RESUMEN
OBJECTIVE: To investigate the expression of glycoprotein non-metastatic melanoma protein B (GPNMB) in prostate cancer and its clinical significance. METHODS: The expression of GPNMB was analysed in 63 prostate cancer and 3 heterosexual hyperplasia prostate tissue and 8 benign prostatic hyperplasia samples by immunohistochemical staining, with integral optical density(IOD) value representing expression level of positive cells. RESULTS: The expression of GPNMB was lower in benign prostatic hyperplasia (BPH, IOD=70 017.49) than in Atypical hyperplasia (IOD=101 547.33, P=0.000 1) . The expression of GPNMB in tumor (IOD= 162 027.54) was higher than in non-tumor group (IOD=79 290.97), which included BPH and atypical hyperplasia (P=0.000 1). But GPNMB expression level was not positively elevated with degree of malignancy of prostate cancer. However, the expression of GPNMB in low pathological grading(IOD=177 944.30) was higher than that in high pathological grading(IOD=150 885.81, P=0.013). CONCLUSION: The abnormal expression of GPNMB may play an important role in the development of prostate cancer and its detection may be useful for the early diagnosis of prostate cancer.
Asunto(s)
Glicoproteínas de Membrana/metabolismo , Neoplasias de la Próstata/metabolismo , Biomarcadores de Tumor/metabolismo , Humanos , Masculino , Próstata/metabolismo , Próstata/patología , Hiperplasia Prostática/metabolismo , Neoplasias de la Próstata/patologíaRESUMEN
OBJECTIVE: To determine whether acute withdrawal of simvastatin treatment in healthy normocholesterolemic men impairs the brachial artery endothelial function. METHODS: The study was performed on 16 healthy, young male subjects with desirable serum levels of cholesterol. They were administered with simvastatin (20 mg/d) for 4 weeks. Endothelial dependent flow-mediated vasodilation (FMD) was assessed on the brachial artery using high-resolution ultrasound, and fasting serum lipid profiles as well as vasoactive substances [NO, endothelin (ET) and 6-keto-PGF1 alpha] were measured. The parameters mentioned above were obtained at indicated time points before and after simvastatin treatment. RESULTS: Simvastatin treatment for 4 weeks significantly improved FMD and reduced low density LDL-C and total TC levels. Withdrawal of simvastatin, however, resulted in dramatic impairment of endothelium-dependent relaxation on the first day after withdrawal [(4.6 +/- 0.48)% and (10.9 +/- 0.89)%, P < 0.01], Furthermore, FMD decreased significantly as compared with baseline level [(4.6 +/- 0.48 )% vs (6.44 +/- 0.47)%, P < 0.01]. Serum NO level varied according to the change of endothelial-dependent relaxation (gamma = 0.496, P < 0.01). After discontinuing simvastatin therapy, plasma ET increased and plasma 6-keto-PGF1 alpha decreased progressively. In addition, serum TC and LDL-C were not significantly modified during the initial 2 days. No correlation was shown between FMD and serum LDL-C level (gamma = -0.172, P = 0.101). CONCLUSIONS: Withdrawal of simvastatin not only abrogates the beneficial effect on endothelial function of healthy normocholesterolemic men rapidly, but also induces further endothelial deterioration as compared with pretreatment status. This adverse effect is independent of serum cholesterol. The underlying mechanism may be related to the suppression of endothelial NO production.
Asunto(s)
Arteria Braquial/efectos de los fármacos , Endotelio Vascular/efectos de los fármacos , Simvastatina/administración & dosificación , 6-Cetoprostaglandina F1 alfa/sangre , Adulto , Anticolesterolemiantes/administración & dosificación , Anticolesterolemiantes/efectos adversos , Arteria Braquial/fisiología , Colesterol/sangre , LDL-Colesterol/sangre , Endotelio Vascular/fisiología , Humanos , Masculino , Óxido Nítrico/sangre , Simvastatina/efectos adversos , Vasodilatación/efectos de los fármacos , Adulto JovenRESUMEN
BACKGROUND: Glycoprotein non-metastatic melanoma protein B (GPNMB) plays an important role in the pathogenesis of inflammatory and malignant diseases. We investigated the expression of GPNMB in benign and malignant skin diseases. METHODS: Tissue microarray was performed in the skin tissues of 102 cases including malignant melanoma (MM), squamous cell carcinoma (SCC), basal cell carcinoma (BCC), and benign dermatosis. The expression of GPNMB in the tissues was detected by immunohistochemistry. Twenty cases of normal skin and adjacent neoplastic normal skin tissues were selected as controls. RESULTS: GPNMB was positively stained in skin malignancies (38/50, 76%), which was significantly higher than that in the control and the benign skin tissues (P = 0.001 and < 0.001 respectively). GPNMB was positively stained in MM (13/15, 87%) and SCC (16/20, 80%) (P < 0.001). Significant higher expression of GPNMB was observed in patients aged ≥ 65 years than those less than 65 years (n = 11 and n = 9 respectively, P = 0.027). No significant difference of the expression rates was observed between normal control and BCC; however, stronger intensity was detected in the latter. Negative or weak expression was observed in the controls. CONCLUSION: Over-expression of GPNMB correlated strongly and might play an important role in the pathogenesis of MM and SCC.