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Find video protocols related to scientific articles indexed in Pubmed.
Mitochondrial Induced and Self-Monitored Intrinsic Apoptosis by Antitumor Theranostic Prodrug: In Vivo Imaging and Precise Cancer Treatment.
J. Am. Chem. Soc.
PUBLISHED: 11-18-2014
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Activation of apoptosis, the cell death machinery, in tumor cells by organelle specific delivery of antitumor theranostic agent is utmost challenge in cancer therapy. Herein, we developed a highly efficient mitochondria targeting antitumor theranostic prodrug 7 that contain two molecules of drug 5'-deoxy-5-fluorouridine, and an apoptotic marker ethidium for self-monitoring intrinsic (mitochondrial) apoptosis after its activation in tumor cells. Theranostic 7 was activated by endogenously produced mitochondrial-overexpressed H2O2 and release drug 5'-deoxy-5-fluorouridine and apoptotic marker ethidium to the tumor cells. The in vitro and in vivo drug release was monitored by observing the fluorescence changes of ethidium. Theranostic 7 exhibited an enhanced cytotoxicity over commercial 5-fluorouracil (an active drug of 5'-deoxy-5-fluorouridine) leading to intrinsic apoptosis monitored by in situ generated ethidium. Enhanced expres-sion of mitochondria-mediated apoptotic genes (NOXA, PUMA, BID, BAX, and BAK), Cyt C, Caspase-3 and -9, and cell surface death receptors was observed after theranostic 7 activation in tumor cells. In vivo and ex-vivo xenografts re-vealed that theranostic 7 significantly inhibited tumor progression and cured the tumor-bearing mice. Such organelle specific theranostic strategies have great potential for the early diagnosis and precise treatment of cancer.
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Pancreatic islet-like three dimensional aggregates derived from human embryonic stem cells ameliorate hyperglycemia in streptozotocin-induced diabetic mice.
Cell Transplant
PUBLISHED: 11-15-2014
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We previously reported the in vitro differentiation of human embryonic stem cells (hESCs) into pancreatic endoderm. Here, we demonstrate that islet-like three-dimensional (3D) aggregates can be derived from the pancreatic endoderm by optimizing our previous protocol. Sequential treatment with Wnt3a, activin A, and noggin induced a transient upregulation of T and MixL1, followed by increased expression of endodermal genes, including FOXA2, SOX17, and CXCR4. Subsequent treatment with retinoic acid highly upregulated PDX1 expression. We also show that inhibition of sonic hedgehog signaling by bFGF/activin ?B and cotreatment with VEGF and FGF7 produced many 3D cellular clusters that express both SOX17 and PDX1. We found for the first time that proteoglycans and vimentin(+) mesenchymal cells were mainly localized in hESC-derived PDX1(+) clusters. Importantly, treatment with chlorate, an inhibitor of proteoglycan sulfation, together with inhibition of Notch signaling significantly increased the expression of NEUROG3 and NEUROD1, promoting a transition from PDX1(+) progenitor cells towards mature pancreatic endocrine cells. Purified dithizone+ 3D aggregates generated by our refined protocol produced pancreatic hormones and released insulin in response to both glucose and pharmacological drugs in vitro. Furthermore, the islet-like 3D aggregates decreased blood glucose levels and continued to exhibit pancreatic features after transplantation into diabetic mice. Generation of islet-like 3D cell aggregates from human pluripotent stem cells may overcome the shortage of cadaveric donor islets for future cases of clinical islet transplantation.
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Effect of pH on the formation of lysosome-alginate beads for antimicrobial activity.
J. Microbiol. Biotechnol.
PUBLISHED: 10-13-2014
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In this study, we developed lysosome-alginate beads for application as an oral drug delivery system (ODDS). The beads harboring lysosomes, which have antimicrobial activity, and various concentrations of alginate were characterized and optimized. For application as an ODDS, pH-dependent lysosome-alginate beads were generated, and the level of lysosome release was investigated by using antimicrobial tests. At low pH, lysosomes were not released from the lysosome-alginate beads; however, at neutral pH, similar to the pH in the intestine, lysosome release was confirmed, as determined by a high antimicrobial activity. This study shows the potential of such an ODDS for the in vivo treatment of infection with pathogens.
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Sonic hedgehog signalling proteins are frequently expressed in retinoblastoma and are associated with aggressive clinicopathological features.
J. Clin. Pathol.
PUBLISHED: 10-10-2014
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This study aimed to examine the expression of Sonic hedgehog (SHH) signalling proteins in retinoblastoma and to evaluate its clinical significance.
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Genetic and epigenetic analysis in korean patients with multiple endocrine neoplasia type 1.
Endocrinol Metab (Seoul)
PUBLISHED: 09-25-2014
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Multiple endocrine neoplasia type 1 (MEN1) is a familial syndrome characterized by the parathyroid, pancreas and pituitary tumors. Parathyroid tumors are the most common clinical manifestations, occurring in more than 90% of MEN1 patients. Heterozygous germline mutations of the MENIN gene underlie the tumorigenesis in MEN1 and epigenetic alterations along with germline mutations may contribute to tumorigenesis. Here, we investigated the associations between genotype and phenotype in Korean MEN1 patients.
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All-solution-processed, multilayered CuInS?/ZnS colloidal quantum-dot-based electroluminescent device.
Opt Lett
PUBLISHED: 08-29-2014
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While significant progress of electroluminescent (EL) quantum dot light-emitting diodes (QD-LEDs) that rely exclusively on Cd-containing II-VI quantum dots (QDs) has been reported over the past two decades with respect to device processing and performance, devices based on non-Cd QDs as an active emissive layer (EML) remain at the early stage of development. In this work, utilizing highly luminescent colloidal CuInS2 (CIS)/ZnS QDs, all-solution-processed multilayered QD-LEDs are fabricated by sequentially spin depositing a hole transport layer of poly(9-vinlycarbazole), an EML of CIS/ZnS QDs, and an electron transport layer of ZnO nanoparticles. Our focus in device fabrication is to vary the thickness of the QD EML, which is one of the primary determinants in EL performance but has not been addressed in earlier reports. The device with an optimal EML thickness exhibits a peak luminance of 1564??cd/m2 and current efficiency of 2.52??cd/A. This record value in efficiency is higher by 3-4 times that of CIS QD-LEDs reported previously.
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The G protein ? subunit G?s is a tumor suppressor in Sonic hedgehog-driven medulloblastoma.
Nat. Med.
PUBLISHED: 08-24-2014
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Medulloblastoma, the most common malignant childhood brain tumor, exhibits distinct molecular subtypes and cellular origins. Genetic alterations driving medulloblastoma initiation and progression remain poorly understood. Herein, we identify GNAS, encoding the G protein G?s, as a potent tumor suppressor gene that, when expressed at low levels, defines a subset of aggressive Sonic hedgehog (SHH)-driven human medulloblastomas. Ablation of the single Gnas gene in anatomically distinct progenitors in mice is sufficient to induce Shh-associated medulloblastomas, which recapitulate their human counterparts. G?s is highly enriched at the primary cilium of granule neuron precursors and suppresses Shh signaling by regulating both the cAMP-dependent pathway and ciliary trafficking of Hedgehog pathway components. Elevation in levels of a G?s effector, cAMP, effectively inhibits tumor cell proliferation and progression in Gnas-ablated mice. Thus, our gain- and loss-of-function studies identify a previously unrecognized tumor suppressor function for G?s that can be found consistently across Shh-group medulloblastomas of disparate cellular and anatomical origins, highlighting G protein modulation as a potential therapeutic avenue.
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Dopamine D(2/3) receptor availability and human cognitive impulsivity: a high-resolution positron emission tomography imaging study with [¹¹C]raclopride.
Acta Neuropsychiatr
PUBLISHED: 08-22-2014
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Human impulsivity is a complex multidimensional construct encompassing cognitive, emotional, and behavioural aspects. Previous animal studies have suggested that striatal dopamine receptors play a critical role in impulsivity. In this study, we investigated the relationship between self-reported impulsiveness and dopamine D(2/3) receptor availability in striatal subdivisions in healthy subjects using high-resolution positron emission tomography (PET) with [11C]raclopride.
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Preparation and pharmaceutical evaluation of new tacrolimus-loaded solid self-emulsifying drug delivery system.
Arch. Pharm. Res.
PUBLISHED: 08-20-2014
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The purpose of this study was to develop a novel tacrolimus-loaded solid self-emulsifying drug delivery system (SEDDS) using Labrafac as an oil phase. The ternary phase diagram was plotted with Labrafac, Labrasol and Lauroglycol used as an oil, surfactant and co-surfactant, respectively. The liquid SEDDS formulated with Labrasol, Lauroglycol and Labrafac (70:15:15, volume ratio) furnished the smallest emulsion globule size. The solid SEDDS was obtained by spray-drying the liquid mixture containing the liquid SEDDS with 5 % tacrolimus and silicon dioxide. Furthermore, dissolution of tacrolimus from the solid SEDDS and pharmacokinetics in rats was studied compared to the commercial product. The solid SEDDS produced relatively larger emulsion globule size than that exhibited by the corresponding liquid SEDDS. However, this size variation was not significantly different. The solid SEDDS with approximately 280 nm emulsion droplet size improved the dissolution of the drug compared to drug power and the commercial product. It resulted in significantly higher plasma concentration, AUC and Cmax, and shorter Tmax values than did the commercial product (p < 0.05). The enormously enhanced oral bioavailability of tacrolimus in rats was attributed to relatively faster absorption due to accelerated dissolution of the drug from the solid SEDDS. Therefore, this novel solid SEDDS prepared with Labrafac as an oil phase is an excellent way to achieve better bioavailability of tacrolimus given via the oral route.
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Valproic acid increases NO production via the SH-PTP1-CDK5-eNOS-Ser(116) signaling cascade in endothelial cells and mice.
Free Radic. Biol. Med.
PUBLISHED: 08-19-2014
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Valproic acid (VPA) with its inhibitory activity of histone deacetylase has been used in the treatment of epilepsy and bipolar disorder associated with cerebrovascular dysfunction. Because nitric oxide (NO) produced by endothelial NO synthase (eNOS) plays a role in the maintenance of vascular function, NO is likely to mediate VPA?s drug effect, but its effect on NO production remains controversial. We investigated whether and how VPA regulates NO production in bovine aortic endothelial cells (BAECs) and mice. VPA increased NO production in BAECs, which was accompanied by a decrease in phosphorylation of eNOS at serine 116 (eNOS-Ser(116)) and cyclin-dependent kinase 5 at tyrosine 15 (CDK5-Tyr(15)). Ectopic expression of p25, a CDK5 activator, restored the VPA-inhibited eNOS-Ser(116) phosphorylation. In silico analysis revealed that the CDK5-Tyr(15) residue might be a substrate for SH2 domain-containing protein tyrosine phosphatase 1 (SH-PTP1), and CDK5 actually interacted with SH-PTP1. VPA increased SH-PTP1 expression and its activity. Stibogluconate, a specific SH-PTP1 inhibitor, reversed the VPA-inhibited phosphorylation of CDK5-Tyr(15) and eNOS-Ser(116). Knockdown of SH-PTP1 using small interfering RNA also reversed all the observed effects of VPA. Finally, both serum NO level and acetylcholine-induced aortic relaxation increased in VPA-medicated male mice. These increases were accompanied by increased SH-PTP1 expression and decreased phosphorylation of CDK5-Tyr(15) and eNOS-Ser(116) in mouse aortas. In conclusion, VPA increases NO production by inhibiting the CDK5-Tyr(15)-eNOS-Ser(116) phosphorylation axis; this process is mediated by SH-PTP1. VPA may be useful in the treatment of NO-related cerebrocardiovascular diseases.
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The prognostic significance of Smad3, Smad4, Smad3 phosphoisoform expression in esophageal squamous cell carcinoma.
Med. Oncol.
PUBLISHED: 08-15-2014
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Smad3 functions as an integrator of diverse signaling, including transforming growth factor ? signaling and the function of Smad3 is complexly regulated by differential phosphorylation at various sites of Smad3. Despite the importance of Smad3 and its various phosphoisoforms, their prognostic significance has rarely been studied. In this study, we demonstrated the prognostic significance of Smad3, its phosphoisoforms, and Smad4 expression by immunohistochemistry in 126 esophageal squamous cell carcinomas. The phosphoisoforms of Smad3 studied in this article included phosphorylation at C-terminal (pSmad3C)(Ser(423/425)) and phosphorylation at the linker region (pSmad3L)(Ser(213)). High expression of Smad3 was associated with shorter overall survival. Co-existence of high expression of pSmad3L(S213) and low expression of pSmad3C(S423/425) were associated with advanced N stage and an independent prognostic factor for overall [hazard ratio (HR) 2.03, 95 % confidence interval (CI) (1.10-3.75), p = 0.023] and disease-free survival [HR 2.41, 95 % CI (1.32-4.39), p = 0.004]. In conclusion, co-existence of high pSmad3L(Ser(213)) expression and low pSmad3C(Ser(423/425)) expression can be considered as immunohistochemical biomarkers for predicting prognosis as well as future therapeutic targets. In addition, our results of combinatory effect of differential phosphorylation of Smad3 on prognosis suggest the mode of action of Smad3 might be logically determined by its phosphorylation pattern.
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Gastroprotective activity of violacein isolated from Chromobacterium violaceum on indomethacin-induced gastric lesions in rats: investigation of potential mechanisms of action.
ScientificWorldJournal
PUBLISHED: 08-05-2014
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Chromobacterium violaceum, Gram-negative bacteria species found in tropical regions of the world, produces a distinct deep violet-colored pigment called violacein. In the present study, we investigated whether violacein can promote a gastroprotective effect and verified the possible mechanisms involved in this action. For this study, an indomethacin-induced gastric ulcer rat model was used. The roles of biomolecules such as MPO, PGE2, pro- and anti-inflammatory cytokines, growth factors, caspase-3, NO, K(+)ATP channels, and ? 2-receptors were investigated. Violacein exhibited significant gastroprotective effect against indomethacin-induced lesions, while pretreatment with L-NAME and glibenclamide (but not with NEM or yohimbine) was able to reverse this action. Pretreatment with violacein also restored cNOS level to normal and led to attenuation of enhanced apoptosis and gastric microvascular permeability. Our results suggest that violacein provides a significant gastroprotective effect in an indomethacin-induced ulcer model through the maintenance of some vital protein molecules, and this effect appears to be mediated, at least in part, by endogenous prostaglandins, NOS, K(+)ATP channel opening, and inhibition of apoptosis and gastric microvascular permeability.
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MicroRNA-200 family members and ZEB2 are associated with brain metastasis in gastric adenocarcinoma.
Int. J. Oncol.
PUBLISHED: 08-02-2014
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Although the incidence of brain metastasis in gastric cancer is relatively low, its prevalence may increase with improved therapy and longer survival tumors. The molecular mechanisms underlying brain metastases are not well understood. To gain insight into the mechanism of brain metastasis, we studied differences in microRNA (miRNA) expression levels in 8 cases of matched primary gastric adenocarcinoma and brain metastatic adenocarcinoma using the Illumina microRNA microarray chip. We identified 6 upregulated and 2 downregulated miRNAs in all 8 cases simultaneously. Interestingly, 2 out of 8 miRNAs (hsa-miR?141-3p and hsa-miR-200b-3p) belonged to the miR-200 family. Online microRNA database searching revealed that ZEB2 is the top-ranked target gene for hsa-miR141-3p and hsa-miR-200b-3p, prompting us to focus ZEB2 expression in brain metastatic adenocarcinoma. We confirmed that ZEB2 expression was markedly downregulated in some brain metastatic samples. In addition, decreased ZEB2 expression was noted by western blot analysis of 2 metastatic gastric adenocarcinoma cell types that were derived by in vivo selection following intracardiac injection of gastric cancer cell lines. In conclusion, we demonstrate that expression of miRNA-200 family members and ZEB2 are associated with brain metastases of gastric adenocarcinoma, not only in matched patient samples, but also in metastatic cell lines that were derived by in vivo selection.
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Correlation between HER2 Overexpression and Clinicopathological Characteristics in Gastric Cancer Patients Who Have Undergone Curative Resection.
J Gastric Cancer
PUBLISHED: 07-17-2014
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At present, a human epidermal growth factor receptor 2 (HER2)-based concept of tumor biology has been established, and trastuzumab (Herceptin®; Genentech/Roche, San Francisco, CA, USA), a monoclonal humanized antibody directed against HER2, is a pivotal agent for the management of HER2 positive (HER2+) metastatic breast cancer. It is also known that HER2 has a predictive value in gastric cancer; however, its association with the prognosis of this disease remains uncertain. The purpose of this study was to evaluate both the relationship between HER2 overexpression in the tumors of gastric cancer patients, and the prognosis of these patients who have had curative resection.
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Toxicity detection in mine water based on proteomic analysis of lysosomal enzymes in Saccharomyces cerevisiae.
Environ Health Toxicol
PUBLISHED: 07-16-2014
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Lysosome is the cell-organelle which is commonly used as biomonitoring tool in environmental pollution. In this study, the lysosomal proteomic of the yeast Saccharomyces cerevisiae was analyzed for utilization in the detection of toxic substances in mine water samples.
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Adult-Onset Sellar and Suprasellar Atypical Teratoid Rhabdoid Tumor Treated with a Multimodal Approach: A Case Report.
Brain Tumor Res Treat
PUBLISHED: 07-15-2014
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We report a very rare case of sellar and suprasellar atypical teratoid rhabdoid tumor (ATRT) in a 42-year-old female patient. The tumor was removed subtotally with a transsphenoidal approach. Histopathologic study showed rhabdoid cells with prominent nucleoli and abundant cytoplasm. Immunohistochemistry for INI1 was completely negative in the tumor cells, consistent with ATRT. After surgery, she received radiotherapy including spinal irradiation with proton beam therapy and subsequent chemotherapy, with no evidence of recurrence for more than 2 years. Up to date, this is the 8th case of an adult-onset ATRT in the sellar or suprasellar region. Despite its rarity, ATRTs should be considered in the differential diagnosis of an unclear malignant sellar or suprasellar lesion in adult patients and the treatment strategies for adult ATRT patients could be differentiated from those of pediatric ATRT patients.
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IKK ? -Targeted Anti-Inflammatory Activities of a Butanol Fraction of Artificially Cultivated Cordyceps pruinosa Fruit Bodies.
Evid Based Complement Alternat Med
PUBLISHED: 07-15-2014
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The inhibitory activities of the Cordyceps pruinosa butanol fraction (Cp-BF) were investigated by determining inflammatory responses of lipopolysaccharide (LPS)-treated RAW264.7 macrophage cells and by evaluating HCl/ethanol (EtOH)-triggered gastric ulcers in mice. The molecular mechanisms of the inhibitory effects of Cp-BF were investigated by identifying target enzymes using biochemical and molecular biological approaches. Cp-BF strongly inhibited the production of NO and TNF-?, release of reactive oxygen species (ROS), phagocytic uptake of FITC-dextran, and mRNA expression levels of interleukin (IL)-6, inducible NO synthase (iNOS), and tumour necrosis factor-alpha (TNF)-? in activated RAW264.7 cells. Cp-BF also strongly downregulated the NF-?B pathway by suppressing IKK? according to luciferase reporter assays and immunoblot analysis. Furthermore, Cp-BF blocked both increased levels of NF-?B-mediated luciferase activities and phosphorylation of p65/p50 observed by IKK? overexpression. Finally, orally administered Cp-BF was found to attenuate gastric ulcer and block the phosphorylation of I?B? induced by HCl/EtOH. Therefore, these results suggest that the anti-inflammatory activity of Cp-BF may be mediated by suppression of IKK? and its downstream NF-?B activation. Since our group has established the mass cultivation conditions by developing culture conditions for Cordyceps pruinosa, the information presented in this study may be useful for developing new anti-inflammatory agents.
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Feasibility and outcomes of hypofractionated simultaneous integrated boost-intensity modulated radiotherapy for malignant gliomas: a preliminary report.
Yonsei Med. J.
PUBLISHED: 06-28-2014
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The aim of this study was to assess the feasibility and efficacy of hypofractionated simultaneous integrated boost-intensity modulated radiotherapy (SIB-IMRT) using three-layered planning target volumes (PTV) for malignant gliomas.
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Impact of aerobic exercise training on endothelial function in acute coronary syndrome.
Ann Rehabil Med
PUBLISHED: 06-26-2014
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To confirm the improvement in arterial endothelial function by aerobic exercise training, flow-mediated dilation (FMD) was tested by ultrasonography.
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Crosstalk between glioma-initiating cells and endothelial cells drives tumor progression.
Cancer Res.
PUBLISHED: 06-24-2014
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Glioma-initiating cells (GIC), which reside within the perivascular microenvironment to maintain self-renewal capacity, are responsible for glioblastoma initiation, progression, and recurrence. However, the molecular mechanisms controlling crosstalk between GICs and endothelial cells are poorly understood. Here, we report that, in both GICs and endothelial cells, platelet-derived growth factor (PDGF)-driven activation of nitric oxide (NO) synthase increases NO-dependent inhibitor of differentiation 4 (ID4) expression, which in turn promotes JAGGED1-NOTCH activity through suppression of miR129 that specifically represses JAGGED1 suppression. This signaling axis promotes tumor progression along with increased GIC self-renewal and growth of tumor vasculature in the xenograft tumors, which is dramatically suppressed by NOTCH inhibitor. ID4 levels correlate positively with NOS2 (NO synthase-2), HES1, and HEY1 and negatively with miR129 in primary GICs. Thus, targeting the PDGF-NOS-ID4-miR129 axis and NOTCH activity in the perivascular microenvironment might serve as an efficacious therapeutic modality for glioblastoma.
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Gastroprotective effect of nymphayol isolated from Nymphaea stellata (Willd.) flowers: Contribution of antioxidant, anti-inflammatory and anti-apoptotic activities.
Chem. Biol. Interact.
PUBLISHED: 06-23-2014
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Gastric ulcer is an illness that affects a great number of people worldwide. The goal of the present research was to assess the anti-ulcerogenic activity of nymphayol (NYM), isolated from Nymphaea stellata, against an ethanol-induced ulcer model in rats. Administration of ethanol elevates the levels of the ulcer index (UI) along with causing tremendous increases in lipid peroxidation and myeloperoxidase (MPO) and significant decreases in gastric mucus, catalase (CAT), superoxide dismutase (SOD), glutathione (GSH), glutathione peroxidase (GPx), and prostaglandin E2 (PGE2). However, the NYM- (45mg/kg) pretreated animals showed considerable increases in antioxidants, gastric mucus, and PGE2 level and significant decreases in UI, lipid peroxidation, and MPO level. Pro-inflammatory cytokines such as interleukin-6 (IL-6), interleukin-1? (IL-1?), tumor necrosis factor-? (TNF-?), and interferon-? (IFN-?) were increased and the level of interleukin-10 (IL-10), an anti-inflammatory cytokine, was decreased in ethanol-induced ulcerated animals, and these inequalities were amended by NYM pretreatment. Pro-apoptotic markers including caspase-8, caspase-9, and caspase-3 were decreased and Bcl-2, an anti-apoptotic marker, was increased through NYM pretreatment, as compared with the ethanol-induced ulcer group. Pretreatment with indomethacin, SC560, rofecoxib, and N?-Nitro-l-arginine methyl ester (l-NAME) considerably prevented the ulcer protective activity of NYM (45mg/kg), indicating the involvement of cyclooxygenase (COX) and nitric oxide synthase (NOS) in NYM-mediated gastroprotection against ethanol-induced ulcer. These outcomes suggest that the gastroprotective effect of NYM might be mediated by adjustment of inflammatory mediators and apoptotic markers and increasing antioxidants.
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Transmission dynamics of oral polio vaccine viruses and vaccine-derived polioviruses on networks.
J. Theor. Biol.
PUBLISHED: 06-23-2014
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One drawback of oral polio vaccine (OPV) is the potential reversion to more transmissible, virulent circulating vaccine-derived polioviruses (cVDPVs), which may cause outbreaks of paralytic poliomyelitis. Previous modeling studies of the transmission of cVDPVs assume an unrealistic homogeneous mixing of the population and/or ignore that OPV viruses and cVDPVs compete for susceptibles, which we show is a key to understanding the dynamics of the transmission of cVDPVs. We examined the transmission of OPV viruses and cVDPVs on heterogeneous, dynamic contact networks using differential equation-based and individual-based models. Despite the lower transmissibility, OPV viruses may outcompete more transmissible cVDPVs in the short run by spreading extensively before cVDPVs emerge. If viruses become endemic, however, cVDPVs eventually dominate and force OPV viruses to extinction. This study improves our understanding of the emergence of cVDPVs and helps develop more detailed models to plan a policy to control paralytic polio associated with the continued use of OPV in many countries.
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Prediction of methylguanine methyltransferase promoter methylation in glioblastoma using dynamic contrast-enhanced magnetic resonance and diffusion tensor imaging.
J. Neurosurg.
PUBLISHED: 06-20-2014
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The methylation status of the methylguanine methyltransferase (MGMT) promoter has been associated with treatment response in glioblastoma. The authors aimed to assess whether MGMT methylation status can be predicted by dynamic contrast-enhanced (DCE) MRI and diffusion tensor imaging (DTI).
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Which Combination of MR Imaging Modalities Is Best for Predicting Recurrent Glioblastoma? Study of Diagnostic Accuracy and Reproducibility.
Radiology
PUBLISHED: 05-30-2014
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Purpose To compare the added value of dynamic contrast material-enhanced (CE) (DCE) magnetic resonance (MR) imaging with that of dynamic susceptibility CE (DSC) MR imaging with the combination of CE T1-weighted imaging and diffusion-weighted (DW) imaging for predicting recurrent glioblastoma. Materials and Methods This retrospective study was approved by the institutional review board, with the requirement for informed patient consent waived. CE T1-weighted images, DW images, DSC MR images, and DCE MR images in 169 patients with pathologically or clinicoradiologically diagnosed recurrent glioblastoma (n = 87) or radiation necrosis (n = 82) were retrospectively reviewed. Histogram cutoffs of quantitative parametric values were calculated from DW images, DSC MR images, and DCE MR images. Area under the receiver operating characteristic curve (Az) and interreader agreement were assessed. Results For predicting recurrent glioblastoma, adding DCE MR imaging to the combination of CE T1-weighted imaging and DW imaging significantly improved Az from 0.84 to 0.96 for reader 1 and from 0.81 to 0.97 for reader 2, respectively. Adding DSC MR imaging also significantly improved Az (0.95 for reader 1 and 0.93 for reader 2). However, there was no significant difference in Az between the combination of CE T1-weighted imaging, DW imaging, and DSC MR imaging and the combination of CE T1-weighted imaging, DW imaging, and DCE MR imaging for both readers. The interreader agreement was highest for the combination of CE T1-weighted imaging, DW imaging, and DCE MR imaging (? = 0.78) and lowest for CE T1-weighted imaging and DW imaging (? = 0.65). Conclusion Adding perfusion MR imaging to the combination of CE T1-weighted imaging and DW imaging significantly improves the prediction of recurrent glioblastoma; however, selection of perfusion MR method does not affect the diagnostic performance. © RSNA, 2014.
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Treatment and Outcomes for Gangliogliomas: A Single-Center Review of 16 Patients.
Brain Tumor Res Treat
PUBLISHED: 05-29-2014
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Ganglioglioma is a rare and slowly growing benign tumor. We investigated the outcomes of patients who underwent different combination treatments.
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CD10 expression is enhanced by Twist1 and associated with poor prognosis in esophageal squamous cell carcinoma with facilitating tumorigenicity in vitro and in vivo.
Int. J. Cancer
PUBLISHED: 05-16-2014
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CD10 expression was identified as a contributor to cancer progression in several cancers; however, the exact biological significance and mechanism of CD10 expression remains unclear. In addition, CD10 expression in esophageal squamous cell carcinoma (ESCC) has not been studied. We investigated the relationship between CD10 and Twist1. Furthermore, we examined the effect of CD10 on tumorigenicity using in vivo and in vitro systems as well as establishing the clinical significance of CD10 expression in ESCC using large clinical samples. CD10 expression was upregulated by Twist1 and there was a strong correlation between mRNA and protein expression. Twist1 can specifically upregulate CD10 at the transcriptional level via an interaction with the promoter region of CD10 and the proximal E-box CAGGTG in the CD10 promoter was identified as a binding site for Twist1. CD10 is frequently expressed in ESCC cell lines and silencing CD10 suppresses migration/invasion and anchorage-independent tumor growth of ESCC cells. Knockdown of CD10 inhibits the growth of ESCC xenograft in nude mice, suggesting that CD10 plays a role in enhancing the tumorigenesis of ESCC. From among 153 ESCC samples, 46 (30.0%) showed varying degrees of CD10 expression in cancer cells. In addition, stromal fibroblasts also showed varying amounts of CD10 expression in 92 (60.9%) tumor samples. CD10 overexpression in cancer cells as well as in stromal fibroblasts was an independent poor prognostic factor in both overall survival and disease-free survival. CD10 could be a promising target for the treatment of ESCC.
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ZNF282 (Zinc finger protein 282), a novel E2F1 co-activator, promotes esophageal squamous cell carcinoma.
Oncotarget
PUBLISHED: 05-14-2014
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Zinc finger protein 282 (ZNF282) is a newly identified transcription factor and little is known about its expression and function. Originally, ZNF282 is known to bind U5RE (U5 repressive element) of HLTV-1 (human T cell leukemia virus type 1) with a repressive effect. Recently we reported that ZNF282 functions as an estrogen receptor co-activator and plays an essential role in breast tumorigenesis. Although these results suggest the possible role of ZNF282 in cancers, clinical significance and function of ZNF282 are completely unknown in most of cancers. Here we found that ZNF282 was frequently overexpressed in esophageal squamous cell carcinoma (ESCC) (n=165) compared with normal esophageal epithelium and its overexpression was correlated with adverse clinical outcome. Multivariate survival analysis indicated that ZNF282 expression was an independent prognostic predictor for poor survival in ESCC (HR: 2.56 (95% CI 1.54-4.26), p<0.001). In addition, depletion of ZNF282 inhibited the cell cycle progression, migration, and invasion of ESCC cells and reduced the tumorigenicity of ESCC xenograft in nude mouse. We further showed that ZNF282 is required for E2F1-mediated gene expression in ESCC cells. Thus, ZNF282 is E2F1 co-activator involved in ESCC and elevated expression of ZNF282 is an independent adverse prognostic factor in ESCC.
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Cytochalasin B modulates macrophage-mediated inflammatory responses.
Biomol Ther (Seoul)
PUBLISHED: 05-12-2014
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The actin cytoskeleton plays an important role in macrophage-mediated inflammatory responses by modulating the activation of Src and subsequently inducing nuclear factor (NF)-?B translocation. In spite of its critical functions, few papers have examined how the actin cytoskeleton can be regulated by the activation of toll-like receptor (TLR). Therefore, in this study, we further characterized the biological value of the actin cytoskeleton in the functional activation of macrophages using an actin cytoskeleton disruptor, cytochalasin B (Cyto B), and explored the actin cytoskeleton's involvement in morphological changes, cellular attachment, and signaling events. Cyto B strongly suppressed the TLR4-mediated mRNA expression of inflammatory genes such as cyclooxygenase (COX)-2, tumor necrosis factor (TNF)-?, and inducible nitric oxide (iNOS), without altering cell viability. This compound also strongly suppressed the morphological changes induced by lipopolysaccharide (LPS), a TLR4 ligand. Cyto B also remarkably suppressed NO production under non-adherent conditions but not in an adherent environment. Cyto B did not block the co-localization between surface glycoprotein myeloid differentiation protein-2 (MD2), a LPS signaling glycoprotein, and the actin cytoskeleton under LPS conditions. Interestingly, Cyto B and PP2, a Src inhibitor, enhanced the phagocytic uptake of fluorescein isothiocyanate (FITC)-dextran. Finally, it was found that Cyto B blocked the phosphorylation of vasodilator-stimulated phosphoprotein (VASP) at 1 min and the phosphorylation of heat shock protein 27 (HSP27) at 5 min. Therefore, our data suggest that the actin cytoskeleton may be one of the key components involved in the control of TLR4-mediated inflammatory responses in macrophages.
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Indoleamine 2,3-dioxygenase (IDO) is frequently expressed in stromal cells of Hodgkin lymphoma and is associated with adverse clinical features: a retrospective cohort study.
BMC Cancer
PUBLISHED: 05-02-2014
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Regulation of tumor microenvironment is closely involved in the prognosis of Hodgkin lymphoma (HL). Indoleamine 2,3-dioxygenase (IDO) is an enzyme acting as immune modulator through suppression of T-cell immunity. This study aims to investigate role of IDO in the microenvironment of HL.
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Electromechanical method coupling non-invasive skin impedance probing and in vivo subcutaneous liquid microinjection: controlling the diffusion pattern of nanoparticles within living soft tissues.
Biomed Microdevices
PUBLISHED: 05-01-2014
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Transdermal drug delivery is the way to transport drug carriers, such as nanoparticles, across the skin barrier to the dermal and/or subcutaneous layer. In order to control the transdermal drug delivery process, based on the heterogeneous and nonlinear structures of the skin tissues, we developed a novel electromechanical method combining in vivo local skin impedance probing, subcutaneous micro-injection of colloidal nanoparticles, and transcutaneous electrical stimulation. Experiments on the nude mice using in vivo fluorescence imaging exhibited significantly different apparent diffusion patterns of the nanoparticles depending on the skin impedance: Anisotropic and isotropic patterns were observed upon injection into low and high impedance points, respectively. This result implies that the physical complexity in living tissues may cause anisotropic diffusion of drug carriers, and can be used as a parameter for controlling drug delivery process. This method also can be combined with microneedle-based drug release systems, micro-fabricated needle-electrodes, and/or advanced in vivo targeting/imaging technologies using nanoparticles.
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A Suggestion of Modified Classification of Trigeminal Schwannomas According to Location, Shape, and Extension.
Brain Tumor Res Treat
PUBLISHED: 04-21-2014
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Comprehensive knowledge of the anatomical features of trigeminal schwannomas (TSs) is essential in planning surgery to achieve complete tumor resection. In the current report, we propose a modified classification of TSs according to their location of origin, shape, and extension into the adjacent compartment, and discuss appropriate surgical strategies with this classification.
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Overexpression of integrin ?v correlates with poor prognosis in colorectal cancer.
J. Clin. Pathol.
PUBLISHED: 04-02-2014
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Integrin ?v subunits are involved in tumour angiogenesis and tumour progression in various types of cancers. Clinical trials evaluating agents targeting integrin ?v are ongoing. Integrin ?v expression has been reported in several cancers in association with tumour progression or poor survival. However, no study has addressed the prognostic influence of integrin ?v expression on survival of patients with colorectal cancer (CRC).
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Blocking the receptor for advanced glycation end product activation attenuates autoimmune myocarditis.
Circ. J.
PUBLISHED: 03-06-2014
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The Receptor for Advanced Glycation End Products (RAGE) is a pattern recognition receptor for endogenous ligands, and is associated with various inflammatory diseases. However, the role of RAGE activation in myocarditis has yet to be examined. The potential role of RAGE in the development of experimental autoimmune myocarditis (EAM) and the effect of RAGE blocking in attenuating the inflammation in the EAM was investigated.
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Cancer-associated fibroblast promote transmigration through endothelial brain cells in three-dimensional in vitro models.
Int. J. Cancer
PUBLISHED: 03-04-2014
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Brain metastases are associated with high morbidity as well as with poor prognosis and survival in breast cancer patients. Despite its clinical importance, metastasis of breast cancer cells through the blood-brain barrier (BBB) is poorly understood. The objective of our study was to investigate whether cancer-associated fibroblasts (CAFs) play crucial roles in breast cancer brain metastasis. Using a cell adhesion assays, in vitro BBB permeability and transmigration assays and soft agar colony formation assays, we investigated the physical roles of CAFs in breast cancer brain metastasis. We also performed immunofluorescence, flow cytometric analysis, Droplet Digital PCR and Simon™ Simple Western System to confirm changes in expression levels. We established two novel three-dimensional (3D) culture systems using a perpendicular slide chamber and applying 3D embedded culture method to reflect brain metastasis conditions. With a newly developed device, CAFs was proven to promote cell adhesion to human brain microvascular endothelial cells, in vitro BBB permeability and transmigration and colony formation of breast cancer cells. Furthermore, CAFs enhanced the invasive migration of breast cancer cells in two kinds of 3D cultures. These 3D models also reliably recapitulate the initial steps of BBB transmigration, micro-metastasis and colonization. Expression of integrin ?5?1 and ?v?3, c-MET and ?2,6-siayltransferase was increased in breast cancer cells that migrated through the BBB. In conclusion, based on our in vitro BBB and co-culture models, our data suggest that CAFs may play a role in breast cancer brain metastasis.
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Novel nonsense GNAS mutation in a 14-month-old boy with plate-like osteoma cutis and medulloblastoma.
J. Dermatol.
PUBLISHED: 02-11-2014
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Plate-like osteoma cutis (PLOC) is a dermatological disorder characterized by superficial ossification and rarely occurs without any underlying tissue abnormalities or pre-existing calcification. The hereditary form of PLOC is mainly due to inactivating mutation in the GNAS gene. Inactivating mutation of the GNAS gene is associated with several diseases, which commonly manifest heterotopic ossification and hormonal resistance; however, the development of malignant neoplasm has never been reported. Herein, we report a case of a patient with a novel nonsense mutation in the GNAS gene, who presented with concurrent PLOC and medulloblastoma.
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HIV Transmissions by Stage and Sex Role in Long-Term Concurrent Sexual Partnerships.
Acta Biotheor.
PUBLISHED: 02-05-2014
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Most mathematical models used to examine the role of different stages of human immunodeficiency virus (HIV) infection unrealistically assume that HIV is transmitted through one-off contacts or that transmission rates are the same between males and females. We sought to examine whether inferences from previous models are robust to the relaxation of those unrealistic assumptions. We developed a model of HIV transmissions through sexual partnerships assuming that (1) sexual partnerships have variable duration, (2) sexual partnerships are concurrent, and (3) the male-to-female transmission rate is higher than the female-to-male transmission rate, with a focus on the third assumption. Assuming a higher rate for male-to-female than female-to-male transmissions decreases the overall transmission of HIV but increases the equilibrium fraction of transmissions during primary HIV infection (PHI) in long-term partnerships, compared to the case where transmission rates are assumed to be symmetric between males an females. Previous modeling studies that assume symmetric transmission rates between males and females may have overestimated the overall spread of HIV, but underestimated the relative contribution of PHI. To make robust inferences on the role of different stages of HIV infection in the sexual spread of HIV, models should take into account that transmission rates may be asymmetric by sex.
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Valproic acid promotes differentiation of hepatocyte-like cells from whole human umbilical cord-derived mesenchymal stem cells.
Tissue Cell
PUBLISHED: 01-30-2014
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Mesenchymal stem cells (MSCs) are mesoderm-derived cells that are considered a good source of somatic cells for treatment of many degenerative diseases. Previous studies have reported the differentiation of mesodermal MSCs into endodermal and ectodermal cell types beyond their embryonic lineages, including hepatocytes and neurons. However, the molecular pathways responsible for the direct or indirect cell type conversion and the functional ability of the differentiated cells remain unclear and need further research. In the present study, we demonstrated that valproic acid (VPA), which is a histone deacetylase inhibitor, induced an increase in the expression of endodermal genes including CXCR4, SOX17, FOXA1, FOXA2, GSC, c-MET, EOMES, and HNF-1? in human umbilical cord derived MSCs (hUCMSCs). In addition, we found that VPA is able to increase these endodermal genes in hUCMSCs by activating signal transduction of AKT and ERK. VPA pretreatment increased hepatic differentiation at the expense of adipogenic differentiation. The effects of VPA on modulating hUCMSCs fate were diminished by blocking AKT and ERK activation using specific signaling inhibitors. Together, our results suggest that VPA contributes to the lineage conversion of hUCMSCs to hepatic cell fate by upregulating the expression of endodermal genes through AKT and ERK activation.
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Analysis on bilateral hindlimb mapping in motor cortex of the rat by an intracortical microstimulation method.
J. Korean Med. Sci.
PUBLISHED: 01-27-2014
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Intracortical microstimulation (ICMS) is a technique that was developed to derive movement representation of the motor cortex. Although rats are now commonly used in motor mapping studies, the precise characteristics of rat motor map, including symmetry and consistency across animals, and the possibility of repeated stimulation have not yet been established. We performed bilateral hindlimb mapping of motor cortex in six Sprague-Dawley rats using ICMS. ICMS was applied to the left and the right cerebral hemisphere at 0.3 mm intervals vertically and horizontally from the bregma, and any movement of the hindlimbs was noted. The majority (80%± 11%) of responses were not restricted to a single joint, which occurred simultaneously at two or three hindlimb joints. The size and shape of hindlimb motor cortex was variable among rats, but existed on the convex side of the cerebral hemisphere in all rats. The results did not show symmetry according to specific joints in each rats. Conclusively, the hindlimb representation in the rat motor cortex was conveniently mapped using ICMS, but the characteristics and inter-individual variability suggest that precise individual mapping is needed to clarify motor distribution in rats.
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Mechanical properties, skin permeation and in vivo evaluations of dexibuprofen-loaded emulsion gel for topical delivery.
Arch. Pharm. Res.
PUBLISHED: 01-16-2014
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The aim of this research was to evaluate the gel properties, skin permeation and in vivo drug efficacy of a novel dexibuprofen-loaded emulsion gel for topical delivery. In this study, the dexibuprofen-loaded emulsion gel and ibuprofen-loaded emulsion gel were prepared with isopropanol, Tween 80, propylene glycol, isopropyl myristate and carbopol. Their mechanical properties such as hardness and adhesiveness were assessed. Moreover, their skin permeation, anti-inflammatory and anti-nociceptive efficacy were evaluated using Franz diffusion cell with the hairless mouse skin, the carrageenan-induced paw oedema test and paw pressure test in rat's hind paws compared with the commercial hydrogel, respectively. The dexibuprofen emulsion gel and ibuprofen emulsion gel provided significantly higher hardness and adhesiveness than the commercial hydrogel. The dexibuprofen emulsion gel enhanced skin permeability by about twofold and 3.5-fold without lag time compared to the ibuprofen emulsion gel and the commercial hydrogel, respectively, suggesting its faster skin permeation. Moreover, the anti-inflammatory efficacy and alleviation in carrageenan-induced inflammation was in the order of dexibuprofen emulsion gel > commercial hydrogel > ibuprofen emulsion gel. The dexibuprofen emulsion gel furnished significantly higher nociceptive thresholds than the ibuprofen emulsion gel and the commercial hydrogel, leading to the most improved anti-nociceptive efficacy. Thus, this dexibuprofen-loaded emulsion gel with good mechanical property, rapid skin permeation and excellent anti-inflammatory and anti-nociceptive efficacy would be a strong candidate for the topical delivery of anti-inflammatory dexibuprofen.
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A review on the medicinal potentials of ginseng and ginsenosides on cardiovascular diseases.
J Ginseng Res
PUBLISHED: 01-06-2014
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Ginseng is widely used for its promising healing and restorative properties as well as for its possible tonic effect in traditional medicine. Nowadays, many studies focus on purified individual ginsenoside, an important constituent in ginseng, and study its specific mechanism of action instead of whole-plant extracts on cardiovascular diseases (CVDs). Of the various ginsenosides, purified ginsenosides such as Rb1, Rg1, Rg3, Rh1, Re, and Rd are the most frequently studied. Although there are many reports on the molecular mechanisms and medical applications of ginsenosides in the treatment of CVDs, many concerns exist in their application. This review discusses current works on the countless pharmacological functions and the potential benefits of ginseng in the area of CVDs.
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The dependence of nitric oxide synthase inhibition caused by cigarette smoking extract on the cellular aging of bovine aortic endothelial cells.
Environ Health Toxicol
PUBLISHED: 01-01-2014
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Cigarette smoking had been recorded as the main cause of impaired endothelium- dependent vasodilation in smokers by reducing nitric oxide (NO), a production of endothelial nitric oxide synthase (eNOS). However, the mechanism of NO impairment via eNOS activity is unclear until now. In this study, cell passage is suggested to be a relevant factor to eNOS expression under cigarette smoking stress.
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Single walled carbon nanotube-based junction biosensor for detection of Escherichia coli.
PLoS ONE
PUBLISHED: 01-01-2014
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Foodborne pathogen detection using biomolecules and nanomaterials may lead to platforms for rapid and simple electronic biosensing. Integration of single walled carbon nanotubes (SWCNTs) and immobilized antibodies into a disposable bio-nano combinatorial junction sensor was fabricated for detection of Escherichia coli K-12. Gold tungsten wires (50 µm diameter) coated with polyethylenimine (PEI) and SWCNTs were aligned to form a crossbar junction, which was functionalized with streptavidin and biotinylated antibodies to allow for enhanced specificity towards targeted microbes. In this study, changes in electrical current (?I) after bioaffinity reactions between bacterial cells (E. coli K-12) and antibodies on the SWCNT surface were monitored to evaluate the sensor's performance. The averaged ?I increased from 33.13 nA to 290.9 nA with the presence of SWCNTs in a 10(8) CFU/mL concentration of E. coli, thus showing an improvement in sensing magnitude. Electrical current measurements demonstrated a linear relationship (R2?=?0.973) between the changes in current and concentrations of bacterial suspension in range of 10(2)-10(5) CFU/mL. Current decreased as cell concentrations increased, due to increased bacterial resistance on the bio-nano modified surface. The detection limit of the developed sensor was 10(2) CFU/mL with a detection time of less than 5 min with nanotubes. Therefore, the fabricated disposable junction biosensor with a functionalized SWCNT platform shows potential for high-performance biosensing and application as a detection device for foodborne pathogens.
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Frontal white matter alterations in short-term medicated panic disorder patients without comorbid conditions: a diffusion tensor imaging study.
PLoS ONE
PUBLISHED: 01-01-2014
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The frontal cortex might play an important role in the fear network, and white matter (WM) integrity could be related to the pathophysiology of panic disorder (PD). A few studies have investigated alterations of WM integrity in PD. The aim of this study was to determine frontal WM integrity differences between patients with PD without comorbid conditions and healthy control (HC) subjects by using diffusion tensor imaging. Thirty-six patients with PD who had used medication within 1 week and 27 age- and sex-matched HC subjects participated in this study. Structural brain magnetic resonance imaging was performed on all participants. Panic Disorder Severity Scale and Beck Anxiety Inventory (BAI) scores were assessed. Tract-based spatial statistics (TBSS) was used for image analysis. TBSS analysis showed decreased fractional anisotropy (FA) in frontal WM and WM around the frontal lobe, including the corpus callosum of both hemispheres, in patients with PD compared to HC subjects. Moreover, voxel-wise correlation analysis revealed that the BAI scores for patients with PD were positively correlated with their FA values for regions showing group differences in the FA of frontal WM of both hemispheres. Altered integrity in frontal WM of patients with PD without comorbid conditions might represent the structural pathophysiology in these patients, and these changes could be related to clinical symptoms of PD.
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Hypofractionated intensity-modulated radiotherapy using simultaneous integrated boost technique with concurrent and adjuvant temozolomide for glioblastoma.
Tumori
PUBLISHED: 12-12-2013
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Aims and background. We assessed the therapeutic efficacy of combined hypofractionated intensity-modulated radiotherapy with temozolomide in patients with primary glioblastoma. Methods and study design. Thirty-nine patients with histologically confirmed glioblastoma were accrued. Using the simultaneous integrated boost technique, a dose of 50 Gy in 5-Gy fractions was applied to the gross tumor volume, together with 40 Gy in 4-Gy fractions and 30 Gy in 3-Gy fractions to the 1- and 2-cm margins from the gross tumor volume, respectively. Patients were also treated with concurrent temozolomide during intensity-modulated radiotherapy, followed by six cycles of adjuvant temozolomide. Results. Median follow-up was 16.8 months (range, 4.3-54.3). Tumor progression was observed in 28 patients (71.8%), and the median time to progression was 6.8 months. Median survival was 16.8 months, and it was affected significantly by the extent of surgery. During adjuvant temozolomide treatment, 3 patients (9.7%) developed grade 3-4 hematologic or hepatic toxicity. Radiation necrosis developed in 7 patients (17.9%) and massive necrosis, requiring emergency surgery, in 1 patient (2.6%). Conclusions. The regimen of hypofractionated intensity-modulated radiotherapy with temozolomide showed a relatively good outcome in patients with glioblastoma. Further studies are required to define the optimal fraction size for glioblastoma using this highly sophisticated radiation technique.
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Correlations of dynamic contrast-enhanced magnetic resonance imaging with morphologic, angiogenic, and molecular prognostic factors in rectal cancer.
Yonsei Med. J.
PUBLISHED: 10-30-2013
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To investigate the correlations between parameters of dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI) and prognostic factors in rectal cancer.
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Syk and Src are major pharmacological targets of a Cerbera manghas methanol extract with kaempferol-based anti-inflammatory activity.
J Ethnopharmacol
PUBLISHED: 10-08-2013
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Cerbera manghas L. (Apocynaceae), a semi-mangrove medicinal plant distributed throughout tropical and subtropical countries, is traditionally known to possess analgesic, anti-inflammatory, anti-convulsant, cardiotonic, and hypotensive activity. In vitro and in vivo anti-inflammatory activities of a methanol extract of the leaves of Cerbera manghas and the underlying molecular mechanisms were investigated to validate the ethnopharmacological use of this plant.
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Association between subjective well-being and depressive symptoms in treatment-resistant schizophrenia before and after treatment with clozapine.
Compr Psychiatry
PUBLISHED: 09-22-2013
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We examined the relationship between subjective well-being and depressive symptoms in patients with treatment-resistant schizophrenia before and after treatment with clozapine to contribute to the growing body of research regarding the determinants of patients perspective of their own well-being in schizophrenia.
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Preoperative N staging of gastric cancer by stomach protocol computed tomography.
J Gastric Cancer
PUBLISHED: 08-07-2013
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Clinical stage of gastric cancer is currently assessed by computed tomography. Accurate clinical staging is important for the tailoring of therapy. This study evaluated the accuracy of clinical N staging using stomach protocol computed tomography.
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IgG4-related sclerosing disease involving the superior vena cava and the atrial septum of the heart.
Yonsei Med. J.
PUBLISHED: 08-07-2013
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A 55-year-old woman presented with frequent episodes of syncope due to sinus pauses. During ambulatory Holter monitoring, atrial fibrillation and first-degree atrioventricular nodal block were observed. Magnetic resonance imaging and CT scans showed a tumor-like mass from the superior vena cava to the right atrial septum. Open chest cardiac biopsy was performed. The tumor was composed of proliferating IgG4-positive plasma cells and lymphocytes with surrounding sclerosis. The patient was diagnosed with IgG4-related sclerosing disease. Because of frequent sinus pauses and syncope, a permanent pacemaker was implanted. The cardiac mass was inoperable, but it did not progress during the one-year follow-up.
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Prognostic implications of anaplastic lymphoma kinase gene aberrations in rhabdomyosarcoma; an immunohistochemical and fluorescence in situ hybridisation study.
J. Clin. Pathol.
PUBLISHED: 08-06-2013
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We investigated the diagnostic and prognostic usefulness of anaplastic lymphoma kinase (ALK) expression in Asian rhabdomyosarcoma (RMS) patients.
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CCAR1 promotes chromatin loading of androgen receptor (AR) transcription complex by stabilizing the association between AR and GATA2.
Nucleic Acids Res.
PUBLISHED: 07-25-2013
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Androgen receptor (AR), a ligand-dependent transcription factor, plays a critical role in prostate cancer onset and progression, and its transcriptional function is mediated largely by distinct nuclear receptor co-regulators. Here, we show that cell cycle and apoptosis regulator 1 (CCAR1) functions as an AR co-activator. CCAR1 interacted with and enhanced the transcriptional activity of AR. Depletion of CCAR1 caused reduction in androgen-dependent expression of a subset of AR target genes. We further showed that CCAR1 is required for recruitment of AR, MED1 and RNA polymerase II to the enhancers of AR target genes and for androgen-induced long-range prostate specific antigen enhancer-promoter interaction. The molecular mechanism underlying CCAR1 function in AR-mediated transcription involves CCAR1-mediated enhanced recruitment of GATA2, a pioneer factor for AR, to AR-binding sites. CCAR1 stabilized the interaction between AR and GATA2 by interacting directly with both proteins, thereby facilitating AR and GATA2 occupancy on the enhancers. Furthermore, CCAR1 depletion inhibited the growth, migration, invasion of prostate cancer cells and reduced the tumorigenicity of prostate cancer cells in vivo. Our results firmly established CCAR1 as an AR co-activator that plays a key role in AR transcription complex assembly and has an important physiological role in androgen signaling and prostate tumorigenesis.
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A practical scoring system to determine whether to proceed with surgical resection in recurrent glioblastoma.
Neuro-oncology
PUBLISHED: 06-25-2013
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To determine the benefit of surgical management in recurrent glioblastoma, we analyzed a series of patients with recurrent glioblastoma who had undergone surgery, and we devised a new scale to predict their survival.
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Mesenchymal differentiation mediated by NF-?B promotes radiation resistance in glioblastoma.
Cancer Cell
PUBLISHED: 06-24-2013
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Despite extensive study, few therapeutic targets have been identified for glioblastoma (GBM). Here we show that patient-derived glioma sphere cultures (GSCs) that resemble either the proneural (PN) or mesenchymal (MES) transcriptomal subtypes differ significantly in their biological characteristics. Moreover, we found that a subset of the PN GSCs undergoes differentiation to a MES state in a TNF-?/NF-?B-dependent manner with an associated enrichment of CD44 subpopulations and radioresistant phenotypes. We present data to suggest that the tumor microenvironment cell types such as macrophages/microglia may play an integral role in this process. We further show that the MES signature, CD44 expression, and NF-?B activation correlate with poor radiation response and shorter survival in patients with GBM.
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Proteomic analysis in Daphnia magna exposed to As(III), As(V) and Cd heavy metals and their binary mixtures for screening potential biomarkers.
Chemosphere
PUBLISHED: 04-02-2013
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In this study, the effects of three widespread heavy metals, As(III), As(V) and Cd, and their binary mixtures on the proteomic profile in D. magna were examined to screen novel protein biomarkers using the two-dimensional gel electrophoresis method (2DE). Ten 20d daphnia were exposed to the LC20 concentrations for each of a total of 8 treatments, including the control, As(III), As(V), Cd, [As(III)+As(V)], [As(III)+Cd], [As(V)+Cd], and [As(III), As(V), Cd], for 24h before protein isolation. Three replicates were performed for each treatment. These protein samples were employed for 2DE experiments with a pH gradient gel strip from pH 3 to pH 10. The protein spots were detected by a silver staining process and their intensities were analyzed by Progenesis software to discover the differentially expressed proteins (DEPs) in response to each heavy metal. A total of 117 differentially expressed proteins (DEPs) were found in daphnia responding to the 8 treatments and mapped onto a 2D proteome map, which provides some information of the molecular weight (MW) and pI value for each protein. All of these DEPs are considered as potential candidates for protein biomarkers in D. magna for detecting heavy metals in the aquatic ecosystem. Comparing the proteomic results among these treatments suggested that exposing D. magna to binary mixtures of heavy metals may result in some complex interactive molecular responses within them, rather than just the simple sum of the proteomic profiles of the individual chemicals, (As(III), As(V), and Cd).
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Identification of prognostic gene signatures of glioblastoma: a study based on TCGA data analysis.
Neuro-oncology
PUBLISHED: 03-15-2013
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The Cancer Genome Atlas (TCGA) project is a large-scale effort with the goal of identifying novel molecular aberrations in glioblastoma (GBM).
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Non-invasively measured aortic wave reflection and pulse pressure amplification are related to the severity of coronary artery disease.
J Cardiol
PUBLISHED: 03-12-2013
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Augmentation index (AIx) and pulse pressure amplification (PPA, here the aortic/brachial pulse pressure ratio) are an age-related emerging risk factor for cardiovascular disease. However, it has not been clearly shown that AIx and PPA predict a high risk of coronary artery disease (CAD).
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Vertebral Distraction during Anterior Cervical Discectomy and Fusion Causes Postoperative Neck Pain.
J Korean Neurosurg Soc
PUBLISHED: 03-10-2013
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Vertebral distraction is routinely performed during anterior cervical discectomy and fusion (ACDF). Overdistraction can injure the facet joints and may cause postoperative neck pain consequently. The purpose of this study was to investigate the clinical relevance of distraction force during ACDF.
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Prognostic factors and therapeutic outcomes in 22 patients with pleomorphic xanthoastrocytoma.
J Korean Neurosurg Soc
PUBLISHED: 03-10-2013
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Pleomorphic xanthoastrocytoma (PXA) is a rare primary low-grade astrocytic tumor classified as WHO II. It is generally benign, but disease progression and malignant transformation have been reported. Prognostic factors for PXA and optimal therapies are not well known.
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Clinical necessity of the immunohistochemical reassessment of para-aortic lymph nodes in resected pancreatic ductal adenocarcinoma.
Oncol Lett
PUBLISHED: 03-07-2013
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Para-aortic lymph node (PALN) metastasis is widely regarded as a systemic disease in cancer. Undetected PALN micrometastases during routine hematoxylin and eosin (HE) staining may be a cause of poor prognosis following a potentially curative pancreatectomy for pancreatic cancer. In the present study, paraffin-embedded PALN tissue blocks from 99 patients who underwent a pancreatectomy were re-evaluated by immunohistochemical staining using cytokeratin (CK)-19. Patients with PALN metastasis were summarized according to the clinicopathological data. A total of 484 PALNs (median, 4.9 nodes per patient; range, 1-19) were evaluated. PALN metastases were revealed in eight patients (8.1%) by routine HE staining of frozen section biopsies and in one patient (1.0%) by HE staining of a permanent section. Only one patient (1.0%) demonstrated micrometastasis by IHC; this patient did not display any adverse pathological characteristics and had a relatively favorable survival period of 41 months. The present study concluded that an additional reassessment for micrometastasis in PALNs using CK-19 immunohistochemistry (IHC) is not a viable method for determining the survival outcome. A careful examination of a frozen section biopsy is sufficient for attempting curative surgery.
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A forensic autopsy case of death in a patient with pseudoxanthoma elasticum--dermatopathologic findings as a clue of the cause of death.
J Forensic Leg Med
PUBLISHED: 03-04-2013
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Pseudoxanthoma elasticum (PXE) is an autosomal recessive disorder, characterized by papular skin lesions and cutaneous laxity caused by fragmentation and mineralization of elastic fibers. Although vascular and retinal aspects of this disease and their associated complications are well characterized, few authors have focused on the increased incidence of epilepsy in patients with PXE. A 28-year-old Korean male was found dead in his work place with bloody-foamy discharge from his mouth and nostrils. He reportedly had a convulsive episode 5 days prior to his death in the work place. The skin showed generalized laxity and many creases with maculopapular pigmentations. A histopathologic examination of the skin revealed Pseudoxanthoma elasticum. Based on the histopathological findings and medical history, death was postulated to be due to an internal cause, possibly related to a seizure attack. Our findings suggest that histopathologic examinations of any lesions found during the forensic autopsy should be encouraged.
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Development of a porcine skin injury model and characterization of the dose-dependent response to high-dose radiation.
J. Radiat. Res.
PUBLISHED: 02-28-2013
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A porcine skin model was developed to characterize the dose-dependent response to high-dose radiation. The dorsal skin of a mini pig was divided into four paraspinal sections, with 11 small irradiation fields (2 cm × 2 cm) in each section, and a single fraction of 15, 30, 50 or 75 Gy was delivered to each section using a 6 MeV electron beam. A spectrophotometer measured gross skin changes, and a biopsy for each radiation dose was performed in the 1st, 2nd, 4th, 6th and 9th weeks for histology, immunostaining with anti-CD31, and western blotting with IL-6 and TGF-?1 to determine the degree of skin damage. After a 4-week latency period, erythema and dry desquamation, moist desquamation, and ulceration appeared at 4, 6 and 9 weeks, respectively. Gross skin toxicity was more pronounced, occurred early and continued to progress with irradiation >50 Gy, whereas complete healing was observed 12 weeks after 15 Gy. Spectrophotometry showed erythema indices rapidly increased during the first 4 weeks after irradiation. The number of eosinophils began rising sharply at 4 weeks and normalized after reaching peaks at 7-8 weeks. Microvessel density showed a biphasic pattern with a transient peak at 1 week, a nadir at 4-6 weeks, and maximum recovery at 9 weeks. Increase in the levels of IL-6 and TGF-?1 was detected soon after irradiation. Most of these parameters indicated complete healing of the skin 12 weeks after 15 Gy. Our porcine skin model provides an effective platform for studying high-dose radiation-induced skin injury, in particular histologic and molecular changes, during the early latency period.
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Evidence for the Primo Vascular System above the Epicardia of Rat Hearts.
Evid Based Complement Alternat Med
PUBLISHED: 02-23-2013
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We for the first time reported evidence for the existence of a novel network, a PVS, abovethe epicardium of the rat heart. (1) We were consecutively able to visualize the PVs and the PNs above the epicardial spaces of five rats hearts by using Cr-Hx spraying or injection. (2) Hematoxylin and eosin (H&E) and toluidine blue staining of the PVs and the PNs showed that they consisted of a basophilic matrix; specifically the PNs contained several mast cells, some of which were degranulating into pericardial space. Also, 4, 6-diamidino-2 phenylindole (DAPI) images of the PVs and the PNs showed that they contained various kinds of cells. (3) Transmission electron microscopic (TEM) longitudinal image of the PVs showed that the sinuses contained many granules with high-electron-density cores in parallel with putative endothelial cells. (4) TEM images of the PNs demonstrated that they consisted of lumen-containing cells surrounded by fibers and that they had mast cells that were degranulating toward the epicardium of the rat heart. The above data suggest that mast-cells-containing novel network exists above the epicardium of the rat heart.
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Validation of the Korean version of the European Organization for Research and Treatment of Cancer brain cancer module (EORTC QLQ-BN20) in patients with brain tumors.
Health Qual Life Outcomes
PUBLISHED: 02-14-2013
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The European Organization for Research and Treatment of Cancer Quality of Life Brain Cancer Module has been translated into Korean, but to date, its reliability and validity have been evaluated in a pilot study alone. The European Organization for Research and Treatment of Cancer Quality of Life Core Questionnaire is, overall, a valid instrument to assess the health-related quality of life in Korean cancer patients, although its reliability and validity have not yet been evaluated in patients with brain tumors. This study aimed at evaluating the psychometric properties of these instruments in patients with brain tumors.
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IDH1 mutation analysis in low cellularity specimen: a limitation of diagnostic accuracy and a proposal for the diagnostic procedure.
Pathol. Res. Pract.
PUBLISHED: 02-02-2013
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Recently, new techniques for detecting IDH1 mutations have been developed. Most studies assessed the mutation status in glioma tissue without consideration of the size of the samples. We assessed the mutation status of IDH1 in simulated small biopsied tissue from 5 low grade gliomas, prepared by grid cutting procedure with direct sequencing, IDH1 immunohistochemistry (IHC), multiplex PCR with single base extension (SBE) assay and PNA-clamping method, and then analyzed the agreement between the methods. Kappa values were 0.53 (direct sequencing), 0.59 (multiplex PCR with SBE assay), and 0.69 (PNA-clamping method). Discrepant results between the methods were observed in lower cellularity samples. Twelve out of 25 cases were classified as wild type by direct sequencing, even with IDH1 IHC-positive cells, whereas 6, 8, and 11 of IHC-negative cases were classified as mutant cases by other 3 methods. In conclusion, newly developed sensitive methods, such as the PNA-clamping method and multiplex PCR with SBE assay, are practically useful in addition to the conventional IDH1 IHC in small biopsied samples.
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?-Synuclein pathology is related to postoperative delirium in patients undergoing gastrectomy.
Neurology
PUBLISHED: 01-30-2013
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The clinical characteristics of postoperative delirium are similar to core features of ?-synuclein-related cognitive disorders, such as dementia with Lewy bodies or Parkinson disease dementia. We therefore investigated the ?-synuclein pathology in patients who experienced postoperative delirium after gastrectomy for stomach cancer.
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Primary cardiac angiofibroma.
Korean Circ J
PUBLISHED: 01-23-2013
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Cardiac Angiofibroma is an uncommon intracardiac tumor. Thus far, only 4 cases of the rare intracardiac tumor have been reported. The present case-report describes an intracardiac angiofibroma in a 57-year-old healthy female. The patient was incidentally diagnosed with a left ventricle mass during echocardiography. We performed cardiac imaging, surgical excision and histological evaluation of the mass. The angiofibroma demonstrated features different from the relatively common cardiac tumors such as fibroma, myxoma and angiosarcoma. The cardiac MRI showed slightly high signal intensity on both T1 and T2, with the central core of lower signal intensity. The resected tumor was a whitish and rubbery mass. Histologically, the tumor showed the benign vascular proliferations associated with the surrounding collagen deposition.
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Early response to high-dose methotrexate, vincristine, and procarbazine chemotherapy-adapted strategy for primary CNS lymphoma: no consolidation therapy for patients achieving early complete response.
Ann. Hematol.
PUBLISHED: 01-18-2013
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Optimal treatment strategies for primary central nervous system lymphoma (PCNSL) have not been established. In this study, we investigated the treatment outcomes and prognostic factors of high-dose methotrexate, vincristine, and procarbazine (MVP) chemotherapy followed by an interim response-adapted intensification strategy in immunocompetent patients with PCNSL. We evaluated the evidence of infection with Epstein-Barr virus (EBV) in both brain tumor tissue and whole blood. Forty patients were retrospectively reviewed. Ten (25 %) patients who achieved complete response (CR) in the interim analysis did not receive any additional consolidation treatment after completion of planned high-dose MVP chemotherapy. Additional radiotherapy (n?=?9) or autologous stem cell transplantation (ASCT) (n?=?7) was performed in patients who did not achieve CR in the interim analysis. The median age was 55 years. The overall CR rate was 62.5 % (n?=?25), and the objective response rate was 75.0 %. Two-year overall survival (OS) was 59.8 %, and 2-year progression-free survival was 47.1 %. Grade 3 or 4 neutropenia and thrombocytopenia occurred in 47.5 and 32.5 % of patients, respectively. Treatment-related mortality was 15.0 % (n?=?6), and four patients developed delayed neurotoxicity. There was no evidence of EBV-encoded RNA expression in brain tumor tissue. Ten (29.4 %) of 34 patients showed detectable EBV-DNA in whole blood. Poor performance status and EBV-DNA positivity in whole blood were significantly associated with inferior OS (p?=?0.032, p?=?0.023, respectively). We suggest that high-dose MVP chemotherapy followed by an early response-adapted intensification strategy may be effective and minimize the number of patients who receive radiotherapy or ASCT in the early course of treatment.
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Novel threadlike structures on the surfaces of mammalian abdominal organs are loose bundles of fibrous stroma with microchannels embedded with fibroblasts and inflammatory cells.
Connect. Tissue Res.
PUBLISHED: 01-18-2013
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Novel threadlike structures (NTSs) on the surfaces of mammalian abdominal organs have recently attracted interests regarding their ability to transport fluid, enable cell migration, and possibly facilitate cancer metastasis. Nevertheless, histological studies of NTSs have been sporadic and often have inconsistent interpretations of the NTS internal structure. In this article, we provide a synthetic and consistent view of the NTS internal structure: the NTS is a loose bundle of fibrous stroma that forms interstitial channels and microsinusoids infiltrated with inflammatory cells. The fibroblasts are embedded in the stroma and mostly aligned along the major axis of the NTS. The sinusoids, which are in inconsecutive cross sections, have boundaries more or less delineated by extracellular fibers, partly surrounded by endothelial-like cells, or both. We compare these morphological features to other well-known connective tissues (i.e., trabecular meshwork and lymphatic capillary) and discuss the biomechanical and biological functions of NTSs based on their structural characteristics.
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Glioma is formed by active Akt1 alone and promoted by active Rac1 in transgenic zebrafish.
Neuro-oncology
PUBLISHED: 01-16-2013
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Ongoing characterization of glioma has revealed that Akt signaling plays a crucial role in gliomagenesis. In mouse models, however, Akt alone was not sufficient to induce glioma.
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What is Visualize?

JoVE Visualize is a tool created to match the last 5 years of PubMed publications to methods in JoVE's video library.

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We use abstracts found on PubMed and match them to JoVE videos to create a list of 10 to 30 related methods videos.

Video X seems to be unrelated to Abstract Y...

In developing our video relationships, we compare around 5 million PubMed articles to our library of over 4,500 methods videos. In some cases the language used in the PubMed abstracts makes matching that content to a JoVE video difficult. In other cases, there happens not to be any content in our video library that is relevant to the topic of a given abstract. In these cases, our algorithms are trying their best to display videos with relevant content, which can sometimes result in matched videos with only a slight relation.