Cimetidine inhibits the adhesion of gastric cancer cells expressing high levels of sialyl Lewis x in human vascular endothelial cells by blocking E-selectin expression

Li, Qing

doi:10.3892/ijmm.2011.618

Cited by 13 publications

(10 citation statements)

References 14 publications

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“…In addition, CD15 ( Syalyl Lewis x , E-selectin ligand) expression did not vary significantly after the treatment. Sialyl Lewis x is constitutively expressed on granulocytes and monocytesand on activated T and B lymphocytes [31]. Taken together, our findings suggest that with decrease in blood pressure, there is a de-activation of the endothelial cells, followed by changes in the adhesion of the circulatory leukocytes.…”

Section: Discussionsupporting

confidence: 55%

The Effects of Arterial Blood Pressure Reduction on Endocan and Soluble Endothelial Cell Adhesion Molecules (CAMs) and CAMs Ligands Expression in Hypertensive Patients on Ca-Channel Blocker Therapy

Tadžić¹,

Mihalj

Včev

et al. 2013

Kidney Blood Press Res

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Background/Aims: To determine the effect of arterial blood pressure (BP) reduction on endocan and soluble cell adhesion molecules' (sCAM) plasma concentration and expression of their ligands on circulatory leukocyte subpopulations. Methods: 24 hypertensive subjects of both sexes (age: 53±8 yrs) were treated with Ca-channel blocker, amlodipin (5-10 mg/day for 8 weeks; to reach BP≤139/89mmHg). The serum sCAMs and endocan concentrations were determined by ELISA kits. Level of ICAM/VCAM ligands on leukocytes was assessed by flow cytometry. Paired t-test, or t-test were used as appropriate, with Pearson's correlation calculated; p<0.05 was considered significant (SigmaPlot v.11). Results: sICAM-1 and sVCAM-1 were decreased (p≤0.001 and p=0.002, respectively), while E-selectin concentration was increased after amlodipin treatment (P=0.014). CD11a/LFA-1 (ICAM-1 and endocan ligand) was significantly increased in all three cell types with BP decrease. CD15 and CD49d/VLA-4 (VCAM-1 ligand) did not change after the treatment. There was significant positive correlation of systolic and diastolic BP with ICAM-1 and VCAM-1, and significant negative correlation of systolic BP with CD11a/LFA-1. Endocan significantly positively correlated with ICAM-1. Conclusions: The increased expression of ICAM/VACM ligands, together with decrease of sCAMs and endocan suggests the de-activation of endothelium with reduction in BP, decreasing the adherence of circulatory leukocytes to endothelium; subsequently decreasing the risk for development of atherosclerosis.

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Section: Discussionsupporting

confidence: 55%

The Effects of Arterial Blood Pressure Reduction on Endocan and Soluble Endothelial Cell Adhesion Molecules (CAMs) and CAMs Ligands Expression in Hypertensive Patients on Ca-Channel Blocker Therapy

Tadžić¹,

Mihalj

Včev

et al. 2013

Kidney Blood Press Res

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“…2 A . Molecular Phylogenetic analysis by Maximum Likelihood method based on the JTT matrix-based model [1]. The tree with the highest log likelihood (−5230.5756) is shown.…”

Section: Resultsmentioning

confidence: 99%

“…Le x , Le y and Sialyl-Le x ), one of the major components of cell surface oligosaccharides. One of them, Sialyl-Le x , is involved, due to its external position, in numerous cell-cell interactions occurring during embryo implantation [1], malignant transformation [2] and inflammation [3]. …”

Section: Introductionmentioning

confidence: 99%

Characterization of bovine FUT7 furthers understanding of FUT7 evolution in mammals

et al. 2012

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BackgroundThe Sialyl-Lewis X (Slex) is a well-known glycan structure involved in leukocyte homing and recruitment to inflammatory sites. SLex is well conserved among species and is mainly synthesized by FucT-VII in vertebrates. The enzyme responsible for its biosynthesis in cattle was not known.ResultsWe cloned a cDNA sequence encoding bovine α3-fucosyltransferase VII that shares 83% identity with its human counterpart. Located at the BTA 11 telomeric region, the 1029 bp open reading frame is spread over two different exons, E1 which also contains the unique 5’-untranslated region and E2 which includes the entire 3’-untranslated region. The bfut7 expression pattern is restricted to thymus and spleen. A single transcript leading to the synthesis of a 342 aa protein was identified. The encoded fucosyltransferase, produced as a recombinant enzyme in COS-1 cells, was shown to be specifically responsible for SLex synthesis in cattle. In addition, we showed that the gene promoter evolved from fish to mammals towards a complex system related to the immune system. But beyond the fact that the gene regulation seems to be conserved among mammals, we also identified 7 SNPs including 3 missense mutations in the coding region in a small panel of animals.ConclusionsThe FUT7 sequence was highly conserved as well as the specific activity of the encoded protein FucT-VII. In addition, our in silico promoter analysis and the high rate of polymorphism suggested that its function is evolving toward a complex system related to the immune system. Furthermore, comparing bovine to human and mouse sequences, it appeared that a decrease in gene regulation was correlated with an increase in mutation rate and wider tissue expression.

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“…In addition to colorectal cancer, the inhibitory effect on cell adhesion has been demonstrated for other cancers, including breast [ 84 ], salivary gland tumours [ 85 ], gastric cancer [ 86 ] and glioblastoma [ 31 ].…”

Section: Mechanism Of Actionmentioning

confidence: 99%

Repurposing drugs in oncology (ReDO)—Cimetidine as an anti-cancer agent

Pantziarka

Bouche

Meheus

et al. 2014

ecancer

251

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Cimetidine, the first H2 receptor antagonist in widespread clinical use, has anti-cancer properties that have been elucidated in a broad range of pre-clinical and clinical studies for a number of different cancer types. These data are summarised and discussed in relation to a number of distinct mechanisms of action. Based on the evidence presented, it is proposed that cimetidine would synergise with a range of other drugs, including existing chemotherapeutics, and that further exploration of the potential of cimetidine as an anti-cancer therapeutic is warranted. Furthermore, there is compelling evidence that cimetidine administration during the peri-operative period may provide a survival benefit in some cancers. A number of possible combinations with other drugs are discussed in the supplementary material accompanying this paper.

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Cimetidine inhibits the adhesion of gastric cancer cells expressing high levels of sialyl Lewis x in human vascular endothelial cells by blocking E-selectin expression

Cited by 13 publications

References 14 publications

The Effects of Arterial Blood Pressure Reduction on Endocan and Soluble Endothelial Cell Adhesion Molecules (CAMs) and CAMs Ligands Expression in Hypertensive Patients on Ca-Channel Blocker Therapy

The Effects of Arterial Blood Pressure Reduction on Endocan and Soluble Endothelial Cell Adhesion Molecules (CAMs) and CAMs Ligands Expression in Hypertensive Patients on Ca-Channel Blocker Therapy

Characterization of bovine FUT7 furthers understanding of FUT7 evolution in mammals

Repurposing drugs in oncology (ReDO)—Cimetidine as an anti-cancer agent

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