ABSTRACT
<p><b>OBJECTIVE</b>To investigate the effects of atorvastatin on advanced glycation end products (AGE) induced monocyte chemoattractant protein-1 (MCP-1) expression in human umbilical vein endothelial cells (HUVECs) and whether this effect could be linked to peroxisome proliferator-activated receptor-γ (PPAR-γ) and nuclear factor-κB (NF-κB).</p><p><b>METHODS</b>Grouping: (1) Blank control group; (2) BSA group; (3) AGE group: cells were incubated with different concentrations of AGE (10(-4), 10(-3), 10(-2) and 10(-1) g/L) for 24 hours; (4) AGE + Atorvastatin group: cells were incubated with different concentrations of atorvastatin (0.1, 1, 10 µmol/L) for 1 hour, then incubated with AGE (10(-1) g/L) for 24 hours; (5) PPAR-γ agonist (15 d-PGJ2) group: cells were incubated with 15 d-PGJ2 (10 µmol/L) for 1 hour, then incubated with AGE (10(-1) g/L) for 24 hours; (6) PPAR-γ inhibitor (GW9662) group: cells were incubated with GW9662 (5000 nmol/L) for 1 hour, then incubated with atorvastatin (1 µmol/L) and AGE (10(-1) g/L) for 24 hours. Collagenase was used to isolate the endothelial cell from human umbilical vein; RT-PCR was performed to examine the mRNA expression of MCP-1 and PPAR-γ; Western blot was performed to detect NF-κB p65 protein.</p><p><b>RESULTS</b>(1) The expression of MCP-1 mRNA was increased in proportion with increasing concentrations of AGEs which could be blocked by atorvastatin in a dose-dependent manner. (2) AGE (10(-1) g/L) significantly downregulated the expression of PPAR-γ mRNA (0.22 ± 0.08 vs. 0.69 ± 0.09, P < 0.01) while upregulated the expression of phospho-NF-κB p65 protein (0.78 ± 0.06 vs. 0.31 ± 0.01, P < 0.01) and nonphospho-NF-κB p65 protein (1.61 ± 0.16 vs. 0.59 ± 0.14, P < 0.01) compared with the control group which could be significantly attenuated by atorvastatin. (3) PPAR-γ agonist decreased the expression of phospho-NF-κB p65 protein (0.21 ± 0.01 vs. 0.78 ± 0.06, P < 0.01), nonphospho-NF-κB p65 protein (0.67 ± 0.14 vs. 1.61 ± 0.16, P < 0.01) and MCP-1 mRNA (0.17 ± 0.02 vs. 0.93 ± 0.12, P < 0.01) compared with AGE (10(-1) g/L) group. (4) PPAR-γ inhibitor antagonized the effect of atorvastatin on the expression of phospho-NF-κB p65 protein, nonphospho-NF-κB p65 protein and MCP-1 mRNA stimulated by AGE in HUVECs (P < 0.01).</p><p><b>CONCLUSION</b>The anti-inflammatory properties of atorvastatin in AGE stimulated HUVECs may partly be attributed to the effect on upregulation of PPAR-γ and downregulation of NF-κB signaling pathway.</p>
Subject(s)
Humans , Atorvastatin , Cells, Cultured , Chemokine CCL2 , Genetics , Metabolism , Glycation End Products, Advanced , Metabolism , Heptanoic Acids , Pharmacology , Human Umbilical Vein Endothelial Cells , Metabolism , PPAR gamma , Metabolism , Pyrroles , Pharmacology , RNA, Messenger , Genetics , Signal Transduction , Transcription Factor RelA , MetabolismABSTRACT
The over expression of fatty acid synthase (FAS), a key enzyme in biosynthesis of fatty acid, can enhance enzyme activity and result in the malignant behavior, special material metabolism and energy metabolism of tumors. The expression of FAS is significantly higher in prostate cancer than in normal prostate tissues, which shows that FAS can be used as a marker in the early diagnosis of prostate cancer. The abnormally increased expression of FAS in prostate cancer may offer a new target for the drug treatment of the disease.
Subject(s)
Humans , Male , Biomarkers, Tumor , Metabolism , Early Diagnosis , Fatty Acid Synthases , Metabolism , Prostatic Neoplasms , DiagnosisABSTRACT
<p><b>OBJECTIVE</b>To investigate the diagnosis, treatment and prognosis of sarcoma of the adult prostate.</p><p><b>METHODS</b>We reported 6 cases of sarcoma of the adult prostate, of which 3 were leiomyosarcoma, 2 rhabdomyosarcoma and 1 malignant neurilemoma, 2 at Ghavimi Stage II, 3 at Stage III and 1 at Stage IV. The patients were aged from 18 to 44 years (mean 31 years) and their disease course ranged from 3 to 12 months (mean 7 months). Five of them received operation, radiotherapy and / or chemotherapy and 1 underwent cystostomy only.</p><p><b>RESULTS</b>Immunohistochemical dyeing showed vimentin to be positive while PSA and PAP negative in all the 6 cases, actin (HHF35) positive in the cases of leiomyosarcoma and rhabdomyosarcoma, and S-100 and lysozyme positive in the case of malignant neurilemoma. One case failed to be followed up, and the other 5 died 2-11 months after the operation.</p><p><b>CONCLUSION</b>Sarcoma of the adult prostate initiates with the symptom of progressive dysuria, which can be diagnosed by DRE test and confirmed by needle biopsy. Early diagnosis and radical surgical resection may offer the best chance of survival, but with poor prognosis.</p>