significantly higher number of CD146+CD31+Lin- cells and significantly lower number of CFU-En colonies than healthy controls. These parameters did not return to normal for at least 3 months after chemotherapy or ASCT. Numbers of CFU-En did not correlate either with numbers of CD34+CD133+Lin- cells or with numbers of CD34+VEGFR2+Lin- cells but they did correlate with numbers of CD4+ lymphocytes and NK cells. In conclusion, we have found that hematological patients have higher number of EC and lower numbers of CFU-En than healthy controls and that these parameters do not return to normal after short-term follow-up. Furthermore, our observations support emerging data that CFU-En represent cell population different from flowcytometrically defined EC and endothelial precursors and that their development requires cooperation of monocytes and CD4+ lymphocytes. However, cells forming CFU-En express endothelial surface markers and can contribute to proper endothelial function by NO production.
- MeSH
- analýza kolonii tvořících jednotek MeSH
- antigen CD146 krev MeSH
- antigeny CD31 krev MeSH
- antigeny CD34 krev MeSH
- autologní transplantace MeSH
- CD antigeny krev MeSH
- endoteliální buňky metabolismus patologie MeSH
- farmakoterapie metody MeSH
- glykoproteiny krev MeSH
- hematologické nádory krev farmakoterapie chirurgie MeSH
- kmenové buňky metabolismus patologie MeSH
- lidé středního věku MeSH
- lidé MeSH
- mladý dospělý MeSH
- peptidy krev MeSH
- protokoly protinádorové kombinované chemoterapie terapeutické užití MeSH
- průtoková cytometrie MeSH
- receptor 2 pro vaskulární endoteliální růstový faktor krev MeSH
- senioři nad 80 let MeSH
- senioři MeSH
- transplantace hematopoetických kmenových buněk metody MeSH
- výsledek terapie MeSH
- Check Tag
- lidé středního věku MeSH
- lidé MeSH
- mladý dospělý MeSH
- mužské pohlaví MeSH
- senioři nad 80 let MeSH
- senioři MeSH
- ženské pohlaví MeSH
- Publikační typ
- časopisecké články MeSH
- práce podpořená grantem MeSH
