ABSTRACT
Cullin1 (Cul1) is a scaffold protein of the ubiquitin E3 ligase Skp1/Cullin1/Rbx1/F-box protein complex, which ubiquitinates a broad range of proteins involved in cell-cycle progression, signal transduction, and transcription. To investigate the role of Cul1 in the development of renal cell carcinoma (RCC), we evaluated the Cul1 expression by immunohistochemistry using a tissue microarray (TMA) containing 307 cases of RCC tissues and 34 normal renal tissues. The Cul1 expression was increased significantly in RCC and was correlated with renal carcinoma histology grade (P = 0.007), tumor size (P = 0.013), and pT status (P = 0.023). Also, we found that silencing of Cul1 leads to increased expression of p21 and p27 that could inhibit the cyclin D1 and cyclin E2 expressions and arrest cell cycle at the G1 phase. Furthermore, knockdown of Cul1 inhibits RCC cell migration and invasion abilities by up-regulating the expression of TIMP-1 which could inhibit the expression of MMP-9. Finally, using bioluminescence imaging, we found that Cul1 knockdown significantly reduced the tumor growth in vivo. Cul1 may constitute a potential therapeutic target in RCC.
Subject(s)
Carcinoma, Renal Cell/metabolism , Cell Movement/physiology , Cell Proliferation/physiology , Cullin Proteins/biosynthesis , Kidney Neoplasms/metabolism , Animals , Blotting, Western , Carcinoma, Renal Cell/genetics , Carcinoma, Renal Cell/therapy , Cell Line, Tumor , Cell Movement/genetics , Cell Proliferation/genetics , Cullin Proteins/genetics , Cyclin-Dependent Kinase Inhibitor p21/metabolism , Cyclin-Dependent Kinase Inhibitor p27/metabolism , G1 Phase Cell Cycle Checkpoints/genetics , G1 Phase Cell Cycle Checkpoints/physiology , Humans , Immunohistochemistry , Kidney Neoplasms/genetics , Kidney Neoplasms/therapy , Matrix Metalloproteinase 9/metabolism , Mice, Inbred BALB C , Mice, Nude , Neoplasm Invasiveness , RNA Interference , RNAi Therapeutics/methods , Tissue Array Analysis , Tissue Inhibitor of Metalloproteinase-1/metabolism , Xenograft Model Antitumor Assays/methodsABSTRACT
PURPOSE: To evaluate the effectiveness and safety of minimally invasive percutaneous nephrolithotomy (mPCNL) without nephrostomy drainage tubes. METHODS: We prospectively enrolled 32 eligible patients with kidney stones at our hospital. Patients were randomly assigned to a conventional mPCNL group (ureteric Double-J stents and nephrostomy drainage tubes) or a tubeless mPCNL group (ureteric catheter but no drainage tubes). A single experienced surgeon performed all operations. RESULTS: At baseline, the two groups had similar age, maximum stone diameter, and gender distribution. There were no significant differences in operation time, presence of postoperative fever, stone clearance, and level of postoperative serum hemoglobin. However, the tubeless mPCNL group had significantly shorter hospital stays (3 vs. 4 days, p = 0.032) and significantly less back pain (5 patients vs. 14 patients, p = 0.003) than the conventional mPCNL group. CONCLUSIONS: No significant differences were found between conventional and tubeless mPCNL in safety issues and stone clearance rate. However, patients treated with tubeless mPCNL had shorter hospitalization stays and were less likely to experience back pain.
Subject(s)
Kidney Calculi/surgery , Minimally Invasive Surgical Procedures/instrumentation , Minimally Invasive Surgical Procedures/methods , Nephrostomy, Percutaneous/instrumentation , Nephrostomy, Percutaneous/methods , Adult , Aged , Back Pain/epidemiology , Drainage/instrumentation , Female , Humans , Incidence , Length of Stay , Male , Middle Aged , Minimally Invasive Surgical Procedures/adverse effects , Nephrostomy, Percutaneous/adverse effects , Prospective Studies , Stents , Treatment Outcome , Urinary CathetersABSTRACT
OBJECTIVE: To study the protection of gene transfer-induced human heme oxygenase-1 over-expression against renal ischemia reperfusion injury in rats. METHODS: The model of kidney ischemia-reperfusion injury was established with Sprague-Dawley rats. In the therapy group (n=18), the left kidney was perfused and preserved with Ad-hHO-1 at 2.5×10(9) pfu/1.0 ml after flushed with 0-4°C HC-A organ storage solution via donor renal aorta. The rats in control groups were perfused with 0.9% saline solution (n=12) or the vector carrying no interest gene Ad-EGFP 2.5×10(9) pfu/1.0 ml (n=18) instead of Ad-hHO-1. BUN and Cr in serum were measured by slide chemical methods. The kidney samples of rats were harvested for assay of histology, immunohistochemistry and quantification of HO enzymatic activity. Apoptosis cells in the kidney were measured by TUNEL. RESULTS: Ad-hHO-1 via donor renal aorta could transfect renal cells of rats effectively, enzymatic activity of HO in treated group [(1.62±0.07) nmol×mg(-1)×min(-1)] is higher than in control groups treated with saline solution team [(1.27±0.07) nmol×mg(-1)×min(-1)] and vector EGFP team [(1.22±0.06) nmol×mg(-1)×min(-1)] (P<0.01). Immunohistochemically, we found that the rats treated with Ad-hHO-1 expressed hHO-1 in kidneys at a high level. Corresponding to this, the level of BUN and Cr, as well as the number of apoptosis cells, were decreased, and the damage in histology by HE staining was ameliorated. CONCLUSION: Over-expression of human HO-1 can protect the kidney from ischemia/reperfusion injury in rats.
