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Pineal cysts are usually asymptomatic; however, they may rarely cause symptoms such as chronic headache, paroxysmal headache with gaze paresis, postural syncope, loss of consciousness, and sudden death. A 30-year-old woman with no specific medical history except chronic headache was found collapsed in a public toilet per se. Postmortem examination revealed no external injuries or internal diseases except a cystic lesion of the pineal gland. Histologic examination showed an internal cyst surrounded by glial tissues and pineal parenchyma that was diagnosed as a glial cyst of the pineal gland. Although the pineal cyst cannot be confirmed as the cause of death, it was considered, as no other cause was evident. Herein, we report a pineal cyst considered as an assumed cause of death.

Livin is one of the most important members of the inhibitor protein (IAP) family. It is overexpressed in several types of tumors and may have prognostic significance. The purpose of this study was to investigate Livin expression in human oral squamous cell carcinomas (OSCCs) and to determine whether Livin affects tumor cell behavior in OSCC cell lines and thus evaluate its potential usefulness in serving as a possible target for molecular-targeted therapy in a preclinical model. The expression of Livin protein was investigated in human OSCC tissues through immunohistochemistry and western blot analysis. To evaluate the impact of Livin knockdown on the behavior of human OSCC cell lines, invasion, migration, proliferation and apoptosis assays using small-interfering RNA (siRNA) were performed. RT-PCR and western blot analysis were used to assess alteration of Livin expression at the mRNA and protein levels. The results revealed that expression of Livin was increased in the human OSCC tissues compared with the adjacent normal mucosa. In addition, immunoreactivity of Livin was expressed in 8 OSCC tissues (44.4%). Knockdown of Livin resulted in significantly reduced cell invasion, migration and proliferation in the human OSCC cells. Livin knockdown induced cell apoptosis in the human OSCC cells. Moreover, Livin inhibited apoptosis by suppressing the activity of caspases in the human OSCC cells. In conclusion, livin is associated with invasive and oncogenic phenotypes such as tumor cell invasion, tumor cell migration, tumor cell proliferation, and resistance to apoptosis in human OSCC cells.

Background Metalloproteinases (MMPs) and their tissue inhibitors of metalloproteinases (TIMPs) are involved in several key pathways of tumor growth, invasion and metastasis, but little is known about their expression according to different molecular subtypes of breast cancer. The aims of this study were to assess the prevalence and clinical significance of MMP and TIMP expression in invasive breast cancer and to determine its association with immunohistochemical-based molecular classification. Methods Tissue microarray sections were immunostained for estrogen receptor-α (ER-α), progesterone receptor (PR), human epidermal growth factor receptor 2 (HER2), cytokeratin (CK) 5/6, epidermal growth factor receptor (EGFR) and with specific antibodies against MMP-1, 2, 7, 9, 11, 13, and 14 and TIMP-1, 2, and 3. Based on the immunostaining data from five of the markers used (ER-α, PR, HER2, EGFR and CK5/6), three major subtypes (123 luminal A, 31 basal-like, and 17 HER2-overexpressing) were selected. Results Statistically significant differences in the expression of MMPs and TIMPs among the three subtypes were found in tumoral MMP7 (P = 0.005), tumoral MMP-9 (P = 0.000), tumoral MMP-13 (P = 0.016) and stromal MMP-13 (P = 0.016). The incidence of tumoral MMP-9 expression in the HER2-overexpressing subtype was significantly higher than in the luminal A subtype (P = 0.021). Tumoral MMP-9 and stromal MMP-13 expression were significantly higher in the HER2-overexpressing subtype than in the basal-like subtype (P = 0.000 and P = 0.016, respectively). Tumoral MMP-7 expression was significantly higher in the basal-like subtype compared to luminal A (P = 0.007) and HER2-overexpressing subtype (P = 0.004). Tumoral MMP-13 showed a higher expression in the basal-like subtype than in the HER2-overexpressing subtype (P = 0.010). In multivariate analysis, stage and stromal MMP-1 expression were significantly related to overall survival. Stage was of independent prognostic significance for disease-free survival. Conclusion We found some variations in MMP and TIMP expression among the immunohistochemical-based molecular subtypes of breast carcinomas, suggesting differences in their tumor pathophysiology. Additional studies are needed to determine the mechanisms underlying the differences of MMP and TIMP expression in the molecular subtypes for the development of specific therapeutic targets for breast cancer subtypes.

The dural tail sign was first described as a thin, tapering rim of dural enhancement, in continuity with meningiomas on enhanced T1-weighted magnetic resonance (MR) images. However, the exact nature of the dural tail is still unclear. This study investigated the immunohistochemical (IHC) characteristics of the dural tail in intracranial meningiomas and the correlation between clinicopathological profiles and tumor invasion of the dural tail. The study group consisted of 36 patients of meningioma with the dural tail noted on MR imaging and in pathological findings, and 18 patients of meningioma without the dural tail as the control group. IHC staining of tumor masses and dural tails for vascular endothelial growth factor (VEGF), epithelial membrane antigen, CD34, Ki-67, and vimentin were performed. The data showed that 61.1 % (22/36) of cases in the study group revealed tumor invasion of dural tail, and 55.6 % (30/54) of all the cases demonstrated dura mater invasion in all the samples. The dura mater invasion was significantly positively related to invasion of the dural tail in the study group (p = 0.009). IHC staining detected higher expression of VEGF and CD34 in the dural tail than in the main tumor mass. Considering the high proportion of patients with tumor invasion into the dural tail, we tried to perform wide resection of the dural tail during intracranial meningioma surgery. Furthermore, VEGF was strongly expressed in tumor cells that invaded into the dural tail, and hence VEGF can be used as a marker to differentiate tumor cells from normal meningeal cells in the dural tail.

Extraversion is a personality frequently discussed as one of the strongest and most consistent factors that relates to individual subjective wellbeing. The goal of this study was to better understand how people with varying degrees of extraversion psychologically and physiologically respond differently to unpleasant circumstances. Emotional responses (e.g., levels of intensity, valence, and arousal) were assessed in determining the sensitivity level to negative stimuli that were specifically designed to provoke physical pain and sadness emotion. Physiological changes (e.g., heart rate (HR), blood volume pulse (BVP), and respiratory sinus arrhythmia (RSA)) were also measured during pain and sadness to observe sympathetic and parasympathetic activities. Our results showed that the degree of extraversion was associated with less unpleasant responses to sadness, less HR responses to both pain and sadness, and greater RSA responses to sadness. The findings suggest that the lower HR reactivity to painful and sad situations and greater RSA reactivity to sad situations in extraversion could be possibly due to increased parasympathetic activity. Additionally, enhanced parasympathetic activity to negative situations may explain an important mechanism underlying the positive connection between extraversion and subjective wellbeing.

Reductions in hippocampal neurite complexity and synaptic plasticity are believed to contribute to the progressive impairment in episodic memory and the mild cognitive decline that occur particularly in the early stages of Alzheimer’s disease (AD). Despite the functional and therapeutic importance for patients with AD, intervention to rescue or normalize dendritic elaboration and synaptic plasticity is scarcely provided. Here we show that overexpression of neuritin, an activity-dependent protein, promoted neurite outgrowth and maturation of synapses in parallel with enhanced basal synaptic transmission in cultured hippocampal neurons. Importantly, exogenous application of recombinant neuritin fully restored dendritic complexity as well as spine density in hippocampal neurons prepared from Tg2576 mice, whereas it did not affect neurite branching of neurons from their wild-type littermates. We also showed that soluble recombinant neuritin, when chronically infused into the brains of Tg2576 mice, normalized synaptic plasticity in acute hippocampal slices, leading to intact long-term potentiation. By revealing the protective actions of soluble neuritin against AD-related neural defects, we provide a potential therapeutic approach for patients with AD.

Recently, Farmer et al. described the case of a 54-year-old Ashkenazi Jewish woman with a five-year course of progressive behavioral variant frontotemporal dementia (bvFTD) who was found at autopsy to have both adult polyglucosan body disease (APBD) (not, however, proven genetically) and frontotemporal lobar degeneration with TDP-43 proteinopathy (FTLD-TDP) [1]. We present the clinical, pathologic, molecular, and genetic findings in a novel case of APBD with GBE1 haploinsufficiency and concomitant frontotemporal lobar degeneration with FUS proteinopathy (FTLD-FUS), as well as the second reported case of APBD with concomitant FTLD-TDP. We also investigated 52 additional FTLD cases for the presence of concomitant APBD.

The tumor necrosis factor-related apoptosis-inducing ligand (TRAIL, Apo-2L) is a recently characterized member of the family of programmed cell death-inducing ligands that includes TNF-alpha and CD95L (FasL). It is well known that TRAIL binds to the death signaling receptors, DR4 and DR5, and initiates the TRAIL death pathway. Activation of this pathway, mediated through a caspase cascade, causes apoptosis. In this study, we hypothesized that oxidative stress facilitates TRAIL-induced apoptosis by promoting caspase activity through cytochrome c release from mitochondria. Human colorectal carcinoma CX-1 cells were treated with various concentrations of TRAIL (12.5-200 ng/ml) and/or sodium nitroprusside (SNP; 0.03-1 mM) for 12 h. SNP, a nitric oxide donor, which had little toxic effect by itself, enhanced TRAIL-induced cytotoxicity. For example, TRAIL-induced apoptosis (200 ng/ml) was increased by a factor of 2.5-fold in the presence of 1 mM SNP. The combined treatment also caused an increase in cytochrome c release, caspase-3 activity, and PARP cleavage. Overexpression of Bcl-2 completely blocked the SNP-promoting effects, but only moderately inhibited TRAIL-induced apoptosis. Similar results were observed in the presence of hydrogen peroxide or peroxynitrite. Taken together, the present studies suggest that SNP enhances TRAIL-induced cytotoxicity by facilitating the mitochondria-mediated caspase signal transduction pathway.

Objective Based on surgical outcomes of patients with infratentorial meningiomas surgically treated at our institution, we analyzed the predictors for surgical resection, recurrence, complication, and survival. Methods Of surgically treated 782 patients with intracranial meningioma, 158 (20.2%) consecutive cases of infratentorial location operated on between April 1993 and May 2013 at out institute were reviewed retrospectively. The patients had a median age of 57.1 years (range, 16--77 years), a female predominance of 79.7%, and a mean follow-up duration of 48.4 months (range, 0.8--242.2 months). Results Gross total resection (Simpson's grade I & II) was achieved in 81.6% (129/158) of patients. Non-skull base location was an independent factor for complete resection. The recurrence rate was 13.3% (21/158) and the 5-, 10-, and 15-year recurrence rates were 8.2%, 12.0%, and 13.3%, respectively. Benign pathology, postoperative KPS over than 90, low peritumoral edema, and complete resection were significantly associated with longer recurrence-free survival rate. The 5-, 10-, and 15-year survival rates were 96.2%, 94.9%, and 94.9%, respectively. Benign pathology, postoperative KPS over than 90 and complete resection were significantly associated with a longer survival rate. The permanent complication rate was 13% (21/158). Skull base location and postoperative KPS less than 90 were independent factors for the occurrence of permanent complication. Conclusion Our experience shows that infratentorial meningiomas represent a continuing challenge for contemporary neurosurgeons. Various factors are related with resection degree, complications, recurrence and survival.

© The Author (2013). Published by Oxford University Press. Sensitivity to social evaluation has been proposed as a potential marker or risk factor for depression, and has also been theorized to increase with pubertal maturation. This study utilized an ecologically valid paradigm to test the hypothesis that adolescents with major depressive disorder (MDD) would show altered reactivity to peer rejection and acceptance relative to healthy controls in a network of ventral brain regions implicated in affective processing of social information. A total of 48 adolescents (ages 11-17), including 21 with a current diagnosis of MDD and 27 age- and gender-matched controls, received rigged acceptance and rejection feedback from fictitious peers during a simulated online peer interaction during functional neuroimaging. MDD youth showed increased activation to rejection relative to controls in the bilateral amygdala, subgenual anterior cingulate, left anterior insula and left nucleus accumbens. MDD and healthy youth did not differ in response to acceptance. Youth more advanced in pubertal maturation also showed increased reactivity to rejection in the bilateral amygdala/parahippocampal gyrus and the caudate/subgenual anterior cingulate, and these effects remained significant when controlling for chronological age. Findings suggest that increased reactivity to peer rejection is a normative developmental process associated with pubertal development, but is particularly enhanced among youth with depression.

This research was conducted in order to find out the effect of creativity and personality education during the past three years. The goal of this research was to identify the effectiveness of application of creativity curriculum to the elementary model schools. Research questions are as follow; Is there any significant difference in the creative thinking ability and creative personality between model and regular schools? The participants of this research were 662 students. The Integrated Creativity Test by Lee & Lew(2012) was used for measuring student's creativity. The results of this research indicated that model elementary school students' creative thinking ability and creative personality were statistically different with regular elementary school students.

Background The incidence of brain metastasis from hepatocellular carcinoma (HCC) is expected to increase as a result of prolonged survival due to the recent advances in HCC treatment. However, there is no definite treatment strategy for brain metastasis from HCC mainly due to its rarity and dismal prognosis. To provide helpful recommendations in treatment of brain metastasis from HCC, the authors aimed to identify prognostic factors that influence survival rates with a review of the recently published data. Methods Thirty-three cases of brain metastasis, whose incidence was 0.65%, were selected from a total of 5015 HCC patients and reviewed retrospectively in terms of clinical and radiological features. Results Median overall survival time after diagnosis of brain metastasis was 10.4 weeks (95% confidence interval [CI], 5.1-15.7 weeks) with 1-, 6- and 12-month survival rates, of 79%, 24% and 6%, respectively. Median survival of the patients treated with surgical resection or surgical resection followed by whole-brain radiation therapy (WBRT) (25.3 weeks; range, 15.8-34.8 weeks) was longer than that of the patients treated with gamma knife surgery (GKS), WBRT, or GKS followed by WBRT (10.4 weeks; range, 7.5-13.3 weeks) as well as that of patients treated with only steroids (1 week; range, 0.0-3.3 weeks) (p vs 2.4 weeks, p = 0.001). Surgical resection (hazard ratio [HR] 0.23, 95% CI 0.08-0.66, p = 0.006) and good liver function at the time of brain metastasis (HR 0.25, 95% CI 0.09-0.69, p = 0.007) were found to be the powerful prognostic factors for favorable survival in the multivariate analysis. In addition, presence of intratumoral hemorrhage was a statistically significant prognostic factor for survival. Conclusion Although HCC patients with brain metastasis showed a very dismal prognosis, surgical intervention was shown to lead to relative prolongation of the survival time, especially in those with preserved hepatic function.

D. Using these operators, we construct the projection operators which decompose a linear vector superfields into irreducible representations. The forms of the irreducible representations are explicitly described, and the equivalence of the representations under supersymmetric transformations is discussed. Finally, we construct spin operators for superfields that satisfy the same commutation relation as the angular momentum operators, [si ,s j ]= ieijksk.

We report a rare case of a thoracic intramedullary subependymoma in a 37-year-old woman. The patient developed a monoparesis of the right leg after a subtotal resection of the tumor. During the 30 months of follow-up the neurological deficit improved and the patient remained symptom free without progression of the remnant tumor. A complete resection of the tumor is usually curative with improved function. However, aggressive surgery may cause either worsening of an existing deficit or the development of new deficits. In patients with poor delineation between the tumor and the spinal cord, subtotal removal and close follow-up should be considered.

Background To investigate the molecular basis for invasion of malignant gliomas, proteomic analysis approach was carried out using two human glioma cell lines, U87MG and U343MG-A that demonstrate different motility and invasiveness in in vitro experiments. Methods High-resolution two-dimensional gel electrophoresis and matrix-assisted laser-desorption/ionization time-of-flight mass spectrometry analysis were performed. Results Nine distinct protein spots that were recognized with significant alteration between the two cell lines. Five of these protein spots were up-regulated in U87MG and four were up-regulated in U343MG-A. Conclusion Among these proteins, cathepsin D was shown to be one of the important proteins which are related with glioma invasion. However, further studies are necessary to reveal the exact role and mechanism of cathepsin D in glioma invasion.

This study examined the extent to which emotional face stimuli differ from the neural reactivity associated with more ecological contextually augmented stimuli. Participants were scanned when they viewed contextually rich pictures depicting both emotional faces and context, and pictures of emotional faces presented alone. Emotional faces alone were more strongly associated with brain activity in paralimbic and social information processing regions, whereas emotional faces augmented by context were associated with increased and sustained activity in regions potentially representing increased complexity and subjective emotional experience. Furthermore, context effects were modulated by emotional intensity and valence. These findings suggest that cortical elaboration that is apparent in contextually augmented stimuli may be missed in studies of emotional faces alone, whereas emotional faces may more selectively recruit limbic reactivity.

Background Class III β-tubulin (TUBB3) is a prognostic marker in various tumors, but the role of TUBB3 in advanced gastric cancer is not clearly defined. We analyzed the significance of TUBB3 expression, along with that of excision repair cross-complementation group 1 (ERCC1) in recurrent and metastatic gastric cancer patients receiving taxane-based first-line palliative chemotherapy. Methods We reviewed the cases of 146 patients with advanced gastric adenocarcinoma who received taxane-based first-line palliative chemotherapy between 2004 and 2010 at Chonnam National University Hwasun Hospital (Gwangju, Korea). Immunohistochemical staining for TUBB3 and ERCC1 was performed using paraffin wax-embedded tumor tissues. We evaluated the patients’ response to chemotherapy, progression-free survival (PFS), and overall survival (OS). Results In total, 146 patients with advanced gastric cancer received docetaxel and cisplatin (n = 15) or paclitaxel and cisplatin (n = 131). The median PFS was significantly shorter for patients with high-level TUBB3 expression than for patients with low-level TUBB3 expression (3.63 vs. 6.67 months, P = 0.001). OS was not associated with TUBB3 expression (13.1 vs. 13.1 months, P = 0.769). By multivariate analysis, only TUBB3 was related to a shorter PFS (HR 2.74, 95% CI 1.91-3.91, P = 0.001). Patients with high-level ERCC1 expression showed a lower response rate than patients with low-level ERCC1 expression (24 vs. 63.2%, P = 0.001); however, ERCC1 had no clinical effect on PFS or OS. Conclusions TUBB3 was a strong predictive marker in recurrent and metastatic gastric cancer patients receiving taxane-based first-line palliative chemotherapy. No clinical impact of ERCC1 was evident in this setting.

To identify promoter methylation as a major silencing mechanism in potential precursor lesions of sporadic diffuse gastric cancer (DGC), we investigated promoter methylation of CDH1 (E-Cadherin gene) in a series of DGCs and matched normal mucosa.The extent of CDH1 gene promoter methylation was explored using methylation-specific polymerase chain reaction (MSP) and pyrosequencing (PS) in 72 DGCs with a matched pair of normal mucosa.MSP and PS revealed CDH1 promoter methylation in 73.6% (53/72) and 77.8% (56/72) of DGC samples, respectively. PS detected CDH1 methylation in 70.8% (51/72) and 72.2% (52/72) of matched normal mucosa from adjacent and remote foci, respectively. In comparison, CDH1 promoter methylation was detected in 12/24 normal gastric mucosa samples without DGC, and this difference was statistically significant (p=0.016).The current study showed that the majority of DGC cases demonstrated concurrent CDH1 promoter methylation in tumor tissues and in non-neoplastic mucosa.

BACKGROUNDS: Expression of Livin, a member of the inhibitors of apoptosis protein family, is associated with tumor development and progression. The aims of this study were to evaluate whether Livin affects oncogenic biological behavior of colorectal cancer cells, and to document the relationship between its expression and various clinicopathological parameters in colorectal cancer. METHODS: We investigated the impact of Livin on tumor cell behavior by using the small interfering RNA and pcDNA3.1 vector in SW480 and DKO1 colorectal cancer cell lines. The expression of Livin was investigated by RT-PCR and immunohistochemistry in coloretcal cancer tissues. The apoptotic cells were visualized by TUNEL assay, and proliferative cells were visualized by Ki-67 antibody staining. RESULTS: Knockdown of Livin suppressed tumor cell migration and invasion in colorectal cancer cells. Knockdown of Livin induced the apoptosis by up-regulating of caspase-3, -7 and PARP activities and the cell cycle arrest by decreasing cyclin D1, cyclin D3, cyclin-dependent kinase 4 and 6, and by inducing p27 expression. The MAPK signaling cascades were significantly blocked by knockdown of Livin. In contrast, overexpression of Livin enhanced tumor cell migration and invasion, and inhibited the apoptosis and cell cycle arrest. The mean apoptotic index (AI) value of Livin positive tumors was significantly lower than AI of Livin negative tumors. However, there was no significant difference between Livin expression and Ki-67 labeling index (KI). Livin expression was significantly increased in colorectal cancer and metastatic lymph node tissues compared to normal colorectal mucosa and non-metastatic lymph node tissues and was associated with tumor stage, lymphovascular invasion, lymph node metastasis and poor survival. CONCLUSIONS: These results indicate that Livin is associated with tumor progression by increasing tumor cell motility and inhibiting apoptosis in colorectal cancer.

Objectives Several human tumor tissues show an aberrant expression and activation of recepteur d’origine nantais (RON). In this paper, we investigate the expression of RON in human laryngeal squamous cell carcinoma (SCC) and evaluate whether RON affects the tumor cell progression in human laryngeal SCC cell line. Methods Immunohistochemistry was used to assess RON expression in human laryngeal SCC. To evaluate the impact of RON knockdown, the cell invasion assay and cell migration assay using small-interfering RNA were performed. Results The expression of RON protein was dominantly observed in laryngeal SCC tissues relative to adjacent normal mucosa in all cases. Knockdown of RON resulted in significantly reduced cell invasion in human laryngeal SCC cells. Cell migration showed a marked decrease in RON knockdown laryngeal SCC cells compared to the negative control laryngeal SCC cells. Laryngeal SCC cell migration was enhanced by incubation with macrophage stimulating protein (MSP). Conclusion RON is highly expressed in human laryngeal SCC. We suggest that RON plays an important role in invasion, and metastasis of laryngeal SCC.

Gene fusion is involved in the development of various types of malignancies. Recent advances in sequencing technology have facilitated identification of gene fusions and have stimulated the research of this field in cancer. In the present study, we performed next-generation transcriptome sequencing in order to discover novel gene fusions in gastric cancer. A total of 282 fusion transcript candidates were detected from 12 gastric cancer cell lines by bioinformatic filtering. Among the candidates, we have validated 19 fusion transcripts, which are 7 inter-chromosomal and 12 intra-chromosomal fusions. A novel DUS4L-BCAP29 fusion transcript was found in 2 out of 12 cell lines and 10 out of 13 gastric cancer tissues. Knockdown of DUS4L-BCAP29 transcript using siRNA inhibited cell proliferation. Soft agar assay further confirmed that this novel fusion transcript has tumorigenic potential. We also identified that microRNA-coding gene PVT1, which is amplified in double minute chromosomes in SNU-16 cells, is recurrently involved in gene fusion. PVT1 produced six different fusion transcripts involving four different genes as fusion partners. Our findings provide better insight into transcriptional and genetic alterations of gastric cancer: namely, the tumorigenic effects of transcriptional read-through and a candidate region for genetic instability.

Background Although pituitary adenoma is one of the most common intracranial tumors, it rarely progresses secondarily into a metastatic carcinoma. Commonalities in reported cases include subtotal resection at presentation, treatment with radiation therapy, and delayed metastatic progression. Pathologic descriptions of these lesions are varying and inconsistent. Case description A 52-year-old male was diagnosed with acromegaly and pituitary tumor in 1996. He underwent four subtotal resections and five courses of stereotactic radiosurgery over 14 years. He developed left eye lateral gaze palsy, and was found to have a distant orbital metastasis with involvement of the left lateral rectus and lateral orbital wall. He underwent left orbital craniotomy via eyebrow incision for resection of this lesion. Pathologic evaluation showed a markedly elevated Ki67 level of 30%. Conclusion While overall incidence of metastatic progression of pituitary adenoma after radiotherapy appears to be low, it appears to be a possible complication, and could be more likely in patients receiving multiple doses of radiotherapy. Our review of reported cases showed that 45/46 (97.8%) of patients developing carcinoma had prior radiation exposure. These patients may also have more aggressive pathologic characteristics of their lesions.

A 63-year-old man complained of intermittent motor weakness of his arm. The magnetic resonance image (MRI) of his brain displayed a high signal lesion in right cingulate gyrus on T2 weighted image. One year later, he showed a stuporous mental status with repeated seizures, and the follow-up brain MRI showed heterogeneously enhanced mass associated with bleeding. He was treated with surgery and radiotherapy for secondary glioblastomas in right cingulate gyrus. One year more later, a mass recurred on the left frontal base, and gliosarcoma was diagnosed. After tumor resection, ventriculoperitoneal shunt, chemotherapy, and re-radiation therapy, all brain lesions were stable. Fourteen months after the diagnosis of gliosarcoma, he complained of dyspnea and back pain. Torso positron emission tomography/computed tomography revealed multiple metastatic lesions in both lungs, pericardium, pleura, liver, lymph nodes, and bones, and metastatic gliosarcoma was diagnosed. One month later, the patient died because of the systemic metastases. We present an unusual case of secondary gliosarcoma with stable brain lesions and extensive systemic metastases.

Chordoid meningioma is an uncommon variant of meningioma, and is very rarely found in the pineal region. We report a case of pineal region chordoid meningioma occurring in a young woman complicated by repetitive hemorrhages in the setting of pregnancy. A 23-year-old woman, 28 weeks pregnant, was transferred to our hospital for further management of a multi-septated, hemorrhagic pineal region mass and hydrocephalus. MRI revealed a heterogeneous T2-hyperintense lesion measuring 1.7 × 1.7 cm in the pineal gland. Resection of the tumor through an occipital transtentorial approach was performed. Histopathologic examination of the lesion confirmed the diagnosis of chordoid meningioma demonstrating cords and clusters of eosinophilic cells with rare cytoplasmic vacuolation arranged in a mucinous stroma. Additionally, there was abundant lymphoplasmacytic infiltration within the tumor. The details of this case are presented with a review of the literature.

Mutations in C9ORF72 resulting in expanded hexanucleotide repeats were recently reported to be the underlying genetic abnormality in chromosome 9p-linked frontotemporal lobar degeneration with TAR DNA-binding protein of 43 kD (TDP-43) proteinopathy (FTLD-TDP), amyotrophic lateral sclerosis (ALS), and frontotemporal lobar degeneration with motor neuron disease (FTLD-MND). Several subsequent publications described the neuropathology as being similar to that seen in cases of FTLD-TDP and ALS without C9ORF72 mutations, except that cases with mutations have p62 and ubiquitin positive, TDP-43 negative inclusions in cerebellum, hippocampus, neocortex, and basal ganglia. The identity of this protein is as yet unknown, and its significance is unclear. With the goal of potentially uncovering the significance of these TDP-43 negative inclusions, we compared the clinical, pathologic, and genetic characteristics in 5 cases of FTLD-TDP and FTLD-MND with C9ORF72 mutations to 20 cases without mutations. We confirmed the apparent specificity of p62 positive, TDP-43 negative inclusions in cerebellum, hippocampus, cortex, and basal ganglia to FTLD with C9ORF72 mutations. p62 positive, TDP-43 negative inclusions in hippocampus correlated with hippocampal atrophy, but no additional correlations were uncovered. However, although ambiguity of TDP sub-typing has previously been reported in cases with C9ORF72 mutations, this is the first report to show that although most FTLD cases with C9ORF72 mutations were TDP type B, some of the pathologic characteristics in these cases were more similar to TDP types A and C than to TDP type B FTLD cases without mutations. These features include greater cortical and hippocampal atrophy, greater ventricular dilatation, more neuronal loss and gliosis in temporal lobe and striatum, and TDP-43 positive fine neuritic profiles in the hippocampus in FTLD cases with C9ORF72 mutations compared to FTLD-TDP type B cases without mutations, implying that the C9ORF72 mutation modifies the pathologic phenotype of FTLD-TDP type B.

Phyllodes tumors (PTs) of the breast are rare biphasic tumors with the potential for invasion and metastatic spread. Matrix metalloproteinases (MMPs) and their tissue inhibitors of metalloproteinases (TIMPs) are involved in several key aspects of tumoral growth, invasion, and metastasis, but little is known of their expression in PTs. The objective of this study was to assess the expression of MMPs and TIMPs in PTs and to determine their association with grade and clinical behavior of PTs. Eighty-two PTs (50 benign, 22 borderline, and 10 malignant) were studied. Automated immunohistochemical staining for MMP-1, -2, -7, -9, -11, -13, and -14 and TIMP-1, -2, and -3 was performed using tissue microarray blocks and the expression of MMPs and TIMPs was assessed in the stromal component. There were no significant differences in the expression of stromal MMPs and TIMPs in the 3 groups of PTs, except for MMP-14. There was a significant increase in stromal MMP-14 expression with increasing PT grade (P

The purpose of this research was to analyze the creative thinking ability of university students in web-based instruction. Up to now the subject ‘Creativity and Problem-solving‘ has been lectured face-to-face in a class as a general education curriculum, but it was developed newly as a web-based online lecture. And after conducting it for a semester, the effectiveness of this lecture on the improvement of the creative thinking ability of university students was validated. The participants were 176 university students who were selected among the classes for creativity conducted at Seoul area in Korea. The creativity test was developed to measure the participants’ creative thinking ability, and the collected data were analyzed by t-test. The results showed that the creative thinking ability with 6 sub-factors were not significantly different between two groups. In addition, the methods of the creativity classes significantly influenced on creative thinking ability. The result of this research implies the direction for creativity education in future.

We developed an ecologically valid virtual peer interaction paradigmthe Chatroom Interact Task in which 60 pre-adolescents and adolescents (ages 9-17 years) were led to believe that they were interacting with other youth in a simulated internet chatroom. Youth received rejection and acceptance feedback from virtual peers. Findings revealed increased pupil dilation, an index of increased activity in cognitive and affective processing regions of the brain, to rejection compared to acceptance trials, which was greater for older youth. Data from a cell-phone Ecological Momentary Assessment (EMA) protocol completed following the task indicated that increased pupillary reactivity to rejection trials was associated with lower feelings of social connected- ness with peers in daily life. Eyetracking analyses revealed attentional biases toward acceptance feedback and away from rejection feedback. Biases toward acceptance feedback were stronger for older youth. Avoidance of rejection feedback was strongest among youth with increased pupillary reactivity to rejection, even in the seconds leading up to and following rejection feedback. These findings suggest that adolescents are sensitive to rejection feedback and seek to anticipate and avoid attending to rejection stimuli. Furthermore, the salience of social rejection and acceptance feedback appears to increase during adolescence.

BACKGROUND AND IMPORTANCE A cavernous hemangioma arising from the abducens nerve has not been previously reported in the literature. Based on the surgical experience with this case, the authors discuss the clinical importance and resectability potential of a duplicated abducens nerve. CLINICAL PRESENTATION A 54-year-old woman presented with a recurrence of diplopia that had occurred 3 years before this admission and had spontaneously resolved without any specific treatment. On admission, there were no specific neurological deficits. Magnetic resonance imaging revealed a cone-shaped mass on the right anterior cerebellopontine angle with hemorrhagic change. Surgical resection via a standard right lateral suboccipital approach was performed. A cystic mass was found emerging from the entry zone of the Dorello canal and encircling the larger branch of the duplicate abducens nerve. Because there was no demarcation between the mass and origin branch, both were removed en bloc. Pathology revealed the presence of a cavernous hemangioma mixed with nerve tissue. Despite preserving a small branch of the duplicate abducens nerve, the patient had permanent right abducens palsy. CONCLUSION A cavernous hemangioma arising from the abducens nerve should be suspected as a possible diagnosis for a cystic mass on the anterior cerebellopontine angle. Although duplication of the abducens nerve has not been clearly confirmed on clinical grounds, sacrificing the larger branch during surgery may lead to permanent abducens palsy, as in our case.

Background Transitional cell carcinoma (TCC) of the female urethra is a rare urological malignancy, and intracranial metastasis of this cancer has not yet been reported in the literature. This review is intended to present a case of multiple intracranial metastasis in a female patient with a remote history of primary urethral TCC. Case Presentation A 49-year-old woman, presented with a prolapsed mass in urethral orifice that was diagnosed as primary urethral TCC with distant lung and multiple bone metastases. The patient subsequently underwent chemotherapy under various regimens. A year later, the patient developed headache and vomiting which as was found to be due to multiple intracranial metastasis. The patient underwent surgical resection of the largest lesion located on the cerebellum, and consecutively gamma knife radiosurgery was performed for other small-sized lesions. Pathological examination of the resected mass revealed a metastatic carcinoma from a known urethral TCC. Serial work-up of systemic metastasis revealed concomitant aggravation of lung, spleen, and liver metastasis. The patient died of lung complication 2 months after the diagnosis of brain metastasis. Conclusion To the best of our knowledge, this is the first reported case of cerebral metastasis from primary urethral TCC, with pathological confirmation. As shown in intracranial metastasis of other urinary tract carcinoma, this case occurred in the setting of uncontrolled systemic disease and led to dismal prognosis in spite of aggressive interventional modalities.

KAI1 COOH-terminal interacting tetraspanin (KITENIN) promotes tumor cell migration, invasion and metastasis in colon, bladder, head and neck cancer. The aims of current study were to evaluate whether KITENIN affects tumor cell behavior in human gastric cancer cell line and to document the expression of KITENIN in a well-defined series of gastric tumors, including complete long-term follow-up, with special reference to patient prognosis.To evaluate the impact of KITENIN knockdown on behavior of a human gastric cancer cell line, AGS, migration, invasion and proliferation assays using small-interfering RNA were performed. The expression of activator protein-1 (AP-1) target genes and AP-1 transcriptional activity were evaluated by reverse transcription-polymerase chain reaction (RT-PCR) and luciferase reporter assay. The expression of KITENIN and AP-1 target genes by RT-PCR and Western blotting or immunohistochemistry was also investigated in human gastric cancer tissues.The knockdown of KITENIN suppressed tumor cell migration, invasion and proliferation in AGS cells. The mRNA expression of matrix metalloproteinase-1 (MMP-1), MMP-3, cyclooxygenase-2 (COX-2), and CD44 was reduced by knockdown of KITENIN in AGS. AP-1 transcriptional activity was significantly decreased by knockdown of KITENIN in AGS cells. KITENIN expression was significantly increased in human cancer tissues at RNA and protein levels. Expression of MMP-1, MMP-3, COX-2 and CD44 were significantly increased in human gastric cancer tissues. Immunostaining of KITENIN was predominantly identified in the cytoplasm of cancer cells. Expression of KITENIN was significantly associated with tumor size, Lauren classification, depth of invasion, lymph node metastasis, tumor stage and poor survival.These results indicate that KITENIN plays an important role in human gastric cancer progression by AP-1 activation.

Nogo-A belongs to the reticulon protein family and is expressed in the inner and outer loops of myelin sheaths of oligodendrocytes. We analyzed the patterns of Nogo-A expression in human gliomas in an effort to identify a useful marker for the characterization of oligodendroglial tumors. We determined the expression of Nogo-A in a panel of 58 astrocytic and oligodendroglial tumors using immunohistochemistry and compared the expression of Nogo-A with Olig-2, a recently identified marker for oligodendrogliomas. To localize Nogo-A expression, immunofluorescent staining was performed using other glial markers (MAP-2 and GFAP). We also confirmed the overexpression of the Nogo-A protein in 53 astrocytic and oligodendroglial tumors using Western blot analysis. Based on immunohistochemical analysis, Nogo-A and Olig-2 had specificity in the detection of oligodendroglial tumors from astrocytic tumors (P=0.001). The level of Nogo-A staining was highly correlated with Olig-2 (P=0.001). The sensitivity and specificity of Nogo-A for oligodendroglial tumors was 86.9% and 57.1%, respectively. Nogo-A expression overlapped that of other oligodendroglial markers, but with different patterns of expression. Western blot analysis revealed that Nogo-A is predominantly expressed in 85.7% of oligodendroglioma cells and 93.7% of anaplastic oligodendroglioma cells. Like other oligodendroglial markers, Nogo-A is highly expressed in oligodendroglial tumors; however, it does not serve as a definite marker specific for oligodendroglial tumors.

The purpose of this study was to investigate the effects of platelet-rich plasma (PRP) and neural-induced human mesenchymal stem cells (nMSCs) on axonal regeneration from a facial nerve axotomy injury in a guinea pig model.Prospective, controlled animal study.Experiments involved the transection and repair of the facial nerve in 24 albino guinea pigs. Four groups were created based on the method of repair: suture only (group I, control group); PRP with suture (group II); nMSCs with suture (group III); and PRP and nMSCs with suture (group IV). Each method of repair was applied immediately after nerve transection. The outcomes measured were: 1) functional outcome measurement (vibrissae and eyelid closure movements); 2) electrophysiologic evaluation; 3) neurotrophic factors assay; and 4) histologic evaluation.With respect to the functional outcome measurement, the functional outcomes improved after transection and reanastomosis in all groups. The control group was the slowest to demonstrate recovery of movement after transection and reanastomosis. The other three groups (groups II, III, and IV) had significant improvement in function compared to the control group 4 weeks after surgery (P.05). On the electrophysiologic evaluation, there was significantly better performances in groups II, III, and IV when compared to group I with respect to the amplitude and excitation area of the compound motor action potentials (MAPs) 4 and 6 weeks after surgery (P.05); group IV had the best performance. A Western blot assay showed that group II had marked expression of several neurotrophic factors. Groups II, III, and IV demonstrated better results in axon counts and myelin thickness when compared with group I. Based on quantitative histology analysis, group IV had the greatest myelinated axon fibers compared to the other groups (P.05).The use of PRP and/or nMSCs promotes facial nerve regeneration in an animal model of facial nerve axotomy. The use of nMSCs showed no benefit over the use of PRP in facial nerve regeneration, but the combined use of PRP and nMSCs showed a greater beneficial effect than use of either alone. This study provides evidence for the potential clinical application of PRP and nMSCs in peripheral nerve regeneration of an acute nerve injury. Laryngoscope, 2010.

Oligodendroglial tumors sometimes show heterogeneous ring enhancement with a central necrotic portion. We aimed to reveal the prognosis of such tumors based on such radiologic findings and compare them to other prognostic factors. Participants were 32 patients with oligodendroglioma (17 oligodendrogliomas, 15 anaplastic oligodendrogliomas) who underwent surgery from 2004 to 2008. We investigated tumor radiologic findings, locations, calcification, whether localized or diffuse type, and enhancement patterns. Of other prognostic factors, we analyzed age, sex, pathology, extent of removal, adjuvant therapy, genetic change in 1p and 19q, and MGMT methylation status. We checked for genetic abnormality in 1p and 19q using the FISH method. To investigate MGMT methylation, we performed methylation-specific PCR (MSP). Mean follow-up duration was 3.2 years. Median age was 42.4 years, and the male:female ratio was 21:11. Out of 17 oligodendrogliomas, 14 (82.4%) showed combined 1p/19q deletion, and 14 (82.4%), methylated MGMT. Among 15 anaplastic oligodendrogliomas, there were 7 (46.6%) with combined 1p/19q deletion and 11 (73.3%) with methylated MGMT. The 4-year recurrence-free survival and overall survival were 77.6 and 100% in oligodendrogliomas and 59.1 and 71.6% in anaplastic oligodendrogliomas, respectively. On univariate analysis, radiologic variable of ring enhancement pattern was statistically significant related with recurrence-free survival (P = 0.003). Variables such as sex (P = 0.03), combined 1p/19q loss (P = 0.04), tumor location (P = 0.02), and anaplastic pathology (P = 0.04) were significantly correlated with overall survival. Cox's regression model revealed that ring enhancement pattern was associated with frequent recurrence (ring enhancement, hazard ratio = 8.281, P = 0.04), and these showed 1p deletion only. Anaplastic oligodendrogliomas with ring enhancement like glioblastomas and without combined 1p/19q loss should receive close follow-up after treatment because of frequent recurrences.

The aim of this study was to evaluate variations of O6-methylguanine-DNA methyltransferase (MGMT) promoter methylation and protein expression after adjuvant treatment in glioblastoma patients. Sixteen patients with a glioblastoma underwent 34 microsurgeries including 18 re-operations. After surgery, patients underwent follow-up with radiotherapy and chemotherapy (temozolomide, ACNU and cisplatin) between 2000 and 2008. To investigate MGMT methylation and MGMT expression, methylation-specific PCR (MSP) and immunohistochemical staining (IHC) were performed. The methylation status of the MGMT promoter was altered in five (27.8%) of 18 re-operation specimens. In four specimens, the MGMT promoter was found to be methylated after primary surgery, but was found to be unmethylated on post-treatment samples. MGMT protein expression was altered in 15 (83.3%) of 18 cases. Fifteen specimens showed higher levels of protein expression as compared to previous samples and three samples demonstrated a similar expression pattern. After irradiation and exposure to steroid and temozolomide 6 and 24 h later, a methylated MGMT promoter and negative protein expression were seen in U343 glioblastoma cell lines which have methylated promoter and negative protein expression. Variations in MGMT promoter methylation and protein expression can occur after treatment. We suggest that changes of MGMT promoter methylation and protein expression might not be related to a direct effect of irradiation and exposure to steroid and temozolomide.

This study was performed to determine whether any clinical parameters measured at diagnosis or during treatment are associated with bleeding in patients with acute promyelocytic leukemia (APL). Ninety patients with APL who were treated with all-transretinoic acid (ATRA) and anthracycline-based chemotherapy were analyzed. There were 24 significant bleeding events, classified by onset as 'hyperacute' (n = 5), 'acute' (n = 11) and 'late' (n = 8). Fifteen patients (17%) died because of bleeding. A poor fibrinogen (FBG) response during ATRA and chemotherapy was associated with an increased risk of bleeding (p = 0.003). Increased LDH and decreased FBG levels were associated with an increased incidence of bleeding, and low PLT count was correlated with death from bleeding. Our findings suggest that LDH/FBG levels and FBG response may be associated with morbidity and mortality from bleeding in patients with APL.

Epigenetic silencing of tumor-related genes by CpG island methylation is an important mechanism for the development of many tumors, including gastric carcinoma. Deregulation of transcription factor 4 (TCF4) by promoter methylation was recently shown to play a key role in gastric carcinogenesis. The extent of methylation in the TCF4 promoter was assessed using methylation-specific polymerase chain reaction (MSP) and pyrosequencing (PS) in 120 gastric carcinoma (GC) samples collected during gastrectomy, and in 40 normal gastric mucosa samples. The PS analysis of GCs revealed a higher frequency of TCF4 methylation (75.8%; 91/120). The methylation frequency for TCF4 by both MSP and PS techniques was significantly higher in advanced (75.0 and 91.7%, respectively) compared with early (60.0 and 60.0%, respectively, p

Hypermethylation of promoters that regulate the expression of DNA repair genes is associated with gastric carcinoma (GC). Little is known regarding the association between age of disease onset and differences in molecular profiles.The two study groups consisted of 100 elderly patients and 100 younger patients. The aberrant DNA methylation patterns of four mismatch repair genes, hMLH1, hMSH2, hMSH3, and MGMT, were compared by bisulfite modification and methylation-specific PCR (MSP).The methylation frequencies for hMLH1 and hMSH3 were significantly higher for the elderly than for the younger GC patients (P0.001 and P = 0.031, respectively). A significant correlation was observed between aberrant hMLH1, hMSH3, and MGMT methylation and the loss of hMLH1, hMSH3, and MGMT protein expression (P0.001, P = 0.002, and P = 0.001, respectively). The prevalence of aberrant hMLH1 and hMSH3 methylation increased significantly with age.These results suggest that the methylation of hMLH1 and hMSH3 is age related and thus may play an important role in gastric carcinogenesis in the elderly. Screening for hMLH1 and hMSH3 methylation may have clinical significance for the evaluation of elderly patients with GC.

Objective The aim of this study was to evaluate the correlation and prognostic significance of MGMT promoter methylation and protein expression in patients with glioblastoma. Methods Eighty-three patients with glioblastoma underwent surgery followed by radiotherapy and temozolomide chemotherapy between October 2000 and June 2008. To investigate the correlation between MGMT methylation and MGMT expression, methylation-specific polymerase chain reaction (MSP) and immunohistochemical staining was performed. To analyze the correlation between MGMT methylation and MGMT expression according to location, biopsies were obtained from 37 different sites within the tumors in 12 patients. Age, sex, Karnofsky Performance Scale status, extent of removal, chemotherapeutic methods, and MGMT promoter methylation and protein expression were analyzed as prognostic factors. Results The total median survival was 15.8 months (range, 12.6-19.1 months). The results of MSP were the same at various sites in 12 patients. A correlation between MSP and immunohistochemical staining was observed in 50% of the patients. In 73 patients, negative MGMT expression was detected in 70.5% of 44 patients with MGMT promoter methylation, and positive expression was observed in 55.2% of the 29 patients with unmethylated promoters. Multivariate analysis revealed that the extent of removal (P = 0.001) and the combination of MGMT promoter methylation and negative MGMT expression (median survival, 20.06 months; P = 0.006) were significantly associated with longer survival. Conclusion We report the feasibility of using MSP combined with immunohistochemical staining as a prognostic factor. The results of the present study suggest that MGMT promoter methylation in combination with negative MGMT expression might be a good prognostic factor in patients with glioblastoma.

To determine the underlying mechanism for the differential expression, the extent of promoter methylation in tumor necrosis factor-related apoptosis-inducing ligand (TRAIL)-related genes acting downstream of TRAIL was examined in early and advanced gastric carcinomas. The extent of promoter methylation in the DR4, DR5, DcR1, DcR2, and CASP8 genes was quantified using bisulfite modification and methylation-specific polymerase chain reaction. The promoters for DcR1, DcR2, and CASP8 were largely unmethylated in early gastric carcinoma, advanced gastric carcinoma, and controls, with no significant difference among them. Protein levels of DR4, DcR1, and DcR2 as revealed by immunohistochemistry correlated with the extent of the respective promoter methylation (P

The The ZigBee is a type of LR-WPAN technology that as low data rate, low power consumption, low cost, wireless networking protocol targeted towards automation and remote control applications. The ZigBee standard defines a comprehensive security architecture and management model, including frame encryption, authentication, and integrity at each layer of the ZigBee protocol stack. In addition, ZigBee defines a Trust Center that provides the essential security functions of key management, network management, and device configuration. But ZigBee specification describes only intra-PAN networks, and the network size is increasing, the energy required for authentication is larger. In this paper, we outlined the basic Trust Center based Authentication (TCA) mechanism. And we propose an enhanced TCA mechanism which improve the performance of current standards in ZigBee Network with mobility node. Through simulation experiments, we showed that the proposed scheme is more energy and memory effective than current scheme. Our scheme provides an optimal and feasible authentication of mobility node in ZigBee networks and is suited for large ZigBee Network.

Loss or reduced E-cadherin expression and aberrant expression of N-cadherin have been associated with invasiveness of human carcinoma cells and poor prognosis. The role of E- and N-cadherin, however, in hepatocellular carcinoma (HCC) has not yet been elucidated. The aim of the present study was to investigate the expression pattern of E- and N-cadherin in surgically resected HCC specimens according to their relationship with clinicopathological features. The expression patterns of E- and N-cadherin were evaluated on immunohistochemistry in 68 specimens of HCC and adjacent non-tumor tissue. The most different expression pattern between HCC and non-tumor tissue was the decreased staining intensity of E-cadherin (n = 37, 54%) and the dot-like discontinuous staining of N-cadherin (n = 35, 55%). Decreased intensity of E-cadherin and discontinuous staining of N-cadherin in HCC was correlated with advanced stage. The risk factors for expression patterns related to recurrence were loss of E-cadherin expression (odds ratio (OR) = 3.6; 95% confidence interval (CI): 1.1-12.4) and discontinuous staining of N-cadherin (OR = 1.6; 95% CI: 0.8-3.2). In conclusion, discontinuous staining of N-cadherin and loss of E-cadherin expression in HCC predicts a high risk of recurrence after surgical treatment.