scholarly journals Increase of MAL-II Binding Alpha2,3-Sialylated Glycan Is Associated with 5-FU Resistance and Short Survival of Cholangiocarcinoma Patients

Medicina ◽  
2019 ◽  
Vol 55 (12) ◽  
pp. 761 ◽  
Author(s):  
Sasiprapa Wattanavises ◽  
Atit Silsirivanit ◽  
Kanlayanee Sawanyawisuth ◽  
Ubon Cha’on ◽  
Sakda Waraasawapati ◽  
...  

Background and objectives: Sialylation plays important roles in tumor progression. Our present study aimed to demonstrate the alteration of sialylation and its role in cholangiocarcinoma (CCA). Materials and Methods: The α2,3- and α2,6-sialylation in CCA tissue was analyzed by lectin-histochemistry using Maackia amurensis lectin-II (MAL-II) and Sambucus nigra agglutinin (SNA). CCA cell lines were treated with the pan-sialylation inhibitor 3Fax-peracetyl-Neu5Ac (3F-Sia) followed by proliferation and chemosensitivity assays. Results: MAL-II binding α2,3-Sialylated Glycan (MAL-SG) and SNA binding α2,6-Sialylated Glycan (SNA-SG) were both elevated in CCA compared with hyperplastic/dysplastic (HP/DP) and normal bile ducts (NBD). The positive staining for MAL-SG or SNA-SG were found in 82% (61/74) of the CCA cases. Higher expression of MAL-SG in CCA was associated with shorter survival of the patients. The median survival of patients with high and low MAL-SG were 167 and 308 days, respectively, with overall survival of 233 days, suggesting the involvement of MAL-SG in CCA progression. MAL-SG expression of CCA cell lines was markedly decreased after treatment with 3F-Sia for 48 to 72 h. While proliferation of CCA cells were not affected by 3F-Sia treatment, their susceptibility to 5-fluorouracil (5-FU) was significantly enhanced. These results suggest that sialylation is involved in the development of 5-FU resistance and the sialylation inhibitor 3F-Sia can be used as a chemosensitizer for CCA. Conclusions: Sialylation is critically involved in the development of chemoresistance of CCA, and sialylation inhibitors may be used as a chemosensitizer in CCA treatment.

2002 ◽  
Vol 303 (1) ◽  
pp. 98-104 ◽  
Author(s):  
Els C.M. Brinkman-Van der Linden ◽  
Justin L. Sonnenburg ◽  
Ajit Varki

2001 ◽  
Vol 46 (No. 3) ◽  
pp. 70-74 ◽  
Author(s):  
L. Vajner ◽  
V. Vortel ◽  
A. Brejcha

: During the 18-year period (1974–1991), the lymphocytic thyroiditis with the finding of serum autoantibodies against thyroglobulin was diagnosed in 180 Beagle dogs (92 males and 88 females). In 107 of them (56 males and 51 females), hyperplasia of parafollicular cells was concurrently encountered. In further 11 cases (3 males and 8 females), solid cellular structures were found in the thyroid parenchyma, in 4 females combined with unilocular or multilocular lymphoepithelial cysts. Grimelius stain revealed the presence of parafollicular cells even at the periphery of cellular nests. Using the lectin histochemistry with Maackia amurensis agglutinin (MAA),Sambucus nigra agglutinin (SNA) and Tritrichomonas mobilensis lectin (TML), the presence of sialylated molecules was demonstrated in the cell membranes and perinuclear cytoplasmic regions of parafollicular cells that formed hyperplastic nodules or were interspersed in “solid cell nests”.


2001 ◽  
Vol 49 (10) ◽  
pp. 1311-1319 ◽  
Author(s):  
Yuji Sato ◽  
Yoshihiro Akimoto ◽  
Hayato Kawakami ◽  
Hiroshi Hirano ◽  
Tamao Endo

The histochemical distribution of sialoglycoconjugates in the CA1 region in the hippocampus formation of 9-week-old rats and 30-month-old rats was examined using electron microscopy in combination with two lectins, Maackia amurensis lectin, specific for Siaα2–3Gal, and Sambucus sieboldiana agglutinin, specific for Siaα2–6Gal. Each lectin stained the plasma membranes of pyramidal cells, indicating that the Siaα2–3Gal and Siaα2–6Gal groups were expressed on their plasma membranes. These lectins also bound to synapses in the stratum lacunosum moleculare. The staining intensity of the lectins in the synapses in these layers was downregulated in the 30-month-old rats. These results indicated that both the Siaα2–3Gal and Siaα2–6Gal groups are expressed on these synapses and that the expression of these sialyl linkages decreases in the aged brain.


2021 ◽  
pp. 112949
Author(s):  
Siyaporn Putthisen ◽  
Atit Silsirivanit ◽  
Orasa Panawan ◽  
Akiko Niibori-Nambu ◽  
Yuki Nishiyama-Ikeda ◽  
...  

2021 ◽  
Vol 38 (3) ◽  
pp. 266-271
Author(s):  
Yosun MATER ◽  
Günnur DEMİRCAN

The importance of early cancer diagnosis has led to development of many different diagnostic methods. In this context, the studies investigating the presence and amount of sugar residues to use as indicators in the identification of cancer cell type have become prominent. In the present study, sialic acids found on the membrane surfaces of ER (+) MCF-7 and ER (-) MDA-MB-231 breast cancer cell lines were labeled using three-dimensional (3D) cell culture (Spheroid) model as the closest method to the patient sample, thus its natural environment, among the cell culture methods. These sugar units that play a role in regulation of important immune characteristics such as recognition, binding and metastasis were made visualizable by applying fluorescent-labeled lectins such as FITC-(Wheat Germ Agglutinin) specifically binding to sialic acid units (GlcNAc, Neu5Ac) including particularly ß-GlcNAc and FITC-(Maackia Amurensis-Lectin-1) specifically binding to Galß4GlcNAc type sialic acids. These glycan units were specifically labeled with FITC-(Maackia Amurensis-Lectin-1) and FITC- (Wheat Germ Agglutinin) and radiation intensities were analyzed relatively. The two different breast cancer cell cultures were compared with respect to change in the amounts of sialic acid residues containing α-2,3- and α-2,6 bonds using fluorescent-labeled lectins. In the present study, we have performed a precise, accurate and rapid determination of the sugar content in the different breast cancer cell surface lines by means of fluorescent-labeled lectins and carried out a relative comparison between the micrographs.


1993 ◽  
Vol 41 (9) ◽  
pp. 1303-1310 ◽  
Author(s):  
V Speirs ◽  
S Eich-Bender ◽  
C R Youngson ◽  
E Cutz

Expression of cell surface antigens of the neural cell adhesion molecule (N-CAM) class was recently shown to be shared by both fetal and neoplastic neuroendocrine cells, including those of the lung. We investigated the expression and localization of MOC-1 antigen on small-cell (neuroendocrine) lung carcinoma cell lines with immunohistochemical methods at the light (LM) and electron microscopy (EM) level and by Western blot. At LM level, using monoclonal antibody (MAb) MOC-1 with the ABC method and immunofluorescence, positive staining was observed on surfaces of cells from all tumor lines examined. Strongest immunostaining was found on cell surfaces of pulmonary small-cell carcinoma-derived cell line NCI-H69 with the majority of cells showing positive staining. An adherent variant of NCI-H69 cell line, H69V, exhibited positive staining in about 60% of cells, whereas only occasional cells of NCI-H727 cell line derived from pulmonary carcinoid tumor were positive for MOC-1 antigen. Western blot analysis confirmed these findings, showing a strong MOC-1-specific band in cell extracts of NCI-H69, with weaker band densities for H69V and NCI-H727. Immunoelectron microscopy (IEM) revealed that MOC-1 was not uniformly distributed on the outer surface of plasma membrane; immunogold particles appeared concentrated in areas of thick cell surface "fuzz" coating, surface microvilli, and in areas of cell-cell contact. In some cells, areas of plasma membrane invaginations and a few intracytoplasmic vesicles were also labeled, suggesting endocytosis. Surface labeling for SEM confirmed the finding of more dense labeling over the microvilli, cell membrane folds, and in areas of cell-cell contact. The cell lines derived from pulmonary neuroendocrine cell tumors can provide a useful model to study the role and function of neural adhesion molecules in pulmonary neoplasia and during lung development.


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