ABSTRACT
Prostate cancer (PCa) is a common disease in elderly men, its incidence ranking the second among all malignancies in males in Western countries and increasing in China in the last decade. Tumor metastasis is the main cause of death of PCa patients. In the development and progression of tumor, the tumorous cells in the infiltration area interact with their microenvironment, undergo epithelial-mesenchymal transition (EMT) and consequently cause distant metastases. So to study the role of EMT in the development and progression of tumor is of great significance for the treatment of PCa. This article reviews the relevant literature of the last 3 years and gives an overview of the factors affecting EMT in prostate cancer, aiming at a therapeutic target.
Subject(s)
Humans , Male , Epithelial-Mesenchymal Transition , Prostatic NeoplasmsABSTRACT
<p><b>OBJECTIVE</b>To study the effect of siRNA targeting ADAM17 (ADAM17-siRNA) on the proliferation of prostate cancer PC-3 cells.</p><p><b>METHODS</b>After transfecting PC-3 cells with ADAM17-siRNA 1 and ADAM17-siRNA 2, we detected the expressions of ADAM17 mRNA and protein by RT- PCR and Western blotting, respectively. We measured the changes in the proliferation and DNA synthesis of PC-3 cells by MTT and bromodeoxyuridine (BrdU) incorporation assay, examined the cell cycle profile by flow cytometry, and determined the expressions of the genes associated with PC-3 cell proliferation by Western blotting.</p><p><b>RESULTS</b>Both ADAM17-siRNA 1 and 2 effectively reduced the expressions of ADAM17 mRNA and protein in the PC-3 cells. Knockdown of ADAM17 with the two siRNAs significantly inhibited cell proliferation as compared with the control group (0.43 +/- 0.57 and 0.44 +/- 0.64 vs 0.80 +/- 0.51, P < 0.05) and down-regulated DNA synthesis (0.48 +/- 0.43 and 0.54 +/- 0.59 vs 0.79 +/- 0.72, P < 0.05). The cell cycle profile showed that the cell population of the G1 phase was markedly higher in both the ADAM17-siRNA groups than in the control ([61.83 +/- 2.41]% and [59.78 +/- 1.92]% vs [41.38 +/- 1.53]%, P < 0.05), but that of the S phase remarkably lower in the former two than in the latter ([23.64 +/- 2.56]% and [25.24 +/- 1.86]% vs [33.51 +/- 1.47]%, P < 0.05), with a concomitant decrease in the expression of the cell cycle protein cyclin D1 and increase in the cyclin-dependent kinase inhibitor p21.</p><p><b>CONCLUSION</b>ADAM17-siRNA can effectively inhibit the proliferation of PC-3 cells by up-regulating cyclin D1 and down-regulating p21 protein, and ADAM17 has a potential value in the gene therapy of prostate cancer.</p>
Subject(s)
Humans , Male , ADAM Proteins , Genetics , Metabolism , ADAM17 Protein , Cell Line, Tumor , Cell Proliferation , Cyclin D1 , Metabolism , Cyclin-Dependent Kinase Inhibitor p21 , Metabolism , Down-Regulation , Prostatic Neoplasms , Genetics , Metabolism , Pathology , RNA Interference , RNA, Messenger , Genetics , RNA, Small Interfering , Genetics , Signal Transduction , TransfectionABSTRACT
<p><b>OBJECTIVE</b>To construct the bait vector pGBKT7-TACEc (cytoplasmic tail of tumor necrosis factor-alpha converting enzyme) of Macthmaker GAL4 Two-hybrid System 3, and to test whether it has self-activation and toxic action.</p><p><b>METHODS</b>TACEc gene was amplified by RT-PCR from the mouse testis, and the EcoRI and BamHI sites were introduced into it. The TACEc gene, after sequenced, was cloned into pGBKT7. Self-activation and toxic action of the recombination vector pGBKT7-TACEc was tested.</p><p><b>RESULTS</b>The pGBKT7-TACEc vector was successfully constructed and proved of no self-activation and toxic action.</p><p><b>CONCLUSION</b>The pGBKT7-TACEc can be applied to the screening of the mouse testis cDNA library in the yeast two-hybrid system.</p>
Subject(s)
Animals , Male , Mice , ADAM Proteins , Genetics , Metabolism , ADAM17 Protein , Cloning, Molecular , DNA, Complementary , Mice, Inbred BALB C , Plasmids , RNA , Reverse Transcriptase Polymerase Chain Reaction , Testis , Metabolism , Two-Hybrid System Techniques , Yeasts , MetabolismABSTRACT
<p><b>OBJECTIVE</b>To investigate the effects of interferon-gamma (IFN-gamma) and tumor necrosis factor alpha (TNF-gamma) on the sperm acrosin activity and the rate of acrosome reaction and to probe into their mechanisms.</p><p><b>METHODS</b>Thirty-six nearly normal semen samples were treated with IFN-gamma and/or TNF-alpha after isolated by 75% Percoll. The sperm acrosin activity was tested by the method of BAEE/ADH Unity, the rate of acrosome reaction observed by Triple-stain technique, the NO concentration measured by HPLC and the activities of Na+ -K+ -ATPase, Ca2+ -ATPase and SOD assayed by kit method.</p><p><b>RESULTS</b>Both IFN-gamma and TNF-gamma could decrease sperm acrosin activity and acrosome reaction (P < 0.05 or P < 0.01). TNF-alpha showed stronger inhibiting effect, IFN-gamma markedly reduced the activities of Na+ -K+ -ATPase, Ca2+ -ATPase and SOD in sperm (P < 0.01), and their synergistic action was weaker. However TNF-alpha produced hardly any effect on Na+ -K+ -ATPase and Ca2+ -ATPase. The NO concentration in sperm was significantly increased by IFN-gamma and/or TNF-alpha (P < 0.01).</p><p><b>CONCLUSION</b>IFN-gamma and TNF-alpha have some inhibiting effect on sperm acrosin activity and the rate of acrosome reaction, which could be attributed to their influence on the activities of Na+ -K+ -ATPase, Ca2+ -ATPase and SOD, the NO concentration and so on.</p>
Subject(s)
Adult , Humans , Male , Middle Aged , Acrosome Reaction , Calcium-Transporting ATPases , Metabolism , Chromatography, High Pressure Liquid , Interferon-gamma , Pharmacology , Nitric Oxide , Metabolism , Sodium-Potassium-Exchanging ATPase , Metabolism , Spermatozoa , Metabolism , Superoxide Dismutase , Metabolism , Tumor Necrosis Factor-alpha , PharmacologyABSTRACT
<p><b>OBJECTIVE</b>To investigate the apoptosis-promoting effect of PDCD5 on human prostate cancer cells PC-3M-1E8.</p><p><b>METHODS</b>PCI-neo and PCI-neo-PDCD5 were transfected into PC-3M-1E8 cells by Lipofectamine 2000, the viability of the cells was analyzed by MTT assay 16 hours after removal of the serum, and the apoptosis was determined by in situ end-labeling and electron microscopy.</p><p><b>RESULTS</b>The viability and growing speed of the transfected cells were significantly decreased and their apoptotic indexes significantly increased as compared with the control group (P < 0.001).</p><p><b>CONCLUSION</b>PDCD5 may significantly inhibit the in vitro growth and promote the apoptosis of human prostate cancer cells PC-3M-1E8.</p>
Subject(s)
Humans , Male , Apoptosis , Genetics , Physiology , Apoptosis Regulatory Proteins , Genetics , Physiology , Cell Line, Tumor , In Situ Nick-End Labeling , Lipids , Chemistry , Neoplasm Proteins , Genetics , Physiology , Plasmids , Chemistry , Genetics , Prostatic Neoplasms , Genetics , Pathology , Reverse Transcriptase Polymerase Chain Reaction , Transfection , MethodsABSTRACT
<p><b>OBJECTIVE</b>To research on the conservative methods used to preserve the femoral head of patients with osteonecrosis of the femoral head.</p><p><b>METHODS</b>In these series surgical procedures the osteonecrotic lesion was removed and various vascularized bone blocks or periosteal flaps with its nutrient vessels were transferred to regain sphericity of the femoral head and reinforce the sequestrum. The current study assessed 1005 patients (1226 hips) operated on from 1989 to 2002 with an average follow-up of 5.1 years (range, 1.5-15 years). The mean age of the patients was 37.4 years (range, 17-65 years).</p><p><b>RESULTS</b>Sixty-one hips (57 patients) had conversion surgery to a total hip arthroplasty because of progressive collapse or severe pain, or both. In the patients without failure, postoperative Harris hip score improved significantly. Of the 1174 reconstructions that were in situ, 1041 (89.4%) were clinically successful, and 878 (75.4%) were radiologically successful. In relation to the stage of necrosis according to the classification system of Ficat and Alert, good results were achieved in 95.3% of the patients with stages II disease, 87.9% with stages III and 60.8% with stages IV.</p><p><b>CONCLUSIONS</b>Conservative methods of vascularized bone block or periosteal flap transfer should be considered in active symptomatic patients to preserve the femoral head. In addition, the earlier the stages of the disease the better outcome could be obtained.</p>
Subject(s)
Adolescent , Adult , Aged , Female , Humans , Male , Middle Aged , Bone Transplantation , Methods , Femur , General Surgery , Femur Head Necrosis , General Surgery , Follow-Up Studies , Microsurgery , Retrospective StudiesABSTRACT
Objective To evaluated the clinical results of treatment of osteonecrosis of the femoral head(ONFH)by using bone flap pedicled with gluteal muscle branch of ascending branch of the lateral femo- ral circumflex artery and transversal branch of the lateral femoral cireumflex artery.Methods Bone flap pedicled with double blood vessels was applied in 32 hips with stageⅡandⅢONFH according to the Fieat staging system.Fifteen hips were in stageⅡand 17 were in stageⅢ.All patients were followed up for a mean of 25 months(range,15-38 months)and were assessed clinically and radiologically according to Harris sco- ring.Selective digital subtraction angiography was performed in 9 cases to confirm the blood reconstruction of femoral head.Results Two cases underwent total hip replacement postoperatively.Preoperative and postop- erative Harris score were 55 and 88.6.Clinical success rate was 90.6% and radiological success rate was 87.5%.DSA demonstrated blood supply was found reconstruction in the necrotic femoral head.Conclusion Transplantation of bone flap pedicled with gluteal muscle branch of ascending branch of the lateral femoral circumflex artery and transversal branch of the lateral femoral circumflex artery appears to be a effective treat- ment for osteonecrosis of the femoral head,blood supply of bone flap and blood reconstruction of femoral head was confirmed.Early clinical results were satisfied.