Sanii, Sanaz;Saffar, Hiva;Tabriz, Hedieh M.;Qorbani, Mostafa;Haghpanah, Vahid;Tavangar, Seyed M.
Asian Pacific Journal of Cancer Prevention
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v.13
no.5
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pp.2175-2178
/
2012
Purpose: Definite diagnosis of follicular thyroid carcinoma (FTC) is based on the presence of capsular or vascular invasion. To date, no reliable and practical method has been introduced to discriminate this malignant neoplasm from follicular thyroid adenoma (FTA) in fine needle aspiration biopsy material. Matrix metalloproteinase-2 (MMP-2), by degrading extracellular matrix, and caspase-3, by induction of apoptosis, have been shown to play important roles in carcinogenesis and aggressive behavior in many tumor types. The aim of this study was to examine expression of MMP-2 and caspase-3 in thyroid follicular neoplasms and to determine their usefulness for differential diagnosis. Method: Sixty FTAs and 41 FTCs were analysed immunohistochemically for MMP-2 and caspase-3. Result: MMP-2 was positive in 4 FTCs (9.8%), but in none of FTAs, with statistical significance (p= 0.025). Caspase-3 was positive in 30 (50%) of FTAs and in 27 (65.9%) of FTCs. Conclusion: Our results show MMP-2 expression only in FTCs and suggest that this protein may be a useful marker to confirm diagnosis of FTC versus FTA with 100% specificity and 100% predictive value of a positive test. We failed to show any differential diagnostic value for caspase-3 in thyroid follicular neoplasms.
Previous evidence showed ${\beta}1$, 3-N-acetylglucosaminyltransferase 8 (${\beta}3GnT8$), which can extend polylactosamine on N-glycans, to be highly expressed in some cancer cell lines and tissues, indicating roles in tumorigenesis. However, so far, the function of ${\beta}3GnT8$ in laryngeal carcinoma has not been characterized. To test any contribution, Hep-2 cells were stably transfected with sense or interference vectors to establish cell lines that overexpressed or were deficient in ${\beta}3GnT8$. Here we showed that cell proliferation was increased in ${\beta}3GnT8$ overexpressed cells but decreased in ${\beta}3GnT8$ knockdown cells using MTT. Furthermore, we demonstrated that change in ${\beta}3GnT8$ expression had significant effects on tumor growth in nude mice.We further provided data suggesting that overexpression of ${\beta}3GnT8$ enhanced the expression of matrix metalloproteinase-2 (MMP-2) and matrix metalloproteinase-9 (MMP-9) at both the mRNA and protein levels, associated with shedding of tissue inhibitors of metalloproteinase TIMP-2. In addition, it caused increased production of transforming growth factor beta 1 (TGF-${\beta}1$), whereas ${\beta}3GnT8$ gene knockdown caused the reverse effect. The results may indicate a novel mechanism by which effects of ${\beta}3GnT8$ in regulating cellular proliferation are mediated, at least in partvia targeting MMPs/TIMPs and TGF-${\beta}1$ in laryngeal carcinoma Hep-2 cells. The finding may lay a foundation for further investigations into the ${\beta}3GnT8$ as a potential target for therapy of laryngeal carcinoma.
This study aims to evaluate the effects of antioxidant activities, protein and mRNA expressions of matrix metalloproteinase (MMP) -1 and procollagen type I C-peptide (PIP) in 70% ethanol extract from Hydnocarpus anthelmintica Pierre (HE). DPPH and ABTS+ radicals scavenging assays were measured for antioxidant activities and HE had 73.5% and 74.4% of scavenging activities at 1,000 ㎍/ml concentration, respectively. And we investigated the inhibition of collagenase by HE, and the result was a 78.8% inhibition effect on concentrations of 1,000 ㎍/ml. In addition, an MTT assay was performed to confirm the toxicity of the CCD-986sk fibroblasts to the HE, and as a result, the cell viability rate was about 91.7% at a concentration of 50 ㎍/ml or less, and subsequent cell experiments were performed at a concentration of 50 ㎍/ml or less. We treated the cells with UVB (20 mJ/cm2) for stimulation, treated HE at various concentrations, and performed ELISA tests and RT-PCR experiments. And HE increased the PIP and mRNA in a dose-dependent manner and showed an expression rate of about 64.2% and 83.4%, respectively, at a concentration of 50 ㎍/ml compared with Cont (50.3% and 45.8%, respectively). And HE suppressed the MMP-1 protein and mRNA in a dose-dependent manner and showed a low expression rate of about 48.7% and 35.9%, respectively, at a concentration of 50 ㎍/ml. These results can be applied to developing anti-wrinkle materials for functional food and cosmetics with HE.
Purpose : Changes in metalloproteinases(MMP) activity have been demonstrated in several disease states, including rheumatoid arthritis and tumor metastasis. More importantly, increased myocardial MMP activity has been reported to occur in both clinical and experimental forms of dilated cardiomyopathy. There was no report about MMP in adriamycin(ADR)-induced cardiomyopathy. The purpose of this study was to investigate gene expression of MMP and tissue inhibitor of metalloproteinases(TIMP) in ADR-induced cardiomyopathy and clarify the relationship between MMP and cytokines. Methods : Male Sprague-Dawley rats were divided into two groups. The first group was control. The second group was given intraperitoneal injections of ADR(5 mg/kg) twice a week over two weeks. Serum concentrations of MMP, TIMP, interleukin(IL)-6 and tumor necrosis factor(TNF)-${\alpha}$ were measured. RNA extraction was performed from frozen rat hearts. Reverse transcription polymerase chain reaction(RT-PCR) was employed. cDNA Microarray analysis was performed by using a set of 5,184 sequence-verified rat cDNA clones. Results : Serum MMP and TIMP levels were not significantly different between the two groups. IL-6 was $36.8{\pm}2.8pg/mL$ and TNF-${\alpha}$$2.2{\pm}2.7pg/mL$ in the ADR group. They were significantly higher than in the control group. Serum MMP correlated significantly with TNF-${\alpha}$(r=0.41, P<0.05). There was no gene expression of MMP, IL-6 or TNF-${\alpha}$ in the hearts of both groups. Gene expression of TIMP was significantly depressed in the hearts of the ADR group. Conclusion : These results suggested a potential role for TNF-${\alpha}$ in the regulation of extracellular matrix remodeling in ADR induced cardiomyopathy. Rapid screening of multiple decreased gene expression by DNA chip may be a useful diagnostic test to detect early cardiac injury before developing ADR induced cardiomyopathy.
Background: Matrix metalloproteinases(MMP) are essential enzymes for tumor invasion and metastasis. Among the MMP family, elevated MMP-9 and stromelysin-3(STR-3) expression have been reported to be poor prognostic factors in lung cancer patients. To evaluate the possibility of a molecular diagnosis of lung cancer using peripheral blood, the mRNA expression level of MMP-9 and STR-3 was measured using a reverse transcriptase-polymerase chain reaction (RT-PCR) in patients with lung cancer. Methods : Ninety six patients(44 patients with lung cancer, 19 pulmonary infection, and 33 control) were included. To detect MMP-9 and STR-3 mRNA expression, RT-PCR was performed in peripheral blood mononuclear cells. ELISA was also used to measure the serum level of MMP-9. Results : MMP-9 was expressed more frequently in patients with a pulmonary infection(18/19, 94.7%) compared to lung cancer patients(26/44, 59.1%) or the controls (23/33, 69.7%) (p=0.018). On the other hand, STR-3 expression was observed more frequently in patients with lung cancer(37/44, 84.1%) compared to the lung infection patients(8/19, 42.1%) or control(20/33, 60.6%) (p=0.003). Among the lung cancer patients, MMP-9 was expressed more frequently when a tumor invaded the lymph nodes(17/24, 70.8%) compared to when a tumor did not(3/13, 23.1%) (p=0.005). The MMP-9 and STR-3 expression levels had no relationship with age, sex, tumor size, distant metastasis, or tumor histology. The serum MMP-9 concentration was not higher in lung cancer patients compared to patients with a pulmonary infection or the control subjects. Conclusion : STR-3 may be used as a diagnostic marker in the peripheral blood of lung cancer patients using RT-PCR. Further studies to evaluate the clinical significance of elevated STR-3 expression in lung cancer patients is recommended.
Min, Bo Ram;Lee, Young Mi;Park, Jae Seok;Choi, Won-Il;Kwon, Kun Young
Tuberculosis and Respiratory Diseases
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v.64
no.1
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pp.22-27
/
2008
Background: Staphylococcus aureus frequently colonizes and infects hospitalized patients. Respiratory infections with Staphylococcus aureus are common in patients with compromised airway defenses. However the mechanisms of S. aureus invasion from colonization to the epithelium are unclear. Cell invasion by S. aureus would require destruction of the extracellular matrix, which is believed to be the result of increased matrix metalloproteinases (MMP) activity. Methods: In this study, respiratory epithelial cells were infected with S. aureus. After removing the extracellular bacteria by washing, the internalized bacteria in the cells were assessed by counting the colonized forming units (CFUs). The cell adhesion proteins, dysadherin and E-cadherin, were evaluated by Western blotting. The MMPs in the bacterial invasion were evaluated by pretreating the cells with GM6001, a MMP inhibitor. Results: The internalization of S. aureus was found to be both time and dose dependent, and the increase in MMP 2 and 9 activity was also dependent on the incubation time and the initial amount of bacterial inoculation. The invasion of S. aureus was attenuated by GM6001 after 12 hours incubation with a multiply of infection (MOI)=50. The expression of dysadherin, a membrane protein, was increased in a time and dose dependent manner, while the expression of E-cadherin was decreased. Conclusion: MMPs may mediate the invasion of S. aureus into epithelial cells.
Background: Expression of matrix metalloproteinases (MMPs) is up-regulated in human cancers. The aim of present study was to investigate the role of MMP-9 C-1562T polymorphism and its interaction with MMP-2 C-735T polymorphism in susceptibility to breast cancer in a population from Western Iran with Kurdish ethnic background. Materials and Methods: The study sample of 205 individuals consisted of 101 breast cancer patients and 104 healthy subjects. MMP-9 C-1562T and MMP-2 C-735T variants were identified using the polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) method. Results: Among 67.4% of studied patients the breast cancer developed in the third and forth decades of the life. The frequency of MMP-9 T allele was 17.3% in patients and 10.1% in controls. The presence of T allele significantly increased the risk of breast cancer by 1.87-fold [OR=1.87 (95% CI 1.05-3.33, p=0.035)]. The frequency of MMP-9 CT+TT genotype tended to be higher in those patients with a family history of cancer in first degree-relatives (36.8%) than those without a family history (28.3%, p=0.37). We observed an interaction between the MMP-9 -1562 T allele with MMP-2 -735 C allele that significantly increased the risk of breast cancer [OR=1.42 (95% CI 1.02-1.98, p=0.036)]. Conclusions: The present study demonstrated that MMP-9 C-1562T polymorphism alone and in combination with MMP-2 C-735T polymorphism increased the risk of breast cancer that might be a useful biomarker in identifying women at risk of developing breast cancer. Also, this study revealed that in most women from Western Iran breast cancer presents in third and fourth decades of life.
Objectives : Fine dust caused by environmental pollution cause oxidative damage and skin aging. In this study, The possibility of using the Codium fragile extract (CFE) as an anti-aging product for skin improvement was evaluated by confirming the protective effect of skin cells from PM10 (particulate matter 10) through inhibition of ROS and MMPs. Methods : In this study, elastase and collagenase inhibitory activities were evaluated. Cell viability was evaluated by treating keratinocytes (HaCaT cell line) with CFE at various concentrations. The cytoprotective effect from PM10 in keratinocyteswas evaluated using the 3-[4,5-dimethylthiazol]-2-yl]-2,5-diphenyl-tetrazoliumbromide (MTT) assay. ROS (reactive oxygen species) was measured in keratinocytes damaged by PM10 using DCF-DA (2′,7′-dichlorofluorescin diacetate) fluorescence staining. As an anti-aging effect of CFE, MMP-1 (matrix metalloproteinase-1) and MMP-1 (matrix metalloproteinase-9) inhibitory activities were evaluated. Results : As a result, CFE decreased the activity of elastase and collagenase. As a result of evaluating the toxicity of CFE, it is non-toxic at a concentration of 10 to 80 ㎍/㎖. Although cell viability of HaCaT cells treated with PM10 decreased, cell viability increased by 38% when treated with CFE 80 ㎍/㎖. Also, ROS decreased by 8.4%, and MMP-1 and MMP-9 decreased at CFE 80 ㎍/㎖. Conclusions : CFE showed excellent cell protection effect, and it is considered that it can be used in anti-aging products for skin improvement by effectively inhibiting ROS and MMPs from keratinocyte damage caused by fine dust.
Gingival tissue samples were obtained during periodontal surgery or tooth extraction. According to the patient's systemic condition & clinical criteria of gingiva, each gingival sample was divided into three groups. Group 1 (n=8) is clinically healthy gingiva without bleeding and no evidence of bone resorption or periodontal pockets, obtained from systemically healthy 8 patients. Group 2 (n=8) is inflamed gingiva from patients with chronic periodontitis. Group 3 (n=8) is inflamed gingiva from patients with chronic periodontitis associated with type 2 diabetes. Tissue samples were prepared and analyzed by Western blotting. The quantification of $IL-1{\beta}$, MMP-13 and TIMP-1 were performed using a densitometer and statistically analyzed by one-way ANOVA followed by Tukey test. 1. The expressions of MMP-13 and TIMP-1 showed increasing tendency in group 2 & 3 compared to group 1. 2. The expressions of $IL-1{\beta}$ & MMP-13 were showed increasing tendency in group 3 compared to group 2. 3. As $IL-1{\beta}$ levels were increasing, MMP-13 showed increasing tendency in group 3, and although $IL-1{\beta}$ , MMP-13 levels were increasing, TIMP-1 levels were similar expressed comparing to group 2. In conclusion, this study demonstrated that the expression levels of MMP-13 and TIMP-1 had increasing tendency in inflamed tissue. It can be assumed that $IL-1{\beta}$ and MMP-13 may be partly involved in the progression of periodontal inflammation associated to type 2 DM.
Background: Obesity weakens acquired immunity and causes infection. This study aimed to investigate the relationship between the inflammatory markers in the gingival crevicular fluid and serum and periodontal bacteria in saliva through obesity control for 4 weeks. Methods: Forty-six subjects with a body mass index (BMI) of ≥23 kg/m2 stayed in the camp for 4 weeks, followed by exercise and a low salt-low fat diet. Body size measurements, oral examinations, blood, saliva, and gingival crevicular fluid were collected before and after the program. C-reactive protein (CRP) in serum, matrix metalloproteinase (MMP)-8, MMP-9, and interleukin (IL)-1β in the gingival sulcus fluid were measured. After extracting bacterial genomic DNA from saliva, the presence of periodontal bacteria were detected using Taq probe. The relationship of each index before and after the program was analyzed through paired t-test and partial correlation analysis. Results: Campylobacter rectus (Cr) increased after the program, and there was no significant change in other bacteria. Serum CRP and Fusobacterium nucleatum (Fn), Aggregatibacter actinomycetemcomitans, Cr, ratio of Fn, and ratio of Cr had a positive relationship at baseline; however, the relationship was not significant after the program. Ratio of Prevotella intermedia had a positive relationship with MMP-9, MMP-8, IL-1β at baseline. Moreover, the ratio of Treponema denticola and the ratio of Tannerella forsythia showed a positive relationship with MMP-8, MMP-9, and IL-1β. The relationship between the ratio of Porphyromonas gingivalis and IL-1β showed a constant positive relationship at baseline and after the program. Conclusion: Obesity control program in subjects with a BMI of ≥23 kg/m2 accompanied by diet and exercise did not affect the changes in periodontal bacteria itself, but changes in the relationship between periodontal bacteria and serum CRP, the relationship between the inflammatory index in the gingival crevicular fluid and periodontal bacteria was observed.
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