scholarly journals Increased Sialylation of Anti-Thomsen-Friedenreich Antigen (CD176) Antibodies in Patients with Gastric Cancer: A Diagnostic and Prognostic Potential

2014 ◽  
Vol 2014 ◽  
pp. 1-11 ◽  
Author(s):  
Oleg Kurtenkov ◽  
Jelena Izotova ◽  
Kersti Klaamas ◽  
Boris Sergeyev

Aim. To study whether alterations in the sialylation of antibodies (Ab) specific to the Thomsen-Friedenreich (TF) glycotope have a diagnostic and prognostic potential in gastric cancer.Methods. Serum samples were taken from patients with gastric carcinoma(n=142)and controls(n=61). The level of TF-specific antibodies and their sialylation was detected using ELISA with synthetic TF-polyacrylamide conjugate as antigen and sialic acid-specificSambucus nigra agglutinin(SNA).Results. The level of TF-specific IgM was significantly decreased in cancer compared with controls(P≤0.001). Cancer patients showed a higher level of SNA binding to anti-TF IgM and IgA(P≤0.001)irrespective of disease stage, tumor morphology, and gender. Changes in the SNA/Ab index demonstrated moderate sensitivity (66–71%) and specificity (60–73%) for stomach cancer. The best diagnostic accuracy (100%) was achieved in 29% patients with high SNA binding and low anti-TF IgM level. This subset of patients demonstrated the poorest survival.Conclusion. Our findings are the first evidence that the increased sialylation of TF-specific Abs combined with a low level of anti-TF IgM is strongly linked to gastric cancer and patients survival, which can be used as a novel biomarker for cancer detection and prognosis.

2015 ◽  
Vol 2015 ◽  
pp. 1-8 ◽  
Author(s):  
Oleg Kurtenkov ◽  
Kersti Klaamas

Aim. To determine whether the naturally occurring Thomsen-Friedenreich (TF) antigen-specific antibodies differ in avidity between cancer patients and controls to find a novel biomarker for stomach cancer.Methods. Serum samples were taken from patients with cancer and controls. The level of TF-specific antibodies and their sialylation were determined using ELISA with synthetic TF-polyacrylamide conjugate as antigen and sialic acid-specificSambucus nigraagglutinin (SNA). The avidity was determined using ammonium thiocyanate as a chaotrope.Results. A significantly higher SNA lectin binding to anti-TF antibodies was found in cancer patients irrespective of disease stage. The avidity of only IgM TF-specific antibodies was significantly higher in cancer patients compared to controls. The SNA-positive anti-TF antibodies of cancer patients showed a significantly higher avidity,P<0.001. The sensitivity and specificity of this increase for gastric cancer were 73.53% and 73.08%, respectively, with a 73.2% diagnostic accuracy. The higher avidity of SNA-reactive anti-TF antibodies was associated with a benefit in survival of stage 3 cancer patients.Conclusion. The SNA-reactive TF-specific antibodies display a significantly higher avidity in gastric cancer patients compared to controls, which can be used as a potential serologic biomarker for gastric cancer. It appears that IgM is the main target responsible for the above changes.


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

1991 ◽  
Vol 278 (3) ◽  
pp. 667-671 ◽  
Author(s):  
L Mach ◽  
W Scherf ◽  
M Ammann ◽  
J Poetsch ◽  
W Bertsch ◽  
...  

A previously unknown haemagglutinin, named Sambucus nigra agglutinin-III (SNA-III), has been purified from the fruit of the elder (Sambucus nigra). Whereas elder bark agglutinin I (SNA-I) is highly specific for terminal alpha 2,6-linked sialic acid residues, SNA-III displays a high affinity for oligosaccharides containing exposed N-acetylgalactosamine and galactose residues. Different N-terminal sequences and the amino acid composition distinguish the fruit lectin from elder bark agglutinin II (SNA-II), which shows a similar carbohydrate specificity. The 40-fold higher affinity of SNA-III for asialofetuin than for human asialo-alpha 1-acid glycoprotein and human asialotransferrin respectively suggests a preference for O-linked glycans. SNA-III occurs mainly as a monomeric glycoprotein, but tends to form di- and oligo-meric aggregates. This aggregation seems to mediate the multivalent interaction, leading to agglutination. SDS/PAGE revealed two major polypeptides with apparent molecular masses of 32 and 33 kDa respectively. This heterogeneity is probably a result of proteolysis in the C-terminal region. Binding to concanavalin A and susceptibility to peptide: N-glycosidase F indicated the presence of N-glycosidically linked oligosaccharides.


2003 ◽  
Vol 22 (4) ◽  
pp. 319-323 ◽  
Author(s):  
Ivana Petrovic ◽  
Svetlana Savin-Zegarac ◽  
Ivona Baricevic ◽  
Dubravka Cvejic

The structure of carbohydrate moiety of purified thyroxine-binding globulin (TBG) was examined by lectin blot and isoelectric focusing (IEF). In lectin blot, TBG reacted positively with the following lectins: Sambucus nigra agglutinin (SNA I), Ricinus commuais agglutinin (RCA I), wheat germ lectin (WGA), phytoheamagglutinin (PHA) and pea lectin (PSA). The obtained results indicate that purified TBG contains N-linked oligosaccharide chains consisting of mannose, galactose, N-acetylglucosamine and sialic acid. Isoelectric focusing of TBG at pl 4.2-4.6 revealed three bands, which confirmed that isolated TBG had retained its structure with?out desialylation. Lectin blot analysis and IEF can be considered to be useful tools in the study of TBG glycosylation.


2018 ◽  
Vol 2018 ◽  
pp. 1-8 ◽  
Author(s):  
Oleg Kurtenkov ◽  
Kaire Innos ◽  
Boris Sergejev ◽  
Kersti Klaamas

Alterations in the glycosylation of serum total immunoglobulins show these antibodies to have a diagnostic potential for cancer but the disease-related Abs to the tumor-associated antigens, including glycans, have still poorly been investigated in this respect. We analysed serum samples from patients with breast carcinoma (n = 196) and controls (n = 64) for the level of Thomsen-Friedenreich (TF) antigen-specific antibody isotypes, their sialylation, interrelationships, and the avidity by using ELISA with the synthetic TF-polyacrylamide conjugate as an antigen and the sialic acid-specificSambucus nigraagglutinin (SNA) and ammonium thiocyanate as a chaotrope. An increased sialylation of IgG and IgM, but a lower SNA reactivity of IgA TF antibodies, and a higher level and avidity of the TF-specific IgA were found in cancer patients. Other cancer-related signatures were the highly significant increase of the IgG/IgA ratio and the very low SNA/IgA index in cancer, including patients with an early stage of the disease. These changes showed a good diagnostic potential with about 80% accuracy. Thus, the level of naturally occurring anti-TF antigen antibodies, their sialylation profile, isotype distribution, and avidity displayed cancer-specific changes that could serve as novel noninvasive Ab-based biomarkers for early breast cancer.


2018 ◽  
Vol 40 (4) ◽  
pp. 323-327 ◽  
Author(s):  
F Tas ◽  
S Karabulut ◽  
K Erturk ◽  
D Duranyildiz

Aim: Caveolin-1 plays a significant role in the pathogenesis of various carcinomas and its expression affects the survival of cancer patients. However, the molecular function of caveolin-1 and its possible clinical importance has remained uncertain in gastric cancer. No clinical trial has examined serum caveolin-1 levels in gastric cancer patients so far, instead all available results were provided from studies conducted on tissue samples. In the current study, we analyzed the soluble serum caveolin-1 levels in gastric cancer patients, and specified its associations with the clinical factors and prognosis. Material and Methods: Sixty-three patients with pathologically confirmed gastric cancer were enrolled into the trial. Serum caveolin-1 concentrations were detected by ELISA method. Thirty healthy subjects were also included in the study. Results: The median age of patients was 62 years, ranging from 28 to 82 years. The serum caveolin-1 levels in gastric cancer patients were significantly higher than those in control group (p < 0.001). The common clinical parameters including patient age, sex, lesion localization, histopathology, histological grade, disease stage, and various serum tumor markers (e.g. LDH, CEA, and CA 19.9) were not found to be associated with serum caveolin-1 levels (p > 0.05). Similarly, no correlation existed between serum caveolin-1 concentration and chemotherapy responsiveness (p = 0.93). Furthermore, serum caveolin-1 level was not found to have a prognostic role (p = 0.16). Conclusion: Even though it is neither predictive nor prognostic, serum caveolin-1 level may be a valuable diagnostic indicator in patients with gastric cancer. Key


2021 ◽  
Vol 22 (13) ◽  
pp. 6972
Author(s):  
Ilona Sadok ◽  
Katarzyna Jędruchniewicz ◽  
Karol Rawicz-Pruszyński ◽  
Magdalena Staniszewska

Metabolites and enzymes involved in the kynurenine pathway (KP) are highly promising targets for cancer treatment, including gastrointestinal tract diseases. Thus, accurate quantification of these compounds in body fluids becomes increasingly important. The aim of this study was the development and validation of the UHPLC-ESI-MS/MS methods for targeted quantification of biologically important KP substrates (tryptophan and nicotinamide) and metabolites(kynurenines) in samples of serum and peritoneal fluid from gastric cancer patients. The serum samples were simply pretreated with trichloroacetic acid to precipitate proteins. The peritoneal fluid was purified by solid-phase extraction before analysis. Validation was carried out for both matrices independently. Analysis of the samples from gastric cancer patients showed different accumulations of tryptophan and its metabolites in different biofluids of the same patient. The protocols will be used for the evaluation of tryptophan and kynurenines in blood and peritoneal fluid to determine correlation with the clinicopathological status of gastric cancer or the disease’s prognosis.


2021 ◽  
Author(s):  
Seiichiro Abe ◽  
Juntaro Matsuzaki ◽  
Kazuki Sudo ◽  
Ichiro Oda ◽  
Hitoshi Katai ◽  
...  

Abstract Background The aim of this study was to identify serum miRNAs that discriminate early gastric cancer (EGC) samples from non-cancer controls using a large cohort. Methods This retrospective case–control study included 1417 serum samples from patients with EGC (seen at the National Cancer Center Hospital in Tokyo between 2008 and 2012) and 1417 age- and gender-matched non-cancer controls. The samples were randomly assigned to discovery and validation sets and the miRNA expression profiles of whole serum samples were comprehensively evaluated using a highly sensitive DNA chip (3D-Gene®) designed to detect 2565 miRNA sequences. Diagnostic models were constructed using the levels of several miRNAs in the discovery set, and the diagnostic performance of the model was evaluated in the validation set. Results The discovery set consisted of 708 samples from EGC patients and 709 samples from non-cancer controls, and the validation set consisted of 709 samples from EGC patients and 708 samples from non-cancer controls. The diagnostic EGC index was constructed using four miRNAs (miR-4257, miR-6785-5p, miR-187-5p, and miR-5739). In the discovery set, a receiver operating characteristic curve analysis of the EGC index revealed that the area under the curve (AUC) was 0.996 with a sensitivity of 0.983 and a specificity of 0.977. In the validation set, the AUC for the EGC index was 0.998 with a sensitivity of 0.996 and a specificity of 0.953. Conclusions A novel combination of four serum miRNAs could be a useful non-invasive diagnostic biomarker to detect EGC with high accuracy. A multicenter prospective study is ongoing to confirm the present observations.


2020 ◽  
Vol 41 (S1) ◽  
pp. s380-s380
Author(s):  
Sree Kalpana Mohankumar ◽  
Vishweshwarayya Hiremath ◽  
Rajashree Koppad

Background: Countries that have good rubella surveillance, report ∼10,000–20,000 rubella cases annually. In India, not many cases of rubella are reported. The Hebballi Agasi ward of Dharwad district in Karnataka state, India, reported rubella cases on the last week of January 2015. Objective: We investigated the outbreak by time, place, person, and clinical symptoms. Methods: We performed a cross-sectional study. We defined a case as any resident of Heballi Agasi who had fever and rash, with or without lymphadenopathy, arthralgia, conjunctivitis, coryza, and cough, after December 15, 2014. We collected sociodemographic details and clinical symptoms of patients. We collected 5 serum samples and sent them to the National Measles Laboratory, Bangalore. We tested for measles and rubella antibodies. We drew an epidemic curve and a spot map. We computed mean age of cases, and we calculated attack rates by mean age and gender. We calculated proportions to describe clinical symptoms, and we interviewed stakeholders regarding rubella vaccination. We continued surveillance until March 2015. Results: The population of Heballi Agasi was 1,458. We identified 15 rubella cases (9 girls and 6 boys). The outbreak lasted between December 10, 2014, and February 21, 2015, with a peak on January 16, 2015. The overall attack rate was 1% (15 of 1,458). The mean age of the cases was 6 years (range, 1–23). The attack rate was high (7.7%) among those aged 1–6 years (11 of 143). The attack rate among those aged >6 years was 0.3% (4 of 1,315). In addition to fever and rash, 93% of cases (14 of 15) had coryza, 47% had cough (7 of 15), and 40% had conjunctivitis (6 of 15). Lymphadenopathy was present in only 1 case (1 of 15), and arthralgia was absent among all 15 cases. There was no death among the cases. All 5 sera were positive for rubella and negative for measles. Rubella vaccination was not given for any of the cases because no rubella vaccination is provided in the routine immunization program. Conclusions: There was a rubella outbreak in Heballi Agasi ward. Children aged 1–6 years were most affected. We recommend rubella vaccination in the routine immunization.Funding: NoneDisclosures: None


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