Gamma-glutamylcyclotransferase promotes the growth of human glioma cells by activating Notch-Akt signaling.

Glioma as an aggressive type tumor is rapidly growing and has become one of the leading cause of cancer-related death worldwide. γ-Glutamylcyclotransferase (GGCT) has been shown as a diagnostic marker in various cancers. To reveal whether there is a correlation between GGCT and human glioma, GGCT expression in human glioma tissues and cell lines was first determined. We found that GGCT expression was up-regulated in human glioma tissues and cell lines. Further, we demonstrate that GGCT knockdown inhibits glioma cell T98G and U251 proliferation and colony formation, whereas GGCT overexpression leads to oppose effects. GGCT overexpression promotes the expression of Notch receptors and activates Akt signaling in glioma cells, and Notch-Akt signaling is activated in glioma tissues with high expression of GGCT. Finally, we show that inhibition of Notch-Akt signaling with Notch inhibitor MK-0752 blocks the effects of GGCT on glioma proliferation and colony formation. In conclusion, GGCT plays a critical role in glioma cell proliferation and may be a potential cancer therapeutic target.

FEATURES OF OPTICAL COHERENCE TOMOGRAPHY FOR THE DIAGNOSIS OF VOGT-KOYANAGI-HARADA DISEASE.

BACKGROUND/PURPOSE: To examine the diagnostic value of optical coherence tomography (OCT) for the detection of acute Vogt-Koyanagi-Harada (VKH) disease. METHODS: Clinical charts and OCT images were retrospectively reviewed for patients consecutively diagnosed with acute VKH, subacute VKH, multifocal central serous chorioretinopathy (CSCR), and posterior scleritis. All patients underwent OCT, fundus photography, and fluorescein angiography (FA) before treatment. The characteristics of OCT and FA were analyzed and recorded. RESULTS: The study included 80 eyes with acute VKH, 32 eyes with subacute VKH, 33 eyes with CSCR, and 13 eyes with posterior scleritis. The most common OCT features of VKH disease were hyperreflective dots (70/80; 88%), subretinal membranous structures (64/80; 80%), retinal detachment higher than 450 µm (63/80; 79%), and retinal pigment epithelium (RPE) folds (44/80; 55%). For the detection of VKH disease, sensitivity and specificity were for subretinal membranous structures 80% and 95.6%, respectively, for high retinal detachment 78.8% and 76.1%, respectively, for subretinal hyperreflective dots, 87.5 and 60.9%, respectively, and for RPE folds 55% and 80.4% respectively. Subretinal membranous structures showed the highest positive predictive value (97.3%) and negative predictive value (65.7%) of all OCT assessed features. CONCLUSION: OCT-related morphological signs have a relatively high predictive value for the diagnosis of acute VKH.

Decreased pygopus 2 expression suppresses glioblastoma U251 cell growth.

Gliomas are common malignant tumors of the human neural system, and Wnt signaling activation is closely related to glioma malignancy. Human Pygopus 2 (Pygo2) was recently discovered to be a component of the Wnt signaling pathway, which is required for ß-catenin/Tcf-dependent transcription. However, the role of Pygo2 in glioblastoma cell growth and survival remains uncertain. In the present study, Pygo2 expression was evaluated in 80 glioma tissue samples. Results demonstrated that tumor grade exhibited a positive correlation with overexpression of Pygo2. In addition, small hairpin RNA (shRNA) was used to specifically knockdown Pygo2 expression in human glioblastoma U251 cell lines. Results showed that inhibition of Pygo2 expression resulted in inhibited cell proliferation and invasiveness, as well as increased cell cycle arrest at the G(1) stage and decreased expression of the Wnt target gene cyclin D1. These results demonstrated that Pygo2 was highly expressed in glioma tissue and required for growth of glioblastoma cells.

Automatic liver segmentation from abdominal CT volumes using graph cuts and border marching.

BACKGROUND AND OBJECTIVE: Identifying liver regions from abdominal computed tomography (CT) volumes is an important task for computer-aided liver disease diagnosis and surgical planning. This paper presents a fully automatic method for liver segmentation from CT volumes based on graph cuts and border marching. METHODS: An initial slice is segmented by density peak clustering. Based on pixel- and patch-wise features, an intensity model and a PCA-based regional appearance model are developed to enhance the contrast between liver and background. Then, these models as well as the location constraint estimated iteratively are integrated into graph cuts in order to segment the liver in each slice automatically. Finally, a vessel compensation method based on the border marching is used to increase the segmentation accuracy. RESULTS: Experiments are conducted on a clinical data set we created and also on the MICCAI2007 Grand Challenge liver data. The results show that the proposed intensity, appearance models, and the location constraint are significantly effective for liver recognition, and the undersegmented vessels can be compensated by the border marching based method. The segmentation performances in terms of VOE, RVD, ASD, RMSD, and MSD as well as the average running time achieved by our method on the SLIVER07 public database are 5.8 ± 3.2%, -0.1 ± 4.1%, 1.0 ± 0.5mm, 2.0 ± 1.2mm, 21.2 ± 9.3mm, and 4.7 minutes, respectively, which are superior to those of existing methods. CONCLUSIONS: The proposed method does not require time-consuming training process and statistical model construction, and is capable of dealing with complicated shapes and intensity variations successfully.

Inhibition of Human Glioma Cell Proliferation Caused by Knockdown of Utrophin Using a Lentivirus-Mediated System.

BACKGROUND: Glioma is the most devastating brain tumor worldwide. Previous studies showed that UTRN (utrophin) was related to cancers, but its role in glioma cells remains uncovered. MATERIALS AND METHODS: RNAi was used to knockdown UTRN in U251 cells using lentivirus system. The knockdown efficiency was validated by real-time quantitative PCR. Cell proliferation, cell cycle, and apoptosis progression were determined by MTT, colony formation analysis, and flow cytometry analysis. Furthermore, some apoptotic markers were examined by Western blot assay. RESULTS: Most cells were infected. Cell proliferation and colony formation ability were suppressed in U251 cells lacking UTRN. Moreover, there was an obvious increase in cell percentage in the G2/M phases and a significant apoptosis in U251 cells after UTRN silencing. Further investigation demonstrated that UTRN knockdown activated caspase and PARP pathways. CONCLUSIONS: Knockdown of UTRN expression by shRNA evidently inhibited cell proliferation and promoted cell apoptosis in glioma cells.

Reduction cranioplasty with the aid of simulated computer imaging for the treatment of hydrocephalic macrocephaly.

OBJECT: The occurrence of hydrocephalic macrocephaly is uncommon. When the condition does occur, it is usually seen in infants and young children. Patients with this disorder have an excessively enlarged head and weak physical conditions. Various surgical techniques of reduction cranioplasty for the treatment of these patients have been reported. In this study, a revised surgical procedure with the aid of simulated computer imaging for the treatment of hydrocephalic macrocephaly is presented. METHODS: Five cases of hydrocephalic macrocephaly in children ranging in age from 16 to 97 months were reviewed. These patients underwent surgical treatment at The First Affiliated Hospital of Xiamen University over a period of 4 years from January 2007 to January 2011. After physical examination, a 3D computer imaging system to simulate the patient's postoperative head appearance and bone reconstruction was established. Afterward, for each case an appropriate surgical plan was designed to select the best remodeling method and cranial shape. Then, prior to performing reduction remodeling surgery in the patient according to the computer-simulated procedures, the surgeon practiced the bone reconstruction technique on a plaster head model made in proportion to the patient's head. In addition, a sagittal bandeau was used to achieve stability and bilateral symmetry of the remodeled cranial vault. Each patient underwent follow-up for 6-32 months. RESULTS: Medium-pressure ventriculoperitoneal shunt surgery or shunt revision procedures were performed in each patient for treating hydrocephalus, and all patients underwent total cranial vault remodeling to reduce the cranial cavity space. Three of the 5 patients underwent a single-stage surgery, while the other 2 patients underwent total cranial vault remodeling in the first stage and the ventriculoperitoneal shunt operation 2 weeks later because of unrecovered hydrocephalus. All patients had good outcome with regard to hydrocephalus and macrocephaly. CONCLUSIONS: There are still no standard surgical strategies for the treatment of hydrocephalic macrocephaly. Based on their experience, the authors suggest using a computer imaging system to simulate a patient's postoperative head appearance and bone reconstruction together with total cranial vault remodeling with shunt surgery in a single-stage or 2-stage procedure for the successful treatment of hydrocephalic macrocephaly.

[Bioaccumulation of mercury in Crassostrea sp. exposed to waste seawater discharged from a coal-fired power plant equipped with a seawater flue-gas desulfurization system].

A field experiment was conducted to study mercury (Hg) bioaccumulation in Crassostrea sp. exposed to waste seawater discharged from a coal-fired power plant equipped with a flue gas desulfurization system. Oysters were cultured in the discharge outlet of the power plant (studying site) and a control site, respectively. The total Hg (THg) concentrations (all counted as dry weight) of seawater in the studying and control sites were determined as (120.6 +/- 55.5) ng x L(-1) (n = 5) and (2.7 +/- 1.0) ng x L(-1) (n = 5), respectively, while methyl Hg (MeHg) concentrations were (0.30 +/- 0.44) ng x L(-1) (n = 5) and (0.28 +/- 0.31) ng x L(-1) (n = 5), respectively. The THg in oyster at the studying site increased dramatically from (138.3 +/- 14.3) ng x g(-1) (n = 6) to (3 012 +/- 289) ng x g(-1) (n = 6) within 7 d, and remained at high levels of 2 935-4 490 ng x g(-1) for the next 34 d. In contrast, the THg in oyster at the control site showed no significant change, and kept at low levels of 60.7-137.5 ng x g(-1). After 41 d exposure, the MeHg in oyster at the studying site had no significant change, ranging from 55.4 ng x g(-1) to 73.1 ng x g(-1), and the content at the control site showed a slight decrease, ranging from 15.6 to 55.6 ng x g(-1). The study showed that THg in the waste seawater discharged at the coal-fired power plant could be quickly bioaccumulated by oyster to a great extent, the potential risk can thus not be ignored. MeHg concentration in the waste seawater was quite low, and no obvious bioaccumulation was found in oyster. Under the study conditions, no self-synthesis of MeHg or transformation of inorganic Hg into MeHg was found.

The role of Pygopus 2 in rat glioma cell growth.

Glioma is a common malignant tumor of the human neural system, and Wnt signaling activation is closely connected with glioma malignancy. Pygopus 2 (Pygo2) was recently discovered as a component of the Wnt signaling pathway regulating ß-catenin/Tcf dependent transcription. However, the role of Pygo2 in glioma cells has not yet been defined. In the current study, we investigated the role of Pygo2 in rat glioma C6 cells for the first time. Our results showed that over-expression of Pygo2 promoted cell proliferation as well as enhanced cell cycle progression from G1 to S phase associated with an increase in the expression of the Wnt target gene cyclin D1. In contrast, knockdown of Pygo2 suppressed cell proliferation with cell cycle block from G1 to S phase and down-regulation of cyclin D1. In addition, the expression of Pygo2 and cyclin D1 in 67 glioma tissue samples was quantified by real-time reverse transcription polymerase chain reaction (RT-PCR) and immunochemistry. The data indicated that tumor grade was significantly associated with over-expression of Pygo2 and cyclin D1. We conclude that Pygo2 is highly expressed in and promotes the growth of glioma cells by an increase in the expression of cyclin D1 to improve G1/S transition.