Zhong, Dong;Ran, Jian-Hua;Tang, Wen-Yuan;Zhang, Xiao-Dong;Tan, Yun;Chen, Gui-Jie;Li, Xiao-Song;Yan, Yi
Asian Pacific Journal of Cancer Prevention
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v.13
no.6
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pp.2897-2901
/
2012
Invasion is usually recognized as the main reason for the high recurrence and death rates of glioma and restricts the efficacy of surgery and other therapies. Therefore, we aimed to investigate the mechanism involved in promotion effects of mda-9/syntenin on human glioma cell migration. The wound healing method was used to test the migration ability of human glioma cells CHG-5 and CHG-hS, stably overexpressing mda-9/syntenin. Western blotting was performed to determine the expression and phosphorylation of focal adhesion kinase (FAK) and JNK in CHG-5 and CHG-hS cells. The migration ability of CHG-hS cells was significantly higher than that of CHG-5 cells in fibronectin (FN)-coated culture plates. Phosphorylation of FAK on tyrosine 397, 576, and 925 sites was increased with time elapsed in CHG-hS cells. However, phosphorylated FAK on the tyrosine 861 site was not changed. Phosphorylated Src, JNK and Akt levels in CHG-hS cells were also significantly upregulated. Phosphorylation of JNK and Akt were abolished by the specific inhibitors SP600125 and LY294002, respectively, and the migration ability of CHG-hS cells was decreased, indicating that the JNK and PI3K/Akt pathways play important roles in regulating mda-9/syntenin-induced human brain glioma migration. Our results indicate Mda-9/syntenin overexpression could activate FAK-JNK and FAK-Akt signaling and then enhance the migration capacity of human brain glioma cells.
Background: Chronic myeloid leukemia (CML) is a myeloproliferative disorder of hematopoietic stem cell scarrying the Philadelphia (Ph) chromosome and an oncogenic BCR-ABL1 fusion gene. The tyrosine kinase inhibitor (TKI) of BCR-ABL1 kinase is a treatment of choice for control of CML. Objective: Recent studies have demonstrated that miRNAs within exosomes from cancer cells play crucial roles in initiation and progression. This study was performed to assess miRNAs within exosomes of K562 cells. Methods: miRNA microarray analysis of K562 cells and K562 cell-derived exosomes was conducted with the 6th generation miRCURYTM LNA Array (v.16.0). Gene ontology and Kyoto Encyclopedia of Genes and Genomes (KEGG) analyses were also carried out. GO terms and signaling pathways were categorized into 66 classes (including homophilic cell adhesion, negative regulation of apoptotic process, cell adhesion) and 26 signaling pathways (such as Wnt). Results: In exosomes, 49 miRNAs were up regulated as compared to K562 cells, and two of them were further confirmed by quantitative real-time PCR. There are differentially expressed miRNAs between K562 cell derived-exosomes and K562 cells. Conclusion: Selectively expressed miRNAs in exosomes may promote the development of CML via effects on interactions (e.g. adhesion) of CML cells with their microenvironment.
Objective: To investigate whether the expression of serum soluble neural cell adhesion molecule (sNCAM) is associated with hepatic encephalopathy (HE) in hepatocelular carcinoma (HCC) patients. Materials and Methods: The Oncomine Cancer Microarray database was used to determine the clinical relevance of NCAM expression in different kinds of human cancers. Sera from 75 HCC cases enrolled in this study were assessed for expression of sNCAM by enzyme linked immunosorbent assay (ELISA). Results: Dependent on the Oncomine Cancer Microarray database analysis, NCAM was down regulated in 10 different kinds of cancer, like bladder cancer, brain and central nervous system cancer, while up-regulated in lung cancer, uterine corpus leiomyoma and sarcoma, compared to normal groups. Puzzlingly, NCAM expression demonstrated no significant difference between normal and HCC groups. However, we found by quantitative ELISA that the level of sNCAM in sera from HCC patients with HE ($347.4{\pm}151.9ng/ml$) was significantly more up-regulated than that in HCC patients without HE ($260.3{\pm}104.2ng/ml$), the p-value being 0.008. sNCAM may be an important risk factor of HE in HCC patients, the correlation coefficients was 0.278 (P<0.05) on rank correlation analysis. Conclusions: This study highlights that up-regulated level of serum sNCAM is associated with HE in HCC patients and suggests that the high expression can be used as an indicator.
This study was performed to determine the effectiveness of poloxamer/sodium alginate mixture(PX/SA) barriers on prevention of post-operative peritoneal adhesion in dogs. Fifteen mongrel dogs were divided into three experimental groups: non-treated group, 2% Sodium Carboxymethylcellulose (SCMC) treated group and PX/SA treated group. In order to induce adhesions, the anti-mesenteric serosa of the ileum was exteriorized and then abraded in a standard manner by scraping with a scalpel blade to create homogeneous petechial hemorrhagic surface over a 1 ${\times}$ 1 cm area. Solution of SCMC was allowed to spread across the intraperitoneal organs through a catheter using a syringe. PX/SA was simply coated over the abraded tissues. On day before and day 1, 4, 7, and 14 after operation, venous blood specimens were collected for measurement of RBC, total WBC and fibrinogen. The adhesions were blindly assessed 3 weeks later by using a computerized tensiometer. The RBC, total WBC and fibrinogen values of three groups showed no statistical significances. The mean tensile strength(gram force, gf) of formed adhesions on day 21 after surgery was 173.05${\pm}$113.48 in the non-treated group, 111.42 ${\pm}$ 38.25 in the SCMC group, and 69.00 ${\pm}$ 45.07 in the PX/SA group. The tensile strength values for adhesion seperation in PX/SA group was lower than those in SCMC group(p < 0.05) and significantly lower than those in the non-treated group(p < 0.05). Our data suggested that PX/SA should be effective on reducing peritoneal adhesion formation in dogs compared with SCMC. PX/SA may be applicable to preventing post-operative intraperitoneal adhesion in dogs.
The liver is normally the major site of glucose metabolism in intact organisms and the most important target organ for the action of insulin. It has been widely accepted that insulin resistance (IR) is closely associated with postoperative recurrence of hepatocellular carcinoma (HCC). However, the relationship between IR and drug resistance in liver cancer cells is unclear. In the present study, IR was induced in HepG2 cells via incubation with a high concentration of insulin. Once the insulin-resistant cell line was established, the stability of HepG2/IR cells was further tested via incubation in insulin-free medium for another 72h. Afterwards, the biological effects of insulin resistance on adhesion, migration, invasion and sensitivity to cis-platinum (DDP) of cells were determined. The results indicated that glucose consumption was reduced in insulin-resistant cells. In addition, the expression of the insulin receptor and glucose transportor-2 was downregulated. Furthermore, HepG2/IR cells displayed markedly enhanced adhesion, migration, and invasion. Most importantly, these cells exhibited a lower sensitivity to DDP. By contrast, HepG2/IR cells exhibited decreased adhesion and invasion after treatment with the insulin sensitizer pioglitazone hydrochloride. The results suggest that IR is closely related to drug resistance as well as adhesion, migration, and invasion in HepG2 cells. These findings may help explain the clinical observation of limited efficacy for chemotherapy on a background of IR, which promotes the invasion and migration of cancer cells.
Mustafa, Ebtihal H;Mahmoud, Huda T;Al-Hudhud, Mariam Y;Abdalla, Maher Y;Ahmad, Iman M;Yasin, Salem R;Elkarmi, Ali Z;Tahtamouni, Lubna H
Asian Pacific Journal of Cancer Prevention
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v.16
no.8
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pp.3213-3222
/
2015
Background: Cancer metastasis depends on cell motility which is driven by cycles of actin polymerization and depolymerization. Reactive oxygen species (ROS) and metabolic oxidative stress have long been associated with cancer. ROS play a vital role in regulating actin dynamics that are sensitive to oxidative modification. The current work aimed at studying the effects of sub-lethal metabolic oxidative stress on actin cytoskeleton, focal adhesion and cell migration. Materials and Methods: T47D human breast cancer cells were treated with 2-deoxy-D-glucose (2DG), L-buthionine sulfoximine (BSO), or doxorubicin (DOX), individually or in combination, and changes in intracellular total glutathione and malondialdehyde (MDA) levels were measured. The expression of three major antioxidant enzymes was studied by immunoblotting, and cells were stained with fluorescent-phalloidin to evaluate changes in F-actin organization. In addition, cell adhesion and degradation ability were measured. Cell migration was studied using wound healing and transwell migration assays. Results: Our results show that treating T47D human breast cancer cells with drug combinations (2DG/BSO, 2DG/DOX, or BSO/DOX) decreased intracellular total glutathione and increased oxidized glutathione, lipid peroxidation, and cytotoxicity. In addition, the drug combinations caused a reduction in cell area and mitotic index, prophase arrest and a decreased ability to form invadopodia. The formation of F-actin aggregates was increased in treated T47D cells. Moreover, combination therapy reduced cell adhesion and the rate of cell migration. Conclusions: Our results suggest that exposure of T47D breast cancer cells to combination therapy reduces cell migration via effects on metabolic oxidative stress.
Background: Dental caries is one of several prevalent oral diseases caused by dental plaque biofilms. This study evaluated the anti-cariogenic effects of a bamboo salt (BS) and sodium fluoride (NaF) mixture on oral bacteria. Methods: The effects of several mixtures of NaF and BS on acid production, growth, and adhesion to glass beads of Streptococcus mutans, and their anti-cariogenic properties were investigated. The growth of S. mutans was measured according to optical density at 3, 6, 9, 12, 15, 18, and 24 hours after treatment using spectrophotometry at a wavelength of 600 nm, while pH was measured using a pH meter. Adhesion of S. mutans was measured according to the weight of glass beads from each group before and after incubation. Gene expression was measured using real-time polymerase chain reaction. Acid production and growth patterns of S. mutans were compared using repeated measures analysis of variance, followed by Scheffe's post-hoc test. The Kruskal-Wallis test was used to compare adhesion, followed by the Mann-Whitney test. Gene expression in the experimental and control samples was compared using the Student's t-test. Results: Growth, acid production, and adhesion of S. mutans were inhibited in all experimental groups. Expression of gft and fructosyltransferase in S. mutans was inhibited in all groups. A mixture of NaF and BS significantly reduced growth, acid production, adhesion, and gene expression of S. mutans compared with the other groups. Conclusion: Results of the present study demonstrated that a mixture of NaF and BS was useful as a mouth rinse in preventing dental caries.
Cho, Young-Suk;Kim, Chan Hyung;Ha, Tae-Sun;Lee, Sang Jin;Ahn, Hee Yul
The Korean Journal of Physiology and Pharmacology
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v.17
no.2
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pp.133-137
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2013
Vascular cell adhesion molecule 1 (VCAM-1), intercellular adhesion molecule 1 (ICAM-1), P- and E-selectin play a pivotal role for initiation of atherosclerosis. Ginsenoside, a class of steroid glycosides, is abundant in Panax ginseng root, which has been used for prevention of illness in Korea. In this study, we investigated the mechanism(s) by which ginsenoside Rg2 may inhibit VCAM-1 and ICAM-1 expressions stimulated with lipopolysaccharide (LPS) in human umbilical vein endothelial cell (HUVEC). LPS increased VCAM-1 and ICAM-1 expression. Ginsenoside Rg2 prevented LPS-mediated increase of VCAM-1 and ICAM-1 expression. On the other hand, JSH, a nuclear factor kappa B (NF-${\kappa}B$) inhibitor, reduced both VCAM-1 and ICAM-1 expression stimulated with LPS. SB202190, inhibitor of p38 mitogen-activated protein kinase (p38 MAPK), and wortmannin, phosphatidylinositol 3-kinase (PI3-kinase) inhibitor, reduced LPS-mediated VCAM-1 but not ICAM-1 expression. PD98059, inhibitor of mitogen-activated protein kinase kinase/extracellular signal-regulated kinase (MEK/ERK) did not affect VCAM-1 and ICAM-1 expression stimulated with LPS. SP600125, inhibitor of c-Jun N-terminal kinase (JNK), reduced LPS-mediated ICAM-1 but not VCAM-1 expression. LPS reduced IkappaB${\alpha}$ ($I{\kappa}B{\alpha}$) expression, in a time-dependent manner within 1 hr. Ginsenoside Rg2 prevented the decrease of $I{\kappa}B{\alpha}$ expression stimulated with LPS. Moreover, ginsenoside Rg2 reduced LPS-mediated THP-1 monocyte adhesion to HUVEC, in a concentration-dependent manner. These data provide a novel mechanism where the ginsenoside Rg2 may provide direct vascular benefits with inhibition of leukocyte adhesion into vascular wall thereby providing protection against vascular inflammatory disease.
This study was performed to evaluate the efficacy of 0.8% sodium hyaluronic acid solution and crosslinked hyaluronic acid mixture for the prevention of postoperative intraperitoneal adhesion in rats. Forty-five animals were divided into three groups ; 0.9% saline treated control group, 1% sodium carboxymethyl cellulose treated group (SCMC), and 0.8% sodium hyaluronic acid solution and crosslinked hyaluronic acid mixture treated group (SHCH). Adhesions were induced by suturing both the ileal serosa and peritoneum abrased until petechial bleeding occurred. Fourteen days later, adhesions were evaluated clinically and histopathologically. The mean tensile strength was significantly decreased in the SCMC and SHCH groups compared to the control group (p < 0.05), and the SHCH group had the lowest tensile strength. The distance of adhesion site was highest in the control group and significantly decreased in the SHCH group comparing control group (p < 0.05). The inflammatory cell infiltration, collagen hyperplasia and neovascularization of the SCMC and SHCH groups were significantly lower than the control group (p < 0.05). Therefore, it was concluded that the SHCH may be useful to prevent postoperative intraperitoneal adhesion in rats.
Background; Pericardial adhesion poses a major problem during re-operative cardiac surgery. The purpose of this study was to determine the effect of sodium carboxymethol cellulose on experimental pericardial adhesions. Material and Method; Twenty-four rabbits were divided into 2 groups of 12 rabbits each and pericardial mesothelial injury was induced by abrasion. Group A included rabbits receiving intrapericardial injection of Ringer's solution, and Group B included rabbits receiving intrapericardial injection of 3% sodium carboxymethoyl cellulose solution. Three weeks after the surgery, the incidence of adhesions in Group A was compared with that in Group B. Result; Pericardial adhesions were evaluated by tenacity and type scores. Tenacity scores of 3 or greater were considered clinically significant adhesion. Pericardial adhesion was found in 100% of rabbits in group A. However 25% of the rabbits in Group B had pericardial adhesions(p<0.0001). Type scores were also considered clinically significant between 2 groups. Conclusion; Our findings demonstrated that intrapericardial injection of 3% sodium carboxymethyl cellulose solution reduced the incidence of pericardial adhesions in an animal models.
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