ABSTRACT
Endothelin-3 (ET-3) is aberrantly expressed in both metastatic melanoma tissues and cultured melanoma cells. Our previous work showed that ET-3 could promote survival of metastatic melanoma cells via its altered expression. In this study, we investigated the mechanisms responsible for these gene-induced phenotypes in melanoma cells. An ET-3 gene sequence-specific shRNA vector pLVTHM-ET3-RNAi was constructed and transfected into human malignant melanoma cells A375 and MMRU, and the resultant molecular events and cellular changes were examined. As compared with the empty-vector group, cell proliferation was slowed down, and the growth inhibition rates were 38.9% in A375 cells and 38.4% in MMRU cells after transfection. In addition, cell invasion capability was also inhibited, with a reduction of 62.2% in A375 cells and 54.3% in MMRU cells. The percentage of apoptotic cells was found to increase. Meanwhile, in both cell lines, secreted protein acidic and rich in cysteine (SPARC) levels were down-regulated together with inhibition of its upstream signaling molecule, NF-κB. Thus, the current results suggested that down-regulated expression of ET3 attenuates the malignant behaviors of human melanoma cells partially by decreasing the expression of SPARC and NF-κB.
ABSTRACT
The rs10954213 polymorphism and the haplotype diversity in interferon regulatory factor 5 (IRF5) play a special role in systemic lupus erythematosus (SLE) but with inconclusive results. We conducted a meta-analysis integrating case-control and haplotype variant studies in multiple ethnic populations to clearly discern the effect of these two variants on SLE. Eleven studies on the relation between rs10954213 polymorpisms in IRF5 and SLE were included and we selected a random effect model to calculate the pooled odds ratios (ORs) and the corresponding 95% confidence interval (95% CI). A total of 6982 cases and 8077 controls were involved in the meta-analysis. The pooled results indicated that A allele was significantly associated with increased risk of SLE as compared with the IRF5 rs10954213 G allele (A vs. G, P<0.00001) in all subjects. The same pattern of the results was also obtained in the European, African American, and Latin American. Asian population had a much lower prevalence of the A allele (49.1%) than any other population studied, and Europeans had the highest frequency of the IRF5 rs10954213 A allele (62.1%). The significant association of increased SLE risk and TCA haplotype was indicated in the contrast of TCA vs. TTA as the pooled OR was 2.14 (P=0.002). The same result was also found in the contrast of TCA vs. TTG as the pooled OR was 1.45 (P=0.004). This meta-analysis suggests that the A allele of rs10954213 and TCA haplotype (rs2004640-rs2070197-rs10954213) in IRF5 is associated with the increased risk of SLE in different ethnic groups, and its prevalence is ethnicity dependent.
ABSTRACT
The rs10954213 polymorphism and the haplotype diversity in interferon regulatory factor 5 (IRF5) play a special role in systemic lupus erythematosus (SLE) but with inconclusive results. We conducted a meta-analysis integrating case-control and haplotype variant studies in multiple ethnic populations to clearly discern the effect of these two variants on SLE. Eleven studies on the relation between rs10954213 polymorpisms in IRF5 and SLE were included and we selected a random effect model to calculate the pooled odds ratios (ORs) and the corresponding 95% confidence interval (95% CI). A total of 6982 cases and 8077 controls were involved in the meta-analysis. The pooled results indicated that A allele was significantly associated with increased risk of SLE as compared with the IRF5 rs10954213 G allele (A vs. G, P<0.00001) in all subjects. The same pattern of the results was also obtained in the European, African American, and Latin American. Asian population had a much lower prevalence of the A allele (49.1%) than any other population studied, and Europeans had the highest frequency of the IRF5 rs10954213 A allele (62.1%). The significant association of increased SLE risk and TCA haplotype was indicated in the contrast of TCA vs. TTA as the pooled OR was 2.14 (P=0.002). The same result was also found in the contrast of TCA vs. TTG as the pooled OR was 1.45 (P=0.004). This meta-analysis suggests that the A allele of rs10954213 and TCA haplotype (rs2004640-rs2070197-rs10954213) in IRF5 is associated with the increased risk of SLE in different ethnic groups, and its prevalence is ethnicity dependent.
Subject(s)
Female , Humans , Male , Genetic Association Studies , Genetic Markers , Genetics , Genetic Predisposition to Disease , Epidemiology , Genetics , Genetic Variation , Genetics , Haplotypes , Genetics , Interferon Regulatory Factors , Genetics , Lupus Erythematosus, Systemic , Epidemiology , Genetics , Polymorphism, Single Nucleotide , Genetics , PrevalenceABSTRACT
Endothelin-3 (ET-3) is aberrantly expressed in both metastatic melanoma tissues and cultured melanoma cells. Our previous work showed that ET-3 could promote survival of metastatic melanoma cells via its altered expression. In this study, we investigated the mechanisms responsible for these gene-induced phenotypes in melanoma cells. An ET-3 gene sequence-specific shRNA vector pLVTHM-ET3-RNAi was constructed and transfected into human malignant melanoma cells A375 and MMRU, and the resultant molecular events and cellular changes were examined. As compared with the empty-vector group, cell proliferation was slowed down, and the growth inhibition rates were 38.9% in A375 cells and 38.4% in MMRU cells after transfection. In addition, cell invasion capability was also inhibited, with a reduction of 62.2% in A375 cells and 54.3% in MMRU cells. The percentage of apoptotic cells was found to increase. Meanwhile, in both cell lines, secreted protein acidic and rich in cysteine (SPARC) levels were down-regulated together with inhibition of its upstream signaling molecule, NF-κB. Thus, the current results suggested that down-regulated expression of ET3 attenuates the malignant behaviors of human melanoma cells partially by decreasing the expression of SPARC and NF-κB.
Subject(s)
Humans , Cell Line, Tumor , Endothelin-3 , Genetics , Gene Silencing , Melanoma , Genetics , Pathology , Osteonectin , GeneticsABSTRACT
<p><b>OBJECTIVE</b>To study the clinical effects of menisci reformation and repair for the treatment of discoid meniscus injuries and to explore the operation methods.</p><p><b>METHODS</b>From Jun. 2005 to Dem. 2009, 28 patients underwent arthroscopic menisci reformation and repair for discoid meniscus, including 23 males and 5 females, ranging in age from 6 to 42 years, with an average of 32 years. The nature of meniscus and the type and range of tear were judged under arthroscope. The menisci reformation and repair were used to treat discoid meniscus tear at the edge. After the operation, the brace was used for 8 weeks, and heavy exercise should be avoided for 6 months. The Lysholm score was adopted to evaluate therapeutic effects.</p><p><b>RESULTS</b>All the patients were followed up ranging from 3 to 36 months, averaged 8 months. The preoperative Lysholm scores ranged from 62 to 74, with a mean of (67.23 +/- 5.24), and the postoperative Lysholm scores ranged from 80 to 96, with a mean of (87.24 +/- 5.26). There was no occurrence of re-tear or re-operation due to symptom recurrence.</p><p><b>CONCLUSION</b>The menisci reformation and repair has better clinical effects on the treatment of discoid meniscus tear and can be regarded as one of the operational options.</p>
Subject(s)
Adolescent , Adult , Child , Female , Humans , Male , Young Adult , Arthroscopy , Methods , Follow-Up Studies , Knee Joint , Magnetic Resonance Imaging , Menisci, Tibial , General Surgery , Tibial Meniscus InjuriesABSTRACT
<p><b>OBJECTIVE</b>To study the clinical and pathologic characteristics of poorly differentiated cutaneous angiosarcoma of scalp.</p><p><b>METHODS</b>Eight cases of poorly differentiated cutaneous angiosarcoma of scalp were enrolled into this study. The clinical manifestations and histopathologic features were analyzed. Immunohistochemical study for CD31, CD34, factor VIII-related antigen, vimentin, AE1/AE3, CAM5. 2, epithelial membrane antigen and carcinoembryonic antigen was performed.</p><p><b>RESULTS</b>The mean age of the patients was 69 years. The male-to-female ratio was 5 : 3. The tumor manifested clinically as bruise-like lesion in early phase, indurated erythematous plaque accompanied by nodules, ulcerations and bleeding in advanced phase. Histologically, the tumor was composed of solid sheets of undifferentiated spindle cells which were not easily recognizable as vascular in origin. Nuclear atypia was always present. The tumor cells in all of the 8 cases strongly expressed CD31, factor VIII-related antigen and vimentin. Weak expression of CD34, AE1/AE3 and CAMS. 2 was noted in 2, 4 and 4 cases, respectively. The staining for epithelial membrane antigen, carcinoembryonic antigen and S-100 was negative. Conclusions Angiosarcoma needs to be excluded by histologic examination whenever bruise-like and erythematous lesions occurring on scalp skin of elderly patients. The endothelial origin of the tumor cells can be confirmed with immunostaining for CD31, CD34 and factor VIII-related antigen.</p>
Subject(s)
Aged , Aged, 80 and over , Female , Humans , Male , Middle Aged , Antigens, CD34 , Allergy and Immunology , Biomarkers, Tumor , Cell Adhesion Molecules , Cell Differentiation , Endothelium , Metabolism , Hemangiosarcoma , Allergy and Immunology , Platelet Endothelial Cell Adhesion Molecule-1 , Allergy and Immunology , Scalp , Pathology , Skin Neoplasms , Allergy and Immunology , Metabolism , Pathology , VimentinABSTRACT
Objective To investigate the expression of osteopontin and matrix metalloproteinase-9 (MMP9),and the relationship of osteopontin and MMP9 in malignant melanoma.Methods Expression of osteopontin and MMP9 was measured by immunohistochemical SP method in 23 patients with primary cuta- neous malignant melanoma,17 patients with metastatic melanoma and 20 patients with pigmented nevus. Results Osteopontin and MMP9 were expressed respectively in 87.5% and 75.0% of 40 malignant melanoma specimens,15.0% and 10.0% of 20 pigmented nevus specimens.The expression of both osteo- pontin and MMP9 was significantly higher (both P＜0.05) in malignant melanoma than in pigmented ne- vus.There was no correlation between the expression of osteopontin and MMP9,with age,sex,lymph node metastasis or location of lesions (P＞0.05).Twenty-nine cases were positive for both osteopontin and MMP9,4 negative for either osteopontin or MMP9.Conclusion Both osteopontin and MMP9 were over- expressed in malignant melanoma,but neither was related to lymph node metastasis.