Prognostic significance of syndecan-1 expression in cervical cancers / 부인종양

OBJECTIVE: Syndecans are reported to have variable expression in several solid tumors and blood cancers. The cause provoking altered expression of syndecans is not known to date. We studied copy number status of syndecan-1 (SDC1) and significance of SDC1 gene product (syndecan-1, SDC1) expression in cervical cancers. METHODS: Using 121 cases of cervical cancer tissues, we screened SDC1 expression pattern using immunohistochemistry. We analyzed the relationship between SDC1 expression and clinicopathological parameters. To find possible causes of the expression change, we exploited interphase fluorescent in situ hybridization to screen copy number alteration of SDC1. RESULTS: Among 121 cases, 101 (83.5%) were positive and 20 (16.4%) were negative for SDC1. Among the parameters, age, histological type, and grade were significantly associated with SDC1 expression (p<0.05). Strong SDC1 expression in the cytoplasm showed better patient survival (p=0.02). In multivariate regression model, grade and SDC1 expression were independent prognostic factors (p<0.05). SDC1 in cervical cancers did not show copy number alteration. CONCLUSION: Strong SDC1 expression in the cytoplasm of tumor cells predicts better patient survival. The change of SDC1 expression in cervical cancers is not caused by copy number alteration of the gene.

Specific structural features of syndecans and heparan sulfate chains are needed for cell signaling

The syndecans, heparan sulfate proteoglycans, are abundant molecules associated with the cell surface and extracellular matrix and consist of a protein core to which heparan sulfate chains are covalently attached. Each of the syndecan core proteins has a short cytoplasmic domain that binds cytosolic regulatory factors. The syndecans also contain highly conserved transmembrane domains and extracellular domains for which important activities are becoming known. These protein domains locate the syndecan on cell surface sites during development and tumor formation where they interact with other receptors to regulate signaling and cytoskeletal organization. The functions of cell surface heparan sulfate proteoglycan have been centered on the role of heparan sulfate chains, located on the outer side of the cell surface, in the binding of a wide array of ligands, including extracellular matrix proteins and soluble growth factors. More recently, the core proteins of the syndecan family transmembrane proteoglycans have also been shown to be involved in cell signaling through interaction with integrins and tyrosine kinase receptors.

mRNA expression of syndecan-1 and heparanase in relation to tumor progression and prognosis of gastric carcinoma / 中华外科杂志

<p><b>OBJECTIVE</b>To investigate mRNA expression of syndecan-1 and heparanase in gastric carcinoma, and their correlation with the growth-pattern, invasion, metastasis and prognosis of gastric carcinoma.</p><p><b>METHODS</b>In situ hybridization technique was used to examine mRNA expression of syndecan-1 and heparanase in 118 specimens of gastric carcinoma.</p><p><b>RESULTS</b>The positive rates of syndecan-1 mRNA and heparanase mRNA were 42.4% and 55.9%, respectively. The expression of syndecan-1 mRNA and heparanase mRNA were related to tumor invasion depth (chi(2) = 32.95, P = 0.001; chi(2) = 23.19, P = 0.001), vessel invasion (chi(2) = 46.22, P = 0.001; chi(2) = 33.78, P = 0.001), lymph node (chi(2) = 28.62, P = 0.001; chi(2) = 25.43, P = 0.001) and distant metastasis (chi(2) = 63.30, P = 0.001; chi(2) = 65.76, P = 0.001), and syndecan-1 mRNA positive expression was related to tumor size (chi(2) = 6.25, P = 0.012). There was a negative relationship between Syndecan-1 mRNA and heparanase mRNA expression (r = -0.844, P = 0.001). The mean survival time of cases with low expression of syndecan-1 mRNA was significantly shorter than that of cases with high expression (r = 36.48, P = 0.001), and meanwhile, the mean survival time of heparanase mRNA positive cases was significantly shorter than that of cases with negative expression (r = 34.41, P = 0.001).</p><p><b>CONCLUSIONS</b>The mRNA expression of syndecan-1 and heparanase can predict the invasion and metastasis of gastric carcinoma, and can be used as markers of prognosis of gastric carcinoma.</p>

Prognostic Evaluation of Nodal Diffuse Large B Cell Lymphoma by Immunohistochemical Profiles with Emphasis on CD138 Expression as a Poor Prognostic Factor

Recently diffuse large B cell lymphoma (DLBCLs) was reported to be subdivided into germinal center B-cell-like (GCB) and activated B-cell-like (ABC) subgroups by using cDNA microarray and immunohistochemical markers. Tissue microarray blocks were created from 51 nodal DLBCLs with control tissue. Immunohistochemical staining for the above markers were performed. The median follow-up period was 26 months. Nodal DLBCLs were subclassified into GCB [CD10+ or CD10-/Bcl-6+/MUM1-, n=17 (33%)] and non-GC subgroups [CD10-/Bcl-6- or CD10-/Bcl-6+/MUM1+, n=35 (67%)], and were alternatively subclassified into pattern A [+ for GCB marker only, n=12 (23%)], B [Co-positive for both markers, n=13 (33%)], C [+ for activation marker only, n=18 (35%)], and D [- for both markers, n=9 (17%)]. Upon survival analysis, the GCB groups showed a relatively better survival than non-GC groups (p=0.0748). Also, pattern C (p=0.0055) and CD138+ (p=0.0008) patients had significantly lower survival rates. By multivariate analysis, CD138 expression alone was considered as an independent risk factor (p=0.031). In summary, our results add to the registration of prognostic implications for previously reported DLBCL subgroups. CD138 may play an important role as a poor prognostic marker. By using immunohistochemistry, a prognostically important subclassification of DLBCLs is possible.

The Effects of Echinacea Extract on the Gene Expression of Monocytes and Monocyte-derived Dendritic Cells / 소아과

PURPOSE: Echinacea, a traditional plant medicine has been used as immune-stimulant. Recent studies have revealed that extract of Echinacea has immunostimulatory effects on human blood mononuclear cells. This study was designed for the purpose of screening the genes associated with immunologic effects of Echinacea on monocytes and dendritic cells using a cDNA microarray chip. METHODS: CD14+monocyte cells were cultured for one day with Echinacea extract (final concentration: 50 microgram/mL) in experiment 1, but were cultured without Echinacea in experiment 2. The gene expression of these cultured monocytes was analyzed using the cDNA microarray chip. Dendritic cells produced from CD14+monocyte were cultured for five days with GM-CSF and IL-4, and then cultured for one day with Echinacea in experiment 3, but were done without Echinacea in experiment 4. RESULTS: In experiments 1 and 2, there were 17 significantly expressed genes with average expression ratios above 2.5, including interferon gamma-inducible protein 30 (IFI 30), CDC (cell-division-cylcle)-like kinase 2 (CLK 2), syndecan binding protein (syntenin), superoxide dismutase 2, etc. In experiments 3 and 4, there were 24 gene, with significantly expressed genes were 24 genes, which were insulin-like growth factor 2 (somatomedin A), methyl-CpG binding domain protein 3, IFI 30, small inducible cytokine subfamily A, member 22, etc. The genes encoding CD44, IFI 30, mannose receptor C type 1 (MRC 1), chemokine receptor 7 (CCR 7), CLK 2, syntenin and cytochrome C oxidase subunit VIII were significantly expressed in both monocytes and dendritic cells cultured with Echinacea. CONCLUSION: This study employed a cDNA microarray chip to elicit the immune-associated gene profile; the expression was enhanced by Echinacea in CD14+monocytes and dendritic cells. Thus we laid the basis for the quantitative and functional analysis of genes induced by Echinacea in monocytes and monocyte-derived dendritic cells.

Gene Expressions of Mouse Submandibular Gland during the Developmental Stage and Their Antisense Inhibition in Organ Culture

This study is aimed to observe the expressions of different genes, including the extracellular matrix proteins, growth factors, and transcription factors during different developmental stages of mouse submandibular gland. Reverse transcription-polymerase chain reaction (RT-PCR) and the antisense inhibition in organ culture system were performed using mouse embryos and newborns. Total 140 mouse embryos (E14(80), E15(20), E16(20), E18(20)) and 30 newborn mice (D2(10), D3(10), D6(10)) obtained from 60 pregnant mice and 3 adult mice (3 weeks old) were used for the cDNA production and the salivary gland organ culture. Syndecan, perlecan, laminin alpha1 chain, TGF beta1, beta 3, and sonic hedgehog mRNAs were expressed in the early stage (E14~E16) of the submandibular gland development, whereas transglutaminase C (TGase C), E-cadherin, epimorphin, laminin beta2 and gamma1 chains, and HGF mRNAs were expressed in the middle and late stages (E16~E18, D2~D6). Antisense inhibition of different genes in the organ culture of E14 mouse embryos of submandibular gland showed specific growth retardation in the development of ductal and acinar cells. Especially, the antisense inhibition of perlecan, E-cadherin, laminin alpha1 chain, laminin beta2 chain, and syndecan mRNA arrested the growth of ductal and acinar cells. While the antisense inhibition of integrin beta5 greatly affected the acinar cell differentiation and also produced cystic dilatation of salivary ducts, the antisense inhibition of fibronectin showed aberrant growth of ectomesenchymal tissues of the mouse submandibular gland.