Inflammation and apoptosis in malignant transformation of sinonasal inverted papilloma: the role of the bridge molecules,cyclooxygenase-2, and nuclear factor κB

Purpose

This study examined the early events in the neoplastic progression of the sinonasal inverted papilloma to squamous cell carcinoma from the viewpoint of chronic inflammation and apoptosis.

Materials and methods

In total, 118 archival slides stained with hematoxylin and eosin from 45 patients were graded according to histopathology (grades I-IV). Their representative portions were transferred to a tissue microarray, sections of which were stained immunohistochemically for cyclooxygenase-2, p53, bax, bcl-2, and nuclear factor κB.

Results

Cyclooxygenase-2 expression was positively correlated with histopathologic grade, with higher expression in advanced grades. p53s were detected in all cores from advanced grades (III, IV), but not in early grades (I, II). The expressions of nuclear factor κB, bax, and bcl-2 were not correlated with the grade.

Conclusions

A p53 mutation seems be a critical event for the malignant transformation of the sinonasal inverted papilloma. Cyclooxygenase-2–mediated inflammatory signals, activated as a consequence of the p53 mutation, may contribute to promoting the proliferation of the advanced sinonasal inverted papilloma.     

A Novel Compound Rasatiol Isolated from Raphanus sativus Has a Potential to Enhance Extracellular Matrix Synthesis in Dermal Fibroblasts

Background

The fibrous proteins of extracellular matrix (ECM) produced by dermal fibroblast contributes to the maintenance of connective tissue integrity.

Objective

This study is carried out to identify the bioactive ingredient from natural products that enhances ECM production in dermal fibroblasts.

Methods

Bioassay-directed fractionation was used to isolate the active ingredient from natural extracts. The effects of rasatiol (isolated from Raphanus sativus) on ECM production in primary cultured human dermal fibroblasts was investigated by enzyme linked immunosorbent assay and western blot analysis.

Results

Rasatiol accelerated fibroblast growth in a dose-dependent manner and increased the production of type 1 collagen, fibronectin and elastin. Phosphorylation of p42/44 extracellular signal-regulated kinase, p38 mitogen-activated protein kinase, and Akt was remarkably increased by rasatiol, indicating that enhanced ECM production is linked to the activation of intracellular signaling cascades.

Conclusion

These results indicate that rasatiol stimulates the fibrous components of ECM production, and may be applied to the maintenance of skin texture.     

The 120-kDa soluble ectodomain of type XVII collagen is recognized by autoantibodies in patients with pemphigoid and linear IgA dermatosis

BACKGROUND: Type XVII collagen promotes adhesion of basal keratinocytes to epidermal basement membrane, and is the target of disease in patients with certain inherited or acquired blistering diseases. Two forms of type XVII collagen are produced by cultured human keratinocytes: a 180-kDa full-length, transmembrane protein, and a recently identified 120-kDa soluble fragment that corresponds to its collagenous ectodomain. OBJECTIVES: We aimed to determine the incidence and pattern of reactivity of autoantibodies against the 180- and 120-kDa forms of type XVII collagen in sera from 40 patients with bullous pemphigoid (BP), pemphigoid gestationis or cicatricial pemphigoid (CP), as well as six patients with linear IgA dermatosis (LAD). METHODS: Various immunochemical techniques were used. RESULTS: These studies found that the 120-kDa fragment of type XVII collagen was bound by circulating autoantibodies in 13 of 38 patients with BP or CP and all six patients with LAD. While many pemphigoid sera had specific reactivity against one but not both forms of this protein, autoantibodies from patients with LAD bound only the soluble ectodomain. CONCLUSIONS: These findings are consistent with the presence of both neoepitopes and cross-reactive epitopes on the ectodomain of type XVII collagen. The finding that sera from patients with LAD showed specific reactivity to epidermal basement membrane suggests that such neoepitopes are present in human skin and that their targeting by autoantibodies may contribute to disease pathogenesis.     

Two Cases of Nevoid Basal Cell CarcinomaSyndrome in One Family

The nevoid basal cell carcinoma syndrome, or Gorlin-Goltz syndrome, is an autosomal dominant multiple system disorder with high penetrance and variable expressions, although it can also arise spontaneously. The diagnostic criteria for nevoid basal cell carcinoma syndrome include multiple basal cell carcinomas, palmoplantar pits, multiple odontogenic keratocysts, skeletal anomalies, positive family history, ectopic calcification and neurological anomalies. We report a brother and sister who were both diagnosed with nevoid basal cell carcinoma syndrome.     

Radiographic Analysis of Instrumented Posterolateral Fusion Mass Using Mixture of Local Autologous Bone and b-TCP (PolyBone?) in a Lumbar Spinal Fusion Surgery

Objective

Although iliac crest autograft is the gold standard for lumbar fusion, the morbidity of donor site leads us to find an alternatives to replace autologous bone graft. Ceramic-based synthetic bone grafts such as hydroxyapatite (HA) and b-tricalcium phosphate (b-TCP) provide scaffolds similar to those of autologous bone, are plentiful and inexpensive, and are not associated with donor morbidity. The present report describes the use of Polybone® (Kyungwon Medical, Korea), a beta-tricalcium phosphate, for lumbar posterolateral fusion and assesses clinical and radiological efficacy as a graft material.

Methods

This study retrospectively analyzed data from 32 patients (11 men, 21 women) who underwent posterolateral fusion (PLF) using PolyBone® from January to August, 2008. Back and leg pain were assessed using a Numeric Rating Scale (NRS), and clinical outcome was assessed using the Oswestry Disability Index (ODI). Serial radiological X-ray follow up were done at 1, 3, 6 12 month. A computed tomography (CT) scan was done in 12 month. Radiological fusion was assessed using simple anterior-posterior (AP) X-rays and computed tomography (CT). The changes of radiodensity of fusion mass showed on the X-ray image were analyzed into 4 stages to assess PLF status.

Results

The mean NRS scores for leg pain and back pain decreased over 12 months postoperatively, from 8.0 to 1.0 and from 6.7 to 1.7, respectively. The mean ODI score also decreased from 60.5 to 17.7. X-rays and CT showed that 25 cases had stage IV fusion bridges at 12 months postoperatively (83.3% success). The radiodensity of fusion mass on X-ray AP image significantly changed at 1 and 6 months.

Conclusion

The present results indicate that the use of a mixture of local autologous bone and PolyBone® results in fusion rates comparable to those using autologous bone and has the advantage of reduced morbidity. In addition, the graft radiodensity ratio significantly changed at postoperative 1 and 6 months, possibly reflecting the inflammatory response and stabilization.     

Multipotent PDGFRβ-expressing cells in the circulation of stroke patients

Tissue pericytes respond to injury, and support vascular and tissue regeneration. The presence of pericytes in the circulation may provide an attractive framework for tissue regeneration. Here, we detected multipotent pericyte-like cells in the circulating blood and determined its profiles during cerebral ischemia. Pericyte-like cells were isolated from the peripheral blood of acute stroke patients or asymptomatic individuals with vascular risk factors by fluorescence or magnetic activated cell sorting with anti-PDGF receptor-beta (PDGFRβ) antibody. The morphologic and molecular features of circulating PDGFRβ(+) cells were compared with tissue pericytes, and the associations with respect to quantity in the blood, culture outcome, and patient characteristics were analyzed. We found an increase in circulating PDGFRβ(+) cells in acute stroke patients compared to controls and a correlation with neurologic impairment. The isolated PDGFRβ(+) cells expressed mesenchymal stem cell markers, proliferated, and were multipotent under permissive culture conditions. The multipotent nature of these cells was comparable to fat-derived PDGFRβ(+) cells. These cells could be obtained by pharmacologic stimulation using bone marrow mobilizer. Circulating PDGFRβ(+) cells will be useful for future research involving endogenous recovery or autologous cell-based therapy.     

Region and frequency specific changes of spectral power in Alzheimer’s disease and mild cognitive impairment

Objectives

To find out whether healthy control (HC), amnestic mild cognitive impairment (aMCI), and Alzheimer’s disease (AD) subjects exhibit region and frequency specific spectral power differences and whether the spectral power changes correlate with domain-specific cognitive function.

Methods

Forty-one AD, 38 aMCI, and 39 HC subjects underwent quantitative EEG and comprehensive neuropsychological tests. Repeated measures analysis of variance was performed to identify differences in EEG spectral power among the three groups by scalp region and EEG frequency. Correlations between region and frequency specific spectral powers and neuropsychological test scores were evaluated.

Results

Temporal and parieto-occipital theta band powers were highest in AD. Whereas, parieto-occipital alpha and frontal and temporal beta 2 band powers were highest in HC and lowest in AD (p < 0.05). Temporal and parieto-occipital theta powers negatively correlated with verbal and visuospatial memory recall, while parieto-occipital alpha and temporal beta 2 powers positively correlated with verbal memory recall (p < 0.01).

Conclusions

Region and frequency specific oscillatory characteristics of EEG reflect domain-specific cognitive function in patients with aMCI and AD.

Significance

Region and frequency specific spectral powers have clinical implications as additional markers differentiating AD, aMCI, and HC.     

Prognostic value of lymph node density in node-positive patients with oral squamous cell carcinoma

Background  

Lymph node density (LND) is superior to TNM nodal status in predicting survival after surgery for bladder and other cancers. Little is known, however, about whether LND can predict survival in patients with oral squamous cell carcinoma (OSCC). We therefore evaluated the utility of LND for predicting survival for patients with OSCC and positive nodes (pN+).