BACKGROUND: Galectin-3 (Gal-3) is a promising target in cancer therapy with a high therapeutic potential due to its abundant localization within the tumor tissue and its involvement in tumor development and proliferation. Potential clinical application of Gal-3-targeted inhibitors is often complicated by their insufficient selectivity or low biocompatibility. Nanomaterials based on N-(2-hydroxypropyl)methacrylamide (HPMA) nanocarrier are attractive for in vivo application due to their good water solubility and lack of toxicity and immunogenicity. Their conjugation with tailored carbohydrate ligands can yield specific glyconanomaterials applicable for targeting biomedicinally relevant lectins like Gal-3. RESULTS: In the present study we describe the synthesis and the structure-affinity relationship study of novel Gal-3-targeted glyconanomaterials, based on hydrophilic HPMA nanocarriers. HPMA nanocarriers decorated with varying amounts of Gal-3 specific epitope GalNAcβ1,4GlcNAc (LacdiNAc) were analyzed in a competitive ELISA-type assay and their binding kinetics was described by surface plasmon resonance. We showed the impact of various linker types and epitope distribution on the binding affinity to Gal-3. The synthesis of specific functionalized LacdiNAc epitopes was accomplished under the catalysis by mutant β-N-acetylhexosaminidases. The glycans were conjugated to statistic HPMA copolymer precursors through diverse linkers in a defined pattern and density using Cu(I)-catalyzed azide-alkyne cycloaddition. The resulting water-soluble and structurally flexible synthetic glyconanomaterials exhibited affinity to Gal-3 in low μM range. CONCLUSIONS: The results of this study reveal the relation between the linker structure, glycan distribution and the affinity of the glycopolymer nanomaterial to Gal-3. They pave the way to specific biomedicinal glyconanomaterials that target Gal-3 as a therapeutic goal in cancerogenesis and other disorders.

• Klíčová slova
• Carbohydrate, ELISA, Galectin-3, Glyconanomaterial, HPMA copolymer, Surface plasmon resonance,
• MeSH
• akrylamidy chemie   metabolismus   MeSH
• galektin 3 metabolismus   MeSH
• galektiny MeSH
• glykokonjugáty chemie   metabolismus   MeSH
• krevní proteiny MeSH
• lidé MeSH
• nanostruktury chemie   MeSH
• nosiče léků chemie   metabolismus   MeSH
• systémy cílené aplikace léků * MeSH
• Check Tag
• lidé MeSH
• Publikační typ
• časopisecké články MeSH
• Názvy látek
• akrylamidy MeSH
• galektin 3 MeSH
• galektiny MeSH
• glykokonjugáty MeSH
• krevní proteiny MeSH
• LGALS3 protein, human MeSH Prohlížeč
• N-(2-hydroxypropyl)methacrylamide MeSH Prohlížeč
• nosiče léků MeSH

Langerhans cells are dendritic antigen-presenting cells residing predominantly in the epidermis. Since endogenous galactoside-binding lectins with the jelly-roll motif (galectins) are known to trigger cellular responses, including mediator release, we investigated by lectin histochemistry the cells' capacity to bind two common members of this family, i.e. galectin-1 and -3. Actually, surrounding keratinocytes express a high level of galectin-3, and these cells can be considered as donors of this lectin to Langerhans cells. Employing biotinylated galectin-1 and -3, and concomitantly an antibody against CD1a as a second marker, to visualize the position of Langerhans cells in the human epidermis, the expression of galectin-3-reactive glycoligands in contrast to the lack of binding of galectin-1 was observed. Although the functional consequences of this selectivity are unclear, these results reveal an example for differential cellular reactivity towards two related endogenous lectins.

• MeSH
• antigeny CD1 analýza   imunologie   MeSH
• CD antigeny analýza   imunologie   MeSH
• diferenciační antigeny imunologie   MeSH
• dospělí MeSH
• epitopy analýza   MeSH
• galektin 1 MeSH
• galektin 3 MeSH
• hemaglutininy imunologie   MeSH
• keratinocyty cytologie   imunologie   MeSH
• kultivované buňky MeSH
• kůže cytologie   imunologie   MeSH
• Langerhansovy buňky cytologie   imunologie   MeSH
• lektiny imunologie   MeSH
• lidé MeSH
• vazebná místa MeSH
• Check Tag
• dospělí MeSH
• lidé MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH
• Názvy látek
• antigeny CD1 MeSH
• CD antigeny MeSH
• diferenciační antigeny MeSH
• epitopy MeSH
• galektin 1 MeSH
• galektin 3 MeSH
• hemaglutininy MeSH
• lektiny MeSH

The synthesis of tailored bioactive carbohydrates usually comprises challenging (de)protection steps, which lowers synthetic yields and increases time demands. We present here a regioselective single-step introduction of benzylic substituents at 3-hydroxy groups of β-d-galactopyranosyl-(1→1)-thio-β-d-galactopyranoside (TDG) employing dibutyltin oxide in good yields. These glycomimetics act as inhibitors of galectins-human lectins, which are biomedically attractive targets for therapeutic inhibition in, for example, cancerogenesis. The affinity of the prepared glycomimetics to galectin-1 and galectin-3 was studied in enzyme-linked immunosorbent (ELISA)-type assays and their potential to inhibit galectin binding on the cell surface was shown. We used our original in vivo biotinylated galectin constructs for easy detection by flow cytometry. The results of the biological experiments were compared with data from molecular modeling with both galectins. The present work reveals a facile and elegant synthetic route for the preparation of TDG-derived glycomimetics that exhibit differing selectivity and affinity to galectins depending on the choice of 3-O-substitution.

• Klíčová slova
• carbohydrates, glycomimetics, glycosides, inhibitors, molecular modeling,
• MeSH
• galaktosa MeSH
• galektin 1 chemie   metabolismus   MeSH
• galektin 3 chemie   metabolismus   MeSH
• galektiny chemie   metabolismus   MeSH
• krevní proteiny MeSH
• lidé MeSH
• molekulární modely MeSH
• sacharidy chemie   MeSH
• thiogalaktosidy chemie   MeSH
• Check Tag
• lidé MeSH
• Publikační typ
• časopisecké články MeSH
• Názvy látek
• galaktosa MeSH
• galektin 1 MeSH
• galektin 3 MeSH
• galektiny MeSH
• krevní proteiny MeSH
• LGALS3 protein, human MeSH Prohlížeč
• sacharidy MeSH
• thiodigalactoside MeSH Prohlížeč
• thiogalaktosidy MeSH

Galectin-3 (Gal-3) participates in many cancer-related metabolic processes. The inhibition of overexpressed Gal-3 by, e.g., β-galactoside-derived inhibitors is hence promising for cancer treatment. The multivalent presentation of such inhibitors on a suitable biocompatible carrier can enhance the overall affinity to Gal-3 and favorably modify the interaction with Gal-3-overexpressing cells. We synthesized a library of C-3 aryl-substituted thiodigalactoside inhibitors and their multivalent N-(2-hydroxypropyl)methacrylamide (HPMA)-based counterparts with two different glycomimetic contents. Glycopolymers with a higher content of glycomimetic exhibited a higher affinity to Gal-3 as assessed by ELISA and biolayer interferometry. Among them, four candidates (with 4-acetophenyl, 4-cyanophenyl, 4-fluorophenyl, and thiophen-3-yl substitution) were selected for further evaluation in cancer-related experiments in cell cultures. These glycopolymers inhibited Gal-3-induced processes in cancer cells. The cyanophenyl-substituted glycopolymer exhibited the strongest antiproliferative, antimigratory, antiangiogenic, and immunoprotective properties. The prepared glycopolymers appear to be prospective modulators of the tumor microenvironment applicable in the therapy of Gal-3-associated cancers.

• MeSH
• galektin 3 * metabolismus   MeSH
• prospektivní studie MeSH
• thiogalaktosidy * farmakologie   MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH
• Názvy látek
• galektin 3 * MeSH
• thiodigalactoside MeSH Prohlížeč
• thiogalaktosidy * MeSH

Galectin-3 (gal-3) is lectin which is presumed to interact with extracellular matrix proteins and cell surface glycoproteins in normal and pathophysiological conditions. The expression of gal-3 at the fetal-maternal interface partially overlaps that of gal-1, suggesting that an interplay between them might be important for hypertensive disorders in pregnancy like preeclampsia. The aim of our study was to test the hypothesis whether galectin-3 could be used as a predictive marker for early-onset preeclampsia development. 32 patients with early-onset preeclampsia were examined, mean age 28.8 ± 5.5; and 22 age matched normal pregnancies mean age 28.5 ± 6.0. The enzyme-linked immunosorbent assay (ELISA) was used for measuring serum galectin-3 levels. There were no significant differences between serum levels of galectin-3 in sera of preeclampsia patients compared to normal pregnant women - 14.1 ± 4.77 vs. 15.7 ± 5.95 ng/ml (p>0.05). Serum galectin-3 levels correlated with maternal age (r=0.33; p=0.03) and BMI (body mass index) (r=0.52; p=0.01). Our data suggest that determination of serum galectin-3 levels may not be a useful method for prediction of early-onset preeclampsia. Studies should be aimed to other categories of biomarkers.

• Klíčová slova
• Biomarker, Early-onset preeclampsia, Galectin-3,
• MeSH
• biologické markery krev   MeSH
• dospělí MeSH
• ELISA MeSH
• galektin 3 * krev   MeSH
• index tělesné hmotnosti MeSH
• lidé MeSH
• mladý dospělý MeSH
• preeklampsie * krev   diagnóza   MeSH
• těhotenství MeSH
• Check Tag
• dospělí MeSH
• lidé MeSH
• mladý dospělý MeSH
• těhotenství MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH
• Názvy látek
• biologické markery MeSH
• galektin 3 * MeSH

Summary Multipotent stem cells (source for interfollicular epidermis, hairs and sebaceous glands) are localized in the bulge region of the outer root sheath of hair follicles, while stem cells giving rise to interfollicular epidermis reside in its basal. Using the multifunctional lectin galectin-1 as a marker to localize accessible binding sites in situ as a step to figure out galectin functionality in stem cells, we studied hair follicle-derived keratinocytes. Specific nuclear binding of galectin-1 associated with expression of DeltaNp63alpha, a potential marker of epidermal stem cells, was detected. Binding of chimera-type galectin-3 to a nuclear site was not found in parallel assays. During the process of ageing in culture when cells acquire properties of senescence, disappearance of the nuclear signal for galectin-1 binding was accompanied by a similar decrease of nuclear DeltaNp63alpha expression and increased binding of galectin-3 to the cell membrane, namely in regions of intercellular contacts. Expression of cytokeratin 10, a marker of the terminal differentiation was seen only in a small fraction of the cell population. These data extend the evidence for nuclear sites with galectin-1 reactivity in squamous epithelial cells, the expression of which is modulated upon senescence. Moreover, the results document the divergence of galectin-1 and -3 on the level of ligand selection in this cell type, underscoring the importance of the technical aspect to employ tissue lectins as probe and to perform a fingerprinting with several markers of the galectin family in parallel.

• MeSH
• buněčná diferenciace MeSH
• galektin 1 metabolismus   MeSH
• galektin 3 metabolismus   MeSH
• keratinocyty metabolismus   MeSH
• keratiny metabolismus   MeSH
• kmenové buňky metabolismus   MeSH
• kultivované buňky MeSH
• lidé MeSH
• stárnutí metabolismus   MeSH
• Check Tag
• lidé MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH
• Názvy látek
• galektin 1 MeSH
• galektin 3 MeSH
• keratiny MeSH

BACKGROUND/AIM: Galectins belong to the family of galactose-binding proteins known to play an important role in the processes of cell proliferation, differentiation, migration and neoplastic progression. Herein, we studied the expression of galectin-3 (Gal-3) in chronic lymphocytic leukemia (CLL). MATERIALS AND METHODS: The expression of Gal-3 was analyzed by means of multiparametric flow cytometry in normal and pathological B-cells from peripheral blood and bone marrow samples of 67 patients with CLL. RESULTS: Pathological B-cells expressed significantly higher levels of cytoplasmic Gal-3 than normal B-cells. Moreover, overexpression of cytoplasmic Gal-3 was observed in the prognostically poorest subgroup of CLL patients, namely those with 17p deletion. CONCLUSION: Our results indicate a possible role of galectin-3 in CLL pathophysiology and its potential value as a prognostic marker and therapeutic target.

• Klíčová slova
• 17p deletion, B-cells, Galectin-3, chronic lymphocytic leukemia, cytogenetics, flow cytometry,
• MeSH
• chromozomální delece * MeSH
• chronická lymfatická leukemie genetika   MeSH
• cytoplazma metabolismus   MeSH
• dospělí MeSH
• galektin 3 genetika   MeSH
• galektiny MeSH
• krevní proteiny MeSH
• lidé středního věku MeSH
• lidé MeSH
• lidské chromozomy, pár 17 genetika   MeSH
• nádorové biomarkery genetika   MeSH
• prognóza MeSH
• regulace genové exprese u nádorů MeSH
• senioři nad 80 let MeSH
• senioři MeSH
• upregulace * 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
• galektin 3 MeSH
• galektiny MeSH
• krevní proteiny MeSH
• LGALS3 protein, human MeSH Prohlížeč
• nádorové biomarkery MeSH

The differential diagnosis of well-differentiated tumors of follicular cell origin remains the most problematic task in thyroid pathology. Specific morphologic criteria (capsular and/or vascular invasion, nuclear characteristics) are crucial in the diagnosis of these neoplasms. However, the assessment of malignant features is inconclusive in some cases. Moreover, oncocytic thyroid tumors remain controversial in a respect to their pathobiology, behavior and management. Therefore, the useful diagnostic/prognostic thyroid markers are awaited. The aim of our study was to evaluate the expression of galectin-3 and thyroid peroxidase (TPO) in benign and malignant thyroid tumors of follicular cell origin. A total of 186 archival thyroid samples including 38 non-oncocytic follicular adenomas, 53 oncocytic (Hürthle cell) adenomas, 6 non-oncocytic follicular carcinomas, 23 oncocytic (Hürthle cell) carcinomas, 43 non-oncocytic papillary carcinomas, and 23 oncocytic papillary carcinomas were analyzed for galectin-3 and TPO expression by immunohistochemistry. Both types of papillary carcinomas showed significant upregulation of galectin-3 in comparison with the other tumor types, likewise, significant differences in galectin-3 expression were discovered between non-oncocytic and oncocytic variants of studied tumors excluding follicular carcinoma. Significant lowering of TPO was revealed in oncocytic adenomas and papillary carcinomas. In conclusion, the combined use of galectin-3 and TPO markers could help to improve the differential diagnosis of thyroid tumors. Differences in the galectin-3 and TPO expression between some oncocytic and non-oncocytic tumors support their separation in the latest WHO classification of thyroid tumors.

• MeSH
• autoantigeny genetika   MeSH
• diferenciální diagnóza MeSH
• galektin 3 genetika   MeSH
• galektiny MeSH
• jodidperoxidasa genetika   MeSH
• krevní proteiny MeSH
• lidé MeSH
• nádorové biomarkery genetika   MeSH
• nádory štítné žlázy klasifikace   diagnóza   MeSH
• proteiny vázající železo genetika   MeSH
• Check Tag
• lidé MeSH
• Publikační typ
• časopisecké články MeSH
• Názvy látek
• autoantigeny MeSH
• galektin 3 MeSH
• galektiny MeSH
• jodidperoxidasa MeSH
• krevní proteiny MeSH
• LGALS3 protein, human MeSH Prohlížeč
• nádorové biomarkery MeSH
• proteiny vázající železo MeSH
• TPO protein, human MeSH Prohlížeč

Galectin-3 (Gal-3) is recognized as a prognostic marker in several cancer types. Its involvement in tumor development and proliferation makes this lectin a promising target for early cancer diagnosis and anti-cancer therapies. Gal-3 recognizes poly-N-acetyllactosamine (LacNAc)-based carbohydrate motifs of glycoproteins and glycolipids with a high specificity for internal LacNAc epitopes. This study analyzes the mode and kinetics of binding of Gal-3 to a series of multivalent neo-glycoproteins presenting complex poly-LacNAc-based oligosaccharide ligands on a scaffold of bovine serum albumin. These neo-glycoproteins rank among the strongest Gal-3 ligands reported, with Kd reaching sub-nanomolar values as determined by surface plasmon resonance. Significant differences in the binding kinetics were observed within the ligand series, showing the tetrasaccharide capped with N,N'-diacetyllactosamine (LacdiNAc) as the strongest ligand of Gal-3 in this study. A molecular model of the Gal-3 carbohydrate recognition domain with docked oligosaccharide ligands is presented that shows the relations in the binding site at the molecular level. The neo-glycoproteins presented herein may be applied for selective recognition of Gal-3 both on the cell surface and in blood serum.

• Klíčová slova
• carbohydrate, galectin-3, galectins in diagnosis, galectins in therapy, glycosyltransferase, molecular modeling, surface plasmon resonance,
• MeSH
• galektin 3 chemie   metabolismus   MeSH
• glykoproteiny chemie   farmakologie   MeSH
• laktosa analogy a deriváty   chemie   MeSH
• lidé MeSH
• ligandy MeSH
• sérový albumin hovězí chemie   MeSH
• simulace molekulového dockingu * MeSH
• vazba proteinů MeSH
• vazebná místa MeSH
• Check Tag
• lidé MeSH
• Publikační typ
• časopisecké články MeSH
• Názvy látek
• galektin 3 MeSH
• glykoproteiny MeSH
• laktosa MeSH
• ligandy MeSH
• N-acetylgalactosaminyl-1-4-N-acetylglucosamine MeSH Prohlížeč
• sérový albumin hovězí MeSH

BACKGROUND: Galectin-3 (GAL3) is linked to the prognosis of patients with heart failure and after heart transplantation (HTx). We assessed the prognostic role of GAL3 in a long-term follow-up after HTx. METHODS: HTx patients (N = 121) were evaluated in a single-center, noninterventional, prospective, observational study. The median follow-up was 96 months (2942 days, interquartile range (IQR) 2408-3264 days), and 40 patients died. GAL3 was measured before HTx, +10 days after HTx, and during the first posttransplant year. Survival analysis (all-cause mortality) was performed with adjustments for clinical and laboratory variables. RESULTS: The median pretransplant GAL3 level was 18.0 μg/L (IQR 14.0-25.9), and higher values were associated with older age, worse kidney function, left ventricular assist device use before HTx, a higher IMPACT score, and mortality. Increased pretransplant GAL3 predicted shorter survival time (HR 2.05, 95% CI 1.09-3.85, p < .05). Similar prognostic power had GAL3 on the 10th posttransplant day (HR 2.03, 95% CI 1.08-3.82, p < .05). GAL3 was an independent predictor of death after adjustment for clinical variables (age, infection, diabetes, smoking, IMPACT score, and troponin). CONCLUSIONS: GAL3 was significantly associated with all-cause mortality after adjusting for clinical and laboratory variables and may serve as an additional prognostic biomarker.

• Klíčová slova
• biomarker, patient survival, risk assessment/risk stratification,
• MeSH
• galektin 3 * MeSH
• galektiny MeSH
• krevní proteiny MeSH
• lidé MeSH
• mortalita * MeSH
• prognóza MeSH
• prospektivní studie MeSH
• srdeční selhání * diagnóza   MeSH
• transplantace srdce * MeSH
• Check Tag
• lidé MeSH
• Publikační typ
• časopisecké články MeSH
• pozorovací studie MeSH
• práce podpořená grantem MeSH
• Názvy látek
• galektin 3 * MeSH
• galektiny MeSH
• krevní proteiny MeSH
• LGALS3 protein, human MeSH Prohlížeč