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1.
Biomed Pharmacother ; 174: 116619, 2024 May.
Artigo em Inglês | MEDLINE | ID: mdl-38643541

RESUMO

Glycosylation of cancerous epithelial MUC1 protein is specifically altered in comparison to that which is presented by healthy cells. One of such changes is appearing tumor-associated carbohydrate antigens (TACAs) which are rare in normal tissues and are highly correlated with poor clinical outcomes and cancer progression. This review summarizes and describes the role of Tn, T antigens, their sialylated forms as well as fucosylated Lewis epitopes in different aspects of tumor development, progression, and metastasis. Finally, applications of MUC1 glycan epitopes as potential targets for therapeutic strategy of cancers are notified. One of the novelties of this review is presentation of TACAs as inherently connected with MUC1 mucin.


Assuntos
Antígenos Glicosídicos Associados a Tumores , Mucina-1 , Neoplasias , Humanos , Mucina-1/metabolismo , Neoplasias/metabolismo , Neoplasias/imunologia , Neoplasias/patologia , Animais , Antígenos Glicosídicos Associados a Tumores/metabolismo , Antígenos Glicosídicos Associados a Tumores/imunologia , Glicosilação , Epitopos/imunologia
2.
Cancers (Basel) ; 15(19)2023 Sep 29.
Artigo em Inglês | MEDLINE | ID: mdl-37835499

RESUMO

Integrins play a fundamental role in the migration and invasiveness of glioblastoma (GBM) cells, making them suitable targets for innovative cancer therapy. The aim of this study was to evaluate the effect of the RGD homodimeric disintegrin VLO4, isolated from Vipera lebetina obtusa venom, on the adhesion, spreading, migration, and survival of LBC3, LN18, and LN229 cell lines. This disintegrin, as a potent antagonist for α5ß1 integrin, showed pro-adhesive properties for these cell lines, the highest for LN229 and the lowest for LBC3. Glioblastoma cells displayed significant differences in the spreading on the immobilized VLO4 and the natural α5ß1 integrin ligand, fibronectin. Solubilized VLO4 showed different cytotoxicity and pro-apoptotic properties among tested cell lines, with the highest against LN18 and none against LN229. Moreover, VLO4 revealed an inhibitory effect on the migration of LBC3 and LN18 cell lines, in contrast to LN229 cells, which were not sensitive to this disintegrin. However, LN229 migration was impaired by VLO5, a disintegrin antagonistic to integrin α9ß1, used in combination with VLO4. A possible mechanism of action of VLO4 may be related to the downregulation of α5ß1 integrin subunit expression, as revealed by Western blot. VLO4 also inhibited cell proliferation and induced caspase-dependent apoptosis in LBC3 and LN18 cell lines. These results indicate that targeting α5ß1 integrin by related VLO4 compounds may be useful in the development of integrin-targeted therapy for glioblastoma.

3.
Int J Mol Sci ; 24(17)2023 Aug 22.
Artigo em Inglês | MEDLINE | ID: mdl-37685842

RESUMO

Specific changes in mucin-type O-glycosylation are common for many cancers, including gastric ones. The most typical alterations include incomplete synthesis of glycan structures, enhanced expression of truncated O-glycans (Tn, T antigens and their sialylated forms), and overexpression of fucosylation. Such altered glycans influence many cellular activities promoting cancer development. Tiliroside is a glycosidic dietary flavonoid with pharmacological properties, including anti-cancer. In this study, we aim to assess the effect of the combined action of anti-MUC1 and tiliroside on some cancer-related factors in AGS gastric cancer cells. Cancer cells were treated with 40, 80, and 160 µM tiliroside, 5 µg/mL anti-MUC1, and flavonoid together with mAb. Real-Time PCR, ELISA, and Western blotting were applied to examine MUC1 expression, specific, tumor-associated antigens, enzymes taking part in their formation, Gal-3, Akt, and NF-κB. MUC1 expression was significantly reduced by mAb action. The combined action of anti-MUC1 and tiliroside was more effective in comparison with monotherapy in the case of C1GalT1, ST3GalT1, FUT4, Gal-3, NF-κB, Akt mRNAs, and Tn antigen, as well as sialyl T antigen expression. The results of our study indicate that applied combined therapy may be a promising anti-gastric cancer strategy.


Assuntos
NF-kappa B , Neoplasias Gástricas , Humanos , Anticorpos Monoclonais/farmacologia , Flavonoides , Fucosiltransferases , Proteínas Proto-Oncogênicas c-akt , Neoplasias Gástricas/imunologia , Neoplasias Gástricas/terapia , Mucina-1/imunologia
4.
Cancers (Basel) ; 15(10)2023 May 09.
Artigo em Inglês | MEDLINE | ID: mdl-37345016

RESUMO

Aberrant glycosylation of cell surface proteins is a very common feature of many cancers. One of the glycoproteins, which undergoes specific alterations in the glycosylation of tumor cells is epithelial MUC1 mucin, which is highly overexpressed in the malignant state. Such changes lead to the appearance of tumor associated carbohydrate antigens (TACAs) on MUC1, which are rarely seen in healthy cells. One of these structures is the Thomsen-Friedenreich disaccharide Galß1-3GalNAc (T or TF antigen), which is typical for about 90% of cancers. It was revealed that increased expression of the T antigen has a big impact on promoting cancer progression and metastasis, among others, due to the interaction of this antigen with the ß-galactose binding protein galectin-3 (Gal-3). In this review, we summarize current information about the interactions between the T antigen on MUC1 mucin and Gal-3, and their impact on cancer progression and metastasis.

5.
Int J Mol Sci ; 23(15)2022 Aug 02.
Artigo em Inglês | MEDLINE | ID: mdl-35955735

RESUMO

Abnormal glycosylation of cancer cells is considered a key factor of carcinogenesis related to growth, proliferation, migration and invasion of tumor cells. Many plant-based polyphenolic compounds reveal potential anti-cancer properties effecting cellular signaling systems. Herein, we assessed the effects of phenolic acid, p-coumaric acid and flavonoids such as kaempferol, astragalin or tiliroside on expression of selected cancer-related glycoforms and enzymes involved in their formation in AGS gastric cancer cells. The cells were treated with 80 and 160 µM of the compounds. RT-PCR, Western blotting and ELISA tests were performed to determine the influence of polyphenolics on analyzed factors. All the examined compounds inhibited the expression of MUC1, ST6GalNAcT2 and FUT4 mRNAs. C1GalT1, St3Gal-IV and FUT4 proteins as well as MUC1 domain, Tn and sialyl T antigen detected in cell lysates were also lowered. Both concentrations of kaempferol, astragalin and tiliroside also suppressed ppGalNAcT2 and C1GalT1 mRNAs. MUC1 cytoplasmic domain, sialyl Tn, T antigens in cell lysates and sialyl T in culture medium were inhibited only by kaempferol and tiliroside. Nuclear factor NF-κB mRNA expression decreased after treatment with both concentrations of kaempferol, astragalin and tiliroside. NF-κB protein expression was inhibited by kaempferol and tiliroside. The results indicate the rationality of application of examined polyphenolics as potential preventive agents against gastric cancer development.


Assuntos
Quempferóis , Neoplasias Gástricas , Ácidos Cumáricos , Flavonoides/farmacologia , Fucosiltransferases , Humanos , Quempferóis/farmacologia , NF-kappa B/metabolismo , Neoplasias Gástricas/patologia
6.
Transl Oncol ; 18: 101348, 2022 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-35121220

RESUMO

The membrane-bound MUC1 mucin is overexpressed and aberrantly glycosylated in many epithelium origin cancers. One of the promising strategies in cancer therapy is combining monoclonal antibodies against cancer related antigens, like MUC1, with chemotherapeutics. In the study we evaluated the potency of cisplatin (cisPt), two pyrazole-platinum(II) complexes PtPz4, PtPz6, and anti-MUC1 mAb applied as monotherapy, as well as the chemotherapeutics administrated with antibody, towards apoptotic response and cancer-related carbohydrate antigens (TACAs) in DLD-1 and HT-29 colon cancer cells. To assess the impact of the tested compounds on the examined factors flow cytometry, RT-PCR, Western blotting and ELISA were utilized. The combined therapy was more potent than monotherapy towards Bcl-2, Bid, caspases and TACAs of both cell lines. Combined therapy applied in DLD-1 cells induced apoptosis, was more effective than monotherapy in relation to p53, Bcl-xL, Bax, and Bim. In HT-29 cells, anti-MUC1 administrated with the drugs was more potent than monotherapy towards Bad. The proposed anti-MUC1/cisPt and pyrazole-platinum(II) complexes PtPz4, PtPz6 combined therapy may be promising anti-colon cancer therapy.

7.
Pharmaceuticals (Basel) ; 14(10)2021 Sep 25.
Artigo em Inglês | MEDLINE | ID: mdl-34681197

RESUMO

Afzelin demonstrates anti-inflammatory and anti-cancer properties. Our purpose was to assess its influence on apoptosis, Bax, caspases, MUC1, cancer-related carbohydrate antigens, enzymes participating in their formation, and galectin-3 in AGS gastric cancer cells. A total of 60 and 120 µM afzelin was used in all experiments. Flow cytometry was applied to determine apoptotic response. Western blotting and RT PCR were used to detect the expression of mentioned factors. Flavonoid at higher concentration revealed slight apoptotic respond. Bax, caspase-3, -8, -9 increased upon afzelin action. Stimulatory effect of the flavonoid on MUC1 cytoplasmic tail and extracellular domain in cell lysates and on MUC1 gene was revealed. MUC1 release into the culture medium was inhibited by the flavonoid. The 60 µM afzelin dose stimulated GalNAcTL5 protein expression and inhibited C1GalT1. ST6GalNAcT mRNA was inhibited by both flavonoid doses. ST3GalT was inhibited by 120 µM afzelin on protein and mRNA level. Lewisa/b protein was reduced by both afzelin concentrations. FUT3 and FUT4 mRNA was inhibited by 120 µM dose of afzelin. Galectin-3 protein increased in cell lysates and decreased in culture supernatant by 60 and 120 µM flavonoid. Galectin-3 gene expression was stimulated by two used concentrations of afzelin in comparison to control. We conclude that afzelin can be considered as the potential anti-cancer agent, supporting conventional cancer treatment.

8.
Pharmaceutics ; 13(7)2021 Jun 26.
Artigo em Inglês | MEDLINE | ID: mdl-34206951

RESUMO

MUC1 mucin is a transmembrane glycoprotein aberrantly overexpressed and underglycosylated in most epithelium origin cancers. Combining chemotherapeutics with monoclonal antibodies toward cancer-related antigens is one of the new strategies in cancer therapies. In this study, we assessed the effectiveness of 10 µM cisplatin (cisPt), two pyrazole-platinum(II) complexes (PtPz4 and PtPz6), and 5 µg/mL anti-MUC1 used as monotherapy, as well as cisplatin and its derivatives combined with mAb on apoptotic response and specific cancer-related sugar antigens in AGS gastric cancer cells. Flow cytometry, RT-PCR, Western blotting, and ELISA tests were applied to determine the influence of examined compounds on analyzed factors. PtPz6 combined with anti-MUC1 revealed the strongest apoptotic response compared to control and monotherapy. The combined action of both cisPt derivatives and anti-MUC1 was more effective than monotherapy in relation to Bad, Bcl-xL, Bcl-2, caspase-9, caspase-3, as well as pro- and cleaved caspase-3 protein, and T, sialyl Tn sugar antigens in cell lysates, and Tn, T, sialyl Tn, sialyl T antigens in culture medium. Additionally, PtPz4 administrated with mAb was revealed to be more potent than used alone with regard to Bax protein and Bid expression, and PtPz6 used in complex with anti-MUC1 revealed more efficient action towards Akt and sialyl T antigen expression. These data indicate the rationality of the potential application of combined treatment of anti-MUC1 and cisPt derivatives in gastric cancer therapy.

9.
Int J Oncol ; 59(3)2021 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-34278474

RESUMO

Mucin 1 (MUC1) is a membrane­bound, highly glycosylated protein that is overexpressed in all stages of malignant transformation. Overexpression of MUC1 together with loss of polarization and hypoglycosylation are associated with resistance to apoptosis, which is the process that results in efficient removal of damaged cells. Inhibition of the apoptotic process is responsible for tumor development, tumor progression and drug resistance. MUC1 is considered as an oncogenic molecule that is involved in various signaling pathways responsible for the regulation of apoptosis. Based on this, the aim of the present study was to discuss the involvement of MUC1 in the divergent mechanisms regulating programmed cell death.


Assuntos
Mucina-1/metabolismo , Neoplasias/metabolismo , Regulação para Cima , Apoptose , Progressão da Doença , Regulação Neoplásica da Expressão Gênica , Glicosilação , Humanos , Transdução de Sinais
10.
Eur J Pharmacol ; 902: 174119, 2021 Jul 05.
Artigo em Inglês | MEDLINE | ID: mdl-33930385

RESUMO

MUC1 seems to be promising target in cancer cells due to its abundant and specifically altered expression as well as differential distribution pattern relative to normal tissues. Rosmarinic acid (RA) is a natural, polyphenolic compound with pharmacological activities, including anti-cancer. Herein, we aim to explore the effect of combined action of anti-MUC1 and RA on selected cancer-related factors in AGS gastric cancer cells. Cancer cells were treated with 100, 200 µM rosmarinic acid, 5 µg/ml anti-MUC1 and acid together with antibody. Western blotting, ELISA and RT-PCR were used to assess the expression of MUC1, selected sugar antigens, enzymes participating in protein glycosylation, Gal-3, p53, pro- and anti-apoptotic factors, and caspases-3,-8,-9 in cancer cells. MUC1 mRNA was significantly suppressed by combined action of anti-MUC1 and RA. Such treatment markedly inhibited expression of cancer-related Tn, T, sialyl Tn, sialyl T, and fucosylated sugar antigens as well as mRNA expression of enzymes participating in their formation: ppGalNAcT2, C1GalT1, ST6GalNAcT2, ST3GalT1 and FUT4. C1GalT1 was suppressed also on protein level. Gal-3, factor likely participating in metastasis, was significantly suppressed on mRNA level by RA administrated with anti-MUC1. Pro-apoptotic Bax protein and Bad mRNA were significantly induced, and anti-apoptotic Bcl-2 mRNA expression was inhibited by such treatment. Combined action of mAb and RA markedly increased caspase-9 mRNA expression. Results of the study indicate that combined action of anti-MUC1 and RA is more effective than monotherapy in relation to examined cancer related factors. Such treatment can be considered as new, promising strategy in gastric cancer therapy.


Assuntos
Antineoplásicos Imunológicos/farmacologia , Antineoplásicos/farmacologia , Cinamatos/farmacologia , Depsídeos/farmacologia , Mucina-1/imunologia , Mucina-1/metabolismo , Neoplasias Gástricas/tratamento farmacológico , Biomarcadores Tumorais/antagonistas & inibidores , Biomarcadores Tumorais/metabolismo , Proteínas Sanguíneas/genética , Proteínas Sanguíneas/metabolismo , Caspase 3/genética , Caspase 3/metabolismo , Caspase 8/genética , Caspase 8/metabolismo , Caspase 9/genética , Caspase 9/metabolismo , Linhagem Celular Tumoral , Sobrevivência Celular/efeitos dos fármacos , Quimioterapia Combinada , Galectinas/genética , Galectinas/metabolismo , Glicosilação/efeitos dos fármacos , Glicosiltransferases/genética , Glicosiltransferases/metabolismo , Humanos , Mucina-1/genética , Proteínas Proto-Oncogênicas c-bcl-2/genética , Proteínas Proto-Oncogênicas c-bcl-2/metabolismo , Neoplasias Gástricas/imunologia , Neoplasias Gástricas/metabolismo , Neoplasias Gástricas/patologia , Proteína Supressora de Tumor p53/genética , Proteína Supressora de Tumor p53/metabolismo , Proteína X Associada a bcl-2/genética , Proteína X Associada a bcl-2/metabolismo , Proteína de Morte Celular Associada a bcl/genética , Proteína de Morte Celular Associada a bcl/metabolismo , Proteína bcl-X/genética , Proteína bcl-X/metabolismo , Ácido Rosmarínico
11.
Biomed Rep ; 14(2): 19, 2021 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-33335725

RESUMO

Luteolin is a natural flavonoid possessing certain beneficial pharmacological properties, including anti-oxidant, anti-inflammatory, anti-microbial and anti-cancer properties. The majority of types of gastric cancer with chronic gastritis are caused by infection with Helicobacter pylori (H. pylori). The present study evaluated the effect of luteolin on a number of selected factors that are potentially involved in gastric cancer development. The study was performed using gastric cancer CRL-1739 cells treated with 30 µM luteolin and H. pylori alone or combined. ELISA and reverse transcription PCR were used to assess the expression levels of MUC1, GalNAcα-R (Tn antigen) and NeuAcα2-3Galß1-3GalNAc-R (sT antigen), ADAM-17, IL-8, IL-10 and NF-κB. H. pylori and luteolin independently and in combination significantly reduced the expression levels of the extracellular domain of MUC1 in gastric cancer cells compared with the untreated control cells. ADAM-17 expression was reduced by treatment with the pathogen and luteolin. Additionally, both factors reduced sT antigen expression. Treatment with 30 ≤M luteolin significantly induced IL-8 expression at the mRNA and protein level, and the mRNA expression levels of IL-10 and NF-κB compared with the control. Both H. pylori and luteolin induced IL-8 protein expression. The present preliminary results suggest that luteolin may be used to treat patients with gastric cancer.

12.
Adv Med Sci ; 63(1): 205-211, 2018 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-29197783

RESUMO

PURPOSE: Attachment of Helicobacter pylori to the mucous epithelial cells and the mucous layer is said to be a crucial step for infection development. Sugar antigens of gastric mucins (MUC5AC, MUC1) can act as receptors for bacterial adhesins. The aim of the study was to investigate if Lotus tetragonolobus and Maackia amurensis lectins influence the level of MUC1, MUC5AC, Lewis b, H type 1, sialyl Lewis x, phospho-IκBα and interleukin 8 in Helicobacter pylori infected gastric cancer cells. MATERIALS AND METHODS: The study was performed with one clinical H. pylori strain and CRL-1739 gastric cancer cells. To assess the levels of mentioned factors immunosorbent ELISA assays were used. RESULTS: Coculture of cells with bacteria had no clear effect on almost all examined structures. After coculture with H. pylori and lectins, a decrease of the level of both mucins, Lewis b and H type 1 antigens was observed. Lectins addition had no effect on sialyl Lewis x. Maackia amurensis caused slight increase of phospho-IκBα while interleukin 8 level was decreased. CONCLUSIONS: Lotus tetragonolobus and Maackia amurensis lectins can mediate in binding of Helicobacter pylori to gastric epithelium.


Assuntos
Antígenos Glicosídicos Associados a Tumores/metabolismo , Helicobacter pylori/fisiologia , Interleucina-8/metabolismo , Lectinas/uso terapêutico , Lotus/química , Maackia/química , Inibidor de NF-kappaB alfa/metabolismo , Neoplasias Gástricas/tratamento farmacológico , Neoplasias Gástricas/microbiologia , Linhagem Celular Tumoral , Helicobacter pylori/efeitos dos fármacos , Humanos , Lectinas/farmacologia , Mucinas/metabolismo , Fosforilação/efeitos dos fármacos
13.
Acta Biochim Pol ; 64(3): 465-470, 2017.
Artigo em Inglês | MEDLINE | ID: mdl-28742884

RESUMO

Cancer cells are characterized by an aberrant increase in protein N-glycosylation and by disruption of E-cadherin-mediated adherens junctions. However, the relationship between alterations in N-glycosylation process and loss of E-cadherin adhesion in cancer remains unclear. The mechanisms of altered expression of adhesive glycoproteins in cancer cells have not been fully elucidated. Thus, the aim of this study was to examine the expression of E-cadherin and sialyl Lewisa/x, NeuAcα2-3Gal, NeuAcα2-6Gal/GalNAc structures in the normal renal tissue and intermediate and cancerous tissues from patients with clear cell RCC. Moreover, we attempted to correlate the E-cadherin expression with some specific sugar residues of renal cancer tissue glycoproteins. The expression of E-cadherin was analysed using ELISA test and immunoblotting. Oligosaccharide structures and sialylation level were detected with ELISA test using specific biotinylated lectins or antibodies. A significant decrease of E-cadherin expression as well as a significant increase in sialylated oligosaccharides level in intermediate zone and renal cancer tissue in comparison to normal renal tissue are reported. Significant decrease in expression of cadherins and increase in sialylation of oligosaccharide structures in renal cancer tissue in comparison to normal renal tissue, and in renal cancer tissue in comparison to intermediate zone of renal tissue, are important for the future research concerning detection and quantification of cadherins and sialylated oligosaccharide structures in urine and cells of urinary sediment as possible non-invasive marker of early RCC.


Assuntos
Caderinas/metabolismo , Carcinoma de Células Renais/metabolismo , Neoplasias Renais/metabolismo , Acetilglucosamina/metabolismo , Idoso , Antígenos CD , Carcinoma de Células Renais/patologia , Feminino , Glicoconjugados/metabolismo , Glicoproteínas/metabolismo , Humanos , Rim/metabolismo , Neoplasias Renais/patologia , Antígenos CD15/metabolismo , Masculino , Pessoa de Meia-Idade , Valores de Referência , Ácidos Siálicos/metabolismo
14.
Clin Exp Nephrol ; 19(4): 732-7, 2015 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-25091456

RESUMO

BACKGROUND: Changes in expression patterns of the sialyl Lewis antigens and MUC1 mucin can be considered as markers for the diagnosis of various cancers. However, there are no reports which have been devoted to analysis of differences in the sialyl Lewis antigens and MUC1 expression patterns as potential discrimination markers among different areas of clear cell renal cell carcinoma (ccRCC). The aim of this study was to determine the level of MUC1 and specific Lewis antigens on glycoproteins in three different areas: tumor (cancer tissue), intermediate zone (adjacent to tumor tissue) and normal renal cortex/medulla (uninvolved by tumor). METHODS: Study was performed on renal tissues taken from 30 patients with clear cell renal cell carcinoma. Relative amounts of sugar structures bound with proteins were determined by ELISA-like test with biotinylated lectins or monoclonal antibodies: anti-MUC1 and anti-sialyl Lewis(a/x). The study presented here provides novel information about relationship between MUC1 and sialyl Lewis antigens in the tumor, intermediate zone and noninvolved areas of normal renal tissue distant of tumor. RESULTS: We have found statistically significant increase of MUC1 and sialic acid linked by α-2,3 bond with galactose in cancer tissue and in intermediate zone comparing to normal renal tissue distant of tumor. Moreover, we observed statistically significant increase of sialic acid linked by α-2,6 bond with Gal/GalNAc and sialyl Lewis(a/x) antigens in cancer tissues only, comparing to normal ones. CONCLUSIONS: MUC1 and sialylated antigens can be involved in renal tumor development and can be considered as potential markers distinguishing normal renal tissue from intermediate zone and from cancer renal cells during ccRCC development.


Assuntos
Carcinoma de Células Renais/metabolismo , Neoplasias Renais/metabolismo , Antígenos CD15/metabolismo , Mucina-1/metabolismo , Idoso , Biomarcadores Tumorais/metabolismo , Feminino , Humanos , Rim/metabolismo , Masculino , Pessoa de Meia-Idade , Antígeno Sialil Lewis X
15.
Adv Clin Exp Med ; 22(3): 347-53, 2013.
Artigo em Inglês | MEDLINE | ID: mdl-23828675

RESUMO

BACKGROUND: Helicobacter pylori is responsible for gastroduodenal diseases such as chronic gastritis, gastric and duodenal ulcers and also gastric malignances. During an infection, gastric mucins, especially secretory MUC5AC, are said to participate in interactions with bacterial adhesins. Recently, epithelial MUC1 mucin has also been proposed to be engaged in infection development. H. pylori surface possesses lipopolisaccharides with Lewis antigens whose role in interactions with gastric mucins has not been elucidated thoroughly so far. OBJECTIVES: To check the involvement of Lewis b and H type 1 structures of H. pylori in adhesion of bacteria to MUC1 mucin. MATERIAL AND METHODS: The study was performed on gastric juices taken from 10 clinical patients and 4 H. pylori strains. Bacteria were assessed for the presence of Lewis b and H type 1 structures by ELISA test. Interactions of H. pylori with MUC1 were analyzed by sandwich ELISA method with bacteria pretreated or not with Lewis b - HSA or H type 1 - HSA glycoconjugates. RESULTS: In the majority of the patients, the slight increase of adhesion of H. pylori to MUC1, after pretreatment of bacteria with H type 1 glycoconjugate was observed. A statistically significant difference was revealed in one strain with a dose of conjugate 50µg/mL (P = 0.05). The influence of Lewis b on adhesion is considered to be contradictory. CONCLUSIONS: H type 1 antigens are suggested to be involved in carbohydrate - carbohydrate interactions of H. pylori with MUC1 mucin.


Assuntos
Aderência Bacteriana , Helicobacter pylori/fisiologia , Antígenos do Grupo Sanguíneo de Lewis/metabolismo , Mucina-1/metabolismo , Adulto , Anticorpos Antibacterianos/imunologia , Feminino , Helicobacter pylori/imunologia , Humanos , Antígenos do Grupo Sanguíneo de Lewis/química , Masculino , Pessoa de Meia-Idade , Ligação Proteica , Adulto Jovem
16.
Acta Biochim Pol ; 60(2): 223-6, 2013.
Artigo em Inglês | MEDLINE | ID: mdl-23772422

RESUMO

Sialic acid and sialyl Lewisa/x are found on N- and O-glycans of many human malignant cells. Carbohydrate antigens can be used as tumor markers, and an increase of their levels in cancer cells is associated with tumor progression. The aim of this study was to assess the level of some Lewis blood group antigens on glycoproteins in tumor (cancer tissue), intermediate zone (adjacent to tumor tissue), and normal renal cortex/medulla (uninvolved by tumor). The study was performed on tissues taken from 30 patients. Relative amounts of sugar structures of proteins with molecular masses above 30 kDa were determined by ELISA-like test with biotinylated lectins: MAA (Maackia amurensis), SNA (Sambucus nigra), and monoclonal antibodies anti-sialyl Lewisa/x.∙ Higher expression of all examined structures was revealed in cancer tissues. Significant increases were observed for sialic acid linked α 2-3 in cancer tissues when compared to healthy ones and also among intermediate and healthy tissues. The sialic acid linked α 2-6 and sialyl Lewisx structures were significantly increased in cancerous cells when compared to normal and intermediate renal tissue. In case of sialyl Lewisa antigen, a significant difference was discovered between normal and intermediate tissue. Our results confirm that the examined Lewis antigens can be involved in tumor development. Their increase in cancer tissues can suggest their specific role in the process.


Assuntos
Biomarcadores Tumorais/biossíntese , Carcinoma de Células Renais/fisiopatologia , Neoplasias Renais/imunologia , Neoplasias Renais/fisiopatologia , Antígenos do Grupo Sanguíneo de Lewis/biossíntese , Idoso , Antígeno CA-19-9 , Feminino , Glicoproteínas/imunologia , Glicoproteínas/metabolismo , Humanos , Rim/metabolismo , Masculino , Pessoa de Meia-Idade , Oligossacarídeos/biossíntese
17.
Folia Histochem Cytobiol ; 50(4): 599-604, 2012.
Artigo em Inglês | MEDLINE | ID: mdl-23264225

RESUMO

Cancer development is associated with the improper glycosylation of proteins. There are alterations in the synthesis and expression of sugar structures. These changes can be important not only in the early stages of tumour development, but also in the next stages connected with cancer invasiveness and its ability to form metastases. Oligosaccharide structures of glycans in tumours deviate from normal cells. Relatively increased degrees of branching and sialylation of N-glycans, enhanced presentation of short-chain mucin-type O-glycans with sialylation, and alterations in the expression of blood group ABO and Lewis epitopes can be observed. The main aim of our study was to assess changes in the glycosylation of proteins in clear cell renal cell carcinoma. This study was performed on tissues taken from 15 patients. The relative amounts of sugar structures of proteins with molecular mass above 30 kDa in tumour (cancer tissue), intermediate zone i.e. tumour-adjacent tissue, and normal tissue uninvolved by tumour, were determined by ELISA-like test with biotinylated lectins highly specific to examined sugar antigens. A higher expression of all examined structures was revealed in cancer tissue. Increased levels of sialic acid, fucose, T and Tn antigens, compared to healthy renal tissue, were characteristic for clear cell renal cell carcinoma.


Assuntos
Saúde , Neoplasias Renais/metabolismo , Neoplasias Renais/patologia , Rim/metabolismo , Rim/patologia , Proteínas/metabolismo , Idoso , Feminino , Glicosilação , Humanos , Lectinas/metabolismo , Masculino , Pessoa de Meia-Idade , Estadiamento de Neoplasias , Estatísticas não Paramétricas , Carga Tumoral
18.
Postepy Hig Med Dosw (Online) ; 66: 60-6, 2012 Jan 30.
Artigo em Polonês | MEDLINE | ID: mdl-22371407

RESUMO

Helicobacter pylori is a Gram-negative bacterium which colonizes the stomach of over 50% of the world's population. The pathogen is responsible for many diseases including gastritis, ulcers and also gastric cancers. It is said that adherence of bacteria to epithelial cells plays a key role in infection development. Two gastric mucins, components of mucus, are assumed to have an important role in protection against adhesion and in this way in progression of infection. These are a secretory MUC5AC mucin, produced by mucous epithelial cells, and a membrane-bound MUC1 mucin, expressed by epical surfaces of epithelial cells. Interactions with bacteria occur between carbohydrate antigens of mucins and specific adhesins of the Helicobacter pylori surface. In this paper we present the latest knowledge about these intriguing interactions of both mucins and their interplay with the pathogen providing protection against infection.


Assuntos
Adesinas Bacterianas/metabolismo , Mucinas Gástricas/metabolismo , Gastrite/metabolismo , Gastrite/microbiologia , Infecções por Helicobacter/metabolismo , Infecções por Helicobacter/microbiologia , Helicobacter pylori/metabolismo , Células Epiteliais/microbiologia , Mucosa Gástrica/metabolismo , Mucosa Gástrica/microbiologia , Humanos , Mucina-5AC/metabolismo , Mucina-1/metabolismo , Neoplasias Gástricas/metabolismo , Neoplasias Gástricas/microbiologia
19.
Clin Chem Lab Med ; 49(5): 885-9, 2011 May.
Artigo em Inglês | MEDLINE | ID: mdl-21288176

RESUMO

BACKGROUND: In cancer tissue, altered glycosylation of proteins is observed. There are some typical changes; for example, sialyl-Lewis(a/x) glycoforms are more abundant in many types of cancers. The current study investigated the differences in glycosylation of proteins between neoplastic and healthy human salivary glands. METHODS: Sugar structures on proteins with a molecular mass above 30 kDa were determined by enzyme-linked immunosorbent assay (ELISA) with biotinylated lectins. RESULTS: The expression of sialic acid in cancer tissues was higher in comparison with healthy ones. The same observations were revealed for Fuc α1-6, α1-2, T, Tn antigens and α1-6 mannose. CONCLUSIONS: Glycosylation of proteins in cancer salivary gland tissues is altered in comparison with healthy tissue.


Assuntos
Ensaio de Imunoadsorção Enzimática/métodos , Neoplasias das Glândulas Salivares/metabolismo , Glândulas Salivares/metabolismo , Proteínas e Peptídeos Salivares/metabolismo , Adulto , Idoso , Feminino , Glicosilação , Humanos , Masculino , Pessoa de Meia-Idade , Peso Molecular , Lectinas de Plantas/metabolismo , Neoplasias das Glândulas Salivares/patologia , Glândulas Salivares/citologia , Glândulas Salivares/patologia , Proteínas e Peptídeos Salivares/química
20.
Clin Biochem ; 42(15): 1565-7, 2009 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-19615986

RESUMO

OBJECTIVES: To compare N-acetyl-beta-hexosaminidase (HEX) activity in the serum and urine of smokers as well as non-smokers with renal cancer, and healthy people. DESIGN AND METHODS: To assess hexosaminidase activity the level of p-nitrophenol released from p-nitrophenol derivatives was measured. RESULTS: The activity of enzyme was significantly higher in cancer group, with the highest activity in non-smokers. CONCLUSIONS: Cigarette smoking can inhibit, by the influence on HEX activity, catabolism of oligosaccharide chains in cancer tissues.


Assuntos
Neoplasias Renais , Fumar , beta-N-Acetil-Hexosaminidases , Biomarcadores Tumorais/sangue , Biomarcadores Tumorais/urina , Humanos , Neoplasias Renais/sangue , Neoplasias Renais/enzimologia , Neoplasias Renais/urina , Nitrofenóis/metabolismo , Oligossacarídeos/metabolismo , Fatores de Risco , Fumar/sangue , Fumar/urina , beta-N-Acetil-Hexosaminidases/sangue , beta-N-Acetil-Hexosaminidases/urina
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