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In patients with typical angina pectoris, inducible myocardial ischaemia and macroscopically normal coronaries (cardiac syndrome X (CSX)), a significantly elevated plasma level of terminal complement complex (TCC), the common end product of complement activation, has been observed without accompanying activation of the classical or the alternative pathways. Therefore, our aim was to clarify the role of the ficolin-lectin pathway in CSX. Eighteen patients with CSX, 37 stable angina patients with significant coronary stenosis (CHD) and 54 healthy volunteers (HC) were enrolled. Serum levels of ficolin-2 and ficolin-3, ficolin-3/MASP-2 complex and ficolin-3-mediated TCC deposition (FCN3-TCC) were determined. Plasma level of TCC was significantly higher in the CSX than in the HC or CHD group (5.45 versus 1.30 versus 2.04 AU/ml, P < 0.001). Serum levels of ficolin-2 and ficolin-3 were significantly lower in the CSX compared to the HC or CHD group (3.60 versus 5.80 or 5.20 μg/ml, P < 0.05; 17.80 versus 24.10 or 26.80 μg/ml, P < 0.05). The ficolin-3/MASP-2 complex was significantly lower in the CSX group compared to the HC group (92.90 versus 144.90 AU/ml, P = 0.006). FCN3-TCC deposition was significantly lower in the CSX group compared to the HC and CHD groups (67.8% versus 143.3% or 159.7%, P < 0.05). In the CSX group, a significant correlation was found between TCC and FCN3-TCC level (r = 0.507, P = 0.032) and between ficolin-3/MASP-2 complex level and FCN3-TCC deposition (r = 0.651, P = 0.003). In conclusion, in patients with typical angina and myocardial ischaemia despite macroscopically normal coronary arteries, low levels of several lectin pathway parameters were observed, indicating complement activation and consumption. Complement activation through the ficolin-lectin pathway might play a role in the complex pathomechanism of CSX., (© 2016 The Foundation for the Scandinavian Journal of Immunology.)

Background and Aims: Galectins are beta-galactoside binding proteins. This ability may have a bearing on cell adhesion and migration/proliferation in human colon cancer cells. In addition to galectins-1 and -3 studied to date, other members of this family not investigated in detail may contribute to modulation of tumour cell features. This evident gap has prompted us to extend galectin analysis beyond the two prototypes. The present study deals with the quantitative determination of immunohistochemical expression of galectin-8 in normal, benign, and malignant human colon tissue samples and in four human colon cancer models (HCT-15, LoVo, CoLo201, and DLD-1) maintained both in vitro as permanent cell lines and in vivo as nude mice xenografts. The role of galectin-8 (and its neutralising antibody) in cell migration was investigated in HCT-15, LoVo, CoLo201, and DLD-1 cell lines., Methods: Immunohistochemical expression of galectin-8 and its overall ability to bind to sugar ligands (revealed glycohistochemically by means of biotinylated histochemically inert carrier bovine serum albumin with alpha- and beta-D-galactose, alpha-D-glucose, and lactose derivatives as ligands) were quantitatively determined using computer assisted microscopy. The presence of galectin-8 mRNA in the four human colon cancer cell lines was examined by reverse transcriptase-polymerase chain reaction. In vitro, cellular localisation of exogenously added galectin-8 in the culture media of these colon cancer cells was visualised by fluorescence microscopy. In vitro galectin-8 mediated effects (and the influence of its neutralising antibody) on migration levels of living HCT-15, LoVo, CoLo201, and DLD-1 cells were quantitatively determined by computer assisted phase contrast microscopy., Results: A marked decrease in immunohistochemical expression of galectin-8 occurred with malignancy development in human colon tissue. Malignant colon tissue exhibited a significantly lower galectin-8 level than normal or benign tissue colon cancers; those with extensive invasion capacities (T3-4/N+/M+) harboured significantly less galectin-8 than colon cancers with localised invasion capacities (T1-2/N0/M0). The four experimental models (HCT-15, LoVo, CoLo201, and DLD-1) had more intense galectin-8 dependent staining in vitro than in vivo. Grafting the four experimental human colon cancer models onto nude mice enabled us to show that the immunohistochemical expression of galectin-8 was inversely related to tumour growth rate. In vitro, galectin-8 reduced the migration rate of only those human experimental models (HCT-15 and CoLo201) that exhibited the lowest growth rate in vivo., Conclusions: Expression of galectin-8 correlated with malignancy development, with suppressor activity, as shown by analysis of clinical samples and xenografts. In vitro, only the two models with low growth rates were sensitive to the inhibitory potential of this galectin. Future investigations in this field should involve fingerprinting of these newly detected galectins, transcending the common focus on galectins-1 and -3.

This study aims to investigate whether the immunohistochemical expression of galectin-8 could be used as a diagnostic marker in tumor tissues of various histogenetic origins including specimens from epithelial (n=145), mesenchymatous (n=16), adipous (n=10) and central and peripheral nervous system (n=25) tissue, and 4 mesotheliomas. Immunohistochemical reactions were carried out with a polyclonal anti-galectin-8 antibody and histological slides from tissues derived from the files of the Laboratory of Anatomopathology of University Erasmus Hospital, Brussels. Formalin-fixed paraffin-embedded tissues of 45 normal cases as well as 41 benign and 114 malignant tumors were studied. Marked decreases in immunohistochemical galectin-8 expression were observed in colon (p=0.001), pancreas (p=0.007), liver (p=0.0008), skin (p=0.002) and larynx (p=0.02) tissue when comparing malignant tissue to normal tissue and/or benign tumors. The reverse relationship was observed for breast tissue (p=0.007). No statistically significant differences (p>0.05) were detected when comparing normal tissue and/or benign to malignant tumors in lung, bladder, kidney, prostate and stomach tissue. Significant galectin-8 expression was also measured in non-epithelial tissue including tumors of the central and peripheral nervous system as well as in skeletal muscle and mesotheliomas. Immunohistochemical monitoring of galectin-8 thus reveals an organ-type-dependent regulation of expression upon malignant transformation of various tissue types of epithelial origin. This observation will prompt further studies to delineate any relationship with prognosis.

Cholesteatoma is a benign disease characterized by the presence of an unrestrained growth and the accumulation of keratin debris in the middle ear cavity. This often recurs, even when surgical resection is thought to be complete. In a previous study we showed that cholesteatomas with the highest apoptotic indices recurred more rapidly and also exhibited a high level of p53 immunopositive cells. In view of their relevance to the characterization of the cell differentiation status, the present study focuses on the expression of retinoid acid receptors (RARs) and galectins in human cholesteatomas. Retinoids control the differentiation processes in keratinocytes while galectins play strikingly modulatory roles at apoptosis and cell adhesion levels in a wide variety of tissue (embryonic, normal and neoplastic). To clarify the expression of these two protein families in human cholesteatomas we examined and quantified the levels of immunohistochemical expression of RARalpha, beta and gamma, and also galectin-1, -3 and -8 in a series of 70 human cholesteatomas. Our data show clearly that predominantly RARbeta and galectin-1 were expressed. The RARgamma concentration was significantly lower than that of the RARalpha; this was also observed for the galectin-8 concentration in comparison with the galectin-3 one. Furthermore, the level of RARbeta expression correlated highly (P=0.00001) with the level of galectin-8 expression, which also correlated significantly with the level of RARalpha and RARgamma expression. In addition, this parameter also correlated with the level of galectin-1 and galectin-3 expression. These data suggest that cholesteatomas may originate in an undifferentiated population of keratinocytes, and that a relation may exist between retinoid activity and galectins.

Objectives: To investigate whether galectins 1, 3, and 8 are expressed in human cholesteatomas and whether any such expression does correlate with the level of apoptosis, which is, as we have previously shown, predictive of recurrence.7, Study Design: The analysis of 52 cholesteatomas resected by the same surgeon by means of canal wall up and canal wall down procedures., Methods: The immunohistochemical levels of expression of galectins 1, 3, and 8 were quantitatively determined (using computer-assisted microscopy) on conventional histological slides by means of specific anti-galectin-1, anti-galectin-3, and anti-galectin-8 antibodies. The level of apoptosis in each cholesteatoma under study had already been determined 7 by means of the in situ labeling of nuclear DNA fragmentation (Tolt-mediated dUTP nick end labeling [TUNEL] staining)., Results: Galectin-1 was expressed markedly in both the epithelial and the connective tissue areas of all the cholesteatomas under study. The levels of expression of galectin-3 and galectin-8 were considerably lower than that of galectin-1. The level of expression of galectin-3 correlated both highly and positively with the level of apoptosis., Conclusions: An upregulation of galectin-3 (known to have an antiapoptotic and antianoikis effect in certain model systems) expression, which is associated with pronounced apoptotic activity, could have a physiologically protective effect against the characteristically substantial apoptotic features occurring in recurrent cholesteatomas.

The toxic galactoside-specific lectin from mistletoe, a component of proprietary extracts with unproven efficacy in oncology, exhibits capacity to trigger enhanced secretion of proinflammatory cytokines at low doses (ng/ml or ng/kg body weight) and reductions of cell viability with increasing concentrations. To infer any tumor selectivity of this activity, cytofluorimetric and cell growth assays with a variety of established human tumor cell lines were performed. Only quantitative changes were apparent, and the toxicity against tumor cells was within the range of that of the tested fibroblast preparations from 5 donors. No indication for any tumor selectivity was observed. In kinetic studies with 8 sarcoma and 4 melanoma lines, this evidence for quantitative variability of the response in interindividual comparison was further underscored. At 50 pg lectin/ml x 10(5) cells, even a growth-stimulatory impact was noted in 5 of 12 tested cases. To mimic in vivo conditions with presence of cytokine-secreting inflammatory and stromal cells, exposure to the lectin was extended to histotypic cultures established from 30 cases of surgically removed tumor. As salient result, 5 specimens from 4 of the 8 tested tumor classes responded with a significant increase of [3H]-thymidine incorporation relative to controls during the culture period of 72 hours, when the lectin was present at a concentration in the described immunomodulatory range (1 ng/ml). A relation of this activity to the extent of the actual proliferative status of the reactive samples could not be delineated. Therefore, a non-negligible percentage of the established tumor cell lines (e.g., 3 from 8 sarcoma lines) can be markedly stimulated by the lectin at a very low dose and with dependence on the cell type. Furthermore, the feasibility to elicit a significant growth enhancement is likewise documented for human tumor explants in 16.6% of the examined cases. In view of the uncontrolled application of lectin-containing extracts in alternative/complementary medicine, the presented results on unquestionably adverse lectin-dependent effects in two culture systems call for rigorous examination of the clinical safety of this unconventional, scientifically entirely experimental treatment modality.

Objective: The profile of glycans and their recognition by endogenous receptors (lectins) are increasingly attributed to disease process. Monitoring this can provide information on the pathogenesis of Sjögren's syndrome (SS). Commonly, plant lectins are employed for phenomenological glycan mapping. To go beyond this approach restricted to binding of exogenous probes, new markers measure ligand properties of glycans to human (not plant) lectins and the presence of sugar receptors completing a protein-carbohydrate recognition system. Carrier-immobilized sugar epitopes (neoglycoproteins) and purified human lectins establish this innovative panel., Methods: The host defence molecules mannan binding lectin, serum amyloid P component, and the macrophage migration inhibitory factor-binding sarcolectin, selected for their involvement in cell destructive mechanisms, were purified and labeled. The plant lectins SNA and MAA were employed to monitor regulation of potential ligand sites for I-type lectins and galectins. Asialofetuin was tested as a "pan-galectin selective" probe. The specific binding characteristics were determined by quantitative morphometry and statistical analysis., Results: Diagnostic information emerged from this analysis. The percentage of stained tissue area was significantly different between SS and control specimens after processing with GlcNAc and Man-bearing neoglycoproteins and the 2 tested serum lectins. For separation of cases of primary and secondary SS, the staining intensity with the asialoglycoprotein, sarcolectin, and the exogenous alpha2,6-sialylated glycan-binding lectin SNA was statistically significant., Conclusion: Saccharide-presenting probes to measure the cellular capacity to bind glycan epitopes and human lectins as sensors for endogenous binding sites have proven to be useful as diagnostic tools. We suggest the differences we observed reflect aberrations from the normal cellular homeostasis with relevance for the pathogenesis of SS and its manifestation as a primary or secondary syndrome.

The purpose of this study was to characterize ligands for galectins, natural galactoside-binding immunoglobulin G subfractions and sarcolectin and also the expression of calcyclin in various benign and malignant thyroid lesions. The extent of the binding of eight glycochemical probes was quantitatively assessed using computer-assisted microscopy on 76 thyroid lesions including 10 not-otherwise-specified multinodular goiters (S&#95;MNG), 11 multinodular goiters with adenomatous hyperplasia (AH&#95;MNG), 8 normomacrovesicular (NM&#95;ADE) and 12 microvesicular (MIC&#95;ADE) adenomas, and 9 papillary (P&#95;CAR), 10 follicular variants of papillary (FvarP&#95;CAR), 7 follicular (F&#95;CAR) and 9 anaplastic (A&#95;CAR) carcinomas. The 8 histochemical probes included 5 animal lectins (including galectins and sarcolectin), 1 polyclonal antibody (raised against calcyclin) and 2 immunoglobulin G subfractions from human serum with selectivity to alpha- and beta-galactosyl residues. The results show that multinodular goiters with adenomatous hyperplasia exhibited histochemical characteristics intermediate to those of normal multinodular goiters and microvesicular adenomas. Normomacrovesicular adenomas behaved very distinctly from microvesicular ones. Microvesicular adenomas were more closely related to differentiated thyroid carcinomas than any other type of benign thyroid lesions of epithelial origin. Papillary and follicular carcinomas seemed to represent the two extremes of the same biological entity with the follicular variant of the papillary carcinoma serving as a biological link between these two extremes. Anaplastic carcinomas behaved in a significantly different manner when compared to the differentiated forms of thyroid carcinomas. The results suggest that the patterns of expression of the glycoconjugates investigated in the present study may constitute useful tools for characterizing lesions in the human thyroid.

Objectives: To investigate in a series of cholesteatomas 1. whether subgroups of cholesteatomas with specific proliferative/apoptotic features exhibit distinct differentiation markers and 2. whether these different subgroups identified at the biological level relate to specific groups of clinically identified cholesteatomas., Study Design: Analysis of 55 cholesteatomas resected by the same surgeon, by means of canal wall up and canal wall down surgical procedures., Methods: Two differentiation markers were used: biotinylated sarcolectin (to identify sarcolectin-binding sites) and a monoclonal antibody directed against calcyclin (which is the S100A6 protein). The growth pattern in cholesteatomas was characterized at three distinct levels: 1. the cell proliferation level determined by means of the MIB-1 antibody, which enables the Ki-67 cell-cycle-related antigen to be identified on archival material; 2. the apoptosis level determined by means of the in situ labeling of nuclear DNA fragmentation (TUNEL staining); and 3. the p53 tumor suppressor gene-related product determined by means of p53 immunohistochemistry., Results: The cholesteatomas that exhibited the highest proportion of apoptotic cells were those which exhibited the highest level of sarcolectin-binding sites (i.e., sialic acids). In contrast, the cholesteatomas exhibiting the lowest level of both proliferation and apoptosis showed the highest level of calcyclin. Recurrent cholesteatomas can be identified from nonrecurrent ones on the basis of three features, namely, the level of apoptotic cells, the way in which the apoptotic cells are distributed (i.e., homogeneously vs. heterogeneously), and the percentage of calcyclin-positive cells., Conclusions: The present data emphasize the existence of distinct subgroups of cholesteatomas identifiable at both cell kinetic and differentiation levels. Some of the biological variables used here to identify distinct biological subgroups of cholesteatomas in turn enabled some biological variables to be identified, so making it possible to classify the cholesteatomas in terms of recurrence versus nonrecurrence.

The current study deals with the setting up of a new tool that enables the benign versus the malignant nature of colorectal adenomas to be determined accurately. The 2 objectives are to determine (1) whether adenomas should, or should not, be included in a 2- or a 3-tier grading system, and (2) whether severe dysplasias and carcinomas in situ share common or different biological characteristics. The levels of expression of different types of glycoconjugates were characterized in a series of 166 colorectal specimens, including 14 normal, 90 dysplastic, and 62 cancerous cases. The glycoconjugate expressions were demonstrated for 5 lectins, namely, Arachis hypogaea (PNA), Dolichos biflorus (DBA), Amaranthus caudatus (ACA), Maackia amurensis (MAA) and Sambucus nigra (SNA). The glycoconjugates demonstrated by these 5 lectins belong to the family of the Thomsen-Friedenreich antigens. The binding patterns of the 5 lectins were quantitatively determined by means of computer-assisted microscopy. The quantitative data were submitted to discriminant analyses. Our results show that the specific glycochemical staining patterns could be identified unambiguously and without misclassification between benign (normal and low dysplasia) and malignant (ie, either as moderate/severe dysplasia, carcinoma in situ, or cancer) cases. The data also strongly suggested that (1) dysplasias seem to be distinguishable in 2 instead of 3 groups, that is, low versus moderate/severe (high); and (2) moderate/severe dysplasias are biologically distinct from carcinomas in situ. The methodology developed can be applied directly in routine diagnosis to identify moderate/severe dysplasia specimens already exhibiting features common to carcinomas, and which therefore should be treated consistently in view of the fact that our data strongly suggest that most moderate/severe dysplasias are still benign, whereas carcinomas in situ are real carcinomatous lesions.

A series of 41 nasal polyps (23 single and 18 massive) and 6 normal nasal mucosa specimens was glycohistochemically investigated. Five plant lectins were used, i.e., the peanut agglutinin (PNA), the wheat germ agglutinin (WGA), the gorse seed agglutinin (UEA-I), the Maackia amurensis agglutinin (MAA), and the elderberry bark agglutinin (SNA). A neoglycoconjugate and 2 animal lectins (CL-14 and CL-16) were also used. Three quantitative features were calculated by means of computer-assisted microscopy: the percentage of tissue area specifically stained by the histochemical probe, the staining intensity, and the heterogeneity level of the staining distribution. The results show that with respect to sialic acid-glycoprotein binding characteristics as determined by SNA, MAA, and WGA probes, the normal nasal mucosa differed markedly (p<.00001) from the polyposal one. The single nasal polyps exhibited glycohistochemical characteristics that differed markedly (p = .0004) from those exhibited by the massive ones. These differences related mainly to the UEA-I, PNA, and the Thomsen-Friedenreich antigen-exposing neoglycoprotein binding characteristics. In conclusion, the present study shows unambiguously that polyposal mucosa, whether of the single or the massive type, exhibits markedly distinct glycohistochemical characteristics when compared to normal nasal mucosa, and that single nasal polyps also differ markedly from massive ones.

Purpose: The aim of our study is to investigate the in vitro effects of plant lectins, galectins and neoglycoconjugates on the proliferation of three human sarcoma cell lines., Methods: Proliferation was assessed by means of the tetrazolium derivative reduction (MTT) assay. In addition, glycohistochemistry was used to make visible the plant-lectin-specific binding sites; the intensity of the lectin binding pattern was quantified by means of image analysis., Results: Depending on the cell lines, the staining intensity and the percentage of labelled cells were different. With respect to growth modulation, the cell lines also responded differently to the probes used. Besides a predominant inhibitory effect elicited by the probes at 50 microg/ml, dose-dependent effects, including growth stimulation, were detectable in several instances. These effects relate to the animal galectins tested and several neoglycoconjugates, e.g. the lactose- and blood-group-A-trisaccharide-bearing probes., Conclusions: Endogenous lectins and lectin-reactive cellular glycoconjugates can apparently affect the regulation of the growth of human sarcoma cells. We suggest that these results are relevant for further histopathological monitoring in correlation with prognosis and in vitro assays to reveal possible clinical applications.

Purpose: Alteration of intracavernous smooth muscle cells has been demonstrated in patients with pure venous leakage. This modification seems correlated with reduction of intracavernous oxygen tension. However, Doppler imaging of the cavernous arteries in these patients is normal. To understand the ischemic factor we studied the endothelium of the terminal arteries with computerized image analysis and immunohistochemical staining with 2 types of lectin in patients with venous leakage and those with normal erections. Lectins are glycoproteins that can be used as histological markers to monitor functional and pathological changes., Materials and Methods: Four patients 44 to 59 years old with normal erections who were operated on for penile cancer and 11 patients 27 to 62 years old with pure venous leakage (flow to maintain erection greater than 15 ml. per minute and cavernous flow velocity greater than 35 cm. per second) were included in the study. Immunohistochemical staining with 2 lectins, wheat germ agglutinin and Ulex europeaus agglutinin I, was performed and analyzed with computerized image analysis. The labeling index which relates to the percentage of staining indicates the distribution of the endothelial cells, and mean optical density which relates to the staining intensity indicates the function of these cells., Results: Mean labeling index values for the 2 lectins were similar in both groups (p >0.05). Mean optical density values for the 2 lectins were significantly greater for the patients with normal erections (p <0.01). Therefore, the distribution of the endothelial cells was the same while their function was different in patients with corporeal veno-occlusive dysfunction., Conclusions: Staining with wheat germ agglutinin and Ulex europeaus agglutinin I lectin types allowed us to detect alteration in the glyco-histochemistry of the endothelial cells of the small arteries, and venous leakage could be the first step in vasculogenic impotence.

The biological importance of oligosaccharide sequences in many different settings is undeniable. Glycan histochemistry has brought together the histological and biochemical approaches and provided insight into the mutual importance of both approaches. The aim of the authors is to take a look at a number of ways in which modern glycohistochemistry contributes to acquiring knowledge about the key role played by carbohydrates in the physiology of vertebrate tissues and human disease. The versatility of lectin and neoglycoconjugate histochemical procedures is emphasized.

The aim of this study is to present a new classification of nasal polyps. This classification is based both on morphologic criteria relating to morphonuclear features from isolated Feulgen-stained nuclei and on glycohistochemical characteristics from histologic slides submitted to three lectins (peanut, wheat germ, and gorse seed agglutinins) and one neoglycoconjugate glycohistochemical stain. While the morphonuclear features (including 30 variables) relate essentially to chromatin pattern, the glycohistochemical stains (including 16 variables) are linked to the presence of specific carbohydrate moieties in cell membranes and cytoplasm. Forty-nine nasal polyps, including single polyps, diffuse polyposis, cystic fibrosis-related polyposis, and aspirin idiosyncracy-related polyposis associated with asthma, were thus characterized. All the variables were obtained quantitatively by means of computer-assisted microscopy. Two complementary methods of data classification were used to determine the actual diagnostic value contributed by each quantitative variable, namely, discriminant analysis, which forms part of multifactorial statistical analysis, and the decision tree technique, which is an artificial intelligence-related algorithm. The data so obtained show that our morphologic classification of nasal polyps fits in with the classification of nasal polyps defined on the basis of clinical criteria.

Lectin binding is known to be able to elicit signalling events relevant for various aspects of cell physiology. The influence of lectin binding on melanoma cells remains relatively unexplored. The aim of our study was to investigate the in vitro effects of five plant lectins, namely peanut (PNA), wheat germ (WGA), concanavalin A (Con-A), Griffonia simplicifolia (GSA-IA4) and Phaseolus vulgaris (PHA-L) agglutinins, on the cell proliferation of melanoma cell lines (SK-MEL-28, HT-144 and C32) cultured in media supplemented with either 10% or 1% fetal calf serum (FCS). Cell proliferation was assessed by means of the tetrazolium derivative reduction (MTT) assay. Four lectin concentrations were tested, namely 0.05, 0.5, 5 and 50 micrograms/ml, in four experimental settings, namely 1, 3, 5 and 7 days after the addition of each lectin to the culture media. Determination of the cell gain compartment (percentage of cells in the S and G2 phases of the cell cycle) was done by means of digital cell image analysis assessed on Feulgen-stained nuclei. Our results demonstrated that of the five lectins under study, four had a globally significant dose-dependent toxic effect on melanoma cell proliferation. The fifth lectin, PNA, had a significant stimulatory effect on the C32 cell line. Low doses of lectins may produce a transient increase in cell proliferation. Increasing the FCS from 1% to 10% in the culture media significantly antagonized lectin-induced toxicity in the three cell lines. The cell kinetics measurements showed that the inhibition of cell growth was merely due to cell death. The present data strongly suggest that some lectins might influence the proliferation of melanoma cells. In addition, because lectins are present in our diet and are able to pass into the systemic circulation, we speculate that lectins may exert an influence on melanoma growth under clinical conditions.

The role of lectins as biosignalling molecules or as markers of human astrocytic tumors remains relatively unexplored. The aim of the present work is to investigate (1) whether or not human astrocytic tumors express specific glycans, evidenced experimentally by means of lectin histochemistry, and (2) whether, in turn, these lectins can significantly modulate astrocytic tumor cell proliferation. Using a cell image processor, we therefore began by quantitatively measuring the histochemical binding pattern of 5 lectins (WGA, PNA, PHA-L, GSA-IA4 and Con A) in 5 astrocytomas, 5 anaplastic astrocytomas and 5 glioblastomas. Secondly, we measured the influence of these 5 lectins on the proliferation of 3 astrocytic tumor cell lines (SW1088, U373 and U87) growing in vitro as monolayers. Cell proliferation was assessed by means of the colorimetric MTT assay. The histochemical lectin staining markedly varied intra- and inter-group. However, some constant results were obtained. Indeed, the staining increased markedly from GSA-IA4 and PHA-L through WGA and PNA to ConA in the three histopathological groups. The assessment of cell proliferation demonstrated that WGA, Con A and PHA-L very significantly decreased proliferation in the 3 astrocytic cell lines in a dose-dependent manner. Astrocytic tumor cells in the confluent growth phase were less sensitive to the WGA, Con A and PHA-L lectin-induced effects than cells in the log growth phase. The GSA-IA4 and PNA lectins had globally very weak effects on the proliferation of the astrocytic tumor cell lines. Increasing the fetal calf serum from 1% to 10% in the culture media significantly antagonized the WGA-, Con A- and PHA-L-induced cell proliferation decrease in the 3 astrocytic cell lines. In conclusion, the present data strongly suggest that some lectins (including WGA, Con A and PHA-L) significantly influence the proliferation of astrocytic tumor cells.

Objective: To find new diagnostic markers in the group of lipomatous tumors., Study Design: The histochemical lectin staining pattern was characterized in a series of 45 lipomatous lesions, including 10 typical lipomas, 6 atypical lipomas, 8 well-differentiated, 6 myxoid, 5 dedifferentiated and 10 pleomorphic liposarcomas. Three lectins were used-peanut (Arachis hypogaea) agglutinin, which binds to terminal Gal(beta 1,3)GalNAc residues; wheat germ (Triticum vulgare) agglutinin (s-WGA, the succinylated form of WGA), which binds to ((1-4)-D-GlcNAc)n and Neu5NAc residues; and jack bean (Concanavalia ensiformis) agglutinin which binds to alpha-D-Man and alpha-D-Glc residues. Histochemical staining was quantitatively measured by means of a cell image processor., Results: In the case of certain carbohydrate residues, typical lipomas closely resemble atypical lipomas, which in turn closely resemble well-differentiated liposarcomas; typical lipomas differ significantly from well-differentiated liposarcomas. This indicates that atypical lipomas, or at least some of them, could represent a biologic link between typical lipomas and well-differentiated liposarcomas. While well-differentiated and pleomorphic liposarcomas differed significantly from each other, the poorly differentiated component of dedifferentiated liposarcomas included histochemical lectin properties, which were common to both well-differentiated and pleomorphic liposarcomas., Conclusion: Some atypical lipomas exhibit glycohistochemical characteristics that are common to those of well-differentiated liposarcoma. The poorly differentiated component of dedifferentiated liposarcomas remains more differentiated in terms of glycohistochemical markers than do poorly differentiated pleomorphic liposarcomas.

Background/aims: Compared with normal colonic mucosa, lectin receptor expression is increased in hyperplastic and neoplastic tissues; some lectins have been shown to influence human colonic epithelial cell proliferation. The aim was to assess further the influence of five lectins (Phaseolus vulgaris (PNA), Griffonia simplicifolia (GSA), concanavalin A (Con A), wheat germ (WGA), and peanut (PHA-L) agglutinins) on cellular growth in three human colorectal cancer cell lines (LoVo, HCT-15 and SW837)., Methods: Cells were cultured in four lectin concentrations (0.1, 1.0, 10, and 100 micrograms/ml) and growth assessed at days 2, 3, 5, and 7. The experiments were performed in media supplemented with either 1% or 10% fetal calf serum (FCS). Growth was assessed using the MTT (3-(4,5)-dimethylthiazol-2-yl)-2,5-diphenyl tetrazolium bromide) colorimetric assay., Results: Growth in each cell line was greatly affected by at least two of the lectins tested. There was some variation in the effect of a given lectin on different cell lines. Lectin effects showed a dose-response and the greatest effects generally resulted from the highest concentrations at the longest culture time. WGA and Con A induced large effects in all cell lines; the effects of Con A were partly blocked by the higher concentration of FCS. PNA had modest and uniform stimulatory effects overall. The effects of GSA and PHA-L varied between cell lines., Conclusions: The lectins studied all have the potential to affect colonic cancer growth in vitro. Many dietary lectins are resistant to digestion and may have important effects in vitro but the definition of their role in human colonic cancer biology must take into account the variability in lectin response.

The objectives of this study were to investigate the value of glycohistochemical staining with three lectin types specific to a particular glycan structure (Arachis hypogaea [PNA], Triticum vulgare [WGA], and concanavalin A [Con A]) as a method of defining possible changes in the collagen structure in the corpora cavernosa in potent and impotent men. The study group consisted of 4 normal potent men and 22 men with various etiologies of impotence. The quantitative histochemical measurements were performed by means of a cell image processor. Two variables for each of the three types of lectins were studied. These were the mean optical density (MOD), which relates to glycohistochemical staining intensity, and the labeling index (LI), which is positively related to the percentage of immunostaining. Only WGA staining made it possible to discriminate significantly between the normal and pathological groups under study. The two parameters (LI, MOD) were significantly higher in the case of WGA staining in the normal group (P = 0.004 and 0.013, respectively). In contrast, only the mean LI value, in the case of the psychogenic and venogenic patients, reached a level of statistical significance (P = 0.005 and 0.001, respectively), when it increased from PNA through WGA to Con A histochemical staining. The two variables (LI, MOD) changed markedly from PNA through WGA to Con A in the arteriogenic patients (P = 0.003 and P < 0.001, respectively). WGA is of diagnostic value in distinguishing between normal and abnormal collagen in the corpora cavernosa. The difference in the lectin staining of the other groups, particularly the arteriogenic group, may be attributed to alterations in the glycosylation of the procollagen that are probably due to changes in the partial pressure of oxygen (PO2) level, an important cofactor in normal glycosylation. WGA staining may therefore be used as a marker to distinguish true psychogenic patients from those with organic diseases. Moreover, it may be used as an additional parameter in selecting the best candidates for penile revascularization.

The glycohistochemical expression of binding sites for eight lectins is characterized in a series of 15 meningothelial, 10 fibroblastic and 15 transitional meningiomas. The correlation between lectin staining and either the proliferation index or ploidy level has also been investigated. The data show that the cytochemical binding of some lectins is of value in distinguishing between the different meningioma subgroups. For example, fibroblastic meningiomas express significantly higher amounts of wheat germ agglutinin (WGA) and Ulex europaeus agglutinin (UEA-I) than the meningothelial sub-type. Diploid tumours express a higher glycine maximus (SBA), Arachis hypogaea (PNA) and Phaseolus vulgaris leukoagglutinin (PHA-L) binding than aneuploid tumours. These differences are probably due to the modification of post-transcriptional glycosylation events linked to tumour ageing. The data also reveal that the increased binding of PHA-L is inversely correlated with the proliferation indices of the tumours.

Background: The development of certain biologic characteristics in human colorectal tumor xenografted onto nude mice are described with respect to their precocious passages, i.e., passaging below 10 onto athymic mice., Experimental Design: The biologic characteristic monitoring involved the determination of modifications occurring in cytoplasmic lectin binding and spontaneous development in nuclear size and DNA content. The lectin immunohistochemistry included the characterization of staining modifications in the glandular parts of the colorectal xenografts of wheat germ, Dolichos biflorus, peanut, Solanum tuberosum and Ulex europaeus I agglutinins. The nuclear modifications were monitored by means of the digital cell image analyses of Feulge-stained nuclei., Results: The results show that although the xenografted human colorectal lines may be relatively stable according to their macroscopic growth over serial passaging, certain of their microscopic characteristics develop markedly. Three lectins, i.e., wheat germ agglutinin, Solanum tuberosum, and Ulex europaeus I, showed a glandular binding which remained relatively stable over serial passaging, whereas the peanut binding exhibited some variations and the DBA binding progressively disappeared. These cytoplasmic modifications occurring over time were less pronounced than those that occurred with respect to nuclear measurements, i.e., size and DNA content., Conclusions: Nuclear DNA content heterogeneity as revealed by DNA histogram typing rather than by DNA index assessments increased markedly in the colorectal xenografts over their serial passaging on nude mice.

The most pertinent works using lectin histochemistry at both light and electron microscopy were reviewed. The results and their eventual interpretation are summarized. The importance of lectins as a histochemical tool is mainly based upon the two following features: they possess a narrow specificity for various carbohydrate residues and they can be linked to different labels (fluorochrome, peroxidase, ferritin, colloidal gold) or be included in immunocytochemical techniques in order to be visualized at conventional, u.v. and electron microscopes. These have the advantage to preserve the cellular and tissular integrity. Various tissues and organs were investigated first as a descriptive manner and then under cell differentiation and ontogenetic points of view. Tissues from laboratory rodents and human were especially studied. Few works regarding other vertebrates have been published. However comparative studies could probably cast some lights regarding functions and phylogenetic evaluation. Finally, lectin histochemistry in pathology seems of great promise as indicated by the growing number of publications.

Galectins are a family of animal lectins with an affinity for β-galactosides. They are differentially expressed by various tissues and appear to be functionally multivalent, exerting a wide range of biological activities both during development and in adult tissue. Galectin-7, a member of this family, contributes to different events associated with the differentiation and development of pluristratified epithelia. It is also associated with epithelial cell migration, which plays a crucial role in the re-epithelialization process of corneal or epidermal wounds. In addition, recent evidence indicates that galectin-7, designated as the product of the p53-induced gene 1 (PIG1), is a regulator of apoptosis through JNK activation and mitochondrial cytochrome c release. Defects in apoptosis constitute one of the major hallmarks of human cancers, and galectin-7 can act as either a positive or a negative regulatory factor in tumour development, depending on the histological type of the tumour. [ABSTRACT FROM AUTHOR]