Expressions of nuclear factor kappaB, inducible nitric oxide synthase, and vascular endothelial growth factor in adenoid cystic carcinoma of salivary glands: correlations with the angiogenesis and clinical outcome.
ABSTRACT To evaluate the expressions of nuclear factor kappaB (NF-kappaB p65), inducible nitric oxide synthase enzyme (iNOS), and vascular endothelial growth factor (VEGF) in relation to angiogenesis (microvessel density, MVD) and clinical outcomes in adenoid cystic carcinoma (ACC) of salivary glands.
Immunohistochemical staining was used to quantify the protein expression levels of NF-kappaB p65, iNOS, and VEGF in 80 surgically resected ACCs and 20 normal salivary tissues. In all cases of ACCs, MVD was evaluated by counting CD34-reactive endothelial cells or endothelial cell clusters.
The nuclear localization of NF-kappaB p65 was only detected in ACC cells. Both iNOS and VEGF staining activities in ACCs were more significant than those in normal gland tissues (P < 0.01). MVD had significant correlations with NF-kappaB p65, iNOS, and VEGF expressions (P < 0.01). In three histologic types of ACCs, the NF-kappaB, iNOS, VEGF expressions, and MVD were significantly higher in solid type than in cribriform and tubular types (P < 0.01). The NF-kappaB, iNOS, VEGF expressions, and MVD were significantly correlated with clinical stage, tumor size, vascular invasion, recurrence, and metastasis (P < 0.05). Multivariate analysis showed NF-kappaB, iNOS and VEGF expression, MVD, solid histotype, and perineural invasion had an independent prognostic effect on overall survival.
The expressions of NF-kappaB p65, iNOS, and VEGF were related with MVD. Clinical outcomes raised the possibility that the overexpression of these cytokines might contribute to tumor angiogenesis and have prognostic value in ACCs.
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ABSTRACT: Bioengineered bone substitutes might represent alternatives to autologous bone grafts in medically compromised patients due to reduced operation time and comorbidity. Due to the lack of an inherent vascular system their dimension is limited to the size of critical bone size defect. To overcome this shortcoming, the experiment tried to create heterotopic bone around vessels. In vivo, a two-component fibrin and thrombin gel containing recombinant bone morphogenic protein (rhBMP-2) and transglutamate vascular endothelial growth factor (TG-VEGF) in different ratios, respectively, was injected into a dimensionally stable membrane tube, wrapped around the femoral vessel bundle in twelve New Zealand white rabbits. Sacrifice occurred eight weeks postoperatively. Microcomputed tomography of the specimens showed significantly increased bone volume in the rhBMP-2 to TG-VEGF ratio of 10 to 1 group. Histology showed new bone formation in close proximity to the vessel bundle. Immunohistochemistry detected increased angiogenesis within the newly formed bone in the rhBMP-2 to TG-VEGF ratios of 3 to 1 and 5 to 1. Heterotopic bone was engineered in vivo around vessels using different rhBMP-2 and TG-VEGF ratios in a fibrin matrix injected into a dimensionally stable membrane tube which prevented direct contact with skeletal muscles.BioMed research international. 01/2014; 2014:571510.
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ABSTRACT: Background There is a need to improve the systemic treatment of advanced adenoid cystic carcinoma (ACC). Response rates to chemotherapy are poor and preliminary investigations of molecularly targeted agents have been disappointing. We evaluate sorafenib, an oral multi-kinase inhibitor, which has an attractive targeting profile for this disease. Materials and Methods In a single-arm phase II trial, patients with unresectable locally recurrent and/or metastatic ACC were treated with sorafenib 400mg bid. Results 23 patients, median age 51 years were recruited from 2009-2011. Median progression-free and overall survivals were 11.3 and 19.6 months, respectively. Progression-free survivals at 6 and 12 months were 69.3% and 46.2%, respectively. Sorafenib was only reasonably well tolerated and 13 (57%) patients experienced grade 3 toxicity. Conclusions Sorafenib showed modest activity in ACC with a 12 month progression-free survival of 46.2%. Sorafenib 400mg bid was associated with significant toxicity and taken together with limited effectiveness cannot be enthusiastically recommended for further evaluation. Head Neck, 2013.Head & Neck 12/2013; · 2.83 Impact Factor
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ABSTRACT: To explore the role of NALP3 inflammasome [NALP3, its effector molecule apoptosis associated speck-like protein (ASC), caspase-1, interleukin (IL)-1βand IL-18] in the development of periapical lesions in rats. Periapical lesions were developed within 21 days after mandibular first molar pulp exposure in Sprague-Dawley rats. The animals were randomly sacrificed at 0, 1, 3, 7, 10, 14 and 21 days after pulpal exposure. The bilateral mandibles were extracted for histological processing, then they were haematoxylin-eosin (HE) stained to examine inflammation infiltration in the apical region and immunohistochemiscally examined for the NALP3 inflammasome signaling pathway. Data were analyzed by one-way analysis of variance and the Pearson(,) s correlation and linear tendency test. NALP3 was detected in the cytoplasm of fibroblasts, monocytes, neutrophils, macrophages and vascular endothelial cells in the periapical region. From day 1 to day 21, the number of NALP3-positive cells ascended and was significantly correlated with the intensity of inflammatory infiltration (r=0.776, P<0.01). ASC, caspase-1, IL-1βand IL-18 were all expressed in the inflammatory periapical tissues. The positive cell counts of IL-1βand IL-18 were significantly correlated with that of NALP3, and r=0.718, P<0.01; r=0.688, P<0.01 respectively. NALP3 inflammasome is expressed in the inflammatory periapical tissues. This cytokine-signaling pathway may therefore be crucial in the regulatory control of inflammatory responses in periapical tissues and the development of periapical lesions. This article is protected by copyright. All rights reserved.International Endodontic Journal 01/2014; · 2.05 Impact Factor