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.
Inverse correlation of phospho-KDR/Flk-1 expression and stage of colorectal cancer: implication of the significance of neoangiogenesis in activated VEGFR-2 expressing early stage colorectal adenocarcinomas.
Pol J Pathol
PUBLISHED: 11-06-2014
Show Abstract
Hide Abstract
The activation of vascular endothelial cell growth factor receptors (VEGFRs) plays an essential role in cancer progression. In this study, we investigated the expression of phosphorylated VEGFR-2 (or phospho-KDR/Flk-1), the activated form of VEGFR-2, in human colorectal adenomas and colorectal adenocarcinomas. Phospho-KDR/Flk-1 showed weak expression in the normal colorectal tissue. Phospho-KDR/Flk-1 was mainly stained in the cytoplasm of colorectal adenomas, and was stained in both the cytoplasm and nuclei colorectal adenocarcinomas. There was no indication of increased phospho-KDR/Flk-1 expression in the colorectal adenocarcinomas, as compared to that of colorectal adenomas. Furthermore, there was an inverse relationship of phospho-KDR/Flk-1 expression with cancer stage (p < 0.0001), lymph node metastasis (p = 0.011), and distant metastasis (p = 0.021) of the colorectal adenocarcinomas. Our results indicate that early stage colorectal adenocarcinomas with highly activated (phosphorylated) VEGFR-2 expression may indicate the significance of neoangiogenesis of the tumors.
Related JoVE Video
Hypoxic regulation of plasminogen activator inhibitor-1 expression in human buccal mucosa fibroblasts stimulated with arecoline.
J. Oral Pathol. Med.
PUBLISHED: 10-06-2014
Show Abstract
Hide Abstract
Oral submucous fibrosis (OSF) is regarded as a pre-cancerous condition with fibrosis in oral subepithelial connective tissue. Hypoxia-inducible factor (HIF)-1? regulates a wide variety of profibrogenic genes, which are closely associated with tissue fibrosis. The aim of this study was to compare HIF-1? expression in normal buccal mucosa tissues and OSF specimens and further explore the potential mechanisms that may lead to the induction of HIF-1? expression.
Related JoVE Video
Chemerin is a novel biomarker of acute coronary syndrome but not of stable angina pectoris.
Cardiovasc Diabetol
PUBLISHED: 10-04-2014
Show Abstract
Hide Abstract
BackgroundRecent evidence demonstrated that the circulating adipokines were associated with the onset of acute coronary syndrome (ACS) including unstable angina pectoris (UAP) and acute myocardial infarction (AMI). As a novel adipokine, chemerin has been related to atherosclerosis and the presence of coronary artery disease. However, the plasma levels of chemerin in patients with ACS have yet to be investigated.MethodsPlasma levels of chemerin and adiponectin were measured by an enzyme-linked immunosorbent assay (ELISA) in 60 patients with stable angina pectoris (SAP), 60 patients with UAP, 60 patients with AMI and 40 control patients. Left ventricular end-diastolic diameter (LVEDD) and left ventricular ejection fraction (LVEF) were measured using a GE ViVid E7 ultrasonography machine, and the severity of coronary stenosis in patients was estimated with a Gensini coronary score following coronary angiography.ResultsPlasma chemerin levels were significantly higher in ACS patients than in the control and SAP groups, while plasma adiponectin levels were significantly lower in ACS patients than the control group. A correlation analysis revealed that plasma chemerin levels were positively correlated with the levels of C-reactive protein (CRP) (r¿=¿0.29, P¿<¿0.01) and LVEDD (r¿=¿0.27, P¿<¿0.01) but negatively correlated with LVEF (r¿=¿-0.45, P¿<¿0.01) and that plasma adiponectin levels were positively correlated with LVEF (r¿=¿0.53, P¿<¿0.01) but negatively correlated with CRP (r¿=¿-0.33, P¿<¿0.01) and LVEDD (r¿=¿-0.30, P¿<¿0.01). Although significant correlations between chemerin, adiponectin and BMI or the Gensini coronary score were found in patients with SAP, neither chemerin nor adiponectin was correlated with BMI and the Gensini coronary score in patients with ACS. Furthermore, both chemerin (OR 1.103, 95% CI 1.065 to 1.142; P¿=¿0.001) and adiponectin (OR 0.871, 95% CI 0.776 to 0.970; P¿=¿0.018) were independently associated with the presence of ACS.ConclusionsChemerin is a novel biomarker of acute coronary syndrome but not of stable angina pectoris.
Related JoVE Video
Potential advantages of Chinese medicine Taohong Siwu Decoction () combined with tissue-plasminogen activator for alleviating middle cerebral artery occlusion-induced embolic stroke in rats.
Chin J Integr Med
PUBLISHED: 09-24-2014
Show Abstract
Hide Abstract
To investigate whether combination treatment with Taohong Siwu Decoction (, TSD) and recombinant tissue-type plasminogen activator (rt-PA) potentiate in reducing infarct volume and alleviate thromboembolic stroke in an in vivo rat model.
Related JoVE Video
The application of flow cytometry for evaluating biological aggressiveness of intracranial meningiomas.
Cytometry B Clin Cytom
PUBLISHED: 09-23-2014
Show Abstract
Hide Abstract
Meningiomas have classically been considered to include benign and atypical/anaplastic tumors. Despite the availability of clinical and pathologic parameters for prognostic prediction prognosis, the behavior of each meningioma may be difficult to predict. Here, we used DNA flow-cytometric studies to predict biological tumor behaviors of intracranial meningiomas.
Related JoVE Video
MALAT1 long non-coding RNA is overexpressed in multiple myeloma and may serve as a marker to predict disease progression.
BMC Cancer
PUBLISHED: 07-10-2014
Show Abstract
Hide Abstract
The pathogenesis of multiple myeloma involves complex genetic and epigenetic events. This study aimed to investigate the role and clinical relevance of the long non-coding RNA (lncRNA), metastasis-associated lung adenocarcinoma transcript 1 (MALAT1) in multiple myeloma.
Related JoVE Video
High-grade glioma in a patient with breast cancer.
Asian J Surg
PUBLISHED: 06-28-2014
Show Abstract
Hide Abstract
Breast cancer is one of the most common origins of metastatic lesions in the central nervous system. Many patients with a breast cancer and concurrent brain tumor(s) were diagnosed to have a metastatic lesion or lesions in the brain, based exclusively on their image findings without further pathologic verification, and received radiotherapy alone thereafter. It is, however, possible that a different pathology such as primary brain malignancy, which actually warrants a specific treatment modality, may occur in such patients with an already known malignancy. We, herein, reported a 61-year-old female patient who suffered from an anaplastic oligodendroglioma 1 year after her diagnosis of breast cancer. Demographic data, characteristic imaging findings, treatment, and outcome of the patient were discussed.
Related JoVE Video
Management of radicular cysts using platelet-rich fibrin and bioactive glass: a report of two cases.
J. Formos. Med. Assoc.
PUBLISHED: 06-26-2014
Show Abstract
Hide Abstract
Platelet-rich fibrin (PRF) created by Choukroun's protocol concentrates most platelets and leukocytes from a blood harvest into a single autologous fibrin biomaterial. However, no current data is available concerning the use of PRF for the treatment of periapical lesions. Two cases of radicular cysts were reported using an interdisciplinary approach, including regular endodontic therapy followed by surgical management with PRF and bioactive glass. Two cases of radicular cysts presented as an incidental radiographic finding, appearing as an apical radiolucency with well-circumscribed sclerotic borders. After regular endodontic retreatment, cystic lining/granulation tissues were enucleated and the periradicular bony defect was grafted using PRF and bioactive glass. Then, PRF was applied to serve as a membrane over the grafted defects. Recall periapical radiographs of Case 1 and cone beam computer tomography of Case 2 showed satisfactory healing of the periapical pathosis. In Case 2, the bony defect appeared completely healed at 4 months surgical reentry and the new bone was clinically very dense and mature. The results of these case reports show that the combination of PRF and bioactive glass is an effective modality of regenerative treatment for radicular cysts.
Related JoVE Video
Single-incision versus conventional laparoscopic appendectomy in 688 patients: a retrospective comparative analysis.
Can J Surg
PUBLISHED: 05-30-2014
Show Abstract
Hide Abstract
Laparoscopic surgery has become the standard for treating appendicitis. The cosmetic benefits of using single-incision laparoscopy are well known, but its duration, complications and time to recovery have not been well documented. We compared 2 laparoscopic approaches for treating appendicitis and evaluated postoperative pain, complications and time to full recovery.
Related JoVE Video
Testing Equality and Interval Estimation in Binary Responses When High Dose Cannot be Used First Under a Three Period Crossover Design.
J Biopharm Stat
PUBLISHED: 05-20-2014
Show Abstract
Hide Abstract
ABSTRACT When comparing two doses of a new drug with a placebo, we may consider using a crossover design subject to the condition that the high dose cannot be administered before the low dose. Under a random effects logistic regression model, we focus our attentions on dichotomous responses when the high dose cannot be used first under a three-period crossover trial. We derive asymptotic test procedures for testing equality between treatments. We further derive interval estimators to assess the magnitude of the relative treatment effects. We employ Monte Carlo simulation to evaluate the performance of these test procedures and interval estimators in a variety of situations. We use the data taken as a part of trial comparing two different doses of an analgesic with a placebo for the relief of primary dysmenorrhea to illustrate the use the proposed test procedures and estimators.
Related JoVE Video
Test Equality Between Two Binary Screening Tests with a Confirmatory Procedure Restricted on Screen Positives.
J Biopharm Stat
PUBLISHED: 05-20-2014
Show Abstract
Hide Abstract
SUMMARY In studies of screening accuracy, we may commonly encounter the data in which a confirmatory procedure is administered to only those subjects with screen positives for ethical concerns. We focus our discussion on simultaneously testing equality of sensitivity and specificity between two binary screening tests when only subjects with screen positives receive the confirmatory procedure. We develop four asymptotic test procedures and one exact test procedure. We derive sample size calculation formula for a desired power of detecting a difference at a given nominal[Formula: see text]-level. We employ Monte Carlo simulation to evaluate the performance of these test procedures and the accuracy of the sample size calculation formula developed here in a variety of situations. Finally, we use the data taken from a study of the prostate-specific-antigen (PSA) test and digital rectal examination (DRE) test on 949 black men to illustrate the practical use of these test procedures and the sample size calculation formula.
Related JoVE Video
Experimental demonstration of a tunable microwave undulator.
Phys. Rev. Lett.
PUBLISHED: 04-23-2014
Show Abstract
Hide Abstract
Static magnetic undulators used by x-ray light sources are fundamentally too limited to achieve shorter undulator periods and dynamic control. To overcome these limitations, we report experimental demonstration of a novel short-period microwave undulator, essentially a Thomson scattering device, that has yielded tunable spontaneous emission and seeded coherent radiation. Its equivalent undulator period (?u) is 13.9 mm while it has achieved an equivalent magnetic field of 0.65 T. For future-generation light sources, this device promises a shorter undulator period, a large aperture, and fast dynamic control.
Related JoVE Video
Eight Weeks of Esomeprazole Therapy Reduces Symptom Relapse, Compared with 4 Weeks, in Patients with Los Angeles Grade A or B Erosive Esophagitis.
Clin. Gastroenterol. Hepatol.
PUBLISHED: 04-11-2014
Show Abstract
Hide Abstract
There is disagreement over the ideal duration of initial proton pump inhibitor (PPI) therapy for gastroesophageal reflux disease, and whether prolonged therapy increases healing of the esophagitis and prevents symptom relapse. We performed a multicenter, prospective, randomized, controlled study to compare the efficacies of 4 weeks vs 8 weeks PPI therapy in reducing reflux symptoms and preventing symptom relapse in patients with Los Angeles grade A or B erosive esophagitis.
Related JoVE Video
Acute cerebral infarct with elevated factor VIII level during the thrombocytopenic stage after hematopoietic stem cell transplant.
Exp Clin Transplant
PUBLISHED: 04-08-2014
Show Abstract
Hide Abstract
Thromboembolism is a complication of hematopoietic stem cell transplant. However, a literature search showed no previous reports of cerebral infarction during the thrombocytopenic stage after hematopoietic stem cell transplant. A 35-year-old woman with acute lymphoblastic leukemia (precursor B-cell type) was treated with hematopoietic stem cell transplant after induction and consolidation chemotherapy. On day 2 after transplant, she was unconscious, and had urinary incontinence and left hemiplegia. A computed tomography scan of the brain showed an acute ischemic infarct in the right middle cerebral artery region and an old infarct at the left thalamus without atherosclerosis. Factor VIII level was elevated (190%; normal range, 60% to 150%). She was treated with rehabilitation and low-dose aspirin. At 6 months after transplant, the leukemia remained in remission and she had no further thromboembolic events. This case suggests that prudent treatment of patients who have hematopoietic stem cell transplant may include monitoring for thromboembolism and testing factor VIII level before transplant.
Related JoVE Video
A fluorescence turn-on probe for cysteine and homocysteine based on thiol-triggered benzothiazolidine ring formation.
Anal. Chim. Acta
PUBLISHED: 03-25-2014
Show Abstract
Hide Abstract
We synthesized a new coumarin-based probe TP, containing a disulfide moiety, to detect biothiols in cells. A fluorescence turn-on response is induced by the thiol-disulfide exchange of the probe, with subsequent intramolecular benzothiazolidine ring formation giving rise to a fluorescent product. The probe exhibits an excellent selectivity for cysteine (Cys) and homocysteine (Hcy) over glutathione (GSH) and other amino acids. The fluorescent probe also exhibits a highly sensitive fluorescence turn-on response to Cys and Hcy with detection limits of 0.8?M for Cys and 0.5?M for Hcy. In addition, confocal fluorescence microscopy imaging using RAW264.7 macrophages demonstrates that the probe TP could be an efficient fluorescent detector for thiols in living cells.
Related JoVE Video
Innovative strategy with potential to increase hemodialysis efficiency and safety.
Sci Rep
PUBLISHED: 03-04-2014
Show Abstract
Hide Abstract
Uremic toxins are mainly represented by blood urine nitrogen (BUN) and creatinine (Crea) whose removal is critically important in hemodialysis (HD) for kidney disease. Patients undergoing HD have a complex illness, resulting from: inadequate removal of organic waste, dialysis-induced oxidative stress and membrane-induced inflammation. Here we report innovative breakthroughs for efficient and safe HD by using a plasmon-induced dialysate comprising Au nanoparticles (NPs)-treated (AuNT) water that is distinguishable from conventional deionized (DI) water. The diffusion coefficient of K3Fe(CN)6 in saline solution can be significantly increased from 2.76, to 4.62 × 10(-6) cm s(-1), by using AuNT water prepared under illumination by green light-emitting diodes (LED). In vitro HD experiments suggest that the treatment times for the removals of 70% BUN and Crea are reduced by 47 and 59%, respectively, using AuNT water instead of DI water in dialysate, while additionally suppressing NO release from lipopolysaccharide (LPS)-induced inflammatory cells.
Related JoVE Video
Brazilin ameliorates high glucose-induced vascular inflammation via inhibiting ROS and CAMs production in human umbilical vein endothelial cells.
Biomed Res Int
PUBLISHED: 03-02-2014
Show Abstract
Hide Abstract
Vascular inflammatory process has been suggested to play a key role in the initiation and progression of atherosclerosis, a major complication of diabetes mellitus. Recent studies have shown that brazilin exhibits antihepatotoxic, antiplatelet, cancer preventive, or anti-inflammatory properties. Thus, we investigated whether brazilin suppresses vascular inflammatory process induced by high glucose (HG) in cultured human umbilical vein endothelial cells (HUVEC). HG induced nitrite production, lipid peroxidation, and intracellular reactive oxygen species formation in HUVEC cells, which was reversed by brazilin. Western blot analysis revealed that brazilin markedly inhibited HG-induced phosphorylation of endothelial nitric oxide synthase. Besides, we investigated the effects of brazilin on the MAPK signal transduction pathway because MAPK families are associated with vascular inflammation under stress. Brazilin blocked HG-induced phosphorylation of extracellular signal-regulated kinase and transcription factor NF-?B. Furthermore, brazilin concentration-dependently attenuated cell adhesion molecules (ICAM-1 and VCAM-1) expression induced by various concentrations of HG in HUVEC. Taken together, the present data suggested that brazilin could suppress high glucose-induced vascular inflammatory process, which may be closely related with the inhibition of oxidative stress, CAMs expression, and NF-?B activation in HUVEC. Our findings may highlight a new therapeutic intervention for the prevention of vascular diseases.
Related JoVE Video
Factors predicting recurrence and postrecurrence survival in completely resected thymic carcinoma.
Ann. Thorac. Surg.
PUBLISHED: 02-12-2014
Show Abstract
Hide Abstract
There are few data on factors predicting recurrence of completely resected thymic carcinoma. This study analyzed prognosticators for recurrence and postrecurrence survival.
Related JoVE Video
Clinical outcomes of robot-assisted intersphincteric resection for low rectal cancer: comparison with conventional laparoscopy and multifactorial analysis of the learning curve for robotic surgery.
Int J Colorectal Dis
PUBLISHED: 02-11-2014
Show Abstract
Hide Abstract
This study evaluated the feasibility of robot-assisted intersphincteric resection (ISR) for low rectal cancer. Further, we attempted to analyze the learning curve for robotic surgery.
Related JoVE Video
Increased expression of carbonic anhydrase IX in oral submucous fibrosis and oral squamous cell carcinoma.
Clin. Chem. Lab. Med.
PUBLISHED: 02-07-2014
Show Abstract
Hide Abstract
Cumulative evidence has demonstrated that carbonic anhydrase IX (CAIX) is upregulated in many types of human cancers. We attempted to evaluate plasma levels of CAIX in patients with oral cancer and investigated whether plasma CAIX is correlated with the progression of this disease.
Related JoVE Video
Successful treatment of oral verrucous hyperplasia with photodynamic therapy combined with cryotherapy--report of 3 cases.
Photodiagnosis Photodyn Ther
PUBLISHED: 02-06-2014
Show Abstract
Hide Abstract
Our previous study showed successful treatment of a large oral verrucous hyperplasia (OVH) with topical 5-aminolevulinic acid-mediated photodynamic therapy combined with cryotherapy (ALA-PDT). In this case series, we extended this combined method for another three OVH lesions in three different patients. The clinical procedure was conducted as follows: the OVH lesions were irradiated with a 635-nm laser 1.5h after topical application of 20% ALA on the lesion for a total of 1000 s, which consisted of five 3-min and one 100-s irradiations separated by five 3-min rests. Cryogun cryotherapy was then performed on the lesion after ALA-PDT. The tumor was cleared after 1-6 treatments. No recurrence of the lesion was found after a follow-up period of 6-24 months. We suggest that our combined treatment protocol may be effective in treating OVH lesions.
Related JoVE Video
Weakly supervised histopathology cancer image segmentation and classification.
Med Image Anal
PUBLISHED: 01-28-2014
Show Abstract
Hide Abstract
Labeling a histopathology image as having cancerous regions or not is a critical task in cancer diagnosis; it is also clinically important to segment the cancer tissues and cluster them into various classes. Existing supervised approaches for image classification and segmentation require detailed manual annotations for the cancer pixels, which are time-consuming to obtain. In this paper, we propose a new learning method, multiple clustered instance learning (MCIL) (along the line of weakly supervised learning) for histopathology image segmentation. The proposed MCIL method simultaneously performs image-level classification (cancer vs. non-cancer image), medical image segmentation (cancer vs. non-cancer tissue), and patch-level clustering (different classes). We embed the clustering concept into the multiple instance learning (MIL) setting and derive a principled solution to performing the above three tasks in an integrated framework. In addition, we introduce contextual constraints as a prior for MCIL, which further reduces the ambiguity in MIL. Experimental results on histopathology colon cancer images and cytology images demonstrate the great advantage of MCIL over the competing methods.
Related JoVE Video
A two-layer structure prediction framework for microscopy cell detection.
Comput Med Imaging Graph
PUBLISHED: 01-25-2014
Show Abstract
Hide Abstract
The task of microscopy cell detection is of great biological and clinical importance. However, existing algorithms for microscopy cell detection usually ignore the large variations of cells and only focus on the shape feature/descriptor design. Here we propose a new two-layer model for cell centre detection by a two-layer structure prediction framework, which is respectively built on classification for the cell centres implicitly using rich appearances and contextual information and explicit structural information for the cells. Experimental results demonstrate the efficiency and effectiveness of the proposed method over competing state-of-the-art methods, providing a viable alternative for microscopy cell detection.
Related JoVE Video
Interleukin 10 and clustering of metabolic syndrome components in pediatrics.
Eur. J. Clin. Invest.
PUBLISHED: 01-23-2014
Show Abstract
Hide Abstract
Interleukin 10 (IL-10) has multifaceted anti-inflammatory properties that are known to regulate insulin sensitivity and atherosclerotic development. However, studies in children are limited and have yielded conflicting results. The aim of this study was to evaluate whether changes in this circulating anti-inflammatory cytokine is a marker for metabolic syndrome.
Related JoVE Video
Notes on testing equality and interval estimation in Poisson frequency data under a three-treatment three-period crossover trial.
Stat Methods Med Res
PUBLISHED: 01-21-2014
Show Abstract
Hide Abstract
When the frequency of event occurrences follows a Poisson distribution, we develop procedures for testing equality of treatments and interval estimators for the ratio of mean frequencies between treatments under a three-treatment three-period crossover design. Using Monte Carlo simulations, we evaluate the performance of these test procedures and interval estimators in various situations. We note that all test procedures developed here can perform well with respect to Type I error even when the number of patients per group is moderate. We further note that the two weighted-least-squares (WLS) test procedures derived here are generally preferable to the other two commonly used test procedures in the contingency table analysis. We also demonstrate that both interval estimators based on the WLS method and interval estimators based on Mantel-Haenszel (MH) approach can perform well, and are essentially of equal precision with respect to the average length. We use a double-blind randomized three-treatment three-period crossover trial comparing salbutamol and salmeterol with a placebo with respect to the number of exacerbations of asthma to illustrate the use of these test procedures and estimators.
Related JoVE Video
Characteristics of endogenous ?-aminobutyric acid (GABA) in human platelets: functional studies of a novel collagen glycoprotein VI inhibitor.
J. Mol. Med.
PUBLISHED: 01-13-2014
Show Abstract
Hide Abstract
gamma-Aminobutyric acid (GABA) is the major inhibitory neurotransmitter in the central nervous system, and it also appears in peripheral tissues. Platelets are anuclear blood cells that play a central role in hemostatic processes. Although platelets possess a GABA uptake system, the functional activity of GABA in platelets has remained unclear. We determined that GABA is abundantly distributed in the platelets at a concentration of approximately 1.03 ng/10(6) cells. GABA (0.5 ?M) specifically inhibited collagen-induced platelet activation accompanied by [Ca(2+)]i mobilization, phospholipase C?2, protein kinase C, Akt phosphorylation, and hydroxyl radical formation. In addition, GABA interfered with fluorescein isothiocyanate-collagen binding to platelet membranes and produced a concentration-dependent shift in the collagen concentration-response curve and a Schild plot slope of -0.96?±?0.11, indicating competitive inhibition. Platelet activation induced by convulxin, a glycoprotein VI agonist, was inhibited by GABA, whereas activation induced by the integrin ?(2)?(1) agonist, aggretin, was not. Immunoprecipitation and surface plasmon resonance revealed that GABA binds directly to glycoprotein VI in human platelets with equilibrium dissociation (binding) constant (K(D)) of 41.4 nM. The closure time of whole blood and the occlusion time of platelet plug formation were significantly prolonged by GABA in vivo. In this study, GABA is a specific inhibitor of collagen glycoprotein VI and may be involved in an endogenous negative feedback mechanism for platelet activation. Thus, GABA may represent a potential target for the development of novel interventions for the treatment of cardiovascular diseases associated with platelet activation, such as stroke and myocardial infarction.
Related JoVE Video
CDKN1A-mediated responsiveness of MLL-AF4-positive acute lymphoblastic leukemia to Aurora kinase-A inhibitors.
Int. J. Cancer
PUBLISHED: 01-13-2014
Show Abstract
Hide Abstract
Overexpression of Aurora kinases is largely observed in many cancers, including hematologic malignancies. In this study, we investigated the effects and molecular mechanisms of Aurora kinase inhibitors in acute lymphoblastic leukemia (ALL). Western blot analysis showed that both Aurora-A and Aurora-B are overexpressed in ALL cell lines and primary ALL cells. Both VE-465 and VX-680 effectively inhibited Aurora kinase activities in nine ALL cell lines, which exhibited different susceptibilities to the inhibitors. Cells sensitive to Aurora kinase inhibitors underwent apoptosis at an IC50 of ?10-30 nM and displayed a phenotype of Aurora-A inhibition, whereas cells resistant to Aurora kinase inhibitors (with an IC50 more than 10 ?M) accumulated polyploidy, which may have resulted from Aurora-B inhibition. Drug susceptibility of ALL cell lines was not correlated with the expression level or activation status of Aurora kinases. Interestingly, RS4;11 and MV4;11 cells, which contain the MLL-AF4 gene, were both sensitive to Aurora kinase-A inhibitors treatment. Complementary DNA (cDNA) microarray analysis suggested that CDKN1A might govern the drug responsiveness of ALL cell lines in a TP53-independent manner. Most importantly, primary ALL cells with MLL-AF4 and CDKN1A expression were sensitive to Aurora kinase inhibitors. Our study suggests CDKN1A could be a potential biomarker in determining the drug responsiveness of Aurora kinase inhibitors in ALL, particularly in MLL-AF4-positive patients.
Related JoVE Video
Mechanisms of ascorbyl radical formation in human platelet-rich plasma.
Biomed Res Int
PUBLISHED: 01-09-2014
Show Abstract
Hide Abstract
Recently, many clinical reports have suggested that the ascorbyl free radical (Asc(?)) can be treated as a noninvasive, reliable, real-time marker of oxidative stress, but its generation mechanisms in human blood have rarely been discussed. In this study, we used upstream substances, enzyme inhibitors, and free radical scavengers to delineate the mechanisms of Asc(?) formation in human platelet-rich plasma (PRP). Our results show that the doublet signal was detected in PRP samples by using electron spin resonance, and the hyperfine splitting of the doublet signal was a(H) = 1.88 gauss and g-factor = 2.00627, which was determined to be the Asc(?). We observed that the inhibitors of NADPH oxidase (NOX), cyclooxygenase (COX), lipoxygenase (LOX), cytochrome P450 (CYP450), mitochondria complex III, and nitric oxide synthase (NOS), but not xanthine oxidase, diminished the intensity of the Asc(?) signal dose dependently. All enzyme inhibitors showed no obvious antioxidant activity during a Fenton reaction assay. In summary, the obtained data suggest that Asc(?) formation is associated with NOX, COX, LOX, CYP450, eNOS, and mitochondria in human PRP.
Related JoVE Video
Arecoline-induced myofibroblast transdifferentiation from human buccal mucosal fibroblasts is mediated by ZEB1.
J. Cell. Mol. Med.
PUBLISHED: 01-08-2014
Show Abstract
Hide Abstract
Oral submucous fibrosis (OSF) is considered as a pre-cancerous condition of the oral mucosa and is highly associated with habitual areca quid chewing. Arecoline is the major alkaloid in areca quid and is thought to be involved in the pathogenesis of OSF. Our previous studies have demonstrated that arecoline could induce epithelial-mesenchymal transition (EMT)-related factors in primary human buccal mucosal fibroblasts (BMFs). Therefore, we investigated the expression of zinc finger E-box binding homeobox 1 (ZEB1), which is a well-known transcriptional factor in EMT, in OSF tissues and its role in arecoline-induced myofibroblast transdifferentiation from BMFs. The expression of ZEB1, as well as the myofibroblast marker ?-smooth muscle actin (?-SMA), was significantly increased in OSF tissues, respectively. With immunofluorescence analysis, arecoline induced the formation of ?-SMA-positive stress fibres in BMFs expressing nuclear ZEB1. Arecoline also induced collagen contraction of BMFs in vitro. By chromatin immunoprecipitation, the binding of ZEB1 to the ?-SMA promoter in BMFs was increased by arecoline. The promoter activity of ?-SMA in BMFs was also induced by arecoline, while knockdown of ZEB1 abolished arecoline-induced ?-SMA promoter activity and collagen contraction of BMFs. Long-term exposure of BMFs to arecoline induced the expression of fibrogenic genes and ZEB1. Silencing of ZEB1 in fibrotic BMFs from an OSF patient also suppressed the expression of ?-SMA and myofibroblast activity. Inhibition of insulin-like growth factor receptor-1 could suppress arecoline-induced ZEB1 activation in BMFs. Our data suggest that ZEB1 may participate in the pathogenesis of areca quid-associated OSF by activating the ?-SMA promoter and inducing myofibroblast transdifferentiation from BMFs.
Related JoVE Video
Anatomical entity recognition with a hierarchical framework augmented by external resources.
PLoS ONE
PUBLISHED: 01-01-2014
Show Abstract
Hide Abstract
References to anatomical entities in medical records consist not only of explicit references to anatomical locations, but also other diverse types of expressions, such as specific diseases, clinical tests, clinical treatments, which constitute implicit references to anatomical entities. In order to identify these implicit anatomical entities, we propose a hierarchical framework, in which two layers of named entity recognizers (NERs) work in a cooperative manner. Each of the NERs is implemented using the Conditional Random Fields (CRF) model, which use a range of external resources to generate features. We constructed a dictionary of anatomical entity expressions by exploiting four existing resources, i.e., UMLS, MeSH, RadLex and BodyPart3D, and supplemented information from two external knowledge bases, i.e., Wikipedia and WordNet, to improve inference of anatomical entities from implicit expressions. Experiments conducted on 300 discharge summaries showed a micro-averaged performance of 0.8509 Precision, 0.7796 Recall and 0.8137 F1 for explicit anatomical entity recognition, and 0.8695 Precision, 0.6893 Recall and 0.7690 F1 for implicit anatomical entity recognition. The use of the hierarchical framework, which combines the recognition of named entities of various types (diseases, clinical tests, treatments) with information embedded in external knowledge bases, resulted in a 5.08% increment in F1. The resources constructed for this research will be made publicly available.
Related JoVE Video
Interruption and non-adherence to long-term adjuvant hormone therapy is associated with adverse survival outcome of breast cancer women--an Asian population-based study.
PLoS ONE
PUBLISHED: 01-01-2014
Show Abstract
Hide Abstract
This study aimed to evaluate the survival rate of women with breast cancer (BC) comparing persistence versus interruption and adherence versus non-adherence to adjuvant hormonal therapy (HT) in Asian population. Newly-diagnosed BC women from 2003 to 2010 were retrospectively identified from the Taiwan National Health Insurance Research Database. HT prescriptions were extracted to define treatment interruption and medication possession ratio. Their impacts on mortality were estimated by Cox regression with time dependent covariates. Interruption (HR: 1.32; 95% CI: 1.20, 1.46; P<0.0001) and non-adherence (HR: 1.45; 95% CI: 1.32, 1.59; P<0.0001) to adjuvant HT were significantly associated with increased mortality. Interruption to tamoxifen in younger patients and in patients receiving surgery (OP) with adjuvant chemotherapy (CT) was associated with increasing mortality rate when compared with their counterparts. Non-adherence to AIs in both younger and senior age groups and in OP with CT group also resulted in increasing risk. Treatment interruption and non-adherence to adjuvant HT were found to be associated with the increasing all-cause mortality of the Asian BC women; a greater impact of interruption and non-adherence on mortality was especially found in the younger BC population.
Related JoVE Video
Oct4 mediates tumor initiating properties in oral squamous cell carcinomas through the regulation of epithelial-mesenchymal transition.
PLoS ONE
PUBLISHED: 01-01-2014
Show Abstract
Hide Abstract
Overexpression of Oct4, an important transcription factor of embryonic stem cells (ESC), has been reported in several cancers. The aim of this study was to determine the emerging role of Oct4 in oral squamous cell carcinoma (OSCC) both in vitro and in vivo.
Related JoVE Video
Melatonin improves neuroplasticity by upregulating the growth-associated protein 43 (GAP-43) and NMDAR-post-synaptic density-95 (PSD95) proteins in cultured neurons exposed to glutamate excitotoxicity and in rats subjected to transient focal cerebral isch
J. Pineal Res.
PUBLISHED: 11-04-2013
Show Abstract
Hide Abstract
Recent evidence shows that the NMDAR-post-synaptic density-95 (PSD95), growth-associated protein 43 (GAP-43) and matrix metalloproteinase-9 (MMP-9) protein enhance neuroplasticity at the subacute stage of stroke. Here, we evaluated whether melatonin would modulate the PSD95, GAP-43 and MMP-9 proteins in cultured neurons exposed to glutamate excitotoxicity and in rats subjected to experimental stroke. Adult male Sprague-Dawley rats were treated with melatonin (5 mg/kg) or vehicle at reperfusion onset after transient occlusion of the right middle cerebral artery (tMCAO) for 90 min. Animals were euthanized for Western immunoblot analyses for the PSD-95 and GAP-43 proteins and gelatin zymography for the MMP-9 activity at 7-day post-insult. Another set of animals was sacrificed for histologic and Golgi-Cox-impregnated sections at 28 days post-insult. In cultured neurons exposed to glutamate excitotoxicity, melatonin significantly up-regulated the GAP-43 and PSD-95 expressions and improved dendritic aborizations (P < 0.05, respectively). Relative to controls, melatonin-treated stroke animals caused a significant improvement of GAP-43 and PSD-95 expressions as well as the MMP-9 activity in the ischemic brain (P < 0.05). Consequently, melatonin also significantly promoted the dendritic spine density and reduced infarction in the ischemic brain, and improved neurobehaviors as well at 28 days post-insult (P < 0.05, respectively). Together, melatonin upregulates GAP-43, PSD-95 and MMP-9 proteins, which likely accounts for its actions to improve neuroplasticity in cultured neurons exposed to glutamate excitotoxicity, and to enhance long-term neuroprotection, neuroplasticity and brain remodeling in stroke rats. This article is protected by copyright. All rights reserved.
Related JoVE Video
High nuclear phosphorylated extracellular signal-regulated kinase expression associated with poor differentiation, larger tumor size, and an advanced stage of breast cancer.
Pol J Pathol
PUBLISHED: 10-30-2013
Show Abstract
Hide Abstract
Extracellular signal-regulated kinase (ERK1/2) is implicated in the malignant behavior of breast cancer cells. However, previous clinical-pathological studies have shown that expression of activated/phosphorylated ERK1/2 is not associated with enhanced proliferation and invasion of mammary carcinomas. ERK1/2 is expressed in the cytoplasm, and activated/phosphorylated ERK1/2 translocates to the nucleus. The aim of this study is to evaluate nuclear phosphorylated ERK1/2 as a biomarker for breast cancer prognosis. The clinical-pathological relation of cytoplasmic/nuclear phosphorylated ERK1/2 was analyzed in 105 surgically resected breast cancer specimens by immunohistochemistry with tissue microarray. The results showed that non-neoplastic breast tissue mainly showed faint phosphorylated ERK1/2 staining. No statistically significant association was found between the level of cytoplasmic phosphorylated ERK1/2 expression and the clinical features of the disease. High nuclear phosphorylated ERK1/2 expression was associated with high grade (poor differentiation, p = = 0.010), high T status (larger tumor size, p = 0.033), and an advanced stage (p = 0.018) of the disease. Thus, nuclear phosphorylated ERK1/2 is associated with enhanced proliferation and invasion of mammary carcinomas and may be a biomarker for breast cancer prognosis and the determination of therapeutic strategies.
Related JoVE Video
Notes on testing noninferiority in ordinal data under the parallel groups design.
J Biopharm Stat
PUBLISHED: 10-22-2013
Show Abstract
Hide Abstract
When testing the noninferiority of an experimental treatment to a standard (or control) treatment in a randomized clinical trial (RCT), we may come across the outcomes of patient response on an ordinal scale. We focus our discussion on testing noninferiority in ordinal data for an RCT under the parallel groups design. We develop simple test procedures based on the generalized odds ratio (GOR). We note that these test procedures not only can account for the information on the order of ordinal responses without assuming any specific parametric structural model, but also can be independent of any arbitrarily subjective scoring system. We further develop sample size determination based on the test procedure using the GOR. We apply Monte Carlo simulation to evaluate the performance of these test procedures and the accuracy of sample size calculation formula proposed here in a variety of situations. Finally, we employ the data taken from a trial comparing once-daily gatifloxican with three-times-daily co-amoxiclav in the treatment of community-acquired pneumonia to illustrate the use of these test procedures and sample size calculation formula.
Related JoVE Video
Trimethoprim/sulfamethoxazole-related acute psychosis in the second course of treatment after a stem cell transplant: case report and literature review.
Exp Clin Transplant
PUBLISHED: 10-17-2013
Show Abstract
Hide Abstract
The case report describes a woman who has an acute psychosis episode during the second course of trimethoprim/sulfamethoxazole therapy, after having an allogeneic hematopoietic stem cell transplant that favored a dose-related effect of this adverse effect.
Related JoVE Video
Outcome of allotransplants in patients with chronic-phase chronic myeloid leukemia following imatinib failure: prognosis revisited.
Anticancer Res.
PUBLISHED: 10-15-2013
Show Abstract
Hide Abstract
The outcome of allotransplants in patients with chronic -phase (CP) chronic myeloid leukemia (CML) who progressed to accelerated phase (AP) or blast phase (BP) following imatinib failure, especially those without preceding suboptimal response, remains unclear.
Related JoVE Video
Hematopathologic discrepancies between referral and review diagnoses: a gap between general pathologists and hematopathologists.
Leuk. Lymphoma
PUBLISHED: 09-05-2013
Show Abstract
Hide Abstract
The World Health Organization (WHO) lymphoma classification has been widely adopted by hematopathologists. However, its practical application by general pathologists is largely unknown. Using a hematopathology consultation program in Taiwan, we reviewed 406 cases. Diagnostic discrepancies were scored based upon whether the divergence would alter disease management according to National Comprehensive Cancer Network guidelines. Major discrepancies accounted for 55% (222/406), minor discrepancies for 5% (20/406) and agreement for 40% (164/406) cases. The more common groups in major discrepancies were non-diagnostic/ambiguous referral reports (116/222, 52%), tumor type revisions (52/222, 23%) and changes from malignant to benign lesions (32/222, 14%). In a total of 259 cases of lymphoma, the concordance rates were 41% (77/187) and 33% (24/72) for B-cell and T/natural killer (NK)-cell lymphomas, respectively. It appears that the WHO approach has made lymphoma classification rather poorly reproducible at least in countries where extensive use of an ancillary technique is not employed by general pathologists.
Related JoVE Video
Hodgkins lymphoma-related vanishing bile duct syndrome: a case report and literature review.
Kaohsiung J. Med. Sci.
PUBLISHED: 08-09-2013
Show Abstract
Hide Abstract
We report the case of a 38-year-old man who developed vanishing bile duct syndrome in association with Hodgkins lymphoma. He was noted to have cervical lymphadenopathy and marked elevation of total serum bilirubin at diagnosis. He achieved complete remission with normalization of serum bilirubin after eight courses of Adriamycin, bleomycin, vinblastine, and dacarbazine chemotherapy followed with autologous hematopoietic cell transplantation. Consecutive liver biopsies performed at diagnosis and at the stage of complete remission revealed the disappearance and regeneration of interlobular bile ducts, respectively. Our case provides pathological evidence that Hodgkins lymphoma-related vanishing bile duct syndrome is a reversible bile duct injury disease. Bilirubin is a reliable serum marker to monitor the treatment response of these cases. The mechanism to develop hyperbilirubinemia with vanishing bile duct in such a case of Hodgkins lymphoma remains to be studied. A literature review was carried out.
Related JoVE Video
Cytotoxicity and genotoxicity of triethyleneglycol-dimethacrylate in macrophages involved in DNA damage and caspases activation.
Environ. Toxicol.
PUBLISHED: 08-08-2013
Show Abstract
Hide Abstract
Triethyleneglycol-dimethacrylate (TEGDMA) is a monomer and widely used in dental composite resins. TEGDMA has been found to exhibit cytotoxicity and genotoxicity on many cells. However, little is known about the potential toxicological implications of TEGDMA on murine macrophage cell line RAW264.7. In this study, TEGDMA demonstrated a cytotoxic effect to RAW264.7 cells in a concentration- and time-dependent manner (p?
Related JoVE Video
Multi-label classification for colon cancer using histopathological images.
Microsc. Res. Tech.
PUBLISHED: 08-03-2013
Show Abstract
Hide Abstract
Colon cancer classification has a significant guidance value in clinical diagnoses and medical prognoses. The classification of colon cancers with high accuracy is the premise of efficient treatment. Our task is to build a system for colon cancer detection and classification based on slide histopathological images. Some former researches focus on single label classification. Through analyzing large amount of colon cancer images, we found that one image may contain cancer regions of multiple types. Therefore, we reformulated the task as multi-label problem. Four kinds of features (Color Histogram, Gray-Level Co-occurrence Matrix, Histogram of Oriented Gradients and Euler number) were introduced to compose our discriminative feature set, extracted from our dataset that includes six single categories and four multi-label categories. In order to evaluate the performance and make comparison with our multi-label model, three commonly used multi-classification methods were designed in our experiment including one-against-all SVM (OAA), one-against-one SVM (OAO) and multi-structure SVM. Four indicators (Precision, Recall, F-measure, and Accuracy) under 3-fold cross-validation were used to validate the performance of our approach. Experiment results show that the precision, recall and F-measure of multi-label method as 73.7%, 68.2%, and 70.8% with all features, which are higher than the other three classifiers. These results demonstrate the effectiveness and efficiency of our method on colon histopathological images analysis.
Related JoVE Video
Lessons we learn from hematopathology consultation in Taiwan.
J. Formos. Med. Assoc.
PUBLISHED: 07-21-2013
Show Abstract
Hide Abstract
The appropriate management of hematology patients depends first on correct diagnoses. Expert review is important in reaching accurate diagnoses. To improve diagnostic accuracy, the Taiwan Society of Pathology and the Taiwan Division of the International Academy of Pathology has been conducting an expert consultation program for general pathologists since 2001. As per this program, we have received a total of 395 cases (406 samples) for review. We found that meaningful diagnostic discrepancies occurred frequently in hematopathology reviews. Ambiguous or nondiagnostic original reports were the major causative factor for the major discrepancy cases, which demonstrates that diagnostic uncertainty is a big problem for referring pathologists. However, the World Health Organization lymphoma classification may be poorly reproducible in countries where extensive use of an ancillary technique is not used by general pathologists. This review is intended to report the misdiagnoses most commonly seen in the hematopathology practice in Taiwan. Awareness of the easily misinterpreted entities helps to achieve the right diagnosis and improve patient care.
Related JoVE Video
Monoclonality and cytogenetic abnormalities in hyaline vascular Castleman disease.
Mod. Pathol.
PUBLISHED: 07-04-2013
Show Abstract
Hide Abstract
Hyaline vascular Castleman disease is traditionally regarded as a reactive hyperplastic process. Occasional cases, however, have been reported with cytogenetic anomalies bringing this concept into question. In this study, we used conventional and methylation-specific polymerase chain reaction methods to assess the human androgen receptor ? (HUMARA) gene in 29 female patients with hyaline vascular Castleman disease and compared the results with three cases of plasma cell Castleman disease and 20 cases of age-matched lymphoid hyperplasia. We also assessed for immunoglobulin gene and T-cell receptor gene rearrangements, and conventional cytogenetic analysis was performed in three cases of hyaline vascular Castleman disease. In cases with informative results, conventional and methylation-specific human androgen receptor ? gene analyses yielded a monoclonal pattern in 10 of 19 (53%) and 17 of 23 (74%) cases of hyaline vascular Castleman disease, respectively. A monoclonal pattern was also detected in three cases of plasma cell Castleman disease but not in cases of lymphoid hyperplasia. The frequency of monoclonality was higher for lesions >5?cm in size (100%) and for the stromal-rich variant (91%). Cytogenetic abnormalities in stromal cells were revealed in two cases of hyaline vascular Castleman disease and no cases showed monoclonal immunoglobulin or T-cell receptor gene rearrangements. Follow-up data showed persistent disease in 4 of 23 (17%) patients. We conclude that hyaline vascular Castleman disease is often a monoclonal proliferation, most likely of lymph node stromal cells.Modern Pathology advance online publication, 8 November 2013; doi:10.1038/modpathol.2013.202.
Related JoVE Video
A gene expression signature of epithelial tubulogenesis and a role for ASPM in pancreatic tumor progression.
Gastroenterology
PUBLISHED: 06-25-2013
Show Abstract
Hide Abstract
Many patients with pancreatic ductal adenocarcinoma (PDAC) develop recurrent or metastatic diseases after surgery, so it is important to identify those most likely to benefit from aggressive therapy. Disruption of tissue microarchitecture is an early step in pancreatic tumorigenesis and a parameter used in pathology grading of glandular tumors. We investigated whether changes in gene expression during pancreatic epithelial morphogenesis were associated with outcomes of patients with PDAC after surgery.
Related JoVE Video
CSE1L modulates Ras-induced cancer cell invasion: correlation of K-Ras mutation and CSE1L expression in colorectal cancer progression.
Am. J. Surg.
PUBLISHED: 06-24-2013
Show Abstract
Hide Abstract
Ras plays an important role in colorectal cancer progression. CSE1L (chromosome segregation 1-like) gene maps to 20q13, a chromosomal region that correlates with colorectal cancer development. We investigated the association of CSE1L with Ras in colorectal cancer progression.
Related JoVE Video
Five interval estimators of the risk difference under stratified randomized clinical trials with noncompliance and repeated measurements.
J Biopharm Stat
PUBLISHED: 06-22-2013
Show Abstract
Hide Abstract
We often employ stratified analysis to control the confounding effect due to centers in a multicenter trial or the confounding effect due to trials in a meta-analysis. On the basis of a general risk additive model, we focus discussion on interval estimation of the risk difference (RD) in repeated binary measurements under a stratified randomized clinical trial (RCT) in the presence of noncompliance. We develop five asymptotic interval estimators for the RD in closed form. These include the interval estimator using the weighted least-squares (WLS) estimator, the WLS interval estimator with tanh (-1)(x) transformation, the Mantel-Haenszel (MH) type interval estimator, the MH interval estimator with tanh (-1)(x) transformation, and the interval estimator using the idea of Fiellers theorem and a randomization-based variance. We employ Monte Carlo simulation to study and compare the finite-sample performance of these interval estimators in a variety of situations. We include an example studying the use of macrophage colony-stimulating factor to reduce the risk of febrile neutropenia events in acute myeloid leukaemia patients published elsewhere to illustrate the use of these estimators.
Related JoVE Video
Optimal allocation of sample sizes to multicenter clinical trials.
J Biopharm Stat
PUBLISHED: 06-22-2013
Show Abstract
Hide Abstract
In this article, we discuss an approach for optimal sample size allocation in designing multicenter clinical trials. The method we studied was adapted from a stratified sampling survey design. The sample size allocated to centers is a function of the centers treatment cost, the standard deviation of the endpoint, and the availability of patients. We illustrate our approach using two hypothetical scenarios derived from our experiences in designing and conducting multicenter clinical trials. Simulation results are also presented.
Related JoVE Video
A novel bioactivity of andrographolide from Andrographis paniculata on cerebral ischemia/reperfusion-induced brain injury through induction of cerebral endothelial cell apoptosis.
Pharm Biol
PUBLISHED: 06-12-2013
Show Abstract
Hide Abstract
Andrographolide, extracted from the leaves of Andrographis paniculata (Burm. f.) Nees (Acanthaceae), is a labdane diterpene lactone. It is widely reported to possess anti-inflammatory and antitumorigenic activities. Cerebral endothelial cells (CECs) play a crucial role in supporting the integrity and the function of the blood-brain barrier (BBB). However, no data are available concerning the effects of andrographolide in CECs. The aim of this study was to examine the detailed mechanisms of andrographolide on CECs.
Related JoVE Video
Imatinib adherence associated clinical outcomes of chronic myeloid leukaemia treatment in Taiwan.
Int J Clin Pharm
PUBLISHED: 05-31-2013
Show Abstract
Hide Abstract
Background Since the launch of imatinib, chronic myeloid leukaemia has become a chronic condition requiring costly long-term treatment. Emerging evidence from several short-term studies has raised concerns on the detrimental clinical outcomes and waste of resources associated with poor adherence to imatinib. Objective This study aims to evaluate the effects of long-term imatinib adherence on clinical treatment responses and mortality. Setting This retrospective cohort study was conducted in a medical centre in southern Taiwan. Method Chronic myeloid leukaemia patients who were prescribed for more than 1 month of imatinib were identified and their medical charts were reviewed from the first date of imatinib prescription to the last date of medical record or upon patients death. Patients basic characteristics, imatinib prescriptions, results of laboratory tests, episodes of imatinib-related side effects and mortality rate were recorded. Main outcome measure Participants basic characteristics, medication possession ratio and their mortality rate; the association between the medication possession ratio and treatment responses. Results Of the 119 included patients, the mean follow-up time was 3.9 ± 2.9 patient-years and the mean medication possession ratio was 89.7 %. At the 18th month of imatinib treatment, 67.2, 54.3 and 34.5 % patients achieved complete cytogenetic, major molecular and complete molecular responses, respectively. There was a significant difference in the 4-year survival rate between the adherence (n = 87) and non-adherence (n = 32) groups (91 vs. 72 %; p = 0.0076). Logistic regression analysis revealed that imatinib adherence was the only factor that significantly influenced the 18th month complete cytogenetic response [odds ratio (OR) 11.6; 95 % confidence interval (CI) 1.7, 114.7; p = 0.0131] and major molecular response (OR 5.1; 95 % CI 1.1, 26.8; p = 0.0351). Cox regression analysis demonstrated that a medication possession ratio greater than 90 % significantly reduced the mortality risk (hazard ratio 0.1; 95 % CI 0.01, 0.60; p = 0.0118). Conclusion Chronic myeloid leukaemia patients long-term adherence to imatinib is significantly associated with the 18th month treatment responses including the cytogenetic response, molecular response and the long-term survival rate in clinical practice.
Related JoVE Video
Disease acceptance and adherence to imatinib in Taiwanese chronic myeloid leukaemia outpatients.
Int J Clin Pharm
PUBLISHED: 05-31-2013
Show Abstract
Hide Abstract
Background The launch of imatinib has turned chronic myeloid leukaemia (CML) into a chronic illness due to the dramatic improvement in survival. Several recent studies have demonstrated that poor adherence to imatinib may hamper the therapeutic outcomes and result in increased medical expenditures, whilst research on exploring the reasons for non-adherence to imatinib is still limited. Objective This study aimed to explore the experience of patients as they journey through their CML treatments and associated imatinib utilisation in order to understand the perceptions, attitudes and concerns that may influence adherence to imatinib treatment. Setting This study was conducted at oncology outpatient clinics in a medical centre in southern Taiwan. Methods CML patients who regularly attended the oncology outpatient clinics to receive imatinib treatment from October 2011 to March 2012 were invited to participate in the study. Semi-structured face-to-face interviews were used to explore patients experiences and views of their treatment, their current CML status and CML-related health conditions, their concerns about imatinib treatment and imatinib-taking behaviours. Patient interviews were recorded, transcribed verbatim and thematically analysed using the constant comparison approach. Main outcome measure Themes related to patients views of the disease and health conditions, worries and concerns influencing imatinib utilisation behaviours are reported. Results Forty-two CML patients participated in the interviews. The emerging themes included: acceptance of current disease and health status, misconceptions about disease progression, factors associated with adherence to imatinib, concerns and management of adverse drug effects. Participants regarded CML as a chronic disease but had misconceptions about disease progression, therapeutic monitoring, resistance to imatinib and symptoms of side effects. Participants were generally adherent to imatinib and favoured long-term prescriptions to avoid regular outpatient visits for medication refills. Experiencing adverse effect was the main reason influencing adherence and led to polypharmacy. Most participants altered medicine-taking behaviours to maintain long-term use of imatinib. Conclusion Taiwanese CML patients are adherent to imatinib but report changing their medication-taking behaviour due to adverse drug effects and associated polypharmacy. Patients misconceptions of the disease and medication suggests that it is necessary to improve communication between patients and healthcare professionals. Routinely providing updated information as part of the patient counselling process should be considered as a means of improving this communication.
Related JoVE Video
Human BDH2, an anti-apoptosis factor, is a novel poor prognostic factor for de novo cytogenetically normal acute myeloid leukemia.
J. Biomed. Sci.
PUBLISHED: 05-30-2013
Show Abstract
Hide Abstract
The relevance of recurrent molecular abnormalities in cytogenetically normal (CN) acute myeloid leukemia (AML) was recently acknowledged by the inclusion of molecular markers such as NPM1, FLT3, and CEBPA as a complement to cytogenetic information within both the World Health Organization and the European Leukemia Net classifications. Mitochondrial metabolism is different in cancer and normal cells. A novel cytosolic type 2-hydroxybutyrate dehydrogenase, BDH2, originally named DHRS6, plays a physiological role in the cytosolic utilization of ketone bodies, which can subsequently enter mitochondria and the tricarboxylic acid cycle. Moreover, BDH2 catalyzes the production of 2, 3-DHBA during enterobactin biosynthesis and participates in 24p3 (LCN2)-mediated iron transport and apoptosis.
Related JoVE Video
The Frequencies of Gastroesophageal and Extragastroesophageal Symptoms in Patients with Mild Erosive Esophagitis, Severe Erosive Esophagitis, and Barretts Esophagus in Taiwan.
Gastroenterol Res Pract
PUBLISHED: 05-29-2013
Show Abstract
Hide Abstract
Background. Gastroesophageal reflux disease (GERD) may present with gastroesophageal and extraesophageal symptoms. Currently, the frequencies of gastroesophageal and extragastroesophageal symptoms in Asian patients with different categories of GERD remain unclear. Aim. To investigate the frequencies of gastroesophageal and extragastroesophageal symptoms in patients with mild erosive esophagitis, severe erosive esophagitis, and Barretts esophagus of GERD. Methods. The symptoms of symptomatic subjects with (1) Los Angeles grade A/B erosive esophagitis, (2) Los Angeles grade C/D erosive esophagitis, and (3) Barretts esophagus proven by endoscopy were prospectively assessed by a standard questionnaire for gastroesophageal and extragastroesophageal symptoms. The frequencies of the symptoms were compared by Chi-square test. Result. Six hundred and twenty-five patients (LA grade A/B: 534 patients; LA grade C/D: 37 patients; Barretts esophagus: 54 patients) were assessed for gastroesophageal and extragastroesophageal symptoms. Patients with Los Angeles grade A/B erosive esophagitis had higher frequencies of symptoms including epigastric pain, epigastric fullness, dysphagia, and throat cleaning than patients with Los Angeles grade C/D erosive esophagitis. Patients with Los Angeles grade A/B erosive esophagitis also had higher frequencies of symptoms including acid regurgitation, epigastric acidity, regurgitation of food, nausea, vomiting, epigastric fullness, dysphagia, foreign body sensation of throat, throat cleaning, and cough than patients with Barretts esophagus. Conclusion. The frequencies of some esophageal and extraesophageal symptoms in patients with Los Angeles grade A/B erosive esophagitis were higher than those in patients with Los Angeles grade C/D erosive esophagitis and Barretts esophagus. The causes of different symptom profiles in different categories of GERD patients merit further investigations.
Related JoVE Video
miR-320 regulates tumor angiogenesis driven by vascular endothelial cells in oral cancer by silencing neuropilin 1.
Angiogenesis
PUBLISHED: 05-11-2013
Show Abstract
Hide Abstract
Tumor angiogenesis is a critical process during cancer progression that modulates tumor growth and metastasis. Here, we identified an anti-angiogenic microRNA, miR-320, which is decreased in oral squamous cell carcinoma (OSCC) cell lines and tumor tissues from OSCC patients, down-regulated in blood vessels and inversely correlated with vascularity in OSCC tissues. Neuropilin 1 (NRP1), an important regulator of angiogenesis, was found to be a target of miR-320. The 3-untranslated region of NRP1 mRNA contains multiple miR-320 binding sites, and its expression was regulated by miR-320. By administering either miR-320 precursor or antagonist, we found that miR-320 suppressed the migration, adhesion and tube formation of vascular endothelial cells. Knockdown of NRP1 abolished antagomiR-320-induced cell migration. Additionally, miR-320 expression was regulated by hypoxia in growth factor-deficient conditions by the hypoxia-inducible factor 1-alpha. Furthermore, lentivirus carrying the miR-320 precursor suppressed the tumorigenicity of OSCC cells and tumor angiogenesis in vivo. Taken together, these data show that miR-320 regulates the function of vascular endothelial cells by targeting NRP1 and has the potential to be developed as an anti-angiogenic or anti-cancer drug.
Related JoVE Video
Relation between fetuin-A levels and fibroblast growth factor 23 with the severity of coronary artery disease measured by SYNTAX scores.
Am. J. Cardiol.
PUBLISHED: 05-08-2013
Show Abstract
Hide Abstract
Diagnosis of coronary artery disease requires invasive procedures that are typically not implemented until clinical warning signs are apparent. The goal of this study was to determine the relation between the severity of coronary artery disease, as measured by the SYNTAX scoring system, with serum levels of fetuin-A and fibroblast growth factor 23 (FGF23) in the general population. We enrolled 165 patients who had stable angina and positive results on treadmill testing or abnormal results on thallium myocardial perfusion scanning showing perfusion defects or who had acute coronary syndromes. Patients were hospitalized for evaluation with angiography, with or without simultaneous percutaneous coronary intervention. SYNTAX Scores were calculated on the basis of the results of coronary angiography using a computer-based questionnaire of sequential and interactive self-guided questions. Univariate analysis was used to assess the significance of fetuin-A and FGF23, as well as gender, age, body mass index, waist circumference, diabetes, hypertension, creatinine, total cholesterol, cholesterol, triglycerides, and high-sensitivity C-reactive protein in relation to cardiovascular disease severity. Multivariate analysis with stepwise regression was used to assess the utility of fetuin-A and FGF23 as predictors of SYNTAX Score. Multivariate analysis showed log fetuin-A to be a significant predictor of SYNTAX Score (p <0.0001) after controlling for the significant factors gender, cholesterol levels, and log high-sensitivity C-reactive protein. Log FGF23 values were also shown by multivariate regression to significantly predict SYNTAX Score (p = 0.0137) after controlling for gender, creatinine, cholesterol, and log high-sensitivity C-reactive protein. In conclusion, fetuin-A and FGF23 can be considered in combination with noninvasive test results as patient selection criteria for performing angiography.
Related JoVE Video
Notes on interval estimation of the generalized odds ratio under stratified random sampling.
J Biopharm Stat
PUBLISHED: 04-25-2013
Show Abstract
Hide Abstract
It is not rare to encounter the patient response on the ordinal scale in a randomized clinical trial (RCT). Under the assumption that the generalized odds ratio (GOR) is homogeneous across strata, we consider four asymptotic interval estimators for the GOR under stratified random sampling. These include the interval estimator using the weighted-least-squares (WLS) approach with the logarithmic transformation (WLSL), the interval estimator using the Mantel-Haenszel (MH) type of estimator with the logarithmic transformation (MHL), the interval estimator using Fiellers theorem with the MH weights (FTMH) and the interval estimator using Fiellers theorem with the WLS weights (FTWLS). We employ Monte Carlo simulation to evaluate the performance of these interval estimators by calculating the coverage probability and the average length. To study the bias of these interval estimators, we also calculate and compare the noncoverage probabilities in the two tails of the resulting confidence intervals. We find that WLSL and MHL can generally perform well, while FTMH and FTWLS can lose either precision or accuracy. We further find that MHL is likely the least biased. Finally, we use the data taken from a study of smoking status and breathing test among workers in certain industrial plants in Houston, Texas, during 1974 to 1975 to illustrate the use of these interval estimators.
Related JoVE Video
Notes on testing noninferiority in multivariate binary data under the matched-pair design.
Stat Methods Med Res
PUBLISHED: 03-15-2013
Show Abstract
Hide Abstract
Since therapeutic efficacy is often measured by multiple endpoints, it will be of use if one can incorporate the information on various variables of response into procedures for testing noninferiority to improve power of a univariate test procedure for each individual variable. On the basis of the proposed mixed effects logistic regression model for multivariate binary data under the matched-pairs design, we develop procedures for testing noninferiority with respect to the odds ratio in multivariate binary data under the matched-pair design. We discuss use of Bonferronis and Scheffes methods to control the inflation in Type I error due to multiple tests. We further employ Monte Carlo simulation to evaluate and compare the performance of these test procedures. Finally, we use the data taken from a crossover clinical trial that monitored several adverse events of an antidepressive drug to illustrate the use of test procedures derived here.
Related JoVE Video
Aqueous Extract of Solanum nigrum Leaves Induces Autophagy and Enhances Cytotoxicity of Cisplatin, Doxorubicin, Docetaxel, and 5-Fluorouracil in Human Colorectal Carcinoma Cells.
Evid Based Complement Alternat Med
PUBLISHED: 03-14-2013
Show Abstract
Hide Abstract
Colorectal cancer is a common cancer worldwide, and chemotherapy is a mainstream approach for advanced and recurrent cases. Development of effective complementary drugs could help improve tumor suppression efficiency and control adverse effects from chemotherapy. The aqueous extract of Solanum nigrum leaves (AE-SN) is an essential component in many traditional Chinese medicine formulas for treating cancer, but there is a lack of evidence verifying its tumor suppression efficacy in colorectal cancer. The purpose of this study is to evaluate the tumor suppression efficacy of AE-SN using DLD-1 and HT-29 human colorectal carcinoma cells and examine the combined drug effect when combined with the chemotherapeutic drugs cisplatin, doxorubicin, docetaxel, and 5-fluorouracil. The results indicated that AE-SN induced autophagy via microtubule-associated protein 1 light chain 3 A/B II accumulation but not caspase-3-dependent apoptosis in both cell lines. The IC50s after 48 hours of treatment were 0.541 and 0.948?mg/ml AE-SN in DLD-1 and HT-29, respectively. AE-SN also demonstrated a combined drug effect with all tested drugs by enhancing cytotoxicity in tumor cells. Our results suggest that AE-SN has potential in the development of complementary chemotherapy for colorectal cancer.
Related JoVE Video
An end-to-end system to identify temporal relation in discharge summaries: 2012 i2b2 challenge.
J Am Med Inform Assoc
PUBLISHED: 03-06-2013
Show Abstract
Hide Abstract
To create an end-to-end system to identify temporal relation in discharge summaries for the 2012 i2b2 challenge. The challenge includes event extraction, timex extraction, and temporal relation identification.
Related JoVE Video
Silencing glucose-regulated protein 78 induced renal cell carcinoma cell line G1 cell-cycle arrest and resistance to conventional chemotherapy.
Urol. Oncol.
PUBLISHED: 02-18-2013
Show Abstract
Hide Abstract
Glucose-regulated protein 78 (Grp78) is an endoplasmic reticulum chaperone; it maintains endoplasmic reticulum homeostasis and modulates unfolded protein response. The protein is overexpressed in various cancer types, including renal cell carcinoma (RCC). Increased Grp78 expression in patients with RCC is correlated with more aggressive tumors and poorer prognoses. This study investigated the role of Grp78 in regulating tumorigenesis and evaluated the potential of Grp78-targeted therapy for RCC.
Related JoVE Video
Effects of self-regulation protocol on physiological and psychological measures in patients with chronic obstructive pulmonary disease.
J Clin Nurs
PUBLISHED: 02-07-2013
Show Abstract
Hide Abstract
This study presents a discussion of the physiological and psychological efficacy of a self-regulation protocol in lowering acute exacerbation symptoms in patients with chronic obstructive pulmonary disease.
Related JoVE Video
High-gain Thompson-scattering x-ray free-electron laser by time-synchronic laterally tilted optical wave.
Phys. Rev. Lett.
PUBLISHED: 02-05-2013
Show Abstract
Hide Abstract
A novel approach to generating coherent x rays with 10(9)-10(10) photons and femtoseconds duration per laser pulse is proposed. This high intensity x-ray source is realized first by the pulse front tilt of a lateral fed laser to extend the electron-laser synchronic interaction time by several orders, which accomplishes the high-gain free-electron-laser-type exponential growth process and coherent emission with highly microbunched electron beam. Second, two methods are presented to enhance the effective optical undulator strength parameter. One is to invoke lenses to focus two counterpropagating lasers that are at normal incidence to the electron beam as a transverse standing wave; the other is to invent a periodic microstructure that can significantly enhance the center electromagnetic field realized by a resonant standing wave and the quadrupole waveguides. The energy coupling efficiency between the electron beam and laser is therefore greatly improved to generate the high brightness x rays, which is demonstrated by analytical and simulation results.
Related JoVE Video
Elevation of S100A4 expression in buccal mucosal fibroblasts by arecoline: involvement in the pathogenesis of oral submucous fibrosis.
PLoS ONE
PUBLISHED: 01-31-2013
Show Abstract
Hide Abstract
S100A4, a member of the calcium-binding proteins, is dramatically elevated in a variety of fibrotic diseases. Areca quid chewing is the most important etiological factor in the pathogenesis of oral submucous fibrosis (OSF). OSF has been considered as a pre-cancerous condition of oral mucosa. The aim of this study was to determine the critical role of S100A4 expression in the pathogenesis of OSF both in vitro and in vivo.
Related JoVE Video
Clinical efficacy of the Er:YAG laser treatment on hypersensitive dentin.
J. Formos. Med. Assoc.
PUBLISHED: 01-25-2013
Show Abstract
Hide Abstract
Dentin hypersensitivity is a common symptomatic condition that causes discomfort and sometimes severe pain. The purpose of this study was to evaluate the clinical efficacy of the erbium-doped:yttrium, aluminum, and garnet (Er:YAG) laser treatment on cervically exposed hypersensitive dentin. Twenty patients with dentin hypersensitivity of caries-free teeth were selected. A visual analog scale (VAS) was used to measure dentin sensitivity in response to air stimulus. A 2-minute Er:YAG laser (energy level: 60 mJ/pulse; repetition rate: 2 Hz) was applied to cervically exposed hypersensitive dentin. After 4 weeks, the hypersensitive teeth were examined again, and the VAS score was measured again and recorded. No complications such as detrimental pulpal effects were observed. Eighteen participants reported significantly reduced dentin hypersensitivity 4 weeks after the laser desensitization treatment. The VAS scores measured 4 weeks after the Er:YAG laser desensitization treatment were significantly decreased as compared with those measured at the baseline (p < 0.05). In conclusion, the Er:YAG laser desensitization treatment can effectively reduce hypersensitivity of cervically exposed hypersensitive dentin.
Related JoVE Video
Association between interleukin 1beta and interleukin 10 concentrations: a cross-sectional study in young adolescents in Taiwan.
BMC Pediatr
PUBLISHED: 01-24-2013
Show Abstract
Hide Abstract
In adults, low circulating interleukin 10 (IL10) has been associated with obesity and type 2 diabetes. However, studies investigating IL10 in overweight and obese children have yielded conflicting results. The aim of this study was to investigate factors associated with serum IL10 concentration in young Chinese adolescents.
Related JoVE Video
Pathogenesis of viruses-associated human cancers: Epstein-Barr virus and hepatitis B virus as two examples.
J. Formos. Med. Assoc.
PUBLISHED: 01-21-2013
Show Abstract
Hide Abstract
Virus-associated human cancers may exhibit two characteristic histopathologic features: (1) the inflammation-rich background as observed in Epstein-Barr virus-associated Hodgkin lymphoma (HL) and nasopharyngeal carcinoma (NPC); and (2) the characteristic nuclear morphology such as the Reed-Sternberg cells in HL. Besides, the hepatocytes of chronic hepatitis B virus (HBV) infection frequently exhibit characteristic ground glass hepatocytes, a phenomenon associated with endoplasmic reticulum stress response induced by the overloaded or malfolded HBV surface antigens. In this review, we explore specifically the pathogenesis of Epstein-Barr virus-associated HL and NPC, and HBV-associated hepatocellular carcinoma based on the observed histopathologic features. We propose that the retention of viral proteins induces inflammation, endoplasmic reticulum stress, and genomic instability in HL, NPC, and hepatocellular carcinoma, whereby the viral oncoproteins may play additional transactivational roles to induce host genes for transformation, invasion, and metastasis. Therapeutic implications based on the pathogenesis of virus-associated cancers are discussed.
Related JoVE Video
Testing and estimation of proportion (or risk) ratio under the matched-pair design with multiple binary endpoints.
Biom J
PUBLISHED: 01-20-2013
Show Abstract
Hide Abstract
The proportion ratio (PR) of responses between an experimental treatment and a control treatment is one of the most commonly used indices to measure the relative treatment effect in a randomized clinical trial. We develop asymptotic and permutation-based procedures for testing equality of treatment effects as well as derive confidence intervals of PRs for multivariate binary matched-pair data under a mixed-effects exponential risk model. To evaluate and compare the performance of these test procedures and interval estimators, we employ Monte Carlo simulation. When the number of matched pairs is large, we find that all test procedures presented here can perform well with respect to Type I error. When the number of matched pairs is small, the permutation-based test procedures developed in this paper is of use. Furthermore, using test procedures (or interval estimators) based on a weighted linear average estimator of treatment effects can improve power (or gain precision) when the treatment effects on all response variables of interest are known to fall in the same direction. Finally, we apply the data taken from a crossover clinical trial that monitored several adverse events of an antidepressive drug to illustrate the practical use of test procedures and interval estimators considered here.
Related JoVE Video
Clinicopathological correlation and prognostic significance of protein kinase c? overexpression in human gastric carcinoma.
PLoS ONE
PUBLISHED: 01-16-2013
Show Abstract
Hide Abstract
This study investigated the PKC? protein expression in gastric carcinoma, and correlated it with clinicopathological parameters. The prognostic significance of PKC? protein expression in gastric carcinoma was analyzed.
Related JoVE Video
Correlations between cytoplasmic CSE1L in neoplastic colorectal glands and depth of tumor penetration and cancer stage.
J Transl Med
PUBLISHED: 01-16-2013
Show Abstract
Hide Abstract
Colorectal carcinomas spread easily to nearby tissues around the colon or rectum, and display strong potential for invasion and metastasis. CSE1L, the chromosome segregation 1-like protein, is implicated in cancer progression and is located in both the cytoplasm and nuclei of tumor cells. We investigated the prognostic significance of cytoplasmic vs. nuclear CSE1L expression in colorectal cancer.
Related JoVE Video
MDM2 promoter polymorphism and p53 codon 72 polymorphism in chronic myeloid leukemia: The association between MDM2 promoter genotype and disease susceptibility, age of onset, and blast-free survival in chronic phase patients receiving imatinib.
Mol. Carcinog.
PUBLISHED: 01-15-2013
Show Abstract
Hide Abstract
The genetic or functional inactivation of the p53 pathway plays an important role with regards to disease progression from the chronic phase (CP) to blast phase (BP) and imatinib treatment response in chronic myeloid leukemia (CML). Two functional single nucleotide polymorphisms (SNPs), p53 R72P and MDM2 SNP309, are associated with alternation of p53 activity, however the association regarding CML susceptibility and BP transformation under imatinib treatment is unclear. The MDM2 SNP309 genotype was determined by polymerase chain reaction-restriction fragment length polymorphism and confirmed by direct sequencing from 116 CML patients, including 104 in the CP at diagnosis, and 162 healthy Taiwanese controls. The p53 R72P polymorphism was examined in all CML patients. The SNP309 G/G genotype was associated with an increased risk of CML susceptibility (OR: 1.82, 95% CI: 1.03-3.22, P?=?0.037), and an earlier age of disease onset (log-rank P?=?0.005) compared with the T/T?+?T/G genotypes. Higher MDM2 mRNA expression was found in G/G genotype compared with T/T (P?=?0.034) and T/T?+?T/G (P?=?0.056) genotypes. No associations were found between the p53 R72P genotypes and clinical parameters and survival outcomes. Among 62 CP patients receiving imatinib as first-line therapy, the G/G genotype was associated with a shorter blast-free survival (log-rank P?=?0.048) and more clonal evolution compared with the T/T?+?T/G genotypes. In patients with advanced diseases at diagnosis, the G/G genotype was associated with a poor overall survival (log-rank P?=?0.006). Closely monitoring CML patients harboring the G/G genotype and further large-scale studies are warranted. © 2013 Wiley Periodicals, Inc.
Related JoVE Video

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.