46 research outputs found
Urachal Actinomycosis Mimicking a Urachal Tumor
A 26-year-old man presented with lower abdominal discomfort and a palpable mass in the right lower quadrant. An abdominal computed tomography (CT) scan revealed an abdominal wall mass that extended from the dome of the bladder. Fluorine-18 fluorodeoxyglucose (FDG) positron-emission tomography/CT (PET/CT) showed hypermetabolic wall thickening around the bladder dome area that extended to the abdominal wall and hypermetabolic mesenteric infiltration. Differential diagnosis included a urachal tumor with invasion into adjacent organs and chronic inflammatory disease. Partial cystectomy with abdominal wall mass excision was performed, and the final pathologic report was consistent with urachal actinomycosis
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MMP9 Processing of HSPB1 Regulates Tumor Progression
Matrix metalloproteinases regulate pathophysiological events by processing matrix proteins and secreted proteins. Previously, we demonstrated that soluble heat shock protein B1 (HSPB1) is released primarily from endothelial cells (ECs) and regulates angiogenesis via direct interaction with vascular endothelial growth factor (VEGF). Here we report that MMP9 can cleave HSPB1 and release anti-angiogenic fragments, which play a key role in tumorprogression. We mapped the cleavage sites and explored their physiological relevance during these processing events. HSPB1 cleavage by MMP9 inhibited VEGF-induced ECs activation and the C-terminal HSPB1 fragment exhibited more interaction with VEGF than did full-length HSPB1. HSPB1 cleavage occurs during B16F10 lung progression in wild-type mice. Also, intact HSPB1 was more detected on tumor endothelium of MMP9 null mice than wild type mice. Finally, we confirmed that secretion of C-terminal HSPB1 fragment was significantly inhibited lung and liver tumor progression of B16F10 melanoma cells and lung tumor progression of CT26 colon carcinoma cells, compared to full-length HSPB1. These data suggest that in vivo MMP9-mediated processing of HSPB1 acts to regulate VEGF-induced ECs activation for tumor progression, releasing anti-angiogenic HSPB1 fragments. Moreover, these findings potentially explain an anti-target effect for the failure of MMP inhibitors in clinical trials, suggesting that MMP inhibitors may have pro-tumorigenic effects by reducing HSPB1 fragmentation
A Multi-institutional Study on Histopathological Characteristics of Surgically Treated Renal Tumors: the Importance of Tumor Size
PURPOSE: The incidence of accidentally detected small renal tumors is increasing throughout the world. In this multi-institutional study performed in Korea, histopathological characteristics of contemporarily surgically removed renal tumors were reviewed with emphasis on tumor size. MATERIALS and METHODS: Between January 1995 and May 2005, 1,702 patients with a mean age of 55 years underwent surgical treatment at 14 training hospitals in Korea for radiologically suspected malignant renal tumors. Clinicopathological factors and patient survival were analyzed. RESULTS: Of the 1,702 tumors, 91.7% were malignant and 8.3% were benign. The percentage of benign tumors was significantly greater among those 4cm (4.5%) (p or = T3 was significantly less among tumors 4cm (26.8%) (p or = 3 was also significantly less among tumors 4cm (50.9%) (p < 0.001). The 5-year cancer-specific survival rate was 82.7%, and T stage (p < 0.001), N stage (p < 0.001), M stage (p = 0.025), and Fuhrman's nuclear (p < 0.001) grade were the only independent predictors of cancer-specific survival. CONCLUSION: In renal tumors, small tumor size is prognostic for favorable postsurgical histopathologies such as benign tumors, low T stages, and low Fuhrman's nuclear grades. Our observations are expected to facilitate urologists to adopt function-preserving approach in the planning of surgery for small renal tumors with favorable predicted outcomes.ope
Evaluating assumptions of scales for subjective assessment of thermal environments – Do laypersons perceive them the way, we researchers believe?
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Atrasentan and renal events in patients with type 2 diabetes and chronic kidney disease (SONAR): a double-blind, randomised, placebo-controlled trial
Background: Short-term treatment for people with type 2 diabetes using a low dose of the selective endothelin A receptor antagonist atrasentan reduces albuminuria without causing significant sodium retention. We report the long-term effects of treatment with atrasentan on major renal outcomes. Methods: We did this double-blind, randomised, placebo-controlled trial at 689 sites in 41 countries. We enrolled adults aged 18–85 years with type 2 diabetes, estimated glomerular filtration rate (eGFR)25–75 mL/min per 1·73 m 2 of body surface area, and a urine albumin-to-creatinine ratio (UACR)of 300–5000 mg/g who had received maximum labelled or tolerated renin–angiotensin system inhibition for at least 4 weeks. Participants were given atrasentan 0·75 mg orally daily during an enrichment period before random group assignment. Those with a UACR decrease of at least 30% with no substantial fluid retention during the enrichment period (responders)were included in the double-blind treatment period. Responders were randomly assigned to receive either atrasentan 0·75 mg orally daily or placebo. All patients and investigators were masked to treatment assignment. The primary endpoint was a composite of doubling of serum creatinine (sustained for ≥30 days)or end-stage kidney disease (eGFR <15 mL/min per 1·73 m 2 sustained for ≥90 days, chronic dialysis for ≥90 days, kidney transplantation, or death from kidney failure)in the intention-to-treat population of all responders. Safety was assessed in all patients who received at least one dose of their assigned study treatment. The study is registered with ClinicalTrials.gov, number NCT01858532. Findings: Between May 17, 2013, and July 13, 2017, 11 087 patients were screened; 5117 entered the enrichment period, and 4711 completed the enrichment period. Of these, 2648 patients were responders and were randomly assigned to the atrasentan group (n=1325)or placebo group (n=1323). Median follow-up was 2·2 years (IQR 1·4–2·9). 79 (6·0%)of 1325 patients in the atrasentan group and 105 (7·9%)of 1323 in the placebo group had a primary composite renal endpoint event (hazard ratio [HR]0·65 [95% CI 0·49–0·88]; p=0·0047). Fluid retention and anaemia adverse events, which have been previously attributed to endothelin receptor antagonists, were more frequent in the atrasentan group than in the placebo group. Hospital admission for heart failure occurred in 47 (3·5%)of 1325 patients in the atrasentan group and 34 (2·6%)of 1323 patients in the placebo group (HR 1·33 [95% CI 0·85–2·07]; p=0·208). 58 (4·4%)patients in the atrasentan group and 52 (3·9%)in the placebo group died (HR 1·09 [95% CI 0·75–1·59]; p=0·65). Interpretation: Atrasentan reduced the risk of renal events in patients with diabetes and chronic kidney disease who were selected to optimise efficacy and safety. These data support a potential role for selective endothelin receptor antagonists in protecting renal function in patients with type 2 diabetes at high risk of developing end-stage kidney disease. Funding: AbbVie
Quantification of Multifunctional Dipeptide YA from Oyster Hydrolysate for Quality Control and Efficacy Evaluation
YA is an angiotensin-I-converting enzyme- (ACE-) inhibitory peptide from oyster hydrolysate with antihypertensive activity. Its antioxidant and anti-inflammatory activity were investigated in this study. YA can dose-dependently quench DPPH and ABTS radical and inhibit lipopolysaccharide-induced nitric oxide in RAW 264.7 cells. YA is a multifunctional peptide and was selected as an indicator for quality control and efficacy evaluation of oyster hydrolysate. A practical HPLC/UV assay for YA quantification was developed and validated. It was proved to be accurate and reliable, according to parameters such as specificity, linearity, precision, and accuracy. The quantity results of YA showed that the stage of enzymatic hydrolysis was a critical control point for quality control; the efficacy of oyster hydrolysate can be enhanced after digested in the gastrointestinal tract due to the release of YA by brush border peptidases. Therefore, YA from oyster hydrolysate is a potential bioactive ingredient for functional foods to combat hypertension
Antioxidant, Liver Protective and Angiotensin I-converting Enzyme Inhibitory Activities of Old Laying Hen Hydrolysate in Crab Meat Analogue
The purpose of this study was to evaluate the antioxidative activities of Crab meat analogue prepared with protein hydrolysates obtained from mechanically deboned chicken meat (MDCM) from spent laying hens. 2,2-diphenyl-1-picrylhydrazyl hydrate (DPPH) radical-scavenging activity was increased by adding MDCM hydrolysates during storage, and activity correlated with the concentration of DPPH added up to 6 weeks of storage. Hydroxyl radical-scavenging activity was increased in all analogues containing MDCM hydrolysates. At 0 days of storage, angiotensin I-converting enzyme (ACE)-inhibitory activity was increased by the addition of MDCM hydrolysates. Activity did not correlate after 6 weeks of storage, in which ACE-inhibitory activity was increased with low concentrations of MDCM hydrolysates, but no ACE-inhibitory activity was observed at higher concentrations. The liver-protecting activity of crab meat analogue was shown to be around 60% of the positive control; however, it was not significantly different among the samples during storage. These results support the use of MDCM as a source of health-promoting constituents in crab meat analogue