JoVE Visualize What is visualize?
Stop Reading. Start Watching.
Advanced Search
Stop Reading. Start Watching.
Regular Search
Find video protocols related to scientific articles indexed in Pubmed.
PLA2G2A overexpression is associated with poor therapeutic response and inferior outcome in rectal cancer patients receiving neoadjuvant concurrent chemoradiotherapy.
Histopathology
PUBLISHED: 11-14-2014
Show Abstract
Hide Abstract
The aim of this study was to investigate the prognostic impact of PLA2G2A expression and its role in predicting the response to neoadjuvant concurrent cheomoradiotherapy (CCRT) in rectal cancer.
Related JoVE Video
A smartphone-centric system for the range of motion assessment in stroke patients.
IEEE J Biomed Health Inform
PUBLISHED: 11-07-2014
Show Abstract
Hide Abstract
The range of motion (ROM) in stroke patients is often severely affected. Poststroke rehabilitation is guided through the use of clinical assessment scales for the rROM. Unfortunately, these scales are not widely utilized in clinical practice as they are excessively time-consuming. Although commercial motion-capture systems are capable of providing the information required for the assessments, most systems are either too costly or lack the convenience required for assessments to be conducted on a daily basis. This paper presents the design and implementation of a smartphone-based system for automated motor assessment using low-cost off-the-shelf inertial sensors. The system was used to automate a portion of the upper-extremity Fugl-Meyer assessment (FMA), which is widely used to quantify motor deficits in stroke survivors. Twelve out of 33 items were selected, focusing mainly on joint angle measurements of the upper body. The system has the ability to automatically identify the assessment item being conducted, and calculate the maximum respective joint angle achieved. Preliminary results show the ability of this system to achieve comparable results to goniometer measurements, while significantly reducing the time required to conduct the assessments. The portability and ease-of-use of the system would simplify the task of conducting range-of-motion assessments.
Related JoVE Video
Determination of the position and orientation of a flat piezoelectric micro-stage by moving the optical axis.
Rev Sci Instrum
PUBLISHED: 11-03-2014
Show Abstract
Hide Abstract
A moving optical axis measurement system with six degrees-of-freedom (DOF) is proposed in this study. The system is very simple and can be placed inside a flat piezoelectric micro-stage. The system comprises three two-DOF optical measurement modules, each having a quadrant photo diode (QPD), a lens, and a laser diode. These three modules and the geometric configuration of their installation allow displacement measurements with up to six-DOF to be made. A mathematical model of this system is also presented. By analyzing the sensitivity and relationship between the displacement of the stage and each of the QPD light spots, movement can be observed. Signal feedback enables multi-axis nano-scale positioning control. We also present a new six-DOF nano stage, which uses piezoelectric actuators for displacement. This stage was used to verify the proposed six-DOF measurement system. Linear and angular resolution of the system can be down to 10 nm and 0.1 arcsec. Linear and angular displacement measurement errors of this six-DOF measurement system are in the range of ±70 nm and ±0.65 arcsec.
Related JoVE Video
Evaluation of the Therapeutic and Diagnostic Effects of PEGylated Liposome-Embedded 188Re on Human Non-Small Cell Lung Cancer Using an Orthotopic Small-Animal Model.
J. Nucl. Med.
PUBLISHED: 10-27-2014
Show Abstract
Hide Abstract
Non-small cell lung cancer (NSCLC) is a highly morbid and mortal cancer type that is difficult to eradicate using conventional chemotherapy and radiotherapy. Little is known about whether radionuclide-based pharmaceuticals can be used for treating NSCLC. Here we embedded the therapeutic radionuclide (188)Re in PEGylated (PEG is polyethylene glycol) liposomes and investigated the biodistribution, pharmacokinetics, and therapeutic efficacy of this nanoradiopharmaceutical on NSCLC using a xenograft lung tumor model and the reporter gene imaging techniques.
Related JoVE Video
Spatial and electrical switching of defect modes in a photonic bandgap device with a polymer-dispersed liquid crystal defect layer.
Opt Express
PUBLISHED: 10-17-2014
Show Abstract
Hide Abstract
This paper investigates the spectral properties of a one-dimensional photonic crystal (PC) containing an inhomogeneous polymer- dispersed liquid crystal (PDLC) as a defect layer. Experimental results indicate that the voltage-induced reorientation of LC molecules between the light-scattering and transparent states in the PDLC enables the electrical tuning of the transmittance of defect-mode peaks in the spectrum of the PC/PDLC cell. Specifically, owing to the unique configuration of the spatial distribution of LC droplet sizes in the defect layer, a concept concerning the spatial switching in the wavelength of defect modes is proposed. As a result, the PC/PDLC hybrid cell is suggested as a potential element for realizing an electrically tunable and spatially switchable photonic bandgap device, which is polarizer-free and requires no alignment layers in the fabrication process.
Related JoVE Video
Development of a steel ball center alignment device based on Michelson interference concept.
Rev Sci Instrum
PUBLISHED: 10-03-2014
Show Abstract
Hide Abstract
This study presents a ball center alignment method based on the Michelson interferometer where one of the reflecting mirrors is replaced by a lens and steel ball. By locating the ball away from the focal length of the lens, the beam is reflected as a spherical wave. The interference ring formed by the planar and spherical waves can be clearly observed using a camera without a lens. The distance of the offset of the ball center can be enhanced by more than 140% using this method. A fast ring profile fitting method can reduce circle fitting time to around a third of that needed for Hough transformation.
Related JoVE Video
A linear gradient line source facilitates the use of diffusion models with high order approximation for efficient, accurate turbid sample optical properties recovery.
Biomed Opt Express
PUBLISHED: 10-01-2014
Show Abstract
Hide Abstract
In this paper, we demonstrate that a scanning MEMS mirror can be employed to create a linear gradient line source that is equivalent to a planar source. This light source setup facilitates the use of diffusion models of increased orders of approximation having closed form solution, and thus enhance the efficiency and accuracy in sample optical properties recovery. In addition, compared with a regular planar light source, the linear gradient line source occupies much less source area and has an elevated measurement efficiency. We employed a ?-P1 diffusion equation with a closed form solution and carried out a phantom study to understand the performance of this new method in determining the absorption and scattering properties of turbid samples. Moreover, our Monte Carlo simulation results indicated that this geometry had probing depths comparable to those of the conventional diffuse reflectance measurement geometry with a source-detector separation of 3 mm. We expect that this new source setup would facilitate the investigating of superficial volumes of turbid samples in the wavelength regions where tissue absorption coefficients are comparable to scattering coefficients.
Related JoVE Video
Fibroblast growth factor receptor 2 overexpression is predictive of poor prognosis in rectal cancer patients receiving neoadjuvant chemoradiotherapy.
J. Clin. Pathol.
PUBLISHED: 09-30-2014
Show Abstract
Hide Abstract
Neoadjuvant concurrent chemoradiotherapy (CCRT) followed by surgery is an increasingly used therapeutic strategy for advanced rectal cancer, but risk stratification and final outcomes remain suboptimal. Recently, the oncogenic role of the fibroblast growth factor/fibroblast growth factor receptor (FGFR) signalling pathway has been recognised; however, its clinical significance in rectal cancer has not been elucidated. In this study, we identify and validate targetable drivers associated with the FGFR signalling pathway in rectal cancer patients treated with CCRT.
Related JoVE Video
Laparoscopic bariatric surgery for the treatment of severe hypertriglyceridemia.
Asian J Surg
PUBLISHED: 08-23-2014
Show Abstract
Hide Abstract
It is well established that severe hypertriglyceridemia can lead to pancreatitis. At present, medical treatment for patients with severe hypertriglyceridemia and repeat pancreatitis attacks is not adequate. The aim of this study was to assess the effectiveness of laparoscopic bariatric surgery in these patients.
Related JoVE Video
Overexpression of REG4 confers an independent negative prognosticator in rectal cancers receiving concurrent chemoradiotherapy.
J Surg Oncol
PUBLISHED: 08-22-2014
Show Abstract
Hide Abstract
Neoadjuvant concurrent chemoradiotherapy (CCRT) followed by surgery is the standard treatment for locally advanced rectal cancer. Through data mining from published transcriptomic database, we identified Regenerating Gene Type IV (REG4) as the most significantly associated gene with resistance to CCRT. This study examined the prognostic impact of REG4 expression in patients with rectal cancer receiving neoadjuvant CCRT.
Related JoVE Video
Melanoma spheroid formation involves laminin-associated vasculogenic mimicry.
Am. J. Pathol.
PUBLISHED: 08-19-2014
Show Abstract
Hide Abstract
Melanoma is a tumor where virulence is conferred on transition from flat (radial) to three-dimensional (tumorigenic) growth. Virulence of tumorigenic growth is governed by numerous attributes, including presence of self-renewing stem-like cells and related formation of patterned networks associated with the melanoma mitogen, laminin, a phenomenon known as vasculogenic mimicry. Vasculogenic mimicry is posited to contribute to melanoma perfusion and nutrition in vivo; we hypothesized that it may also play a role in stem cell-driven spheroid formation in vitro. Using a model of melanoma in vitro tumorigenesis, laminin-associated networks developed in association with three-dimensional melanoma spheroids. Real-time PCR analysis of laminin subunits showed that spheroids formed from anchorage-independent melanoma cells expressed increased ?4 and ?1 laminin chains and ?4 laminin expression was confirmed by in situ hybridization. Association of laminin networks with melanoma stem cell-associated nestin and vascular endothelial growth factor receptor-1 also was documented. Moreover, knockdown of nestin gene expression impaired laminin expression and network formation within spheroids. Laminin networks were remarkably similar to those observed in melanoma xenografts in mice and to those seen in patient melanomas. These data indicate that vasculogenic mimicry-like laminin networks, in addition to their genesis in vivo, are integral to the extracellular architecture of melanoma spheroids in vitro, where they may serve as stimulatory scaffolds to support three-dimensional growth.
Related JoVE Video
Radioprotective effects of Antrodia cinnamomea are enhanced on immune cells and inhibited on cancer cells.
Int. J. Radiat. Biol.
PUBLISHED: 08-11-2014
Show Abstract
Hide Abstract
Abstract Purpose: The radioprotective effects of Antrodia cinnamomea (AC) were investigated for understanding the potential usefulness of AC as an adjunct treatment for reducing radiation side-effects.
Related JoVE Video
Single-anastomosis gastric bypass (SAGB): appraisal of clinical evidence.
Obes Surg
PUBLISHED: 07-25-2014
Show Abstract
Hide Abstract
Single-anastomosis (mini-) gastric bypass (SAGB) was proposed by Dr. Robert Rutledge. Criticism and prejudice against this procedure was raised by surgeons who preferred a more difficult procedure, laparoscopic Roux-en-Y gastric bypass (RYGB). Increasing data indicates the procedure is an effective and durable bariatric procedure. SAGB has lower operation risks compared to RYGB. The weight loss is better after SAGB because of a greater malabsorptive component than RYGB, but SAGB had a higher incidence of micronutrient deficiencies. Randomized controlled trial and long-term data demonstrate that SAGB can be regarded as a simpler and safer alternative to RYGB. We propose this procedure to be renamed "single-anastomosis gastric bypass (SAGB)" because the key feature of SAGB is the "single anastomosis" compared with the two anastomoses of RYGB.
Related JoVE Video
A hybrid NMR/SAXS-based approach for discriminating oligomeric protein interfaces using Rosetta.
Proteins
PUBLISHED: 07-23-2014
Show Abstract
Hide Abstract
Oligomeric proteins are important targets for structure determination in solution. While in most cases the fold of individual subunits can be determined experimentally, or predicted by homology-based methods, protein-protein interfaces are challenging to determine de novo using conventional NMR structure determination protocols. Here we focus on a member of the bet-V1 superfamily, Aha1 from Colwellia psychrerythraea. This family displays a broad range of crystallographic interfaces none of which can be reconciled with the NMR and SAXS data collected for Aha1. Unlike conventional methods relying on a dense network of experimental restraints, the sparse data are used to limit conformational search during optimization of a physically realistic energy function. This work highlights a new approach for studying minor conformational changes due to structural plasticity within a single dimeric interface in solution. © Proteins 2014;. © 2014 Wiley Periodicals, Inc.
Related JoVE Video
Ultralow-threshold single-mode lasing based on a one-dimensional asymmetric photonic bandgap structure with liquid crystal as a defect layer.
Opt Lett
PUBLISHED: 07-01-2014
Show Abstract
Hide Abstract
In this Letter, we propose defect-mode lasing from a one-dimensional asymmetric photonic structure with dye-doped nematic liquid crystal as a central defect layer. The local field intensity of the distinguished single defect mode at the overlapped photonic band edges is drastically enhanced by the asymmetric structure consisting of two distinct multilayer photonic crystals. With high density of states of photons, effective output lasing emission and maximum input excitation are ensured. As a result, the single-mode lasing with a low excitation threshold of 0.2???J/pulse is achieved due to the combination of the defect layer and the photonic band edge effect.
Related JoVE Video
Tunable narrow-bandpass filter based on an asymmetric photonic bandgap structure with a dual-mode liquid crystal.
Opt Express
PUBLISHED: 07-01-2014
Show Abstract
Hide Abstract
A one-dimensional asymmetric photonic crystal with dual-frequency liquid crystal as a central defect layer was demonstrated. Such asymmetric structure was characterized by the dramatic increase in intensity of the electric field of light localized at the overlapped photonic bandgap edges, thereby enhancing the observed transmittance of the spectral windows originating from the defect layer. The defect layer was made of a dual-mode liquid crystal that exhibited not only electrical tunability and switchability but also optical bistability. Consequently, tunable and bistable defect modes can be realized in the photonic structure. This asymmetric photonic crystal structure is promising and should be further explored for photonic device applications.
Related JoVE Video
Laparoscopic sleeve gastrectomy versus single anastomosis (mini-) gastric bypass for the treatment of type 2 diabetes mellitus: 5-year results of a randomized trial and study of incretin effect.
Obes Surg
PUBLISHED: 06-27-2014
Show Abstract
Hide Abstract
Bariatric surgery may be beneficial in mildly obese patients with poorly controlled diabetes. The optimal procedure to achieve diabetes remission is unknown. In 2011, we published the short-term results of a pilot study designed to evaluate the efficacy of diabetic control and the role of duodenal exclusion in mildly obese diabetic patients undergoing laparoscopic sleeve gastrectomy (SG) vs. a laparoscopic single anastomosis (mini-) gastric bypass (SAGB). This study analyzes the 5-year results and evaluates the incretin effect.
Related JoVE Video
Recruitment and Screening for a Randomized Trial Investigating Roux-en-Y Gastric Bypass versus Intensive Medical Management for Treatment of Type 2 Diabetes.
Obes Surg
PUBLISHED: 05-28-2014
Show Abstract
Hide Abstract
Large-scale randomized clinical trials are needed to assess the role of Roux-en-Y gastric bypass (RYGB) in treating patients with type 2 diabetes mellitus (T2DM). Recruitment challenges must be understood.
Related JoVE Video
Nestin depletion induces melanoma matrix metalloproteinases and invasion.
Lab. Invest.
PUBLISHED: 05-27-2014
Show Abstract
Hide Abstract
Matrix metalloproteinases (MMPs) are key biological mediators of processes as diverse as wound healing, embryogenesis, and cancer progression. Although MMPs may be induced through multiple signaling pathways, the precise mechanisms for their regulation in cancer are incompletely understood. Because cytoskeletal changes are known to accompany MMP expression, we sought to examine the potential role of the poorly understood cytoskeletal protein, nestin, in modulating melanoma MMPs. Nestin knockdown (KD) upregulated the expression of specific MMPs and MMP-dependent invasion both through extracellular matrix barriers in vitro and in peritumoral connective tissue of xenografts in vivo. The development of three-dimensional melanospheres that in vitro partially recapitulate noninvasive tumorigenic melanoma growth was inhibited by nestin KD, although ECM invasion by aberrant melanospheres that did form was enhanced. Mechanistically, nestin KD-dependent melanoma invasion was associated with intracellular redistribution of phosphorylated focal adhesion kinase and increased melanoma cell responsiveness to transforming growth factor-beta, both implicated in pathways of melanoma invasion. The results suggest that the heretofore poorly understood intermediate filament, nestin, may serve as a novel mediator of MMPs critical to melanoma virulence.Laboratory Investigation advance online publication, 3 November 2014; doi:10.1038/labinvest.2014.130.
Related JoVE Video
Overexpression of CPS1 is an independent negative prognosticator in rectal cancers receiving concurrent chemoradiotherapy.
Tumour Biol.
PUBLISHED: 05-26-2014
Show Abstract
Hide Abstract
Locally advanced rectal cancers are currently treated with neoadjuvant concurrent chemoradiotherapy (CCRT) followed by surgery, but stratification of risk and final outcomes remain suboptimal. In view of the fact that glutamine metabolism is usually altered in cancer, we profiled and validated the significance of genes involved in this pathway in rectal cancers treated with CCRT. From a published transcriptome of rectal cancers (GSE35452), we focused on glutamine metabolic process-related genes (GO:0006541) and found upregulation of carbamoyl phosphate synthetase 1 (CPS1) gene most significantly predicted poor response to CCRT. We evaluated the expression levels of CPS1 using immunohistochemistry to analyze tumor specimens obtained during colonoscopy from 172 rectal cancer patients. Expression levels of CPS1 were further correlated with major clinicopathological features and survivals in this validation cohort. To further confirm CPS1 expression levels, Western blotting was performed for human colon epithelial primary cell (HCoEpiC) and four human colon cancer cells, including HT29, SW480, LoVo, and SW620. CPS1 overexpression was significantly related to advanced posttreatment tumor (T3, T4; P?=?0.006) and nodal status (N1, N2; P?
Related JoVE Video
Acquired Chiari malformation type I associated with a supratentorial fistulous arteriovenous malformation: a case report.
Childs Nerv Syst
PUBLISHED: 05-21-2014
Show Abstract
Hide Abstract
A case of acquired Chiari malformation type I with frontal fistulous arteriovenous malformation (AVM) is presented, and the pathophysiology is discussed. The tonsillar herniation and hydrocephalus both resolved after AVM was excised. This case provides some insight into the complex hemodynamic change exerted by the fistulous AVM and the mechanism of the development of acquired Chiari malformation type I.
Related JoVE Video
The PEGylated liposomal doxorubicin improves the delivery and therapeutic efficiency of 188Re-Liposome by modulating phagocytosis in C26 murine colon carcinoma tumor model.
Nucl. Med. Biol.
PUBLISHED: 05-16-2014
Show Abstract
Hide Abstract
Liposome in delivering radionuclide for cancer therapy has been expansively studied; however, liposome itself can be deliberately entrapped and destroyed by the reticuloendothelial system, causing an insufficiency of the drug delivery, which in turn would restrict the effectiveness of the drug. In this study, mice with subcutaneous implantation of C26 murine colon cancer received an experimental treatment regimen in which mice took delivery of PEGylated liposomal doxorubicin (LipoDox) first, after a three-day interval, of Rhenium-188 encapsulated into PEGylated liposome ((188)Re-Liposome) subsequently and by which suppressed the functioning of reticuloendothelial system for the short term. The data showed that based upon the biodistribution assay and the evaluation of the therapeutic efficacy, (188)Re-Liposome was more sufficiently delivered to tumor sites in mice with this treatment regimen than mice without the regimen, and that cancer mortalities in mice with the treatment regimen were much lower than the mortalities in mice without the regimen. Taken together, a new strategy proposed in this study significantly improved both the (188)Re-Liposome delivery and the effectiveness of (188)Re-Liposome, suggesting that the strategy can be an ideal treatment for cancer.
Related JoVE Video
Modified laparoscopic technique for fixation of peritoneal dialysis catheter.
Surg Laparosc Endosc Percutan Tech
PUBLISHED: 04-23-2014
Show Abstract
Hide Abstract
Continuous ambulatory peritoneal dialysis (CAPD) is a treatment for patients with end-stage renal disease (ESRD). Peritoneal dialysis catheters are usually placed using a small laparotomy. This traditional technique is usually safe if well executed, but it cannot be safely performed if the patient has had a previous abdominal operation. A minimally invasive procedure may progress safely by laparoscopic intervention. However, dysfunction of the catheter during a laparoscopic intervention is a common complication related to CAPD. This usually involves intra-abdominal migration of the catheter, even with one intra-abdominal fixation. In an effort to increase catheter survival, we tested a modified laparoscopic technique with two intra-abdominal fixations of a Tenckhoff catheter.
Related JoVE Video
AMACR overexpression as a poor prognostic factor in patients with nasopharyngeal carcinoma.
Tumour Biol.
PUBLISHED: 04-22-2014
Show Abstract
Hide Abstract
The molecular prognostic adjunct in patients with nasopharyngeal carcinomas (NPCs) still remains obscured. Through data mining from published transcriptomic database, alpha-methylacyl-CoA racemase (AMACR) was first identified as a differentially upregulated gene in NPC tissues, which is a key enzyme for isometric conversion of fatty acids entering the ?-oxidation. Given the roles of AMACR in prognostication and frontline therapeutic regimen of common carcinomas, such as prostate cancer, we explored AMACR immunoexpression status and its clinical significance in NPC patients. AMACR immunohistochemistry was retrospectively performed and analyzed using H-score for biopsy specimens from 124 NPC patients who received standard treatment without distant metastasis at initial diagnosis. Those cases with H-score larger than the median value were construed as featuring AMACR overexpression. The findings were correlated with the clinicopathological variables, disease-specific survival (DSS), distant metastasis-free survival (DMFS), and local recurrence-free survival (LRFS). Endogenous AMACR protein expressions were assessed by real-time reverse-transcription polymerase chain reaction (RT-PCR) and Western blotting in NPC cells and non-neoplastic mucosal cells. AMACR overexpression was significantly associated with increment of primary tumor status (P?=?0.009) and univariately predictive of adverse outcomes for DSS, DMFS, and LRFS. In the multivariate comparison, AMACR overexpression still remained prognostically independent to portend worse DSS (P?=?0.006, hazard ratio?=?2.129), DMFS (P?=?0.001, hazard ratio?=?2.795), and LRFS (P?=?0.041, hazard ratio?=?2.009), together with advanced American Joint of Cancer Committee (AJCC) stages III-IV. Compared with non-neoplastic cells, both HONE1 and TW01 NPC cells demonstrated markedly increased AMACR expression. AMACR overexpression was identified as an important prognosticator and a potential therapeutic target in the future.
Related JoVE Video
The predictors of successful percutaneous coronary intervention in ostial left anterior descending artery chronic total occlusion.
Catheter Cardiovasc Interv
PUBLISHED: 04-06-2014
Show Abstract
Hide Abstract
Percutaneous coronary intervention (PCI) to chronic total occlusion (CTO) has become one of the treatment strategies in recent era. The ostium of the left anterior descending artery (LAD) is one of the most difficult positions for CTO revascularization. Until now, limited data has been made available for the prediction of successful ostial LAD CTO PCI.
Related JoVE Video
Label-free immunodetection of the cancer biomarker CA125 using high-?n liquid crystals.
J Biomed Opt
PUBLISHED: 04-03-2014
Show Abstract
Hide Abstract
A label-free and array-based optical liquid-crystal (LC) immunodetection technique for the detection of CA125 antigen, a protein biomarker most frequently used for ovarian cancer detection, was demonstrated with a nematic LC with larger birefringence (?n) to promote sensitivity in detecting biomolecules. The LC-based immunodetection offers an alternative and sensitive approach for the detection of biomarker proteins, with the potential of replacing conventional immunoassays used in biochemical studies and clinical laboratories.
Related JoVE Video
Single dose acute toxicity testing for N,N-bis(2-mercaptoethyl)-N',N' diethylethylenediamine in beagles.
Regul. Toxicol. Pharmacol.
PUBLISHED: 03-29-2014
Show Abstract
Hide Abstract
N,N-Bis(2-mercaptoethyl)-N',N'-diethylenediamine (BMEDA) is used in the preparation of the (188)Re-BMEDA-liposome as a chelator to deliver rhenium 188 into liposomes. Although the safety of the (188)Re-BMEDA-liposome had been established, the use of BMEDA in preparing the liposome is of interest; however, an assessment of its safety is warranted. In this present work, we report on the acute toxicity study of BMEDA in beagles to identify doses causing no adverse effect and doses causing life-threatening toxicity. In a single dose 14-day systemic toxicity study conducted in beagles, BMEDA was without compound-related adverse effects at doses of up to 2mg/kg in a series of clinical observations and clinical pathology examinations. The results of these studies could aid in choosing doses for repeat-dose studies and in the selection of starting doses for Phase 1 human studies.
Related JoVE Video
Overexpression of ANXA1 confers independent negative prognostic impact in rectal cancers receiving concurrent chemoradiotherapy.
Tumour Biol.
PUBLISHED: 03-26-2014
Show Abstract
Hide Abstract
Neoadjuvant concurrent chemoradiation therapy (CCRT) is an increasingly common therapeutic strategy for rectal cancer. Clinically, it remains a major challenge to predict therapeutic response and patient outcomes after CCRT. Annexin I (ANXA1), encoded by ANXA1, is a Ca(2+)/phospholipid-binding protein that mediates actin dynamics and cellular proliferation, as well as suggesting tumor aggressiveness and predicting therapeutic response in certain malignancies. However, expression of ANXA1 has never been reported in rectal cancer receiving CCRT. This study examined the predictive and prognostic impact of ANXA1 expression in patients with rectal cancer following neoadjuvant CCRT. We identified ANXA1 as associated with resistance to CCRT through data mining from a published transcriptomic dataset. Its immunoexpression was retrospectively assessed using H scores on pre-treatment biopsies from 172 rectal cancer patients treated with neoadjuvant CCRT followed by curative surgery. Results were correlated with clinicopathological features, therapeutic response, tumor regression grade (TRG), and metastasis-free survival (MeFS), as well as local recurrent-free survival (LRFS) and disease-specific survival (DSS). High expression of ANXA1 was associated with advanced pre-treatment tumor status (T3, T4, p?=?0.022), advanced pre-treatment nodal status (N1, N2, p?=?0.004), advanced post-treatment tumor status (T3, T4, p?
Related JoVE Video
Thermodielectric generation of defect modes in a photonic liquid crystal.
Opt Express
PUBLISHED: 03-26-2014
Show Abstract
Hide Abstract
Photonic defect modes induced by in situ formation of an ill-defined defect layer is demonstrated in a cholesteric liquid crystal (CLC). The local deformation of the one-dimensionally periodic helical structure is achieved by means of the thermodielectric effect, which alters the pitch in the middle of the cholesteric structure. The defect-mode peak in the photonic band gap appears in the transmission spectrum only when the incident circularly polarized light has the same handedness as that of the CLC structure. The wavelength of the deformation-induced defect mode can be tuned upon varying the dielectric heating power by simply applying a frequency-modulated voltage.
Related JoVE Video
Laparoscopic Nissen fundoplication with gastric plication as a potential treatment of morbidly obese patients with GERD, first experience and results.
Obes Surg
PUBLISHED: 03-11-2014
Show Abstract
Hide Abstract
Laparoscopic Nissen fundoplication is an effective treatment for gastroesophageal reflux disease (GERD). However, there is no consensus for the surgical treatment of GERD in morbidly obese patients.
Related JoVE Video
Gastrointestinal metabolic surgery for the treatment of type 2 diabetes mellitus.
World J. Gastroenterol.
PUBLISHED: 03-07-2014
Show Abstract
Hide Abstract
Medical therapy for type 2 diabetes mellitus is ineffective in the long term due to the progressive nature of the disease, which requires increasing medication doses and polypharmacy. Conversely, bariatric surgery has emerged as a cost-effective strategy for obese diabetic individuals; it has low complication rates and results in durable weight loss, glycemic control and improvements in the quality of life, obesity-related co-morbidity and overall survival. The finding that glucose homeostasis can be achieved with a weight loss-independent mechanism immediately after bariatric surgery, especially gastric bypass, has led to the paradigm of metabolic surgery. However, the primary focus of metabolic surgery is the alteration of the physio-anatomy of the gastrointestinal tract to achieve glycemic control, metabolic control and cardio-metabolic risk reduction. To date, metabolic surgery is still not well defined, as it is used most frequently for less obese patients with poorly controlled diabetes. The mechanism of glycemic control is still incompletely understood. Published research findings on metabolic surgery are promising, but many aspects still need to be defined. This paper examines the proposed mechanism of diabetes remission, the efficacy of different types of metabolic procedures, the durability of glucose control, and the risks and complications associated with this procedure. We propose a tailored approach for the selection of the ideal metabolic procedure for different groups of patients, considering the indications and prognostic factors for diabetes remission.
Related JoVE Video
Cyclin-dependent kinase 4 overexpression is mostly independent of gene amplification and constitutes an independent prognosticator for nasopharyngeal carcinoma.
Tumour Biol.
PUBLISHED: 02-22-2014
Show Abstract
Hide Abstract
Data mining in the public domain demonstrates that cyclin-dependent kinase 4 (CDK4) is highly expressed in nasopharyngeal carcinomas (NPC). Associated with cyclin-D, CDK4 phosphorylates and inactivates retinoblastoma (Rb) protein family members and mediates progression through the G1- to the S-phase of the cell cycle. Amplification and overexpression of CDK4 has been identified in various human malignancies. However, its expression and amplification has never been systemically evaluated in NPC. This study aimed to evaluate the amplification and expression status, correlation with clinicopathological features, and prognostic implications of CDK4 based on public domain dataset and in our well-defined cohort of NPC patients. The association between CDK4 transcript level and gene dosage was explored by analysis of an independent public domain dataset. We retrospectively assessed CDK4 immunoexpression in biopsies of 124 consecutive NPC patients devoid of initial distant metastasis and treated according to consistent guidelines. The results were correlated with clinicopathological features, local recurrence-free survival (LRFS), distant metastasis-free survival (DMeFS), and disease-specific survival (DSS). High levels of CDK4 protein were positively correlated with the T 3, 4 status (p = 0.024); N 2, 3 status (p < 0.001); and the American Joint Committee on Cancer stage 3, 4 (p < 0.001). Multivariate analysis suggested high CDK4 expression was an independent prognostic indicator of worse DMeFS (p = 0.001, hazard ratio (HR)?= 3.226) and DSS (p = 0.037, HR = 1.838). Although CDK4 is frequently upregulated, its gene locus is very uncommonly amplified in NPC. CDK4 overexpression is mostly independent with gene amplification and represents a potential prognostic biomarker in NPC and may indicate tumor aggressiveness through cell cycle dysregulation.
Related JoVE Video
Deficiency in asparagine synthetase expression in rectal cancers receiving concurrent chemoradiotherapy: negative prognostic impact and therapeutic relevance.
Tumour Biol.
PUBLISHED: 02-19-2014
Show Abstract
Hide Abstract
Locally advanced rectal cancers are currently treated with neoadjuvant concurrent chemoradiotherapy (CCRT) followed by surgery, but risk stratification and final outcomes remain suboptimal. In this study, we identify and validate targetable metabolic drivers relevant to the prognosis of patients with rectal cancer treated with CCRT. Using a published transcriptome of rectal cancers, we found that asparagine synthetase (ASNS) gene significantly predicted the response to CCRT. From 172 patients with rectal cancer, the expression levels of ASNS, using immunohistochemistry assays, were further evaluated in tumor specimens initially obtained by using colonoscopy. Expression levels of ASNS were further correlated with major clinicopathological features and clinical survivals in this valid cohort. ASNS deficiency was significantly related to advanced posttreatment tumor (T3, T4; P = .015) and nodal status (N1, N2; P = .004) and inferior tumor regression grade (P < .001). In survival analyses, ASNS deficiency was significantly associated with shorter local recurrence-free survival (LRFS; P = .0039), metastasis-free survival (MeFS; P = .0001), and disease-specific survival (DSS; P = .0006). Furthermore, ASNS deficiency was independently predictive of worse outcomes for MeFS (P = .012, hazard ratio = 3.691) and DSS (P = .022, hazard ratio = 2.845), using multivariate analysis. ASNS deficiency is correlated with poor therapeutic response and worse survivals in patients with rectal cancer receiving neoadjuvant CCRT. These findings indicate that ASNS is a prognostic factor with therapeutic potential for treating rectal cancer.
Related JoVE Video
Bariatric surgery decreased the serum level of an endotoxin-associated marker: lipopolysaccharide-binding protein.
Surg Obes Relat Dis
PUBLISHED: 02-12-2014
Show Abstract
Hide Abstract
Recent studies have shown serum lipopolysaccharide binding protein (LBP) is associated with obesity and related metabolic disorder. Bariatric surgery can significantly reduce weight, but reports about the change of LBP after bariatric surgery are limited. We investigated LBP concentration and its associations with clinical variables.
Related JoVE Video
Combined therapeutic efficacy of (188)Re-liposomes and sorafenib in an experimental colorectal cancer liver metastasis model by intrasplenic injection of C26-luc murine colon cancer cells.
Mol Clin Oncol
PUBLISHED: 01-20-2014
Show Abstract
Hide Abstract
Rhenium-188 ((188)Re) displays abundant intermediate energy ? emission and possesses a physical half-life of 16.9 h. Sorafenib is an orally available multikinase inhibitor that targets Raf kinases and vascular endothelial growth factor receptors (VEGFRs). Sorafenib has demonstrated preclinical and clinical activity against several types of tumors, such as renal cell and colorectal carcinoma. In this study, we investigated the efficacy of radiotherapeutics of (188)Re-liposomes combined with sorafenib in a C26-luc metastatic colorectal liver tumour mouse model. Liver metastases were established by intrasplenic injection of C26-luc murine colon cancer cells. Based on the results of the toxicity assessment, an administration dose of 80% the maximum tolerated dose was selected. (188)Re-liposomes were administered on day 1, when metastases of several hundred micrometers in diameter were observed. In the combination therapy group, 10 mg/kg sorafenib (co-developed and co-marketed by Bayer and Onyx Pharmaceuticals as Nexavar) was administered every other day for 1 week and the survival of mice was assessed. The tumor growth was more significantly inhibited in the (188)Re-liposome plus sorafenib group compared with the (188)Re-liposome alone, sorafenib alone and untreated normal saline groups (P=0.0000). Furthermore, (188)Re-liposomes combined with sorafenib achieved higher survival rates compared with the (188)Re-liposome alone, sorafenib alone and untreated normal saline groups (P=0.0000). These results support the use of combined radio-chemotherapy with (188)Re-liposomes plus sorafenib as a viable treatment option in the adjuvant setting for liver metastases of colorectal cancer.
Related JoVE Video
Evaluation of stromal HGF immunoreactivity as a biomarker for melanoma response to RAF inhibitors.
Mod. Pathol.
PUBLISHED: 01-17-2014
Show Abstract
Hide Abstract
Of more than 150?000 published studies evaluating new biomarkers, fewer than 100 biomarkers have been implemented for patient care. One reason for this is lack of rigorous testing by the medical community to validate claims for biomarker clinical relevance, and potential reluctance to publish negative results when confirmation is not obtained. Here we sought to determine the utility and reproducibility of immunohistochemical detection of hepatocyte growth factor (HGF) in melanoma tissue, an approach of potential assistance in defining patients with innate resistance to BRAF inhibitor therapy. To this end, a published and a revised method that retained sensitivity but with greater specificity for HGF detection, were evaluated in cells known to endogenously express HGF, and in models where HGF is upregulated via cytokine induction and via overexpression by gene transfection. Consequent patient evaluation in collaboration with the Melanoma Institute Australia of a cohort of 41 melanoma specimens with extensive clinical annotation failed to validate HGF immunohistochemistry as a predictor of response to BRAF inhibitors. Targeted therapies for advanced melanoma and other cancers show great promise, and rigorous validation studies are thus indicated for approaches that seek to personalize such therapies to maximize therapeutic efficacy.
Related JoVE Video
Pharmacokinetics of BMEDA after intravenous administration in beagle dogs.
Molecules
PUBLISHED: 01-08-2014
Show Abstract
Hide Abstract
The pharmacokinetics of N,N-bis(2-mercapatoethly)-N',N'-diethylenediamine (BMEDA), a molecule that can form a chelate with rhenium-188 (188Re) to produce the 188Re-BMEDA-liposomes, was studied. In this work, beagles received a single injection of BMEDA, at doses of 1, 2, or 5 mg/kg; the concentration of BMEDA in the beagles' plasma was then analyzed and determined by liquid chromatography-mass spectrometry/mass spectrometry. Based on the pharmacokinetic parameters of BMEDA, we found that male and female animals shared similar patterns indicating that the pharmacokinetics of BMEDA is independent of gender differences. In addition, the pharmacokinetics of BMEDA was seen to be non-linear because the increase of mean AUC0-t and AUC0-? values tend to be greater than dose proportional while the mean Vss and CL values of BMEDA appeared to be dose dependent. The information on the pharmacokinetics of BMEDA generated from this study will serve as a basis to design appropriate pharmacology and toxicology studies for future human use.
Related JoVE Video
Acute gastric remnant dilatation, a rare early complication of laparoscopic mini-gastric bypass.
Asian J Endosc Surg
PUBLISHED: 01-06-2014
Show Abstract
Hide Abstract
Several thousands of laparoscopic mini-gastric bypass have been performed globally by a number of surgeons. There is growing evidence that mini-gastric bypass is a safe and effective procedure. We report a rare case of massive gastric remnant dilation in a 45-year-old man after laparoscopic mini-gastric bypass. Acute gastric dilatation is a surgical emergency. In our case, a triad of clinical suspicion, laboratory profile, and emergency radiologic investigation were essential for early diagnosis and management. Image-guided gastrostomy tube placement provides an effective decompression of the gastric remnant. A literature review revealed no previous reports of similar complications in mini-gastric bypass.
Related JoVE Video
Impairment of gastrointestinal quality of life in severely obese patients.
World J. Gastroenterol.
PUBLISHED: 01-02-2014
Show Abstract
Hide Abstract
To investigate the common gastro-intestinal symptoms and quality of life in severely obese subjects.
Related JoVE Video
Destruxin B inhibits hepatocellular carcinoma cell growth through modulation of the Wnt/?-catenin signaling pathway and epithelial-mesenchymal transition.
Toxicol In Vitro
PUBLISHED: 01-02-2014
Show Abstract
Hide Abstract
The aberrant activation of Wnt/?-catenin signaling plays an important role in the carcinogenesis and progression of hepatocellular carcinoma (HCC). Therefore, the Wnt/?-catenin signaling molecules are attractive candidates for the development of targeted therapies for this disease. The present study showed that destruxin B (DB) inhibits the proliferation and induces the apoptosis of HCC cells by decreasing the protein expression of anti-apoptotic Bcl-2 and Bcl-xL and increasing the expression of the proapoptotic protein Bax. More importantly, DB also attenuates Wnt-signaling in HCC cells by downregulating ?-catenin, Tcf4, and ?-catenin/Tcf4 transcriptional activity, which results in the decreased expression of ?-catenin target genes, such as cyclin D1, c-myc, and survivin. Furthermore, DB affects the migratory and invasive abilities of Sk-Hep1 cells through the suppression of markers of the epithelial-mesenchymal transition (EMT). A synergistic anti-proliferative and migratory effect was achieved using the combination of DB and sorafenib in Sk-Hep1 cells. In conclusion, DB acts as a novel Wnt/?-catenin inhibitor and reduces the aggressiveness and invasive potential of HCC by altering the cells' EMT status and mobility. DB in combination with sorafenib may be considered for future clinical use for the management of metastatic HCC.
Related JoVE Video
Lactose-free milk prolonged endurance capacity in lactose intolerant Asian males.
J Int Soc Sports Nutr
PUBLISHED: 01-01-2014
Show Abstract
Hide Abstract
Several studies on Caucasian volunteers have proven that milk is an effective recovery drink for athletes. Such benefit, however, cannot be directly applied to the lactose-intolerant Asian population. This study investigated the effects of ingesting water (WT), sports drink (SPD) and lactose-free milk (LFM) on cycling capacity.
Related JoVE Video
Tumor-associated macrophages in stage IIIA pN2 non-small cell lung cancer after neoadjuvant chemotherapy and surgery.
Am J Transl Res
PUBLISHED: 01-01-2014
Show Abstract
Hide Abstract
Most of the patients with stage IIIA pN2 non-small cell lung cancer (NSCLC) develop recurrence after surgery. It is not clear whether post neoadjuvant chemotherapy tumor-associated macrophages is associated with recurrence.
Related JoVE Video
Safety and feasibility of coronary stenting in unprotected left main coronary artery disease in the real world clinical practice-a single center experience.
PLoS ONE
PUBLISHED: 01-01-2014
Show Abstract
Hide Abstract
This study evaluated the feasibility, safety, and prognostic outcome in patients with significant unprotected left main coronary artery (ULMCA) disease undergoing stenting.
Related JoVE Video
Endovascular treatment and computed imaging follow-up of 14 anterior condylar dural arteriovenous fistulas.
Interv Neuroradiol
PUBLISHED: 01-01-2014
Show Abstract
Hide Abstract
We report our experience in treating the anterior condylar dural arteriovenous fistula (DAVF) and confirm the location of the coils in the follow-up images after successful endovascular treatment. We retrospectively reviewed the 14 patients with anterior condylar DAVF treated successfully in our institute. Twelve of them had CT or MR follow-up images. All the patients had intravascular coiling of the fistula. Seven of our patients had retrograde drainage to different sinuses. Three had ocular symptoms as a clinical manifestation. We treated nine patients with coils alone (eight transvenous, one transarterial), four with adjuvant transarterial treatment with particles or liquid embolic for minimal residual after coiling packing. One patient had failed onyx treatment and successful treatment by following transvenous packing. All patients had total obliteration of the DAVF fistula on immediate post-procedure angiogram or on the follow-up images and no evidence of recurrence clinically. The mean follow-up period was 34.2 months (standard deviation=39.8). Twelve patients had computed images (CT alone in four, MR alone in five, both CT and MR in three). These findings were analyzed by four certified neuroradiologists. We found 100% of the coils at the anterior condylar veins inside the hypoglossal canal, 54.2% at the lateral lower clivus, and only 14.2% at the anterior condylar confluence which is ventrolateral to the anterior orifice of the hypoglossal canal. Intravascular coiling is the treatment of choice in patients with anterior condylar DAVF. All the coils were found at the anterior condylar veins inside the hypoglossal canal after successful treatment.
Related JoVE Video
Interferon-? suppresses activin A/NF-E2 induction of erythroid gene expression through the NF-?B/c-Jun pathway.
Am. J. Physiol., Cell Physiol.
PUBLISHED: 12-11-2013
Show Abstract
Hide Abstract
Interferon (IFN)-? is a proinflammatory cytokine that is linked to erythropoiesis inhibition and may contribute to anemia. However, the mechanism of IFN-?-inhibited erythropoiesis is unknown. Activin A, a member of the transforming growth factor (TGF)-? superfamily, induces the erythropoiesis of hematopoietic progenitor cells. In this study, a luciferase reporter assay showed that IFN-? suppressed activin A-induced ?-globin promoter activation in K562 erythroblast cells in a dose-dependent manner. Activin A reversed the suppressive effect of IFN-? on the luciferase activity of ?-globin promoter in a dose-dependent manner. IFN-? also suppressed the activation of activin A-induced ?-globin promoter. IFN-? reduced the mRNA expression of ?-globin, ?-globin, NF-E2p45, and GATA-1 induced by activin A. The results also showed that IFN-? induced c-Jun expression when NF-?Bp65 and c-Jun bound to two AP-1-binding sites on the c-Jun promoter. The luciferase activity of ?-globin and ?-globin promoters were enhanced by wild-type c-Jun and eliminated by dominant-negative (DN) c-Jun. The suppressive effects of IFN-? on the mRNA expression of ?-globin and ?-globin were absent in cells expressing DN c-Jun. The ability of NF-E2 to enhance activin A-induced ?-globin promoter activation decreased when c-Jun was present, and IFN-? treatment further enhanced the decreasing effect of c-Jun. Chromatin immunoprecipitation revealed that NF-E2p45 bound to the upstream regulatory element (HS-40) of the ?-globin gene cluster in response to activin A, whereas c-Jun eliminated this binding. These results suggest that IFN-? modulates NF-?B/c-Jun to antagonize activin A-mediated NF-E2 transcriptional activity on globin gene expression.
Related JoVE Video
Predictors of remission of type 2 diabetes mellitus in obese patients after gastrointestinal surgery.
Obes Res Clin Pract
PUBLISHED: 12-07-2013
Show Abstract
Hide Abstract
Summary: Background: Gastroenterology is a beneficial treatment of morbidly obese type 2 diabetes mellitus (T2DM). We aimed to identify the predictors for the treatment of T2DM obese patients.Methods: A retrospective study consisting of 531 patients undergoing laparoscopic gastric banding (LGB), laparoscopic mini-gastric bypass (LMGB) and laparoscopic sleeve gastrectomy (LSG) from January 2004 to May 2007 was performed. Patients with preoperative fasting serum glucose concentration of more than 126 mg/dl were diagnosed as T2DM. A postoperatively fasting serum glucose level of less than 110 mg/dl was considered to be remission of T2DM.Results: Of the 531 patients, 62 (11.6%) were diagnosed as T2DM, including 23 men and 39 women, with a mean age of 31.8 ± 9.2 years, and a mean body mass index (BMI) of 40.0 kg/m(2). The mean glucose at 3, 6, and 12 months after surgery were 100.1 mg/dl, 95.1 mg/dl and 91.8 mg/dl, respectively. The mean body weight loss one year after surgery was 9.4% for LGB, 31.4% for LSG and 37.1% for LMGB, respectively. Among these operation methods (LGB, LMGB and LSG), the BMI, body weight, waist circumference, serum lipid profile and serum factors associated with glucose metabolism were significantly different during the one-year postoperative follow-up. Remission rate of T2DM was achieved in 84.8%, 58.8% and 58.3% of patients for LMGB, LGB and LSG, respectively. The best operative method for the remission of T2DM was LMGB. Using an artificial neural network (ANN) data mining technique, waist circumference, operative methods and C-peptide were significantly predictors for the remission of T2 DM.Conclusion: One year after gastrointestinal surgery, improvement of serum lipid profiles and serum data related to glucose metabolism in the different operative methods were noticed. LMGB seems to be the most effective procedure for the reduction of serum glucose levels compared with LAGB and LSG.
Related JoVE Video
Clinical application of perfusion computed tomography in neurosurgery.
J. Neurosurg.
PUBLISHED: 11-22-2013
Show Abstract
Hide Abstract
Object Currently, perfusion CT (PCT) is a valuable imaging technique that has been successfully applied to the clinical management of patients with ischemic stroke and aneurysmal subarachnoid hemorrhage (SAH). However, recent literature and the authors experience have shown that PCT has many more important clinical applications in a variety of neurosurgical conditions. Therefore, the authors share their experiences of its application in various diseases of the cerebrovascular, neurotraumatology, and neurooncology fields and review the pertinent literature regarding expanding PCT applications for neurosurgical conditions, including pitfalls and future developments. Methods A pertinent literature search was conducted of English-language articles describing original research, case series, and case reports from 1990 to 2011 involving PCT and with relevance and applicability to neurosurgical disorders. Results In the cerebrovascular field, PCT is already in use as a diagnostic tool for patients suspected of having an ischemic stroke. Perfusion CT can be used to identify and define the extent of the infarct core and ischemic penumbra core, and thus aid patient selection for acute reperfusion therapy. For patients with aneurysmal SAH, PCT provides assessment of early brain injury, cerebral ischemia, and infarction, in addition to vasospasm. It may also be used to aid case selection for aggressive treatment of patients with poor SAH grade. In terms of oncological applications, PCT can be used as an imaging biomarker to assess angiogenesis and response to antiangiogenetic treatments, differentiate between glioma grades, and distinguish recurrent tumor from radiation necrosis. In the setting of traumatic brain injury, PCT can detect and delineate contusions at an early stage. In patients with mild head injury, PCT results have been shown to correlate with the severity and duration of postconcussion syndrome. In patients with moderate or severe head injury, PCT results have been shown to correlate with patients functional outcome. Conclusions Perfusion CT provides quantitative and qualitative data that can add diagnostic and prognostic value in a number of neurosurgical disorders, and also help with clinical decision making. With emerging new technical developments in PCT, such as characterization of blood-brain barrier permeability and whole-brain PCT, this technique is expected to provide more and more insight into the pathophysiology of many neurosurgical conditions.
Related JoVE Video
Gastrointestinal quality of life following bariatric surgery in Asian patients.
Hepatogastroenterology
PUBLISHED: 11-13-2013
Show Abstract
Hide Abstract
Bariatric surgery is the only proven method that produces sustained weight loss. We aimed to investigate the Gastrointestinal Quality of Life Index (GIQLI) differences between obese patients following laparoscopic mini-gastric bypass (LMGB), laparoscopic adjustable gastric banding (LAGB) and laparoscopic sleeve gastrectomy (LSG) in this study.
Related JoVE Video
Preparation and evaluation of collagen I/ gellan gum/?-TCP microspheres as bone graft substitute materials.
Conf Proc IEEE Eng Med Biol Soc
PUBLISHED: 10-11-2013
Show Abstract
Hide Abstract
Collagen I is the main component of protein in bone and exhibits many excellent applications in biomedical fields. Gellan gum possesses good biocompatible, biodegradable and good mechanical property, and shows great potentials as tissue engineering scaffold or cell culture substrate. Therefore, the aim of this study was to use collagen I, gellan gum and ?-TCP to prepare collagen I/gellan gum/?-TCP microspheres by emulsion method as bone graft substitute materials. The preliminary results showed that collagen I/gellan gum/?-TCP microspheres had particle size distribution between 500-1000 µP in diameter and exhibited better mechanical strength. These microspheres also showed good biocompatibility in cell activity test.
Related JoVE Video
Lower operation voltage in dual-frequency cholesteric liquid crystals based on the thermodielectric effect.
Opt Express
PUBLISHED: 10-10-2013
Show Abstract
Hide Abstract
Dual-frequency cholesteric liquid crystal (DFCLC) devices characteristically require high operation voltage, which hinders their further development in thin-film-transistor driving. Here we report on a lower-voltage switching method based on the thermodielectric effect. This technique entails applying a high-frequency voltage to occasion dielectric oscillation heating so to induce the increase in crossover frequency. The subsequent change in dielectric anisotropy of the DFCLC allows the switching, with a lower operation voltage, from the planar state to the focal conic or homeotropic state. The temperature rise incurred by the dielectric heating is described.
Related JoVE Video
Activin A induction of erythroid differentiation sensitizes K562 chronic myeloid leukemia cells to a subtoxic concentration of imatinib.
Am. J. Physiol., Cell Physiol.
PUBLISHED: 10-02-2013
Show Abstract
Hide Abstract
Chronic myeloid leukemia (CML) is a hematopoietic stem/progenitor cell disorder in which Bcr-Abl oncoprotein inhibits cell differentiation. Differentiation induction is considered an alternative strategy for treating CML. Activin A, a member of the transforming growth factor-? superfamily, induces erythroid differentiation of CML cells through the p38 MAPK pathway. In this study, treatment of the K562 CML stem/progenitor cell line with activin A followed by a subtoxic concentration of the Bcr-Abl inhibitor imatinib strongly induced growth inhibition and apoptosis compared with simultaneous treatment with activin A and imatinib. Imatinib-induced growth inhibition and apoptosis following activin A pretreatment were dose- and time-dependent. Imatinib-induced growth inhibition and apoptosis were also dependent on the pretreatment dose of activin A. More than 90% of the activin A-induced increases in glycophorin A-positive cells were sensitive to imatinib. However, only some of original glycophorin A-positive cells in the activin A treatment group were sensitive to imatinib. Sequential treatment with activin A and imatinib decreased Bcr-Abl, procaspase-3, Mcl-1, and Bcl-xL and also induced cleavage of procaspase-3/poly(ADP-ribose)polymerase. The reduction of erythroid differentiation in p38 MAPK dominant-negative mutants or by short hairpin RNA knockdown of p38 MAPK decreased the growth inhibition and apoptosis mediated by sequential treatment with activin A and imatinib. Furthermore, the same inhibition level of multidrug resistance 1 expression was observed in cells treated with activin A alone, treated sequentially with activin A and imatinib, or treated simultaneously with activin A and imatinib. The p38 MAPK inhibitor SB-203580 can restore activin A-inhibited multidrug resistance 1 expression. Taken together, our results suggest that a subtoxic concentration of imatinib could exhibit strong cytotoxicity against erythroid-differentiated K562 CML cells.
Related JoVE Video
Gender, body mass index, and PPAR? polymorphism are good indicators in hyperuricemia prediction for Han Chinese.
Genet Test Mol Biomarkers
PUBLISHED: 09-26-2013
Show Abstract
Hide Abstract
Hyperuricemia is closely associated with obesity and metabolic abnormalities, which is also an independent risk factor for cardiovascular diseases. The PPAR? gene, which is linked to obesity and metabolic abnormalities in Han Chinese, might be considered a top candidate gene that is involved in hyperuricemia. This study recruited 457 participants, aged 20-40 years old, to investigate the associations of the PPAR? gene and metabolic parameters with hyperuricemia. Three tag-single nucleotide polymorphisms, rs2292101, rs4684846, and rs1822825, of the PPAR? gene were selected to explore their association with hyperuricemia. Risk genotypes on rs1822825 of the PPAR? gene exhibited statistical significance with hyperuricemia (odds ratio: 1.9; 95% confidence interval: 1.05-3.57). Although gender, body mass index (BMI), serum total cholesterol concentration, or protein intake per day were statistically associated with hyperuricemia, the combination of BMI, gender, and rs1822825, rather than that of age, serum lipid profile, blood pressure, and protein intake per day, satisfied the predictability for hyperuricemia (sensitivity: 69.3%; specificity: 83.7%) in Taiwan-born obese Han Chinese. BMI, gender, and the rs1822825 polymorphism in the PPAR? gene appeared good biomarkers in hyperuricemia; therefore, these powerful indicators may be included in the prediction of hyperuricemia to increase the accuracy of the analysis.
Related JoVE Video
Multiple Mechanisms for E2F Binding Inhibition by Phosphorylation of the Retinoblastoma Protein C-Terminal Domain.
J. Mol. Biol.
PUBLISHED: 08-28-2013
Show Abstract
Hide Abstract
The retinoblastoma protein C-terminal domain (RbC) is necessary for the tumor suppressor proteins activities in growth suppression and E2F transcription factor inhibition. Cyclin-dependent kinase phosphorylation of RbC contributes to Rb inactivation and weakens the Rb-E2F inhibitory complex. Here we demonstrate two mechanisms for how RbC phosphorylation inhibits E2F binding. We find that phosphorylation of S788 and S795 weakens the direct association between the N-terminal portion of RbC (RbC(N)) and the marked-box domains of E2F and its heterodimerization partner DP. Phosphorylation of these sites and S807/S811 also induces an intramolecular association between RbC and the pocket domain, which overlaps with the site of E2F transactivation domain binding. A reduction in E2F binding affinity occurs with S788/S795 phosphorylation that is additive with the effects of phosphorylation at other sites, and we propose a structural mechanism that explains this additivity. We find that different Rb phosphorylation events have distinct effects on activating E2F family members, which suggests a novel mechanism for how Rb may differentially regulate E2F activities.
Related JoVE Video
Overexpression of stathmin 1 confers an independent prognostic indicator in nasopharyngeal carcinoma.
Tumour Biol.
PUBLISHED: 08-17-2013
Show Abstract
Hide Abstract
Data mining on public domain identified that stathmin 1 (STMN1) transcript was significantly higher expressed in nasopharyngeal carcinoma (NPC). Also known as the oncoprotein 18, STMN1 performs an important function in regulating rapid microtubule remodeling of the cytoskeleton in response to the cellular conditions. Immunoexpression of STMN1 was retrospectively assessed in biopsies of 124 consecutive NPC patients without initial distant metastasis and treated with consistent guidelines. The outcome was correlated with clinicopathological features and patient survivals. Results indicated that high STMN1 expressions (50 %) were correlated with advanced age (p?=?0.027), higher T stage (p?=?0.003), and overall clinical stage (p?=?0.006) by the 7th American Joint Committee of Cancer Staging. In multivariate analyses, high STMN1 expression emerged as an independent prognosticator for worse disease-specific survival (p?=?0.001), distal metastasis-free survival (p?=?0.003), and local recurrence-free survival (p?=?0.006). Exogenous expression of E2F transcription factor 1 (E2F1) or/and its dimeric partner, transcription factor Dp-1 (TFDP1), notably induced the STMN1 protein level in a NPC-derived cell line, TW01. Accordingly, high STMN1 protein level is commonly associated with adverse prognosticators and confers tumor aggressiveness in patients with NPC, and its upregulation might be attributed to E2F1 and/or TFDP1 transactivation.
Related JoVE Video
Fibronectin overexpression is associated with latent membrane protein 1 expression and has independent prognostic value for nasopharyngeal carcinoma.
Tumour Biol.
PUBLISHED: 08-12-2013
Show Abstract
Hide Abstract
Despite recent improvements in the diagnosis and treatment, the final outcomes in patients with nasopharyngeal carcinomas (NPC) still remain suboptimal. Through data mining from published transcriptomic database with further bioinformatic validation, fibronectin (FN1) was identified as a differentially upregulated gene in NPC tissues, which implicates the transition from epithelial to mesenchymal phenotype (EMT) and promotes metastasis. Given the roles of fibronectin in risk stratification and in the frontline therapeutics of common carcinomas, such as renal cell cancer, we explored fibronectin immunoexpression status and its associations with clinicopathological variables and survival in a well-defined cohort of NPC patients. Fibronectin immunohistochemistry was retrospectively performed and analyzed using H-score for 124 biopsy specimens from NPC patients who received standard treatment without distant metastasis at initial diagnosis. Those cases with H-score higher than the median value were regarded as fibronectin overexpression. The findings were correlated with clinicopathological variables, EBV latent membrane protein 1 (LMP1) expression, disease-specific survival (DSS), distant metastasis-free survival (DMFS), and local recurrence-free survival (LRFS). Fibronectin overexpression was significantly associated with American Joint Committee on Cancer (AJCC) stages III-IV (p?=?0.019) and LMP1 expression (p?=?0.004), and univariately predictive of adverse outcomes for DSS, DMFS, and LRFS (all p?
Related JoVE Video
Hybrid organic-inorganic materials for novel photonic applications.
Appl Opt
PUBLISHED: 08-06-2013
Show Abstract
Hide Abstract
This novel joint feature issue on "Hybrid organic-inorganic materials for photonic applications" in Applied Optics and Optics Materials Express comprises 14 papers on liquid crystals, polymers, photoconductive materials, and gratings and filters. It is hoped that this feature issue encourages and stimulates further research into hybrid materials with enhanced linear and nonlinear optical properties, their mechanisms of operation, and their applications.
Related JoVE Video
A sesquiterpene lactone antrocin from Antrodia camphorata negatively modulates JAK2/STAT3 signaling via microRNA let-7c and induces apoptosis in lung cancer cells.
Carcinogenesis
PUBLISHED: 07-23-2013
Show Abstract
Hide Abstract
Lung cancer is the leading cause of cancer deaths worldwide and current therapies fail to treat this disease in majority of cases. Antrodia camphorata is a medicinal mushroom being widely used as food dietary supplement for cancer prevention. The sesquiterpene lactone antrocin is the most potent among >100 secondary metabolites isolated from A. camphorata. However, the molecular mechanisms of antrocin-mediated anticancer effects remain unclear. In this study, we found that antrocin inhibited cell proliferation in two non-small-cell lung cancer cells, namely H441 (wild-type epidermal growth factor receptor, IC50 = 0.75 ?M) and H1975 (gefitnib-resistant mutant T790M, IC50 = 0.83 ?M). Antrocin dose dependently suppressed colony formation and induced apoptosis as evidenced by activated caspase-3 and increased Bax/Bcl2 ratio. Gene profiling studies indicated that antrocin downregulated Janus kinase/signal transducer and activator of transcription (JAK/STAT) signaling pathway. We further demonstrated that antrocin suppressed both constitutively activated and interleukin 6-induced STAT3 phosphorylation and its subsequent nuclear translocation. Such inhibition is found to be achieved through the suppression of JAK2 and interaction between STAT3 and extracellular signal-regulated kinase. Additionally, antrocin increased microRNA let-7c expression and suppressed STAT signaling. The combination of antrocin and JAK2/STAT3 gene silencing significantly increased apoptosis in H441 cells. Such dual interruption of JAK2 and STAT3 pathways also induced downregulation of antiapoptotic protein mcl-1 and increased caspase-3 expression. In vivo intraperitoneal administration of antrocin significantly suppressed the growth of lung cancer tumor xenografts. Our results indicate that antrocin may be a potential therapeutic agent for human lung cancer cells through constitutive inhibition of JAK2/STAT3 pathway.
Related JoVE Video
NMR structure and MD simulations of the AAA protease intermembrane space domain indicates peripheral membrane localization within the hexaoligomer.
FEBS Lett.
PUBLISHED: 07-16-2013
Show Abstract
Hide Abstract
We have determined the solution NMR structure of the intermembrane space domain (IMSD) of the human mitochondrial ATPase associated with various activities (AAA) protease known as AFG3-like protein 2 (AFG3L2). Our structural analysis and molecular dynamics results indicate that the IMSD is peripherally bound to the membrane surface. This is a modification to the location of the six IMSDs in a model of the full length yeast hexaoligomeric homolog of AFG3L2 determined at low resolution by electron cryomicroscopy [1]. The predicted protein-protein interaction surface, located on the side furthest from the membrane, may mediate binding to substrates as well as prohibitins.
Related JoVE Video
Solution NMR structure of CD1104B from pathogenic Clostridium difficile reveals a distinct ?-helical architecture and provides first structural representative of protein domain family PF14203.
J. Struct. Funct. Genomics
PUBLISHED: 07-03-2013
Show Abstract
Hide Abstract
A high-quality structure of the 68-residue protein CD1104B from Clostridium difficile strain 630 exhibits a distinct all ?-helical fold. The structure presented here is the first representative of bacterial protein domain family PF14203 (currently 180 members) of unknown function (DUF4319) and reveals that the side-chains of the only two strictly conserved residues (Glu 8 and Lys 48) form a salt bridge. Moreover, these two residues are located in the vicinity of the largest surface cleft which is predicted to contribute to a surface area involved in protein-protein interactions. This, along with its coding in transposon CTn4, suggests that CD1104B (and very likely all members of Pfam 14203) functions by interacting with other proteins required for the transfer of transposons between different bacterial species.
Related JoVE Video
Randomized controlled trials in bariatric surgery.
Obes Surg
PUBLISHED: 07-03-2013
Show Abstract
Hide Abstract
To fill a void in the literature, we performed a literature search and subsequently reviewed randomized controlled trials (RCTs) in the field of obesity surgery that were published over the past 40 years. All RCTs published in the English between January 1972 and December 2011 were identified through a literature search using the PubMed database. The following search terms were used: "bariatric surgery", "obesity surgery", and "weight reducing surgery". Studies of basic science and anesthesia-related pain management were excluded. The extracted trials were divided into four groups: comparisons of different interventions, intraoperative surgical techniques, preoperative evaluation, and postoperative care. The literature search produced 753 manuscripts, of which 168 met the eligibility criteria. Among 168 papers, 32 % compared different interventions, 48 % assessed intraoperative surgical techniques, 18 % assessed postoperative care, and the remaining 2 % assessed preoperative evaluation. The RCTs were published in 47 different journals, most commonly in Obesity Surgery (28.6 %) and the Annals of Surgery (11.9 %). Trials were conducted in 25 different countries, with the greatest contribution from the USA (35.1 %). There was a progressive increase in published trials from 1972 to 2011, with 119 RCTs (70.8 %) being published over the last decade. A trend for an increasing number of published RCTs in the field of bariatric surgery was observed over the recent years. Although data from large, adequately powered, long-term RCTs are still lacking, any surgical intervention appears to be more effective than medical care for the treatment of morbid obesity.
Related JoVE Video
TOP2A overexpression as a poor prognostic factor in patients with nasopharyngeal carcinoma.
Tumour Biol.
PUBLISHED: 06-24-2013
Show Abstract
Hide Abstract
Despite the advances in diagnostic imaging and treatment modalities, the risk stratification and final outcomes in patients with nasopharyngeal carcinomas (NPC) still remain suboptimal. Through data mining from published transcriptomic database, topoisomerase II? (TOP2A) was first identified as a differentially upregulated gene in NPC tissues, which implicates cell division via selective cleavage, rearrangement, and re-ligation of DNA strands. Given the roles of TOP2A in prognostication and in the frontline therapeutic regimen of common carcinomas, such as breast cancer, we explored TOP2A immunoexpression status and its associations with clinicopathological variables and survival in a well-defined cohort of NPC patients. TOP2A immunohistochemistry was retrospectively performed and analyzed using H-score method for biopsy specimens from 124 NPC patients who received standard treatment without distant metastasis at initial diagnosis. Those cases with H-score larger than the median value were construed as featuring TOP2A overexpression. The findings were correlated with the clinicopathological variables, disease-specific survival (DSS) and distant metastasis-free survival (DMFS). TOP2A overexpression was significantly associated with American Joint of Cancer Committee (AJCC) stages III-IV (p?=?0.019) and univariately predictive of adverse outcomes for DSS (p?=?0.0078) and DMFS (p?=?0.0003). In the multivariate comparison, TOP2A overexpression remained prognostically independent to portend worse DSS (p?=?0.047, hazard ratio?=?1.732) and DMFS (p?=?0.003, hazard ratio?=?2.569), together with advanced AJCC stages III-IV. TOP2A expression is upregulated in a subset of NPCs and its increased immunoexpression significantly correlated with advanced stages and tumor aggressiveness, justifying the potentiality of TOP2A as a prognostic biomarker and a novel therapeutic target of NPC.
Related JoVE Video
Deficiency in expression and epigenetic DNA Methylation of ASS1 gene in nasopharyngeal carcinoma: negative prognostic impact and therapeutic relevance.
Tumour Biol.
PUBLISHED: 06-13-2013
Show Abstract
Hide Abstract
The risk stratification and final outcomes in patients with nasopharyngeal carcinomas (NPC) still remain suboptimal. Our principal goals were to identify and validate targetable metabolic drivers relevant to pathogenesis of NPC using a published transcriptome. One prominently downregulated gene regulating amino acid metabolism was found to be argininosuccinate synthetase (ASS1). Attributable to epigenetic DNA methylation, ASS1 deficiency may link to the therapeutic sensitivity to the arginine-depriving agents and promote tumor aggressiveness through its newly identified tumor suppressor function. ASS1 immunohistochemistry was therefore examined in a well-defined cohort of 124 NPC biopsy specimens and in the neck lymph node metastases of another ten independent cases. For the latter, bisulphite pyrosequencing was performed to evaluate the extent of ASS1 gene methylation. ASS1 protein deficiency was identified in 64 of 124 cases (51.6 %), significantly related to T3-T4 status (p?=?0.006), and univariately associated with inferior local recurrence-free survival (p?=?0.0427), distant metastasis-free survival (DMFS; p?=?0.0036), and disease-specific survival (DSS; p?=?0.0069). Together with advanced AJCC stages III-IV, ASS1 protein deficiency was also independently predictive of worse outcomes for the DFMS (p?=?0.010, hazard ratio?=?2.241) and DSS (p?=?0.020, hazard ratio?=?1.900). ASS1 promoter hypermethylation was detected in eight of ten neck nodal metastatic lesions by bisulphite pyrosequencing and associated with ASS1 protein deficiency (p?
Related JoVE Video
Nicotinamide N-methyltransferase overexpression is associated with Akt phosphorylation and indicates worse prognosis in patients with nasopharyngeal carcinoma.
Tumour Biol.
PUBLISHED: 06-06-2013
Show Abstract
Hide Abstract
Nicotinamide N-methyltransferase (NNMT) is overexpressed in many human cancers and is associated with poor prognosis. Akt (also known as protein kinase B) is an evolutionarily conserved serine/threonine kinase, serving as a downstream effector of the phosphatidylinositol 3-kinase signaling pathway. NNMT was first identified as a differentially upregulated gene in nasopharyngeal cancer tissues through data mining from published transcriptomic databases. Since no prior study has attempted to evaluate the clinical significance of NNMT or phosphorylated Akt (pAkt) expression in nasopharyngeal cancer, this study explores their expression in a large cohort of patients with nasopharyngeal cancer. The study included 124 nasopharyngeal cancer patients who were free of distant metastasis at initial diagnosis. Pathological slides were reviewed and clinical findings collected. We evaluated the expression of NNMT and pAkt immunohistochemically, stratified them into two groups (high and low expression) and examined the correlation with disease-specific survival (DSS), metastasis-free survival (MeFS), local recurrence-free survival (LRFS), and various clinicopathological factors. NNMT expression was significantly positively associated with pAkt expression. The high expression of both markers was significantly associated with an increment of tumor stage (p?=?0.006 and p?=?0.006, respectively). High expression of NNMT correlated significantly with a more aggressive clinical course and a significantly shorter DSS. Furthermore, NNMT expression and pAkt expression were strongly predictive of MeFS (p?=?0.008; p?=?0.0063) and LRFS (p?=?0.005; p?=?0.0125). In multivariate analysis, high expression of NNMT remained as a robust prognosticator for both end points evaluated. It independently portended inferior DSS (p?=?0.02, HR?=?1.976) and worse MeFS (p?=?0.029, HR?=?2.022) after tumor stage (p?=?0.033, HR?=?2.150; p?=?0.028, HR?=?2.942, for DSS and LRFS, respectively). We found NNMT positively correlated with pAkt expression and was independent adverse prognosticators of patient survival. NNMT therefore has potential utility as an indicator for prognosis, predicting treatment response to chemotherapy or radiation therapy, and even as a therapeutic target in the future.
Related JoVE Video
Role of stress-inducible protein-1 in recruitment of bone marrow derived cells into the ischemic brains.
EMBO Mol Med
PUBLISHED: 05-15-2013
Show Abstract
Hide Abstract
Stress-inducible protein-1 (STI-1) is the proposed ligand for the cellular prion protein (PrP(C) ), which is thought to facilitate recovery following stroke. Whether STI-1 expression is affected by stroke and how its signalling facilitates recovery remain elusive. Brain slices from patients that died of ischemic stroke were collected for STI-1 immunohistochemistry. These findings were compared to results from cell cultures, mice with or without the PrP(C) knockout, and rats. Based on these findings, molecular and pharmacological interventions were administered to investigate the underlying mechanisms and to test the possibility for therapy in experimental stroke models. STI-1 was upregulated in the ischemic brains from humans and rodents. The increase in STI-1 expression in vivo was not cell-type specific, as it was found in neurons, glia and endothelial cells. Likewise, this increase in STI-1 expression can be mimicked by sublethal hypoxia in primary cortical cultures (PCCs) in vitro, and appear to have resulted from the direct binding of the hypoxia inducible factor-1? (HIF-1?) to the STI-1 promoter. Importantly, this STI-1 signalling promoted bone marrow derived cells (BMDCs) proliferation and migration in vitro and recruitment to the ischemic brain in vivo, and augmenting its signalling facilitated neurological recovery in part by recruiting BMDCs to the ischemic brain. Our results thus identified a novel mechanism by which ischemic insults can trigger a self-protective mechanism to facilitate recovery.
Related JoVE Video
MPT0B169, a new tubulin inhibitor, inhibits cell growth and induces G2/M arrest in nonresistant and paclitaxel-resistant cancer cells.
Pharmacology
PUBLISHED: 05-03-2013
Show Abstract
Hide Abstract
The polymerization of tubulin molecules forms microtubules which are considered an attractive target for cancer treatment. Herein, we synthesized a new tubulin inhibitor, MPT0B169 (2-dimethylamino-N-[1-(4-methoxy-benzenesulfonyl)-2,?3-dihydro-1H-indol-7-yl]-acetamide) and demonstrated its action in leukemia cell lines HL60 and NB4 and lymphoma cell line U937. We found that MPT0B169 prevented tubulin assembly by binding the colchicine-binding site of tubulin in vitro. MPT0B169 also induced tubulin depolymerization in vivo. MPT0B169 inhibited the growth of HL60, NB4, and U937 cells in dose- and time-dependent manners. It also inhibited the growth of paclitaxel-resistant cancer cells. In addition, MPT0B169 caused G2/M cell cycle arrest in nonresistant and paclitaxel-resistant cancer cells, with a concomitant increase in cyclin B1 levels and cyclin-dependent kinase 1 (CDK1) phosphorylation. These results suggest that MPT0B169, a tubulin inhibitor, inhibits cell growth and induces G2/M cell cycle arrest of cancer cells through the disruption of tubulin polymerization.
Related JoVE Video
A comparative study of primary and recurrent human glioblastoma multiforme using the small animal imaging and molecular expressive profiles.
Mol Imaging Biol
PUBLISHED: 05-01-2013
Show Abstract
Hide Abstract
Glioblastoma multiforme (GBM) is the most malignant brain tumor with the characteristics of highly infiltrative growth and recurrent rate. In this study, we used animal imaging and molecular expressive profiles to investigate the characteristics of the primary tumor (GBM-3) cells and recurrent tumor (S1R1) cells from different GBM patients.
Related JoVE Video
Clinicopathological significance of HuR expression in gallbladder carcinoma: with special emphasis on the implications of its nuclear and cytoplasmic expression.
Tumour Biol.
PUBLISHED: 04-21-2013
Show Abstract
Hide Abstract
Gallbladder carcinoma (GBC) is a relatively rare disease which pathogenesis is less clarified. Human antigen R (HuR), a RNA-binding protein, modulates the expressions of various cancer-related proteins by stabilizing or regulating the transcription of the corresponding messenger RNA. The significance of HuR expression in a large cohort with GBCs is yet to be evaluated. In total, 164 cases of GBC were selected, and immunostaining for HuR was performed. HuR nuclear (HuR-N) expression and HuR cytoplasmic (HuR-C) expression were evaluated by using a histochemical score. The results of HuR expression were correlated with various clinicopathological factors, disease-specific survival (DSS), and disease-free survival (DFS) in 161 patients with follow-up data. HuR-N overexpression was strongly associated with high histological grade (p = 0.001), vascular invasion (p < 0.001), and high Ki-67 labeling index (p < 0.001). HuR-C overexpression was significantly related to higher primary tumor status (p < 0.001), advanced tumor stage (p < 0.001), histological type (p = 0.006), high histological grade (p < 0.001), vascular and perineurial invasion (p < 0.001 and p = 0.002, respectively), tumor necrosis (p = 0.042), and high Ki-67 labeling index (p = 0.002). Besides, HuR-C overexpression also correlates with HuR-N overexpression (p < 0.001) and cyclin A overexpression (p = 0.026). HuR-N overexpression correlated with poor DFS (p = 0.0348) in univariate analysis, but HuR-C overexpression strongly correlated with a worse DSS and DFS in both univariate (both p < 0.0001) and multivariate (DSS, p = 0.006; DFS, p = 0.001) analyses. Subcellular localization of HuR expression correlates with different adverse phenotypes of GBC. Besides, HuR-C overexpression is an independent prognostic factor for dismal DSS and DFS, suggesting its roles in tumorigenesis or carcinogenesis and as a potential prognostic marker of GBC.
Related JoVE Video
Differential influences of gastric bypass and sleeve gastrectomy on plasma nesfatin-1 and obestatin levels in patients with type 2 diabetes mellitus.
Curr. Pharm. Des.
PUBLISHED: 04-16-2013
Show Abstract
Hide Abstract
The mechanisms by which bariatric surgeries, including gastric bypass (GB) and sleeve gastrectomy (SG), achieve remission of type 2 diabetes mellitus (T2DM) and sustained weight reduction are unknown. We hypothesized that the novel anorexic hormone nesfatin-1 and another new hormone obestatin might contribute to the marked improvement in glycemic homeostasis and weight loss in diabetics after GB and SG.
Related JoVE Video
simple hit counter

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.

How does it work?

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.