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Find video protocols related to scientific articles indexed in Pubmed.
Wilms tumour suppressor, WT1, suppresses epigenetic silencing of the beta-catenin gene.
J. Biol. Chem.
PUBLISHED: 10-22-2014
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The mammalian kidney is derived from progenitor cells in intermediate mesoderm. During embryogenesis, progenitor cells expressing the Wilms tumour suppressor gene, WT1, are induced to differentiate in response to WNT signals from the ureteric bud. In hereditary Wilms tumours, clonal loss of WT1 precludes the beta-catenin pathway response and leads to precancerous nephrogenic rests. We hypothesized that WT1 normally primes progenitor cells for differentiation by suppressing the enhancer of zeste2 gene (EZH2), involved in epigenetic silencing of differentiation genes. In human mesenchymal stem cells (amMSC), we show that exogenous WT1B represses EZH2 transcription. This leads to a dramatic decrease in the repressive lysine27 tri-methylation mark on histone H3 that silences beta-catenin gene expression. As a result, amMSC acquire responsiveness to WNT9b and increase expression of genes that mark the onset of nephron differentiation. Our observations suggest that bi-allelic loss of WT1 sustains the inhibitory histone methylation state that characterizes Wilms tumours.
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Anticancer effects on human pancreatic cancer cells of triterpenoids, polysaccharides and 1,3-?-d-glucan derived from the fruiting body of Antrodia camphorata.
Food Funct
PUBLISHED: 10-15-2014
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Antrodia camphorata is a fungus native to Taiwan, and it is considered a precious medicinal agent. We analyzed triterpenoids, polysaccharides and 1,3-?-d-glucan, three major effective components in A. camphorata extracts (ACE). ACE exhibited a selective cytotoxic effect on BxPC-3 human pancreatic cancer cells. ACE markedly inhibited the migration ability of BxPC-3 cells. Treatment of BxPC-3 cells with ACE resulted in the increase of cells in the sub-G1 phase and G2/M phase arrest. Apoptosis was confirmed by validating phosphatidylserine externalization, the observation of characteristic chromatin condensation, and nuclear DNA fragmentation. ACE induced apoptosis in BxPC-3 cells through a mitochondria-dependent pathway by triggering an appropriate balance of bax/bcl-2, cytochrome c release, activation of caspase-9 and -3, and poly(ADP-ribose) polymerase cleavage. ACE shows great therapeutic potential due to its cytotoxic effects against BxPC-3 cells which include inhibiting cell migration and inducing mitochondria-mediated apoptosis.
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Prognostic Scoring Models for Patients Undergoing Sorafenib Treatment for Advanced Stage Hepatocellular Carcinoma in Real-Life Practice.
Am. J. Clin. Oncol.
PUBLISHED: 10-01-2014
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The purpose of this study was to build prognostic models capable of estimating the outcomes of individual sorafenib-treated advanced stage hepatocellular carcinoma (HCC) patients based on specific patient and tumor factors.
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Ascidiaceihabitans donghaensis gen. nov., sp. nov., isolated from a golden sea squirt Halocynthia aurantium.
Int. J. Syst. Evol. Microbiol.
PUBLISHED: 09-11-2014
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A Gram-stain-negative, aerobic, non-motile and coccoid, ovoid or rod-shaped bacterial strain, designated RSS1-M3T, was isolated from a golden sea squirt (Halocynthia aurantium) collected from the East Sea, South Korea. Strain RSS1-M3T grew optimally at 30 °C, at pH 7.0-8.0 and in presence of 2.0 % (w/v) NaCl. Strain RSS1-M3T exhibited the highest 16S rRNA gene sequence similarity value (96.55 %) to the type strain of Pelagicola litoralis. Neighbour-joining and maximum-likelihood phylogenetic trees based on 16S rRNA gene sequences revealed that strain RSS1-M3T clustered with the type strains of Planktotalea frisia, Pacificibacter maritimus, Roseovarius marinus and 'Halocynthiibacter namhaensis', showing sequence similarity values of 94.88-96.32 %. Strain RSS1-M3T contained Q-10 as the predominant ubiquinone and C18:1 ?7c and C16:0 as the major fatty acids. The polar lipid profile of strain RSS1-M3T containing phosphatidylcholine, phosphatidylglycerol, phosphatidylethanolamine, diphosphatidylglycerol, one unidentified aminolipid and one unidentified lipid as major components was distinguished from those of the phylogenetically related genera. The DNA G+C content of strain RSS1-M3T was 55.8 mol%. On the basis of the phylogenetic, chemotaxonomic and phenotypic properties, strain RSS1-M3T is considered to represent a new genus and species within the class Alphaproteobacteria, for which the name Ascidiaceihabitans donghaensis gen. nov., sp. nov. is proposed. The type strain is RSS1-M3T (= KCTC 42118T = CECT 8599T).
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Factors affecting institutionalized older peoples' self-perceived dry mouth.
Qual Life Res
PUBLISHED: 08-24-2014
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The purpose of this study was to determine the factors affecting institutionalized older peoples' self-perceived dry mouth.
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Urinary neutrophil gelatinase-associated lipocalin and clinical outcomes in chronic kidney disease patients.
Clin. Chem. Lab. Med.
PUBLISHED: 08-07-2014
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Abstract Background: Tubulointerstitial damage is a final common pathway of most renal diseases. Whether urinary neutrophil gelatinase-associated lipocalin (uNGAL), a biomarker for renal tubular damage, is of prognostic value for clinical outcomes in chronic kidney disease (CKD) patients has not been well investigated. Methods: The uNGAL and proteinuria levels were measured among a cohort of 473 advanced CKD patients of various etiologies recruited during 2002-2009. Results: The estimated glomerular filtration rate (eGFR) was 32.3±22.0 mL/min/1.73 m2 with a urine protein-to-creatinine ratio (UPCR) 680 (255-1248) mg/g and 132 (27.9%) participants had diabetes. The baseline uNGAL level was significantly associated with male gender, eGFR, UPCR, and hemoglobin. The hazard ratio (HR) of the highest uNGAL tertile for end-stage renal disease (ESRD) was 3.44 (95% CI 1.47-8.06, p=0.004). With the adjustment of urine creatinine and urine protein, HR of the highest urine NGAL-to-creatinine ratio (UNCR) tertile and the highest urine NGAL-to-protein ratio (UNPR) tertile was 3.06 (95% CI 1.19-7.90, p=0.02) and 2.10 (95% CI 1.13-3.89, p=0.02), respectively. UNPR increased the prediction of survival model for ESRD. HR of the highest UNCR tertile and UNPR tertile for cardiovascular (CV) events was 2.21 (95% CI 0.81-5.98, p=0.08) and 2.79 (95% CI 1.25-6.26, p=0.01), respectively. None of these were associated with all-cause mortality. Conclusions: Elevated uNGAL in CKD patients is associated with risks for ESRD and probably CV events. UNPR could improve the prediction for ESRD.
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Prevalence and prediction of coronary artery disease in patients with liver cirrhosis: a registry-based matched case-control study.
Circulation
PUBLISHED: 08-05-2014
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There is conflict regarding the prevalence of coronary artery disease (CAD) in patients with liver cirrhosis. This study aimed to investigate the prevalence of silent CAD in comparison with the general population, and to identify the relevant risk factors in patients with liver cirrhosis.
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Human brain asymmetry in microstructural connectivity demonstrated by diffusional kurtosis imaging.
Brain Res.
PUBLISHED: 06-30-2014
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Structural asymmetry of whole brain white matter (WM) pathways, i.e., the connectome, has been demonstrated using fiber tractography based on diffusion tensor imaging (DTI). However, DTI-based tractography fails to resolve axonal fiber bundles that intersect within an imaging voxel, and therefore may not fully characterize the extent of asymmetry. The goal of this study was to assess structural asymmetry with tractography based on diffusional kurtosis imaging (DKI), which improves upon DTI-based tractography by delineating intravoxel crossing fibers. DKI images were obtained from 42 healthy subjects. By using automatic segmentation, gray matter (GM) was parcellated into anatomically defined regions of interest (ROIs). WM pathways were reconstructed with both DKI- and DTI-based tractography. The connectivity between the ROIs was quantified with the streamlines connecting the ROIs. The asymmetry index (AI) was utilized to quantify hemispheric differences in the connectivity of cortical ROIs and of links interconnecting cortical ROIs. Our results demonstrated that leftward asymmetrical ROIs and links were observed in frontal, parietal, temporal lobes, and insula. Rightward asymmetrical ROI and links were observed in superior frontal lobe, cingulate cortex, fusiform, putamen, and medial temporal lobe. Interestingly, these observed structural asymmetries were incompletely identified with DTI-based tractography. These results suggest that DKI-based tractography can improve the identification of asymmetrical connectivity patterns, thereby serving as an additional tool in the evaluation of the structural bases of functional lateralization.
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Prognostic Nomograms for Prediction of Recurrence and Survival After Curative Liver Resection for Hepatocellular Carcinoma.
Ann. Surg.
PUBLISHED: 06-21-2014
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To develop clinical predictive nomograms generating per-patient numerical probabilities of postoperative recurrence-free and overall survival at specific times.
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Cognitive and epilepsy outcomes after epilepsy surgery caused by focal cortical dysplasia in children: early intervention maybe better.
Childs Nerv Syst
PUBLISHED: 06-04-2014
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Focal cortical dysplasia (FCD) is a specific malformation of cortical development harboring intrinsic epileptogenicity, and most of the patients develop drug-resistant epilepsy in early childhood. The detrimental effects of early and frequent seizures on cognitive function in children are significant clinical issues. In this study, we evaluate the effects of early surgical intervention of FCD on epilepsy outcome and cognitive development.
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No association between the IL28B SNP and response to peginterferon plus ribavirin combination treatment in Korean chronic hepatitis C patients.
Clin Mol Hepatol
PUBLISHED: 05-29-2014
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There are few available data regarding the association between the single nucleotide polymorphisms (SNPs) of the gene encoding interleukin 28B (IL28B) and a sustained virologic response (SVR) to peginterferon (PEG-IFN) plus ribavirin (RBV) therapy in Korean chronic hepatitis C patients.
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Genomic portrait of resectable hepatocellular carcinomas: Implications of RB1 and FGF19 aberrations for patient stratification.
Hepatology
PUBLISHED: 04-29-2014
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Hepatic resection is the most curative treatment option for early-stage hepatocellular carcinoma, but is associated with a high recurrence rate, which exceeds 50% at 5 years after surgery. Understanding the genetic basis of hepatocellular carcinoma at surgically curable stages may enable the identification of new molecular biomarkers that accurately identify patients in need of additional early therapeutic interventions. Whole exome sequencing and copy number analysis was performed on 231 hepatocellular carcinomas (72% with hepatitis B viral infection) that were classified as early-stage hepatocellular carcinomas, candidates for surgical resection. Recurrent mutations were validated by Sanger sequencing. Unsupervised genomic analyses identified an association between specific genetic aberrations and postoperative clinical outcomes. Recurrent somatic mutations were identified in nine genes, including TP53, CTNNB1, AXIN1, RPS6KA3, and RB1. Recurrent homozygous deletions in FAM123A, RB1, and CDKN2A, and high-copy amplifications in MYC, RSPO2, CCND1, and FGF19 were detected. Pathway analyses of these genes revealed aberrations in the p53, Wnt, PIK3/Ras, cell cycle, and chromatin remodeling pathways. RB1 mutations were significantly associated with cancer-specific and recurrence-free survival after resection (multivariate P?=?0.038 and P?=?0.012, respectively). FGF19 amplifications, known to activate Wnt signaling, were mutually exclusive with CTNNB1 and AXIN1 mutations, and significantly associated with cirrhosis (P?=?0.017). Conclusion: RB1 mutations can be used as a prognostic molecular biomarker for resectable hepatocellular carcinoma. Further study is required to investigate the potential role of FGF19 amplification in driving hepatocarcinogenesis in patients with liver cirrhosis and to investigate the potential of anti-FGF19 treatment in these patients. (Hepatology 2014).
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Apolipoprotein C-III is an amyloid-?-binding protein and an early marker for Alzheimer's disease.
J. Alzheimers Dis.
PUBLISHED: 04-02-2014
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It has been demonstrated that peripheral injection of anti-amyloid-? (A?) antibodies to patients with Alzheimer's disease (AD) and AD transgenic mice facilitate A? clearance. We hypothesized that peripheral circulating A?-binding proteins also possess the ability to enhance A? clearance and the levels of circulating A?-binding proteins could serve as early AD biomarkers. Circulating A?-binding proteins were isolated from plasma and identified by LC-MS/MS. Their levels were compared among non-demented individuals without AD family history (ND), with AD family history (ND-FH), and patients with mild AD. The results showed that most of the identified A?-binding proteins were apolipoproteins, i.e., apoA-I, apoB-100, apoC-III, and apoE. A? bound preferentially to apoA-I-enriched HDL, followed by apoC-III- and apoE-enriched VLDL, and bound less favorably to apoB-100-enriched LDL. Levels of apoA-I were reduced in AD patients and could be used to discriminate AD from ND groups (AUC: 0.93); whereas levels of apoC-III were reduced in both ND-FH and AD groups and could be used to differentiate ND-FH from ND individuals (AUC: 0.81). Both the levels of apoA-1 and apoC-III positively correlated with CASI and MMSE scores. In conclusion, these results suggest that plasma apoA-I could be a sensitive AD biomarker and individuals with low plasma levels of apoC-III are at risk for AD.
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Low-copy number protein detection by electrode nanogap-enabled dielectrophoretic trapping for surface-enhanced Raman spectroscopy and electronic measurements.
Nano Lett.
PUBLISHED: 03-10-2014
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We report a versatile analysis platform, based on a set of nanogap electrodes, for the manipulation and sensing of biomolecules, as demonstrated here for low-copy number protein detection. An array of Ti nanogap electrode with sub-10 nm gap size function as templates for alternating current dielectrophoresis-based molecular trapping, hot spots for surface-enhanced Raman spectroscopy as well as electronic measurements, and fluorescence imaging. During molecular trapping, recorded Raman spectra, conductance measurements across the nanogaps, and fluorescence imaging show unambiguously the presence and characteristics of the trapped proteins. Our platform opens up a simple way for multifunctional low-concentration heterogeneous sample analysis without the need for target preconcentration.
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Clinical implications of preoperative and intraoperative liver biopsies for evaluating donor steatosis in living related liver transplantation.
Liver Transpl.
PUBLISHED: 02-25-2014
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The role of liver biopsy in selecting optimal donors is an area of continuing controversy in living donor liver transplantation (LDLT). Our aim was to assess the potential implications of preoperative and intraoperative biopsies for evaluating donor liver fat content. Three thousand eight hundred fifty-nine consecutive subjects underwent predonation needle biopsy of the right lobe, and 1766 of these subjects actually donated their livers for LDLT and underwent intraoperative wedge biopsies of paired right and left lobes. The preoperative workup protocol also included abdominal ultrasonography (USG) and computed tomography (CT). Intersample agreement on steatosis grades (<5%, 5% to <15%, 15% to <30%, and ?30%) was calculated, and clinicometabolic factors related to sampling variability were evaluated. For detecting ?30% steatosis in the 3859 potential donors, USG and CT had sensitivities of 84.9% and 57.3%, specificities of 76.3% and 92.7%, positive predictive values of 29.6% and 48.0%, and negative predictive values of 97.7% and 94.8%, respectively. Analyses of the 1766 actual donors showed that with respect to the total steatosis grades of intraoperative right and left biopsies versus preoperative biopsy, 36.7% and 36.0% of the pairs, respectively, differed from the weighted ? values of 0.44 and 0.40. Similar agreement levels existed for macrovesicular and microvesicular steatosis subtypes. The per-subject agreement rate for the total steatosis grade between intraoperative right and left biopsies was 83.6%. According to a multivariate analysis, independent factors affecting the variability of the total steatosis results from preoperative and intraoperative biopsies (major features) were higher systolic blood pressure, body mass index, and alanine aminotransferase values and lower high-density lipoprotein cholesterol values. In conclusion, imaging may be insufficiently sensitive for evaluating donor hepatic steatosis. Preoperative and selective intraoperative liver biopsies are mandatory for assessing donor steatosis in LDLT unless preoperative imaging demonstrates no fat.
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Comparison of quasispecies diversity of HCV between chronic hepatitis c and hepatocellular carcinoma by Ultradeep pyrosequencing.
Biomed Res Int
PUBLISHED: 02-21-2014
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Hepatitis C virus (HCV) exists as population of closely related genetic variants known as quasispecies. HCV quasispecies diversity is strongly influenced by host immune pressure on virus. Quasispecies diversity is expected to decline as host immune response to HCV decreases over natural course of progressing from chronic hepatitis C (CHC) to hepatocellular carcinoma (HCC).
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Reappraisal of serum alpha-foetoprotein as a surveillance test for hepatocellular carcinoma during entecavir treatment.
Liver Int.
PUBLISHED: 02-21-2014
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The aim of this study was to re-evaluate the diagnostic performance of alpha-foetoprotein (AFP) as a surveillance test for hepatocellular carcinoma (HCC) in patients with hepatitis B virus-related chronic liver disease who were treated with entecavir (ETV).
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Mortality, liver transplantation, and hepatocellular carcinoma among patients with chronic hepatitis B treated with entecavir vs lamivudine.
Gastroenterology
PUBLISHED: 02-04-2014
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Little is known about whether the antiviral agent entecavir is more effective than a less potent drug, lamivudine, in reducing the risk of death and hepatocellular carcinoma (HCC) in patients with chronic hepatitis B.
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Role of 15-hydroxyprostaglandin dehydrogenase down-regulation on the prognosis of hepatocellular carcinoma.
Clin Mol Hepatol
PUBLISHED: 01-21-2014
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The role of prostaglandin E2 (PGE2) in the modulation of cell growth is well established in colorectal cancer. The aim of this study was to elucidate the significance of 15-hydroxyprostaglandin dehydrogenase (15-PGDH) down-regulation on the prognosis of hepatocellular carcinoma (HCC) patients.
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Prognostic performance of preoperative gadoxetic acid-enhanced MRI in resectable hepatocellular carcinoma.
J Magn Reson Imaging
PUBLISHED: 01-17-2014
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To assess the impact of preoperative evaluation by gadoxetic acid-enhanced magnetic resonance imaging (MRI) on early recurrence outcomes after hepatocellular carcinoma (HCC) resection.
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Most frequent location of the sentinel lymph nodes.
Asian J Surg
PUBLISHED: 01-14-2014
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Inappropriate skin incisions can make sentinel lymph node dissection difficult. A knowledge of the most common locations of the hotspot in the axilla helps in planning the incision. This information also helps to locate the lymph node preoperatively by ultrasound. The aim of this prospective study was to determine the most common location of the sentinel lymph node in the axilla.
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Clinical significance of the best response during repeated transarterial chemoembolization in the treatment of hepatocellular carcinoma.
J. Hepatol.
PUBLISHED: 01-14-2014
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We assessed the clinical implications of the best response compared with the initial response during repeated transarterial chemoembolization (TACE) for hepatocellular carcinoma (HCC).
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Decision-making factors affecting different family members regarding the placement of relatives in long-term care facilities.
BMC Health Serv Res
PUBLISHED: 01-10-2014
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The aim of this research was to investigate factors affecting different family members' decisions regarding the placement of relatives in long-term car (LTC) facilities in Taiwan. The objective was to investigate the correlations between family members' personal traits, the living conditions of residents in the LTC facilities, and family members' experiences with LTC facilities.
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A public health framework for developing local preventive services guidelines.
Public Health Rep
PUBLISHED: 01-04-2014
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In this article, we describe the San Francisco Department of Public Health's (SFDPH's) framework for developing evidence-based screening and vaccination recommendations. We first reviewed our local data using surveillance and syndemic data. We then compiled and compared existing federal, state, and local recommendations. Then we identified differences as compared with our local evidence; where more evidence was required to make a recommendation, we culled from additional data sources and conducted additional analyses. Lastly, we developed our guidelines by confirming existing recommendations or making new recommendations based on this process. In the end, we successfully developed evidence-based clinical screening and prevention guidelines that have been adopted by the SFDPH Health Commission. We encourage the use of this framework in other public health settings at the local level.
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Association of angiopoietin-2 with renal outcome in chronic kidney disease.
PLoS ONE
PUBLISHED: 01-01-2014
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The pathophysiological mechanisms of renal function progression in chronic kidney disease (CKD) have still not been completely explored. In addition to well-known traditional risk factors, non-traditional risk factors, such as endothelial dysfunction, have gradually attracted physicians' attention. Angiopoietin-2 (Ang-2) impairs endothelial function through preventing angiopoietin-1 from binding to Tie2 receptor. Whether Ang-2 is associated with renal function progression in CKD is unknown.
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Tandem array of nanoelectronic readers embedded coplanar to a fluidic nanochannel for correlated single biopolymer analysis.
Biomicrofluidics
PUBLISHED: 01-01-2014
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We have developed a two-step electron-beam lithography process to fabricate a tandem array of three pairs of tip-like gold nanoelectronic detectors with electrode gap size as small as 9?nm, embedded in a coplanar fashion to 60?nm deep, 100?nm wide, and up to 150??m long nanochannels coupled to a world-micro-nanofluidic interface for easy sample introduction. Experimental tests with a sealed device using DNA-protein complexes demonstrate the coplanarity of the nanoelectrodes to the nanochannel surface. Further, this device could improve transverse current detection by correlated time-of-flight measurements of translocating samples, and serve as an autocalibrated velocimeter and nanoscale tandem Coulter counters for single molecule analysis of heterogeneous samples.
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Hypoglycemia induces tau hyperphosphorylation.
Curr Alzheimer Res
PUBLISHED: 11-12-2013
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Cerebral hypoglycemia/hypometabolism is associated with Alzheimers disease (AD) and is routinely used to assist clinical diagnosis of AD by brain imaging. However, whether cerebral hypoglycemia/hypometabolism contributes to the development of AD or is a response of reduced neuronal activity remains unclear. To investigate the causal relationship, we cultured the differentiated N2a neuroblastoma cells in glucose/pyruvate-deficient media (GDM). Shortly after the N2a cells cultured in the GDM, the mitochondria membrane potential was reduced and the AMP-activated-proteinkinase (AMPK), an energy sensor, was activated. Treatment of GDM not only increased the levels of tau phosphorylation at Ser(262) and Ser(396), but also increased the levels of active forms of GSK3? and GSK3?, two known kinases for tau phosphorylation, of the N2a cells. The levels of activated Akt, a mediator downstream to AMPK and upstream to GSK3?/?, were reduced by the GDM treatment. The effect of hypoglycemia was further examined in vivo by intracerebroventricular (icv) injection of streptozotocin (STZ) to the Wistar rats. STZ selectively injuries glucose transporter type 2-bearing cells which are primarily astrocytes in the rat brain, hence, interrupts glucose transportation from blood vessel to neuron. STZicv injection induced energy crisis in the brain regions surrounding the ventricles, as indicated by higher pAMPK levels in the hippocampus, but not cortex far away from the ventricles. STZ-icv treatment increased the levels of phosphorylated tau and activated GSK3?, but decreased the levels of activated Akt in the hippocampus. The hippocampus-dependent spatial learning and memory was impaired by the STZ-icv treatment. In conclusion, our works suggest that hypoglycemia enhances the AMPK-Akt-GSK3 pathway and leads to tau hyperphosphorylation.
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Lipocalin 2 induces the epithelial-mesenchymal transition in stressed endometrial epithelial cells: possible correlation with endometriosis development in a mouse model.
Reproduction
PUBLISHED: 11-07-2013
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Lipocalin 2 (LCN2) is an induced stressor that promotes the epithelial-mesenchymal transition (EMT). We previously demonstrated that the development of endometriosis in mice correlates with the secretion of LCN2 in the uterus. Here, we sought to clarify the relationship between LCN2 and EMT in endometrial epithelial cells and to determine whether LCN2 plays a role in endometriosis. Antibodies that functionally inhibit LCN2 slowed the growth of ectopic endometrial tissue in a mouse model of endometriosis, suggesting that LCN2 promotes the formation of endometriotic lesions. Using nutrient deprivation as a stressor, LCN2 expression was induced in cultured primary endometrial epithelial cells. As LCN2 levels increased, the cells transitioned from a round to a spindle-like morphology and dispersed. Immunochemical analyses revealed decreased levels of cytokeratin and increased levels of fibronectin in these endometrial cells, adhesive changes that correlate with induction of cell migration and invasion. Lcn2 knockdown also indicated that LCN2 promotes EMT and migration of endometrial epithelial cells. Our results suggest that stressful cellular microenvironments cause uterine tissues to secrete LCN2 and that this results in EMT of endometrial epithelial cells, which may correlate with the development of ectopic endometriosis. These findings shed light on the role of LCN2 in the pathology of endometrial disorders.
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Macromolecular ion accelerator mass spectrometer.
Analyst
PUBLISHED: 10-31-2013
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We present a newly developed macromolecular ion accelerator mass spectrometer that combines a dual-ion-trap device and a macromolecular ion accelerator (MIA) to achieve the capability of analyzing samples with a mixture of large biomolecules. MIA greatly increases detection efficiency. The dual ion trap includes a quadrupole ion trap (QIT) and a linear ion trap (LIT) in tandem. The dual ion trap is mounted ahead of the MIA. The QIT is used to store multiple species, and the LIT is employed to capture the ions that are sequentially ejected out of the QIT. Subsequent to their capture, the ions inside of the LIT are extracted and transferred to the MIA. The synchronization between the QIT and MIA is bridged by the LIT. A sample containing a mixture of several large biomolecules was employed to examine the performance of this new type of mass spectrometer. The result reveals that larger biomolecules show a comparable signal to smaller biomolecules, even though the mixture contains equal quantities of each type of protein. The overall assembly produces a nearly constant detection efficiency over a broad mass range. Thus, this device provides an alternative platform to analyze complex large-protein mixtures.
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HBsAg seroclearance after nucleoside analogue therapy in patients with chronic hepatitis B: clinical outcomes and durability.
Gut
PUBLISHED: 10-25-2013
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Little is known about the long-term clinical outcome and durability of HBsAg seroclearance following nucleos(t)ide analogue (NUC) therapy in patients with chronic hepatitis B (CHB).
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Radioembolization With Yttrium-90 Resin Microspheres in Hepatocellular Carcinoma: A Multicenter Prospective Study.
Am. J. Clin. Oncol.
PUBLISHED: 09-26-2013
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The aim of this prospective study was to reveal the efficacy and safety of Yttrium-90 (Y) radioembolization in Korean patients with hepatocellular carcinoma (HCC).
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Hepatocyte nuclear factor 1? is a novel prognostic marker independent of the Milan criteria in transplantable hepatocellular carcinoma: a retrospective analysis based on tissue microarrays.
Liver Transpl.
PUBLISHED: 09-04-2013
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We retrospectively investigated the prognostic value of hepatocyte nuclear factor 1 (HNF1) proteins in 159 liver transplant patients with hepatocellular carcinoma (HCC), including 36 (22.6%) exceeding the Milan criteria. The expression of alpha-fetoprotein (AFP), HNF1?, and HNF1? was examined with immunohistochemistry on duplicate tissue microarray slides containing HCC tumor explants. The times to recurrence and cancer death were analyzed with a Cox regression model and were compared according to the expression of markers of interest. We compared risk predictions with area under the receiver operator curves (AUROCs) and C statistics. AFP, HNF1?, and HNF1? were positive in 22.6%, 46.5%, and 61.0% of the tumor immunoprofiles, respectively. Although several variables were associated with the times to recurrence and cancer death in univariate Cox analyses, only AFP expression for the time to recurrence and the Milan criteria and HNF1? expression for the times to recurrence and cancer death remained significant after multivariate adjustments. The expression of HNF1? (but not HNF1?) was related to a serum AFP level ? 200 ng/mL, microvascular invasion, and AFP expression (P < 0.05 for all). A subgroup analysis showed that in the group meeting the Milan criteria, recurrence and cancer death rates at 10 years in the HNF1?-negative patients were approximately one-tenth of those in the HNF1?-positive patients, but the difference was not significant in the group exceeding the Milan criteria. The addition of HNF1? expression to the Milan criteria increased the C statistics and AUROCs for both recurrence and mortality (P < 0.05 for all). In conclusion, the immunohistological detection of HNF1? predicts recurrence and HCC-specific death after transplantation and provides an additive benefit in comparison with the Milan selection criteria on their own.
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Re-evaluating transarterial chemoembolization for the treatment of Hepatocellular Carcinoma: Consensus recommendations and review by an International Expert Panel.
Liver Int.
PUBLISHED: 08-29-2013
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Patients with unresectable hepatocellular carcinoma (HCC) usually receive transarterial chemoembolization (TACE) or systemic therapies with intermediate and advanced-stage disease. However, intermediate-stage HCC patients often have unsatisfactory clinical outcomes with repeated TACE and there is considerable uncertainty surrounding the criteria for repeating or stopping TACE treatment. In July 2012, an Expert Panel Opinion on Interventions in Hepatocellular Carcinoma (EPOIHCC) was re-convened in Shanghai in an attempt to provide a consensus on the practice of TACE, particularly in regard to evaluating TACE failure. To that end, current clinical practice throughout Asia was reviewed in detail including safety and efficacy data on TACE alone as well as in combination with targeted systemic therapies for intermediate HCC. This review summarizes the evidence discussed at the meeting and provides expert recommendations regarding the use of TACE for unresectable intermediate-stage HCC. A key consensus of the Expert Panel was that the current definitions of TACE failure are not useful in differentiating between situations where TACE is no longer effective in controlling disease locally vs. systemically. By redefining these concepts, it may be possible to provide a clearer indication of when TACE should be repeated and more importantly, when TACE should be discontinued.
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Microstructural integrity of early- versus late-myelinating white matter tracts in medial temporal lobe epilepsy.
Epilepsia
PUBLISHED: 07-30-2013
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Patients with medial temporal lobe epilepsy (MTLE) exhibit structural brain damage involving gray matter (GM) and white matter (WM). The mechanisms underlying tissue loss in MTLE are unclear and may be associated with a combination of seizure excitotoxicity and WM vulnerability. The goal of this study was to investigate whether late-myelinating WM tracts are more vulnerable to injury in MTLE compared with early myelinating tracts.
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Sorafenib alone versus sorafenib combined with transarterial chemoembolization for advanced-stage hepatocellular carcinoma: results of propensity score analyses.
Radiology
PUBLISHED: 07-17-2013
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To compare the time to progression (TTP) and overall survival (OS) in patients with advanced-stage hepatocellular carcinoma (HCC) who are undergoing sorafenib treatment combined with transarterial chemoembolization (TACE) versus sorafenib monotherapy.
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When and How Should Physicians Determine the Need for Palliative and Hospice Care for Patients With End-Stage Liver Disease?: An Experience in Taiwan.
Am J Hosp Palliat Care
PUBLISHED: 07-15-2013
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We analyzed one case of end-stage liver disease and discussed whether the palliative care should be considered for this case. The medical record of a 56-year-old woman with alcoholic liver cirrhosis admitted to our hospital due to hypovolemic shock and esophageal varices (EV) was reviewed. The EV with active bleeding were arrested by panendoscopic intervention. However, repeat surgery revealed transmural laceration over the cardia, and immediate surgery and splenectomy were needed. The patient died postoperatively in the surgical intensive care unit due to bleeding tendency and hypovolemic shock. We suggest that palliative care and/or hospice care should have been considered for this patient before the crisis developed and that physicians require education about timely palliative and hospice care for patients with end-stage nonmalignant disease.
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Biomolecular dual-ion-trap mass analyzer.
Analyst
PUBLISHED: 07-05-2013
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We developed the first dual-ion-trap mass analyzer which can detect ions with a high mass-to-charge ratio (m/z > 6000). The first ion trap is a quadrupole ion trap (QIT), which was operated by step scanning of the trapping frequency for a sample containing mixtures of biomolecules. The second ion trap, linear ion trap (LIT), was utilized to capture selected ions ejected out of the QIT so that all ions from the QIT can be examined one by one. It was found that the ions can be transferred from the QIT to the LIT with ~60% efficiency for large biomolecular ions with high m/z. This is by far the highest transfer efficiency in the dual ion trap device for high-mass ions.
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Randomized trial of the virologic response during up to two years of entecavir-adefovir combination therapy in multiple-drug-refractory chronic hepatitis B virus patients.
Antimicrob. Agents Chemother.
PUBLISHED: 05-06-2013
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A 1-year trial with entecavir plus adefovir resulted in a rate of virological response (VR) higher than that seen with lamivudine plus adefovir in multiple-drug-refractory chronic hepatitis B (CHB) patients. This extension study enrolled 89 of 90 patients who completed a 52-week randomized trial comparing treatment with entecavir plus adefovir (EA) to treatment with lamivudine plus adefovir (LA). At the baseline of the original study, all patients had lamivudine-resistant hepatitis B virus (HBV) and serum HBV DNA > 2,000 IU/ml despite prior lamivudine plus adefovir therapy. Of the 89 enrolled patients, 45 initially randomized to receive entecavir plus adefovir and the other 44 randomized to receive lamivudine plus adefovir received entecavir plus adefovir for an additional 52 weeks (EA-EA and LA-EA, respectively). The proportions of patients with a VR (serum HBV DNA < 60 IU/ml) gradually increased in both groups and were comparable at week 104 (42.2% in the EA-EA group and 34.1% in the LA-EA group; P = 0.51). The mean reductions in serum HBV DNA from baseline in the two groups were similar (-2.8 log10 IU/ml and -2.8 log10 IU/ml, respectively; P = 0.87). At week 104, the number of patients who retained the preexisting HBV mutants resistant to adefovir or entecavir had decreased from 8 to 2 in the EA-EA group and from 15 to 6 in the LA-EA group (P = 0.27). Both study groups had favorable safety profiles. In conclusion, up to 104 weeks of entecavir plus adefovir treatment was associated with a progressive VR, a decrease of levels of preexisting drug-resistant mutants, and no selection for additional resistance mutants of HBV in multiple-drug-refractory CHB patients. (This study has been registered at ClinicalTrials.gov under registration no. NCT01023217.).
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Clinical and epidemiological features of hepatitis C virus infection in South Korea: a prospective, multicenter cohort study.
J. Med. Virol.
PUBLISHED: 04-22-2013
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The epidemiological and clinical features of hepatitis C virus (HCV) infection in South Korea were examined in a prospective, multicenter cohort study that included 1,173 adult patients with positive results for anti-HCV antibody who completed a questionnaire survey on the risk factors for HCV infection from January 2007 to December 2011 at five university hospitals. The HCV cohort had a mean age of 55.4 years with 48.3% men, and diagnostic categories of acute hepatitis (n?=?63, 5.3%), past infection (n?=?37, 3.2%), chronic hepatitis (n?=?777, 66.2%), cirrhosis of the liver (n?=?179, 15.3%), and hepatocellular carcinoma (n?=?117, 10.0%). The major HCV genotypes were genotype 1 (52.7%) and genotype 2 (45.3%). Liver biopsy was performed in 301 patients (25.7%), and 42.8% of the subjects received antiviral therapy against HCV. The behavioral risk factors possibly related to HCV infection were intravenous drug use (5%), needle stick injury (7%), blood transfusion before 1995 (19%), sexual relationship with more than three partners (28%), piercings (35%), tattoos (36%), surgery (43%), acupuncture (83%), diagnostic endoscopy (85%), and dental procedures (93%). Age, intravenous drug use, needle stick injury, transfusion before 1995, and tattoos were the independent risk factors of HCV infection.
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Two-week schedule of hypofractionated radiotherapy as a local salvage treatment for small hepatocellular carcinoma.
J. Gastroenterol. Hepatol.
PUBLISHED: 04-18-2013
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In cases of small hepatocellular carcinoma (HCC) where established curative treatment cannot be applied, stereotactic body radiotherapy (SBRT) has been used as a non-invasive alternative treatment modality. However, short-course SBRT may not be safe if the tumor is located around a critical normal organ. Therefore, we applied hypofractionated radiotherapy for these tumors and evaluated outcomes of this treatment.
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Clinical and epidemiological characteristics of Korean patients with hepatitis C virus genotype 6.
Clin Mol Hepatol
PUBLISHED: 03-25-2013
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The distribution of hepatitis C virus (HCV) genotypes varies geographically. In Korea, genotypes 1 and 2 comprise more than 90% of HCV infections, while genotype 6 is very rare. This study compared the clinical and epidemiological characteristics of patients with genotype 6 HCV infection with those infected with HCV genotypes 1 and 2.
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Learning curve of single-port laparoscopic appendectomy for noncomplicated acute appendicitis: a preliminary analysis compared with conventional laparoscopic appendectomy.
J Laparoendosc Adv Surg Tech A
PUBLISHED: 03-21-2013
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The aim of this study was to delineate the learning curve of single-port laparoscopic appendectomy for noncomplicated appendicitis.
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Counteracting the activation of pAkt by inhibition of MEK/Erk inhibition reduces actin disruption-mediated apoptosis in PTEN-null PC3M prostate cancer cell lines.
Oncol Lett
PUBLISHED: 03-11-2013
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The actin cytoskeleton is important in the maintenance of cellular homeostasis and in signal transduction pathways leading to cell growth and apoptotic cell death in eukaryotic cells. Disruption of actin dynamics is associated with morphological changes in cancer cells. Deletion of phosphatase and tensin homolog (PTEN), a tumor suppressor gene involved in the regulation of the cell cycle and apoptosis, leads to cytoskeleton disruption and double-strand breaks (DSBs). To study the mechanism(s) of actin disruption-mediated apoptosis and its potential application for anticancer therapy, PTEN-null PC3M prostate cancer cells were treated with latrunculin B (LB). LB induced destabilization of the actin microfilament and apoptosis in a dose-dependent manner, as demonstrated by morphological changes and nuclear condensation in the PC3M cells. In addition, it resulted in an increase in the levels of ?H2AX recruitment, implicating the induction of DNA damage, including DSBs. Induction of Bax, with little effect on Bcl-2 expression, indicated that actin disruption causes apoptosis through activation of Bax signaling in PC3M cells. Treatment with U20126, a mitogen-activated protein kinase kinase (MEK) inhibitor, resulted in attenuated induction of DSBs and apoptosis through activation of protein kinase B (Akt), suggesting that LB-mediated actin dysfunction induces DSBs via the MEK/extracellular signal-regulated kinase (Erk) pathway in cells. Therefore, counteracting activation of phosphorylated Akt stemming from the inhibition of MEK/Erk resulted in attenuation of actin disruption-induced apoptotic events in the PC3M cells. The results of this study provide information not only for use in delineation of the molecular association between actin disruption and tumorigenesis, but also for the development of a strategy for actin-based anticancer chemotherapy against highly metastatic prostate cancer.
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Carcinoembryonic antigen (CEA) level, CEA ratio, and treatment outcome of rectal cancer patients receiving pre-operative chemoradiation and surgery.
Radiat Oncol
PUBLISHED: 02-26-2013
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To investigate serum carcinoembryonic antigen (CEA) as a prognostic factor for rectal cancer patients receiving pre-operative chemoradiotherapy (CRT).
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Efficacy and safety of pegylated interferon-?2a in patients with lamivudine-resistant HBeAg-positive chronic hepatitis B.
Antivir. Ther. (Lond.)
PUBLISHED: 02-21-2013
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Lamivudine resistance develops in up to 80% of patients with chronic hepatitis B (CHB) after 5 years of treatment. Cross-resistance between nucleoside/nucleotide analogues limits management options in these patients. To investigate the role of pegylated interferon-?2a as rescue therapy in these patients, the efficacy and safety of pegylated interferon-?2a between treatment-naive patients and lamivudine-resistant patients with hepatitis B e antigen (HBeAg)-positive CHB were compared.
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A gasless laparoscopic technique of wide excision for gastric gastrointestinal stromal tumor versus open method.
World J Surg Oncol
PUBLISHED: 02-15-2013
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Traditional open surgery for gastrointestinal stromal tumors (GIST) requires a long incision. Moreover, the gas-filling laparoscopic technique used in GIST surgery still has its limitations. Therefore, we developed a gasless laparoscopic (GL) surgery for GIST and compared it with traditional open surgery.
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Laparoscopy Decreases the Laparotomy Rate in Hemodynamically Stable Patients With Blunt Abdominal Trauma.
Surg Innov
PUBLISHED: 01-28-2013
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Background. This study evaluated the use of laparoscopy in hemodynamically stable patients with blunt abdominal trauma. Methods. We retrospectively reviewed the medical records of hemodynamically stable blunt abdominal trauma patients. Patients admitted from July 1, 2003, to June 30, 2006 (prior to the adoption of laparoscopy for patients with blunt abdominal trauma) were categorized as group A. Patients admitted from July 1, 2007, to June 30, 2010, when laparoscopy was included in the algorithm for the management of blunt abdominal trauma, were categorized as group B. Results. There were 47 patients in group A and 57 patients in group B. There were no significant differences in demographic characteristics, injury severity score, and injuries requiring surgical intervention between the groups (all, P > .05). Patients in group B had a shorter hospital stay (11 days vs 21 days, P < .001) and shorter ICU stay (0 [0, 1] days vs 0 [0, 9] days, P = .029). In group A, 6 of 47 patients (12.8%) underwent a nontherapeutic laparotomy. In contrast, 9 of 57 patients (15.8%) in group B avoided a nontherapeutic laparotomy because no significant intra-abdominal findings warranting an intervention were disclosed by laparoscopy. The incidence of laparotomy for patients with significant injuries in group B was lower than in group A (4.2% vs 100.0%; P < .001). There was no difference in the complication rate between the groups. Conclusions. Laparoscopy is feasible and safe for the diagnosis and treatment of hemodynamically stable patients with blunt abdominal trauma and can reduce the laparotomy rate.
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Consensus recommendations and review by an International Expert Panel on Interventions in Hepatocellular Carcinoma (EPOIHCC).
Liver Int.
PUBLISHED: 01-18-2013
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Hepatocellular carcinoma (HCC) presents with a high burden of disease in East Asian countries. Intermediate-stage HCC as defined by the Barcelona Clinic Liver Cancer (BCLC) staging system poses a clinical challenge as it includes a heterogeneous population of patients that can vary widely in terms of tumour burden, liver function and disease aetiology. Intermediate HCC patients often have unsatisfactory clinical outcomes with repeated transarterial chemoembolization (TACE, due to non-response of the target tumour or the development of further metastasis indicating progressive disease. In September 2011, an Expert Panel Opinion on Interventions in Hepatocellular Carcinoma (EPOIHCC) was convened in HK in an attempt to provide a consensus on the practice of TACE. To that end, current clinical practice throughout Asia was reviewed in detail including safety and efficacy data on TACE alone as well as in combination with targeted systemic therapies. This review summarises the evidence discussed at the meeting and provides expert recommendation regarding the available therapeutic options for unresectable intermediate stage HCC. A key consensus of the Expert Panel was that in order to improve patient outcomes and long-term survival, the possibility of using TACE in combination with targeted agents given systemically should be explored. While the currently available clinical data is promising, the expected completion of several pivotal phase II and III RCTs will provide further evidence in support of the rationale for combination therapy regimens.
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Clinical usefulness of endoscopic palliation in patients with biliary obstruction caused by hepatocellular carcinoma.
Digestion
PUBLISHED: 01-15-2013
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To evaluate the clinical usefulness of endoscopic biliary drainage (EBD) in patients with hepatocellular carcinoma (HCC).
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Recurrences of hepatocellular carcinoma following complete remission by transarterial chemoembolization or radiofrequency therapy: Focused on the recurrence patterns.
Hepatol. Res.
PUBLISHED: 01-15-2013
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In this study, we analyzed the rates and patterns of recurrences in hepatocellular carcinoma (HCC) patients who had achieved complete remission (CR) by transarterial chemoembolization (TACE) or radiofrequency ablation (RFA), and also examined the differences of recurrence patterns between TACE-treated and RFA-treated groups.
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Sensitivities of statistical distribution model and diffusion kurtosis model in varying microstructural environments: a Monte Carlo study.
J. Magn. Reson.
PUBLISHED: 01-12-2013
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The aim of this study was to investigate the microstructural sensitivity of the statistical distribution and diffusion kurtosis (DKI) models of non-monoexponential signal attenuation in the brain using diffusion-weighted MRI (DWI). We first developed a simulation of 2-D water diffusion inside simulated tissue consisting of semi-permeable cells and a variable cell size. We simulated a DWI acquisition of the signal in a volume using a pulsed gradient spin echo (PGSE) pulse sequence, and fitted the models to the simulated DWI signals using b-values up to 2500 s/mm(2). For comparison, we calculated the apparent diffusion coefficient (ADC) of the monoexponential model (b-value=1000 s/mm(2)). In separate experiments, we varied the cell size (5-10-15 ?m), cell volume fraction (0.50-0.65-0.80), and membrane permeability (0.001-0.01-0.1mm/s) to study how the fitted parameters tracked simulated microstructural changes. The ADC was sensitive to all the simulated microstructural changes except the decrease in membrane permeability. The ADC increased with larger cell size, smaller cell volume fraction, and larger membrane permeability. The ?stat of the statistical distribution model increased exclusively with a decrease in cell volume fraction. The Kapp of the DKI model was exclusively increased with decreased cell size and decreased with increasing membrane permeability. These results suggest that the non-monoexponential models of water diffusion have different, specific microstructural sensitivity, and a combination of the models may give insights into the microstructural underpinning of tissue pathology.
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Urinary neutrophil gelatinase-associated lipocalin levels predict cisplatin-induced acute kidney injury better than albuminuria or urinary cystatin C levels.
Kaohsiung J. Med. Sci.
PUBLISHED: 01-11-2013
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Cisplatin-induced acute kidney injury (AKI) is a major concern among clinicians in prescribing cisplatin-based chemotherapy. This study evaluated and compared the ability of urinary biomarkers, including urinary neutrophil gelatinase-associated lipocalin (NGAL), cystatin C, and the urinary albumin to creatinine ratio (ACR) to predict cisplatin-induced AKI. Thirty-three cancer patients receiving cisplatin-based chemotherapy were prospectively studied, including 10 (30%) who developed AKI (the study group). Changes of urinary biomarkers were compared at 4 hours, 8 hours, and 12 hours, and 1 day, 2 days, 3 days, and 4 days after cisplatin intravenous infusions (75mg/m(2)) versus the baseline. There was a significant increase in urinary NGAL levels from 12 hours to 4 days (p<0.05) compared to baseline after cisplatin infusion in the AKI group. The magnitude of these changes over time differed significantly by group (p<0.001). The area under the receiver operating curve describing the relationship between urinary NGAL levels and AKI within 12 hours was 0.865 (95% confidence interval=0.691-1.000). Urinary NGAL levels independently predicted AKI 12 hours after cisplatin (p=0.045) after adjustments for age, gender, body mass index, baseline serum creatinine, and urinary total protein. Urinary NGAL levels may be an early biomarker of AKI in patients receiving cisplatin-based treatment.
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High effectiveness of peginterferon alfa-2a plus ribavirin therapy in Korean patients with chronic hepatitis C in clinical practice.
Clin Mol Hepatol
PUBLISHED: 01-10-2013
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Identifying the impact of a patients ethnicity on treatment responses in clinical practice may assist in providing individualized treatment regimens for chronic hepatitis C (CHC). The effectiveness of standard peginterferon plus ribavirin therapy and the need for triple combination therapy with protease inhibitors in Koreans remain matters of debate. These issues were investigated in the present study.
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Optimal measurement modality and method for evaluation of responses to transarterial chemoembolization of hepatocellular carcinoma based on enhancement criteria.
J Vasc Interv Radiol
PUBLISHED: 01-09-2013
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To determine the usefulness of enhancement by iodized oil deposits on computed tomography (CT) following transarterial chemoembolization for hepatocellular carcinoma (HCC), and to compare the reliability of such CT imaging with that of magnetic resonance (MR) imaging.
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Lack of association between hepatitis B virus pre-S mutations and recurrence after surgical resection in hepatocellular carcinoma.
J. Med. Virol.
PUBLISHED: 01-07-2013
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Pre-S mutation of hepatitis B virus (HBV) is known to be a risk factor for hepatocarcinogenesis. A previous study suggested that pre-S mutation(s) may associate with increased recurrence after surgical resection. In the present study, 64 patients with HBV-related hepatocellular carcinoma (HCC) were categorized into two groups according to the presence or absence of pre-S mutation(s). The clinicopathological variables of the two groups were analyzed to assess the relationship between pre-S mutations and postoperative recurrence. Nineteen patients (29.7%) had pre-S mutations;13 had a pre-S deletion, three had a pre-S2 start codon mutation, two patients had both a pre-S deletion, and a pre-S2 start codon mutation, and one patient had a pre-S2 insertion. The two groups did not differ in terms of baseline clinicopathological parameters. Cirrhosis and satellite lesion(s) were predictive factors for postoperative recurrence and poor overall survival. Recurrence-free survival (P?=?0.320) and overall survival (P?=?0.238) did not differ significantly when pre-S mutations were present. In conclusion, this study did not find evidence supporting the notion that pre-S mutation(s) are associated with postoperative recurrence after surgical resection.
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Predisposing factors of hepatocellular carcinoma recurrence following complete remission in response to transarterial chemoembolization.
Dig. Dis. Sci.
PUBLISHED: 01-02-2013
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The aim of our study was to determine the predictors of recurrences in hepatocellular carcinoma (HCC) patients who had achieved complete remission (CR) by transarterial chemoembolization (TACE).
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Identification of traditional medicinal plant extracts with novel anti-influenza activity.
PLoS ONE
PUBLISHED: 01-01-2013
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The emergence of drug resistant variants of the influenza virus has led to a need to identify novel and effective antiviral agents. As an alternative to synthetic drugs, the consolidation of empirical knowledge with ethnopharmacological evidence of medicinal plants offers a novel platform for the development of antiviral drugs. The aim of this study was to identify plant extracts with proven activity against the influenza virus. Extracts of fifty medicinal plants, originating from the tropical rainforests of Borneo used as herbal medicines by traditional healers to treat flu-like symptoms, were tested against the H1N1 and H3N1 subtypes of the virus. In the initial phase, in vitro micro-inhibition assays along with cytotoxicity screening were performed on MDCK cells. Most plant extracts were found to be minimally cytotoxic, indicating that the compounds linked to an ethnomedical framework were relatively innocuous, and eleven crude extracts exhibited viral inhibition against both the strains. All extracts inhibited the enzymatic activity of viral neuraminidase and four extracts were also shown to act through the hemagglutination inhibition (HI) pathway. Moreover, the samples that acted through both HI and neuraminidase inhibition (NI) evidenced more than 90% reduction in virus adsorption and penetration, thereby indicating potent action in the early stages of viral replication. Concurrent studies involving Receptor Destroying Enzyme treatments of HI extracts indicated the presence of sialic acid-like component(s) that could be responsible for hemagglutination inhibition. The manifestation of both modes of viral inhibition in a single extract suggests that there may be a synergistic effect implicating more than one active component. Overall, our results provide substantive support for the use of Borneo traditional plants as promising sources of novel anti-influenza drug candidates. Furthermore, the pathways involving inhibition of hemagglutination could be a solution to the global occurrence of viral strains resistant to neuraminidase drugs.
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Stereotactic body radiation therapy as an alternative treatment for small hepatocellular carcinoma.
PLoS ONE
PUBLISHED: 01-01-2013
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Even with early stage hepatocellular carcinoma (HCC), patients are often ineligible for surgical resection, transplantation, or local ablation due to advanced cirrhosis, donor shortage, or difficult location. Stereotactic body radiation therapy (SBRT) has been established as a standard treatment option for patients with stage I lung cancer, who are not eligible for surgery, and may be a promising alternative treatment for patients with small HCC who are not eligible for curative treatment.
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Genetic variation in the NOC gene is associated with body mass index in Chinese subjects.
PLoS ONE
PUBLISHED: 01-01-2013
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Circadian clock genes are critical regulators of energy homeostasis and metabolism. However, whether variation in the circadian genes is associated with metabolic phenotypes in humans remains to be explored. In this study, we systemically genotyped 20 tag single nucleotide polymorphisms (SNPs) in 8 candidate genes involved in circadian clock, including CLOCK, BMAL1(ARNTL), PER1, PER2, CRY1, CRY2, CSNK1E,, and NOC(CCRN4L) in 1,510 non-diabetic Chinese subjects in Taipei and Yunlin populations in Taiwan. Their associations with metabolic phenotypes were analyzed. We found that genetic variation in the NOC gene, rs9684900 was associated with body mass index (BMI) (P = 0.0016, Bonferroni corrected P = 0.032). Another variant, rs135764 in the CSNK1E gene was associated with fasting glucose (P = 0.0023, Bonferroni corrected P = 0.046). These associations were consistent in both Taipei and Yunlin populations. Significant epistatic and joint effects between SNPs on BMI and related phenotypes were observed. Furthermore, NOC mRNA levels in human abdominal adipose tissue were significantly increased in obese subjects compared to non-obese controls.
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Which response criteria best help predict survival of patients with hepatocellular carcinoma following chemoembolization? A validation study of old and new models.
Radiology
PUBLISHED: 12-20-2011
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To identify differences in radiologic assessment methods and determine optimal imaging criteria for response evaluation in hepatocellular carcinoma (HCC) patients treated with chemoembolization.
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Suppressive effects of entecavir on hepatitis B virus and hepatocellular carcinoma.
J. Gastroenterol. Hepatol.
PUBLISHED: 09-03-2011
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We investigated the efficacy and effectiveness of entecavir in hepatitis B virus (HBV)-related hepatocellular carcinoma (HCC) patients.
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Applicability of the BCLC staging system to patients with hepatocellular carcinoma in Korea: analysis at a single center with a liver transplant center.
Korean J Hepatol
PUBLISHED: 07-16-2011
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The Barcelona Clinic Liver Cancer (BCLC) staging system is logical for the staging and treatment of hepatocellular carcinoma (HCC) because it was based on survival data. This study evaluated the applicability of the BCLC staging system and reasons for divergence from BCLC-recommended treatments in Korean HCC patients.
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Immune and inflammatory gene signature in rat cerebrum in subarachnoid hemorrhage with microarray analysis.
Mol Med Rep
PUBLISHED: 07-12-2011
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Cerebral vasospasm following subarachnoid hemorrhage (SAH) has been studied in terms of a contraction of the major cerebral arteries, but the effect of cerebrum tissue in SAH is not yet well understood. To gain insight into the biology of SAH-expressing cerebrum, we employed oligonucleotide microarrays to characterize the gene expression profiles of cerebrum tissue at the early stage of SAH. Functional gene expression in the cerebrum was analyzed 2 h following stage 1-hemorrhage in Sprague-Dawley rats. mRNA was investigated by performing microarray and quantitative real-time PCR analyses, and protein expression was determined by Western blot analysis. In this study, 18 upregulated and 18 downregulated genes displayed at least a 1.5-fold change. Five genes were verified by real-time PCR, including three upregulated genes [prostaglandin E synthase (PGES), CD14 antigen, and tissue inhibitor of metalloproteinase 1 (TIMP1)] as well as two downregulated genes [KRAB-zinc finger protein-2 (KZF-2) and ?-aminobutyric acid B receptor 1 (GABA B receptor)]. Notably, there were functional implications for the three upregulated genes involved in the inflammatory SAH process. However, the mechanisms leading to decreased KZF-2 and GABA B receptor expression in SAH have never been characterized. We conclude that oligonucleotide microarrays have the potential for use as a method to identify candidate genes associated with SAH and to provide novel investigational targets, including genes involved in the immune and inflammatory response. Furthermore, understanding the regulation of MMP9/TIMP1 during the early stages of SAH may elucidate the pathophysiological mechanisms in SAH rats.
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Evaluation of lentiviral-mediated expression of sodium iodide symporter in anaplastic thyroid cancer and the efficacy of in vivo imaging and therapy.
J Oncol
PUBLISHED: 07-01-2011
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Anaplastic thyroid carcinoma (ATC) is one of the most deadly cancers. With intensive multimodalities of treatment, the survival remains low. ATC is not sensitive to (131)I therapy due to loss of sodium iodide symporter (NIS) gene expression. We have previously generated a stable human NIS-expressing ATC cell line, ARO, and the ability of iodide accumulation was restored. To make NIS-mediated gene therapy more applicable, this study aimed to establish a lentiviral system for transferring hNIS gene to cells and to evaluate the efficacy of in vitro and in vivo radioiodide accumulation for imaging and therapy. Lentivirus containing hNIS cDNA were produced to transduce ARO cells which do not concentrate iodide. Gene expression, cell function, radioiodide imaging and treatment were evaluated in vitro and in vivo. Results showed that the transduced cells were restored to express hNIS and accumulated higher amount of radioiodide than parental cells. Therapeutic dose of (131)I effectively inhibited the tumor growth derived from transduced cells as compared to saline-treated mice. Our results suggest that the lentiviral system efficiently transferred and expressed hNIS gene in ATC cells. The transduced cells showed a promising result of tumor imaging and therapy.
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Haemoglobin A1c is associated with carotid intima-media thickness in a Chinese population.
Clin. Endocrinol. (Oxf)
PUBLISHED: 06-15-2011
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The association between haemoglobin A1c (HbA1c) levels and subclinical atherosclerosis in carotid arteries in Chinese populations is unknown. AIM, DESIGN AND METHODS: The objective of this study was to investigate this relationship and evaluate the ability of HbA1c levels to predict carotid atherosclerosis in a Chinese population. This was a cross-sectional study, which included 541 subjects without known diabetes (Taiwan Lifestyle Study). About 67 (9·2%) subjects were newly diagnosed with diabetes during the study. Carotid intima-media thickness (IMT) and the presence of carotid plaques were determined using ultrasonography.
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Acute hepatitis C in Korea: different modes of infection, high rate of spontaneous recovery, and low rate of seroconversion.
J. Med. Virol.
PUBLISHED: 05-14-2011
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The epidemiology and clinical outcomes of acute hepatitis C are different geographically. This study aimed to investigate the mode of infection, clinical characteristics, and outcomes of acute hepatitis C in Korea. Forty-seven patients with acute hepatitis C were enrolled consecutively in a study conducted in seven medical centers. The patients with the mean age of 45.8 years had mostly mild symptoms. A healthcare-related procedure was the most common exposure history (42.5%): acupuncture (17%), surgery (10.6%), needle-stick injury (8.5%), and other medical procedures (6.4%). There was no case of intravenous drug use. Twenty-one patients (44.7%) recovered spontaneously. Among the 16 patients who received antiviral therapy (34%), all of the 12 evaluable patients had a sustained virologic response, while 10 patients (21.3%) who did not receive antiviral therapy progressed to chronic infection. The overall seroconversion rate of anti-HCV antibody was 61.7%. The patients who recovered spontaneously had significantly lower rate of seroconversion compared with the patients who did not clear spontaneously the infection. In conclusion, acute hepatitis C in Korea was related to various healthcare procedures, including acupuncture, characterized by high rates of spontaneous recovery and low rates of seroconversion, which may be associated with different modes of infection and ethnic differences. The characteristics of acute hepatitis C in Asian countries warrants further study.
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X-PROP: a fast and robust diffusion-weighted propeller technique.
Magn Reson Med
PUBLISHED: 04-18-2011
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Diffusion-weighted imaging (DWI) has shown great benefits in clinical MR exams. However, current DWI techniques have shortcomings of sensitivity to distortion or long scan times or combinations of the two. Diffusion-weighted echo-planar imaging (EPI) is fast but suffers from severe geometric distortion. Periodically rotated overlapping parallel lines with enhanced reconstruction diffusion-weighted imaging (PROPELLER DWI) is free of geometric distortion, but the scan time is usually long and imposes high Specific Absorption Rate (SAR) especially at high fields. TurboPROP was proposed to accelerate the scan by combining signal from gradient echoes, but the off-resonance artifacts from gradient echoes can still degrade the image quality. In this study, a new method called X-PROP is presented. Similar to TurboPROP, it uses gradient echoes to reduce the scan time. By separating the gradient and spin echoes into individual blades and removing the off-resonance phase, the off-resonance artifacts in X-PROP are minimized. Special reconstruction processes are applied on these blades to correct for the motion artifacts. In vivo results show its advantages over EPI, PROPELLER DWI, and TurboPROP techniques.
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Noninvasive diagnostic criteria for hepatocellular carcinoma in hepatic masses >2 cm in a hepatitis B virus-endemic area.
Liver Int.
PUBLISHED: 04-11-2011
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Noninvasive criteria for diagnosing hepatocellular carcinoma (HCC) suggested by the American Association for the Study of Liver Diseases (AASLD) in 2005 consisted of serum ?-fetoprotein (AFP) level >200 ng/ml or a typical enhancement pattern (arterial enhancement and portal/delayed washed out) on dynamic imaging of hepatic mass(es) >2 cm in a cirrhotic liver.
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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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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.