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Find video protocols related to scientific articles indexed in Pubmed.
Effects of Palm and Sunflower Oils on Serum Cholesterol and Fatty Liver in Rats.
J Med Food
PUBLISHED: 11-14-2014
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Abstract Palm oil is a common cooking ingredient used in the commercial food industry as the second largest consumed vegetable oil in the world. Because of its lower cost and highly saturated nature, it usually maintains a solid form at room temperature and is used as a cheap substitute for butter. However, there has been a growing health concern about palm oil because of the link between dietary fats and coronary heart disease. Palm oil contains ?49% saturated fat, a relatively high concentration compared with other vegetable oils. Consequently, high intakes of saturated fat from palm oil induce a larger increase in plasma concentrations of total cholesterol and low-density lipoproteins. In the present study, we examined the hyperlipidemia of palm oil and the risk of cardiovascular disease (CVD) using a rat model in comparison with sunflower oil with a relatively low level of saturated fat. On in vivo examination using Sprague-Dawley (SD) rats for 22 days, there were no significant differences in serum lipid levels, suggesting that palm oil may not cause hyperlipidemia and elevate CVD risk. However, liver samples obtained from SD rats fed with palm oil showed a lot of large lipid inclusions stained with the Oil Red O working solution, but not much lipid accumulation was observed in rats treated with sunflower oil. In addition, lipid accumulation in the mixed oil group fed the combination of palm and sunflower (1:1) oil was shown to be at an intermediary level between the palm oil group and sunflower oil group. Taken together, these results indicate that palm oil, a highly saturated form of vegetable oil, may induce dysfunction of the liver lipid metabolism before affecting serum lipid levels. On the other hand, sunflower oil, a highly unsaturated vegetable oil, was shown to be well metabolized in liver.
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Transcriptional program of Kpna2/Importin-?2 regulates cellular differentiation-coupled circadian clock development in mammalian cells.
Proc. Natl. Acad. Sci. U.S.A.
PUBLISHED: 11-13-2014
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The circadian clock in mammalian cells is cell-autonomously generated during the cellular differentiation process, but the underlying mechanisms are not understood. Here we show that perturbation of the transcriptional program by constitutive expression of transcription factor c-Myc and DNA methyltransferase 1 (Dnmt1) ablation disrupts the differentiation-coupled emergence of the clock from mouse ESCs. Using these model ESCs, 484 genes are identified by global gene expression analysis as factors correlated with differentiation-coupled circadian clock development. Among them, we find the misregulation of Kpna2 (Importin-?2) during the differentiation of the c-Myc-overexpressed and Dnmt1(-/-) ESCs, in which sustained cytoplasmic accumulation of PER proteins is observed. Moreover, constitutive expression of Kpna2 during the differentiation culture of ESCs significantly impairs clock development, and KPNA2 facilitates cytoplasmic localization of PER1/2. These results suggest that the programmed gene expression network regulates the differentiation-coupled circadian clock development in mammalian cells, at least in part via posttranscriptional regulation of clock proteins.
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New Bipolar Host Materials for Realizing Blue Phosphorescent Organic Light-Emitting Diodes with High Efficiency at 1000 cd/m(2.)
ACS Appl Mater Interfaces
PUBLISHED: 11-06-2014
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New host molecules such as 9-(6-(9H-carbazol-9-yl)pyridin-3-yl)-6-(9H-carbazol-9-yl)-9H-pyrido[2,3-b]indole (pPCB2CZ) and 9-(6-(9H-carbazol-9-yl)pyridin-2-yl)-6-(9H-carbazol-9-yl)-9H-pyrido[2,3-b]indole (mPCB2CZ) were designed and synthesized for blue phosphorescent organic light-emitting diodes (PhOLEDs). The glass transition temperatures of two host molecules were measured higher than 120 °C, and the identical triplet energies were determined to be 2.92 eV for both molecules. The bis(3,5-difluoro-2-(2-pyridyl)phenyl-(2-carboxypyridyl)iridium(III) (FIrpic)-doped mPCB2CZ-based PhOLED exhibited practically useful driving voltage of 4.8 V in a simple organic three layer device configuration which has a smaller number of interfaces in conventional multilayer PhOLEDs. Also, the high quantum efficiency of 23.7% is reported at the practically useful brightness value of 1000 cd/m(2).
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A Novel Electrode With Electromagnetic Tip Tracking in Ultrasonography-Guided Radiofrequency Ablation: A Phantom, Ex Vivo, and In Vivo Experimental Study.
Invest Radiol
PUBLISHED: 11-01-2014
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The objective of this study was to compare the targeting and ablation performance between a newly developed radiofrequency (RF) electrode embedded with an electromagnetic position sensor (EMPS) at the electrode tip and a conventional RF electrode.
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Peptides with the same composition, hydrophobicity, and hydrophobic moment bind to phospholipid bilayers with different affinities.
J Phys Chem B
PUBLISHED: 10-20-2014
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We investigated the dependence of membrane binding on amino acid sequence for a series of amphipathic peptides derived from ?-lysin. ?-Lysin is a 26 amino acid, N-terminally formylated, hemolytic peptide that forms an amphipathic ?-helix bound at membrane-water interfaces. A shortened peptide, lysette, was derived from ?-lysin by deletion of the four N-terminal amino acid residues. Five variants of lysette were synthesized by altering the amino acid sequence such that the overall hydrophobic moment remained essentially the same for all peptides. Peptide-lipid equilibrium dissociation constants and helicities of peptides bound to zwitterionic lipid vesicles were determined by stopped-flow fluorescence and circular dichroism. We found that binding to phosphatidylcholine bilayers was a function of the helicity of the bound peptide alone and independent of the a priori hydrophobic moment or the ability to form intramolecular salt bridges. Molecular dynamics (MD) simulations on two of the peptides suggest that sequence determines the insertion depth into the bilayer. The location of the two aspartate residues at the C-terminus of lysette-2 leads to a loss of helical content in the simulations, which correlates with faster desorption from the bilayer as compared to lysette. We also found a systematic deviation of the experimentally determined dissociation constant and that predicted by the Wimley-White interfacial hydrophobicity scale. The reason for the discrepancy remains unresolved but appears to correlate with a predominance of isoleucine over leucine residues in the lysette family of peptides.
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Salmonella osteomyelitis of the femoral diaphysis in a healthy individual.
Am J. Orthop.
PUBLISHED: 10-11-2014
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In reviewing the literature, we found few cases of Salmonella osteomyelitis of the femoral diaphysis in a healthy patient. Most are typically associated with sickle cell anemia or immunosuppressed patients. We report on the successful treatment of Salmonella osteomyelitis in the mid-diaphyseal region of the femur caused by Salmonella species in a healthy individual.
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Comparison of the Cardiac MicroPET Images Obtained Using [(18)F]FPTP and [(13)N]NH3 in Rat Myocardial Infarction Models.
ACS Med Chem Lett
PUBLISHED: 10-09-2014
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The short half-life of current positron emission tomography (PET) cardiac tracers limits their widespread clinical use. We previously developed a (18)F-labeled phosphonium cation, [(18)F]FPTP, that demonstrated sharply defined myocardial defects in a corresponding infarcted myocardium. The aim of this study was to compare the image properties of PET scans obtained using [(18)F]FPTP with those obtained using [(13)N]NH3 in rat myocardial infarction models. Perfusion abnormality was analyzed in 17 segments of polar map images. The myocardium-to-liver and myocardium-to-lung ratios of [(18)F]FPTP were 10.48 and 2.65 times higher, respectively, than those of [(13)N]NH3 in images acquired 30 min after tracer injection. The myocardial defect size measured by [(18)F]FPTP correlated more closely with the hypoperfused area measured by quantitative 2,3,5-triphenyltetrazolium chloride staining (r = 0.89, P < 0.01) than did [(13)N]NH3 (r = 0.84, P < 0.01). [(18)F]FPTP might be useful as a replacement for the myocardial agent [(13)N]NH3 in cardiac PET/CT applications.
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Metabolic orchestration between cancer cells and tumor microenvironment as a co-evolutionary source of chemoresistance in ovarian cancer: A therapeutic implication.
Biochem. Pharmacol.
PUBLISHED: 08-25-2014
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Our group reported a significant association between hexokinase II overexpression and chemoresistance in ovarian cancer, suggesting that aerobic glycolysis in the so-called Warburg effect might contribute to cancer progression. However, a growing body of evidence indicates contradictory findings with regard to the Warburg effect, such as high mitochondrial activity in highly invasive tumors and low ATP contribution of glycolysis in ovarian cancer. As a solution for the dilemma of the Warburg effect, the "reverse Warburg effect" was proposed in which aerobic glycolysis might occur in the stromal compartment of the tumor rather than in the cancer cells, indicating that the glycolytic tumor stroma feed the cancer cells through a type of symbiotic relationship. The reverse Warburg effect acting on the relationship between cancer cells and cancer-associated fibroblasts has evolved into dynamic interplay between cancer cells and multiple tumor stromal compartments, including cancer-associated fibroblasts, the extracellular matrix, endothelial cells, mesenchymal stem cells, adipocytes, and tumor-associated macrophages. Peritoneal cavities including ascites and the omentum also form a unique environment that is highly receptive for carcinomatosis in the advanced stages of ovarian cancer. The complicated but ingeniously orchestrated stroma-mediated cancer metabolism in ovarian cancer provides great heterogeneity in tumors with chemoresistance, which makes the disease thus far difficult to cure by single stromal-targeting agents. This review will discuss the experimental and clinical evidence of the cross-talk between cancer cells and various components of tumor stroma in terms of heterogeneous chemoresistance with focal points for therapeutic intervention in ovarian cancer.
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The effect of ? contacts between metal ions and fluorophores on the fluorescence of PET sensors: implications for sensor design for cations and anions.
Inorg Chem
PUBLISHED: 08-21-2014
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The idea that M···C ? contacts between diamagnetic heavy metal ions such as Pb(II), Ag(I), Pd(II), or Hg(II) and the anthracenyl fluorophore of adpa ((N-(9-anthracenylmethyl)-N-(2-pyridinylmethyl)-2-pyridinemethanamine) are responsible for quenching the fluorescence of the complexes of these metal ions with adpa is explored crystallographically. The structures of [Pb(adpa)(NO3)2] (1), [Ag(adpa)NO3] (2), [Pd(adpa)NO3]NO3 (3), [Zn(adpa)(NO3)2] (4), and [Cd(adpa)Br2] (5) are reported. The ? contacts with the fluorophore are for 1 are a Pb···C ? contact of 3.178 Å; for 2, an Ag···C ? contact of 3.016 Å; and for 3, a Pd···C ? contact of 2.954 Å on the axial site of the Pd(II) ion. The Zn(II) ion in 4 has no Zn···C ? contact, with the anthracenyl fluorophore rotated completely away from the Zn(II) ion. These structures confirm that in the Pb(II), Ag(I), and Pd(II) complexes of adpa, which experience strong quenching of fluorescence, there are strong M···C ? contacts, as expected if it is the ? contacts that quench fluorescence. In contrast, for the Zn(II) adpa complex, which forms no ? contact, there is a strong increase in fluorescence intensity. The structure of 5 shows a long Cd···C ? contact at 3.369 Å, in contrast to a previously reported structure with two coordinated nitrates where the Cd···C ? contact is 3.097 Å. The long Cd···C ? contact in [Cd(adpa)Br2] suggests how coordination of Br(-), as well as other more covalently bound ligands such as Cl(-), SCN(-), and S2O3(2-), cause an increase in fluorescence intensity, reported for the Cd(II)adpa complex in 50% CH3OH/H2O. Coordination of covalently bound ligands to the Cd(II) weakens the Cd···C ? contact and so enhances fluorescence, whereas more ionically bound ligands such as SO4(2-), NO3(-), or H2O produce a strong Cd···C ? contact and weakened fluorescence. Complexes of the Cd(II)/adpa type may form the basis for a new type of anion/small molecule sensor. The tendency of metal ions to form ? contacts with aromatic groups is analyzed in terms of the frequency of occurrence of ? contacted structures in the literature, as well as by DFT calculations on the adpa complexes.
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Initial experience of integrated PET/MR mammography in patients with invasive ductal carcinoma.
Hell J Nucl Med
PUBLISHED: 08-18-2014
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The purpose of this study was to evaluate the feasibility of integrated fluorine-18-fluorodeoxyglucose positron emission tomography/magnetic resonance ((18)F-FDG PET/MR) mammography in invasive ductal carcinoma (IDC) patients. From August 2012 to March 2013, we enrolled 42 consecutive breast cancer patients who received whole- body PET/MR and subsequent PET/MR mammography by an integrated PET/MR scanner and were scheduled for surgery within 2 weeks after the of scan. On the whole body PET/MR, 2-point Dixon VIBE, coronal T1w image, axial T2w image, and post-contrast T1 sequences were acquired with simultaneous PET acquisition. For PET/MR mammography, T1w, T2w, and dynamic contrast-enhancement (DCE) sequences were acquired using a breast coil during simultaneous PET acquisition. We compared the detectability of the lesions between whole-body PET/MR and PET/MR mammography. Forty-eight IDC (1.89±1.19cm of width) were diagnosed in 42 women. Lesion conspicuity in (18)F-FDG PET was equivalent between whole-body PET/MR and PET/MR mammography; both PET/MR images showed 38 hypermetabolic masses. In the analysis of 10 IDC with <1.0cm wide lesions, only 1 IDC showed (18)F-FDG uptake, and 4 IDC were noted on whole-body PET/MR; however, all 10 IDC showed a depictable mass on PET/MR mammography. In the analysis of 38 IDC >1.0cm wide, 37 IDC showed (18)F-FDG uptake, and 38 IDC were detected on both whole-body PET/MR and PET/MR mammography. The overall sensitivity was 79.2% (38/48) on PET, 87.5% (42/48) on whole-body PET/MR, and 100% on PET/MR mammography. The SUV between whole-body PET/MR and PET/MR mammography showed strong and highly significant correlation (r=0.987, P<0.001). In conclusion, our results, although in a limited number of cases show that integrated PET/MR mammography is feasible and has the advantage of combining high-resolution breast images with metabolic images. Furthermore, PET/MR mammography could provide an accurate diagnosis in case of IDC that are less than 1cm in size.
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L1 cell adhesion molecule expression is associated with pelvic lymph node metastasis and advanced stage in diabetic patients with endometrial cancer: a matched case control study.
J Cancer Prev
PUBLISHED: 07-28-2014
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Diabetic patients with endometrial cancer had more lymph node metastasis than non-diabetic patients with endometrial cancer. L1 cell adhesion molecule (L1CAM) could be possibly associated with lymph node metastasis in diabetic patients with endometrial cancer via epithelial-mesenchymal transition. We aimed to investigate the association between L1CAM expression and lymph node metastasis in diabetic patients with endometrial cancer.
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Intramedullary spinal cord metastasis from rectal cancer.
Ann Coloproctol
PUBLISHED: 07-08-2014
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Intramedullary spinal cord metastasis (ISCM) is an uncommon condition of the central nervous system (CNS) cause by systemic malignant tumors. Most ISCM cases are known to occur in patients with lung cancer and breast cancer; however, ISCM also very rarely occurs in patients with colorectal cancer. For the first time in Korea, we experienced a case of ISCM arising from rectal cancer, where a 75-year-old man presented with an abruptly-developed left-foot drop and numbness in both legs. The patient had lung metastases from rectal cancer that had been treated with chemotherapy. Magnetic resonance imaging revealed an intramedullary nodular lesion at the T12 level. ISCM was diagnosed and treated with steroids and radiotherapy. The patient's neurological symptoms were relieved for a while after treatment, but his condition deteriorated progressively. He died 4 months after ISCM had been diagnosed.
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One-pot self-templating synthesis of Pt hollow nanostructures and their catalytic properties for CO oxidation.
Chemistry
PUBLISHED: 06-17-2014
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Nanoporous Pt hollow nanostructures with octahedral and hexagonal frame-like morphologies were prepared by a novel one-pot self-templating route with no assistance from a preformed template or shape-directing agent. The hexagonal frame-like Pt hollow structures exhibited significantly enhanced catalytic activity toward CO oxidation reaction compared to the octahedral Pt hollow nanostructures due to the higher oxidation state of Pt.
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Intratumoral Metabolic Heterogeneity for Prediction of Disease Progression After Concurrent Chemoradiotherapy in Patients with Inoperable Stage III Non-Small-Cell Lung Cancer.
Nucl Med Mol Imaging
PUBLISHED: 06-06-2014
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We evaluated the value of variable (18)F-FDG PET/CT parameters for the prediction of disease progression after concurrent chemoradiotherapy (CCRT) in patients with inoperable stage III non-small-cell lung cancer (NSCLC).
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Early metabolic response on 18F-fluorodeoxyglucose-positron-emission tomography/computed tomography after concurrent chemoradiotherapy for advanced stage III non-small cell lung cancer is correlated with local tumor control and survival.
Anticancer Res.
PUBLISHED: 04-30-2014
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We evaluated the relationship of early metabolic responses on (18)F-fluorodeoxyglucose-positron-emission tomography/computed tomography (PET/CT) performed within one month after concurrent chemoradiotherapy (CCRT) with local tumor control and survival in patients with advanced stage III non-small cell lung cancer (NSCLC).
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Effects of anti-obesity drugs, phentermine and mahuang, on the behavioral patterns in Sprague-Dawley rat model.
Lab Anim Res
PUBLISHED: 04-07-2014
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According to WHO global estimates from 2008, more than 1.4 billion adults were overweight and among them, over 200 million men and 300 million women were obese. Although the main treatment modalities for overweight and obese individuals remain dieting and physical exercise, the synthetic anti-obesity medications have been increasingly used due to their perceived convenience. Generally, anti-obesity medications are classified as appetite suppressants or fat absorption blockers. In the present study, we examined the adverse side-effects in respect of behavior changes of phentermine and Ephedra sinica (mahuang) that are anti-obesity drugs currently distributed to domestic consumers. Phentermine is mainly classified as an anorexing agent and mahuang a thermogenic agent. Because phentermine and mahuang are considered to display effectiveness through the regulation of nerve system, their potential influences of on behavioral changes were examined employing animal experiments. From the results of experiments testing locomotor activity through the use of treadmill, rota-rod, and open field system, phentermine and mahuang were commonly revealed to induce behavioral changes of rats by reducing a motor ability, an ability to cope with an external stimulus, and a sense of balance or by augmenting wariness or excitement. These adverse effects of phenternime and mahuang in behavioral changes need to be identified in humans and anti-obesity medications such as phentermine and mahuang should be prescribed for only obesity where it is anticipated that the benefits of the treatment outweigh their potential risks.
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Safety of less aggressive surgery for stage IA1 squamous cell carcinoma of the cervix.
J. Obstet. Gynaecol. Res.
PUBLISHED: 04-02-2014
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To determine the risk of extracervical disease in patients with stage IA1 squamous cell carcinoma of the cervix.
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Cellular dynamics after injection of mesoderm-derived human embryonic kidney 293 cells and fibroblasts into developing chick embryos.
J Cancer Prev
PUBLISHED: 03-04-2014
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This study was conducted to compare localization of transformed or differentiated cells after injection into developing chick embryos. Mesoderm-derived chicken embryonic fibroblasts (CEFs), retrieved from normal tissues and artificially transformed human embryonic kidney (HEK) 293 cells, were injected into the dorsal aorta of stage 17 embryos, incubated for 60 h, and post-injection survival and tissue localization after injection were monitored. Overall survival rates were 43% to 57%, and there was no significant difference between the two cell types (P=0.4453). Migration into various tissues was observed after injection of the HEK 293 cells, and this was greatly reduced after CEF transfer (P<0.0127). Tumorigenic activity was detected in the HEK 293 transferred cells and the major organ colonized was the highly vascularized yolk sac. From these results, we suggest that cell transformation alters post-injected migration activity of cells at organogenesis.
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The association between occupational exposures and cigarette smoking among operating engineers.
Arch Environ Occup Health
PUBLISHED: 02-11-2014
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The purpose of this study was to determine the relationship between occupational exposures and cigarette smoking among operating engineers. A cross-sectional survey was conducted with operating engineers (N = 412) from a midwestern state in the United States. The survey included validated questions on cigarette smoking, occupational exposures, demographics, comorbidities, and health behaviors. About 35% were current smokers. Those exposed to asphalt fumes, heat stress, concrete dust, and welding fumes were less likely to smoke (odds ratio [OR] = .79, 95% confidence interval [CI]: .64-.98). Other factors associated with smoking included younger age (OR = .97, 95% CI: .94-.99), problem drinking (OR = 1.07, 95% CI: 1.03-1.12), lower Body Mass Index (OR = .95, 95% CI: .90-.99), and being separated/widowed/divorced (OR = 2.24, 95% CI: 1.19-4.20). Further investigation is needed for better understanding about job-specific exposure patterns and their impact on cigarette smoking among operating engineers.
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Estimation of measurement uncertainty for the quantification of 11-nor-delta 9-tetrahydrocannabinol-9-carboxylic acid and its glucuronide in urine using liquid chromatography-tandem mass spectrometry.
J Anal Toxicol
PUBLISHED: 02-10-2014
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Recently, the estimation of the measurement uncertainty has become a significant issue in the quality control of forensic drug testing. In the present study, the uncertainty of the measurement was calculated for the quantification of 11-nor-delta 9-tetrahydrocannabinol-9-carboxylic acid (THC-COOH) and its glucuronide conjugate (THC-COOH-glu) in urine using liquid chromatography-tandem mass spectrometry. The procedure was based on liquid-liquid extraction of a volume of urine (800 µL) with ethyl acetate. The sources of uncertainty were identified and classified into four major categories as follows: standard preparation, calibration curve, method precision and bias. The overall contribution of combined standard uncertainty on THC-COOH increased in the order of standard preparation (0.9%), method precision (10.4%), calibration curve (30.3%) and bias (58.4%) and, while calibration curve (53.0%) and bias (40.4%) gave the bigger contributions to the combined standard uncertainty for THC-COOH-glu than method precision and standard preparation, which accounted for 6.3 and 0.3%, respectively. The reliability of a measurement was expressed by stating the expanded uncertainty of the measurement result at 95% confidence level. The concentrations of THC-COOH and THC-COOH-glu in the urine sample with their expanded uncertainties were 10.20 ± 1.14 ng/mL and 25.42 ± 5.01 ng/mL, respectively.
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Pre- and intra-operative variables associated with surgical complications in elderly patients with gynecologic cancer: the clinical value of comprehensive geriatric assessment.
J Geriatr Oncol
PUBLISHED: 02-05-2014
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The aim of this study is to evaluate the associations of pre- and intra-operative variables including comprehensive geriatric assessment (CGA) with surgical complications in elderly patients who underwent primary surgery for gynecologic cancer.
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Peritoneal cytology: a risk factor of recurrence for non-endometrioid endometrial cancer.
Gynecol. Oncol.
PUBLISHED: 01-30-2014
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We compared the impact of positive peritoneal cytology on prognosis between patients with endometrioid and non-endometrioid endometrial carcinoma.
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The role of omentectomy and random peritoneal biopsies as part of comprehensive surgical staging in apparent early-stage epithelial ovarian cancer.
Ann. Surg. Oncol.
PUBLISHED: 01-30-2014
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Comprehensive surgical staging plays an important role in apparent early-stage epithelial ovarian cancer (eEOC). However, few studies have evaluated how often upstaging occurs solely as a result of microscopic metastases identified from omentectomy and random peritoneal biopsies. The purpose of this study was to evaluate the significance of omentectomy and random peritoneal biopsies for normal-appearing tissues in eEOC.
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The Effect of Indigocarmine on Improvement of the Polyp Detection Rate during Colonoscopic Examination with Hood Cap.
Intest Res
PUBLISHED: 01-28-2014
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Hood cap-assisted chromocolonoscopy using indigocarmine is expected to improve the detection rate of colorectal polyps, especially adenomatous polyps. Therefore, aim of the present study was to evaluate the usefulness of hood cap-assisted chromocolonoscopy in routine colonoscopic examinations.
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Prevalence and prognostic value of human papillomavirus genotypes in tonsillar squamous cell carcinoma: A Korean multicenter study.
Cancer
PUBLISHED: 01-24-2014
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This study was aimed at investigating the change in the prevalence of human papillomavirus (HPV) genotypes in tonsillar squamous cell carcinoma (TSCC) and the association of the HPV genotype with the prognosis.
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Phosphorylation of LSD1 by PKC? is crucial for circadian rhythmicity and phase resetting.
Mol. Cell
PUBLISHED: 01-22-2014
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The circadian clock is a self-sustaining oscillator that controls daily rhythms. For the proper circadian gene expression, dynamic changes in chromatin structure are important. Although chromatin modifiers have been shown to play a role in circadian gene expression, the in vivo role of circadian signal-modulated chromatin modifiers at an organism level remains to be elucidated. Here, we provide evidence that the lysine-specific demethylase 1 (LSD1) is phosphorylated by protein kinase C? (PKC?) in a circadian manner and the phosphorylated LSD1 forms a complex with CLOCK:BMAL1 to facilitate E-box-mediated transcriptional activation. Knockin mice bearing phosphorylation-defective Lsd1(SA/SA) alleles exhibited altered circadian rhythms in locomotor behavior with attenuation of rhythmic expression of core clock genes and impaired phase resetting of circadian clock. These data demonstrate that LSD1 is a key component of the molecular circadian oscillator, which plays a pivotal role in rhythmicity and phase resetting of the circadian clock.
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Impact of underweight after treatment on prognosis of advanced-stage ovarian cancer.
J Immunol Res
PUBLISHED: 01-11-2014
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This study aimed to investigate the impact of underweight status on the prognosis of advanced-stage ovarian cancer. A total of 360 patients with stage III-IV epithelial ovarian cancer were enrolled and divided into three groups by body mass indexes (BMIs): underweight (BMI?
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Prognosis of adenosquamous carcinoma compared with adenocarcinoma in uterine cervical cancer: a systematic review and meta-analysis of observational studies.
Int. J. Gynecol. Cancer
PUBLISHED: 01-11-2014
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The aim of this study was to compare the survival outcomes of adenosquamous carcinoma (ASC) and adenocarcinoma (AC) of the cervix.
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Preoperative PET/CT standardized FDG uptake values of pelvic lymph nodes as a significant prognostic factor in patients with endometrial cancer.
Eur. J. Nucl. Med. Mol. Imaging
PUBLISHED: 01-08-2014
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Using integrated PET/CT, we evaluated the prognostic relevance of preoperative pelvic lymph node (LN) (18)F-FDG uptake in endometrioid endometrial cancer.
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Safety of Fertility-Sparing Surgery in Primary Mucinous Carcinoma of the Ovary.
Cancer Res Treat
PUBLISHED: 01-05-2014
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The aim of this study is to evaluate the safety of fertility-sparing surgery as the treatment for patients with primary mucinous epithelial ovarian cancer.
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The Arabidopsis PLAT Domain Protein1 Is Critically Involved in Abiotic Stress Tolerance.
PLoS ONE
PUBLISHED: 01-01-2014
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Despite the completion of the Arabidopsis genome sequence, for only a relatively low percentage of the encoded proteins experimental evidence concerning their function is available. Plant proteins that harbour a single PLAT (Polycystin, Lipoxygenase, Alpha-toxin and Triacylglycerol lipase) domain and belong to the PLAT-plant-stress protein family are ubiquitously present in monocot and dicots. However, the function of PLAT-plant-stress proteins is still poorly understood. Therefore, we have assessed the function of the uncharacterised Arabidopsis PLAT-plant-stress family members through a combination of functional genetic and physiological approaches. PLAT1 overexpression conferred increased abiotic stress tolerance, including cold, drought and salt stress, while loss-of-function resulted in opposite effects on abiotic stress tolerance. Strikingly, PLAT1 promoted growth under non-stressed conditions. Abiotic stress treatments induced PLAT1 expression and caused expansion of its expression domain. The ABF/ABRE transcription factors, which are positive mediators of abscisic acid signalling, activate PLAT1 promoter activity in transactivation assays and directly bind to the ABRE elements located in this promoter in electrophoretic mobility shift assays. This suggests that PLAT1 represents a novel downstream target of the abscisic acid signalling pathway. Thus, we showed that PLAT1 critically functions as positive regulator of abiotic stress tolerance, but also is involved in regulating plant growth, and thereby assigned a function to this previously uncharacterised PLAT domain protein. The functional data obtained for PLAT1 support that PLAT-plant-stress proteins in general could be promising targets for improving abiotic stress tolerance without yield penalty.
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The value of CT for disease detection and prognosis determination in combined pulmonary fibrosis and emphysema (CPFE).
PLoS ONE
PUBLISHED: 01-01-2014
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Several imaging-based indices were constructed quantitatively using the emphysema index (EI) and fibrosis score (FS) on high-resolution computed tomography (HRCT). We evaluated the ability of these indices to predict mortality compared to physiologic results. Additionally, prognostic predictive factors were compared among subgroups with biopsy-proven fibrotic idiopathic interstitial pneumonia (IIP) (biopsy-proven CPFE) and in a separate cohort with subclinical CPFE.
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C57BL/6N mutation in Cytoplasmic FMRP interacting protein 2 regulates cocaine response.
Science
PUBLISHED: 12-21-2013
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The inbred mouse C57BL/6J is the reference strain for genome sequence and for most behavioral and physiological phenotypes. However, the International Knockout Mouse Consortium uses an embryonic stem cell line derived from a related C57BL/6N substrain. We found that C57BL/6N has a lower acute and sensitized response to cocaine and methamphetamine. We mapped a single causative locus and identified a nonsynonymous mutation of serine to phenylalanine (S968F) in Cytoplasmic FMRP interacting protein 2 (Cyfip2) as the causative variant. The S968F mutation destabilizes CYFIP2, and deletion of the C57BL/6N mutant allele leads to acute and sensitized cocaine-response phenotypes. We propose that CYFIP2 is a key regulator of cocaine response in mammals and present a framework to use mouse substrains to identify previously unknown genes and alleles regulating behavior.
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"Nondefect" of arterial enhancing rim on hepatobiliary phase in 3.0-T gadolinium-ethoxybenzyl-diethylenetriamine pentaacetic Acid-enhanced liver magnetic resonance imaging: distinguishing hepatic abscess from metastasis.
J Comput Assist Tomogr
PUBLISHED: 11-26-2013
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The objective of this study was to retrospectively determine the findings of Gd-EOB-DTPA (gadolinium ethoxybenzyl diethylenetriamine pentaacetic acid)-enhanced magnetic resonance imaging (MRI) to distinguish abscess from metastasis of the liver.
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Phosphorylation of the Cryptochrome 1 C-terminal Tail Regulates Circadian Period Length.
J. Biol. Chem.
PUBLISHED: 10-24-2013
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The Cryptochrome (CRY) proteins are critical components of the mammalian circadian clock and act to rhythmically repress the activity of the transcriptional activators CLOCK and BMAL1 at the heart of the clock mechanism. The CRY proteins are part of a large repressive complex, the components of which are not completely known. Using mass spectroscopy, we identified the catalytic subunit of DNA-dependent protein kinase as a CRY-interacting protein and found that loss or inhibition of this kinase results in circadian rhythms with abnormally long periods. We then identified serine 588 in the C-terminal tail of mouse CRY1 as a potential DNA-PK phosphorylation site but surprisingly found that the phosphomimetic mutation S588D also results in long period rhythms, similar to the loss of DNA-PK. Consistent with this, we found that phosphorylation of this site is increased in cells lacking DNA-PK, suggesting that DNA-PK negatively regulates the phosphorylation of this site most likely through indirect means. Furthermore, we found that phosphorylation of this site increases the stability of the CRY1 protein and prevents FBXL3-mediated degradation. The phosphorylation of this site is robustly rhythmic in mouse liver nuclei, peaking in the middle of the circadian day at a time when CRY1 levels are declining. Therefore, these data suggest a new role for the C-terminal tail of CRY1 in which phosphorylation rhythmically regulates CRY1 stability and contributes to the proper circadian period length.
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Role of Fluorophore-Metal Interaction in Photoinduced Electron Transfer (PET) Sensors: Time-Dependent Density Functional Theory (TDDFT) Study.
J Phys Chem A
PUBLISHED: 10-07-2013
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The origins of fluorescence quenching by Hg(II) ion chelation and fluorescence enhancement by Zn(II) ion chelation to a PET sensor are investigated. Specifically, the fluorescence quenching and enhancing mechanisms associated with the ligand ADPA (N-(9-anthracenylmethyl)-N-(2-pyridinylmethyl)-2-pyridinemethanamine), protonated ADPA and metal bound (Zn(II) and Hg(II)) ADPA are studied via density functional theory (DFT) and time-dependent DFT (TDDFT) methods. The study found that a structural change in the excited state of ADPA induces reordering of the frontier molecular orbitals, and the S1 ? S0 transition becomes a charge transfer transition from the fluorophore to the tertiary nitrogen of the dipicolylamine (DPA) unit, which is forbidden. Protonation on the tertiary amine or chelation of Zn(II) prevents such changes, and the HOMO-LUMO transition is contained within the fluorophore. Therefore, fluorescence is restored. The chelation of Hg(II), on the other hand, promotes extensive interaction between the Hg(II) ion and the fluorophore, which is reflected in the short Hg(II)-fluorophore distance (3.11 Å). A noticeable structural change upon the S0 ? S1 transition is observed in the Hg(II)-ADPA system as well, where the resulting S1 ? S0 transition becomes a charge transfer transition from mercury to the fluorophore and the fluorescence is thus quenched. Therefore, the present DFT/TDDFT calculations reproduce the fluorescence on-off behavior associated with the entire ADPA family of complexes, which illustrates that the combination of DFT and TDDFT calculations, including excited state geometry optimization, can be a valuable tool to uncover the detailed fluorescence sensing mechanisms.
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Mechanism of chelation enhanced fluorescence in complexes of cadmium(II), and a possible new type of anion sensor.
Chem. Commun. (Camb.)
PUBLISHED: 09-14-2013
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The Cd(II) complex of adpa (N-(9-anthracenylmethyl)-N,N-di-(picolyl)amine) in MeOH-H2O has increased fluorescence intensity with [Cl(-)], a new type of anion sensor. The structure of [Cd(adpa)(NO3)2] has a proposed fluorescence-quenching ?-contact between Cd and the fluorophore, while the Cl in [Cd(adpa)Cl2] disrupts the ?-contact, restoring fluorescence.
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Neurolymphomatosis of Brachial Plexus in Patients with Non-Hodgkins Lymphoma.
Case Rep Oncol Med
PUBLISHED: 08-27-2013
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Neurolymphomatosis (NL) is a rare clinical disease where neoplastic cells invade the cranial nerves and peripheral nerve roots, plexus, or other nerves in patients with hematologic malignancy. Most NL cases are caused by B-cell non-Hodgkins lymphoma (NHL). Diagnosis can be made by imaging with positron emission tomography (PET) and magnetic resonance imaging (MRI). We experienced two cases of NL involving the brachial plexus in patients with NHL. One patient, who had NHL with central nervous system (CNS) involvement, experienced complete remission after 8 cycles of R-CHOP (rituximab, cyclophosphamide, doxorubicin, vincristine, and prednisone) chemotherapy but relapsed into NL of the brachial plexus 5 months later. The other patient, who suffered from primary central nervous system lymphoma (PCNSL), had been undergoing chemoradiotherapy but progressed to NL of the brachial plexus.
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Improvements to the FIGO staging for ovarian cancer: reconsideration of lymphatic spread and intraoperative tumor rupture.
J Gynecol Oncol
PUBLISHED: 07-27-2013
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To evaluate the improvement in prognosis prediction with reassignment of International Federation of Gynecology and Obstetrics (FIGO) stages for ovarian carcinoma.
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A high-mobility terselenophene and diketopyrrolopyrrole containing copolymer in solution-processed thin film transistors.
Chem. Commun. (Camb.)
PUBLISHED: 07-06-2013
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A new diketopyrrolopyrrole (DPP)-based ?-conjugated copolymer containing terselenophene units has been successfully synthesized. Its hole mobility reaches around 5.0 cm(2) V(-1) s(-1) in thin film transistors made from thermally annealed films. This proves that a longer terselenophene unit induced excellent charge transport properties.
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Clinical implication of F-18 FDG PET/CT in patients with secondary hemophagocytic lymphohistiocytosis.
Ann. Hematol.
PUBLISHED: 06-20-2013
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The contribution that F-18 fluoro-2-deoxyglucose positron emission tomography/computed tomography (F-18 FDG) PET/CT makes to the diagnosis of malignancy in patients with hemophagocytic lymphohistiocytosis (HLH) is still uncertain. The aim of this study was to evaluate the diagnostic performance of F-18 FDG PET/CT for the detection of underlying malignancy, to investigate the correlation between PET and laboratory parameters, and to identify prognosis-related factors in patients with secondary HLH. We enrolled 14 patients who were diagnosed with HLH and referred for F-18 FDG PET/CT to exclude malignancy. The diagnostic performance of F-18 FDG PET/CT for malignancy detection was assessed. The correlations between PET and laboratory parameters were determined. The prognostic significance of the following factors was evaluated: PET and laboratory parameters, age in years, presence of underlying malignancy, and fever and splenomegaly. Six of the 14 patients had malignancies (four with lymphoma, one with multiple myeloma, and one with colonic malignancy). Sensitivity, specificity, and diagnostic accuracy of F-18 FDG PET/CT for malignancy detection were 83, 62.5, and 71.4 %, respectively. F-18 FDG uptake in the bone marrow and spleen was positively correlated with neutrophil count and C-reactive protein. All of the PET parameters, but none of the clinical or laboratory parameters, were significantly associated with patient outcome, as determined by univariate analysis. Given the small sample size, F-18 FDG PET/CT was useful for detecting underlying malignancy, and PET parameters correlated with laboratory parameters that reflected inflammatory status. F-18 FDG PET/CT might provide prognostic information for the management of patients with secondary HLH.
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Engineering of bacteria for the visualization of targeted delivery of a cytolytic anticancer agent.
Mol. Ther.
PUBLISHED: 06-09-2013
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A number of recent reports have demonstrated that attenuated Salmonella typhimurium are capable of targeting both primary and metastatic tumors. The use of bacteria as a vehicle for the delivery of anticancer drugs requires a mechanism that precisely regulates and visualizes gene expression to ensure the appropriate timing and location of drug production. To integrate these functions into bacteria, we used a repressor-regulated tetracycline efflux system, in which the expression of a therapeutic gene and an imaging reporter gene were controlled by divergent promoters (tetAP and tetRP) in response to extracellular tetracycline. Attenuated S. typhimurium was transformed with the expression plasmids encoding cytolysin A, a therapeutic gene, and renilla luciferase variant 8, an imaging reporter gene, and administered intravenously to tumor-bearing mice. The engineered Salmonella successfully localized to tumor tissue and gene expression was dependent on the concentration of inducer, indicating the feasibility of peripheral control of bacterial gene expression. The bioluminescence signal permitted the localization of gene expression from the bacteria. The engineered bacteria significantly suppressed both primary and metastatic tumors and prolonged survival in mice. Therefore, engineered bacteria that carry a therapeutic and an imaging reporter gene for targeted anticancer therapy can be designed as a theranostic agent.
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MicroRNA-185 oscillation controls circadian amplitude of mouse Cryptochrome 1 via translational regulation.
Mol. Biol. Cell
PUBLISHED: 05-22-2013
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Mammalian circadian rhythm is observed not only at the suprachiasmatic nucleus, a master pacemaker, but also throughout the peripheral tissues. Investigation of the regulation of clock gene expression has mainly focused on transcriptional and posttranslational modifications, and little is known about the posttranscriptional regulation of these genes. In the present study, we investigate the role of microRNAs (miRNAs) in the posttranscriptional regulation of the 3-untranslated region (UTR) of the mouse Cryptochrome 1 (mCry1) gene. Knockdown of Drosha, Dicer, or Argonaute2 increased mCry1-3UTR reporter activity. The presence of the miRNA recognition element of mCry1 that is important for miR-185 binding decreased mCRY1 protein, but not mRNA, level. Cytoplasmic miR-185 levels were nearly antiphase to mCRY1 protein levels. Furthermore, miR-185 knockdown elevated the amplitude of mCRY1 protein oscillation. Our results suggest that miR-185 plays a role in the fine-tuned regulation of mCRY1 protein expression by controlling the rhythmicity of mCry1 mRNA translation.
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SB365, Pulsatilla saponin D, targets c-Met and exerts antiangiogenic and antitumor activities.
Carcinogenesis
PUBLISHED: 05-13-2013
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SB365, Pulsatilla saponin D isolated from the root of Pulsatilla koreana, has exhibited potential beneficial effects as a chemopreventive agent for critical health conditions including cancer. However, the molecular mechanisms underlying the activity of SB365 remain unknown. Here, we examined anticancer efficacy of SB365 against gastric cancer and its mechanism of action. SB365 effectively inhibited the growth of gastric cancer cells. Its apoptotic effect was accompanied by increased evidence of cleaved caspase-3 and poly(ADP ribose) polymerase. To elucidate the anticancer mechanism of SB365, we used an array of 42 different receptor tyrosine kinases (RTKs). Of the 42 different phospho-RTKs, SB365 strongly inhibited expression of activated c-mesenchymal-epithelial transition factor (c-Met) in gastric cancer cells. Also, the activation of the c-Met signal cascade components, including Akt and mammalian target of rapamycin, was inhibited by SB365 in a dose-dependent manner. In angiogenesis studies, SB365 inhibited tube formation in hepatocyte growth factor (HGF)-induced human umbilical vein endothelial cells and suppressed microvessel sprouting from the rat aortic ring, ex vivo, and blood vessel formation in the Matrigel plug assay in mice. In xenograft animal models, SB365 significantly delayed tumor growth in a dose-dependent manner. In tumor tissue, SB365 suppressed c-Met signaling, proliferation and angiogenesis and induced apoptosis. These findings suggest that SB365 docks at an allosteric site on c-Met and thereby targets c-Met signaling pathway, cell growth/angiogenesis inhibition and apoptosis induction. Therefore, SB365 may be a novel drug candidate for the treatment of gastric cancer.
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Rapid and sensitive determination of propofol glucuronide in hair by liquid chromatography and tandem mass spectrometry.
J Pharm Biomed Anal
PUBLISHED: 05-09-2013
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A fast, sensitive and selective liquid chromatography-tandem mass spectrometry (LC-MS/MS) method for the detection and quantitation of propofol glucuronide in human hair has been developed and validated. Propofol glucuronide was extracted from 10mg of hair using a simple methanol extraction method, with recovery greater than 91% at 3 quality control samples (15, 100, 4000 pg/mg). A reversed phase column (C8) was used to analyze and the mobile phase was composed of ammonium formate and acetonitrile gradient at a flow rate of 0.2 mL/min. The lower limit of quantitation (LLOQ) was 5 pg/mg and the assay was linear to 5000 pg/mg. The intra- and inter-day precision (% CV, coefficient of variation) ranged from 1.26 to 4.50% while the accuracy (% RE, relative error) were -4.24 to 4.4%. The matrix effects were monitored at 3 different concentrations and the %CV of the results for these concentrations was less than 10.6%. Propofol glucuronide was stable during processing and analysis in human hair. The procedure was validated and applied to the analysis of hair samples in human subjects previously administered in propofol.
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Indirect Radionuclide Coronary Angiography to Evaluate Gradients of Myocardial Blood Flow and Flow Reserve Through Coronary Stenosis Using N-13 Ammonia PET/CT.
Chonnam Med J
PUBLISHED: 03-13-2013
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Although quantitative evaluation of myocardial blood flow (MBF) and myocardial flow reserve (MFR) has been perceived as an attractive advantage of positron emission tomography (PET) over other cardiac imaging technologies, application of the information to specific coronary lesions is a difficult task for nuclear cardiologists. We hypothesized that changes in MBF and MFR over a coronary lesion could be identified by use of a hybrid technology of CT coronary angiography (CTCA) and N-13 ammonia PET. To evaluate this hypothesis, we measured the gradient of MBF and MFR through coronary stenosis in seven patients (M:F=3:4, median age 56 years) with coronary artery disease who underwent N-13 ammonia PET, CTCA, and interventional coronary angiography. Two patients had proximal left anterior descending (LAD) coronary artery disease and five patients had mid to distal LAD disease. Mean global stress and rest MBF were 2.62±0.58 and 1.03±0.19 ml/min/g, respectively. Mean global MFR was 2.6±0.73. Regional stress and rest MBF in the LAD territory were 2.36±0.75 and 0.96±0.21 ml/min/g, respectively. Regional MFR in the LAD territory was 2.55±0.83 ml/min/g. Stress MBF changed dramatically according to the location of coronary stenosis. It dropped acutely in proximal lesions, whereas it diminished gradually in mid to distal lesions. In conclusion, by use of a hybrid technology of CTCA and PET, it was feasible to make a direct correlation of coronary lesions with the gradient of MFR and CFR through coronary stenosis, which indicated the severity of the coronary lesion. We named this technique indirect radionuclide coronary angiography.
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Protocol of a randomized controlled trial of sun protection interventions for operating engineers.
BMC Public Health
PUBLISHED: 03-11-2013
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Skin cancer are increasing and some types of skin cancer are among the most lethal cancers yet are easily preventable. However, sun protection interventions are rarely implemented among outdoor workers. Our prior work shows that Michigan Operating Engineers (heavy equipment operators) spend an average of 4-5 hours in the sun, about one-third reported getting sun burned at least once a summer, and over half burned more than once a summer. About three-quarters of the sample never or only sometimes used sun block.
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SB365, Pulsatilla saponin D suppresses proliferation and induces apoptosis of pancreatic cancer cells.
Oncol. Rep.
PUBLISHED: 03-08-2013
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Pulsatilla koreana has been used as a traditional medicine for the treatment of various diseases. The purpose of this study was to determine whether SB365, Pulsatilla saponin D isolated from the root of Pulsatilla koreana inhibits the progression of pancreatic cancer. We found that SB365 strongly suppressed the growth and proliferation of 5 human pancreatic cancer cell lines (MIAPaCa-2, BXPC-3, PANC-1, AsPC-1 and HPAC). The apoptotic effect of SB365 was demonstrated by increased levels of cleaved caspase-3 and decreased Bcl-2 expression via mitochondrial membrane potential, as well as elevated numbers of terminal deoxynucleotidyl-transferase-mediated dUTP nick end labeling (TUNEL)-positive apoptotic cells. SB365 was also found to exert an anti-angiogenic effect by decreasing the expression of HIF-1? and VEGF, major factors of angiogenesis, which was confirmed by the suppression of tumor sphere formation of pancreatic cancer cells. An in vivo mouse xenograft study showed that SB365 significantly inhibited tumor growth through the induction of apoptosis and inhibition of angiogenesis with strong anticancer activity. Therefore, SB365 is a good candidate as a natural product for use in the treatment of pancreatic cancer.
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Association of overexpression of hexokinase II with chemoresistance in epithelial ovarian cancer.
Clin. Exp. Med.
PUBLISHED: 03-02-2013
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This aim of this study was to evaluate the relationship between hexokinase II expression and chemoresistance in epithelial ovarian cancer. One hundred and eleven paraffin-embedded specimens from patients with epithelial ovarian cancer were immunohistochemically stained for hexokinase II. Subsequently, the association between hexokinase II overexpression and clinicopathologic characteristics including chemoresistance was assessed. Survival analyses were also performed for evaluating the prognostic value of hexokinase II overexpression. Tumor recurrence within 6 months after termination of first-line chemotherapy was considered to indicate chemoresistance. Hexokinase II overexpression was associated with chemoresistance (p = 0.029) and was an independent risk factor for chemoresistance [odds ratio (OR) 3.37; 95 % confidence interval (CI) 1.07-10.62; p = 0.038] along with non-optimal debulking surgery (OR 4.93; 95 % CI 1.43-16.98; p = 0.011). Hexokinase II overexpression was significantly associated with decreased progression-free survival (p = 0.002) and showed a similar trend for overall survival (p = 0.101). Cox regression analysis revealed that hexokinase II overexpression was an independent prognostic factor for early recurrence (hazard ratio 2.63; 95 % CI 1.40-4.92; p = 0.002). Our findings suggest that hexokinase II overexpression is associated with short progression-free survival, which could be associated with chemoresistance in epithelial ovarian cancer.
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Prognostic value of preoperative metabolic tumor volume measured by ¹?F-FDG PET/CT and MRI in patients with endometrial cancer.
Gynecol. Oncol.
PUBLISHED: 02-27-2013
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Tumor metabolic activity is a significant prognostic factor for endometrial cancer; however, there are few reports on the clinical importance of metabolic tumor volume (MTV) in patients with endometrial cancer. Therefore, we evaluated the prognostic value of preoperative MTV measured by (18)F-FDG PET/CT and MRI in a group of these patients.
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Factors associated with sleep quality among operating engineers.
J Community Health
PUBLISHED: 02-09-2013
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Blue collar workers generally report high job stress and are exposed to loud noises at work and engage in many of risky health behavioral factors, all of which have been associated with poor sleep quality. However, sleep quality of blue collar workers has not been studied extensively, and no studies have focused Operating Engineers (heavy equipment operators) among whom daytime fatigue would place them at high risk for accidents. Therefore, the purpose of this study was to determine variables associated with sleep quality among Operating Engineers. This was a cross-sectional survey design with a dependent variable of sleep quality and independent variables of personal and related health behavioral factors. A convenience sample of 498 Operating Engineers was recruited from approximately 16,000 Operating Engineers from entire State of Michigan in 2008. Linear regression was used to determine personal and related health behavior factors associated with sleep quality. Multivariate analyses showed that personal factors related to poor sleep quality were younger age, female sex, higher pain, more medical comorbidities and depressive symptoms and behavioral factors related to poor sleep quality were nicotine dependence. While sleep scores were similar to population norms, approximately 34 % (n = 143) showed interest in health services for sleep problems. While many personal factors are not changeable, interventions to improve sleep hygiene as well as interventions to treat pain, depression and smoking may improve sleep quality resulting in less absenteeism, fatal work accidents, use of sick leave, work disability, medical comorbidities, as well as subsequent mortality.
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Competing E3 ubiquitin ligases govern circadian periodicity by degradation of CRY in nucleus and cytoplasm.
Cell
PUBLISHED: 01-30-2013
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Period determination in the mammalian circadian clock involves the turnover rate of the repressors CRY and PER. We show that CRY ubiquitination engages two competing E3 ligase complexes that either lengthen or shorten circadian period in mice. Cloning of a short-period circadian mutant, Past-time, revealed a glycine to glutamate missense mutation in Fbxl21, an F-box protein gene that is a paralog of Fbxl3 that targets the CRY proteins for degradation. While loss of function of FBXL3 leads to period lengthening, mutation of Fbxl21 causes period shortening. FBXL21 forms an SCF E3 ligase complex that slowly degrades CRY in the cytoplasm but antagonizes the stronger E3 ligase activity of FBXL3 in the nucleus. FBXL21 plays a dual role: protecting CRY from FBXL3 degradation in the nucleus and promoting CRY degradation within the cytoplasm. Thus, the balance and cellular compartmentalization of competing E3 ligases for CRY determine circadian period of the clock in mammals.
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Factors associated with smoking among operating engineers.
Workplace Health Saf
PUBLISHED: 01-23-2013
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Although disparities in smoking prevalence between white collar workers and blue collar workers have been documented, reasons for these disparities have not been well studied. The objective of this study was to determine variables associated with smoking among Operating Engineers, using the Health Promotion Model as a guide. With cross-sectional data from a convenience sample of 498 Operating Engineers, logistic regression was used to determine personal and health behaviors associated with smoking. Approximately 29% of Operating Engineers currently smoked cigarettes. Multivariate analyses showed that younger age, unmarried, problem drinking, physical inactivity, and a lower body mass index were associated with smoking. Operating Engineers were at high risk of smoking, and smokers were more likely to engage in other risky health behaviors, which supports bundled health behavior interventions.
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Extra-thoracic tumor burden but not thoracic tumor burden on (18)F-FDG PET/CT is an independent prognostic biomarker for extensive-disease small cell lung cancer.
Lung Cancer
PUBLISHED: 01-18-2013
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The aim of this study was to evaluate the relationship and difference in prognostic significance between whole-body tumor burden, thoracic tumor burden, and extra-thoracic tumor burden on (18)F-FDG PET/CT for patients with extensive-disease small cell lung cancer (ED-SCLC).
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Feasibility of Oxaliplatin, Leucovorin, and 5-Fluorouracil (FOLFOX-4) Chemotherapy in Heavily Pretreated Patients with Recurrent Epithelial Ovarian Cancer.
Cancer Res Treat
PUBLISHED: 01-18-2013
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The purpose of this study is to evaluate the efficacy and toxicity of oxaliplatin, leucovorin, and 5-fluorouracil (FOLFOX-4) chemotherapy in heavily pretreated patients with recurrent epithelial ovarian cancer (EOC).
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Changes in (18)f-fluorodeoxyglucose uptake in the spinal cord in a healthy population on serial positron emission tomography/computed tomography.
Chonnam Med J
PUBLISHED: 01-10-2013
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We aimed to determine the changes in (18)F-fluorodeoxyglucose (FDG) uptake in the spinal cord on two serial positron emission tomography/computed tomography (PET/CT) scans in a healthy population. We retrospectively enrolled healthy people who underwent PET/CT twice for cancer screening. We excluded those who had degenerative vertebral disease, neurologic disease, or a history of a vertebral operation. The standardized uptake value (SUVmax) of the spinal cord of each mid-vertebral body was obtained by drawing a region of interest on an axial image of PET/CT. For analysis, the cord-to-background ratio (CTB) was used (CTB=SUVmax of each level/SUVmax of L5 level). Differences in pattern, sex, age, and intervals of the two serial PET/CT scans were analyzed. A total of 60 PET/CT images of 30 people were analyzed. The mean interval between the two PET/CT imaging studies was 2.80±0.94 years. On the follow-up PET/CT, significant change was shown only at the level of the C6 and T10 vertebrae (p<0.005). Mean CTB showed a decreasing pattern from cervical to lumbar vertebrae. There were two peaks at the lower cervical level (C4-6) and at the lower thoracic level (T12). Neither sex nor age significantly affected CTB. The FDG uptake of the spinal cord changed significantly on follow-up PET/CT only at the level of the C6 and T10 vertebrae. This finding is valuable as a baseline reference in the follow-up of metabolic changes in the spinal cord.
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Clinical Usefulness of (18)F-FDG PET/CT in the Detection of Early Recurrence in Treated Cervical Cancer Patients with Unexplained Elevation of Serum Tumor Markers.
Chonnam Med J
PUBLISHED: 01-10-2013
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We investigated the diagnostic value of (18)F-fluorodeoxyglucose positron emission tomography/computed tomography (PET/CT) for restaging of treated uterine cervix squamous cell cancer with tumor maker elevation that was not explained by other conventional evaluation. We enrolled 32 cases who underwent PET/CT for the restaging of treated cervical cancer with tumor marker elevation that was not explained by recent conventional evaluation. All enrolled cases had squamous cell carcinoma. Increased tumor markers included squamous cell carcinoma antigen (SCC Ag) and carcinoembryonic antigen (CEA). PET/CT findings were determined by pathologic confirmation or clinical follow-up. We compared PET/CT accuracy and clinical parameters including normalization of tumor markers in both the SCC Ag elevation group and the CEA elevation group. The sensitivity, specificity, positive predictive value, and negative predictive value of PET/CT in detecting recurrence were 100%, 83.3%, 82.4%, and 100%, respectively. Accuracy was significantly different between the SCC Ag elevation group and the CEA elevation group (p=0.0169). PET/CT with SCC Ag elevation was more accurate (100%) than PET/CT with CEA elevation (66.7%). Normalization of tumor markers was observed more often in the SCC Ag elevation group than in the CEA elevation group (p=0.0429). PET/CT showed high negative predictive value and sensitivity in the restaging of cervical cancer with unexplained tumor marker elevation. PET/CT was more accurate in patients with SCC Ag elevation than in those with CEA elevation.
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Silencing of Nicotiana benthamiana Neuroblastoma-Amplified Gene causes ER stress and cell death.
BMC Plant Biol.
PUBLISHED: 01-08-2013
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Neuroblastoma Amplified Gene (NAG) was identified as a gene co-amplified with the N-myc gene, whose genomic amplification correlates with poor prognosis of neuroblastoma. Later it was found that NAG is localized in endoplasmic reticulum (ER) and is a component of the syntaxin 18 complex that is involved in Golgi-to-ER retrograde transport in human cells. Homologous sequences of NAG are found in plant databases, but its function in plant cells remains unknown.
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Impact of Chemoradiation on Prognosis in Stage IVB Cervical Cancer with Distant Lymphatic Metastasis.
Cancer Res Treat
PUBLISHED: 01-02-2013
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The purpose of this study was to determine whether chemoradiation (CCR) is efficient for improving prognosis, compared with systemic chemotherapy (SC), in patients with stage IVB cervical cancer who have distant lymphatic metastasis.
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Usf1, a suppressor of the circadian Clock mutant, reveals the nature of the DNA-binding of the CLOCK:BMAL1 complex in mice.
Elife
PUBLISHED: 01-01-2013
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Genetic and molecular approaches have been critical for elucidating the mechanism of the mammalian circadian clock. Here, we demonstrate that the Clock?19 mutant behavioral phenotype is significantly modified by mouse strain genetic background. We map a suppressor of the Clock?19 mutation to a ?900 kb interval on mouse chromosome 1 and identify the transcription factor, Usf1, as the responsible gene. A SNP in the promoter of Usf1 causes elevation of its transcript and protein in strains that suppress the Clock mutant phenotype. USF1 competes with the CLOCK:BMAL1 complex for binding to E-box sites in target genes. Saturation binding experiments demonstrate reduced affinity of the CLOCK?19:BMAL1 complex for E-box sites, thereby permitting increased USF1 occupancy on a genome-wide basis. We propose that USF1 is an important modulator of molecular and behavioral circadian rhythms in mammals. DOI:http://dx.doi.org/10.7554/eLife.00426.001.
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Identification of diverse modulators of central and peripheral circadian clocks by high-throughput chemical screening.
Proc. Natl. Acad. Sci. U.S.A.
PUBLISHED: 12-19-2011
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The circadian clock coordinates daily oscillations of essential physiological and behavioral processes. Conversely, aberrant clocks with damped amplitude and/or abnormal period have been associated with chronic diseases and aging. To search for small molecules that perturb or enhance circadian rhythms, we conducted a high-throughput screen of approximately 200,000 synthetic compounds using Per2lucSV reporter fibroblast cells and validated 11 independent classes of molecules with Bmal1:luciferase reporter cells as well as with suprachiasmatic nucleus and peripheral tissue explants. Four compounds were found to lengthen the period in both central and peripheral clocks, including three compounds that inhibited casein kinase I? in vitro and a unique benzodiazepine derivative acting through a non-GABA(A) receptor target. In addition, two compounds acutely induced Per2lucSV reporter bioluminescence, delayed the rhythm, and increased intracellular cAMP levels, but caused rhythm damping. Importantly, five compounds shortened the period of peripheral clocks; among them, four compounds also enhanced the amplitude of central and/or peripheral reporter rhythms. Taken together, these studies highlight diverse activities of drug-like small molecules in manipulating the central and peripheral clocks. These small molecules constitute a toolbox for probing clock regulatory mechanisms and may provide putative lead compounds for treatment of clock-associated diseases.
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Methionine sulfoxide reductase A regulates cell growth through the p53-p21 pathway.
Biochem. Biophys. Res. Commun.
PUBLISHED: 10-24-2011
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MsrA is an oxidoreductase that catalyzes the stereospecific reduction of methionine-S-sulfoxide to methionine. Although MsrA is well-characterized as an antioxidant and has been implicated in the aging process and cellular senescence, its roles in cell proliferation are poorly understood. Here, we report a critical role of MsrA in normal cell proliferation and describe the regulation mechanism of cell growth by this protein. Down-regulation of MsrA inhibited cell proliferation, but MsrA overexpression did not promote it. MsrA deficiency led to an increase in p21, a major cyclin-dependent kinase inhibitor, thereby causing cell cycle arrest at the G(2)/M stage. While protein levels of p53 were not altered upon MsrA deficiency, its acetylation level was significantly elevated, which subsequently activated p21 transcription. The data suggest that MsrA is a regulator of cell growth that mediates the p53-p21 pathway.
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Self-assembled peptide architecture with a tooth shape: folding into shape.
J. Am. Chem. Soc.
PUBLISHED: 10-18-2011
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Molecular self-assembly is the spontaneous association of molecules into structured aggregates by which nature builds complex functional systems. While numerous examples have focused on 2D self-assembly to understand the underlying mechanism and mimic this process to create artificial nano- and microstructures, limited progress has been made toward 3D self-assembly on the molecular level. Here we show that a helical ?-peptide foldamer, an artificial protein fragment, with well-defined secondary structure self-assembles to form an unprecedented 3D molecular architecture with a molar tooth shape in a controlled manner in aqueous solution. Powder X-ray diffraction analysis, combined with global optimization and Rietveld refinement, allowed us to propose its molecular arrangement. We found that four individual left-handed helical monomers constitute a right-handed superhelix in a unit cell of the assembly, similar to that found in the supercoiled structure of collagen.
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A pyrene-imidazolium derivative that selectively recognizes G-quadruplex DNA.
Biomaterials
PUBLISHED: 10-11-2011
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G-quadruplexes, formed of four stranded guanine bases stabilized by monovalent cations, serve important role in cancer cell growth and control gene expression in telomere. Since there are various types of quadruplex structures, rapid and simple screening methods with high selectivity, sensitivity and nontoxicity are required for understanding about the biological roles of quadruplex DNA as well as in designing therapeutics. Herein, we report a pyrene-imidazolium derivative, JY-1, which can with high selectivity recognize G-quadruplex using fluorescence and NMR spectroscopy. This is the first example based on the imidazolium derivative, which can detect the G-quadruplex directly to utilize the excimer/monomer emission change in pyrene fluorophore. The selectivity of strong binding to a specific sequence can allow for quadruplex sensing and the detection method presented here is very simple, using fluorescence and NMR study. Also, the groove binding characteristic of JY-1 to the G-quadruplex has a relatively low nonspecific toxicity and the structure-specific differences in fluorescent character between DNA duplex and G-quadruplex may offer more discovery and application in biological study.
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HS-116, a novel phosphatidylinositol 3-kinase inhibitor induces apoptosis and suppresses angiogenesis of hepatocellular carcinoma through inhibition of the PI3K/AKT/mTOR pathway.
Cancer Lett.
PUBLISHED: 10-04-2011
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The phosphatidylinositol 3-kinase (PI3K) pathway plays a central role in cell proliferation and survival of human cancers. As PI3K is active in many cancer patients, resulting in cancer development and progression, we developed an azaindole derivative, HS-116 as a novel PI3K inhibitor. This study aimed to clarify the anticancer effect of HS-116 in human hepatocellular carcinoma (HCC). To identify the effect of HS-116 on HCC cells, a PI3K assay, 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay, flow cytometry, and Western blotting were conducted. IC(50) of HS-116 for PI3K? was 31nM, and it effectively suppressed the phosphorylation of PI3K downstream factors such as AKT, mTOR, p70S6K, and 4EBP1. Also, HS-116 induced apoptosis by increasing the proportion of sub-G1 apoptotic cells from 1.8% to 35% and increasing the expressions of Bax, cleaved-caspase-3, and cleaved-PARP as well as decreasing the expression of Bcl-2. In addition, chromatin condensation and apoptotic bodies were detected in HS-116-treated HCC cells. Furthermore, HS-116 decreased protein expression of hypoxia-inducible factor-1? (HIF-1?) and vascular endothelial growth factor (VEGF), and inhibited the tube formation and migration of human umbilical vein endothelial cells (HUVECs). In vivo, the ability of mice to vascularize subcutaneously implanted Matrigel plugs was diminished when the mice were treated with HS-116. These results show that HS-116 inhibits the PI3K/AKT/mTOR pathway via apoptosis and anti-angiogenesis in HCC cells. We suggest that HS-116 may be an effective novel therapeutic candidate against HCC.
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Isolation and structural characterization of the elusive 1:1 adduct of hydrazine and carbon dioxide.
Chem. Commun. (Camb.)
PUBLISHED: 09-15-2011
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A solid hydrazine was isolated as a crystalline powder by reacting aqueous hydrazine with supercritical CO(2). Its structure determined by single crystal X-ray diffraction shows a zwitterionic form of NH(3)(+)NHCO(2)(-). The solid hydrazine is remarkably stable but is as reactive as liquid hydrazine even in the absence of solvents.
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93-kDa twin-domain serine protease inhibitor (Serpin) has a regulatory function on the beetle Toll proteolytic signaling cascade.
J. Biol. Chem.
PUBLISHED: 08-23-2011
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Serpins are protease inhibitors that play essential roles in the down-regulation of extracellular proteolytic cascades. The core serpin domain is highly conserved, and typical serpins are encoded with a molecular size of 35-50 kDa. Here, we describe a novel 93-kDa protein that contains two complete, tandemly arrayed serpin domains. This twin serpin, SPN93, was isolated from the larval hemolymph of the large beetle Tenebrio molitor. The N-terminal serpin domain of SPN93 forms a covalent complex with the Spätzle-processing enzyme, a terminal serine protease of the Toll signaling cascade, whereas the C-terminal serpin domain of SPN93 forms complexes with a modular serine protease and the Spätzle-processing enzyme-activating enzyme, which are two different enzymes of the cascade. Consequently, SPN93 inhibited ?-1,3-glucan-mediated Toll proteolytic cascade activation in an in vitro system. Site-specific proteolysis of SPN93 at the N-terminal serpin domain was observed after activation of the Toll proteolytic cascade in vivo, and down-regulation of SPN93 by RNAi sensitized ?-1,3-glucan-mediated larval death. Therefore, SPN93 is the first serpin that contains twin tandemly arrayed and functionally active serpin domains that have a regulatory role in the larval Toll proteolytic signaling cascade.
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Body mass index and survival in patients with epithelial ovarian cancer.
J. Obstet. Gynaecol. Res.
PUBLISHED: 08-10-2011
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There is controversy regarding the effect of obesity on the treatment and survival of ovarian cancer. This study examined the impact of obesity on the treatment and survival outcomes of epithelial ovarian cancer.
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Unusual metal ion selectivities of the highly preorganized tetradentrate ligand 1,10-phenanthroline-2,9-dicarboxamide: a thermodynamic and fluorescence study.
Inorg Chem
PUBLISHED: 07-26-2011
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Some metal ion complexing properties of the ligand PDAM (1,10-phenanthroline-2,9-dicarboxamide) in aqueous solution are reported. Using UV-visible spectroscopy to follow the intense ?-?* transitions of PDAM as a function of metal ion concentration, log K(1) values in 0.1 M NaClO(4) and at 25 °C are, for Cu(II), 3.56(5); Ni(II), 3.06(5); Zn(II), 3.77(5); Co(II), 3.8(1); Mg(II), 0.1(1); Ca(II), 1.94(4); and Ba(II), 0.7(1). For more strongly bound metal ions, competition reactions between PDAM and EDTA (ethylenedinitrilo-tetraacetic acid) or tetren (1,4,7,10,13-pentaazatridecane), monitored following the UV spectrum of PDAM, gave the following log K(1) values in 0.1 M NaClO(4) and at 25 °C: Cd(II), 7.1(1); Pb(II), 5.82(5); In(III), 9.4(1); and Bi(III), 9.4(1). The very low log K(1)(PDAM) values for small metal ions such as Cu(II) or Zn(II) are unprecedented for a phen-based ligand (phen = 1,10-phenanthroline), which is rationalized in terms of the low basicity of the N donors of the ligand (pK(a) = 0.6) and the fact that PDAM has a best-fit size corresponding to large metal ions of ionic radius ~1.0 Å. Large metal ions with ionic radius ?1.0 Å show large increases in log K(1) relative to their phen complexes, which in turn produces unparalleled selectivities, such as a 3.5 log units greater log K(1)(PDAM) for Cd(II) than for Cu(II). PDAM shows strong fluorescence in aqueous solution, suggesting that its carboxamide groups do not produce a fluorescence-quenching photon-induced electron transfer (PET) effect. Only Ca(II) produces a weak CHEF (chelation enhanced fluorescence) effect with PDAM, while all other metal ions tested produce a decrease in fluorescence, a CHEQ (chelation enhanced quenching effect). The production of the CHEQ effect is rationalized in terms of the idea that coordination of metal ions to PDAM stabilizes a canonical form of the carboxamide groups that promotes a PET effect.
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